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Transplantation palliative care: The time is ripe

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Over 10 years ago, a challenge was made in a surgical publication for increased collaboration between the fields of transplantation and palliative care.1

Since that time not much progress has been made bringing these fields together in a consistent way that would mutually benefit patients and the specialties. However, other progress has been made, particularly in the field of palliative care, which could brighten the prospects and broaden the opportunities to accomplish collaboration between palliative care and transplantation.

Growth of palliative services

During the past decade there has been a robust proliferation of hospital-based palliative care programs in the United States. In all, 67% of U.S. hospitals with 50 or more beds report palliative care teams, up from 63% in 2011 and 53% in 2008.

Azoulay_Daniel_FRANCE.jpg
Dr. Daniel Azoulay
In addition, the number of hospice and palliative medicine fellowship programs and certified physicians, including surgeons, has increased across the country. There are approximately 120 training fellowships in hospice and palliative medicine and more than 7,000 physicians certified in hospice and palliative medicine through the American Board of Medical Specialties and American Osteopathic Association.

Only a decade ago, critical care and palliative care were generally considered mutually exclusive. Evidence is trickling in to suggest that this is no longer the case. Although palliative care was not an integral part of critical care at that time, patients, families, and even practitioners began to demand these services. Cook and Rocker have eloquently advocated the rightful place of palliative care in the ICU.2

Studies in recent years have shown that the integration of palliative care into critical care decreases in length of ICU and hospital stay, decreases costs, enhances patient/family satisfaction, and promotes a more rapid consensus about goals of care, without increasing mortality. The ICU experience to date could be considered a reassuring precedent for transplantation palliative care.

Integration of palliative care with transplantation

Early palliative care intervention has been shown to improve symptom burden and depression scores in end-stage liver disease patients awaiting transplant. In addition, early palliative care consultation in conjunction with cancer treatment has been associated with increased survival in non–small-cell lung cancer patients. It has been demonstrated that early integration of palliative care in the surgical ICU alongside disease-directed curative care can be accomplished without change in mortality, while improving end-of-life practice in liver transplant patients.3

Dunn_Geoffrey_P_PA_web.jpg
Dr. Geoffrey P. Dunn
Transplantation palliative care is a species of surgical palliative care, which is defined as the treatment of suffering and the promotion of quality of life for seriously or terminally ill patients under surgical care. Despite the dearth of information about palliative care for patients under the care of transplant surgeons, clearly there are few specialties with so many patients need of palliative care support. There is no “Stage I” disease in the world of transplantation. Any patient awaiting transplantation, any patient’s family considering organ donation from a critically ill loved one, and any transplant patient with chronic organ rejection or other significant morbidity is appropriate for palliative care consultation. Palliative care support addresses two needs critically important for successful transplantation outcomes: improved medical compliance that comes with diligent symptom control and psychosocial support.

What palliative care can do for transplant patients

What does palliative care mean for the person (and family) awaiting transplantation? For the cirrhotic patient with cachexia, ascites, and encephalopathy, it means access to the services of a team trained in the management of these symptoms. Palliative care teams can also provide psychosocial and spiritual support for patients and families who are intimidated by the complex navigation of the health care system and the existential threat that end-stage organ failure presents to them. Skilled palliative care and services can be the difference between failing and extended life with a higher quality of life for these very sick patients

Resuscitation of a patient, whether through restoration of organ function or interdicting the progression of disease, begins with resuscitation of hope. Nothing achieves this more quickly than amelioration of burdensome symptoms for the patient and family.

The barriers for transplant surgeons and teams referring and incorporating palliative care services in their practices are multiple and profound. The unique dilemma facing the transplant team is to balance the treatment of the failing organ, the treatment of the patient (and family and friends), and the best use of the graft, a precious gift of society.

Palliative surgery has been defined as any invasive procedure in which the main intention is to mitigate physical symptoms in patients with noncurable disease without causing premature death. The very success of transplantation over the past 3 decades has obscured our memory of transplantation as a type of palliative surgery. It is a well-known axiom of reconstructive surgery that the reconstructed site should be compared to what was there, not to “normal.” Even in the current era of improved immunosuppression and posttransplant support services, one could hardly describe even a successful transplant patient’s experience as “normal.” These patients’ lives may be extended and/or enhanced but they need palliative care before, during, and after transplantation. The growing availability of trained palliative care clinicians and teams, the increased familiarity of palliative and end-of-life care to surgical residents and fellows, and quality metrics measuring palliative care outcomes will provide reassurance and guidance to address reservations about the convergence of the two seemingly opposite realities.
 

 

 

A modest proposal

We propose that palliative care be presented to the entire spectrum of transplantation care: on the ward, in the ICU, and after transplantation. More specific “triggers” for palliative care for referral of transplant patients should be identified. Wentlandt et al.4 have described a promising model for an ambulatory clinic, which provides early, integrated palliative care to patients awaiting and receiving organ transplantation. In addition, we propose an application for grant funding for a conference and eventual formation of a work group of transplant surgeons and team members, palliative care clinicians, and patient/families who have experienced one of the aspects of the transplant spectrum. We await the subspecialty certification in hospice and palliative medicine of a transplant surgeon. Outside of transplantation, every other surgical specialty in the United States has diplomates certified in hospice and palliative medicine. We await the benefits that will accrue from research about the merging of these fields.

1. Molmenti EP, Dunn GP: Transplantation and palliative care: The convergence of two seemingly opposite realities. Surg Clin North Am. 2005;85:373-82.

2. Cook D, Rocker G. Dying with dignity in the intensive care unit. N Engl J Med. 2014;370:2506-14.

3. Lamba S, Murphy P, McVicker S, Smith JH, and Mosenthal AC. Changing end-of-life care practice for liver transplant patients: structured palliative care intervention in the surgical intensive care unit. J Pain Symptom Manage. 2012; 44(4):508-19.

4. Wentlandt, K., Dall’Osto, A., Freeman, N., Le, L. W., Kaya, E., Ross, H., Singer, L. G., Abbey, S., Clarke, H. and Zimmermann, C. (2016), The Transplant Palliative Care Clinic: An early palliative care model for patients in a transplant program. Clin Transplant. 2016 Nov 4; doi: 10.1111/ctr.12838.

Dr. Azoulay is a transplantation specialist of Assistance Publique – Hôpitaux de Paris, and the University of Paris. Dr. Dunn is medical director of the Palliative Care Consultation Service at the University of Pittsburgh Medical Center Hamot, and vice-chair of the ACS Committee on Surgical Palliative Care.

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Over 10 years ago, a challenge was made in a surgical publication for increased collaboration between the fields of transplantation and palliative care.1

Since that time not much progress has been made bringing these fields together in a consistent way that would mutually benefit patients and the specialties. However, other progress has been made, particularly in the field of palliative care, which could brighten the prospects and broaden the opportunities to accomplish collaboration between palliative care and transplantation.

Growth of palliative services

During the past decade there has been a robust proliferation of hospital-based palliative care programs in the United States. In all, 67% of U.S. hospitals with 50 or more beds report palliative care teams, up from 63% in 2011 and 53% in 2008.

Azoulay_Daniel_FRANCE.jpg
Dr. Daniel Azoulay
In addition, the number of hospice and palliative medicine fellowship programs and certified physicians, including surgeons, has increased across the country. There are approximately 120 training fellowships in hospice and palliative medicine and more than 7,000 physicians certified in hospice and palliative medicine through the American Board of Medical Specialties and American Osteopathic Association.

Only a decade ago, critical care and palliative care were generally considered mutually exclusive. Evidence is trickling in to suggest that this is no longer the case. Although palliative care was not an integral part of critical care at that time, patients, families, and even practitioners began to demand these services. Cook and Rocker have eloquently advocated the rightful place of palliative care in the ICU.2

Studies in recent years have shown that the integration of palliative care into critical care decreases in length of ICU and hospital stay, decreases costs, enhances patient/family satisfaction, and promotes a more rapid consensus about goals of care, without increasing mortality. The ICU experience to date could be considered a reassuring precedent for transplantation palliative care.

Integration of palliative care with transplantation

Early palliative care intervention has been shown to improve symptom burden and depression scores in end-stage liver disease patients awaiting transplant. In addition, early palliative care consultation in conjunction with cancer treatment has been associated with increased survival in non–small-cell lung cancer patients. It has been demonstrated that early integration of palliative care in the surgical ICU alongside disease-directed curative care can be accomplished without change in mortality, while improving end-of-life practice in liver transplant patients.3

Dunn_Geoffrey_P_PA_web.jpg
Dr. Geoffrey P. Dunn
Transplantation palliative care is a species of surgical palliative care, which is defined as the treatment of suffering and the promotion of quality of life for seriously or terminally ill patients under surgical care. Despite the dearth of information about palliative care for patients under the care of transplant surgeons, clearly there are few specialties with so many patients need of palliative care support. There is no “Stage I” disease in the world of transplantation. Any patient awaiting transplantation, any patient’s family considering organ donation from a critically ill loved one, and any transplant patient with chronic organ rejection or other significant morbidity is appropriate for palliative care consultation. Palliative care support addresses two needs critically important for successful transplantation outcomes: improved medical compliance that comes with diligent symptom control and psychosocial support.

What palliative care can do for transplant patients

What does palliative care mean for the person (and family) awaiting transplantation? For the cirrhotic patient with cachexia, ascites, and encephalopathy, it means access to the services of a team trained in the management of these symptoms. Palliative care teams can also provide psychosocial and spiritual support for patients and families who are intimidated by the complex navigation of the health care system and the existential threat that end-stage organ failure presents to them. Skilled palliative care and services can be the difference between failing and extended life with a higher quality of life for these very sick patients

Resuscitation of a patient, whether through restoration of organ function or interdicting the progression of disease, begins with resuscitation of hope. Nothing achieves this more quickly than amelioration of burdensome symptoms for the patient and family.

The barriers for transplant surgeons and teams referring and incorporating palliative care services in their practices are multiple and profound. The unique dilemma facing the transplant team is to balance the treatment of the failing organ, the treatment of the patient (and family and friends), and the best use of the graft, a precious gift of society.

Palliative surgery has been defined as any invasive procedure in which the main intention is to mitigate physical symptoms in patients with noncurable disease without causing premature death. The very success of transplantation over the past 3 decades has obscured our memory of transplantation as a type of palliative surgery. It is a well-known axiom of reconstructive surgery that the reconstructed site should be compared to what was there, not to “normal.” Even in the current era of improved immunosuppression and posttransplant support services, one could hardly describe even a successful transplant patient’s experience as “normal.” These patients’ lives may be extended and/or enhanced but they need palliative care before, during, and after transplantation. The growing availability of trained palliative care clinicians and teams, the increased familiarity of palliative and end-of-life care to surgical residents and fellows, and quality metrics measuring palliative care outcomes will provide reassurance and guidance to address reservations about the convergence of the two seemingly opposite realities.
 

 

 

A modest proposal

We propose that palliative care be presented to the entire spectrum of transplantation care: on the ward, in the ICU, and after transplantation. More specific “triggers” for palliative care for referral of transplant patients should be identified. Wentlandt et al.4 have described a promising model for an ambulatory clinic, which provides early, integrated palliative care to patients awaiting and receiving organ transplantation. In addition, we propose an application for grant funding for a conference and eventual formation of a work group of transplant surgeons and team members, palliative care clinicians, and patient/families who have experienced one of the aspects of the transplant spectrum. We await the subspecialty certification in hospice and palliative medicine of a transplant surgeon. Outside of transplantation, every other surgical specialty in the United States has diplomates certified in hospice and palliative medicine. We await the benefits that will accrue from research about the merging of these fields.

1. Molmenti EP, Dunn GP: Transplantation and palliative care: The convergence of two seemingly opposite realities. Surg Clin North Am. 2005;85:373-82.

2. Cook D, Rocker G. Dying with dignity in the intensive care unit. N Engl J Med. 2014;370:2506-14.

3. Lamba S, Murphy P, McVicker S, Smith JH, and Mosenthal AC. Changing end-of-life care practice for liver transplant patients: structured palliative care intervention in the surgical intensive care unit. J Pain Symptom Manage. 2012; 44(4):508-19.

4. Wentlandt, K., Dall’Osto, A., Freeman, N., Le, L. W., Kaya, E., Ross, H., Singer, L. G., Abbey, S., Clarke, H. and Zimmermann, C. (2016), The Transplant Palliative Care Clinic: An early palliative care model for patients in a transplant program. Clin Transplant. 2016 Nov 4; doi: 10.1111/ctr.12838.

Dr. Azoulay is a transplantation specialist of Assistance Publique – Hôpitaux de Paris, and the University of Paris. Dr. Dunn is medical director of the Palliative Care Consultation Service at the University of Pittsburgh Medical Center Hamot, and vice-chair of the ACS Committee on Surgical Palliative Care.

 

Over 10 years ago, a challenge was made in a surgical publication for increased collaboration between the fields of transplantation and palliative care.1

Since that time not much progress has been made bringing these fields together in a consistent way that would mutually benefit patients and the specialties. However, other progress has been made, particularly in the field of palliative care, which could brighten the prospects and broaden the opportunities to accomplish collaboration between palliative care and transplantation.

Growth of palliative services

During the past decade there has been a robust proliferation of hospital-based palliative care programs in the United States. In all, 67% of U.S. hospitals with 50 or more beds report palliative care teams, up from 63% in 2011 and 53% in 2008.

Azoulay_Daniel_FRANCE.jpg
Dr. Daniel Azoulay
In addition, the number of hospice and palliative medicine fellowship programs and certified physicians, including surgeons, has increased across the country. There are approximately 120 training fellowships in hospice and palliative medicine and more than 7,000 physicians certified in hospice and palliative medicine through the American Board of Medical Specialties and American Osteopathic Association.

Only a decade ago, critical care and palliative care were generally considered mutually exclusive. Evidence is trickling in to suggest that this is no longer the case. Although palliative care was not an integral part of critical care at that time, patients, families, and even practitioners began to demand these services. Cook and Rocker have eloquently advocated the rightful place of palliative care in the ICU.2

Studies in recent years have shown that the integration of palliative care into critical care decreases in length of ICU and hospital stay, decreases costs, enhances patient/family satisfaction, and promotes a more rapid consensus about goals of care, without increasing mortality. The ICU experience to date could be considered a reassuring precedent for transplantation palliative care.

Integration of palliative care with transplantation

Early palliative care intervention has been shown to improve symptom burden and depression scores in end-stage liver disease patients awaiting transplant. In addition, early palliative care consultation in conjunction with cancer treatment has been associated with increased survival in non–small-cell lung cancer patients. It has been demonstrated that early integration of palliative care in the surgical ICU alongside disease-directed curative care can be accomplished without change in mortality, while improving end-of-life practice in liver transplant patients.3

Dunn_Geoffrey_P_PA_web.jpg
Dr. Geoffrey P. Dunn
Transplantation palliative care is a species of surgical palliative care, which is defined as the treatment of suffering and the promotion of quality of life for seriously or terminally ill patients under surgical care. Despite the dearth of information about palliative care for patients under the care of transplant surgeons, clearly there are few specialties with so many patients need of palliative care support. There is no “Stage I” disease in the world of transplantation. Any patient awaiting transplantation, any patient’s family considering organ donation from a critically ill loved one, and any transplant patient with chronic organ rejection or other significant morbidity is appropriate for palliative care consultation. Palliative care support addresses two needs critically important for successful transplantation outcomes: improved medical compliance that comes with diligent symptom control and psychosocial support.

What palliative care can do for transplant patients

What does palliative care mean for the person (and family) awaiting transplantation? For the cirrhotic patient with cachexia, ascites, and encephalopathy, it means access to the services of a team trained in the management of these symptoms. Palliative care teams can also provide psychosocial and spiritual support for patients and families who are intimidated by the complex navigation of the health care system and the existential threat that end-stage organ failure presents to them. Skilled palliative care and services can be the difference between failing and extended life with a higher quality of life for these very sick patients

Resuscitation of a patient, whether through restoration of organ function or interdicting the progression of disease, begins with resuscitation of hope. Nothing achieves this more quickly than amelioration of burdensome symptoms for the patient and family.

The barriers for transplant surgeons and teams referring and incorporating palliative care services in their practices are multiple and profound. The unique dilemma facing the transplant team is to balance the treatment of the failing organ, the treatment of the patient (and family and friends), and the best use of the graft, a precious gift of society.

Palliative surgery has been defined as any invasive procedure in which the main intention is to mitigate physical symptoms in patients with noncurable disease without causing premature death. The very success of transplantation over the past 3 decades has obscured our memory of transplantation as a type of palliative surgery. It is a well-known axiom of reconstructive surgery that the reconstructed site should be compared to what was there, not to “normal.” Even in the current era of improved immunosuppression and posttransplant support services, one could hardly describe even a successful transplant patient’s experience as “normal.” These patients’ lives may be extended and/or enhanced but they need palliative care before, during, and after transplantation. The growing availability of trained palliative care clinicians and teams, the increased familiarity of palliative and end-of-life care to surgical residents and fellows, and quality metrics measuring palliative care outcomes will provide reassurance and guidance to address reservations about the convergence of the two seemingly opposite realities.
 

 

 

A modest proposal

We propose that palliative care be presented to the entire spectrum of transplantation care: on the ward, in the ICU, and after transplantation. More specific “triggers” for palliative care for referral of transplant patients should be identified. Wentlandt et al.4 have described a promising model for an ambulatory clinic, which provides early, integrated palliative care to patients awaiting and receiving organ transplantation. In addition, we propose an application for grant funding for a conference and eventual formation of a work group of transplant surgeons and team members, palliative care clinicians, and patient/families who have experienced one of the aspects of the transplant spectrum. We await the subspecialty certification in hospice and palliative medicine of a transplant surgeon. Outside of transplantation, every other surgical specialty in the United States has diplomates certified in hospice and palliative medicine. We await the benefits that will accrue from research about the merging of these fields.

1. Molmenti EP, Dunn GP: Transplantation and palliative care: The convergence of two seemingly opposite realities. Surg Clin North Am. 2005;85:373-82.

2. Cook D, Rocker G. Dying with dignity in the intensive care unit. N Engl J Med. 2014;370:2506-14.

3. Lamba S, Murphy P, McVicker S, Smith JH, and Mosenthal AC. Changing end-of-life care practice for liver transplant patients: structured palliative care intervention in the surgical intensive care unit. J Pain Symptom Manage. 2012; 44(4):508-19.

4. Wentlandt, K., Dall’Osto, A., Freeman, N., Le, L. W., Kaya, E., Ross, H., Singer, L. G., Abbey, S., Clarke, H. and Zimmermann, C. (2016), The Transplant Palliative Care Clinic: An early palliative care model for patients in a transplant program. Clin Transplant. 2016 Nov 4; doi: 10.1111/ctr.12838.

Dr. Azoulay is a transplantation specialist of Assistance Publique – Hôpitaux de Paris, and the University of Paris. Dr. Dunn is medical director of the Palliative Care Consultation Service at the University of Pittsburgh Medical Center Hamot, and vice-chair of the ACS Committee on Surgical Palliative Care.

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Who Gets to Determine Whether Home Is “Unsafe” at the End of Life?

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Sometimes a patient at the end of life (EOL) just wants to go home. We recently treated such a patient, “Joe,” a 66-year-old veteran with end-stage chronic obstructive pulmonary disorder (COPD), severe hearing loss, and heavy alcohol use. A neighbor brought Joe to the hospital when he developed a urinary tract infection. Before hospitalization, Joe spent his days in bed. His neighbor was his designated health care agent (HCA) and caregiver, dropping off meals and bringing Joe to medical appointments. Joe had no other social support. In the hospital, Joe could not participate in physical therapy (PT) evaluations due to severe dyspnea on exertion. He was recommended for home PT, a home health aide, and home nursing, but Joe declined these services out of concern for encroachment on his independence. Given his heavy alcohol use, limited support, and functional limitations, the hospitalist team felt that Joe would be best served in a skilled nursing facility. As the palliative care team, we were consulted and felt that he was eligible for hospice. Joe simply wanted to go home.

Many patients like Joe experience functional decline at EOL, leading to increased care needs and transitions between sites of care.1 Some hospitalized patients at EOL want to transition directly to home, but due to their limited functioning and social support, discharge home may be deemed unsafe by health care professionals (HCPs). Clinicians then face the difficult balancing act of honoring patient wishes and avoiding a bad outcome. For patients at EOL, issues of capacity and risk become particularly salient. Furthermore, the unique structure of the US Department of Veterans Affairs (VA) health system and the psychosocial needs of some veterans add additional considerations for complex EOL discharges.2

End-of-life Decision Making

While patients may express strong preferences regarding their health care, their decision-making ability may worsen as they approach EOL. Contributing factors include older age, effects of hospitalization, treatment adverse effects, and comorbidities, including cognitive impairment. Studies of terminally ill patients show high rates of impaired decisional capacity.3,4 It is critical to assess capacity as part of discharge planning. Even when patients have the capacity, families and caregivers have an important voice, since they are often instrumental in maintaining patients at home.

Defining Risk

Determining whether a discharge is risky or unsafe is highly subjective, with differing opinions among clinicians and between patients and clinicians.5-7 In a qualitative study by Coombs and colleagues, HCPs tended toward a risk-averse approach to discharge decisions, sometimes favoring discharge to care facilities despite patient preferences.6 This approach also reflects pressures from the health care system to decrease the length of stay and reduce readmissions, important metrics for patient care and cost containment. However, keeping patients hospitalized or in nursing facilities does not completely mitigate risks (eg, falls) and carries other hazards (eg, nosocomial infections), as highlighted during the COVID-19 pandemic.7,8 The prospect of malpractice lawsuits and HCP moral distress about perceived risky home situations can also understandably affect decision making.

At the same time, risk calculation changes depending on the patient’s clinical status and priorities. Coombs and colleagues found that in contrast to clinicians, patients nearing EOL are willing to accept increasing risks and suboptimal living conditions to remain at home.6 What may be intolerable for a younger, healthier patient with a long life expectancy may be acceptable for someone who is approaching EOL. In our framework, a risky home discharge at EOL is considered one in which other adverse events, such as falls or inadequate symptom management, are likely.

Ethical Considerations

Unsafe discharges are challenging in part because some of the pillars of medical ethics can conflict. Prior articles have analyzed the ethical concerns of unsafe discharges in detail.9-11 Briefly, when patients wish to return home against initial medical recommendations, treatment teams may focus on the principles of beneficence and nonmaleficence, as exemplified by the desire to minimize harm, and justice, in which clinicians consider resource allocation and risks that a home discharge poses to family members, caregivers, and home health professionals. However, autonomy is important to consider as well. The concept of dignity of risk highlights the imperative to respect others’ decisions even when they increase the chance of harm, particularly given the overall shift in medicine from paternalism to shared decision making.12 Accommodating patient choice in how and where health care is received allows patients to regain some control over their lives, thereby enhancing their quality of life and promoting patient dignity, especially in their remaining days.13

Discharge Risk Framework

Our risk assessment framework helps clinicians more objectively identify factors that increase or decrease risk, inform discharge planning, partner with patients and families, give patients a prominent role in EOL decisions, and mitigate the risk of a bad outcome. This concept has been used in psychiatry, in which formal suicide assessment includes identifying risk factors and protective factors to estimate suicide risk and determine interventions.14 Similar to suicide risk estimation, this framework is based on clinical judgment rather than a specific calculation.

While this framework serves as a guide for determining and mitigating risk, we encourage teams to consider legal or ethical consultations in challenging cases, such as those in which patients lack both capacity and an involved HCA.

 

 

Step 1: Determine the patient’s capacity regarding disposition planning. Patients at EOL are at a higher risk of impaired decision-making capabilities; therefore, capacity evaluation is a critical step.

table_1.png

Step 2: Identify risk factors and protective factors for discharge home. Risk factors are intrinsic and extrinsic factors that increase risk such as functional or sensory impairments. Protective factors are intrinsic and extrinsic factors that decrease risk, including a good understanding of illness and consistent connection with the health care system (Table 1).

table_2.png

Step 3: Determine discharge to home risk level based on identified risk factors and protective factors. Patients may be at low, moderate, or high risk of having an adverse event, such as a fall or inadequate symptom control (Table 2).

Step 4: Identify risk mitigation strategies. These should be tailored to the patient based on the factors identified in Step 2. Examples include home nursing and therapy, mental health treatment, a medical alert system, and frequent contact between the patient and health care team.

Step 5: Meet with inpatient and outpatient HCP teams. Meetings should include the primary care professional (PCP) or relevant subspecialist, such as an oncologist for patients with cancer. For veterans receiving care solely at a local VA medical center, this can be easier to facilitate, but for veterans who receive care through both VA and non-VA systems, this step may require additional coordination. We also recommend including interdisciplinary team members, such as social workers, case managers, and the relevant home care or hospice agency. Certain agencies may decline admission if they perceive increased risk, such as no 24-hour care, perceived self-neglect, and limited instrumental support. During this meeting, HCPs discuss risk mitigation strategies identified in Step 4 and create a plan to propose to patients and families.

Step 6: Meet with patient, HCA, and family members. In addition to sharing information about prognosis, assessing caregiver capabilities and burden can guide conversations about discharge. The discharge plan should be determined through shared decision making.11 If the patient lacks capacity regarding disposition planning, this should be shared with the HCA. However, even when patients lack capacity, it is important to continue to engage them to understand their goals and preferences.

Step 7: Maximize risk mitigation strategies. If a moderate- or high-risk discharge is requested, the health care team should maximize risk mitigation strategies. For low-risk discharges, risk mitigation strategies can still promote safety, especially since risk increases as patients progress toward EOL. In some instances, patients, their HCAs, or caregivers may decline all risk mitigation strategies despite best efforts to communicate and negotiate options. In such circumstances, we recommend discussing the case with the outpatient team for a warm handoff. HCPs should also document all efforts (helpful from a legal standpoint as well as for the patient’s future treatment teams) and respect the decision to discharge home.

Applying the Framework

Our patient Joe provides a good illustration of how to implement this EOL framework. He was deemed to have the capacity to make decisions regarding discharge (Step 1). We determined his risk factors and protective factors for discharge (Step 2). His poor functional status, limited instrumental support, heavy alcohol use, rejection of home services, and communication barriers due to severe hearing impairment all increased his risk. Protective factors included an appreciation of functional limitations, intact cognition, and an involved HCA. Based on his limited instrumental support and poor function but good insight into limitations, discharge home was deemed to be of moderate risk (Step 3). Although risk factors such as alcohol use and severe hearing impairment could have raised his level to high risk, we felt that his involved HCA maintained him in the moderate-risk category.

We worked with the hospitalist team, PT, and audiology to identify multiple risk mitigation strategies: frequent phone calls between the HCA and outpatient palliative care team, home PT to improve transfers from bed to bedside commode, home nursing services either through a routine agency or hospice, and hearing aids for better communication (Steps 4 and 5). We then proposed these strategies to Joe and his HCA (Step 6). Due to concerns about infringement on his independence, Joe declined all home services but agreed to twice-daily check-ins by his HCA, frequent communication between his HCA and our team, and new hearing aids.

Joe returned home with the agreed-upon risk mitigation strategies in place (Step 7). Despite clinicians’ original reservations about sending Joe home without formal services, his HCA maintained close contact with our team, noting that Joe remained stable and happy to be at home in the months following discharge.

Conclusions

Fortunately, VA HCPs operate in an integrated health care system with access to psychological, social, and at-home medical support that can help mitigate risks. Still, we have benefitted from having a tool to help us evaluate risk systematically. Even if patients, families, and HCPs disagree on ideal discharge plans, this tool helps clinicians approach discharges methodically while maintaining open communication and partnership with patients. In doing so, our framework reflects the shift in medical culture from a patriarchal approach to shared decision-making practices regarding all aspects of medical care. Furthermore, we hope that this can help reduce clinician moral distress stemming from these challenging cases.

Future research on best practices for discharge risk assessment and optimizing home safety are needed. We also hope to evaluate the impact and effectiveness of our framework through interviews with key stakeholders. For Joe and other veterans like him, where to spend their final days may be the last important decision they make in life, and our framework allows for their voices to be better heard throughout the decision-making process.

Acknowledgments

We thank Brooke Lifland, MD, for her theoretical contributions to the concept behind this paper.

References

1. Committee on Approaching Death: Addressing Key End of Life Issues; Institute of Medicine. Dying in America: Improving Quality and Honoring Individual Preferences Near the End of Life. Washington (DC): National Academies Press (US); March 19, 2015.

2. Casarett D, Pickard A, Amos Bailey F, et al. Important aspects of end-of-life care among veterans: implications for measurement and quality improvement. J Pain Symptom Manage. 2008;35(2):115-125. doi:10.1016/j.jpainsymman.2007.03.008

3. Kolva E, Rosenfeld B, Brescia R, Comfort C. Assessing decision-making capacity at end of life. Gen Hosp Psychiatry. 2014;36(4):392-397. doi:10.1016/j.genhosppsych.2014.02.013

4. Kolva E, Rosenfeld B, Saracino R. Assessing the decision-making capacity of terminally ill patients with cancer. Am J Geriatr Psychiatry. 2018;26(5):523-531. doi:10.1016/j.jagp.2017.11.012

5. Macmillan MS. Hospital staff’s perceptions of risk associated with the discharge of elderly people from acute hospital care. J Adv Nurs. 1994;19(2):249-256. doi:10.1111/j.1365-2648.1994.tb01078.x

6. Coombs MA, Parker R, de Vries K. Managing risk during care transitions when approaching end of life: A qualitative study of patients’ and health care professionals’ decision making. Palliat Med. 2017;31(7):617-624. doi:10.1177/0269216316673476

7. Hyslop B. ‘Not safe for discharge’? Words, values, and person-centred care. Age Ageing. 2020;49(3):334-336. doi:10.1093/ageing/afz170

8. Goodacre S. Safe discharge: an irrational, unhelpful and unachievable concept. Emerg Med J. 2006;23(10):753-755. doi:10.1136/emj.2006.037903

9. Swidler RN, Seastrum T, Shelton W. Difficult hospital inpatient discharge decisions: ethical, legal and clinical practice issues. Am J Bioeth. 2007;7(3):23-28. doi:10.1080/15265160601171739

10. Hill J, Filer W. Safety and ethical considerations in discharging patients to suboptimal living situations. AMA J Ethics. 2015;17(6):506-510. Published 2015 Jun 1. doi:10.1001/journalofethics.2015.17.6.ecas2-1506

11. West JC. What is an ethically informed approach to managing patient safety risk during discharge planning?. AMA J Ethics. 2020;22(11):E919-E923. Published 2020 Nov 1. doi:10.1001/amajethics.2020.919

12. Mukherjee D. Discharge decisions and the dignity of risk. Hastings Cent Rep. 2015;45(3):7-8. doi:10.1002/hast.441

13. Wheatley VJ, Baker JI. “Please, I want to go home”: ethical issues raised when considering choice of place of care in palliative care. Postgrad Med J. 2007;83(984):643-648. doi:10.1136/pgmj.2007.058487

14. Work Group on Suicidal Behaviors. Practice guideline for the assessment and treatment of patients with suicidal behaviors. Am J Psychiatry. 2003;160(suppl 11):1-60.

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Jessica X. Zuo, MDa,b; Andrea Ruskin, MDc; Margaret R. Bauer, PhDc

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aUniversity of Pennsylvania, Philadelphia

bCorporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania

cVeterans Affairs Connecticut Healthcare System, West Haven

Author disclosures

At the time of this work, Jessica Zuo was funded as a Geriatric Medicine Education Fellow by the Connecticut Older Adult Collaboration for Health 4M (COACH 4M) grant, a Geriatric Workforce Enhancement Program funded by the Health Resources and Services Administration (HRSA). The COACH 4M grant and HRSA had no role in the development of this work or the preparation of this manuscript. The authors report no actual or potential conflicts of interest with regard to this article.

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The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

Ethics and consent

Verbal consent was obtained from the veteran reported.

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Jessica X. Zuo, MDa,b; Andrea Ruskin, MDc; Margaret R. Bauer, PhDc

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bCorporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania

cVeterans Affairs Connecticut Healthcare System, West Haven

Author disclosures

At the time of this work, Jessica Zuo was funded as a Geriatric Medicine Education Fellow by the Connecticut Older Adult Collaboration for Health 4M (COACH 4M) grant, a Geriatric Workforce Enhancement Program funded by the Health Resources and Services Administration (HRSA). The COACH 4M grant and HRSA had no role in the development of this work or the preparation of this manuscript. The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

Ethics and consent

Verbal consent was obtained from the veteran reported.

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Jessica X. Zuo, MDa,b; Andrea Ruskin, MDc; Margaret R. Bauer, PhDc

Correspondence: Jessica Zuo(jessica.zuo@va.gov)

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aUniversity of Pennsylvania, Philadelphia

bCorporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania

cVeterans Affairs Connecticut Healthcare System, West Haven

Author disclosures

At the time of this work, Jessica Zuo was funded as a Geriatric Medicine Education Fellow by the Connecticut Older Adult Collaboration for Health 4M (COACH 4M) grant, a Geriatric Workforce Enhancement Program funded by the Health Resources and Services Administration (HRSA). The COACH 4M grant and HRSA had no role in the development of this work or the preparation of this manuscript. The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

Ethics and consent

Verbal consent was obtained from the veteran reported.

Article PDF
Article PDF

Sometimes a patient at the end of life (EOL) just wants to go home. We recently treated such a patient, “Joe,” a 66-year-old veteran with end-stage chronic obstructive pulmonary disorder (COPD), severe hearing loss, and heavy alcohol use. A neighbor brought Joe to the hospital when he developed a urinary tract infection. Before hospitalization, Joe spent his days in bed. His neighbor was his designated health care agent (HCA) and caregiver, dropping off meals and bringing Joe to medical appointments. Joe had no other social support. In the hospital, Joe could not participate in physical therapy (PT) evaluations due to severe dyspnea on exertion. He was recommended for home PT, a home health aide, and home nursing, but Joe declined these services out of concern for encroachment on his independence. Given his heavy alcohol use, limited support, and functional limitations, the hospitalist team felt that Joe would be best served in a skilled nursing facility. As the palliative care team, we were consulted and felt that he was eligible for hospice. Joe simply wanted to go home.

Many patients like Joe experience functional decline at EOL, leading to increased care needs and transitions between sites of care.1 Some hospitalized patients at EOL want to transition directly to home, but due to their limited functioning and social support, discharge home may be deemed unsafe by health care professionals (HCPs). Clinicians then face the difficult balancing act of honoring patient wishes and avoiding a bad outcome. For patients at EOL, issues of capacity and risk become particularly salient. Furthermore, the unique structure of the US Department of Veterans Affairs (VA) health system and the psychosocial needs of some veterans add additional considerations for complex EOL discharges.2

End-of-life Decision Making

While patients may express strong preferences regarding their health care, their decision-making ability may worsen as they approach EOL. Contributing factors include older age, effects of hospitalization, treatment adverse effects, and comorbidities, including cognitive impairment. Studies of terminally ill patients show high rates of impaired decisional capacity.3,4 It is critical to assess capacity as part of discharge planning. Even when patients have the capacity, families and caregivers have an important voice, since they are often instrumental in maintaining patients at home.

Defining Risk

Determining whether a discharge is risky or unsafe is highly subjective, with differing opinions among clinicians and between patients and clinicians.5-7 In a qualitative study by Coombs and colleagues, HCPs tended toward a risk-averse approach to discharge decisions, sometimes favoring discharge to care facilities despite patient preferences.6 This approach also reflects pressures from the health care system to decrease the length of stay and reduce readmissions, important metrics for patient care and cost containment. However, keeping patients hospitalized or in nursing facilities does not completely mitigate risks (eg, falls) and carries other hazards (eg, nosocomial infections), as highlighted during the COVID-19 pandemic.7,8 The prospect of malpractice lawsuits and HCP moral distress about perceived risky home situations can also understandably affect decision making.

At the same time, risk calculation changes depending on the patient’s clinical status and priorities. Coombs and colleagues found that in contrast to clinicians, patients nearing EOL are willing to accept increasing risks and suboptimal living conditions to remain at home.6 What may be intolerable for a younger, healthier patient with a long life expectancy may be acceptable for someone who is approaching EOL. In our framework, a risky home discharge at EOL is considered one in which other adverse events, such as falls or inadequate symptom management, are likely.

Ethical Considerations

Unsafe discharges are challenging in part because some of the pillars of medical ethics can conflict. Prior articles have analyzed the ethical concerns of unsafe discharges in detail.9-11 Briefly, when patients wish to return home against initial medical recommendations, treatment teams may focus on the principles of beneficence and nonmaleficence, as exemplified by the desire to minimize harm, and justice, in which clinicians consider resource allocation and risks that a home discharge poses to family members, caregivers, and home health professionals. However, autonomy is important to consider as well. The concept of dignity of risk highlights the imperative to respect others’ decisions even when they increase the chance of harm, particularly given the overall shift in medicine from paternalism to shared decision making.12 Accommodating patient choice in how and where health care is received allows patients to regain some control over their lives, thereby enhancing their quality of life and promoting patient dignity, especially in their remaining days.13

Discharge Risk Framework

Our risk assessment framework helps clinicians more objectively identify factors that increase or decrease risk, inform discharge planning, partner with patients and families, give patients a prominent role in EOL decisions, and mitigate the risk of a bad outcome. This concept has been used in psychiatry, in which formal suicide assessment includes identifying risk factors and protective factors to estimate suicide risk and determine interventions.14 Similar to suicide risk estimation, this framework is based on clinical judgment rather than a specific calculation.

While this framework serves as a guide for determining and mitigating risk, we encourage teams to consider legal or ethical consultations in challenging cases, such as those in which patients lack both capacity and an involved HCA.

 

 

Step 1: Determine the patient’s capacity regarding disposition planning. Patients at EOL are at a higher risk of impaired decision-making capabilities; therefore, capacity evaluation is a critical step.

table_1.png

Step 2: Identify risk factors and protective factors for discharge home. Risk factors are intrinsic and extrinsic factors that increase risk such as functional or sensory impairments. Protective factors are intrinsic and extrinsic factors that decrease risk, including a good understanding of illness and consistent connection with the health care system (Table 1).

table_2.png

Step 3: Determine discharge to home risk level based on identified risk factors and protective factors. Patients may be at low, moderate, or high risk of having an adverse event, such as a fall or inadequate symptom control (Table 2).

Step 4: Identify risk mitigation strategies. These should be tailored to the patient based on the factors identified in Step 2. Examples include home nursing and therapy, mental health treatment, a medical alert system, and frequent contact between the patient and health care team.

Step 5: Meet with inpatient and outpatient HCP teams. Meetings should include the primary care professional (PCP) or relevant subspecialist, such as an oncologist for patients with cancer. For veterans receiving care solely at a local VA medical center, this can be easier to facilitate, but for veterans who receive care through both VA and non-VA systems, this step may require additional coordination. We also recommend including interdisciplinary team members, such as social workers, case managers, and the relevant home care or hospice agency. Certain agencies may decline admission if they perceive increased risk, such as no 24-hour care, perceived self-neglect, and limited instrumental support. During this meeting, HCPs discuss risk mitigation strategies identified in Step 4 and create a plan to propose to patients and families.

Step 6: Meet with patient, HCA, and family members. In addition to sharing information about prognosis, assessing caregiver capabilities and burden can guide conversations about discharge. The discharge plan should be determined through shared decision making.11 If the patient lacks capacity regarding disposition planning, this should be shared with the HCA. However, even when patients lack capacity, it is important to continue to engage them to understand their goals and preferences.

Step 7: Maximize risk mitigation strategies. If a moderate- or high-risk discharge is requested, the health care team should maximize risk mitigation strategies. For low-risk discharges, risk mitigation strategies can still promote safety, especially since risk increases as patients progress toward EOL. In some instances, patients, their HCAs, or caregivers may decline all risk mitigation strategies despite best efforts to communicate and negotiate options. In such circumstances, we recommend discussing the case with the outpatient team for a warm handoff. HCPs should also document all efforts (helpful from a legal standpoint as well as for the patient’s future treatment teams) and respect the decision to discharge home.

Applying the Framework

Our patient Joe provides a good illustration of how to implement this EOL framework. He was deemed to have the capacity to make decisions regarding discharge (Step 1). We determined his risk factors and protective factors for discharge (Step 2). His poor functional status, limited instrumental support, heavy alcohol use, rejection of home services, and communication barriers due to severe hearing impairment all increased his risk. Protective factors included an appreciation of functional limitations, intact cognition, and an involved HCA. Based on his limited instrumental support and poor function but good insight into limitations, discharge home was deemed to be of moderate risk (Step 3). Although risk factors such as alcohol use and severe hearing impairment could have raised his level to high risk, we felt that his involved HCA maintained him in the moderate-risk category.

We worked with the hospitalist team, PT, and audiology to identify multiple risk mitigation strategies: frequent phone calls between the HCA and outpatient palliative care team, home PT to improve transfers from bed to bedside commode, home nursing services either through a routine agency or hospice, and hearing aids for better communication (Steps 4 and 5). We then proposed these strategies to Joe and his HCA (Step 6). Due to concerns about infringement on his independence, Joe declined all home services but agreed to twice-daily check-ins by his HCA, frequent communication between his HCA and our team, and new hearing aids.

Joe returned home with the agreed-upon risk mitigation strategies in place (Step 7). Despite clinicians’ original reservations about sending Joe home without formal services, his HCA maintained close contact with our team, noting that Joe remained stable and happy to be at home in the months following discharge.

Conclusions

Fortunately, VA HCPs operate in an integrated health care system with access to psychological, social, and at-home medical support that can help mitigate risks. Still, we have benefitted from having a tool to help us evaluate risk systematically. Even if patients, families, and HCPs disagree on ideal discharge plans, this tool helps clinicians approach discharges methodically while maintaining open communication and partnership with patients. In doing so, our framework reflects the shift in medical culture from a patriarchal approach to shared decision-making practices regarding all aspects of medical care. Furthermore, we hope that this can help reduce clinician moral distress stemming from these challenging cases.

Future research on best practices for discharge risk assessment and optimizing home safety are needed. We also hope to evaluate the impact and effectiveness of our framework through interviews with key stakeholders. For Joe and other veterans like him, where to spend their final days may be the last important decision they make in life, and our framework allows for their voices to be better heard throughout the decision-making process.

Acknowledgments

We thank Brooke Lifland, MD, for her theoretical contributions to the concept behind this paper.

Sometimes a patient at the end of life (EOL) just wants to go home. We recently treated such a patient, “Joe,” a 66-year-old veteran with end-stage chronic obstructive pulmonary disorder (COPD), severe hearing loss, and heavy alcohol use. A neighbor brought Joe to the hospital when he developed a urinary tract infection. Before hospitalization, Joe spent his days in bed. His neighbor was his designated health care agent (HCA) and caregiver, dropping off meals and bringing Joe to medical appointments. Joe had no other social support. In the hospital, Joe could not participate in physical therapy (PT) evaluations due to severe dyspnea on exertion. He was recommended for home PT, a home health aide, and home nursing, but Joe declined these services out of concern for encroachment on his independence. Given his heavy alcohol use, limited support, and functional limitations, the hospitalist team felt that Joe would be best served in a skilled nursing facility. As the palliative care team, we were consulted and felt that he was eligible for hospice. Joe simply wanted to go home.

Many patients like Joe experience functional decline at EOL, leading to increased care needs and transitions between sites of care.1 Some hospitalized patients at EOL want to transition directly to home, but due to their limited functioning and social support, discharge home may be deemed unsafe by health care professionals (HCPs). Clinicians then face the difficult balancing act of honoring patient wishes and avoiding a bad outcome. For patients at EOL, issues of capacity and risk become particularly salient. Furthermore, the unique structure of the US Department of Veterans Affairs (VA) health system and the psychosocial needs of some veterans add additional considerations for complex EOL discharges.2

End-of-life Decision Making

While patients may express strong preferences regarding their health care, their decision-making ability may worsen as they approach EOL. Contributing factors include older age, effects of hospitalization, treatment adverse effects, and comorbidities, including cognitive impairment. Studies of terminally ill patients show high rates of impaired decisional capacity.3,4 It is critical to assess capacity as part of discharge planning. Even when patients have the capacity, families and caregivers have an important voice, since they are often instrumental in maintaining patients at home.

Defining Risk

Determining whether a discharge is risky or unsafe is highly subjective, with differing opinions among clinicians and between patients and clinicians.5-7 In a qualitative study by Coombs and colleagues, HCPs tended toward a risk-averse approach to discharge decisions, sometimes favoring discharge to care facilities despite patient preferences.6 This approach also reflects pressures from the health care system to decrease the length of stay and reduce readmissions, important metrics for patient care and cost containment. However, keeping patients hospitalized or in nursing facilities does not completely mitigate risks (eg, falls) and carries other hazards (eg, nosocomial infections), as highlighted during the COVID-19 pandemic.7,8 The prospect of malpractice lawsuits and HCP moral distress about perceived risky home situations can also understandably affect decision making.

At the same time, risk calculation changes depending on the patient’s clinical status and priorities. Coombs and colleagues found that in contrast to clinicians, patients nearing EOL are willing to accept increasing risks and suboptimal living conditions to remain at home.6 What may be intolerable for a younger, healthier patient with a long life expectancy may be acceptable for someone who is approaching EOL. In our framework, a risky home discharge at EOL is considered one in which other adverse events, such as falls or inadequate symptom management, are likely.

Ethical Considerations

Unsafe discharges are challenging in part because some of the pillars of medical ethics can conflict. Prior articles have analyzed the ethical concerns of unsafe discharges in detail.9-11 Briefly, when patients wish to return home against initial medical recommendations, treatment teams may focus on the principles of beneficence and nonmaleficence, as exemplified by the desire to minimize harm, and justice, in which clinicians consider resource allocation and risks that a home discharge poses to family members, caregivers, and home health professionals. However, autonomy is important to consider as well. The concept of dignity of risk highlights the imperative to respect others’ decisions even when they increase the chance of harm, particularly given the overall shift in medicine from paternalism to shared decision making.12 Accommodating patient choice in how and where health care is received allows patients to regain some control over their lives, thereby enhancing their quality of life and promoting patient dignity, especially in their remaining days.13

Discharge Risk Framework

Our risk assessment framework helps clinicians more objectively identify factors that increase or decrease risk, inform discharge planning, partner with patients and families, give patients a prominent role in EOL decisions, and mitigate the risk of a bad outcome. This concept has been used in psychiatry, in which formal suicide assessment includes identifying risk factors and protective factors to estimate suicide risk and determine interventions.14 Similar to suicide risk estimation, this framework is based on clinical judgment rather than a specific calculation.

While this framework serves as a guide for determining and mitigating risk, we encourage teams to consider legal or ethical consultations in challenging cases, such as those in which patients lack both capacity and an involved HCA.

 

 

Step 1: Determine the patient’s capacity regarding disposition planning. Patients at EOL are at a higher risk of impaired decision-making capabilities; therefore, capacity evaluation is a critical step.

table_1.png

Step 2: Identify risk factors and protective factors for discharge home. Risk factors are intrinsic and extrinsic factors that increase risk such as functional or sensory impairments. Protective factors are intrinsic and extrinsic factors that decrease risk, including a good understanding of illness and consistent connection with the health care system (Table 1).

table_2.png

Step 3: Determine discharge to home risk level based on identified risk factors and protective factors. Patients may be at low, moderate, or high risk of having an adverse event, such as a fall or inadequate symptom control (Table 2).

Step 4: Identify risk mitigation strategies. These should be tailored to the patient based on the factors identified in Step 2. Examples include home nursing and therapy, mental health treatment, a medical alert system, and frequent contact between the patient and health care team.

Step 5: Meet with inpatient and outpatient HCP teams. Meetings should include the primary care professional (PCP) or relevant subspecialist, such as an oncologist for patients with cancer. For veterans receiving care solely at a local VA medical center, this can be easier to facilitate, but for veterans who receive care through both VA and non-VA systems, this step may require additional coordination. We also recommend including interdisciplinary team members, such as social workers, case managers, and the relevant home care or hospice agency. Certain agencies may decline admission if they perceive increased risk, such as no 24-hour care, perceived self-neglect, and limited instrumental support. During this meeting, HCPs discuss risk mitigation strategies identified in Step 4 and create a plan to propose to patients and families.

Step 6: Meet with patient, HCA, and family members. In addition to sharing information about prognosis, assessing caregiver capabilities and burden can guide conversations about discharge. The discharge plan should be determined through shared decision making.11 If the patient lacks capacity regarding disposition planning, this should be shared with the HCA. However, even when patients lack capacity, it is important to continue to engage them to understand their goals and preferences.

Step 7: Maximize risk mitigation strategies. If a moderate- or high-risk discharge is requested, the health care team should maximize risk mitigation strategies. For low-risk discharges, risk mitigation strategies can still promote safety, especially since risk increases as patients progress toward EOL. In some instances, patients, their HCAs, or caregivers may decline all risk mitigation strategies despite best efforts to communicate and negotiate options. In such circumstances, we recommend discussing the case with the outpatient team for a warm handoff. HCPs should also document all efforts (helpful from a legal standpoint as well as for the patient’s future treatment teams) and respect the decision to discharge home.

Applying the Framework

Our patient Joe provides a good illustration of how to implement this EOL framework. He was deemed to have the capacity to make decisions regarding discharge (Step 1). We determined his risk factors and protective factors for discharge (Step 2). His poor functional status, limited instrumental support, heavy alcohol use, rejection of home services, and communication barriers due to severe hearing impairment all increased his risk. Protective factors included an appreciation of functional limitations, intact cognition, and an involved HCA. Based on his limited instrumental support and poor function but good insight into limitations, discharge home was deemed to be of moderate risk (Step 3). Although risk factors such as alcohol use and severe hearing impairment could have raised his level to high risk, we felt that his involved HCA maintained him in the moderate-risk category.

We worked with the hospitalist team, PT, and audiology to identify multiple risk mitigation strategies: frequent phone calls between the HCA and outpatient palliative care team, home PT to improve transfers from bed to bedside commode, home nursing services either through a routine agency or hospice, and hearing aids for better communication (Steps 4 and 5). We then proposed these strategies to Joe and his HCA (Step 6). Due to concerns about infringement on his independence, Joe declined all home services but agreed to twice-daily check-ins by his HCA, frequent communication between his HCA and our team, and new hearing aids.

Joe returned home with the agreed-upon risk mitigation strategies in place (Step 7). Despite clinicians’ original reservations about sending Joe home without formal services, his HCA maintained close contact with our team, noting that Joe remained stable and happy to be at home in the months following discharge.

Conclusions

Fortunately, VA HCPs operate in an integrated health care system with access to psychological, social, and at-home medical support that can help mitigate risks. Still, we have benefitted from having a tool to help us evaluate risk systematically. Even if patients, families, and HCPs disagree on ideal discharge plans, this tool helps clinicians approach discharges methodically while maintaining open communication and partnership with patients. In doing so, our framework reflects the shift in medical culture from a patriarchal approach to shared decision-making practices regarding all aspects of medical care. Furthermore, we hope that this can help reduce clinician moral distress stemming from these challenging cases.

Future research on best practices for discharge risk assessment and optimizing home safety are needed. We also hope to evaluate the impact and effectiveness of our framework through interviews with key stakeholders. For Joe and other veterans like him, where to spend their final days may be the last important decision they make in life, and our framework allows for their voices to be better heard throughout the decision-making process.

Acknowledgments

We thank Brooke Lifland, MD, for her theoretical contributions to the concept behind this paper.

References

1. Committee on Approaching Death: Addressing Key End of Life Issues; Institute of Medicine. Dying in America: Improving Quality and Honoring Individual Preferences Near the End of Life. Washington (DC): National Academies Press (US); March 19, 2015.

2. Casarett D, Pickard A, Amos Bailey F, et al. Important aspects of end-of-life care among veterans: implications for measurement and quality improvement. J Pain Symptom Manage. 2008;35(2):115-125. doi:10.1016/j.jpainsymman.2007.03.008

3. Kolva E, Rosenfeld B, Brescia R, Comfort C. Assessing decision-making capacity at end of life. Gen Hosp Psychiatry. 2014;36(4):392-397. doi:10.1016/j.genhosppsych.2014.02.013

4. Kolva E, Rosenfeld B, Saracino R. Assessing the decision-making capacity of terminally ill patients with cancer. Am J Geriatr Psychiatry. 2018;26(5):523-531. doi:10.1016/j.jagp.2017.11.012

5. Macmillan MS. Hospital staff’s perceptions of risk associated with the discharge of elderly people from acute hospital care. J Adv Nurs. 1994;19(2):249-256. doi:10.1111/j.1365-2648.1994.tb01078.x

6. Coombs MA, Parker R, de Vries K. Managing risk during care transitions when approaching end of life: A qualitative study of patients’ and health care professionals’ decision making. Palliat Med. 2017;31(7):617-624. doi:10.1177/0269216316673476

7. Hyslop B. ‘Not safe for discharge’? Words, values, and person-centred care. Age Ageing. 2020;49(3):334-336. doi:10.1093/ageing/afz170

8. Goodacre S. Safe discharge: an irrational, unhelpful and unachievable concept. Emerg Med J. 2006;23(10):753-755. doi:10.1136/emj.2006.037903

9. Swidler RN, Seastrum T, Shelton W. Difficult hospital inpatient discharge decisions: ethical, legal and clinical practice issues. Am J Bioeth. 2007;7(3):23-28. doi:10.1080/15265160601171739

10. Hill J, Filer W. Safety and ethical considerations in discharging patients to suboptimal living situations. AMA J Ethics. 2015;17(6):506-510. Published 2015 Jun 1. doi:10.1001/journalofethics.2015.17.6.ecas2-1506

11. West JC. What is an ethically informed approach to managing patient safety risk during discharge planning?. AMA J Ethics. 2020;22(11):E919-E923. Published 2020 Nov 1. doi:10.1001/amajethics.2020.919

12. Mukherjee D. Discharge decisions and the dignity of risk. Hastings Cent Rep. 2015;45(3):7-8. doi:10.1002/hast.441

13. Wheatley VJ, Baker JI. “Please, I want to go home”: ethical issues raised when considering choice of place of care in palliative care. Postgrad Med J. 2007;83(984):643-648. doi:10.1136/pgmj.2007.058487

14. Work Group on Suicidal Behaviors. Practice guideline for the assessment and treatment of patients with suicidal behaviors. Am J Psychiatry. 2003;160(suppl 11):1-60.

References

1. Committee on Approaching Death: Addressing Key End of Life Issues; Institute of Medicine. Dying in America: Improving Quality and Honoring Individual Preferences Near the End of Life. Washington (DC): National Academies Press (US); March 19, 2015.

2. Casarett D, Pickard A, Amos Bailey F, et al. Important aspects of end-of-life care among veterans: implications for measurement and quality improvement. J Pain Symptom Manage. 2008;35(2):115-125. doi:10.1016/j.jpainsymman.2007.03.008

3. Kolva E, Rosenfeld B, Brescia R, Comfort C. Assessing decision-making capacity at end of life. Gen Hosp Psychiatry. 2014;36(4):392-397. doi:10.1016/j.genhosppsych.2014.02.013

4. Kolva E, Rosenfeld B, Saracino R. Assessing the decision-making capacity of terminally ill patients with cancer. Am J Geriatr Psychiatry. 2018;26(5):523-531. doi:10.1016/j.jagp.2017.11.012

5. Macmillan MS. Hospital staff’s perceptions of risk associated with the discharge of elderly people from acute hospital care. J Adv Nurs. 1994;19(2):249-256. doi:10.1111/j.1365-2648.1994.tb01078.x

6. Coombs MA, Parker R, de Vries K. Managing risk during care transitions when approaching end of life: A qualitative study of patients’ and health care professionals’ decision making. Palliat Med. 2017;31(7):617-624. doi:10.1177/0269216316673476

7. Hyslop B. ‘Not safe for discharge’? Words, values, and person-centred care. Age Ageing. 2020;49(3):334-336. doi:10.1093/ageing/afz170

8. Goodacre S. Safe discharge: an irrational, unhelpful and unachievable concept. Emerg Med J. 2006;23(10):753-755. doi:10.1136/emj.2006.037903

9. Swidler RN, Seastrum T, Shelton W. Difficult hospital inpatient discharge decisions: ethical, legal and clinical practice issues. Am J Bioeth. 2007;7(3):23-28. doi:10.1080/15265160601171739

10. Hill J, Filer W. Safety and ethical considerations in discharging patients to suboptimal living situations. AMA J Ethics. 2015;17(6):506-510. Published 2015 Jun 1. doi:10.1001/journalofethics.2015.17.6.ecas2-1506

11. West JC. What is an ethically informed approach to managing patient safety risk during discharge planning?. AMA J Ethics. 2020;22(11):E919-E923. Published 2020 Nov 1. doi:10.1001/amajethics.2020.919

12. Mukherjee D. Discharge decisions and the dignity of risk. Hastings Cent Rep. 2015;45(3):7-8. doi:10.1002/hast.441

13. Wheatley VJ, Baker JI. “Please, I want to go home”: ethical issues raised when considering choice of place of care in palliative care. Postgrad Med J. 2007;83(984):643-648. doi:10.1136/pgmj.2007.058487

14. Work Group on Suicidal Behaviors. Practice guideline for the assessment and treatment of patients with suicidal behaviors. Am J Psychiatry. 2003;160(suppl 11):1-60.

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Bauer, PhDc</bylineText> <bylineFull/> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:"> <name/> <rightsInfo> <copyrightHolder> <name/> </copyrightHolder> <copyrightNotice/> </rightsInfo> </provider> <abstract/> <metaDescription>Sometimes a patient at the end of life (EOL) just wants to go home. We recently treated such a patient, “Joe,” a 66-year-old veteran with end-stage chronic obst</metaDescription> <articlePDF/> <teaserImage/> <title>Who Gets to Determine Whether Home Is “Unsafe” at the End of Life?</title> <deck/> <eyebrow>Commentary</eyebrow> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear>2023</pubPubdateYear> <pubPubdateMonth>November</pubPubdateMonth> <pubPubdateDay/> <pubVolume>40</pubVolume> <pubNumber>11</pubNumber> <wireChannels/> <primaryCMSID/> <CMSIDs> <CMSID>2951</CMSID> <CMSID>3639</CMSID> </CMSIDs> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>FED</publicationCode> <pubIssueName>November 2023</pubIssueName> <pubArticleType>Feature Articles | 3639</pubArticleType> <pubTopics/> <pubCategories/> <pubSections> <pubSection>Feature | 2951<pubSubsection/></pubSection> </pubSections> <journalTitle>Fed Pract</journalTitle> <journalFullTitle>Federal Practitioner</journalFullTitle> <copyrightStatement>Copyright 2017 Frontline Medical Communications Inc., Parsippany, NJ, USA. All rights reserved.</copyrightStatement> </publicationData> </publications_g> <publications> <term canonical="true">16</term> </publications> <sections> <term canonical="true">52</term> </sections> <topics> <term canonical="true">223</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Who Gets to Determine Whether Home Is “Unsafe” at the End of Life?</title> <deck/> </itemMeta> <itemContent> <p class="abstract"><b>Background: </b>At the end of life, some patients wish to be discharged directly home from the hospital, but health care teams may consider this unsafe, raising concerns for capacity and risk. However, defining risk is subjective and impacted by values, preferences, and clinical status. Accommodating patient preferences in discharge destinations can promote autonomy, dignity, and quality of life at the end of life.<br/><br/><b>Observations: </b>We developed a risk assessment framework to help clinicians objectively identify risk factors and protective factors and develop a comprehensive discharge plan. We applied this framework to a veteran nearing the end of life and he was able to successfully return home from the hospital.<b>Conclusions: </b>Approaching end-of-life discharges with a framework can inform discharge planning and lessen the risk of adverse events. Importantly, this framework can help clinicians communicate better and partner with patients and their loved ones in prioritizing patient values and preferences.</p> <p><span class="Drop">S</span>ometimes a patient at the end of life (EOL) just wants to go home. We recently treated such a patient, “Joe,” a 66-year-old veteran with end-stage chronic obstructive pulmonary disorder (COPD), severe hearing loss, and heavy alcohol use. A neighbor brought Joe to the hospital when he developed a urinary tract infection. Before hospitalization, Joe spent his days in bed. His neighbor was his designated health care agent (HCA) and caregiver, dropping off meals and bringing Joe to medical appointments. Joe had no other social support. In the hospital, Joe could not participate in physical therapy (PT) evaluations due to severe dyspnea on exertion. He was recommended for home PT, a home health aide, and home nursing, but Joe declined these services out of concern for encroachment on his independence. Given his heavy alcohol use, limited support, and functional limitations, the hospitalist team felt that Joe would be best served in a skilled nursing facility. As the palliative care team, we were consulted and felt that he was eligible for hospice. Joe simply wanted to go home.</p> <p>Many patients like Joe experience functional decline at EOL, leading to increased care needs and transitions between sites of care.<sup>1</sup> Some hospitalized patients at EOL want to transition directly to home, but due to their limited functioning and social support, discharge home may be deemed unsafe by health care professionals (HCPs). Clinicians then face the difficult balancing act of honoring patient wishes and avoiding a bad outcome. For patients at EOL, issues of capacity and risk become particularly salient. Furthermore, the unique structure of the US Department of Veterans Affairs (VA) health system and the psychosocial needs of some veterans add additional considerations for complex EOL discharges.<sup>2</sup></p> <h2>End-of-life Decision Making</h2> <p>While patients may express strong preferences regarding their health care, their decision-making ability may worsen as they approach EOL. Contributing factors include older age, effects of hospitalization, treatment adverse effects, and comorbidities, including cognitive impairment. Studies of terminally ill patients show high rates of impaired decisional capacity.<sup>3,4</sup> It is critical to assess capacity as part of discharge planning. Even when patients have the capacity, families and caregivers have an important voice, since they are often instrumental in maintaining patients at home.</p> <h3>Defining Risk</h3> <p>Determining whether a discharge is risky or unsafe is highly subjective, with differing opinions among clinicians and between patients and clinicians.<sup>5-7</sup> In a qualitative study by Coombs and colleagues, HCPs tended toward a risk-averse approach to discharge decisions, sometimes favoring discharge to care facilities despite patient preferences.<sup>6</sup> This approach also reflects pressures from the health care system to decrease the length of stay and reduce readmissions, important metrics for patient care and cost containment. However, keeping patients hospitalized or in nursing facilities does not completely mitigate risks (eg, falls) and carries other hazards (eg, nosocomial infections), as highlighted during the COVID-19 pandemic.<sup>7,8</sup> The prospect of malpractice lawsuits and HCP moral distress about perceived risky home situations can also understandably affect decision making. </p> <p>At the same time, risk calculation changes depending on the patient’s clinical status and priorities. Coombs and colleagues found that in contrast to clinicians, patients nearing EOL are willing to accept increasing risks and suboptimal living conditions to remain at home.<sup>6</sup> What may be intolerable for a younger, healthier patient with a long life expectancy may be acceptable for someone who is approaching EOL. In our framework, a risky home discharge at EOL is considered one in which other adverse events, such as falls or inadequate symptom management, are likely.</p> <h3>Ethical Considerations</h3> <p>Unsafe discharges are challenging in part because some of the pillars of medical ethics can conflict. Prior articles have analyzed the ethical concerns of unsafe discharges in detail.<sup>9-11</sup> Briefly, when patients wish to return home against initial medical recommendations, treatment teams may focus on the principles of beneficence and nonmaleficence, as exemplified by the desire to minimize harm, and justice, in which clinicians consider resource allocation and risks that a home discharge poses to family members, caregivers, and home health professionals. However, autonomy is important to consider as well. The concept of dignity of risk highlights the imperative to respect others’ decisions even when they increase the chance of harm, particularly given the overall shift in medicine from paternalism to shared decision making.<sup>12</sup> Accommodating patient choice in how and where health care is received allows patients to regain some control over their lives, thereby enhancing their quality of life and promoting patient dignity, especially in their remaining days.<sup>13</sup> </p> <h2>Discharge Risk Framework </h2> <p>Our risk assessment framework helps clinicians more objectively identify factors that increase or decrease risk, inform discharge planning, partner with patients and families, give patients a prominent role in EOL decisions, and mitigate the risk of a bad outcome. This concept has been used in psychiatry, in which formal suicide assessment includes identifying risk factors and protective factors to estimate suicide risk and determine interventions.<sup>14</sup> Similar to suicide risk estimation, this framework is based on clinical judgment rather than a specific calculation.</p> <p>While this framework serves as a guide for determining and mitigating risk, we encourage teams to consider legal or ethical consultations in challenging cases, such as those in which patients lack both capacity and an involved HCA.</p> <p><b>Step 1: Determine the patient’s capacity regarding disposition planning.</b> Patients at EOL are at a higher risk of impaired decision-making capabilities; therefore, capacity evaluation is a critical step.<b>Step 2: Identify risk factors and protective factors for discharge home.</b> Risk factors are intrinsic and extrinsic factors that increase risk such as functional or sensory impairments. Protective factors are intrinsic and extrinsic factors that decrease risk, including a good understanding of illness and consistent connection with the health care system (Table 1).<b>Step 3: Determine discharge to home risk level based on identified risk factors and protective factors.</b> Patients may be at low, moderate, or high risk of having an adverse event, such as a fall or inadequate symptom control (Table 2).<br/><br/><b>Step 4: Identify risk mitigation strategies.</b> These should be tailored to the patient based on the factors identified in Step 2. Examples include home nursing and therapy, mental health treatment, a medical alert system, and frequent contact between the patient and health care team.<b>Step 5: Meet with inpatient and outpatient HCP teams.</b> Meetings should include the primary care professional (PCP) or relevant subspecialist, such as an oncologist for patients with cancer. For veterans receiving care solely at a local VA medical center, this can be easier to facilitate, but for veterans who receive care through both VA and non-VA systems, this step may require additional coordination. We also recommend including interdisciplinary team members, such as social workers, case managers, and the relevant home care or hospice agency. Certain agencies may decline admission if they perceive increased risk, such as no 24-hour care, perceived self-neglect, and limited instrumental support. During this meeting, HCPs discuss risk mitigation strategies identified in Step 4 and create a plan to propose to patients and families.<br/><br/><b>Step 6: Meet with patient, HCA, and family members.</b> In addition to sharing information about prognosis, assessing caregiver capabilities and burden can guide conversations about discharge. The discharge plan should be determined through shared decision making.<sup>11</sup> If the patient lacks capacity regarding disposition planning, this should be shared with the HCA. However, even when patients lack capacity, it is important to continue to engage them to understand their goals and preferences.<b>Step 7: Maximize risk mitigation strategies.</b> If a moderate- or high-risk discharge is requested, the health care team should maximize risk mitigation strategies. For low-risk discharges, risk mitigation strategies can still promote safety, especially since risk increases as patients progress toward EOL. In some instances, patients, their HCAs, or caregivers may decline all risk mitigation strategies despite best efforts to communicate and negotiate options. In such circumstances, we recommend discussing the case with the outpatient team for a warm handoff. HCPs should also document all efforts (helpful from a legal standpoint as well as for the patient’s future treatment teams) and respect the decision to discharge home.</p> <h3>Applying the Framework</h3> <p>Our patient Joe provides a good illustration of how to implement this EOL framework. He was deemed to have the capacity to make decisions regarding discharge (Step 1). We determined his risk factors and protective factors for discharge (Step 2). His poor functional status, limited instrumental support, heavy alcohol use, rejection of home services, and communication barriers due to severe hearing impairment all increased his risk. Protective factors included an appreciation of functional limitations, intact cognition, and an involved HCA. Based on his limited instrumental support and poor function but good insight into limitations, discharge home was deemed to be of moderate risk (Step 3). Although risk factors such as alcohol use and severe hearing impairment could have raised his level to high risk, we felt that his involved HCA maintained him in the moderate-risk category. </p> <p>We worked with the hospitalist team, PT, and audiology to identify multiple risk mitigation strategies: frequent phone calls between the HCA and outpatient palliative care team, home PT to improve transfers from bed to bedside commode, home nursing services either through a routine agency or hospice, and hearing aids for better communication (Steps 4 and 5). We then proposed these strategies to Joe and his HCA (Step 6). Due to concerns about infringement on his independence, Joe declined all home services but agreed to twice-daily check-ins by his HCA, frequent communication between his HCA and our team, and new hearing aids. <br/><br/>Joe returned home with the agreed-upon risk mitigation strategies in place (Step 7). Despite clinicians’ original reservations about sending Joe home without formal services, his HCA maintained close contact with our team, noting that Joe remained stable and happy to be at home in the months following discharge. </p> <h2>Conclusions</h2> <p>Fortunately, VA HCPs operate in an integrated health care system with access to psychological, social, and at-home medical support that can help mitigate risks. Still, we have benefitted from having a tool to help us evaluate risk systematically. Even if patients, families, and HCPs disagree on ideal discharge plans, this tool helps clinicians approach discharges methodically while maintaining open communication and partnership with patients. In doing so, our framework reflects the shift in medical culture from a patriarchal approach to shared decision-making practices regarding all aspects of medical care. Furthermore, we hope that this can help reduce clinician moral distress stemming from these challenging cases.</p> <p>Future research on best practices for discharge risk assessment and optimizing home safety are needed. We also hope to evaluate the impact and effectiveness of our framework through interviews with key stakeholders. For Joe and other veterans like him, where to spend their final days may be the last important decision they make in life, and our framework allows for their voices to be better heard throughout the decision-making process. </p> <h3> Acknowledgments </h3> <p> <em>We thank Brooke Lifland, MD, for her theoretical contributions to the concept behind this paper.</em> </p> <h3> Author affiliations </h3> <p> <em><sup>a</sup>University of Pennsylvania, Philadelphia<br/><br/><sup>b</sup>Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania<br/><br/><sup>c</sup>Veterans Affairs Connecticut Healthcare System, West Haven</em> </p> <h3> Author disclosures </h3> <p> <em>At the time of this work, Jessica Zuo was funded as a Geriatric Medicine Education Fellow by the Connecticut Older Adult Collaboration for Health 4M (COACH 4M) grant, a Geriatric Workforce Enhancement Program funded by the Health Resources and Services Administration (HRSA). The COACH 4M grant and HRSA had no role in the development of this work or the preparation of this manuscript. The authors report no actual or potential conflicts of interest with regard to this article.</em> </p> <h3> Disclaimer </h3> <p> <em>The opinions expressed herein are those of the authors and do not necessarily reflect those of <i>Federal Practitioner,</i> Frontline Medical Communications Inc., the US Government, or any of its agencies.</em> </p> <h3> Ethics and consent </h3> <p> <em>Verbal consent was obtained from the veteran reported.</em> </p> <h3> References </h3> <p class="reference"> 1. Committee on Approaching Death: Addressing Key End of Life Issues; Institute of Medicine. <i>Dying in America: Improving Quality and Honoring Individual Preferences Near the End of Life</i>. Washington (DC): National Academies Press (US); March 19, 2015.<br/><br/> 2. Casarett D, Pickard A, Amos Bailey F, et al. Important aspects of end-of-life care among veterans: implications for measurement and quality improvement. <i>J Pain Symptom Manage</i>. 2008;35(2):115-125. doi:10.1016/j.jpainsymman.2007.03.008<br/><br/> 3. Kolva E, Rosenfeld B, Brescia R, Comfort C. Assessing decision-making capacity at end of life. <i>Gen Hosp Psychiatry</i>. 2014;36(4):392-397. doi:10.1016/j.genhosppsych.2014.02.013<br/><br/> 4. Kolva E, Rosenfeld B, Saracino R. Assessing the decision-making capacity of terminally ill patients with cancer. <i>Am J Geriatr Psychiatry</i>. 2018;26(5):523-531. doi:10.1016/j.jagp.2017.11.012<br/><br/> 5. Macmillan MS. Hospital staff’s perceptions of risk associated with the discharge of elderly people from acute hospital care. <i>J Adv Nurs</i>. 1994;19(2):249-256. doi:10.1111/j.1365-2648.1994.tb01078.x<br/><br/> 6. Coombs MA, Parker R, de Vries K. Managing risk during care transitions when approaching end of life: A qualitative study of patients’ and health care professionals’ decision making. <i>Palliat Med</i>. 2017;31(7):617-624. doi:10.1177/0269216316673476<br/><br/> 7. Hyslop B. ‘Not safe for discharge’? Words, values, and person-centred care. <i>Age Ageing</i>. 2020;49(3):334-336. doi:10.1093/ageing/afz170<br/><br/> 8. Goodacre S. Safe discharge: an irrational, unhelpful and unachievable concept. <i>Emerg Med J</i>. 2006;23(10):753-755. doi:10.1136/emj.2006.037903<br/><br/> 9. Swidler RN, Seastrum T, Shelton W. Difficult hospital inpatient discharge decisions: ethical, legal and clinical practice issues. <i>Am J Bioeth</i>. 2007;7(3):23-28. doi:10.1080/15265160601171739<br/><br/>10. Hill J, Filer W. Safety and ethical considerations in discharging patients to suboptimal living situations. <i>AMA J Ethics</i>. 2015;17(6):506-510. Published 2015 Jun 1. doi:10.1001/journalofethics.2015.17.6.ecas2-1506<br/><br/>11. West JC. What is an ethically informed approach to managing patient safety risk during discharge planning?. <i>AMA J Ethics</i>. 2020;22(11):E919-E923. Published 2020 Nov 1. doi:10.1001/amajethics.2020.919<br/><br/>12. Mukherjee D. Discharge decisions and the dignity of risk. <i>Hastings Cent Rep</i>. 2015;45(3):7-8. doi:10.1002/hast.441<br/><br/>13. Wheatley VJ, Baker JI. “Please, I want to go home”: ethical issues raised when considering choice of place of care in palliative care. <i>Postgrad Med J</i>. 2007;83(984):643-648. doi:10.1136/pgmj.2007.058487<br/><br/>14. Work Group on Suicidal Behaviors. Practice guideline for the assessment and treatment of patients with suicidal behaviors. <i>Am J Psychiatry</i>. 2003;160(suppl 11):1-60.</p> </itemContent> </newsItem> </itemSet></root>
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Comprehensive and Equitable Care for Vulnerable Veterans With Integrated Palliative, Psychology, and Oncology Care

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Veterans living with cancer need comprehensive assessment that includes supportive psychosocial care. The National Comprehensive Cancer Network (NCCN) and American College of Surgeons Commission on Cancer require accredited cancer centers to evaluate psychosocial distress and provide appropriate triage and treatment for all patients.1-3 Implementing psychosocial distress screening can be difficult because of procedural barriers and time constraints, clinic and supportive care resources, and lack of knowledge about how to access supportive services.

Distress screening protocols must be designed to address the specific needs of each population. To improve screening for cancer-related distress, deliver effective supportive services, and gain agreement on distress screening standards of care, the Coleman Foundation supported development of the Coleman Supportive Oncology Collaborative (CSOC), a project of 135 interdisciplinary health care professionals from 25 Chicago-area cancer care institutions.4

The Jesse Brown US Department of Veterans Affairs (VA) Medical Center (JBVAMC) was chosen to assess cancer-related concerns among veterans using the CSOC screening tool and to improve access to supportive oncology. JBVAMC provides care to approximately 49,000 veterans in Chicago, Illinois, and northwestern Indiana. The JBVAMC patient population includes a large number of veterans with dual diagnoses (co-occurring substance use and mental health disorders) and veterans experiencing homelessness.

Delivering integrated screening and oncologic care that is culture and age appropriate is particularly important for veterans given their unique risk factors. The veteran population is considered vulnerable in terms of health status, psychological functioning, and social context. Veterans who use the VA health system as a principal source of care have poorer health, greater comorbid medical conditions, and an increased risk of mortality and suicide compared with the general population.5,6 Poorer health status in veterans also may relate to old age, low income, poor education, psychological health, and minority race.7-9

Past studies point to unique risk factors for cancer and poor cancer adjustment among veterans, which may complicate cancer treatment and end-of-life/survivorship care. Veteran-specific risk factors include military-related exposures, particularly Agent Orange and morbidity/mortality secondary to comorbid medical and psychiatric conditions (eg, chronic obstructive pulmonary disease, diabetes mellitus, and posttraumatic stress disorder [PTSD]).10-12 Moreover, the geriatric veteran population continues to grow,with increasing rates of cancer that require unique considerations for effective cancer care.13,14 Despite this, there are minimal data to inform best practices and supportive care approaches for veterans with cancer. Lack of guidelines specific to veterans and other populations with increased psychosocial challenges may impede successful cancer care, making distress screening procedures particularly important. This is especially the case for the JBVAMC, which serves primarily African American urban-dwelling veterans who experience high rates of cancer disparities, including increased rates of mortality and increased levels of psychosocial distress.15,16

The goals of this program were to (1) examine levels of psychological, physical, financial, and treatment-related distress in a large sample of urban-dwelling veterans; (2) create a streamlined, sustainable process to screen a large number of veterans receiving cancer care in the outpatient setting and connect them with available supportive services; and (3) educate oncology physicians, nurses, and other staff about cancer-related distress and concerns using in-service trainings and interpersonal interactions to improve patient care. Our program was based on a Primary Care Mental Health Integration (PCMHI) model that embeds health psychologists in general medical clinics to better reach veterans dealing with mental health issues. We tailored for palliative care involvement.

Studies of this model have shown that mental health integration improves access to mental health services and mental health treatment outcomes and has higher patient and provider satisfaction.17 We were also influenced by the construct of the patient aligned care team (PACT) social worker who, in this veteran-centered approach, often functions as a care coordinator. Social work responsibilities include assessment of patients’ stressors including adjusting to the medical conditions, identifying untreated or undertreated mental health or substance abuse issues, economic instability, legal problems, and inadequate housing and transportation, which can often be exacerbated during cancer treatment.18

 

 



We screened for distress-related needs that included mental health concerns, physical needs including uncontrolled symptoms or adverse effects of cancer treatment, physical function complaints (eg, pain and fatigue), nutrition concerns, treatment or care related concerns, family and caregiver needs, along with financial challenges (housing and food) and insurance-related support. The goal of this article is to describe the development and implementation of this VA-specific distress screening program and reflect on the lessons learned for the application of streamlined distress screening and triage in similar settings throughout the VA health system and other similar settings.

Methods

This institutional review board at JBVAMC reviewed and exempted this quality improvement program using the SQUIRE framework.19 It was led by a group of palliative care clinicians, psychologists, and administrators who have worked with the oncology service for many years, primarily in the care of hospitalized patients. Common palliative care services include providing care for patients with serious illness diagnosis through the illness trajectory.

Setting

At the start of this program, we assessed the current clinic workflow to determine how to best screen and assist veterans experiencing distress. We met with team members individually to identify the best method of clinic integration, including attending medical oncologists, medical oncology fellows, psychology interns, oncology nursing staff, the oncology nurse coordinator, and clinic clerks.

The JBVAMC provides cancer care through 4 half-day medical hematology-oncology clinics that serve about 50 patients per half-day clinic. The clinics are staffed by hematology-oncology fellows supervised by hematology-oncology attending physicians, who are affiliated with 2 academic medical centers. These clinics are staffed by 3 registered nurses (RNs) and a licensed practical nurse (LPN) and are adjacent to a chemotherapy infusion clinic with unique nursing staff. The JBVAMC also provides a variety of supportive care services, including extensive mental health and substance use treatment, physical and occupational therapy, acupuncture, nutrition, social work, and housing services. Following our assessment, it was evident that there were a low number of referrals from oncology clinics to supportive care services, mostly due to lack of knowledge of resources and unclear referral procedures.

Based on clinical volume, we determined that our screening program could best be implemented through a stepped approach beginning in one clinic and expanding thereafter. We began by having a palliative care physician and health psychology intern embedded in 1 weekly half-day clinic and a health psychology intern embedded in a second weekly half-day clinic. Our program included 2 health psychology interns (for each academic year of the program) who were supervised by a JBVA health psychologist.

About 15 months after successful integration within the first 2 half-day clinics, we expanded the screening program to staff an additional half-day medical oncology clinic with a palliative care APRN. This allowed us to expand the screening tool distribution and collection to 3 of 4 of the weekly half-day oncology clinics as well as to meet individually with veterans experiencing high levels of distress. Veterans were flagged as having high distress levels by either the results of their completed screening tool or by referral from a medical oncology physician. We initially established screening in clinics that were sufficiently staffed to ensure that screens were appropriately distributed and reviewed. Patients seen in nonparticipating clinics were referred to outpatient social work, mental health and/or outpatient palliative care according to oncology fellows’ clinical assessments of the patient. All oncology fellows received education about distress screening and methods for referring to supportive care. Our clinic screening program extended from February 2017 through January 2020.

Screening

Program staff screened patients with new cancer diagnoses, then identified patients for follow-up screens. This tracking allowed staff to identify patients with oncology appointments that day and cross-reference patients needing a follow-up screen.

 

 

Following feedback from the clinic nurses, we determined that nurses would provide the distress tool to patients in paper form after they completed their assessment of vitals and waited to be seen by their medical oncologist. The patient would then deliver their completed form to the nurse who would combine it with the patient’s clinic notes for the oncologist to review. Veterans who reported elevated 4-question Patient Health Questionnaire (PHQ-4) scores ≥ 6 were seen immediately by program staff. Veterans were referred to social work or psychiatry services for a same day visit if they endorsed a high level of psychological distress during clinical examination. They were referred for other supportive care services if they were determined to have practical, family, or nutrition unmet distress needs by either the program staff or oncology fellows. Program staff provided guidance to medical oncology fellows for needed referrals including social work, mental health, and palliative care follow ups (eAppendix A available at doi:10.12788/fp.0158).

Veterans referred for supportive care services were contacted by the relevant clinical administrator by phone to schedule an intake; for social work referrals, patients were either seen in a walk-in office located in a colocated building or contacted by a social worker by phone.

Our screening tool was the Coleman Foundation Supportive Oncology Collaborative Screening Tool, compiled from validated instruments. Patients completed this screening tool, which includes the PHQ-4, NCCN problem list concerns, adapted Mini Nutrition Assessment and PROMIS Pain and Fatigue measure (eAppendix B available at doi:10.12788/fp.0158).20-22

We also worked with the VA Computerized Patient Record System (CPRS) to create an electronic template for the screening tool. Completed screening tools were manually entered by the physician, psychologists, or APRN into the CPRS chart.

We analyzed the different supportive care services available at the JBVAMC and noticed that many supportive services were available, yet these services were often separated. Therefore, we created a consult flowsheet to assist oncologists in placing referrals. These supportive care services include mental health services, a cancer support group, home health care, social services, nutrition, physical medicine and rehabilitation, and other specialty services.

Patient Education

The psychology and nursing staff created a patient information bulletin board where patients could access information about supportive services available at JBVAMC. This board required frequent replenishment of handouts because patients consulted the board regularly. Handouts and folders about common clinical issues also were placed in the clinic treatment rooms. We partnered with 2 local cancer support centers, Gilda’s Club and the Cancer Support Center, to make referrals for family members and/or caregivers who would benefit from additional support.

We provided in-service trainings for oncology fellows, including trainings on PTSD and substance abuse and their relationship to cancer care at the VA. These topics were chosen based on the feedback program staff received about perceived knowledge gaps from the oncology fellows. This program allowed for multiple informal conversations between that program staff and oncology fellows about overall patient care. We held trainings with the cancer coordinator and clinical nursing staff on strategies to identify and follow-up on cancer-related distress, and with oncology fellows to review the importance of distress screening and to instruct fellows on instructions for the consult flowsheet.

 

 

Funding

This program was funded by the Chicago-based Coleman Foundation as part of the CSOC. Funding was used to support a portion of time for administrative and clinical work of program staff, as well as data collection and analysis.

Results

We established 3 half-day integrated clinics where patients were screened and referred for services based on supportive oncology needs. In addition to our primary activities to screen and refer veterans, we held multiple educational sessions for colleagues, developed a workflow template, and integrated patient education materials into the clinics.

Screening

Veterans completed 1010 distress screens in 3 of 4 half-day oncology clinics over the 2.5-year project period. Veterans were screened at initial diagnosis and every 3 months, or during changes in their clinical care or disease status. As a result, 579 patients completed screening, with some patients doing several follow-up screens during their care. Integration of palliative care providers and health psychologists was instrumental in facilitating screening in these busy general medical oncology clinics. Most veterans were receptive to completing surveys with few refusing to fill out the survey.23 Medical oncology fellows often used the completed screener to inform their review of systems (by reviewing the Coleman screener Physical and Other Concerns section) and connect with the supportive care staff present in clinic for patient’s identifying severe needs (ie, mental health distress or complex psychosocial needs). Veterans’ rates of distress needs and successfuloutcomes of integration with mental health and social work services have been reported elsewhere.23

fdp03828s_t1.png

The mean (SD) age for veterans in this cohort was 72 (9.5) years. Participants were primarily African American veterans (70%), with mostly advanced disease (Table 1). Participants endorsed elevated distress needs compared with other patient populations screened in Chicago through the CSOC for depressed mood, pain, housing, transportation, and physical, nutrition, and treatment concerns.23 Elevated presence of needs was especially prominent for food, housing and insurance/medical needs; physical concerns; nutrition, and treatment- or care-related concerns. Veterans in this cohort reported extensive financial and housing concerns: 10.4% reported food and housing concerns, 18.6% reported transportation concerns, and 9.0% reported issues paying for medical care or medications (Table 2).20 Anecdotally, many experienced job loss or strain with their cancer diagnosis or were living at the poverty level before their diagnosis.

fdp03828s_t2.png


Social work referrals were often triggered due to transportation barriers to appointments/medication access, and food and/or housing insecurity. Social workers assisted with referrals for housing, transportation, financial reimbursement, on-site or community-based food banks, home health support, familial support, and hospice services. Social work consults increased 166% from 2016 (the year before the program start date) to the end of 2019.  

Based on this increased volume of referrals for social work in our oncology clinics, an oncology-specific social worker was hired at the completion of our program to be based in all 4 half-day oncology clinics in response to results of our quality improvement intervention. The social worker currently sees all patients with a new cancer diagnosis and supports oncology fellows to identify veterans needing a palliative care referral or referrals to other supportive services.

Throughout program implementation, traditional areas of palliative care focus were particularly important as veterans reported significant concerns with understanding their illness (67.4%), wanting to understand their prognosis (71.3%), and having questions about their treatment options (55.1%).20 The palliative care providers spent time educating patients about their disease, coordinating goals of care conversations, promoting patients’ engagement in decision making, and making a large number of referrals to hospice and home health to support veterans at home. 

 

 

Discussion

This project created a successful program to screen veterans for psychosocial distress and triage them to appropriate services. During the project, patients in VA-outpatient oncology clinics reported significant cancer-related distress due to baseline psychosocial needs, changes in emotional and physical functioning, logistical and financial challenges of receiving cancer care, and lack of instrumental support.23

Staff education supported successful buy-in, development and implementation of supportive oncology programs. We used a combination of in-service trainings, online trainings, and handouts to provide evidence for distress screening.24 Highlighting the evidence-base that demonstrates how cancer-related distress screening improves cancer and quality of life outcomes helped to address physician reluctance to accept the additional requirements needed to address veterans’ psychosocial needs and care concerns. To increase buy-in and collaboration among team members and foster heightened understanding between providers and patients, we recommend creating accessible education for all staff levels.

One specific area of education we focused on was primary palliative care, which includes the core competencies of communication and symptom management recommended for generalists and specialists of all disciplines.25 Program staff supported oncology fellows in developing their primary palliative care skills by being available to discuss basic symptom management and communication issues. VA cancer care programs could benefit from ongoing palliative care education of oncology staff to facilitate primary palliative care as well as earlier integration of secondary palliative care when needed.26 Secondary palliative care or care provided directly by the palliative care team assists with complex symptom management or communication issues. For these needs, oncology fellows were encouraged to refer to either the palliative care staff available in one of the half-day clinics or to the outpatient palliative care clinic. As a unique strength, the VA allows veterans to receive concurrent cancer-directed therapy and hospice care, which enables earlier referrals to hospice care and higher quality end-of-life care and emphasizes the need for primary palliative care in oncology.27,28

Integrating supportive oncology team members, such as licensed clinical social worker and psychology interns, was successful. This was modeled on the VA PACT, which focuses on prevention, health promotion, coordination and chronic disease management.29 Social determinants of health have a major impact on health outcomes especially in veteran-specific and African American populations, making screening for distress critical.30-32 The VA Office of Health Equity actively addresses health inequities by supporting initiation of screening programs for social determinants of health, including education, employment, exposure to abuse and violence, food insecurity, housing instability, legal needs, social isolation, transportation needs, and utility needs. This is especially needed for African-American individuals who are not only more likely to experience cancer, but also more likely to be negatively impacted by the consequences of cancer diagnosis/treatment, such as complications related to one’s job security, access to care, adverse effects, and other highly distressing needs.33,34

Our program found that veterans with cancer often had concerns associated with food and housing insecurity, transportation and paying for medication or medical care, and screening allowed health care providers to detect and address these social determinants of health through referrals to VA and community-specific programs. Social workers integrated into VA cancer clinics are uniquely equipped to coordinate distress screening and support continuity of care by virtue of their training, connections to preexisting VA supportive services, and knowledge of community resources. This model could be used in other VA specialty clinics serving veterans with chronic illness and those with high levels of physical frailty.35

Our ability to roll out distress screening was scaffolded by technological integration into existing VA systems (eg, screening results in CPRS and electronic referrals). Screening procedures could have been even more efficient with improved technology (Table 3). For example, technological limitations made it challenging to easily identify patients due for screening, requiring a cumbersome process of tracking, collecting and entering patients’ paper forms. Health care providers seeking to develop a distress screening program should consider investing in technology that allows for identification of patients requiring screening at a predetermined interval, completion of screening via tablet or personal device, integration of screening responses into the electronic health record, and automatic generation of notifications to the treating physician and appropriate support services.

fdp03828s_t3.png


We also established partnerships with community cancer support groups to offer both referral pathways and in-house programming. Veterans’ cancer care programs could benefit from identifying and securing community partnerships to capitalize on readily available low-cost or no-cost options for supportive oncology in the community. Further, as was the case in our program, cancer support centers may be willing to collaborate with VA hospitals to provide services on site (eg, support groups, art therapy). This would extend the reach of these supportive services while allowing VA employees to address the extensive psychosocial needs of individual veterans.

Conclusions

Veterans with cancer benefited from enhanced screening and psychosocial service availability, similar to a PCMHI model. Robust screening programs helped advocate for veterans dealing with the effects of poverty through identification of need and referral to existing VA programs and services quickly and efficiently. Providing comprehensive care within ambulatory cancer clinics can address cancer-related distress and any potential barriers to care in real time. VA hospitals typically offer an array of supportive services to address veterans’ psychosocial needs, yet these services tend to be siloed. Integrated referrals can help to resolve such access barriers. Since many veterans with burdensome cancers are not able to see their VA primary care physician regularly, offering comprehensive care within medical oncology ensures complete and integrated care that includes psychosocial screening.

We believe that this program is an example of a mechanism for oncologists and palliative care clinicians to integrate their care in a way that identifies needs and triages services for vulnerable veterans. As colleagues have written, “it is fundamental to our commitment to veterans that we ensure comparable, high quality care regardless of a veteran’s gender, race, or where they live.”34 Health care providers may underestimate the extensive change a cancer diagnosis can have on a patient’s quality of life. Cancer diagnosis and treatment have a large impact on all individuals, but this impact may be greater for individuals in poverty due to inability to work from home, inflexible work hours, and limited support structures. By creating screening programs with psychosocial integration in oncology clinics such as we have described, we hope to improve access to more equitable care for vulnerable veterans.

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References

1. National Comprehensive Cancer Network. NCCN guidelines distress management. Version 2.2021. Updated January 5, 2021. Accessed July 8, 2021. http://www.nccn.org/professionals/physician_gls/pdf/distress.pdf

2. American College of Surgeons, Commission on Cancer. Cancer program standards 2012: ensuring patient-centered care. Version 1.2.1. Published 2021. Accessed July 8, 2021. https://www.facs.org/~/media/files/quality%20programs/cancer/coc/programstandards2012.ashx

3. Jacobsen PB, Ransom S. Implementation of NCCN distress management guidelines by member institutions. J Natl Compr Canc Netw. 2007;5(1):99-103. doi:10.6004/jnccn.2007.0010

4. The Coleman Supportive Oncology Collaborative. Training tools. Accessed July 14, 2021. https://www.supportiveoncologycollaborative.org/training-tools

5. Agha Z, Lofgren RP, VanRuiswyk JV, Layde PM. Are patients at Veterans Affairs medical centers sicker? A comparative analysis of health status and medical resource use. Arch Intern Med. 2000;160(21):3252-3257. doi:10.1001/archinte.160.21.3252

6. Bullman T, Schneiderman A, Gradus JL. Relative importance of posttraumatic stress disorder and depression in predicting risk of suicide among a cohort of Vietnam veterans. Suicide Life Threat Behav. 2019;49(3):838-845. doi:10.1111/sltb.12482

7. Kazis LE, Miller DR, Clark J, et al. Health-related quality of life in patients served by the Department of Veterans Affairs: results from the Veterans Health Study. Arch Intern Med. 1998;158(6):626-632. doi:10.1001/archinte.158.6.626

8. O’Toole BI, Marshall RP, Grayson DA, et al. The Australian Vietnam Veterans Health Study: III. Psychological health of Australian Vietnam veterans and its relationship to combat. Int J Epidemiol. 1996;25(2):331-340. doi:10.1093/ije/25.2.331

9. Vincent C, Chamberlain K, Long N. Mental and physical health status in a community sample of New Zealand Vietnam War veterans. Aust J Public Health. 1994;18(1):58-62. doi:10.1111/j.1753-6405.1994.tb00196.x

10. US Department of Veterans Affairs. Veterans’ diseases associated with Agent Orange. Updated June 16, 2021. Accessed July 8, 2021. http://www.publichealth.va.gov/exposures/agentorange/diseases.asp#veterans

11. Hwa KJ, Dua MM, Wren SM, Visser BC. Missing the obvious: psychosocial obstacles in Veterans with hepatocellular carcinoma. HBP (Oxford). 2015;17(12):1124-1129. doi:10.1111/hpb.12508

12. Saha S, Freeman M, Toure J, Tippens KM, Weeks C, Ibrahim S. Racial and ethnic disparities in the VA health care system: a systematic review. J Gen Intern Med. 2008;23(5):654-671. doi:10.1007/s11606-008-0521-4

13. Amaral EFL, Pollard MS, Mendelsohn J, Cefalu M. Current and future demographics of the veteran population, 2014-2024. Popul Rev. 2018;57(1):28-60. doi:10.1353/prv.2018.0002

14. Mohile SG, Dale W, Somerfield MR, et al. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol. 2018;36(22):2326-2347. doi:10.1200/JCO.2018.78.8687

15. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212-236. doi:10.3322/caac.20121

16. Cimino T, Said K, Safier L, Harris H, Kinderman A. Psychosocial distress among oncology patients in the safety net. Psychooncology. 2020;29(11):1927-1935. doi:10.1002/pon.5525

17. Molander R, Hodgkins K, Johnson C, White A, Frazier E, Krahn D. Interprofessional education in patient aligned care team primary care-mental health integration. Fed Pract. 2017;34(6):40-48.

18. Parikh DA, Ragavan M, Dutta R, et al. Financial toxicity of cancer care: an analysis of financial burden in three distinct health care systems [published online ahead of print, 2021 Apr 7]. JCO Oncol Pract. 2021;OP2000890. doi:10.1200/OP.20.00890

19. Ogrinc G, Davies L, Goodman D, Batalden P, Davidoff F, Stevens D. SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): revised publication guidelines from a detailed consensus process. BMJ Qual Saf. 2016;25(12):986-992. doi:10.1136/bmjqs-2015-004411

20. Weldon CB, Gerhart JI, Penedo FJ, et al. Correlates of distress for cancer patients: results from multi-institution use of holistic patient-reported screening tool. J Clin Oncol. 2019;37(15)(suppl):11587-11587. doi:10.1200/JCO.2019.37.15_suppl.11587

21. Kroenke K, Spitzer RL, Williams JB, Löwe B. The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review. Gen Hosp Psychiatry. 2010;32(4):345-359. doi:10.1016/j.genhosppsych.2010.03.006

22. Kaiser MJ, Bauer JM, Ramsch C, et al. Validation of the Mini Nutritional Assessment short-form (MNA-SF): a practical tool for identification of nutritional status. J Nutr Health Aging. 2009;13(9):782-788. doi:10.1007/s12603-009-0214-7

23. Azizoddin DR, Lakin JR, Hauser J, et al. Meeting the guidelines: implementing a distress screening intervention for veterans with cancer. Psychooncology. 2020;29(12):2067-2074. doi:10.1002/pon.5565

24. Carlson LE, Waller A, Mitchell AJ. Screening for distress and unmet needs in patients with cancer: review and recommendations. J Clin Oncol. 2012;30(11):1160-1177. doi:10.1200/JCO.2011.39.5509

25. Quill TE, Abernethy AP. Generalist plus specialist palliative care—creating a more sustainable model. N Engl J Med. 2013;368(13):1173-1175. doi:10.1056/NEJMp1215620

26. Weissman DE, Meier DE. Identifying patients in need of a palliative care assessment in the hospital setting: a consensus report from the Center to Advance Palliative Care. J Palliat Med. 2011;14(1):17-23. doi:10.1089/jpm.2010.0347

27. Kumar P, Wright AA, Hatfield LA, Temel JS, Keating NL. Family perspectives on hospice care experiences of patients with cancer. J Clin Oncol. 2017;35(4):432-439. doi:10.1200/JCO.2016.68.9257

28. Mor V, Joyce NR, Coté DL, et al. The rise of concurrent care for veterans with advanced cancer at the end of life. Cancer. 2016;122(5):782-790. doi:10.1002/cncr.29827

29. US Department of Veterans Affairs. Patient care services: Patient aligned care team (PACT). Updated November 5, 2020. Accessed July 8, 2021. https://www.patientcare.va.gov/primarycare/PACT.asp

30. US Department of Veterans Affairs, Veterans Health Administration. VHA health equity action plan. Published September 27, 2019. Accessed July 8, 2021. https://www.va.gov/HEALTHEQUITY/docs/Health_Equity_Action_Plan_Final_022020.pdf

31. Alcaraz KI, Wiedt TL, Daniels EC, Yabroff KR, Guerra CE, Wender RC. Understanding and addressing social determinants to advance cancer health equity in the United States: a blueprint for practice, research, and policy. CA Cancer J Clin. 2020;70(1):31-46. doi:10.3322/caac.21586

32. Atkins D, Kilbourne A, Lipson L. Health equity research in the Veterans Health Administration: we’ve come far but aren’t there yet. Am J Public Health. 2014;104(suppl 4):S525-526. doi:10.2105/AJPH.2014.302216

33. American Cancer Society. Cancer Facts & Figures for African Americans 2019-2021. Atlanta: American Cancer Society; 2019.

34. Hastert TA, Kirchhoff AC, Banegas MP, et al. Work changes and individual, cancer-related, and work-related predictors of decreased work participation among African American cancer survivors. Cancer Med. 2020;9(23):9168-9177. doi:10.1002/cam4.3512

35. Bekelman DB, Nowels CT, Allen LA, Shakar S, Kutner JS, Matlock DD. Outpatient palliative care for chronic heart failure: a case series. J Palliat Med. 2011;14(7):815-821. doi:10.1089/jpm.2010.050

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Joanna Martin and Joshua Hauser are Palliative Care Physicians; Jane Weber is a Palliative Care Nurse Practitioner; and Tyra Oliver is a Palliative Care and Hematology Oncology Clinical Social Worker; all at Jesse Brown VA Medical Center in Chicago, Illinois. Christine Weldon is Adjunct Faculty in Hematology and Oncology; Joanna Martin is a Health System Clinician; and Joshua Hauser is a Palliative Care Physician; all at Northwestern Feinberg School of Medicine in Illinois. Christine Weldon is Director at the Center for Business Models in Healthcare in Illinois. Desiree Azizoddin is a Research Scientist at Brigham and Women’s Hospital and Affiliate Research Faculty, Department of Psychosocial Oncology and Palliative Care, Dana Farber Cancer Institute, and Harvard Medical School, in Massachusetts. Lauren Rynar is an Assistant Professor, Supportive Oncology at Rush University Medical Center in Chicago.
Correspondence: Joanna Martin (joanna.martin3@va.gov)

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The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

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Joanna Martin and Joshua Hauser are Palliative Care Physicians; Jane Weber is a Palliative Care Nurse Practitioner; and Tyra Oliver is a Palliative Care and Hematology Oncology Clinical Social Worker; all at Jesse Brown VA Medical Center in Chicago, Illinois. Christine Weldon is Adjunct Faculty in Hematology and Oncology; Joanna Martin is a Health System Clinician; and Joshua Hauser is a Palliative Care Physician; all at Northwestern Feinberg School of Medicine in Illinois. Christine Weldon is Director at the Center for Business Models in Healthcare in Illinois. Desiree Azizoddin is a Research Scientist at Brigham and Women’s Hospital and Affiliate Research Faculty, Department of Psychosocial Oncology and Palliative Care, Dana Farber Cancer Institute, and Harvard Medical School, in Massachusetts. Lauren Rynar is an Assistant Professor, Supportive Oncology at Rush University Medical Center in Chicago.
Correspondence: Joanna Martin (joanna.martin3@va.gov)

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The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

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Joanna Martin and Joshua Hauser are Palliative Care Physicians; Jane Weber is a Palliative Care Nurse Practitioner; and Tyra Oliver is a Palliative Care and Hematology Oncology Clinical Social Worker; all at Jesse Brown VA Medical Center in Chicago, Illinois. Christine Weldon is Adjunct Faculty in Hematology and Oncology; Joanna Martin is a Health System Clinician; and Joshua Hauser is a Palliative Care Physician; all at Northwestern Feinberg School of Medicine in Illinois. Christine Weldon is Director at the Center for Business Models in Healthcare in Illinois. Desiree Azizoddin is a Research Scientist at Brigham and Women’s Hospital and Affiliate Research Faculty, Department of Psychosocial Oncology and Palliative Care, Dana Farber Cancer Institute, and Harvard Medical School, in Massachusetts. Lauren Rynar is an Assistant Professor, Supportive Oncology at Rush University Medical Center in Chicago.
Correspondence: Joanna Martin (joanna.martin3@va.gov)

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The authors report no actual or potential conflicts of interest with regard to this article.

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The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

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Veterans living with cancer need comprehensive assessment that includes supportive psychosocial care. The National Comprehensive Cancer Network (NCCN) and American College of Surgeons Commission on Cancer require accredited cancer centers to evaluate psychosocial distress and provide appropriate triage and treatment for all patients.1-3 Implementing psychosocial distress screening can be difficult because of procedural barriers and time constraints, clinic and supportive care resources, and lack of knowledge about how to access supportive services.

Distress screening protocols must be designed to address the specific needs of each population. To improve screening for cancer-related distress, deliver effective supportive services, and gain agreement on distress screening standards of care, the Coleman Foundation supported development of the Coleman Supportive Oncology Collaborative (CSOC), a project of 135 interdisciplinary health care professionals from 25 Chicago-area cancer care institutions.4

The Jesse Brown US Department of Veterans Affairs (VA) Medical Center (JBVAMC) was chosen to assess cancer-related concerns among veterans using the CSOC screening tool and to improve access to supportive oncology. JBVAMC provides care to approximately 49,000 veterans in Chicago, Illinois, and northwestern Indiana. The JBVAMC patient population includes a large number of veterans with dual diagnoses (co-occurring substance use and mental health disorders) and veterans experiencing homelessness.

Delivering integrated screening and oncologic care that is culture and age appropriate is particularly important for veterans given their unique risk factors. The veteran population is considered vulnerable in terms of health status, psychological functioning, and social context. Veterans who use the VA health system as a principal source of care have poorer health, greater comorbid medical conditions, and an increased risk of mortality and suicide compared with the general population.5,6 Poorer health status in veterans also may relate to old age, low income, poor education, psychological health, and minority race.7-9

Past studies point to unique risk factors for cancer and poor cancer adjustment among veterans, which may complicate cancer treatment and end-of-life/survivorship care. Veteran-specific risk factors include military-related exposures, particularly Agent Orange and morbidity/mortality secondary to comorbid medical and psychiatric conditions (eg, chronic obstructive pulmonary disease, diabetes mellitus, and posttraumatic stress disorder [PTSD]).10-12 Moreover, the geriatric veteran population continues to grow,with increasing rates of cancer that require unique considerations for effective cancer care.13,14 Despite this, there are minimal data to inform best practices and supportive care approaches for veterans with cancer. Lack of guidelines specific to veterans and other populations with increased psychosocial challenges may impede successful cancer care, making distress screening procedures particularly important. This is especially the case for the JBVAMC, which serves primarily African American urban-dwelling veterans who experience high rates of cancer disparities, including increased rates of mortality and increased levels of psychosocial distress.15,16

The goals of this program were to (1) examine levels of psychological, physical, financial, and treatment-related distress in a large sample of urban-dwelling veterans; (2) create a streamlined, sustainable process to screen a large number of veterans receiving cancer care in the outpatient setting and connect them with available supportive services; and (3) educate oncology physicians, nurses, and other staff about cancer-related distress and concerns using in-service trainings and interpersonal interactions to improve patient care. Our program was based on a Primary Care Mental Health Integration (PCMHI) model that embeds health psychologists in general medical clinics to better reach veterans dealing with mental health issues. We tailored for palliative care involvement.

Studies of this model have shown that mental health integration improves access to mental health services and mental health treatment outcomes and has higher patient and provider satisfaction.17 We were also influenced by the construct of the patient aligned care team (PACT) social worker who, in this veteran-centered approach, often functions as a care coordinator. Social work responsibilities include assessment of patients’ stressors including adjusting to the medical conditions, identifying untreated or undertreated mental health or substance abuse issues, economic instability, legal problems, and inadequate housing and transportation, which can often be exacerbated during cancer treatment.18

 

 



We screened for distress-related needs that included mental health concerns, physical needs including uncontrolled symptoms or adverse effects of cancer treatment, physical function complaints (eg, pain and fatigue), nutrition concerns, treatment or care related concerns, family and caregiver needs, along with financial challenges (housing and food) and insurance-related support. The goal of this article is to describe the development and implementation of this VA-specific distress screening program and reflect on the lessons learned for the application of streamlined distress screening and triage in similar settings throughout the VA health system and other similar settings.

Methods

This institutional review board at JBVAMC reviewed and exempted this quality improvement program using the SQUIRE framework.19 It was led by a group of palliative care clinicians, psychologists, and administrators who have worked with the oncology service for many years, primarily in the care of hospitalized patients. Common palliative care services include providing care for patients with serious illness diagnosis through the illness trajectory.

Setting

At the start of this program, we assessed the current clinic workflow to determine how to best screen and assist veterans experiencing distress. We met with team members individually to identify the best method of clinic integration, including attending medical oncologists, medical oncology fellows, psychology interns, oncology nursing staff, the oncology nurse coordinator, and clinic clerks.

The JBVAMC provides cancer care through 4 half-day medical hematology-oncology clinics that serve about 50 patients per half-day clinic. The clinics are staffed by hematology-oncology fellows supervised by hematology-oncology attending physicians, who are affiliated with 2 academic medical centers. These clinics are staffed by 3 registered nurses (RNs) and a licensed practical nurse (LPN) and are adjacent to a chemotherapy infusion clinic with unique nursing staff. The JBVAMC also provides a variety of supportive care services, including extensive mental health and substance use treatment, physical and occupational therapy, acupuncture, nutrition, social work, and housing services. Following our assessment, it was evident that there were a low number of referrals from oncology clinics to supportive care services, mostly due to lack of knowledge of resources and unclear referral procedures.

Based on clinical volume, we determined that our screening program could best be implemented through a stepped approach beginning in one clinic and expanding thereafter. We began by having a palliative care physician and health psychology intern embedded in 1 weekly half-day clinic and a health psychology intern embedded in a second weekly half-day clinic. Our program included 2 health psychology interns (for each academic year of the program) who were supervised by a JBVA health psychologist.

About 15 months after successful integration within the first 2 half-day clinics, we expanded the screening program to staff an additional half-day medical oncology clinic with a palliative care APRN. This allowed us to expand the screening tool distribution and collection to 3 of 4 of the weekly half-day oncology clinics as well as to meet individually with veterans experiencing high levels of distress. Veterans were flagged as having high distress levels by either the results of their completed screening tool or by referral from a medical oncology physician. We initially established screening in clinics that were sufficiently staffed to ensure that screens were appropriately distributed and reviewed. Patients seen in nonparticipating clinics were referred to outpatient social work, mental health and/or outpatient palliative care according to oncology fellows’ clinical assessments of the patient. All oncology fellows received education about distress screening and methods for referring to supportive care. Our clinic screening program extended from February 2017 through January 2020.

Screening

Program staff screened patients with new cancer diagnoses, then identified patients for follow-up screens. This tracking allowed staff to identify patients with oncology appointments that day and cross-reference patients needing a follow-up screen.

 

 

Following feedback from the clinic nurses, we determined that nurses would provide the distress tool to patients in paper form after they completed their assessment of vitals and waited to be seen by their medical oncologist. The patient would then deliver their completed form to the nurse who would combine it with the patient’s clinic notes for the oncologist to review. Veterans who reported elevated 4-question Patient Health Questionnaire (PHQ-4) scores ≥ 6 were seen immediately by program staff. Veterans were referred to social work or psychiatry services for a same day visit if they endorsed a high level of psychological distress during clinical examination. They were referred for other supportive care services if they were determined to have practical, family, or nutrition unmet distress needs by either the program staff or oncology fellows. Program staff provided guidance to medical oncology fellows for needed referrals including social work, mental health, and palliative care follow ups (eAppendix A available at doi:10.12788/fp.0158).

Veterans referred for supportive care services were contacted by the relevant clinical administrator by phone to schedule an intake; for social work referrals, patients were either seen in a walk-in office located in a colocated building or contacted by a social worker by phone.

Our screening tool was the Coleman Foundation Supportive Oncology Collaborative Screening Tool, compiled from validated instruments. Patients completed this screening tool, which includes the PHQ-4, NCCN problem list concerns, adapted Mini Nutrition Assessment and PROMIS Pain and Fatigue measure (eAppendix B available at doi:10.12788/fp.0158).20-22

We also worked with the VA Computerized Patient Record System (CPRS) to create an electronic template for the screening tool. Completed screening tools were manually entered by the physician, psychologists, or APRN into the CPRS chart.

We analyzed the different supportive care services available at the JBVAMC and noticed that many supportive services were available, yet these services were often separated. Therefore, we created a consult flowsheet to assist oncologists in placing referrals. These supportive care services include mental health services, a cancer support group, home health care, social services, nutrition, physical medicine and rehabilitation, and other specialty services.

Patient Education

The psychology and nursing staff created a patient information bulletin board where patients could access information about supportive services available at JBVAMC. This board required frequent replenishment of handouts because patients consulted the board regularly. Handouts and folders about common clinical issues also were placed in the clinic treatment rooms. We partnered with 2 local cancer support centers, Gilda’s Club and the Cancer Support Center, to make referrals for family members and/or caregivers who would benefit from additional support.

We provided in-service trainings for oncology fellows, including trainings on PTSD and substance abuse and their relationship to cancer care at the VA. These topics were chosen based on the feedback program staff received about perceived knowledge gaps from the oncology fellows. This program allowed for multiple informal conversations between that program staff and oncology fellows about overall patient care. We held trainings with the cancer coordinator and clinical nursing staff on strategies to identify and follow-up on cancer-related distress, and with oncology fellows to review the importance of distress screening and to instruct fellows on instructions for the consult flowsheet.

 

 

Funding

This program was funded by the Chicago-based Coleman Foundation as part of the CSOC. Funding was used to support a portion of time for administrative and clinical work of program staff, as well as data collection and analysis.

Results

We established 3 half-day integrated clinics where patients were screened and referred for services based on supportive oncology needs. In addition to our primary activities to screen and refer veterans, we held multiple educational sessions for colleagues, developed a workflow template, and integrated patient education materials into the clinics.

Screening

Veterans completed 1010 distress screens in 3 of 4 half-day oncology clinics over the 2.5-year project period. Veterans were screened at initial diagnosis and every 3 months, or during changes in their clinical care or disease status. As a result, 579 patients completed screening, with some patients doing several follow-up screens during their care. Integration of palliative care providers and health psychologists was instrumental in facilitating screening in these busy general medical oncology clinics. Most veterans were receptive to completing surveys with few refusing to fill out the survey.23 Medical oncology fellows often used the completed screener to inform their review of systems (by reviewing the Coleman screener Physical and Other Concerns section) and connect with the supportive care staff present in clinic for patient’s identifying severe needs (ie, mental health distress or complex psychosocial needs). Veterans’ rates of distress needs and successfuloutcomes of integration with mental health and social work services have been reported elsewhere.23

fdp03828s_t1.png

The mean (SD) age for veterans in this cohort was 72 (9.5) years. Participants were primarily African American veterans (70%), with mostly advanced disease (Table 1). Participants endorsed elevated distress needs compared with other patient populations screened in Chicago through the CSOC for depressed mood, pain, housing, transportation, and physical, nutrition, and treatment concerns.23 Elevated presence of needs was especially prominent for food, housing and insurance/medical needs; physical concerns; nutrition, and treatment- or care-related concerns. Veterans in this cohort reported extensive financial and housing concerns: 10.4% reported food and housing concerns, 18.6% reported transportation concerns, and 9.0% reported issues paying for medical care or medications (Table 2).20 Anecdotally, many experienced job loss or strain with their cancer diagnosis or were living at the poverty level before their diagnosis.

fdp03828s_t2.png


Social work referrals were often triggered due to transportation barriers to appointments/medication access, and food and/or housing insecurity. Social workers assisted with referrals for housing, transportation, financial reimbursement, on-site or community-based food banks, home health support, familial support, and hospice services. Social work consults increased 166% from 2016 (the year before the program start date) to the end of 2019.  

Based on this increased volume of referrals for social work in our oncology clinics, an oncology-specific social worker was hired at the completion of our program to be based in all 4 half-day oncology clinics in response to results of our quality improvement intervention. The social worker currently sees all patients with a new cancer diagnosis and supports oncology fellows to identify veterans needing a palliative care referral or referrals to other supportive services.

Throughout program implementation, traditional areas of palliative care focus were particularly important as veterans reported significant concerns with understanding their illness (67.4%), wanting to understand their prognosis (71.3%), and having questions about their treatment options (55.1%).20 The palliative care providers spent time educating patients about their disease, coordinating goals of care conversations, promoting patients’ engagement in decision making, and making a large number of referrals to hospice and home health to support veterans at home. 

 

 

Discussion

This project created a successful program to screen veterans for psychosocial distress and triage them to appropriate services. During the project, patients in VA-outpatient oncology clinics reported significant cancer-related distress due to baseline psychosocial needs, changes in emotional and physical functioning, logistical and financial challenges of receiving cancer care, and lack of instrumental support.23

Staff education supported successful buy-in, development and implementation of supportive oncology programs. We used a combination of in-service trainings, online trainings, and handouts to provide evidence for distress screening.24 Highlighting the evidence-base that demonstrates how cancer-related distress screening improves cancer and quality of life outcomes helped to address physician reluctance to accept the additional requirements needed to address veterans’ psychosocial needs and care concerns. To increase buy-in and collaboration among team members and foster heightened understanding between providers and patients, we recommend creating accessible education for all staff levels.

One specific area of education we focused on was primary palliative care, which includes the core competencies of communication and symptom management recommended for generalists and specialists of all disciplines.25 Program staff supported oncology fellows in developing their primary palliative care skills by being available to discuss basic symptom management and communication issues. VA cancer care programs could benefit from ongoing palliative care education of oncology staff to facilitate primary palliative care as well as earlier integration of secondary palliative care when needed.26 Secondary palliative care or care provided directly by the palliative care team assists with complex symptom management or communication issues. For these needs, oncology fellows were encouraged to refer to either the palliative care staff available in one of the half-day clinics or to the outpatient palliative care clinic. As a unique strength, the VA allows veterans to receive concurrent cancer-directed therapy and hospice care, which enables earlier referrals to hospice care and higher quality end-of-life care and emphasizes the need for primary palliative care in oncology.27,28

Integrating supportive oncology team members, such as licensed clinical social worker and psychology interns, was successful. This was modeled on the VA PACT, which focuses on prevention, health promotion, coordination and chronic disease management.29 Social determinants of health have a major impact on health outcomes especially in veteran-specific and African American populations, making screening for distress critical.30-32 The VA Office of Health Equity actively addresses health inequities by supporting initiation of screening programs for social determinants of health, including education, employment, exposure to abuse and violence, food insecurity, housing instability, legal needs, social isolation, transportation needs, and utility needs. This is especially needed for African-American individuals who are not only more likely to experience cancer, but also more likely to be negatively impacted by the consequences of cancer diagnosis/treatment, such as complications related to one’s job security, access to care, adverse effects, and other highly distressing needs.33,34

Our program found that veterans with cancer often had concerns associated with food and housing insecurity, transportation and paying for medication or medical care, and screening allowed health care providers to detect and address these social determinants of health through referrals to VA and community-specific programs. Social workers integrated into VA cancer clinics are uniquely equipped to coordinate distress screening and support continuity of care by virtue of their training, connections to preexisting VA supportive services, and knowledge of community resources. This model could be used in other VA specialty clinics serving veterans with chronic illness and those with high levels of physical frailty.35

Our ability to roll out distress screening was scaffolded by technological integration into existing VA systems (eg, screening results in CPRS and electronic referrals). Screening procedures could have been even more efficient with improved technology (Table 3). For example, technological limitations made it challenging to easily identify patients due for screening, requiring a cumbersome process of tracking, collecting and entering patients’ paper forms. Health care providers seeking to develop a distress screening program should consider investing in technology that allows for identification of patients requiring screening at a predetermined interval, completion of screening via tablet or personal device, integration of screening responses into the electronic health record, and automatic generation of notifications to the treating physician and appropriate support services.

fdp03828s_t3.png


We also established partnerships with community cancer support groups to offer both referral pathways and in-house programming. Veterans’ cancer care programs could benefit from identifying and securing community partnerships to capitalize on readily available low-cost or no-cost options for supportive oncology in the community. Further, as was the case in our program, cancer support centers may be willing to collaborate with VA hospitals to provide services on site (eg, support groups, art therapy). This would extend the reach of these supportive services while allowing VA employees to address the extensive psychosocial needs of individual veterans.

Conclusions

Veterans with cancer benefited from enhanced screening and psychosocial service availability, similar to a PCMHI model. Robust screening programs helped advocate for veterans dealing with the effects of poverty through identification of need and referral to existing VA programs and services quickly and efficiently. Providing comprehensive care within ambulatory cancer clinics can address cancer-related distress and any potential barriers to care in real time. VA hospitals typically offer an array of supportive services to address veterans’ psychosocial needs, yet these services tend to be siloed. Integrated referrals can help to resolve such access barriers. Since many veterans with burdensome cancers are not able to see their VA primary care physician regularly, offering comprehensive care within medical oncology ensures complete and integrated care that includes psychosocial screening.

We believe that this program is an example of a mechanism for oncologists and palliative care clinicians to integrate their care in a way that identifies needs and triages services for vulnerable veterans. As colleagues have written, “it is fundamental to our commitment to veterans that we ensure comparable, high quality care regardless of a veteran’s gender, race, or where they live.”34 Health care providers may underestimate the extensive change a cancer diagnosis can have on a patient’s quality of life. Cancer diagnosis and treatment have a large impact on all individuals, but this impact may be greater for individuals in poverty due to inability to work from home, inflexible work hours, and limited support structures. By creating screening programs with psychosocial integration in oncology clinics such as we have described, we hope to improve access to more equitable care for vulnerable veterans.

Veterans living with cancer need comprehensive assessment that includes supportive psychosocial care. The National Comprehensive Cancer Network (NCCN) and American College of Surgeons Commission on Cancer require accredited cancer centers to evaluate psychosocial distress and provide appropriate triage and treatment for all patients.1-3 Implementing psychosocial distress screening can be difficult because of procedural barriers and time constraints, clinic and supportive care resources, and lack of knowledge about how to access supportive services.

Distress screening protocols must be designed to address the specific needs of each population. To improve screening for cancer-related distress, deliver effective supportive services, and gain agreement on distress screening standards of care, the Coleman Foundation supported development of the Coleman Supportive Oncology Collaborative (CSOC), a project of 135 interdisciplinary health care professionals from 25 Chicago-area cancer care institutions.4

The Jesse Brown US Department of Veterans Affairs (VA) Medical Center (JBVAMC) was chosen to assess cancer-related concerns among veterans using the CSOC screening tool and to improve access to supportive oncology. JBVAMC provides care to approximately 49,000 veterans in Chicago, Illinois, and northwestern Indiana. The JBVAMC patient population includes a large number of veterans with dual diagnoses (co-occurring substance use and mental health disorders) and veterans experiencing homelessness.

Delivering integrated screening and oncologic care that is culture and age appropriate is particularly important for veterans given their unique risk factors. The veteran population is considered vulnerable in terms of health status, psychological functioning, and social context. Veterans who use the VA health system as a principal source of care have poorer health, greater comorbid medical conditions, and an increased risk of mortality and suicide compared with the general population.5,6 Poorer health status in veterans also may relate to old age, low income, poor education, psychological health, and minority race.7-9

Past studies point to unique risk factors for cancer and poor cancer adjustment among veterans, which may complicate cancer treatment and end-of-life/survivorship care. Veteran-specific risk factors include military-related exposures, particularly Agent Orange and morbidity/mortality secondary to comorbid medical and psychiatric conditions (eg, chronic obstructive pulmonary disease, diabetes mellitus, and posttraumatic stress disorder [PTSD]).10-12 Moreover, the geriatric veteran population continues to grow,with increasing rates of cancer that require unique considerations for effective cancer care.13,14 Despite this, there are minimal data to inform best practices and supportive care approaches for veterans with cancer. Lack of guidelines specific to veterans and other populations with increased psychosocial challenges may impede successful cancer care, making distress screening procedures particularly important. This is especially the case for the JBVAMC, which serves primarily African American urban-dwelling veterans who experience high rates of cancer disparities, including increased rates of mortality and increased levels of psychosocial distress.15,16

The goals of this program were to (1) examine levels of psychological, physical, financial, and treatment-related distress in a large sample of urban-dwelling veterans; (2) create a streamlined, sustainable process to screen a large number of veterans receiving cancer care in the outpatient setting and connect them with available supportive services; and (3) educate oncology physicians, nurses, and other staff about cancer-related distress and concerns using in-service trainings and interpersonal interactions to improve patient care. Our program was based on a Primary Care Mental Health Integration (PCMHI) model that embeds health psychologists in general medical clinics to better reach veterans dealing with mental health issues. We tailored for palliative care involvement.

Studies of this model have shown that mental health integration improves access to mental health services and mental health treatment outcomes and has higher patient and provider satisfaction.17 We were also influenced by the construct of the patient aligned care team (PACT) social worker who, in this veteran-centered approach, often functions as a care coordinator. Social work responsibilities include assessment of patients’ stressors including adjusting to the medical conditions, identifying untreated or undertreated mental health or substance abuse issues, economic instability, legal problems, and inadequate housing and transportation, which can often be exacerbated during cancer treatment.18

 

 



We screened for distress-related needs that included mental health concerns, physical needs including uncontrolled symptoms or adverse effects of cancer treatment, physical function complaints (eg, pain and fatigue), nutrition concerns, treatment or care related concerns, family and caregiver needs, along with financial challenges (housing and food) and insurance-related support. The goal of this article is to describe the development and implementation of this VA-specific distress screening program and reflect on the lessons learned for the application of streamlined distress screening and triage in similar settings throughout the VA health system and other similar settings.

Methods

This institutional review board at JBVAMC reviewed and exempted this quality improvement program using the SQUIRE framework.19 It was led by a group of palliative care clinicians, psychologists, and administrators who have worked with the oncology service for many years, primarily in the care of hospitalized patients. Common palliative care services include providing care for patients with serious illness diagnosis through the illness trajectory.

Setting

At the start of this program, we assessed the current clinic workflow to determine how to best screen and assist veterans experiencing distress. We met with team members individually to identify the best method of clinic integration, including attending medical oncologists, medical oncology fellows, psychology interns, oncology nursing staff, the oncology nurse coordinator, and clinic clerks.

The JBVAMC provides cancer care through 4 half-day medical hematology-oncology clinics that serve about 50 patients per half-day clinic. The clinics are staffed by hematology-oncology fellows supervised by hematology-oncology attending physicians, who are affiliated with 2 academic medical centers. These clinics are staffed by 3 registered nurses (RNs) and a licensed practical nurse (LPN) and are adjacent to a chemotherapy infusion clinic with unique nursing staff. The JBVAMC also provides a variety of supportive care services, including extensive mental health and substance use treatment, physical and occupational therapy, acupuncture, nutrition, social work, and housing services. Following our assessment, it was evident that there were a low number of referrals from oncology clinics to supportive care services, mostly due to lack of knowledge of resources and unclear referral procedures.

Based on clinical volume, we determined that our screening program could best be implemented through a stepped approach beginning in one clinic and expanding thereafter. We began by having a palliative care physician and health psychology intern embedded in 1 weekly half-day clinic and a health psychology intern embedded in a second weekly half-day clinic. Our program included 2 health psychology interns (for each academic year of the program) who were supervised by a JBVA health psychologist.

About 15 months after successful integration within the first 2 half-day clinics, we expanded the screening program to staff an additional half-day medical oncology clinic with a palliative care APRN. This allowed us to expand the screening tool distribution and collection to 3 of 4 of the weekly half-day oncology clinics as well as to meet individually with veterans experiencing high levels of distress. Veterans were flagged as having high distress levels by either the results of their completed screening tool or by referral from a medical oncology physician. We initially established screening in clinics that were sufficiently staffed to ensure that screens were appropriately distributed and reviewed. Patients seen in nonparticipating clinics were referred to outpatient social work, mental health and/or outpatient palliative care according to oncology fellows’ clinical assessments of the patient. All oncology fellows received education about distress screening and methods for referring to supportive care. Our clinic screening program extended from February 2017 through January 2020.

Screening

Program staff screened patients with new cancer diagnoses, then identified patients for follow-up screens. This tracking allowed staff to identify patients with oncology appointments that day and cross-reference patients needing a follow-up screen.

 

 

Following feedback from the clinic nurses, we determined that nurses would provide the distress tool to patients in paper form after they completed their assessment of vitals and waited to be seen by their medical oncologist. The patient would then deliver their completed form to the nurse who would combine it with the patient’s clinic notes for the oncologist to review. Veterans who reported elevated 4-question Patient Health Questionnaire (PHQ-4) scores ≥ 6 were seen immediately by program staff. Veterans were referred to social work or psychiatry services for a same day visit if they endorsed a high level of psychological distress during clinical examination. They were referred for other supportive care services if they were determined to have practical, family, or nutrition unmet distress needs by either the program staff or oncology fellows. Program staff provided guidance to medical oncology fellows for needed referrals including social work, mental health, and palliative care follow ups (eAppendix A available at doi:10.12788/fp.0158).

Veterans referred for supportive care services were contacted by the relevant clinical administrator by phone to schedule an intake; for social work referrals, patients were either seen in a walk-in office located in a colocated building or contacted by a social worker by phone.

Our screening tool was the Coleman Foundation Supportive Oncology Collaborative Screening Tool, compiled from validated instruments. Patients completed this screening tool, which includes the PHQ-4, NCCN problem list concerns, adapted Mini Nutrition Assessment and PROMIS Pain and Fatigue measure (eAppendix B available at doi:10.12788/fp.0158).20-22

We also worked with the VA Computerized Patient Record System (CPRS) to create an electronic template for the screening tool. Completed screening tools were manually entered by the physician, psychologists, or APRN into the CPRS chart.

We analyzed the different supportive care services available at the JBVAMC and noticed that many supportive services were available, yet these services were often separated. Therefore, we created a consult flowsheet to assist oncologists in placing referrals. These supportive care services include mental health services, a cancer support group, home health care, social services, nutrition, physical medicine and rehabilitation, and other specialty services.

Patient Education

The psychology and nursing staff created a patient information bulletin board where patients could access information about supportive services available at JBVAMC. This board required frequent replenishment of handouts because patients consulted the board regularly. Handouts and folders about common clinical issues also were placed in the clinic treatment rooms. We partnered with 2 local cancer support centers, Gilda’s Club and the Cancer Support Center, to make referrals for family members and/or caregivers who would benefit from additional support.

We provided in-service trainings for oncology fellows, including trainings on PTSD and substance abuse and their relationship to cancer care at the VA. These topics were chosen based on the feedback program staff received about perceived knowledge gaps from the oncology fellows. This program allowed for multiple informal conversations between that program staff and oncology fellows about overall patient care. We held trainings with the cancer coordinator and clinical nursing staff on strategies to identify and follow-up on cancer-related distress, and with oncology fellows to review the importance of distress screening and to instruct fellows on instructions for the consult flowsheet.

 

 

Funding

This program was funded by the Chicago-based Coleman Foundation as part of the CSOC. Funding was used to support a portion of time for administrative and clinical work of program staff, as well as data collection and analysis.

Results

We established 3 half-day integrated clinics where patients were screened and referred for services based on supportive oncology needs. In addition to our primary activities to screen and refer veterans, we held multiple educational sessions for colleagues, developed a workflow template, and integrated patient education materials into the clinics.

Screening

Veterans completed 1010 distress screens in 3 of 4 half-day oncology clinics over the 2.5-year project period. Veterans were screened at initial diagnosis and every 3 months, or during changes in their clinical care or disease status. As a result, 579 patients completed screening, with some patients doing several follow-up screens during their care. Integration of palliative care providers and health psychologists was instrumental in facilitating screening in these busy general medical oncology clinics. Most veterans were receptive to completing surveys with few refusing to fill out the survey.23 Medical oncology fellows often used the completed screener to inform their review of systems (by reviewing the Coleman screener Physical and Other Concerns section) and connect with the supportive care staff present in clinic for patient’s identifying severe needs (ie, mental health distress or complex psychosocial needs). Veterans’ rates of distress needs and successfuloutcomes of integration with mental health and social work services have been reported elsewhere.23

fdp03828s_t1.png

The mean (SD) age for veterans in this cohort was 72 (9.5) years. Participants were primarily African American veterans (70%), with mostly advanced disease (Table 1). Participants endorsed elevated distress needs compared with other patient populations screened in Chicago through the CSOC for depressed mood, pain, housing, transportation, and physical, nutrition, and treatment concerns.23 Elevated presence of needs was especially prominent for food, housing and insurance/medical needs; physical concerns; nutrition, and treatment- or care-related concerns. Veterans in this cohort reported extensive financial and housing concerns: 10.4% reported food and housing concerns, 18.6% reported transportation concerns, and 9.0% reported issues paying for medical care or medications (Table 2).20 Anecdotally, many experienced job loss or strain with their cancer diagnosis or were living at the poverty level before their diagnosis.

fdp03828s_t2.png


Social work referrals were often triggered due to transportation barriers to appointments/medication access, and food and/or housing insecurity. Social workers assisted with referrals for housing, transportation, financial reimbursement, on-site or community-based food banks, home health support, familial support, and hospice services. Social work consults increased 166% from 2016 (the year before the program start date) to the end of 2019.  

Based on this increased volume of referrals for social work in our oncology clinics, an oncology-specific social worker was hired at the completion of our program to be based in all 4 half-day oncology clinics in response to results of our quality improvement intervention. The social worker currently sees all patients with a new cancer diagnosis and supports oncology fellows to identify veterans needing a palliative care referral or referrals to other supportive services.

Throughout program implementation, traditional areas of palliative care focus were particularly important as veterans reported significant concerns with understanding their illness (67.4%), wanting to understand their prognosis (71.3%), and having questions about their treatment options (55.1%).20 The palliative care providers spent time educating patients about their disease, coordinating goals of care conversations, promoting patients’ engagement in decision making, and making a large number of referrals to hospice and home health to support veterans at home. 

 

 

Discussion

This project created a successful program to screen veterans for psychosocial distress and triage them to appropriate services. During the project, patients in VA-outpatient oncology clinics reported significant cancer-related distress due to baseline psychosocial needs, changes in emotional and physical functioning, logistical and financial challenges of receiving cancer care, and lack of instrumental support.23

Staff education supported successful buy-in, development and implementation of supportive oncology programs. We used a combination of in-service trainings, online trainings, and handouts to provide evidence for distress screening.24 Highlighting the evidence-base that demonstrates how cancer-related distress screening improves cancer and quality of life outcomes helped to address physician reluctance to accept the additional requirements needed to address veterans’ psychosocial needs and care concerns. To increase buy-in and collaboration among team members and foster heightened understanding between providers and patients, we recommend creating accessible education for all staff levels.

One specific area of education we focused on was primary palliative care, which includes the core competencies of communication and symptom management recommended for generalists and specialists of all disciplines.25 Program staff supported oncology fellows in developing their primary palliative care skills by being available to discuss basic symptom management and communication issues. VA cancer care programs could benefit from ongoing palliative care education of oncology staff to facilitate primary palliative care as well as earlier integration of secondary palliative care when needed.26 Secondary palliative care or care provided directly by the palliative care team assists with complex symptom management or communication issues. For these needs, oncology fellows were encouraged to refer to either the palliative care staff available in one of the half-day clinics or to the outpatient palliative care clinic. As a unique strength, the VA allows veterans to receive concurrent cancer-directed therapy and hospice care, which enables earlier referrals to hospice care and higher quality end-of-life care and emphasizes the need for primary palliative care in oncology.27,28

Integrating supportive oncology team members, such as licensed clinical social worker and psychology interns, was successful. This was modeled on the VA PACT, which focuses on prevention, health promotion, coordination and chronic disease management.29 Social determinants of health have a major impact on health outcomes especially in veteran-specific and African American populations, making screening for distress critical.30-32 The VA Office of Health Equity actively addresses health inequities by supporting initiation of screening programs for social determinants of health, including education, employment, exposure to abuse and violence, food insecurity, housing instability, legal needs, social isolation, transportation needs, and utility needs. This is especially needed for African-American individuals who are not only more likely to experience cancer, but also more likely to be negatively impacted by the consequences of cancer diagnosis/treatment, such as complications related to one’s job security, access to care, adverse effects, and other highly distressing needs.33,34

Our program found that veterans with cancer often had concerns associated with food and housing insecurity, transportation and paying for medication or medical care, and screening allowed health care providers to detect and address these social determinants of health through referrals to VA and community-specific programs. Social workers integrated into VA cancer clinics are uniquely equipped to coordinate distress screening and support continuity of care by virtue of their training, connections to preexisting VA supportive services, and knowledge of community resources. This model could be used in other VA specialty clinics serving veterans with chronic illness and those with high levels of physical frailty.35

Our ability to roll out distress screening was scaffolded by technological integration into existing VA systems (eg, screening results in CPRS and electronic referrals). Screening procedures could have been even more efficient with improved technology (Table 3). For example, technological limitations made it challenging to easily identify patients due for screening, requiring a cumbersome process of tracking, collecting and entering patients’ paper forms. Health care providers seeking to develop a distress screening program should consider investing in technology that allows for identification of patients requiring screening at a predetermined interval, completion of screening via tablet or personal device, integration of screening responses into the electronic health record, and automatic generation of notifications to the treating physician and appropriate support services.

fdp03828s_t3.png


We also established partnerships with community cancer support groups to offer both referral pathways and in-house programming. Veterans’ cancer care programs could benefit from identifying and securing community partnerships to capitalize on readily available low-cost or no-cost options for supportive oncology in the community. Further, as was the case in our program, cancer support centers may be willing to collaborate with VA hospitals to provide services on site (eg, support groups, art therapy). This would extend the reach of these supportive services while allowing VA employees to address the extensive psychosocial needs of individual veterans.

Conclusions

Veterans with cancer benefited from enhanced screening and psychosocial service availability, similar to a PCMHI model. Robust screening programs helped advocate for veterans dealing with the effects of poverty through identification of need and referral to existing VA programs and services quickly and efficiently. Providing comprehensive care within ambulatory cancer clinics can address cancer-related distress and any potential barriers to care in real time. VA hospitals typically offer an array of supportive services to address veterans’ psychosocial needs, yet these services tend to be siloed. Integrated referrals can help to resolve such access barriers. Since many veterans with burdensome cancers are not able to see their VA primary care physician regularly, offering comprehensive care within medical oncology ensures complete and integrated care that includes psychosocial screening.

We believe that this program is an example of a mechanism for oncologists and palliative care clinicians to integrate their care in a way that identifies needs and triages services for vulnerable veterans. As colleagues have written, “it is fundamental to our commitment to veterans that we ensure comparable, high quality care regardless of a veteran’s gender, race, or where they live.”34 Health care providers may underestimate the extensive change a cancer diagnosis can have on a patient’s quality of life. Cancer diagnosis and treatment have a large impact on all individuals, but this impact may be greater for individuals in poverty due to inability to work from home, inflexible work hours, and limited support structures. By creating screening programs with psychosocial integration in oncology clinics such as we have described, we hope to improve access to more equitable care for vulnerable veterans.

References

1. National Comprehensive Cancer Network. NCCN guidelines distress management. Version 2.2021. Updated January 5, 2021. Accessed July 8, 2021. http://www.nccn.org/professionals/physician_gls/pdf/distress.pdf

2. American College of Surgeons, Commission on Cancer. Cancer program standards 2012: ensuring patient-centered care. Version 1.2.1. Published 2021. Accessed July 8, 2021. https://www.facs.org/~/media/files/quality%20programs/cancer/coc/programstandards2012.ashx

3. Jacobsen PB, Ransom S. Implementation of NCCN distress management guidelines by member institutions. J Natl Compr Canc Netw. 2007;5(1):99-103. doi:10.6004/jnccn.2007.0010

4. The Coleman Supportive Oncology Collaborative. Training tools. Accessed July 14, 2021. https://www.supportiveoncologycollaborative.org/training-tools

5. Agha Z, Lofgren RP, VanRuiswyk JV, Layde PM. Are patients at Veterans Affairs medical centers sicker? A comparative analysis of health status and medical resource use. Arch Intern Med. 2000;160(21):3252-3257. doi:10.1001/archinte.160.21.3252

6. Bullman T, Schneiderman A, Gradus JL. Relative importance of posttraumatic stress disorder and depression in predicting risk of suicide among a cohort of Vietnam veterans. Suicide Life Threat Behav. 2019;49(3):838-845. doi:10.1111/sltb.12482

7. Kazis LE, Miller DR, Clark J, et al. Health-related quality of life in patients served by the Department of Veterans Affairs: results from the Veterans Health Study. Arch Intern Med. 1998;158(6):626-632. doi:10.1001/archinte.158.6.626

8. O’Toole BI, Marshall RP, Grayson DA, et al. The Australian Vietnam Veterans Health Study: III. Psychological health of Australian Vietnam veterans and its relationship to combat. Int J Epidemiol. 1996;25(2):331-340. doi:10.1093/ije/25.2.331

9. Vincent C, Chamberlain K, Long N. Mental and physical health status in a community sample of New Zealand Vietnam War veterans. Aust J Public Health. 1994;18(1):58-62. doi:10.1111/j.1753-6405.1994.tb00196.x

10. US Department of Veterans Affairs. Veterans’ diseases associated with Agent Orange. Updated June 16, 2021. Accessed July 8, 2021. http://www.publichealth.va.gov/exposures/agentorange/diseases.asp#veterans

11. Hwa KJ, Dua MM, Wren SM, Visser BC. Missing the obvious: psychosocial obstacles in Veterans with hepatocellular carcinoma. HBP (Oxford). 2015;17(12):1124-1129. doi:10.1111/hpb.12508

12. Saha S, Freeman M, Toure J, Tippens KM, Weeks C, Ibrahim S. Racial and ethnic disparities in the VA health care system: a systematic review. J Gen Intern Med. 2008;23(5):654-671. doi:10.1007/s11606-008-0521-4

13. Amaral EFL, Pollard MS, Mendelsohn J, Cefalu M. Current and future demographics of the veteran population, 2014-2024. Popul Rev. 2018;57(1):28-60. doi:10.1353/prv.2018.0002

14. Mohile SG, Dale W, Somerfield MR, et al. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol. 2018;36(22):2326-2347. doi:10.1200/JCO.2018.78.8687

15. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212-236. doi:10.3322/caac.20121

16. Cimino T, Said K, Safier L, Harris H, Kinderman A. Psychosocial distress among oncology patients in the safety net. Psychooncology. 2020;29(11):1927-1935. doi:10.1002/pon.5525

17. Molander R, Hodgkins K, Johnson C, White A, Frazier E, Krahn D. Interprofessional education in patient aligned care team primary care-mental health integration. Fed Pract. 2017;34(6):40-48.

18. Parikh DA, Ragavan M, Dutta R, et al. Financial toxicity of cancer care: an analysis of financial burden in three distinct health care systems [published online ahead of print, 2021 Apr 7]. JCO Oncol Pract. 2021;OP2000890. doi:10.1200/OP.20.00890

19. Ogrinc G, Davies L, Goodman D, Batalden P, Davidoff F, Stevens D. SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): revised publication guidelines from a detailed consensus process. BMJ Qual Saf. 2016;25(12):986-992. doi:10.1136/bmjqs-2015-004411

20. Weldon CB, Gerhart JI, Penedo FJ, et al. Correlates of distress for cancer patients: results from multi-institution use of holistic patient-reported screening tool. J Clin Oncol. 2019;37(15)(suppl):11587-11587. doi:10.1200/JCO.2019.37.15_suppl.11587

21. Kroenke K, Spitzer RL, Williams JB, Löwe B. The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review. Gen Hosp Psychiatry. 2010;32(4):345-359. doi:10.1016/j.genhosppsych.2010.03.006

22. Kaiser MJ, Bauer JM, Ramsch C, et al. Validation of the Mini Nutritional Assessment short-form (MNA-SF): a practical tool for identification of nutritional status. J Nutr Health Aging. 2009;13(9):782-788. doi:10.1007/s12603-009-0214-7

23. Azizoddin DR, Lakin JR, Hauser J, et al. Meeting the guidelines: implementing a distress screening intervention for veterans with cancer. Psychooncology. 2020;29(12):2067-2074. doi:10.1002/pon.5565

24. Carlson LE, Waller A, Mitchell AJ. Screening for distress and unmet needs in patients with cancer: review and recommendations. J Clin Oncol. 2012;30(11):1160-1177. doi:10.1200/JCO.2011.39.5509

25. Quill TE, Abernethy AP. Generalist plus specialist palliative care—creating a more sustainable model. N Engl J Med. 2013;368(13):1173-1175. doi:10.1056/NEJMp1215620

26. Weissman DE, Meier DE. Identifying patients in need of a palliative care assessment in the hospital setting: a consensus report from the Center to Advance Palliative Care. J Palliat Med. 2011;14(1):17-23. doi:10.1089/jpm.2010.0347

27. Kumar P, Wright AA, Hatfield LA, Temel JS, Keating NL. Family perspectives on hospice care experiences of patients with cancer. J Clin Oncol. 2017;35(4):432-439. doi:10.1200/JCO.2016.68.9257

28. Mor V, Joyce NR, Coté DL, et al. The rise of concurrent care for veterans with advanced cancer at the end of life. Cancer. 2016;122(5):782-790. doi:10.1002/cncr.29827

29. US Department of Veterans Affairs. Patient care services: Patient aligned care team (PACT). Updated November 5, 2020. Accessed July 8, 2021. https://www.patientcare.va.gov/primarycare/PACT.asp

30. US Department of Veterans Affairs, Veterans Health Administration. VHA health equity action plan. Published September 27, 2019. Accessed July 8, 2021. https://www.va.gov/HEALTHEQUITY/docs/Health_Equity_Action_Plan_Final_022020.pdf

31. Alcaraz KI, Wiedt TL, Daniels EC, Yabroff KR, Guerra CE, Wender RC. Understanding and addressing social determinants to advance cancer health equity in the United States: a blueprint for practice, research, and policy. CA Cancer J Clin. 2020;70(1):31-46. doi:10.3322/caac.21586

32. Atkins D, Kilbourne A, Lipson L. Health equity research in the Veterans Health Administration: we’ve come far but aren’t there yet. Am J Public Health. 2014;104(suppl 4):S525-526. doi:10.2105/AJPH.2014.302216

33. American Cancer Society. Cancer Facts & Figures for African Americans 2019-2021. Atlanta: American Cancer Society; 2019.

34. Hastert TA, Kirchhoff AC, Banegas MP, et al. Work changes and individual, cancer-related, and work-related predictors of decreased work participation among African American cancer survivors. Cancer Med. 2020;9(23):9168-9177. doi:10.1002/cam4.3512

35. Bekelman DB, Nowels CT, Allen LA, Shakar S, Kutner JS, Matlock DD. Outpatient palliative care for chronic heart failure: a case series. J Palliat Med. 2011;14(7):815-821. doi:10.1089/jpm.2010.050

References

1. National Comprehensive Cancer Network. NCCN guidelines distress management. Version 2.2021. Updated January 5, 2021. Accessed July 8, 2021. http://www.nccn.org/professionals/physician_gls/pdf/distress.pdf

2. American College of Surgeons, Commission on Cancer. Cancer program standards 2012: ensuring patient-centered care. Version 1.2.1. Published 2021. Accessed July 8, 2021. https://www.facs.org/~/media/files/quality%20programs/cancer/coc/programstandards2012.ashx

3. Jacobsen PB, Ransom S. Implementation of NCCN distress management guidelines by member institutions. J Natl Compr Canc Netw. 2007;5(1):99-103. doi:10.6004/jnccn.2007.0010

4. The Coleman Supportive Oncology Collaborative. Training tools. Accessed July 14, 2021. https://www.supportiveoncologycollaborative.org/training-tools

5. Agha Z, Lofgren RP, VanRuiswyk JV, Layde PM. Are patients at Veterans Affairs medical centers sicker? A comparative analysis of health status and medical resource use. Arch Intern Med. 2000;160(21):3252-3257. doi:10.1001/archinte.160.21.3252

6. Bullman T, Schneiderman A, Gradus JL. Relative importance of posttraumatic stress disorder and depression in predicting risk of suicide among a cohort of Vietnam veterans. Suicide Life Threat Behav. 2019;49(3):838-845. doi:10.1111/sltb.12482

7. Kazis LE, Miller DR, Clark J, et al. Health-related quality of life in patients served by the Department of Veterans Affairs: results from the Veterans Health Study. Arch Intern Med. 1998;158(6):626-632. doi:10.1001/archinte.158.6.626

8. O’Toole BI, Marshall RP, Grayson DA, et al. The Australian Vietnam Veterans Health Study: III. Psychological health of Australian Vietnam veterans and its relationship to combat. Int J Epidemiol. 1996;25(2):331-340. doi:10.1093/ije/25.2.331

9. Vincent C, Chamberlain K, Long N. Mental and physical health status in a community sample of New Zealand Vietnam War veterans. Aust J Public Health. 1994;18(1):58-62. doi:10.1111/j.1753-6405.1994.tb00196.x

10. US Department of Veterans Affairs. Veterans’ diseases associated with Agent Orange. Updated June 16, 2021. Accessed July 8, 2021. http://www.publichealth.va.gov/exposures/agentorange/diseases.asp#veterans

11. Hwa KJ, Dua MM, Wren SM, Visser BC. Missing the obvious: psychosocial obstacles in Veterans with hepatocellular carcinoma. HBP (Oxford). 2015;17(12):1124-1129. doi:10.1111/hpb.12508

12. Saha S, Freeman M, Toure J, Tippens KM, Weeks C, Ibrahim S. Racial and ethnic disparities in the VA health care system: a systematic review. J Gen Intern Med. 2008;23(5):654-671. doi:10.1007/s11606-008-0521-4

13. Amaral EFL, Pollard MS, Mendelsohn J, Cefalu M. Current and future demographics of the veteran population, 2014-2024. Popul Rev. 2018;57(1):28-60. doi:10.1353/prv.2018.0002

14. Mohile SG, Dale W, Somerfield MR, et al. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol. 2018;36(22):2326-2347. doi:10.1200/JCO.2018.78.8687

15. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212-236. doi:10.3322/caac.20121

16. Cimino T, Said K, Safier L, Harris H, Kinderman A. Psychosocial distress among oncology patients in the safety net. Psychooncology. 2020;29(11):1927-1935. doi:10.1002/pon.5525

17. Molander R, Hodgkins K, Johnson C, White A, Frazier E, Krahn D. Interprofessional education in patient aligned care team primary care-mental health integration. Fed Pract. 2017;34(6):40-48.

18. Parikh DA, Ragavan M, Dutta R, et al. Financial toxicity of cancer care: an analysis of financial burden in three distinct health care systems [published online ahead of print, 2021 Apr 7]. JCO Oncol Pract. 2021;OP2000890. doi:10.1200/OP.20.00890

19. Ogrinc G, Davies L, Goodman D, Batalden P, Davidoff F, Stevens D. SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): revised publication guidelines from a detailed consensus process. BMJ Qual Saf. 2016;25(12):986-992. doi:10.1136/bmjqs-2015-004411

20. Weldon CB, Gerhart JI, Penedo FJ, et al. Correlates of distress for cancer patients: results from multi-institution use of holistic patient-reported screening tool. J Clin Oncol. 2019;37(15)(suppl):11587-11587. doi:10.1200/JCO.2019.37.15_suppl.11587

21. Kroenke K, Spitzer RL, Williams JB, Löwe B. The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review. Gen Hosp Psychiatry. 2010;32(4):345-359. doi:10.1016/j.genhosppsych.2010.03.006

22. Kaiser MJ, Bauer JM, Ramsch C, et al. Validation of the Mini Nutritional Assessment short-form (MNA-SF): a practical tool for identification of nutritional status. J Nutr Health Aging. 2009;13(9):782-788. doi:10.1007/s12603-009-0214-7

23. Azizoddin DR, Lakin JR, Hauser J, et al. Meeting the guidelines: implementing a distress screening intervention for veterans with cancer. Psychooncology. 2020;29(12):2067-2074. doi:10.1002/pon.5565

24. Carlson LE, Waller A, Mitchell AJ. Screening for distress and unmet needs in patients with cancer: review and recommendations. J Clin Oncol. 2012;30(11):1160-1177. doi:10.1200/JCO.2011.39.5509

25. Quill TE, Abernethy AP. Generalist plus specialist palliative care—creating a more sustainable model. N Engl J Med. 2013;368(13):1173-1175. doi:10.1056/NEJMp1215620

26. Weissman DE, Meier DE. Identifying patients in need of a palliative care assessment in the hospital setting: a consensus report from the Center to Advance Palliative Care. J Palliat Med. 2011;14(1):17-23. doi:10.1089/jpm.2010.0347

27. Kumar P, Wright AA, Hatfield LA, Temel JS, Keating NL. Family perspectives on hospice care experiences of patients with cancer. J Clin Oncol. 2017;35(4):432-439. doi:10.1200/JCO.2016.68.9257

28. Mor V, Joyce NR, Coté DL, et al. The rise of concurrent care for veterans with advanced cancer at the end of life. Cancer. 2016;122(5):782-790. doi:10.1002/cncr.29827

29. US Department of Veterans Affairs. Patient care services: Patient aligned care team (PACT). Updated November 5, 2020. Accessed July 8, 2021. https://www.patientcare.va.gov/primarycare/PACT.asp

30. US Department of Veterans Affairs, Veterans Health Administration. VHA health equity action plan. Published September 27, 2019. Accessed July 8, 2021. https://www.va.gov/HEALTHEQUITY/docs/Health_Equity_Action_Plan_Final_022020.pdf

31. Alcaraz KI, Wiedt TL, Daniels EC, Yabroff KR, Guerra CE, Wender RC. Understanding and addressing social determinants to advance cancer health equity in the United States: a blueprint for practice, research, and policy. CA Cancer J Clin. 2020;70(1):31-46. doi:10.3322/caac.21586

32. Atkins D, Kilbourne A, Lipson L. Health equity research in the Veterans Health Administration: we’ve come far but aren’t there yet. Am J Public Health. 2014;104(suppl 4):S525-526. doi:10.2105/AJPH.2014.302216

33. American Cancer Society. Cancer Facts & Figures for African Americans 2019-2021. Atlanta: American Cancer Society; 2019.

34. Hastert TA, Kirchhoff AC, Banegas MP, et al. Work changes and individual, cancer-related, and work-related predictors of decreased work participation among African American cancer survivors. Cancer Med. 2020;9(23):9168-9177. doi:10.1002/cam4.3512

35. Bekelman DB, Nowels CT, Allen LA, Shakar S, Kutner JS, Matlock DD. Outpatient palliative care for chronic heart failure: a case series. J Palliat Med. 2011;14(7):815-821. doi:10.1089/jpm.2010.050

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The Worst and the Best of 2019

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Readers may recall that at the end of each calendar as opposed to fiscal year—I know it is hard to believe time exists outside the Federal system—Federal Practitioner publishes my ethics-focused version of the familiar year-end roundup. This year I am reversing the typical order of most annual rankings by putting the worst first for 2 morally salient reasons.

The first is that, sadly, it is almost always easier to identify multiple incidents that compete ignominiously for the “worst” of federal health care. Even more disappointing, it is comparatively difficult to find stories for the “best” that are of the same scale and scope as the bad news. This is not to say that every day there are not individual narratives of courage and compassion reported in US Department of Defense, US Public Health Service, and US Department of Veterans Affairs (VA), and hundreds more unsung heroes.

The second reason is that as human beings our psychology is such that we gravitate toward the worst things more powerfully and persistently than we do the best. This is in part why it is more difficult to find uplifting stories and why the demoralizing ones affect us so strongly. In an exhaustive review of the subject, psychologists Roy Baumeister and colleagues conclude that,

When equal measures of good and bad are present, however, the psychological effects of bad ones outweigh those of the good ones. This may in fact be a general principle or law of psychological phenomena, possibly reflecting the innate predispositions of the psyche or at least reflecting the almost inevitable adaptation of each individual to the exigencies of daily life.2

I am thus saving the best for last in the hope that it will be more memorable and impactful than the worst.

Unique to this year’s look-back, both the negative and the positive accounts come from the domain of end-of-life care. And unlike prior reviews where the lack of administrative vigilance and professional competence affected hundreds of patients, families, and staff, each of this year’s incidents involve a single patient.

An incident that occurred in September 2019 at a VA Community Living Center (CLC) in Georgia stood out in infamy apart from all others. It was the report of a veteran in a VA nursing home who had been bitten more than 100 times by ants crawling all over his room. He died shortly afterward. In a scene out of a horror movie tapping into the most primeval human fears, his daughter Laquana Ross described her father, a Vietnam Air Force veteran with cancer, to media and VA officials in graphic terms. “I understand mistakes happen,” she said. “I’ve had ants. But he was bit by ants two days in a row. They feasted on him.”3

In this new era of holding its senior executive service accountable, the outraged chair of the Senate Veterans Affairs Committee demanded that heads roll, and the VA acted rapidly to comply.4 The VA Central Office placed the network director on administrative leave, reassigned the chief medical officer, and initiated quality and safety reviews as well as an administrative investigative board to scrutinize how the parent Atlanta VA medical center managed the situation. In total, 9 officials connected to the incident were placed on leave. The VA apologized, with VA Secretary Robert Wilke zeroing in on the core values involved in the tragedy, “This is about basic humanity and dignity,” he said. “I don’t care what steps were taken to address the issues. We did not treat a vet with the dignity that he and his family deserved.”5 Yet it was the veteran’s daughter, with unbelievable charity, who asked the most crucial question that must be answered within the framework of a just culture if similar tragedies are not to occur in the future, “I know the staff, without a shadow of doubt, respected my dad and even loved him,” Ross said. “But what’s their ability to assess situations and fix things?”3

To begin to give Ms. Ross the answer she deserves, we must understand that the antithesis of love is not hate but indifference; of compassion, it is not cruelty but coldness. A true just culture reserves individual blame for those who have ill-will and adopts a systems perspective of organizational improvement toward most other types of errors.6 This means that the deplorable conditions in the CLC cannot be charged to the failure of a single staff member to fulfil their obligations but to collective collapse at many levels of the organization. Just culture is ethically laudable and far superior to the history in federal service of capricious punishment or institutional apathy that far too often were the default reactions to media exposures or congressional ire. Justice, though necessary, is not sufficient to achieve virtue. Those who work in health care also must be inspired to offer mercy, kindness, and compassion, especially in our most sacred privilege to provide care of the dying.

The best of 2019 illustrates this distinction movingly. This account also involves a Vietnam veteran, this time a Marine also dying of cancer, which happened just about a month after the earlier report. To be transparent it occurred at my home VA medical center in New Mexico. I was peripherally involved in the case as a consultant but had no role in the wondrous things that transpired. The last wish of a patient dying in the hospice unit on campus was to see his beloved dog who had been taken to the local city animal shelter when he was hospitalized because he had no friends or family to look after the companion animal. A social worker on the palliative care team called the animal shelter and explained the patient did not have much time left but wanted to see his dog before he died. Working together with support from facility leadership, shelter workers brought the dog to visit with the patient for an entire day while hospice staff cried with joy and sadness.7

As the epigraph for this editorial from Dame Cicely Saunders, the founder of the modern hospice movement, says, the difference between unspeakable pain and meaningful suffering can be measured in the depth of compassion caregivers show to the dying. It is this quality of mercy that in one case condemns, and in the other praises, us all as health care and administrative professionals in the service of our country. Baumeister and colleagues suggest that the human tendency to magnify the bad and minimize the good in everyday myopia may in a wider vision actually be a reason for hope:

It may be that humans and animals show heightened awareness of and responded more quickly to negative information because it signals a need for change. Hence, the adaptiveness of self-regulation partly lies in the organism’s ability to detect when response modifications are necessary and when they are unnecessary. Moreover, the lessons learned from bad events should ideally be retained permanently so that the same dangers or costs are not encountered repeatedly. Meanwhile, good events (such as those that provide a feeling of satisfaction and contentment) should ideally wear off so that the organism is motivated to continue searching for more and better outcomes.2

Let us all take this lesson into our work in 2020 so that when it comes time to write this column next year in the chilling cold of late autumn there will be more stories of light than darkness from which to choose.

References

1. Saunders C. The management of patients in the terminal stage. In: Raven R, ed. Cancer, Vol. 6. London: Butterworth and Company; 1960:403-417.

2. Baumeister RF, Bratslavasky E, Finkenauer C, Vohs KD. Bad is stronger than good. Rev General Psychol. 2001;5(4);323-370.

3. Knowles H. ‘They feasted on him’: Ants at VA nursing home bite a veteran 100 times before his death, daughter says. Washington Post. September 17, 2019. https://www.washingtonpost.com/health/2019/09/13/they-feasted-him-ants-va-nursing-home-bit-veteran-times-before-his-death-daughter-says. Accessed November 25, 2019.

4. Axelrod T. GOP senator presses VA after veteran reportedly bitten by ants in nursing home. https://thehill.com/homenews/senate/461196-gop-senator-presses-va-after-veteran-reportedly-bitten-by-ants-at-nursing. Published September 12, 2019. Accessed November 25, 2019.

5. Kime P. Nine VA leaders, staff placed on leave amid anti-bite scandal. https://www.military.com/daily-news/2019/09/17/nine-va-leaders-staff-placed-leave-amid-ant-bite-scandal.html. Published September 17, 2019. Accessed November 22, 2019.

6. Sculli GL, Hemphill R. Culture of safety and just culture. https://www.patientsafety.va.gov/docs/joe/just_culture_2013_tagged.pdf. Accessed November 22, 2019.

7. Hughes M. A Vietnam veteran in hospice care got to see his beloved dog one last time. https://www.cnn.com/2019/10/21/us/veteran-dying-wish-dog-trnd/index.html. Published October 21, 2019. Accessed November 22, 2019.

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Related Articles

Readers may recall that at the end of each calendar as opposed to fiscal year—I know it is hard to believe time exists outside the Federal system—Federal Practitioner publishes my ethics-focused version of the familiar year-end roundup. This year I am reversing the typical order of most annual rankings by putting the worst first for 2 morally salient reasons.

The first is that, sadly, it is almost always easier to identify multiple incidents that compete ignominiously for the “worst” of federal health care. Even more disappointing, it is comparatively difficult to find stories for the “best” that are of the same scale and scope as the bad news. This is not to say that every day there are not individual narratives of courage and compassion reported in US Department of Defense, US Public Health Service, and US Department of Veterans Affairs (VA), and hundreds more unsung heroes.

The second reason is that as human beings our psychology is such that we gravitate toward the worst things more powerfully and persistently than we do the best. This is in part why it is more difficult to find uplifting stories and why the demoralizing ones affect us so strongly. In an exhaustive review of the subject, psychologists Roy Baumeister and colleagues conclude that,

When equal measures of good and bad are present, however, the psychological effects of bad ones outweigh those of the good ones. This may in fact be a general principle or law of psychological phenomena, possibly reflecting the innate predispositions of the psyche or at least reflecting the almost inevitable adaptation of each individual to the exigencies of daily life.2

I am thus saving the best for last in the hope that it will be more memorable and impactful than the worst.

Unique to this year’s look-back, both the negative and the positive accounts come from the domain of end-of-life care. And unlike prior reviews where the lack of administrative vigilance and professional competence affected hundreds of patients, families, and staff, each of this year’s incidents involve a single patient.

An incident that occurred in September 2019 at a VA Community Living Center (CLC) in Georgia stood out in infamy apart from all others. It was the report of a veteran in a VA nursing home who had been bitten more than 100 times by ants crawling all over his room. He died shortly afterward. In a scene out of a horror movie tapping into the most primeval human fears, his daughter Laquana Ross described her father, a Vietnam Air Force veteran with cancer, to media and VA officials in graphic terms. “I understand mistakes happen,” she said. “I’ve had ants. But he was bit by ants two days in a row. They feasted on him.”3

In this new era of holding its senior executive service accountable, the outraged chair of the Senate Veterans Affairs Committee demanded that heads roll, and the VA acted rapidly to comply.4 The VA Central Office placed the network director on administrative leave, reassigned the chief medical officer, and initiated quality and safety reviews as well as an administrative investigative board to scrutinize how the parent Atlanta VA medical center managed the situation. In total, 9 officials connected to the incident were placed on leave. The VA apologized, with VA Secretary Robert Wilke zeroing in on the core values involved in the tragedy, “This is about basic humanity and dignity,” he said. “I don’t care what steps were taken to address the issues. We did not treat a vet with the dignity that he and his family deserved.”5 Yet it was the veteran’s daughter, with unbelievable charity, who asked the most crucial question that must be answered within the framework of a just culture if similar tragedies are not to occur in the future, “I know the staff, without a shadow of doubt, respected my dad and even loved him,” Ross said. “But what’s their ability to assess situations and fix things?”3

To begin to give Ms. Ross the answer she deserves, we must understand that the antithesis of love is not hate but indifference; of compassion, it is not cruelty but coldness. A true just culture reserves individual blame for those who have ill-will and adopts a systems perspective of organizational improvement toward most other types of errors.6 This means that the deplorable conditions in the CLC cannot be charged to the failure of a single staff member to fulfil their obligations but to collective collapse at many levels of the organization. Just culture is ethically laudable and far superior to the history in federal service of capricious punishment or institutional apathy that far too often were the default reactions to media exposures or congressional ire. Justice, though necessary, is not sufficient to achieve virtue. Those who work in health care also must be inspired to offer mercy, kindness, and compassion, especially in our most sacred privilege to provide care of the dying.

The best of 2019 illustrates this distinction movingly. This account also involves a Vietnam veteran, this time a Marine also dying of cancer, which happened just about a month after the earlier report. To be transparent it occurred at my home VA medical center in New Mexico. I was peripherally involved in the case as a consultant but had no role in the wondrous things that transpired. The last wish of a patient dying in the hospice unit on campus was to see his beloved dog who had been taken to the local city animal shelter when he was hospitalized because he had no friends or family to look after the companion animal. A social worker on the palliative care team called the animal shelter and explained the patient did not have much time left but wanted to see his dog before he died. Working together with support from facility leadership, shelter workers brought the dog to visit with the patient for an entire day while hospice staff cried with joy and sadness.7

As the epigraph for this editorial from Dame Cicely Saunders, the founder of the modern hospice movement, says, the difference between unspeakable pain and meaningful suffering can be measured in the depth of compassion caregivers show to the dying. It is this quality of mercy that in one case condemns, and in the other praises, us all as health care and administrative professionals in the service of our country. Baumeister and colleagues suggest that the human tendency to magnify the bad and minimize the good in everyday myopia may in a wider vision actually be a reason for hope:

It may be that humans and animals show heightened awareness of and responded more quickly to negative information because it signals a need for change. Hence, the adaptiveness of self-regulation partly lies in the organism’s ability to detect when response modifications are necessary and when they are unnecessary. Moreover, the lessons learned from bad events should ideally be retained permanently so that the same dangers or costs are not encountered repeatedly. Meanwhile, good events (such as those that provide a feeling of satisfaction and contentment) should ideally wear off so that the organism is motivated to continue searching for more and better outcomes.2

Let us all take this lesson into our work in 2020 so that when it comes time to write this column next year in the chilling cold of late autumn there will be more stories of light than darkness from which to choose.

Readers may recall that at the end of each calendar as opposed to fiscal year—I know it is hard to believe time exists outside the Federal system—Federal Practitioner publishes my ethics-focused version of the familiar year-end roundup. This year I am reversing the typical order of most annual rankings by putting the worst first for 2 morally salient reasons.

The first is that, sadly, it is almost always easier to identify multiple incidents that compete ignominiously for the “worst” of federal health care. Even more disappointing, it is comparatively difficult to find stories for the “best” that are of the same scale and scope as the bad news. This is not to say that every day there are not individual narratives of courage and compassion reported in US Department of Defense, US Public Health Service, and US Department of Veterans Affairs (VA), and hundreds more unsung heroes.

The second reason is that as human beings our psychology is such that we gravitate toward the worst things more powerfully and persistently than we do the best. This is in part why it is more difficult to find uplifting stories and why the demoralizing ones affect us so strongly. In an exhaustive review of the subject, psychologists Roy Baumeister and colleagues conclude that,

When equal measures of good and bad are present, however, the psychological effects of bad ones outweigh those of the good ones. This may in fact be a general principle or law of psychological phenomena, possibly reflecting the innate predispositions of the psyche or at least reflecting the almost inevitable adaptation of each individual to the exigencies of daily life.2

I am thus saving the best for last in the hope that it will be more memorable and impactful than the worst.

Unique to this year’s look-back, both the negative and the positive accounts come from the domain of end-of-life care. And unlike prior reviews where the lack of administrative vigilance and professional competence affected hundreds of patients, families, and staff, each of this year’s incidents involve a single patient.

An incident that occurred in September 2019 at a VA Community Living Center (CLC) in Georgia stood out in infamy apart from all others. It was the report of a veteran in a VA nursing home who had been bitten more than 100 times by ants crawling all over his room. He died shortly afterward. In a scene out of a horror movie tapping into the most primeval human fears, his daughter Laquana Ross described her father, a Vietnam Air Force veteran with cancer, to media and VA officials in graphic terms. “I understand mistakes happen,” she said. “I’ve had ants. But he was bit by ants two days in a row. They feasted on him.”3

In this new era of holding its senior executive service accountable, the outraged chair of the Senate Veterans Affairs Committee demanded that heads roll, and the VA acted rapidly to comply.4 The VA Central Office placed the network director on administrative leave, reassigned the chief medical officer, and initiated quality and safety reviews as well as an administrative investigative board to scrutinize how the parent Atlanta VA medical center managed the situation. In total, 9 officials connected to the incident were placed on leave. The VA apologized, with VA Secretary Robert Wilke zeroing in on the core values involved in the tragedy, “This is about basic humanity and dignity,” he said. “I don’t care what steps were taken to address the issues. We did not treat a vet with the dignity that he and his family deserved.”5 Yet it was the veteran’s daughter, with unbelievable charity, who asked the most crucial question that must be answered within the framework of a just culture if similar tragedies are not to occur in the future, “I know the staff, without a shadow of doubt, respected my dad and even loved him,” Ross said. “But what’s their ability to assess situations and fix things?”3

To begin to give Ms. Ross the answer she deserves, we must understand that the antithesis of love is not hate but indifference; of compassion, it is not cruelty but coldness. A true just culture reserves individual blame for those who have ill-will and adopts a systems perspective of organizational improvement toward most other types of errors.6 This means that the deplorable conditions in the CLC cannot be charged to the failure of a single staff member to fulfil their obligations but to collective collapse at many levels of the organization. Just culture is ethically laudable and far superior to the history in federal service of capricious punishment or institutional apathy that far too often were the default reactions to media exposures or congressional ire. Justice, though necessary, is not sufficient to achieve virtue. Those who work in health care also must be inspired to offer mercy, kindness, and compassion, especially in our most sacred privilege to provide care of the dying.

The best of 2019 illustrates this distinction movingly. This account also involves a Vietnam veteran, this time a Marine also dying of cancer, which happened just about a month after the earlier report. To be transparent it occurred at my home VA medical center in New Mexico. I was peripherally involved in the case as a consultant but had no role in the wondrous things that transpired. The last wish of a patient dying in the hospice unit on campus was to see his beloved dog who had been taken to the local city animal shelter when he was hospitalized because he had no friends or family to look after the companion animal. A social worker on the palliative care team called the animal shelter and explained the patient did not have much time left but wanted to see his dog before he died. Working together with support from facility leadership, shelter workers brought the dog to visit with the patient for an entire day while hospice staff cried with joy and sadness.7

As the epigraph for this editorial from Dame Cicely Saunders, the founder of the modern hospice movement, says, the difference between unspeakable pain and meaningful suffering can be measured in the depth of compassion caregivers show to the dying. It is this quality of mercy that in one case condemns, and in the other praises, us all as health care and administrative professionals in the service of our country. Baumeister and colleagues suggest that the human tendency to magnify the bad and minimize the good in everyday myopia may in a wider vision actually be a reason for hope:

It may be that humans and animals show heightened awareness of and responded more quickly to negative information because it signals a need for change. Hence, the adaptiveness of self-regulation partly lies in the organism’s ability to detect when response modifications are necessary and when they are unnecessary. Moreover, the lessons learned from bad events should ideally be retained permanently so that the same dangers or costs are not encountered repeatedly. Meanwhile, good events (such as those that provide a feeling of satisfaction and contentment) should ideally wear off so that the organism is motivated to continue searching for more and better outcomes.2

Let us all take this lesson into our work in 2020 so that when it comes time to write this column next year in the chilling cold of late autumn there will be more stories of light than darkness from which to choose.

References

1. Saunders C. The management of patients in the terminal stage. In: Raven R, ed. Cancer, Vol. 6. London: Butterworth and Company; 1960:403-417.

2. Baumeister RF, Bratslavasky E, Finkenauer C, Vohs KD. Bad is stronger than good. Rev General Psychol. 2001;5(4);323-370.

3. Knowles H. ‘They feasted on him’: Ants at VA nursing home bite a veteran 100 times before his death, daughter says. Washington Post. September 17, 2019. https://www.washingtonpost.com/health/2019/09/13/they-feasted-him-ants-va-nursing-home-bit-veteran-times-before-his-death-daughter-says. Accessed November 25, 2019.

4. Axelrod T. GOP senator presses VA after veteran reportedly bitten by ants in nursing home. https://thehill.com/homenews/senate/461196-gop-senator-presses-va-after-veteran-reportedly-bitten-by-ants-at-nursing. Published September 12, 2019. Accessed November 25, 2019.

5. Kime P. Nine VA leaders, staff placed on leave amid anti-bite scandal. https://www.military.com/daily-news/2019/09/17/nine-va-leaders-staff-placed-leave-amid-ant-bite-scandal.html. Published September 17, 2019. Accessed November 22, 2019.

6. Sculli GL, Hemphill R. Culture of safety and just culture. https://www.patientsafety.va.gov/docs/joe/just_culture_2013_tagged.pdf. Accessed November 22, 2019.

7. Hughes M. A Vietnam veteran in hospice care got to see his beloved dog one last time. https://www.cnn.com/2019/10/21/us/veteran-dying-wish-dog-trnd/index.html. Published October 21, 2019. Accessed November 22, 2019.

References

1. Saunders C. The management of patients in the terminal stage. In: Raven R, ed. Cancer, Vol. 6. London: Butterworth and Company; 1960:403-417.

2. Baumeister RF, Bratslavasky E, Finkenauer C, Vohs KD. Bad is stronger than good. Rev General Psychol. 2001;5(4);323-370.

3. Knowles H. ‘They feasted on him’: Ants at VA nursing home bite a veteran 100 times before his death, daughter says. Washington Post. September 17, 2019. https://www.washingtonpost.com/health/2019/09/13/they-feasted-him-ants-va-nursing-home-bit-veteran-times-before-his-death-daughter-says. Accessed November 25, 2019.

4. Axelrod T. GOP senator presses VA after veteran reportedly bitten by ants in nursing home. https://thehill.com/homenews/senate/461196-gop-senator-presses-va-after-veteran-reportedly-bitten-by-ants-at-nursing. Published September 12, 2019. Accessed November 25, 2019.

5. Kime P. Nine VA leaders, staff placed on leave amid anti-bite scandal. https://www.military.com/daily-news/2019/09/17/nine-va-leaders-staff-placed-leave-amid-ant-bite-scandal.html. Published September 17, 2019. Accessed November 22, 2019.

6. Sculli GL, Hemphill R. Culture of safety and just culture. https://www.patientsafety.va.gov/docs/joe/just_culture_2013_tagged.pdf. Accessed November 22, 2019.

7. Hughes M. A Vietnam veteran in hospice care got to see his beloved dog one last time. https://www.cnn.com/2019/10/21/us/veteran-dying-wish-dog-trnd/index.html. Published October 21, 2019. Accessed November 22, 2019.

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Palliative Care: Ave atque vale

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Thu, 03/28/2019 - 14:31

Dame Cicely Saunders, the founder of the modern hospice movement, gave me this advice early in my palliative medicine career: “Never stop thanking those who help you along.” There are many to thank and much to be thankful for since the palliative care series in ACS Surgery News commenced in September 2012. The series proposal was enthusiastically endorsed by the then Editor, Layton F. Rikkers, and promptly launched owing to the personal interest of the first series editor, Elizabeth Wood. Their strong advocacy continues with the current co-editors, Karen Deveney and Tyler Hughes and the ever-watchful eye and assistance of managing editor, Therese Borden.

Dunn_Geoffrey_P_PA_web.jpg
%3Cp%3EDr.%20Geoffrey%20P.%20Dunn%3C%2Fp%3E

The purpose of the series was to keep the concept of surgical palliative care visible to the Fellowship through the reflections of surgeons and surgeons in training, while commenting on timely issues relevant to palliative care. We were fortunate to be coupled with Peter Angelos’s astute, widely read series on ethics. Our respective areas of interest widely overlap and have come into sharper focus for the surgical community over roughly the same period of time.

It was my hope that our contributions on palliative care would emulate the qualities and quality of Dr. Angelos’s articles – commentaries that would be of interest to the entire spectrum of surgical specialties and venues of practice. While the ethics column focused on doing the right thing, we would be focused on how to do the right thing in our response to suffering. Thanks are due to ACS Surgery News for its consistent representation of the new specialty of surgical palliative care on a par with other surgical specialties. It is culturally significant that this advocacy included strong support from laypeople.

I have been gratified and am thankful for the frequent uplifting discussions and debates triggered by palliative care columns in well-thumbed copies of ACS Surgery News in our OR lounge.

I didn’t have to look far to find inspiration and direction for the advocacy of palliative care in surgical practice. My father, David D. Dunn, MD, FACS, who represented everything noble, humane, and sensible in surgery, was a community-based general surgeon practicing in an era when the “general surgeon” performed thoracic, vascular, trauma, pediatric, and plastic surgery in addition to abdominal surgery. He had extensive experience with responding to suffering in a fundamentally affirmative way. He founded the first hospice in our community to meet the needs of a proud, cantankerous, elderly man septic with a gangrenous leg who declined amputation. He also witnessed mass suffering when he commanded a field hospital tasked with the resuscitation of survivors of a liberated Nazi concentration camp. The experience could have easily destroyed him from the resulting cynicism about humanity or PTSD. But instead he claimed he learned the first step in responding to mass calamity is the resuscitation of hope. He recalled a rescued physician who was given a clean lab coat and a stethoscope even before he was given his first real meal in years. He believed the hallmarks of steadfastness and non-abandonment are the core of the surgical persona. Late in his long life that ended just before this series launched, he observed, “It’s all palliative when you get right down to it. You [meaning the next generation] have to figure out the details and do your bit.”

The future is bright to “figure out the details and do your bit” for surgeons interested in palliative care. A number of young surgeons and surgeons in training, some who have done fellowships and become ABS certified in Hospice and Palliative Medicine, have had the opportunity to be heard and their specialty field be recognized by the greater surgical community because of ACS Surgery News.

I once asked a physically and emotionally exhausted family member of an “ICU to nowhere” patient why he thought patients get “stuck” in the ICU. He answered eloquently, “People just don’t think they should die.” The prevailing biophysical and increasingly “corporate” framework for care of the seriously ill is handicapped by its inability to effectively respond to the psychological and spiritual questions raised by this comment. Inability of surgeons to reconcile personal moral imperatives with big data and corporate medicine may be contributing to burnout, one of the most frequently acknowledged problems for surgeons today. Disease management alone, even if completely evidence-based, will not break this type of gridlock nor leave patients, families, and practitioners with a lasting sense of support. We will always need a broader framework that gives us a lens through which we can see and a voice with which we can answer the serious concerns that trouble our seriously ill patients and their families. I thank ACS Surgery News for conscientiously providing us a lens and a voice over the past 7 years.

 

Dr. Dunn was formerly the medical director of the palliative care consultation service at the University of Pittsburgh Medical Center Hamot in Erie, Pa., and Chair of the ACS Committee on Surgical Palliative Care.

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Dame Cicely Saunders, the founder of the modern hospice movement, gave me this advice early in my palliative medicine career: “Never stop thanking those who help you along.” There are many to thank and much to be thankful for since the palliative care series in ACS Surgery News commenced in September 2012. The series proposal was enthusiastically endorsed by the then Editor, Layton F. Rikkers, and promptly launched owing to the personal interest of the first series editor, Elizabeth Wood. Their strong advocacy continues with the current co-editors, Karen Deveney and Tyler Hughes and the ever-watchful eye and assistance of managing editor, Therese Borden.

Dunn_Geoffrey_P_PA_web.jpg
%3Cp%3EDr.%20Geoffrey%20P.%20Dunn%3C%2Fp%3E

The purpose of the series was to keep the concept of surgical palliative care visible to the Fellowship through the reflections of surgeons and surgeons in training, while commenting on timely issues relevant to palliative care. We were fortunate to be coupled with Peter Angelos’s astute, widely read series on ethics. Our respective areas of interest widely overlap and have come into sharper focus for the surgical community over roughly the same period of time.

It was my hope that our contributions on palliative care would emulate the qualities and quality of Dr. Angelos’s articles – commentaries that would be of interest to the entire spectrum of surgical specialties and venues of practice. While the ethics column focused on doing the right thing, we would be focused on how to do the right thing in our response to suffering. Thanks are due to ACS Surgery News for its consistent representation of the new specialty of surgical palliative care on a par with other surgical specialties. It is culturally significant that this advocacy included strong support from laypeople.

I have been gratified and am thankful for the frequent uplifting discussions and debates triggered by palliative care columns in well-thumbed copies of ACS Surgery News in our OR lounge.

I didn’t have to look far to find inspiration and direction for the advocacy of palliative care in surgical practice. My father, David D. Dunn, MD, FACS, who represented everything noble, humane, and sensible in surgery, was a community-based general surgeon practicing in an era when the “general surgeon” performed thoracic, vascular, trauma, pediatric, and plastic surgery in addition to abdominal surgery. He had extensive experience with responding to suffering in a fundamentally affirmative way. He founded the first hospice in our community to meet the needs of a proud, cantankerous, elderly man septic with a gangrenous leg who declined amputation. He also witnessed mass suffering when he commanded a field hospital tasked with the resuscitation of survivors of a liberated Nazi concentration camp. The experience could have easily destroyed him from the resulting cynicism about humanity or PTSD. But instead he claimed he learned the first step in responding to mass calamity is the resuscitation of hope. He recalled a rescued physician who was given a clean lab coat and a stethoscope even before he was given his first real meal in years. He believed the hallmarks of steadfastness and non-abandonment are the core of the surgical persona. Late in his long life that ended just before this series launched, he observed, “It’s all palliative when you get right down to it. You [meaning the next generation] have to figure out the details and do your bit.”

The future is bright to “figure out the details and do your bit” for surgeons interested in palliative care. A number of young surgeons and surgeons in training, some who have done fellowships and become ABS certified in Hospice and Palliative Medicine, have had the opportunity to be heard and their specialty field be recognized by the greater surgical community because of ACS Surgery News.

I once asked a physically and emotionally exhausted family member of an “ICU to nowhere” patient why he thought patients get “stuck” in the ICU. He answered eloquently, “People just don’t think they should die.” The prevailing biophysical and increasingly “corporate” framework for care of the seriously ill is handicapped by its inability to effectively respond to the psychological and spiritual questions raised by this comment. Inability of surgeons to reconcile personal moral imperatives with big data and corporate medicine may be contributing to burnout, one of the most frequently acknowledged problems for surgeons today. Disease management alone, even if completely evidence-based, will not break this type of gridlock nor leave patients, families, and practitioners with a lasting sense of support. We will always need a broader framework that gives us a lens through which we can see and a voice with which we can answer the serious concerns that trouble our seriously ill patients and their families. I thank ACS Surgery News for conscientiously providing us a lens and a voice over the past 7 years.

 

Dr. Dunn was formerly the medical director of the palliative care consultation service at the University of Pittsburgh Medical Center Hamot in Erie, Pa., and Chair of the ACS Committee on Surgical Palliative Care.

Dame Cicely Saunders, the founder of the modern hospice movement, gave me this advice early in my palliative medicine career: “Never stop thanking those who help you along.” There are many to thank and much to be thankful for since the palliative care series in ACS Surgery News commenced in September 2012. The series proposal was enthusiastically endorsed by the then Editor, Layton F. Rikkers, and promptly launched owing to the personal interest of the first series editor, Elizabeth Wood. Their strong advocacy continues with the current co-editors, Karen Deveney and Tyler Hughes and the ever-watchful eye and assistance of managing editor, Therese Borden.

Dunn_Geoffrey_P_PA_web.jpg
%3Cp%3EDr.%20Geoffrey%20P.%20Dunn%3C%2Fp%3E

The purpose of the series was to keep the concept of surgical palliative care visible to the Fellowship through the reflections of surgeons and surgeons in training, while commenting on timely issues relevant to palliative care. We were fortunate to be coupled with Peter Angelos’s astute, widely read series on ethics. Our respective areas of interest widely overlap and have come into sharper focus for the surgical community over roughly the same period of time.

It was my hope that our contributions on palliative care would emulate the qualities and quality of Dr. Angelos’s articles – commentaries that would be of interest to the entire spectrum of surgical specialties and venues of practice. While the ethics column focused on doing the right thing, we would be focused on how to do the right thing in our response to suffering. Thanks are due to ACS Surgery News for its consistent representation of the new specialty of surgical palliative care on a par with other surgical specialties. It is culturally significant that this advocacy included strong support from laypeople.

I have been gratified and am thankful for the frequent uplifting discussions and debates triggered by palliative care columns in well-thumbed copies of ACS Surgery News in our OR lounge.

I didn’t have to look far to find inspiration and direction for the advocacy of palliative care in surgical practice. My father, David D. Dunn, MD, FACS, who represented everything noble, humane, and sensible in surgery, was a community-based general surgeon practicing in an era when the “general surgeon” performed thoracic, vascular, trauma, pediatric, and plastic surgery in addition to abdominal surgery. He had extensive experience with responding to suffering in a fundamentally affirmative way. He founded the first hospice in our community to meet the needs of a proud, cantankerous, elderly man septic with a gangrenous leg who declined amputation. He also witnessed mass suffering when he commanded a field hospital tasked with the resuscitation of survivors of a liberated Nazi concentration camp. The experience could have easily destroyed him from the resulting cynicism about humanity or PTSD. But instead he claimed he learned the first step in responding to mass calamity is the resuscitation of hope. He recalled a rescued physician who was given a clean lab coat and a stethoscope even before he was given his first real meal in years. He believed the hallmarks of steadfastness and non-abandonment are the core of the surgical persona. Late in his long life that ended just before this series launched, he observed, “It’s all palliative when you get right down to it. You [meaning the next generation] have to figure out the details and do your bit.”

The future is bright to “figure out the details and do your bit” for surgeons interested in palliative care. A number of young surgeons and surgeons in training, some who have done fellowships and become ABS certified in Hospice and Palliative Medicine, have had the opportunity to be heard and their specialty field be recognized by the greater surgical community because of ACS Surgery News.

I once asked a physically and emotionally exhausted family member of an “ICU to nowhere” patient why he thought patients get “stuck” in the ICU. He answered eloquently, “People just don’t think they should die.” The prevailing biophysical and increasingly “corporate” framework for care of the seriously ill is handicapped by its inability to effectively respond to the psychological and spiritual questions raised by this comment. Inability of surgeons to reconcile personal moral imperatives with big data and corporate medicine may be contributing to burnout, one of the most frequently acknowledged problems for surgeons today. Disease management alone, even if completely evidence-based, will not break this type of gridlock nor leave patients, families, and practitioners with a lasting sense of support. We will always need a broader framework that gives us a lens through which we can see and a voice with which we can answer the serious concerns that trouble our seriously ill patients and their families. I thank ACS Surgery News for conscientiously providing us a lens and a voice over the past 7 years.

 

Dr. Dunn was formerly the medical director of the palliative care consultation service at the University of Pittsburgh Medical Center Hamot in Erie, Pa., and Chair of the ACS Committee on Surgical Palliative Care.

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Surgical palliative care – 20 years on

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Wed, 01/02/2019 - 10:14

It was a banner year in 1998 for the moral and ethical evolution of the College. That year saw the release of its Statement of Principles of End-of-Life Care, a seminal document for the emerging framework of surgical palliative care and the first light of the work of my colleague, Peter Angelos, MD, FACS, which did much to make made ethics a less arcane element of surgical practice. These developments followed the 1997 Clinical Congress during which the College joined the then-active national debate about physician-assisted suicide.

Dunn_Geoffrey_P_PA_web.jpg
%3Cp%3EDr.%20Geoffrey%20P.%20Dunn%3C%2Fp%3E

The national debate eventually culminated with the U.S. Supreme Court’s two 1997 rulings that physician-assisted suicide is not a protected liberty interest under the Constitution. These rulings in Vacco v. Quill and Washington v. Glucksberg deferred to the states the legalization of physician-assisted suicide.

Kill the suffering, not the patient

It was ironic that the College’s attention to surgical palliative care started, literally, with a dead end. The 1997 symposium’s focus on physician-assisted suicide revealed how little there was in the surgeon’s toolbox to assist seriously ill patients and their families. At this well-attended event with a distinguished panel of surgeons and ethicists moderated by the late Thomas Krizek, MD, FACS, I heard fear of death, fear of suffering, and fear of our helplessness as practitioners in the face of our patients’ deaths. The debate was about control, not the effective response to the many species of suffering encountered in surgical practice.

Hospice care and the nascent concept of palliative care were acknowledged by both sides of the debate as beneficial but as distinctly apart from surgery. The need for improved palliative care was the one unifying idea that emerged from that day’s discussion. All sides seemed to agree that striving to mitigate suffering during the course of any serious illness would be preferable to allowing it to continue unabated until silencing it with deliberate death as a last resort. The ensuing challenge for surgeons would be the reconciliation of cure and palliation, each so much a part of surgical history, especially in the past 200 years. This would prove to be a tall order as surgeons had done such a tidy job separating these two priorities without even realizing it since the second World War. Nothing less than the soul of surgery (and medicine) would be at stake from the relentless technocratic “progress” that threatened to swallow health care and so many other aspects of our culture – a culture that perhaps has been too intoxicated by the individual “pursuit of life, liberty, and happiness” while overlooking the suffering of one’s neighbor.

Recent evidence of burnout raises the possibility that we surgeons have internalized this conflict. Because of our sacred fellowship in healing, are we now, as we were 20 years ago, in the midst of a new spiritual crisis? As the operative repertoire and our professional status become increasingly transient we will be compelled to ground our identities in something more fulfilling and enduring.

 

 

Hope in fellowship

Now, as in 1998, there is hope. Hope lies in our fellowship. The focus of palliative care as understood by surgeons has broadened considerably, encouraged by the gradual public acceptance of palliative approaches to care extending beyond hospice care and the generally favorable experiences surgeons have had with palliative care teams, some of which have been directed by surgeons. There are now dozens of surgeons currently certified in Hospice and Palliative Medicine by the American Board of Surgery who are much more skilled in palliative care than anyone practicing in 1998. The ABS’s decision (2006) to offer certification in Hospice and Palliative Medicine was, in itself, an indication of how far things had progressed since 1998.

Several challenges to contemporary surgery will benefit from the growing reservoir of palliative care expertise such as enhanced communication skill, opioid management, and burnout. The concept of shared decision making is only one example. The multidimensional understanding of suffering, a cardinal principle of palliative philosophy, could transform the current dilemma of “What do we do about opioids?” to the scientific and social research question, “What should be done with opioid receptors and countless other receptors that shape the pain experience?” And lastly, the current postgraduate educational focus on communication and burnout indicate a readiness for introspection and fellowship by surgeons, a necessary prerequisite in meeting any existential or spiritual challenge to our art.

We have come a long way in 20 years but there are still miles to go before we sleep.

Dr. Dunn was formerly the medical director of the palliative care consultation service at the University of Pittsburgh Medical Center Hamot in Erie, Pa., and Chair of the ACS Committee on Surgical Palliative Care.

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It was a banner year in 1998 for the moral and ethical evolution of the College. That year saw the release of its Statement of Principles of End-of-Life Care, a seminal document for the emerging framework of surgical palliative care and the first light of the work of my colleague, Peter Angelos, MD, FACS, which did much to make made ethics a less arcane element of surgical practice. These developments followed the 1997 Clinical Congress during which the College joined the then-active national debate about physician-assisted suicide.

Dunn_Geoffrey_P_PA_web.jpg
%3Cp%3EDr.%20Geoffrey%20P.%20Dunn%3C%2Fp%3E

The national debate eventually culminated with the U.S. Supreme Court’s two 1997 rulings that physician-assisted suicide is not a protected liberty interest under the Constitution. These rulings in Vacco v. Quill and Washington v. Glucksberg deferred to the states the legalization of physician-assisted suicide.

Kill the suffering, not the patient

It was ironic that the College’s attention to surgical palliative care started, literally, with a dead end. The 1997 symposium’s focus on physician-assisted suicide revealed how little there was in the surgeon’s toolbox to assist seriously ill patients and their families. At this well-attended event with a distinguished panel of surgeons and ethicists moderated by the late Thomas Krizek, MD, FACS, I heard fear of death, fear of suffering, and fear of our helplessness as practitioners in the face of our patients’ deaths. The debate was about control, not the effective response to the many species of suffering encountered in surgical practice.

Hospice care and the nascent concept of palliative care were acknowledged by both sides of the debate as beneficial but as distinctly apart from surgery. The need for improved palliative care was the one unifying idea that emerged from that day’s discussion. All sides seemed to agree that striving to mitigate suffering during the course of any serious illness would be preferable to allowing it to continue unabated until silencing it with deliberate death as a last resort. The ensuing challenge for surgeons would be the reconciliation of cure and palliation, each so much a part of surgical history, especially in the past 200 years. This would prove to be a tall order as surgeons had done such a tidy job separating these two priorities without even realizing it since the second World War. Nothing less than the soul of surgery (and medicine) would be at stake from the relentless technocratic “progress” that threatened to swallow health care and so many other aspects of our culture – a culture that perhaps has been too intoxicated by the individual “pursuit of life, liberty, and happiness” while overlooking the suffering of one’s neighbor.

Recent evidence of burnout raises the possibility that we surgeons have internalized this conflict. Because of our sacred fellowship in healing, are we now, as we were 20 years ago, in the midst of a new spiritual crisis? As the operative repertoire and our professional status become increasingly transient we will be compelled to ground our identities in something more fulfilling and enduring.

 

 

Hope in fellowship

Now, as in 1998, there is hope. Hope lies in our fellowship. The focus of palliative care as understood by surgeons has broadened considerably, encouraged by the gradual public acceptance of palliative approaches to care extending beyond hospice care and the generally favorable experiences surgeons have had with palliative care teams, some of which have been directed by surgeons. There are now dozens of surgeons currently certified in Hospice and Palliative Medicine by the American Board of Surgery who are much more skilled in palliative care than anyone practicing in 1998. The ABS’s decision (2006) to offer certification in Hospice and Palliative Medicine was, in itself, an indication of how far things had progressed since 1998.

Several challenges to contemporary surgery will benefit from the growing reservoir of palliative care expertise such as enhanced communication skill, opioid management, and burnout. The concept of shared decision making is only one example. The multidimensional understanding of suffering, a cardinal principle of palliative philosophy, could transform the current dilemma of “What do we do about opioids?” to the scientific and social research question, “What should be done with opioid receptors and countless other receptors that shape the pain experience?” And lastly, the current postgraduate educational focus on communication and burnout indicate a readiness for introspection and fellowship by surgeons, a necessary prerequisite in meeting any existential or spiritual challenge to our art.

We have come a long way in 20 years but there are still miles to go before we sleep.

Dr. Dunn was formerly the medical director of the palliative care consultation service at the University of Pittsburgh Medical Center Hamot in Erie, Pa., and Chair of the ACS Committee on Surgical Palliative Care.

It was a banner year in 1998 for the moral and ethical evolution of the College. That year saw the release of its Statement of Principles of End-of-Life Care, a seminal document for the emerging framework of surgical palliative care and the first light of the work of my colleague, Peter Angelos, MD, FACS, which did much to make made ethics a less arcane element of surgical practice. These developments followed the 1997 Clinical Congress during which the College joined the then-active national debate about physician-assisted suicide.

Dunn_Geoffrey_P_PA_web.jpg
%3Cp%3EDr.%20Geoffrey%20P.%20Dunn%3C%2Fp%3E

The national debate eventually culminated with the U.S. Supreme Court’s two 1997 rulings that physician-assisted suicide is not a protected liberty interest under the Constitution. These rulings in Vacco v. Quill and Washington v. Glucksberg deferred to the states the legalization of physician-assisted suicide.

Kill the suffering, not the patient

It was ironic that the College’s attention to surgical palliative care started, literally, with a dead end. The 1997 symposium’s focus on physician-assisted suicide revealed how little there was in the surgeon’s toolbox to assist seriously ill patients and their families. At this well-attended event with a distinguished panel of surgeons and ethicists moderated by the late Thomas Krizek, MD, FACS, I heard fear of death, fear of suffering, and fear of our helplessness as practitioners in the face of our patients’ deaths. The debate was about control, not the effective response to the many species of suffering encountered in surgical practice.

Hospice care and the nascent concept of palliative care were acknowledged by both sides of the debate as beneficial but as distinctly apart from surgery. The need for improved palliative care was the one unifying idea that emerged from that day’s discussion. All sides seemed to agree that striving to mitigate suffering during the course of any serious illness would be preferable to allowing it to continue unabated until silencing it with deliberate death as a last resort. The ensuing challenge for surgeons would be the reconciliation of cure and palliation, each so much a part of surgical history, especially in the past 200 years. This would prove to be a tall order as surgeons had done such a tidy job separating these two priorities without even realizing it since the second World War. Nothing less than the soul of surgery (and medicine) would be at stake from the relentless technocratic “progress” that threatened to swallow health care and so many other aspects of our culture – a culture that perhaps has been too intoxicated by the individual “pursuit of life, liberty, and happiness” while overlooking the suffering of one’s neighbor.

Recent evidence of burnout raises the possibility that we surgeons have internalized this conflict. Because of our sacred fellowship in healing, are we now, as we were 20 years ago, in the midst of a new spiritual crisis? As the operative repertoire and our professional status become increasingly transient we will be compelled to ground our identities in something more fulfilling and enduring.

 

 

Hope in fellowship

Now, as in 1998, there is hope. Hope lies in our fellowship. The focus of palliative care as understood by surgeons has broadened considerably, encouraged by the gradual public acceptance of palliative approaches to care extending beyond hospice care and the generally favorable experiences surgeons have had with palliative care teams, some of which have been directed by surgeons. There are now dozens of surgeons currently certified in Hospice and Palliative Medicine by the American Board of Surgery who are much more skilled in palliative care than anyone practicing in 1998. The ABS’s decision (2006) to offer certification in Hospice and Palliative Medicine was, in itself, an indication of how far things had progressed since 1998.

Several challenges to contemporary surgery will benefit from the growing reservoir of palliative care expertise such as enhanced communication skill, opioid management, and burnout. The concept of shared decision making is only one example. The multidimensional understanding of suffering, a cardinal principle of palliative philosophy, could transform the current dilemma of “What do we do about opioids?” to the scientific and social research question, “What should be done with opioid receptors and countless other receptors that shape the pain experience?” And lastly, the current postgraduate educational focus on communication and burnout indicate a readiness for introspection and fellowship by surgeons, a necessary prerequisite in meeting any existential or spiritual challenge to our art.

We have come a long way in 20 years but there are still miles to go before we sleep.

Dr. Dunn was formerly the medical director of the palliative care consultation service at the University of Pittsburgh Medical Center Hamot in Erie, Pa., and Chair of the ACS Committee on Surgical Palliative Care.

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Depression Screening and Treatment: A Missed Opportunity in Lung Cancer Care (FULL)

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Depression Screening and Treatment: A Missed Opportunity in Lung Cancer Care
The integrated VA system is well positioned to be a leader in depression screening and treatment, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources.

About Research in Context

In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

Although depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.1-3 These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.4-8 This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes.

In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.9-11 During treatment, depression can amplify physical symptoms and interfere with effective coping.12,13

Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.14 Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.3 This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.15

Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.16,17

Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.18 These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.19 The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective.

Special Considerations for Veterans

There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.20-22 According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.23 However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.24 In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.25,26 A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.27

 

 

Depression Screening and Treatment

Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.11,28,29 Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.28 Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.28 These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment.

In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.30 Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.30

Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.

Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.31 Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.3

Conclusion

Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorshi —ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer.

The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings.

 

 

Overall, there is minimal evidence that depression treatment can improve lung cancer survival; however, the lack of high-quality studies is a considerable limitation. Given the significant impact of depression on survival among patients with lung cancer, additional funding and resources are urgently needed to combat this debilitating comorbid disease.

Acknowledgments
This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.

 

Click here to read the digital edition. 

References

1. Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients. JAMA. 1983;249(6):751-757.

2. Walker J, Holm Hansen C, Martin P, et al. Prevalence of depression in adults with cancer: a systematic review. Ann Oncol. 2013;24(4):895-900.

3. Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

4. Linden W, Vodermaier A, Mackenzie R, Greig D. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord. 2012;141(2-3):343-351.

5. Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr. 2004;(32):57-71.

6. Brown Johnson CG, Brodsky JL, Cataldo JK. Lung cancer stigma, anxiety, depression, and quality of life. J Psychosoc Oncol. 2014;32(1):59-73.

7. Cataldo JK, Jahan TM, Pongquan VL. Lung cancer stigma, depression, and quality of life among ever and never smokers. Eur J Oncol Nurs. 2012;16(3):264-269.

8. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2010. https://seer.cancer.gov/archive/csr/1975_2010/. Revised February 21, 2014. Accessed July 12, 2017.

9. Li M, Boquiren V, Lo C, et al. Depression and anxiety in supportive oncology. In: Davis M, Feyer P, Ortner P, Zimmermann C, eds. Supportive Oncology. 1st ed. Philadelphia, PA: Elsevier; 2011:528-540.

10. Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology. 2010;19(7):734-741.

11. Lazenby M, Ercolano E, Grant M, Holland JC, Jacobsen PB, McCorkle R. Supporting Commission on Cancer-mandated psychosocial distress screening with implementation strategies. J Oncol Pract. 2015;11(3):e413-e420.

12. Mystakidou K, Tsilika E, Parpa E, Katsouda E, Galanos A, Vlahos L. Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference. Cancer Nurs. 2006;29(5):400-405.

13. Passik SD, Dugan W, McDonald MV, Rosenfeld B, Theobald DE, Edgerton S. Oncologists’ recognition of depression in their patients with cancer. J Clin Oncol. 1998;16(4):1594-1600.

14. Rahuma M, Kamel M, Nasar A, et al. Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population based analysis. Am J Respir Crit Care Med. 2017;195:A6730.

15. Sullivan DR, Ganzini L, Duckart JP, et al. Treatment receipt and outcomes among lung cancer patients with depression. Clin Oncol (R Coll Radiol). 2014;26(1):25-31.

16. Merckaert I, Libert Y, Messin S, Milani M, Slachmuylder JL, Razavi D. Cancer patients’ desire for psychological support: prevalence and implications for screening patients psychological needs. Psychooncology. 2010;19(2):141-149.

17. Harrison JD, Young JM, Price MA, Butow PN, Solomon MJ. What are the unmet supportive care needs of people with cancer? A systematic review. Support Care Cancer. 2009;17(8):1117-1128.

18. Wu HS, Harden JK. Symptom burden and quality of life in survivorship: a review of the literature. Cancer Nurs. 2015;38(1):E29-E54.

19. Mols F, Husson O, Roukema JA, van de Poll-Franse LV. Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry. J Cancer Surviv. 2013;7(3):484-492.

20. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004;351(1):13-22.

21. Fortney JC, Curran GM, Hunt JB, et al. Prevalence of probable mental disorders and help-seeking behaviors among veteran and non-veteran community college students. Gen Hosp Psychiatry. 2016;38:99-104.

22. Pickett T, Rothman D, Crawford EF, Brancu M, Fairbank JA, Kudler HS. Mental health among military personnel and veterans. N C Med J. 2015;76(5):299-306.

23. U.S. Department of Veterans Affairs, Veterans Health Administration. One in ten older vets is depressed. https://www.va.gov/health/NewsFeatures/20110624a.asp. Updated April 17, 2015. Accessed July 12, 2017.

24. Fontana A, Rosenheck R. Treatment-seeking veterans of Iraq and Afghanistan: comparison with veterans of previous wars. J Nerv Ment Dis. 2008;196(7):513-521.

25. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry. 2000;61(suppl 5):4-12; discussion, 13-14.

26. Kartha A, Brower V, Saitz R, Samet JH, Keane TM, Liebschutz J. The impact of trauma exposure and post-traumatic stress disorder on healthcare utilization among primary care patients. Med Care. 2008;46(4):388-393.

27. National Cancer Institute. Cancer-related post-traumatic stress (PDQ®)–Patient version. https://www.cancer.gov/about-cancer/coping/survivorship/new-normal/ptsd-pdq. Updated July 7, 2015. Accessed July 12, 2017.

28. Andersen BL, DeRubeis RJ, Berman BS, et al; American Society of Clinical Oncology. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32(15):1605-1619.

29. Howell D, Keller-Olaman S, Oliver TK, et al. A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue. Curr Oncol. 2013;20(3):e233-e246.

30. Kroenke K, Wu J, Bair MJ, Krebs EE, Damush TM, Tu W. Reciprocal relationship between pain and depression: a 12-month longitudinal analysis in primary care. J Pain. 2011;12(9):964-973.

31. Walker J, Hansen CH, Martin P, et al; SMaRT (Symptom Management Research Trials) Oncology-3 Team. Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT oncology-3): a multicentre randomised controlled trial in patients with lung cancer. Lancet Oncol. 2014;15(10):1168-1176.

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Dr. Sullivan is an investigator, and Dr. Teo is a core investigator, both in the HSR&D Center to Improve Veteran Involvement in Care at VA Portland Health Care System in Oregon. Dr. Sullivan is an assistant professor in the Department of Medicine, in the Division of Pulmonary and Critical Care Medicine, and Dr. Teo is an assistant professor in the Department of Psychiatry and School of Public Health, both at Oregon Health & Science University in Portland.

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Dr. Sullivan is an investigator, and Dr. Teo is a core investigator, both in the HSR&D Center to Improve Veteran Involvement in Care at VA Portland Health Care System in Oregon. Dr. Sullivan is an assistant professor in the Department of Medicine, in the Division of Pulmonary and Critical Care Medicine, and Dr. Teo is an assistant professor in the Department of Psychiatry and School of Public Health, both at Oregon Health & Science University in Portland.

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The integrated VA system is well positioned to be a leader in depression screening and treatment, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources.
The integrated VA system is well positioned to be a leader in depression screening and treatment, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources.

About Research in Context

In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

Although depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.1-3 These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.4-8 This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes.

In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.9-11 During treatment, depression can amplify physical symptoms and interfere with effective coping.12,13

Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.14 Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.3 This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.15

Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.16,17

Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.18 These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.19 The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective.

Special Considerations for Veterans

There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.20-22 According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.23 However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.24 In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.25,26 A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.27

 

 

Depression Screening and Treatment

Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.11,28,29 Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.28 Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.28 These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment.

In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.30 Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.30

Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.

Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.31 Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.3

Conclusion

Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorshi —ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer.

The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings.

 

 

Overall, there is minimal evidence that depression treatment can improve lung cancer survival; however, the lack of high-quality studies is a considerable limitation. Given the significant impact of depression on survival among patients with lung cancer, additional funding and resources are urgently needed to combat this debilitating comorbid disease.

Acknowledgments
This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.

 

Click here to read the digital edition. 

About Research in Context

In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

Although depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.1-3 These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.4-8 This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes.

In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.9-11 During treatment, depression can amplify physical symptoms and interfere with effective coping.12,13

Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.14 Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.3 This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.15

Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.16,17

Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.18 These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.19 The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective.

Special Considerations for Veterans

There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.20-22 According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.23 However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.24 In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.25,26 A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.27

 

 

Depression Screening and Treatment

Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.11,28,29 Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.28 Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.28 These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment.

In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.30 Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.30

Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.

Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.31 Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.3

Conclusion

Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorshi —ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer.

The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings.

 

 

Overall, there is minimal evidence that depression treatment can improve lung cancer survival; however, the lack of high-quality studies is a considerable limitation. Given the significant impact of depression on survival among patients with lung cancer, additional funding and resources are urgently needed to combat this debilitating comorbid disease.

Acknowledgments
This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.

 

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References

1. Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients. JAMA. 1983;249(6):751-757.

2. Walker J, Holm Hansen C, Martin P, et al. Prevalence of depression in adults with cancer: a systematic review. Ann Oncol. 2013;24(4):895-900.

3. Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

4. Linden W, Vodermaier A, Mackenzie R, Greig D. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord. 2012;141(2-3):343-351.

5. Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr. 2004;(32):57-71.

6. Brown Johnson CG, Brodsky JL, Cataldo JK. Lung cancer stigma, anxiety, depression, and quality of life. J Psychosoc Oncol. 2014;32(1):59-73.

7. Cataldo JK, Jahan TM, Pongquan VL. Lung cancer stigma, depression, and quality of life among ever and never smokers. Eur J Oncol Nurs. 2012;16(3):264-269.

8. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2010. https://seer.cancer.gov/archive/csr/1975_2010/. Revised February 21, 2014. Accessed July 12, 2017.

9. Li M, Boquiren V, Lo C, et al. Depression and anxiety in supportive oncology. In: Davis M, Feyer P, Ortner P, Zimmermann C, eds. Supportive Oncology. 1st ed. Philadelphia, PA: Elsevier; 2011:528-540.

10. Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology. 2010;19(7):734-741.

11. Lazenby M, Ercolano E, Grant M, Holland JC, Jacobsen PB, McCorkle R. Supporting Commission on Cancer-mandated psychosocial distress screening with implementation strategies. J Oncol Pract. 2015;11(3):e413-e420.

12. Mystakidou K, Tsilika E, Parpa E, Katsouda E, Galanos A, Vlahos L. Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference. Cancer Nurs. 2006;29(5):400-405.

13. Passik SD, Dugan W, McDonald MV, Rosenfeld B, Theobald DE, Edgerton S. Oncologists’ recognition of depression in their patients with cancer. J Clin Oncol. 1998;16(4):1594-1600.

14. Rahuma M, Kamel M, Nasar A, et al. Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population based analysis. Am J Respir Crit Care Med. 2017;195:A6730.

15. Sullivan DR, Ganzini L, Duckart JP, et al. Treatment receipt and outcomes among lung cancer patients with depression. Clin Oncol (R Coll Radiol). 2014;26(1):25-31.

16. Merckaert I, Libert Y, Messin S, Milani M, Slachmuylder JL, Razavi D. Cancer patients’ desire for psychological support: prevalence and implications for screening patients psychological needs. Psychooncology. 2010;19(2):141-149.

17. Harrison JD, Young JM, Price MA, Butow PN, Solomon MJ. What are the unmet supportive care needs of people with cancer? A systematic review. Support Care Cancer. 2009;17(8):1117-1128.

18. Wu HS, Harden JK. Symptom burden and quality of life in survivorship: a review of the literature. Cancer Nurs. 2015;38(1):E29-E54.

19. Mols F, Husson O, Roukema JA, van de Poll-Franse LV. Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry. J Cancer Surviv. 2013;7(3):484-492.

20. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004;351(1):13-22.

21. Fortney JC, Curran GM, Hunt JB, et al. Prevalence of probable mental disorders and help-seeking behaviors among veteran and non-veteran community college students. Gen Hosp Psychiatry. 2016;38:99-104.

22. Pickett T, Rothman D, Crawford EF, Brancu M, Fairbank JA, Kudler HS. Mental health among military personnel and veterans. N C Med J. 2015;76(5):299-306.

23. U.S. Department of Veterans Affairs, Veterans Health Administration. One in ten older vets is depressed. https://www.va.gov/health/NewsFeatures/20110624a.asp. Updated April 17, 2015. Accessed July 12, 2017.

24. Fontana A, Rosenheck R. Treatment-seeking veterans of Iraq and Afghanistan: comparison with veterans of previous wars. J Nerv Ment Dis. 2008;196(7):513-521.

25. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry. 2000;61(suppl 5):4-12; discussion, 13-14.

26. Kartha A, Brower V, Saitz R, Samet JH, Keane TM, Liebschutz J. The impact of trauma exposure and post-traumatic stress disorder on healthcare utilization among primary care patients. Med Care. 2008;46(4):388-393.

27. National Cancer Institute. Cancer-related post-traumatic stress (PDQ®)–Patient version. https://www.cancer.gov/about-cancer/coping/survivorship/new-normal/ptsd-pdq. Updated July 7, 2015. Accessed July 12, 2017.

28. Andersen BL, DeRubeis RJ, Berman BS, et al; American Society of Clinical Oncology. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32(15):1605-1619.

29. Howell D, Keller-Olaman S, Oliver TK, et al. A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue. Curr Oncol. 2013;20(3):e233-e246.

30. Kroenke K, Wu J, Bair MJ, Krebs EE, Damush TM, Tu W. Reciprocal relationship between pain and depression: a 12-month longitudinal analysis in primary care. J Pain. 2011;12(9):964-973.

31. Walker J, Hansen CH, Martin P, et al; SMaRT (Symptom Management Research Trials) Oncology-3 Team. Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT oncology-3): a multicentre randomised controlled trial in patients with lung cancer. Lancet Oncol. 2014;15(10):1168-1176.

References

1. Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients. JAMA. 1983;249(6):751-757.

2. Walker J, Holm Hansen C, Martin P, et al. Prevalence of depression in adults with cancer: a systematic review. Ann Oncol. 2013;24(4):895-900.

3. Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

4. Linden W, Vodermaier A, Mackenzie R, Greig D. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord. 2012;141(2-3):343-351.

5. Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr. 2004;(32):57-71.

6. Brown Johnson CG, Brodsky JL, Cataldo JK. Lung cancer stigma, anxiety, depression, and quality of life. J Psychosoc Oncol. 2014;32(1):59-73.

7. Cataldo JK, Jahan TM, Pongquan VL. Lung cancer stigma, depression, and quality of life among ever and never smokers. Eur J Oncol Nurs. 2012;16(3):264-269.

8. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2010. https://seer.cancer.gov/archive/csr/1975_2010/. Revised February 21, 2014. Accessed July 12, 2017.

9. Li M, Boquiren V, Lo C, et al. Depression and anxiety in supportive oncology. In: Davis M, Feyer P, Ortner P, Zimmermann C, eds. Supportive Oncology. 1st ed. Philadelphia, PA: Elsevier; 2011:528-540.

10. Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology. 2010;19(7):734-741.

11. Lazenby M, Ercolano E, Grant M, Holland JC, Jacobsen PB, McCorkle R. Supporting Commission on Cancer-mandated psychosocial distress screening with implementation strategies. J Oncol Pract. 2015;11(3):e413-e420.

12. Mystakidou K, Tsilika E, Parpa E, Katsouda E, Galanos A, Vlahos L. Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference. Cancer Nurs. 2006;29(5):400-405.

13. Passik SD, Dugan W, McDonald MV, Rosenfeld B, Theobald DE, Edgerton S. Oncologists’ recognition of depression in their patients with cancer. J Clin Oncol. 1998;16(4):1594-1600.

14. Rahuma M, Kamel M, Nasar A, et al. Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population based analysis. Am J Respir Crit Care Med. 2017;195:A6730.

15. Sullivan DR, Ganzini L, Duckart JP, et al. Treatment receipt and outcomes among lung cancer patients with depression. Clin Oncol (R Coll Radiol). 2014;26(1):25-31.

16. Merckaert I, Libert Y, Messin S, Milani M, Slachmuylder JL, Razavi D. Cancer patients’ desire for psychological support: prevalence and implications for screening patients psychological needs. Psychooncology. 2010;19(2):141-149.

17. Harrison JD, Young JM, Price MA, Butow PN, Solomon MJ. What are the unmet supportive care needs of people with cancer? A systematic review. Support Care Cancer. 2009;17(8):1117-1128.

18. Wu HS, Harden JK. Symptom burden and quality of life in survivorship: a review of the literature. Cancer Nurs. 2015;38(1):E29-E54.

19. Mols F, Husson O, Roukema JA, van de Poll-Franse LV. Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry. J Cancer Surviv. 2013;7(3):484-492.

20. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004;351(1):13-22.

21. Fortney JC, Curran GM, Hunt JB, et al. Prevalence of probable mental disorders and help-seeking behaviors among veteran and non-veteran community college students. Gen Hosp Psychiatry. 2016;38:99-104.

22. Pickett T, Rothman D, Crawford EF, Brancu M, Fairbank JA, Kudler HS. Mental health among military personnel and veterans. N C Med J. 2015;76(5):299-306.

23. U.S. Department of Veterans Affairs, Veterans Health Administration. One in ten older vets is depressed. https://www.va.gov/health/NewsFeatures/20110624a.asp. Updated April 17, 2015. Accessed July 12, 2017.

24. Fontana A, Rosenheck R. Treatment-seeking veterans of Iraq and Afghanistan: comparison with veterans of previous wars. J Nerv Ment Dis. 2008;196(7):513-521.

25. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry. 2000;61(suppl 5):4-12; discussion, 13-14.

26. Kartha A, Brower V, Saitz R, Samet JH, Keane TM, Liebschutz J. The impact of trauma exposure and post-traumatic stress disorder on healthcare utilization among primary care patients. Med Care. 2008;46(4):388-393.

27. National Cancer Institute. Cancer-related post-traumatic stress (PDQ®)–Patient version. https://www.cancer.gov/about-cancer/coping/survivorship/new-normal/ptsd-pdq. Updated July 7, 2015. Accessed July 12, 2017.

28. Andersen BL, DeRubeis RJ, Berman BS, et al; American Society of Clinical Oncology. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32(15):1605-1619.

29. Howell D, Keller-Olaman S, Oliver TK, et al. A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue. Curr Oncol. 2013;20(3):e233-e246.

30. Kroenke K, Wu J, Bair MJ, Krebs EE, Damush TM, Tu W. Reciprocal relationship between pain and depression: a 12-month longitudinal analysis in primary care. J Pain. 2011;12(9):964-973.

31. Walker J, Hansen CH, Martin P, et al; SMaRT (Symptom Management Research Trials) Oncology-3 Team. Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT oncology-3): a multicentre randomised controlled trial in patients with lung cancer. Lancet Oncol. 2014;15(10):1168-1176.

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Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. </i>J Clin Oncol<i>. 2016;34(33):3984</i><i>-3991.</i></p> <p><span class="dropcap">A</span>lthough depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.<sup>1-3 </sup>These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.<sup>4-8</sup> This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes. </p> <p>In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.<sup>9-11</sup> During treatment, depression can amplify physical symptoms and interfere with effective coping.<sup>12,13</sup> <br/><br/>Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.<sup>14</sup> Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.<sup>3</sup> This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.<sup>15 <br/><br/></sup>Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.<sup>16,17</sup><br/><br/>Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.<sup>18</sup> These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.<sup>19</sup> The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective. </p> <h2>Special Considerations for Veterans</h2> <p>There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.<sup>20-22</sup> According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.<sup>23 </sup>However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.<sup>24</sup> In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.<sup>25,26</sup> A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.<sup>27</sup> </p> <h2>Depression Screening and Treatment </h2> <p>Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.<sup>11,28,29</sup> Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.<sup>28</sup> Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.<sup>28 </sup>These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment. </p> <p>In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.<sup>30</sup> Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.<sup>30</sup> <br/><br/>Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.<br/><br/>Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.<sup>31</sup> Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.<sup>3 </sup></p> <h2>Conclusion</h2> <p>Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorship—ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer. </p> <p>The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings. <br/><br/>Overall, there is minimal evidence that depression treatment can improve lung cancer survival; however, the lack of high-quality studies is a considerable limitation. Given the significant impact of depression on survival among patients with lung cancer, additional funding and resources are urgently needed to combat this debilitating comorbid disease. </p> <h2>Acknowledgments</h2> <p> <em> This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&amp;D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.<hl name="33282"/> </em> </p> <h2>Author disclosures </h2> <p> <em> The authors report no actual or potential conflicts of interest with regard to this article. </em> </p> <h2>Disclaimer</h2> <p> <em> The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. </em> </p> <h2>References</h2> <p class="reference"> 1. Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients.<em> JAMA. </em>1983;249(6):751-757.<br/><br/> 2. Walker J, Holm Hansen C, Martin P, et al. Prevalence of depression in adults with cancer: a systematic review. <em>Ann Oncol.</em> 2013;24(4):895-900.<br/><br/> 3. Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. <i>J Clin Oncol.</i> 2016;34(33):3984-3991.<br/><br/> 4. Linden W, Vodermaier A, Mackenzie R, Greig D. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age.<i> J Affect Disord.</i> 2012;141(2-3):343-351.<br/><br/> 5. Massie MJ. Prevalence of depression in patients with cancer.<i> J Natl Cancer Inst Monogr.</i> 2004;(32):57-71.<br/><br/> 6. Brown Johnson CG, Brodsky JL, Cataldo JK. Lung cancer stigma, anxiety, depression, and quality of life. <i>J Psychosoc Oncol.</i> 2014;32(1):59-73.<br/><br/> 7. Cataldo JK, Jahan TM, Pongquan VL. Lung cancer stigma, depression, and quality of life among ever and never smokers. <i>Eur J Oncol Nurs. </i>2012;16(3):264-269.<br/><br/> 8. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2010. <span class="Hyperlink"><a href="https://seer.cancer.gov/archive/csr/1975_2010/">https://seer.cancer.gov/archive/csr/1975_2010/</a></span>. Revised February 21, 2014. Accessed July 12, 2017.<br/><br/> 9. Li M, Boquiren V, Lo C, et al. Depression and anxiety in supportive oncology. In: Davis M, Feyer P, Ortner P, Zimmermann C, eds. <i>Supportive Oncology. </i>1st ed. Philadelphia, PA: Elsevier; 2011:528-540.<br/><br/>10. Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. <i>Psychooncology. </i>2010;19(7):734-741.<br/><br/>11. Lazenby M, Ercolano E, Grant M, Holland JC, Jacobsen PB, McCorkle R. Supporting Commission on Cancer-mandated psychosocial distress screening with implementation strategies. <i>J Oncol Pract.</i> 2015;11(3):e413-e420.<br/><br/>12. Mystakidou K, Tsilika E, Parpa E, Katsouda E, Galanos A, Vlahos L. Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference.<i> Cancer Nurs.</i> 2006;29(5):400-405.<br/><br/>13. Passik SD, Dugan W, McDonald MV, Rosenfeld B, Theobald DE, Edgerton S. Oncologists’ recognition of depression in their patients with cancer. <i>J Clin Oncol. </i>1998;16(4):1594-1600.<br/><br/>14. Rahuma M, Kamel M, Nasar A, et al. Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population based analysis. <i>Am J Respir Crit Care Med. </i>2017;195:A6730.<br/><br/>15. Sullivan DR, Ganzini L, Duckart JP, et al. Treatment receipt and outcomes among lung cancer patients with depression.<i> Clin Oncol (R Coll Radiol). </i>2014;26(1):25-31.<br/><br/>16. Merckaert I, Libert Y, Messin S, Milani M, Slachmuylder JL, Razavi D. Cancer patients’ desire for psychological support: prevalence and implications for screening patients psychological needs. <i>Psychooncology.</i> 2010;19(2):141-149.<br/><br/>17. Harrison JD, Young JM, Price MA, Butow PN, Solomon MJ. What are the unmet supportive care needs of people with cancer? A systematic review. <i>Support Care Cancer. </i>2009;17(8):1117-1128.<br/><br/>18. Wu HS, Harden JK. Symptom burden and quality of life in survivorship: a review of the literature. <i>Cancer Nurs. </i>2015;38(1):E29-E54.<br/><br/>19. Mols F, Husson O, Roukema JA, van de Poll-Franse LV. Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry.<i> J Cancer Surviv.</i> 2013;7(3):484-492.<br/><br/>20. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. <i>N Engl J Med. </i>2004;351(1):13-22.<br/><br/>21. Fortney JC, Curran GM, Hunt JB, et al. Prevalence of probable mental disorders and help-seeking behaviors among veteran and non-veteran community college students.<i> Gen Hosp Psychiatry.</i> 2016;38:99-104.<br/><br/>22. Pickett T, Rothman D, Crawford EF, Brancu M, Fairbank JA, Kudler HS. Mental health among military personnel and veterans. <i>N C Med J.</i> 2015;76(5):299-306.<br/><br/>23. U.S. Department of Veterans Affairs, Veterans Health Administration. One in ten older vets is depressed. <span class="Hyperlink"><a href="https://www.va.gov/health/NewsFeatures/20110624a.asp">https://www.va.gov/health/NewsFeatures/20110624a.asp</a></span>. Updated April 17, 2015. Accessed July 12, 2017. <br/><br/>24. Fontana A, Rosenheck R. Treatment-seeking veterans of Iraq and Afghanistan: comparison with veterans of previous wars. <i>J Nerv Ment Dis.</i> 2008;196(7):513-521.<br/><br/>25. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. <i>J Clin Psychiatry. </i>2000;61(suppl 5):4-12; discussion, 13-14.<br/><br/>26. Kartha A, Brower V, Saitz R, Samet JH, Keane TM, Liebschutz J. The impact of trauma exposure and post-traumatic stress disorder on healthcare utilization among primary care patients. <i>Med Care.</i> 2008;46(4):388-393.<br/><br/>27. National Cancer Institute. Cancer-related post-traumatic stress (PDQ®)–Patient version. <span class="Hyperlink"><a href="https://www.cancer.gov/about-cancer/coping/survivorship/new-normal/ptsd-pdq">https://www.cancer.gov/about-cancer/coping/survivorship/new-normal/ptsd-pdq</a></span>. Updated July 7, 2015. Accessed July 12, 2017.<br/><br/>28. Andersen BL, DeRubeis RJ, Berman BS, et al; American Society of Clinical Oncology. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation.<i> J Clin Oncol.</i> 2014;32(15):1605-1619.<br/><br/>29. Howell D, Keller-Olaman S, Oliver TK, et al. A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue. <i>Curr Oncol. </i>2013;20(3):e233-e246.<br/><br/>30. Kroenke K, Wu J, Bair MJ, Krebs EE, Damush TM, Tu W. Reciprocal relationship between pain and depression: a 12-month longitudinal analysis in primary care. <i>J Pain. </i>2011;12(9):964-973.<br/><br/>31. Walker J, Hansen CH, Martin P, et al; SMaRT (Symptom Management Research Trials) Oncology-3 Team. Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT oncology-3): a multicentre randomised controlled trial in patients with lung cancer. <i>Lancet Oncol.</i> 2014;15(10):1168-1176.</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>bio</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
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The opioid epidemic, surgeons, and palliative care

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Recent public and professional attention to what is now called the opioid epidemic has obvious implications for surgery and palliative care. Because of the status of “epidemic,” there is a sense of urgency within the surgical and palliative care community to reevaluate the assessment and treatment of patients for whom opioid therapy is being considered.

Dunn_Geoffrey_P_PA_web.jpg
Dr. Geoffrey P. Dunn
The American College of Surgeons has hastened to recognize this problem as is evident in this year’s Clinical Congress symposia, PS407 Postoperative Pain Control: Strategies of Decreasing the Need for Narcotics: Part I and PS408 Surgeons’ Methods and Responses to Dealing with the Opioid Epidemic – Part II. Even with its collective experience with opioid use in hospice and palliative care, the palliative care community freely acknowledges its lack of preparation to meet the challenges resulting from the societal consequences of addiction, overdosage, and criminal activity stemming from the availability of opioids. A major concern for palliative care practitioners is to preserve the availability of opioid therapy without hindering reform of opioid use, a problem that will grow as more patients receive palliative care earlier in the course of life-limiting illness.

Although the liberal use of opioids is a common stereotype of palliative care, the use of opioids in the palliative care setting is part of a complex assessment and treatment process. Opioid use in this setting is analogous to palliative surgery in the surgical palliative care setting: It is one tool, and it is most effective and safe when based on an assessment of the more general picture. A fundamental concept of palliative care, “total pain,” provides a basis for improved pain management that goes far beyond the use and dependency on opioid therapy. Dame Cicely Saunders, who was mentored by a surgeon and later became a Fellow of the Royal College of Surgeons, defined the concept of total pain as the suffering that encompasses all of a person’s physical, psychological, social, spiritual, and practical struggles (BMJ. 2005 Jul 23;331[7510]:238). Blake Cady, a preeminent surgeon and surgical educator, once wrote that the day-to-day decisions in surgery are best made in the context of a surgical philosophy of care (J Am Coll Surg. 2005 Feb;200[2]:285-90). This applies to all interventions. Total-pain assessment provides us the opportunity to identify nonphysical factors associated with pain that might not indicate opioid use or even contraindicate their use. Existential distress or spiritual pain in a delirious or underassessed patient can be indistinguishable from physical distress. Socioeconomic factors, such as an inability to pay for medical care, can present as pain.

Surgeons are uniquely positioned as “listening posts” in the overall campaign to curb opioid misuse. They can identify patients at risk for or diagnosed with substance use disorder so they can be managed or referred for specialist treatment appropriately.

Awareness of other dimensions of pain will enhance their efficacy in this role.

Opioid sparing is a key tactic in the strategy for controlling opioid use and minimizing opioid-induced side effects. Occasionally surgical or interventional radiologic procedures are useful for this purpose.

There are immediate, specific actions surgeons can take in order to constructively participate in opioid use reform:

  • Expand your patient’s pain history to include nonphysical dimensions of pain and refer appropriately.
  • Know your opioids; carry an opioid conversion table. Errors in opioid conversion can result in significant undertreatment of pain but can result in overdosage just as easily.
  • Know your pharmacist. Pharmacists are valuable allies in safe opioid prescribing and monitoring practices.
  • Be wary of “standardized” order sets that include opioids. There is no standard dose or standard patient as we are rapidly learning from genomics.
  • Utilize your state’s patient drug-monitoring program – a new pain for clinicians, but some headaches are worth it. It clearly has already put the brakes on opioid prescribing.

Given the recent public and professional attention to the problems of opioid misuse, there is a long-overdue opportunity to reassess not only the indications and management of opioid therapy but also our more general approach to the management of pain. There is now an opportunity for surgeons to play a major role in improving opioid-prescribing practice. One potentially successful approach could be better assessment and management of pain through an awareness and application of palliative care principles. Like all encounters with uncertainty, the best way out of the current opioid dilemma is the way through: Surgeons should not abandon opioids but – in conjunction with nurses, palliative care practitioners, pharmacists, and pain and anesthesia specialists – reinvent their role in the war on suffering.


 

Dr. Dunn is the medical director of the palliative care consultation service at the University of Pittsburgh Medical Center Hamot in Erie, Pa., and vice chair of the ACS Committee on Surgical Palliative Care.

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Recent public and professional attention to what is now called the opioid epidemic has obvious implications for surgery and palliative care. Because of the status of “epidemic,” there is a sense of urgency within the surgical and palliative care community to reevaluate the assessment and treatment of patients for whom opioid therapy is being considered.

Dunn_Geoffrey_P_PA_web.jpg
Dr. Geoffrey P. Dunn
The American College of Surgeons has hastened to recognize this problem as is evident in this year’s Clinical Congress symposia, PS407 Postoperative Pain Control: Strategies of Decreasing the Need for Narcotics: Part I and PS408 Surgeons’ Methods and Responses to Dealing with the Opioid Epidemic – Part II. Even with its collective experience with opioid use in hospice and palliative care, the palliative care community freely acknowledges its lack of preparation to meet the challenges resulting from the societal consequences of addiction, overdosage, and criminal activity stemming from the availability of opioids. A major concern for palliative care practitioners is to preserve the availability of opioid therapy without hindering reform of opioid use, a problem that will grow as more patients receive palliative care earlier in the course of life-limiting illness.

Although the liberal use of opioids is a common stereotype of palliative care, the use of opioids in the palliative care setting is part of a complex assessment and treatment process. Opioid use in this setting is analogous to palliative surgery in the surgical palliative care setting: It is one tool, and it is most effective and safe when based on an assessment of the more general picture. A fundamental concept of palliative care, “total pain,” provides a basis for improved pain management that goes far beyond the use and dependency on opioid therapy. Dame Cicely Saunders, who was mentored by a surgeon and later became a Fellow of the Royal College of Surgeons, defined the concept of total pain as the suffering that encompasses all of a person’s physical, psychological, social, spiritual, and practical struggles (BMJ. 2005 Jul 23;331[7510]:238). Blake Cady, a preeminent surgeon and surgical educator, once wrote that the day-to-day decisions in surgery are best made in the context of a surgical philosophy of care (J Am Coll Surg. 2005 Feb;200[2]:285-90). This applies to all interventions. Total-pain assessment provides us the opportunity to identify nonphysical factors associated with pain that might not indicate opioid use or even contraindicate their use. Existential distress or spiritual pain in a delirious or underassessed patient can be indistinguishable from physical distress. Socioeconomic factors, such as an inability to pay for medical care, can present as pain.

Surgeons are uniquely positioned as “listening posts” in the overall campaign to curb opioid misuse. They can identify patients at risk for or diagnosed with substance use disorder so they can be managed or referred for specialist treatment appropriately.

Awareness of other dimensions of pain will enhance their efficacy in this role.

Opioid sparing is a key tactic in the strategy for controlling opioid use and minimizing opioid-induced side effects. Occasionally surgical or interventional radiologic procedures are useful for this purpose.

There are immediate, specific actions surgeons can take in order to constructively participate in opioid use reform:

  • Expand your patient’s pain history to include nonphysical dimensions of pain and refer appropriately.
  • Know your opioids; carry an opioid conversion table. Errors in opioid conversion can result in significant undertreatment of pain but can result in overdosage just as easily.
  • Know your pharmacist. Pharmacists are valuable allies in safe opioid prescribing and monitoring practices.
  • Be wary of “standardized” order sets that include opioids. There is no standard dose or standard patient as we are rapidly learning from genomics.
  • Utilize your state’s patient drug-monitoring program – a new pain for clinicians, but some headaches are worth it. It clearly has already put the brakes on opioid prescribing.

Given the recent public and professional attention to the problems of opioid misuse, there is a long-overdue opportunity to reassess not only the indications and management of opioid therapy but also our more general approach to the management of pain. There is now an opportunity for surgeons to play a major role in improving opioid-prescribing practice. One potentially successful approach could be better assessment and management of pain through an awareness and application of palliative care principles. Like all encounters with uncertainty, the best way out of the current opioid dilemma is the way through: Surgeons should not abandon opioids but – in conjunction with nurses, palliative care practitioners, pharmacists, and pain and anesthesia specialists – reinvent their role in the war on suffering.


 

Dr. Dunn is the medical director of the palliative care consultation service at the University of Pittsburgh Medical Center Hamot in Erie, Pa., and vice chair of the ACS Committee on Surgical Palliative Care.

 

Recent public and professional attention to what is now called the opioid epidemic has obvious implications for surgery and palliative care. Because of the status of “epidemic,” there is a sense of urgency within the surgical and palliative care community to reevaluate the assessment and treatment of patients for whom opioid therapy is being considered.

Dunn_Geoffrey_P_PA_web.jpg
Dr. Geoffrey P. Dunn
The American College of Surgeons has hastened to recognize this problem as is evident in this year’s Clinical Congress symposia, PS407 Postoperative Pain Control: Strategies of Decreasing the Need for Narcotics: Part I and PS408 Surgeons’ Methods and Responses to Dealing with the Opioid Epidemic – Part II. Even with its collective experience with opioid use in hospice and palliative care, the palliative care community freely acknowledges its lack of preparation to meet the challenges resulting from the societal consequences of addiction, overdosage, and criminal activity stemming from the availability of opioids. A major concern for palliative care practitioners is to preserve the availability of opioid therapy without hindering reform of opioid use, a problem that will grow as more patients receive palliative care earlier in the course of life-limiting illness.

Although the liberal use of opioids is a common stereotype of palliative care, the use of opioids in the palliative care setting is part of a complex assessment and treatment process. Opioid use in this setting is analogous to palliative surgery in the surgical palliative care setting: It is one tool, and it is most effective and safe when based on an assessment of the more general picture. A fundamental concept of palliative care, “total pain,” provides a basis for improved pain management that goes far beyond the use and dependency on opioid therapy. Dame Cicely Saunders, who was mentored by a surgeon and later became a Fellow of the Royal College of Surgeons, defined the concept of total pain as the suffering that encompasses all of a person’s physical, psychological, social, spiritual, and practical struggles (BMJ. 2005 Jul 23;331[7510]:238). Blake Cady, a preeminent surgeon and surgical educator, once wrote that the day-to-day decisions in surgery are best made in the context of a surgical philosophy of care (J Am Coll Surg. 2005 Feb;200[2]:285-90). This applies to all interventions. Total-pain assessment provides us the opportunity to identify nonphysical factors associated with pain that might not indicate opioid use or even contraindicate their use. Existential distress or spiritual pain in a delirious or underassessed patient can be indistinguishable from physical distress. Socioeconomic factors, such as an inability to pay for medical care, can present as pain.

Surgeons are uniquely positioned as “listening posts” in the overall campaign to curb opioid misuse. They can identify patients at risk for or diagnosed with substance use disorder so they can be managed or referred for specialist treatment appropriately.

Awareness of other dimensions of pain will enhance their efficacy in this role.

Opioid sparing is a key tactic in the strategy for controlling opioid use and minimizing opioid-induced side effects. Occasionally surgical or interventional radiologic procedures are useful for this purpose.

There are immediate, specific actions surgeons can take in order to constructively participate in opioid use reform:

  • Expand your patient’s pain history to include nonphysical dimensions of pain and refer appropriately.
  • Know your opioids; carry an opioid conversion table. Errors in opioid conversion can result in significant undertreatment of pain but can result in overdosage just as easily.
  • Know your pharmacist. Pharmacists are valuable allies in safe opioid prescribing and monitoring practices.
  • Be wary of “standardized” order sets that include opioids. There is no standard dose or standard patient as we are rapidly learning from genomics.
  • Utilize your state’s patient drug-monitoring program – a new pain for clinicians, but some headaches are worth it. It clearly has already put the brakes on opioid prescribing.

Given the recent public and professional attention to the problems of opioid misuse, there is a long-overdue opportunity to reassess not only the indications and management of opioid therapy but also our more general approach to the management of pain. There is now an opportunity for surgeons to play a major role in improving opioid-prescribing practice. One potentially successful approach could be better assessment and management of pain through an awareness and application of palliative care principles. Like all encounters with uncertainty, the best way out of the current opioid dilemma is the way through: Surgeons should not abandon opioids but – in conjunction with nurses, palliative care practitioners, pharmacists, and pain and anesthesia specialists – reinvent their role in the war on suffering.


 

Dr. Dunn is the medical director of the palliative care consultation service at the University of Pittsburgh Medical Center Hamot in Erie, Pa., and vice chair of the ACS Committee on Surgical Palliative Care.

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The Challenges of Precision Medicine and New Advances in Molecular Diagnostic Testing in Hematolymphoid Malignancies: Impact on the VHA (FULL)

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The Challenges of Precision Medicine and New Advances in Molecular Diagnostic Testing in Hematolymphoid Malignancies: Impact on the VHA

In January 2015, President Obama introduced the Precision Medicine Initiative, a program set up to identify new biomedical discoveries for the development of a personalized knowledge base of disease entities and individualized treatments. Advances in precision medicine typically involve the use of targeted therapies tailored to individual genetic characteristics identified with molecular testing. The goals are to improve survival and reduce adverse effects. With an initial budget of $215 million, this initiative presented a unique opportunity to combine efforts in genomic discovery, bioinformatic analysis, and health information technology to move toward data-driven, evidence-based precision medicine.1

The VHA is the largest comprehensive health care system in the U. S. and has more than 1,700 care sites serving nearly 9 million veterans each year. The budget for this single-payer system is proposed by the President and approved by Congress. As the VHA must treat a diverse and aging veteran population in an environment of rising costs and budget constraints, limited resources must be monitored and appropriated for the most cost-effective health care delivery. Precision medicine offers a model in which physicians can select the most appropriate diagnostic tests in defined clinical settings to direct clinical care. It supports the testing needed to subdivide each disease category into distinct subcategories. Nevertheless, the need for fiscal responsibility in a capitated health care system recommends testing in cases in which it can change therapy or prognosis rather than for purely academic reasons.

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Pathology and Laboratory Medicine Service

Given limited resources and an increasing number of requests for advanced molecular testing, the VA Pathology and Laboratory Medicine Service (P&LMS) formed the Molecular Genetics Pathology Workgroup (MGPW) in September 2013. The charter listed the tasks of the MGPW to “provide recommendations on how to effectively use molecular genetics tests, promote increased quality and availability of testing within the VHA, encourage internal referral testing, provide an organizational structure for Molecular Genetics Testing Consortia, and create a P&LMS policy for molecular genetic testing in general, specifically addressing the issues surrounding laboratory developed testing.” The MGPW has 4 subcommittees: molecular oncology, pharmacogenetics, hematopathology molecular genetics (HMG), and genetic medicine. Since its inception, the HMG subcommittee has had several objectives:

  • Standardize the molecular testing nomenclature for and develop practice guidelines for acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, lymphoma, and plasma cell neoplasms;
  • Develop standardized reporting guidelines for current VA molecular laboratories;
  • Identify new tests as they are being reported in the literature and collaborate with hematology and oncology services to evaluate the clinical utility of these tests for VA patients;
  • Network current VA molecular laboratories, perform fact-finding for these laboratories, and compile test menus; and
  • Assess for the formation of VA-wide interfacility consultation services for hematopathology so that all VA facilities, regardless of their complexity, will be able to access the expertise of hematopathology-trained pathologists (Appendix).

fed03405050s_appendix.png

The HMG subcommittee met monthly and discussed various diagnostic entities in hematopathology. For hematolymphoid malignancies, it was generally agreed that the traditional laboratory tools of morphology, flow cytometry, and immunohistochemistry (IHC) are standard in initial assessment and often in diagnosis. As the clinical molecular and cytogenetic assays of karyotype, fluorescence in situ hybridization (FISH), advanced DNA sequencing, microarray, and highly sensitive polymerase chain reaction (PCR) analysis affect diagnosis, subclassification, minimal residual disease (MRD) monitoring, prognosis, and therapy selection, their use is marked by a high degree of variability. As a result, standardization is needed. As each laboratory develops and reports ancillary testing, the variable reporting formats may generate postanalytic errors.

A detailed description of all molecular methodologies is beyond the scope of this article. For practicing pathologists, challenges remain in overall cost and reimbursement, extensive and time-consuming data analysis, and in some cases, interpretation differences.

Myeloid Neoplasms

Myeloid malignancies were divided into AML, MPN, and MDS. Next-generation sequencing (NGS) information for these malignancies was used to identify various contributory functional categories, including cell signaling (FLT3, KIT, JAK2, MPL, KRAS/NRAS, PTPN11, NF1, CSF3R); transcription (CEBPA, RUNX1, GATA1/GATA2, PHF6, ETV6); splicing (SF3B1, SRSF2, ZRSR2, U2AF1); epigenetics (DNMT3A, TET2, IDH1/IDH2, ASXL1, EZH2, SUZ12, KDM6A); cohesin complex (STAG2, SMC1A, SMC3, RAD21); and cell cycle (TP53, NPM1).2

Acute Myeloid Leukemia

The HMG subcommittee reviewed the literature on prognostically significant genes in myeloid leukemias. Karyotype abnormalities, such as t(8;21) and inv(16), collectively known as the core-binding factor (CBF) leukemias, t(15;17), t(11q23) (KMT2A/MLL), and so forth, are recurrent lesions in AML. Included in the minimum set of genes recommended by the National Comprehensive Cancer Network (NCCN) for AML prognosis evaluation are nucleolar protein nucleophosmin (NPM1), CCAAT/enhancer-binding protein α (CEBPA), and fms-related tyrosine kinase 3 (FLT3).3 Presence of NPM1 and CEBPA mutations generally is thought to confer a favorable prognosis in AML with a normal karyotype. However, FLT3 with or without NPM1 confers an adverse prognosis. Any KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) mutation changes an otherwise better CBF AML prognosis to a poor prognosis. The methods used to detect these gene mutations are based on either PCR analysis or sequencing.

Some of the chromosomal translocations, such as inv(16)/t(16;16) in AML and t(15;17) in acute promyelocytic leukemia, can be monitored with FISH or reverse transcription–PCR (RT-PCR) analysis. As NPM1 mutations tend to be seen in recurrence, they can be used as molecular markers for MRD. Other mutations that provide important prognostic information in AML include:

  • Activating insertions/duplications in the FLT3 receptor tyrosine kinase, which can be detected with PCR sizing assays;
  • Mutations in the KIT receptor tyrosine kinase, which can be detected with DNA sequencing or more limited hotspot PCR;
  • Mutations in the DNA methyltransferase, DNMT3A, a poor prognostic indicator seen in 22% of cases of AML, also detected with gene sequencing or more limited hotspot PCR; and
  • Another set of genes, TET2, IDH1, IDH2, KRAS, NRAS, EZH2, and ASXL1, is mutated in MPN as well as AML and MDS, making a common molecular panel with next-generation sequencing useful in diagnosing and risk-stratifying all myeloid neoplasms.

The HMG subcommittee agreed that, for de novo AML, chromosomal karyotype is the standard of care, necessary in detecting known cytogenetic abnormalities as well as a wide range of lesions that might indicate a diagnosis of AML with myelodysplasia-related changes at time of diagnosis. In addition, molecular analysis of FLT3 is useful in determining prognosis, and CEBPA (biallelic) and NPM1 mutations are good prognostic factors in normal-karyotype AML. KMT2A (MLL) rearrangements should be tested with FISH if the lineage is ambiguous. The PML-RARA fusion gene also should be tested with FISH if morphologic and flow cytometry results suggest acute promyelocytic leukemia (Table). At this time, testing for TP53, DNMT3A, RAS, and other such mutations is not recommended because it is not cost-effective for the VA.

fed03405050s_t.png

Myeloproliferative Neoplasms

Myeloproliferative neoplasms are clonal hematopoietic stem cell disorders characterized by proliferation of at least 1 myeloid lineage: granulocytic, erythroid, or megakaryocytic. Myeloproliferative neoplasms show a range of recurrent chromosomal translocations, such as BCR-ABL1 fusion in chronic myelogenous leukemia (CML) that can be detected with RT-PCR analysis as well as FISH. In CML, BCR-ABL1 fusion transcript levels detected by a quantitative PCR (qPCR) method are now used to monitor the course of CML therapy with tyrosine kinase inhibitors (TKIs) and to trigger a treatment change in drug-resistant cases. Given the importance of qPCR in clinical management, significant progress has been made in standardizing both the PCR protocol and the reference materials used to calibrate the BCR-ABL1 PCR assay. BCR-ABL1–negative MPN, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are most commonly associated with mutations in the tyrosine kinase JAK2. Mutations in CALR and MPL are seen in a subset of patients with ET and PMF as well, whereas PV is essentially exclusively a disease of JAK2 mutations.

Chronic myelogenous leukemia is the prototypical MPN. To establish the initial diagnosis, FISH and/or qPCR for BCR-ABL1 fusion should be used. If CML is confirmed, the sample can be reflexed to qPCR BCR-ABL1 on the initial peripheral blood and/or bone marrow sample(s) to establish the patient’s baseline. In addition, a bone marrow sample (aspirate) should be used for a complete karyotype and for morphologic confirmation of disease phase.

 

 

For follow-up assessment of CML patients’ response to TKI treatment, qPCR for BCR-ABL1 should be tested with a peripheral blood sample or a bone marrow sample every 3 months.4 A peripheral blood sample is more commonly used because it is conveniently obtained. Early molecular response as indicated by a BCR-ABL1 transcript ratio of < 10% on the International Scale at 3 months, has a strong prognostic value.5 Major molecular response as indicated by a BCR-ABL1 transcript ratio of < 0.1% on the International Scale at 12 to 18 months is also highly prognostic.5

After the peripheral blood sample becomes negative for BCR-ABL1 by qPCR, testing bone marrow samples may be considered. If important treatment response benchmarks are not achieved, or response is lost with rising BCR-ABL1 levels (TKI resistance), ABL1 kinase domain mutation analysis as well as repeat FISH (to assess for copy number multiplication) should be performed to guide further management. Patients with the ABL1 T315I mutation are resistant to all first-line TKIs but may respond to later third-generation TKIs.6

BCR-ABL1–negative MPNs include PV, ET, and PMF. Bone marrow morphology remains the cornerstone of ET and PMF diagnosis. The discovery of JAK2, CALR, and MPL mutations has contributed to how these disorders are diagnosed.7-12 Besides providing the clonality proof that is crucial for diagnosis, the molecular markers influence the prognosis. The JAK2 (p.V617F) or less common JAK2 exon 12 mutations, which are detected in more than 95% of PV cases, are used as molecular markers to confirm diagnosis.7 Further, the JAK2 (p.V617F), CALR (exon 9), and MPL (exon 10) mutations are detected in ET (~60%, 25%, and 3%-5%, respectively) and PMF (~55%, 30%, and 5%, respectively).12 If ET or PMF is suspected clinically, first JAK2 (p.V617F) mutation analysis should be performed, then CALR mutation analysis, and finally MPL mutation analysis. Although novel gain-of-function JAK2 and MPL mutations were recently discovered in triple-negative ET (negative for canonical mutations in JAK2, CALR, and MPL) and PMF by whole exome sequencing,13 clinical testing is not readily available. Besides its utility in the initial diagnosis of ET and PMF, the JAK2 or CALR mutation assay also may be considered for bone marrow transplantation follow-up (Table).14

Despite the continuing debate on the classification of eosinophilic myeloid disorders, the discovery of the FIP1L1-PDGFRA fusion represents a major milestone in the understanding of these disorders.15,16 Unlike PDGFRB (5q33) and FGFR1 (8p11) rearrangements, which can be detected with routine chromosomal analysis (cytogenetics), the cryptic FIP1L1-PDGFRA fusion must be detected with FISH (for CHIC2 deletion) or RT-PCR analysis. It should be pointed out that, as most eosinophilia is reactive or secondary, molecular testing for FIP1L1-PDGFRA fusion is indicated only when primary hypereosinophilia or hypereosinophilic syndrome (HES) is suspected. This is particularly the case in the following hypereosinophilia accompanying conditions: CML-like morphology, but BCR-ABL1–negative; chronic myelomonocytic leukemia (CMML)–like morphology with a normal karyotype; and new onset of cardiac damage or dysfunction.17

Primary eosinophilic myeloid disorders with PDGFRA or PDGFRB rearrangements can be treated with TKIs (eg, imatinib). Next-generation sequencing may be considered in cases of presumed HES when there is no identifiable karyotypic or FISH abnormality. Recent studies have found that cases of HES with somatic mutations indicating clonality had adverse clinical outcomes similar to those of cases of chronic eosinophilic leukemia.18

The discovery of CSF3R mutations offers a new molecular marker for the diagnosis of chronic neutrophilic leukemia (CNL), an MPN.19 The CSF3R (p.T618I) mutation or another activating CSF3R mutation is now used as a diagnostic criterion for CNL. Identification of specific CSF3R mutations may have therapeutic implications as well. The test should be ordered only for patients with clinical and morphologic findings suggestive of CNL; reactive neutrophilic leukocytosis (eg, infection, inflammation) should be ruled out before the test is ordered.

Myelodysplastic Syndrome

Myelodysplastic syndrome is a group of clonal bone marrow disorders characterized by ineffective hematopoiesis, manifested by morphologic dysplasia in ≥ 1 hematopoietic lineages and peripheral cytopenias (hemoglobin level, < 10 g/dL; platelet count, < 100×103/µL; absolute neutrophil count, < 1.8×103/µL). Diagnosis and classification of MDS depend mainly on the degree of morphologic dysplasia and blast percentages, as determined by examining well-prepared cellular bone marrow aspirate smears and/or biopsy touch preparations and peripheral blood smears.

Conventional karyotyping is an essential part of the diagnostic workup for all presumptive cases of MDS and is of both diagnostic and prognostic importance.20 About 60% of MDS cases have recurrent cytogenetic abnormalities, which can be detected with conventional karyotyping. If a high-quality cytogenetic analysis cannot be performed (eg, the bone marrow sample is inadequate), or if quick turnaround is required, an alternative FISH panel may be used to detect some of the common MDS-associated chromosomal abnormalities (eg, 5q deletion, 7q deletion/monosomy 7, +8, 20q deletion).21 Sequencing with FISH also can be useful for assessing MRD by detecting a previously identified chromosomal abnormality.

Targeted sequencing of a limited number of genes can detect mutations in the vast majority of patients with MDS. The most commonly mutated genes in MDS are SF3B1, TET2, SRSF2, ASXL1, DNMT3A, RUNX1, U2AF1, TP53, and EZH2. Mutations in SRSF2 cause RNA splicing abnormalities. In addition, mutations in TP53, EZH2, RUNX1, and ASXL1 are associated with poor prognosis,22,23 whereas mutations in SF3B1 confer better event-free survival.24 Despite these developments, the HMG subcommittee agreed that NGS-based mutation panels are not cost-effective for the VA population at this time and should not be included in a MDS workup. Only in rare situations and when clinically indicated (to change disease classification or patient management) should evaluation for specific gene mutations be considered—for instance, the SF3B1 mutation for patients with probable MDS with ring sideroblasts, if ring sideroblasts are < 15%.25

Myelodysplastic/Myeloproliferative Neoplasms

Myelodysplastic/myeloproliferative neoplasms are a group of myeloid neoplasms with clinical, laboratory, and morphologic features that overlap both MDS and MPN. In MDS/MPN, the karyotype is often normal or shows abnormalities in common with MDS.

In cases of unexplained monocytosis for which there is clinical concern for CMML, morphologic evaluation and conventional chromosomal karyotyping should be performed after other secondary causes and known myeloproliferative and myelodysplastic entities have been excluded. If concomitant hypereosinophilia is present and the karyotype is normal, FISH or PCR-based assay should be performed to rule out FIP1L1-PDGFRA rearrangements. BCR-ABL1, PDGFRB, FGFR1, and t(8;9)/PCM1-JAK2 rearrangements typically are detected with high-quality cytogenetic analysis and thus do not require targeted molecular assays. Although certain gene mutations (eg, SRSF2, TET2, ASXL1, CBL) are commonly detected in CMML, the HMG subcommittee does not recommend sequencing-based mutation panels, as there is insufficient information for testing for prognostic or treatment stratification.

If MDS/MPN with ring sideroblasts and thrombocytosis is suspected on the basis of the clinical and morphologic criteria, molecular tests for the JAK2 (p.V617F) and SF3B1 mutations may be considered in an effort to help confirm the diagnosis.

Atypical CML is a rare MDS/MPN subtype that is now better characterized molecularly with SETBP1 and/or ETNK1 mutations, which are detectable in up to a third of cases. If clinical suspicion is high, sequencing may be diagnostically helpful.

Lymphoid Neoplasms

Chronic Lymphocytic Leukemia

In CLL, recurrent chromosomal abnormalities (eg, deletions of 13q, trisomy 12, deletions of 11q, deletions of 17p) have clear prognostic value and can be detected with FISH. Other prognostic information, such as somatic mutation of immunoglobulin heavy chain variable (IgHV) genes, TP53 mutations, SF3B1, and NOTCH1 mutation, are mostly derived from PCR-based assays. The discovery of recurrently mutated genes in CLL has increased with the use of highly sensitive sequencing methods constructing a more detailed landscape of CLL at genetic, epigenetic, and cellular levels. A recent literature review summarizes the vast heterogeneity of CLL with recurrent pathogenetic findings in MYD88, SF3B1, TP53, ATM, and NOTCH1 signaling pathways.26 The treatment of CLL is rapidly evolving, and many clinical trials are proposing a change from the “watch and wait” paradigm to treatment upon initial presentation based on molecular findings. Additional testing based on new treatment options from current clinical trials will be recommended.

 

 

Flow cytometry and morphology are standard for CLL diagnosis. The HMG subcommittee recommends FISH for del(13q14), del(11q), trisomy 12, and del(17p) at time of diagnosis or immediately before therapy initiation. Zeta-chain (ζ-chain) associated protein 70 (ZAP-70) by flow cytometry and IgHV mutation status are optional (use depends on test availability). For high-risk CLL cases, PCR-based or sequencing-based assays should be used to detect the TP53 mutation, especially in CLL patients who are candidates for treatment with recently approved CLL-targeted therapies such as ibrutinib (irreversible inhibitor of Bruton tyrosine kinase) and idelalisib (PI3Kγ inhibitor). Recent studies have shown that NOTCH1 and SF3B1 mutations may have prognostic significance, but routine testing is not recommended at this time.27-29

Other B-Cell Lymphoproliferative Disorders

Unlike the common molecular changes in CLL, in other mature B-cell lymphomas, chromosomal translocations that juxtapose a variety of different oncogenes next to an Ig gene enhancer usually are—and those that switch regions less commonly are—important initiating events that can be detected with PCR, DNA sequencing, or FISH. In follicular lymphoma (FL), Burkitt lymphoma, marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL), these oncogenes driven by an Ig gene enhancer typically include BCL2, MYC, MALT1, and CCND1 (cyclin D1), respectively. Molecular variants of these lymphomas that lack these classical translocations often activate homologous genes (eg, cyclin D3/CCND3 is activated in variants of MCL).

Morphology, flow cytometry, and IHC are routinely used for diagnosis. In inconclusive cases, Ig gene rearrangement by PCR may be used. The Table summarizes common molecular changes in B-cell lymphomas.

Mantle cell lymphoma. MCL is a non-Hodgkin lymphoma subtype characterized by t(11;14) (q13;q32) translocations that in the majority of cases lead to overexpression of cyclin D1 (BCL1). Recent molecular profiling has identified an MCL variant that is cyclin D1–negative but SOX11-positive and may have a more aggressive clinical course.30SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive MCL.

Lymphoplasmacytic lymphoma. Lymphoplasmacytic lymphoma (LPL), MZL, and CLL/small lymphocytic lymphoma are well-defined clinicopathologic entities. However, distinguishing LPL from MZL and atypical cases of CLL can sometimes be difficult because of overlapping clinical and morphologic features. Recent studies have identified a recurrent L265P mutation in the MYD88 gene in 90% to 95% of LPL cases with IgM paraprotein and in 40% to 50% of the rare non-IgM LPL cases. In contrast, the mutation is much less frequently present in MZL and other low-grade B-cell neoplasms (2%-7%).31 Therefore, testing for this abnormality can be a diagnostic aid in these difficult-to-classify cases. In addition, from a therapeutic perspective, presence or absence of MYD88 mutation may prove more significant than presence of a specific paraprotein or histopathologic features. Ibrutinib has shown efficacy in LPL and demonstrates improved response rates in patients with MYD88 mutation compared with that of their mutation-negative counterparts.32 Several MYD88 inhibitors are in clinical trials. This again indicates the need to more accurately identify and subclassify these non-IgM LPL cases to ensure appropriate molecular evaluation.

Hairy cell leukemia. Flow cytometry and morphology are usually sufficient for a hairy cell leukemia (HCL) diagnosis. However, rare cases are difficult to distinguish variant HCL from other mimics. The BRAF V600E mutation recently was described as a disease-defining molecular marker for HCL—present in nearly all HCL cases but virtually absent in HCL mimics. Therefore, detection of the BRAF mutation by IHC stain with specific antibody or PCR analysis is highly sensitive and specific for the diagnosis of HCL.33

Diffuse large B-cell lymphoma. Recent molecular analysis has created various risk stratification schemata for diffuse large B-cell lymphoma (DLBCL). The HGM subcommittee agrees that well-preserved morphology, IHC, flow cytometry, and FISH-specific markers (BCL2, BCL6, cMYC) are sufficient for diagnostic, prognostic, and therapeutic purposes. Although a wide range of genes have been implicated in the pathogenesis of DLBCL, sequencing and gene expression profiling are not cost-effective at this time and do not add benefit to patient treatment.

The MYD88 L265P mutation has been identified in DLBCL, particularly the activated B-cell-like type and primary central nervous system lymphoma (PCNSL), and may have implications for ibrutinib therapy. PCNSL commonly manifests aggressive clinical behavior and has a poor prognosis. It has been proposed that the MYD88 mutation can be used as a genetic hallmark for PCNSL to distinguish CNS involvement by systemic DLBCL from PCNSL.34

Plasma cell neoplasms. Flow cytometry is acceptable for the diagnosis of plasma cell neoplasms and for residual disease follow-up. Chromosomal karyotype or FISH for IGH/CCND1, IGH/MMSET, and IGH/CMAF dual fusion probes is recommended in conjunction with morphology, IHC, and flow cytometry. In plasma cell myeloma, several genetic mutations can be detected with NGS, including mutations in NRAS, KRAS, TP53, BCL7A, DIS3, and FAM46C.35 Less commonly, BRAF mutations, previously described in melanoma and several other solid tumors, can be detected with DNA sequencing in 4% of multiple myeloma cases, which may prove promising for targeted therapy with BRAF inhibitors. However, current therapeutic decisions are based on genetic and clinical factors, and sequence-based assays are not recommended at this time.

Follicular lymphoma. Cytology, histology, and IHC typically are sufficient for diagnosing FL. In difficult-to-diagnose cases and in cases with scant material, additional tests may help with diagnosis. Eighty to ninety percent of FL cases have t(14;18)(q32;q21), which places the BCL2 gene transcription under the control of the IGH promoter. In addition, about 10% of FL cases have 3q27 aberrancies at the BCL6 gene.36-38 More recently, cases of FL with bulky inguinal disease negative for IGH-BCL2 and BCL6 translocations were found to have 1p36 deletions. These 1p36-deleted FLs typically have a diffuse pattern and a good prognosis.39 For t(14;18), 3q27, or 1p36, FISH is a sensitive means for detecting these translocations, as is PCR for IGH-BCL2.40 There are reports that t(14;18) can be detected in a substantial fraction of otherwise healthy donors at levels and rates that depend on the type of detection test used.41-43 In addition, between one-fourth and one-third of de novo DLBCLs show t(14;18), and about one-third show BCL6 abnormalities at 3q27. Therefore, these genetic changes are not specific for FL and should not be used to subtype a lymphoma as follicular in origin.

Use of IGH-BCL2 as a marker for MRD is still controversial. Some studies have found that a postinduction and posttransplantation IGH-BCL2-positive finding by PCR predicted relapse.44,45 However, others studies have not found significance to postinduction IGH-BCL2 positivity.46 The NCCN guidelines recommend testing for IGH-BCL2 or BCL6 translocations or 1p36 deletion only if this testing is needed for diagnosis. The guidelines do not recommend using these genetic assays in follow-up biopsies, as the importance of treating early relapse has not been definitively demonstrated.

Therefore, if a lymphoma has morphologic, histologic, and IHC findings consistent with FL, then cytogenetic, FISH, or PCR testing is not needed for diagnosis but may be used as confirmation. Follow-up molecular and cytogenetic testing should be avoided if the original cytogenetic abnormality is unknown. That is, IGH-BCL2 FISH should be performed in follow-up samples only if the original lymphoma is known to contain the translocation. As follow-up genetic testing is of disputed clinical significance even in cases in which the original molecular change is known, the NCCN recommendations for therapy are no different. The HMG subcommittee does not recommend molecular or cytogenetic testing in FL beyond what is required for initial diagnosis.

T-Cell Lymphomas

Mature T-Cell Lymphoma and Leukemia

For mature T-cell lymphoma (TCL) and leukemia, the clinical and morphologic criteria have a very important role in the initial workup. However, IHC immunophenotyping is crucial for definitive diagnosis and subclassification. Flow cytometry is routinely used in diagnosing diseases such as T-cell prolymphocytic leukemia (TPLL), T-cell large granular lymphocytic (LGL) leukemia, and Sézary syndrome. T-cell clonality studies, preferably with BIOMED-II–validated primers against targets such as T-cell receptor γ (TCR-γ) and TCR-β, are commonly used as ancillary tests in the evaluation of TCL and T-cell leukemia. Clonality testing, however, comes with an important caveat: A gene rearrangement study is never a substitute for thorough morphologic and immunophenotypic evaluation. Clonality is not proof of malignancy.

Significant advances in TCL classification have led to revisions and the inclusion of new provisional entities in the 2016 World Health Organization classification of lymphoid neoplasms.47 Many of these changes originated in studies of gene expression profiling and the genetic landscape of T-cell neoplasms. Even though subsets of peripheral TCL not otherwise specified (PTCL-NOS) have been recognized on the basis of phenotypic and molecular abnormalities with possible clinical implications, in most cases molecular testing is not part of routine practice. Typically, only a few cytogenetic abnormalities and genetic mutations are used in the evaluation of TCL and T-cell leukemia.

 

 

A group of T-cell lymphoproliferative disorders with expression of T follicular helper cell markers can be identified with IHC. These disorders include angioimmunoblastic TCL; follicular TCL, a new entity that is a PTCL-NOS subset; and primary cutaneous CD4-positive small/medium T-cell lymphoproliferative disorder. The neoplastic cells should express at least 2 or 3 T follicular helper cell–related antigens, including CD279/PD1, CD10, BCL6, CXCL13, ICOS, SAP, and CCR5; the most commonly used are PD1, BCL6, and CD10. Recurrent fusion of ITK-SYK translocation t(5;9) or CTLA4-CD28 is also common in follicular TCL. Although recurrent mutation is found in these entities, conventional karyotyping or IHC should be sufficient for diagnosis.

Cutaneous γ-Δ T-Cell Lymphoma

Among cutaneous TCLs, primary cutaneous γ-Δ TCL is clinically aggressive (median survival, 15 months). By definition, the cells are of the TCR-γ-Δ phenotype. When available, this phenotype is best shown with IHC staining for TCR-γ or TCR-Δ with appropriate detection methods. In routine practice, however, absence of β-F1 expression is sufficient to infer the TCR-γ-Δ phenotype.48

Peripheral T-Cell Lymphoma

Gene expression profiling analysis of PTCLs has identified at least 3 subtypes characterized by overexpression of GATA3, TBX21, and cytotoxic genes and expression of the corresponding proteins with IHC.47 These subtypes are associated with different clinical behavior and therapy responses. The GATA3 subtype has an inferior prognosis and shows a high level of T helper type 2 cytokines, which can be identified with IHC. As IHC-stained GATA3 has been available as a marker of urothelial carcinoma at most IHC laboratories, GATA3 IHC staining also may be considered in the evaluation of PTCLs.

Many monoclonal antibody therapies are being used as primary or secondary regimens in the treatment of TCL. Clinical trials are working to establish their efficacy. If treatment with a monoclonal antibody is being considered, it is appropriate to conduct IHC to demonstrate the presence of the target antigen and at follow-up, to demonstrate the efficacy of treatment. These therapies include alemtuzumab, which targets CD52, and brentuximab, which targets CD30.

T-Cell Large Granular Lymphocytic Leukemia

T-cell LGL leukemia is a complex diagnosis that requires persistent clonal expansion of LGLs and clinically peripheral blood cytopenia. In many cases, the diagnosis is difficult to establish, as benign large granular lymphocytosis with clonal T cells may occur in conjunction with viral infections or autoimmune disorders. Somatic mutations in the STAT3 (signal transducer and activator of transcription 3) gene are found in 40% of patients with T-cell LGL leukemia.49 More recently, somatic mutations in the STAT5B gene were identified in 2% of T-cell LGL leukemia subsets. The clinical course of T-cell LGL leukemia in patients with the STAT5B mutation is aggressive and fatal, clearly different from the relatively favorable course of typical T-cell LGL leukemia.50 The HMG subcommittee recommends considering a STAT3 and STAT5B mutation study for selected cases in which it is difficult to distinguish true T-cell LGL leukemia from its reactive expansions.

T-Cell Prolymphocytic Leukemia

T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive disease and is most commonly associated with a prolymphocytic morphology and expression of CD4. However, since a specific immunophenotypic profile of T-PLL has not been identified, flow cytometry is not adequate in isolation for definitive classification as T-PLL.51 A diagnosis of T-PLL often requires cytogenetics or a FISH study to confirm a suspected case. Most TPLL cases harbor characteristic chromosomal abnormalities involving 14q11.2 (TCR α/Δ), 14q32 (TCL1 gene), or Xq28 (MTCP1 gene); abnormalities of chromosomes 8 and 12p; and deletions of the long arm of chromosomes 5, 6, 11, and 13.52 In routine practice, a TPLL diagnosis should be confirmed with inv(14) (paracentric inversion of chromosome 14) or t(14;14) by conventional cytogenetic studies and/or rearrangement of the TCL1 gene by FISH. In addition, ATM and JAK3 mutations are highly recurrent in TPLL and may aid in the diagnosis of challenging cases.53

Anaplastic Large Cell Lymphoma

The World Health Organization recognizes 3 distinct types of anaplastic large cell lymphoma (ALCL): systemic anaplastic lymphoma kinase (ALK)–positive ALCL, systemic ALK-negative ALCL, and primary cutaneous ALCL. Systemic ALK-positive ALCLs consistently have ALK gene rearrangements and favorable outcomes. The most common translocation is the t(2;5) rearrangement of NPM1 and ALK, though other ALK partners are also possible. In contrast, systemic ALK-negative ALCLs lack ALK gene rearrangements and as a whole have outcomes inferior to those of systemic ALK-positive ALCLs. However, studies have found systemic ALK-negative ALCL to be a genetically and clinically heterogeneous entity.54 About 30% of cases have rearrangements of the DUSP22-IRF4 locus on 6p25.3 (DUSP22 rearrangement), and these cases have favorable outcomes similar to those of systemic ALK-positive ALCL.55 Only 8% of patients have TP63 rearrangements and very poor outcomes. The remaining cases lack ALK, DUSP22, and TP63 rearrangements and have intermediate outcomes. The HMG subcommittee recommends considering DUSP22 rearrangement by FISH in the evaluation of systemic ALK-negative ALCL.

Conclusion

The pathologic diagnosis, classification, and risk stratification of lymphoma and leukemia require an approach that integrates morphology, flow cytometry, cytogenetics, and molecular pathology. Rapidly evolving molecular techniques currently allow for detailed description of the molecular defects in lymphoma and leukemia, including driver mutations, amplification/deletion events, and clonal evolution. Unfortunately, the technical ability to catalogue the molecular defects in lymphoma and leukemia, often at great expense, is outpacing the ability to use this detailed information in treating patients with hematologic malignancies. The challenge, then, is to identify best practices for the diagnosis and classification of lymphoma and leukemia in VHA hospitals that incorporate the most useful molecular tests without wasting financial resources.

In this report, the HMG subcommittee of the MGPW has presented its recommendations for molecular testing in AML, MPN, MDS, and lymphomas in the context of standard morphologic and immunophenotypic approaches to hematopathology diagnosis and classification. Adoption of these recommendations by VHA hospitals and clinics should help ensure that all VA patients with hematologic malignancies benefit from the latest advances in precision medicine.

Within the vast and comprehensive national VHA health care system are multiple centers of expertise in hematopathology. In addition, multiple VA clinical molecular diagnostic laboratories are performing state-of-the-art testing. The HMG subcommittee proposes that, to make best use of these expert resources, the VHA should establish an interfacility hematopathology consultation service. This service would allow any VA pathologist to consult a board-certified hematopathologist regarding use of ancillary molecular genetic testing in the diagnosis of hematologic malignancy.

In addition, the HMG subcommittee recommends consolidating VA molecular diagnostic reference laboratories and having them perform molecular testing for other VA hospitals rather than using commercial reference laboratories, where testing standards are not uniform and results may be difficult to interpret. Several well-established VA clinical laboratories with technical expertise and informatics support are already performing selected molecular diagnostic testing. These laboratories’ resources should be expanded, where practical, to cost-effectively provide VA expertise to all veterans and to improve access to appropriate molecular diagnostic testing.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner , Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

 

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29. Weissmann S, Roller A, Jeromin S, et al. Prognostic impact and landscape of NOTCH1 mutations in chronic lymphocytic leukemia (CLL): a study on 852 patients. Leukemia. 2013;27(12):2393-2396.

30. Vegliante MC, Palomero J, Pérez-Galán P, et al. SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma. Blood. 2013;121(12):2175-2185.

31. King RL, Gonsalves WI, Ansell SM, et al. Lymphoplasmacytic lymphoma with a non-IgM paraprotein shows clinical and pathologic heterogeneity and may harbor MYD88 L265P mutations. Am J Clin Pathol. 2016;145(6):843-851.

32. Insuasti-Beltran G, Gale JM, Wilson CS, Foucar K, Czuchlewski DR. Significance of MYD88 L265P mutation status in the subclassification of low-grade B-cell lymphoma/leukemia. Arch Pathol Lab Med. 2015;139(8):1035-1041.

33. Wang XJ, Kim A, Li S. Immunohistochemical analysis using a BRAF V600E mutation specific antibody is highly sensitive and specific for the diagnosis of hairy cell leukemia. Int J Clin Exp Pathol. 2014;7(7):4323-4328.

34. Nakamura T, Tateishi K, Niwa T, et al. Recurrent mutations of CD79B and MYD88 are the hallmark of primary central nervous system lymphomas. Neuropathol Appl Neurobiol. 2016;42(3):279-290.

35. Chapman MA, Lawrence MS, Keats JJ, et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011;471(7339):467-472.

36. Bosga-Bouwer AG, van Imhoff GW, Boonstra R, et al. Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t(14;18), 3q27, or other translocations: t(14;18) and 3q27 are mutually exclusive. Blood. 2003;101(3):1149-1154.

37. Gu K, Fu K, Jain S, et al. t(14;18)-negative follicular lymphomas are associated with a high frequency of BCL6 rearrangement at the alternative breakpoint region. Mod Pathol. 2009;22(9):1251-1257.

38. Katzenberger T, Ott G, Klein T, Kalla J, Müller-Hermelink HK, Ott MM. Cytogenetic alterations affecting BCL6 are predominantly found in follicular lymphomas grade 3B with a diffuse large B-cell component. Am J Pathol. 2004;165(2):481-490.

39. Katzenberger T, Kalla J, Leich E, et al. A distinctive subtype of t(14;18)-negative nodal follicular non-Hodgkin lymphoma characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36. Blood. 2009;113(5):1053-1061.

40. Belaud-Rotureau MA, Parrens M, Carrere N, et al. Interphase fluorescence in situ hybridization is more sensitive than BIOMED-2 polymerase chain reaction protocol in detecting IGH-BCL2 rearrangement in both fixed and frozen lymph node with follicular lymphoma. Hum Pathol. 2007;38(2):365-372.

41. Limpens J, Stad R, Vos C, et al. Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Blood. 1995;85(9):2528-2536.

42. Schmitt C, Balogh B, Grundt A, et al. The bcl-2/IgH rearrangement in a population of 204 healthy individuals: occurrence, age and gender distribution, breakpoints, and detection method validity. Leuk Res. 2006;30(6):745-750.

43. Summers KE, Goff LK, Wilson AG, Gupta RK, Lister TA, Fitzgibbon J. Frequency of the Bcl-2/IgH rearrangement in normal individuals: implications for the monitoring of disease in patients with follicular lymphoma. J Clin Oncol. 2001;19(2):420-424.

44. Galimberti S, Luminari S, Ciabatti E, et al. Minimal residual disease after conventional treatment significantly impacts on progression-free survival of patients with follicular lymphoma: the FIL FOLL05 trial. Clin Cancer Res. 2014;20(24):6398-6405.

45. Ladetto M, Lobetti-Bodoni C, Mantoan B, et al; Fondazione Italiana Linfomi. Persistence of minimal residual disease in bone marrow predicts outcome in follicular lymphomas treated with a rituximab-intensive program. Blood. 2013;122(23):3759-3766.

46. van Oers MHJ, Tönnissen E, Van Glabbeke M, et al. BCL-2/IgH polymerase chain reaction status at the end of induction treatment is not predictive for progression-free survival in relapsed/resistant follicular lymphoma: results of a prospective randomized EORTC 20981 phase III intergroup study. J Clin Oncol. 2010;28(13):2246-2252.

47. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-2390.

48. Dewar R, Andea AA, Guitart J, Arber DA, Weiss LM. Best practices in diagnostic immunohistochemistry: workup of cutaneous lymphoid lesions in the diagnosis of primary cutaneous lymphoma. Arch Pathol Lab Med. 2015;139(3):338-350.

49. Koskela HLM, Eldfors S, Ellonen P, et al. Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med. 2012;366(20):1905-1913.

50. Rajala HL, Eldfors S, Kuusanmäki H, et al. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood. 2013;121(22):4541-4550.

51. Chen X, Cherian S. Immunophenotypic characterization of T-cell prolymphocytic leukemia. Am J Clin Pathol. 2013;140(5):727-735.

52. Delgado P, Starshak P, Rao N, Tirado C. A comprehensive update on molecular and cytogenetic abnormalities in T-cell prolymphocytic leukemia (T-PLL). J Assoc Genet Technol. 2012;38(4):193-198.

53. Stengel A, Kern W, Zenger M, et al. Genetic characterization of T-PLL reveals two major biologic subgroups and JAK3 mutations as prognostic marker. Genes Chromosomes Cancer. 2016;55(1):82-94.

54. Thompson MA, Stumph J, Henrickson SE, et al. Differential gene expression in anaplastic lymphoma kinase-positive and anaplastic lymphoma kinase-negative anaplastic large cell lymphomas. Hum Pathol. 2005;36(5):494-504.

55. King R, Dao L, McPhail E, et al. Morphologic features of ALK-negative anaplastic large cell lymphomas with DUSP22 rearrangements. Am J Surg Pathol. 2016;40(1):36-43.

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Dr. Wang-Rodriguez is the chief of pathology at VISN 22 Consolidated Pathology and Laboratory Medicine Services, and Dr. Phan is the director of Molecular Pathology Laboratory at the VA Greater Los Angeles Healthcare System in California. Dr. Yunes is a staff hematopathologist, and Dr. Ehsan is the chief of Pathology and Laboratory Medicine Services, both at the South Texas Veterans Healthcare System in San Antonio. Dr. Ma is a staff pathologist at the Syracuse VAMC in New York. Dr. Baddoura is chief of Pathology and Laboratory Medicine Services at the Orlando VAMC in Florida. Dr. Mosse is chief of Pathology and Laboratory Medicine Services at the Tennessee Valley Healthcare System in Nashville. Dr. Kim is a staff hematopathologist at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Lu is chief of Pathology and Laboratory Medicine Services at the San Francisco VA Health Care System in California. Dr. Dong is director of Hematopathology at the VA Puget Sound Health Care System in Seattle, Washington. Dr. Schichman is chief of Pathology and Laboratory Medicine Services at the Central Arkansas Veterans Healthcare System in Little Rock. Dr. Icardi is the VA national director of Pathology and Laboratory Medicine Services.

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Dr. Wang-Rodriguez is the chief of pathology at VISN 22 Consolidated Pathology and Laboratory Medicine Services, and Dr. Phan is the director of Molecular Pathology Laboratory at the VA Greater Los Angeles Healthcare System in California. Dr. Yunes is a staff hematopathologist, and Dr. Ehsan is the chief of Pathology and Laboratory Medicine Services, both at the South Texas Veterans Healthcare System in San Antonio. Dr. Ma is a staff pathologist at the Syracuse VAMC in New York. Dr. Baddoura is chief of Pathology and Laboratory Medicine Services at the Orlando VAMC in Florida. Dr. Mosse is chief of Pathology and Laboratory Medicine Services at the Tennessee Valley Healthcare System in Nashville. Dr. Kim is a staff hematopathologist at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Lu is chief of Pathology and Laboratory Medicine Services at the San Francisco VA Health Care System in California. Dr. Dong is director of Hematopathology at the VA Puget Sound Health Care System in Seattle, Washington. Dr. Schichman is chief of Pathology and Laboratory Medicine Services at the Central Arkansas Veterans Healthcare System in Little Rock. Dr. Icardi is the VA national director of Pathology and Laboratory Medicine Services.

Author and Disclosure Information

Dr. Wang-Rodriguez is the chief of pathology at VISN 22 Consolidated Pathology and Laboratory Medicine Services, and Dr. Phan is the director of Molecular Pathology Laboratory at the VA Greater Los Angeles Healthcare System in California. Dr. Yunes is a staff hematopathologist, and Dr. Ehsan is the chief of Pathology and Laboratory Medicine Services, both at the South Texas Veterans Healthcare System in San Antonio. Dr. Ma is a staff pathologist at the Syracuse VAMC in New York. Dr. Baddoura is chief of Pathology and Laboratory Medicine Services at the Orlando VAMC in Florida. Dr. Mosse is chief of Pathology and Laboratory Medicine Services at the Tennessee Valley Healthcare System in Nashville. Dr. Kim is a staff hematopathologist at Brigham and Women’s Hospital in Boston, Massachusetts. Dr. Lu is chief of Pathology and Laboratory Medicine Services at the San Francisco VA Health Care System in California. Dr. Dong is director of Hematopathology at the VA Puget Sound Health Care System in Seattle, Washington. Dr. Schichman is chief of Pathology and Laboratory Medicine Services at the Central Arkansas Veterans Healthcare System in Little Rock. Dr. Icardi is the VA national director of Pathology and Laboratory Medicine Services.

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In January 2015, President Obama introduced the Precision Medicine Initiative, a program set up to identify new biomedical discoveries for the development of a personalized knowledge base of disease entities and individualized treatments. Advances in precision medicine typically involve the use of targeted therapies tailored to individual genetic characteristics identified with molecular testing. The goals are to improve survival and reduce adverse effects. With an initial budget of $215 million, this initiative presented a unique opportunity to combine efforts in genomic discovery, bioinformatic analysis, and health information technology to move toward data-driven, evidence-based precision medicine.1

The VHA is the largest comprehensive health care system in the U. S. and has more than 1,700 care sites serving nearly 9 million veterans each year. The budget for this single-payer system is proposed by the President and approved by Congress. As the VHA must treat a diverse and aging veteran population in an environment of rising costs and budget constraints, limited resources must be monitored and appropriated for the most cost-effective health care delivery. Precision medicine offers a model in which physicians can select the most appropriate diagnostic tests in defined clinical settings to direct clinical care. It supports the testing needed to subdivide each disease category into distinct subcategories. Nevertheless, the need for fiscal responsibility in a capitated health care system recommends testing in cases in which it can change therapy or prognosis rather than for purely academic reasons.

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Pathology and Laboratory Medicine Service

Given limited resources and an increasing number of requests for advanced molecular testing, the VA Pathology and Laboratory Medicine Service (P&LMS) formed the Molecular Genetics Pathology Workgroup (MGPW) in September 2013. The charter listed the tasks of the MGPW to “provide recommendations on how to effectively use molecular genetics tests, promote increased quality and availability of testing within the VHA, encourage internal referral testing, provide an organizational structure for Molecular Genetics Testing Consortia, and create a P&LMS policy for molecular genetic testing in general, specifically addressing the issues surrounding laboratory developed testing.” The MGPW has 4 subcommittees: molecular oncology, pharmacogenetics, hematopathology molecular genetics (HMG), and genetic medicine. Since its inception, the HMG subcommittee has had several objectives:

  • Standardize the molecular testing nomenclature for and develop practice guidelines for acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, lymphoma, and plasma cell neoplasms;
  • Develop standardized reporting guidelines for current VA molecular laboratories;
  • Identify new tests as they are being reported in the literature and collaborate with hematology and oncology services to evaluate the clinical utility of these tests for VA patients;
  • Network current VA molecular laboratories, perform fact-finding for these laboratories, and compile test menus; and
  • Assess for the formation of VA-wide interfacility consultation services for hematopathology so that all VA facilities, regardless of their complexity, will be able to access the expertise of hematopathology-trained pathologists (Appendix).

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The HMG subcommittee met monthly and discussed various diagnostic entities in hematopathology. For hematolymphoid malignancies, it was generally agreed that the traditional laboratory tools of morphology, flow cytometry, and immunohistochemistry (IHC) are standard in initial assessment and often in diagnosis. As the clinical molecular and cytogenetic assays of karyotype, fluorescence in situ hybridization (FISH), advanced DNA sequencing, microarray, and highly sensitive polymerase chain reaction (PCR) analysis affect diagnosis, subclassification, minimal residual disease (MRD) monitoring, prognosis, and therapy selection, their use is marked by a high degree of variability. As a result, standardization is needed. As each laboratory develops and reports ancillary testing, the variable reporting formats may generate postanalytic errors.

A detailed description of all molecular methodologies is beyond the scope of this article. For practicing pathologists, challenges remain in overall cost and reimbursement, extensive and time-consuming data analysis, and in some cases, interpretation differences.

Myeloid Neoplasms

Myeloid malignancies were divided into AML, MPN, and MDS. Next-generation sequencing (NGS) information for these malignancies was used to identify various contributory functional categories, including cell signaling (FLT3, KIT, JAK2, MPL, KRAS/NRAS, PTPN11, NF1, CSF3R); transcription (CEBPA, RUNX1, GATA1/GATA2, PHF6, ETV6); splicing (SF3B1, SRSF2, ZRSR2, U2AF1); epigenetics (DNMT3A, TET2, IDH1/IDH2, ASXL1, EZH2, SUZ12, KDM6A); cohesin complex (STAG2, SMC1A, SMC3, RAD21); and cell cycle (TP53, NPM1).2

Acute Myeloid Leukemia

The HMG subcommittee reviewed the literature on prognostically significant genes in myeloid leukemias. Karyotype abnormalities, such as t(8;21) and inv(16), collectively known as the core-binding factor (CBF) leukemias, t(15;17), t(11q23) (KMT2A/MLL), and so forth, are recurrent lesions in AML. Included in the minimum set of genes recommended by the National Comprehensive Cancer Network (NCCN) for AML prognosis evaluation are nucleolar protein nucleophosmin (NPM1), CCAAT/enhancer-binding protein α (CEBPA), and fms-related tyrosine kinase 3 (FLT3).3 Presence of NPM1 and CEBPA mutations generally is thought to confer a favorable prognosis in AML with a normal karyotype. However, FLT3 with or without NPM1 confers an adverse prognosis. Any KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) mutation changes an otherwise better CBF AML prognosis to a poor prognosis. The methods used to detect these gene mutations are based on either PCR analysis or sequencing.

Some of the chromosomal translocations, such as inv(16)/t(16;16) in AML and t(15;17) in acute promyelocytic leukemia, can be monitored with FISH or reverse transcription–PCR (RT-PCR) analysis. As NPM1 mutations tend to be seen in recurrence, they can be used as molecular markers for MRD. Other mutations that provide important prognostic information in AML include:

  • Activating insertions/duplications in the FLT3 receptor tyrosine kinase, which can be detected with PCR sizing assays;
  • Mutations in the KIT receptor tyrosine kinase, which can be detected with DNA sequencing or more limited hotspot PCR;
  • Mutations in the DNA methyltransferase, DNMT3A, a poor prognostic indicator seen in 22% of cases of AML, also detected with gene sequencing or more limited hotspot PCR; and
  • Another set of genes, TET2, IDH1, IDH2, KRAS, NRAS, EZH2, and ASXL1, is mutated in MPN as well as AML and MDS, making a common molecular panel with next-generation sequencing useful in diagnosing and risk-stratifying all myeloid neoplasms.

The HMG subcommittee agreed that, for de novo AML, chromosomal karyotype is the standard of care, necessary in detecting known cytogenetic abnormalities as well as a wide range of lesions that might indicate a diagnosis of AML with myelodysplasia-related changes at time of diagnosis. In addition, molecular analysis of FLT3 is useful in determining prognosis, and CEBPA (biallelic) and NPM1 mutations are good prognostic factors in normal-karyotype AML. KMT2A (MLL) rearrangements should be tested with FISH if the lineage is ambiguous. The PML-RARA fusion gene also should be tested with FISH if morphologic and flow cytometry results suggest acute promyelocytic leukemia (Table). At this time, testing for TP53, DNMT3A, RAS, and other such mutations is not recommended because it is not cost-effective for the VA.

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Myeloproliferative Neoplasms

Myeloproliferative neoplasms are clonal hematopoietic stem cell disorders characterized by proliferation of at least 1 myeloid lineage: granulocytic, erythroid, or megakaryocytic. Myeloproliferative neoplasms show a range of recurrent chromosomal translocations, such as BCR-ABL1 fusion in chronic myelogenous leukemia (CML) that can be detected with RT-PCR analysis as well as FISH. In CML, BCR-ABL1 fusion transcript levels detected by a quantitative PCR (qPCR) method are now used to monitor the course of CML therapy with tyrosine kinase inhibitors (TKIs) and to trigger a treatment change in drug-resistant cases. Given the importance of qPCR in clinical management, significant progress has been made in standardizing both the PCR protocol and the reference materials used to calibrate the BCR-ABL1 PCR assay. BCR-ABL1–negative MPN, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are most commonly associated with mutations in the tyrosine kinase JAK2. Mutations in CALR and MPL are seen in a subset of patients with ET and PMF as well, whereas PV is essentially exclusively a disease of JAK2 mutations.

Chronic myelogenous leukemia is the prototypical MPN. To establish the initial diagnosis, FISH and/or qPCR for BCR-ABL1 fusion should be used. If CML is confirmed, the sample can be reflexed to qPCR BCR-ABL1 on the initial peripheral blood and/or bone marrow sample(s) to establish the patient’s baseline. In addition, a bone marrow sample (aspirate) should be used for a complete karyotype and for morphologic confirmation of disease phase.

 

 

For follow-up assessment of CML patients’ response to TKI treatment, qPCR for BCR-ABL1 should be tested with a peripheral blood sample or a bone marrow sample every 3 months.4 A peripheral blood sample is more commonly used because it is conveniently obtained. Early molecular response as indicated by a BCR-ABL1 transcript ratio of < 10% on the International Scale at 3 months, has a strong prognostic value.5 Major molecular response as indicated by a BCR-ABL1 transcript ratio of < 0.1% on the International Scale at 12 to 18 months is also highly prognostic.5

After the peripheral blood sample becomes negative for BCR-ABL1 by qPCR, testing bone marrow samples may be considered. If important treatment response benchmarks are not achieved, or response is lost with rising BCR-ABL1 levels (TKI resistance), ABL1 kinase domain mutation analysis as well as repeat FISH (to assess for copy number multiplication) should be performed to guide further management. Patients with the ABL1 T315I mutation are resistant to all first-line TKIs but may respond to later third-generation TKIs.6

BCR-ABL1–negative MPNs include PV, ET, and PMF. Bone marrow morphology remains the cornerstone of ET and PMF diagnosis. The discovery of JAK2, CALR, and MPL mutations has contributed to how these disorders are diagnosed.7-12 Besides providing the clonality proof that is crucial for diagnosis, the molecular markers influence the prognosis. The JAK2 (p.V617F) or less common JAK2 exon 12 mutations, which are detected in more than 95% of PV cases, are used as molecular markers to confirm diagnosis.7 Further, the JAK2 (p.V617F), CALR (exon 9), and MPL (exon 10) mutations are detected in ET (~60%, 25%, and 3%-5%, respectively) and PMF (~55%, 30%, and 5%, respectively).12 If ET or PMF is suspected clinically, first JAK2 (p.V617F) mutation analysis should be performed, then CALR mutation analysis, and finally MPL mutation analysis. Although novel gain-of-function JAK2 and MPL mutations were recently discovered in triple-negative ET (negative for canonical mutations in JAK2, CALR, and MPL) and PMF by whole exome sequencing,13 clinical testing is not readily available. Besides its utility in the initial diagnosis of ET and PMF, the JAK2 or CALR mutation assay also may be considered for bone marrow transplantation follow-up (Table).14

Despite the continuing debate on the classification of eosinophilic myeloid disorders, the discovery of the FIP1L1-PDGFRA fusion represents a major milestone in the understanding of these disorders.15,16 Unlike PDGFRB (5q33) and FGFR1 (8p11) rearrangements, which can be detected with routine chromosomal analysis (cytogenetics), the cryptic FIP1L1-PDGFRA fusion must be detected with FISH (for CHIC2 deletion) or RT-PCR analysis. It should be pointed out that, as most eosinophilia is reactive or secondary, molecular testing for FIP1L1-PDGFRA fusion is indicated only when primary hypereosinophilia or hypereosinophilic syndrome (HES) is suspected. This is particularly the case in the following hypereosinophilia accompanying conditions: CML-like morphology, but BCR-ABL1–negative; chronic myelomonocytic leukemia (CMML)–like morphology with a normal karyotype; and new onset of cardiac damage or dysfunction.17

Primary eosinophilic myeloid disorders with PDGFRA or PDGFRB rearrangements can be treated with TKIs (eg, imatinib). Next-generation sequencing may be considered in cases of presumed HES when there is no identifiable karyotypic or FISH abnormality. Recent studies have found that cases of HES with somatic mutations indicating clonality had adverse clinical outcomes similar to those of cases of chronic eosinophilic leukemia.18

The discovery of CSF3R mutations offers a new molecular marker for the diagnosis of chronic neutrophilic leukemia (CNL), an MPN.19 The CSF3R (p.T618I) mutation or another activating CSF3R mutation is now used as a diagnostic criterion for CNL. Identification of specific CSF3R mutations may have therapeutic implications as well. The test should be ordered only for patients with clinical and morphologic findings suggestive of CNL; reactive neutrophilic leukocytosis (eg, infection, inflammation) should be ruled out before the test is ordered.

Myelodysplastic Syndrome

Myelodysplastic syndrome is a group of clonal bone marrow disorders characterized by ineffective hematopoiesis, manifested by morphologic dysplasia in ≥ 1 hematopoietic lineages and peripheral cytopenias (hemoglobin level, < 10 g/dL; platelet count, < 100×103/µL; absolute neutrophil count, < 1.8×103/µL). Diagnosis and classification of MDS depend mainly on the degree of morphologic dysplasia and blast percentages, as determined by examining well-prepared cellular bone marrow aspirate smears and/or biopsy touch preparations and peripheral blood smears.

Conventional karyotyping is an essential part of the diagnostic workup for all presumptive cases of MDS and is of both diagnostic and prognostic importance.20 About 60% of MDS cases have recurrent cytogenetic abnormalities, which can be detected with conventional karyotyping. If a high-quality cytogenetic analysis cannot be performed (eg, the bone marrow sample is inadequate), or if quick turnaround is required, an alternative FISH panel may be used to detect some of the common MDS-associated chromosomal abnormalities (eg, 5q deletion, 7q deletion/monosomy 7, +8, 20q deletion).21 Sequencing with FISH also can be useful for assessing MRD by detecting a previously identified chromosomal abnormality.

Targeted sequencing of a limited number of genes can detect mutations in the vast majority of patients with MDS. The most commonly mutated genes in MDS are SF3B1, TET2, SRSF2, ASXL1, DNMT3A, RUNX1, U2AF1, TP53, and EZH2. Mutations in SRSF2 cause RNA splicing abnormalities. In addition, mutations in TP53, EZH2, RUNX1, and ASXL1 are associated with poor prognosis,22,23 whereas mutations in SF3B1 confer better event-free survival.24 Despite these developments, the HMG subcommittee agreed that NGS-based mutation panels are not cost-effective for the VA population at this time and should not be included in a MDS workup. Only in rare situations and when clinically indicated (to change disease classification or patient management) should evaluation for specific gene mutations be considered—for instance, the SF3B1 mutation for patients with probable MDS with ring sideroblasts, if ring sideroblasts are < 15%.25

Myelodysplastic/Myeloproliferative Neoplasms

Myelodysplastic/myeloproliferative neoplasms are a group of myeloid neoplasms with clinical, laboratory, and morphologic features that overlap both MDS and MPN. In MDS/MPN, the karyotype is often normal or shows abnormalities in common with MDS.

In cases of unexplained monocytosis for which there is clinical concern for CMML, morphologic evaluation and conventional chromosomal karyotyping should be performed after other secondary causes and known myeloproliferative and myelodysplastic entities have been excluded. If concomitant hypereosinophilia is present and the karyotype is normal, FISH or PCR-based assay should be performed to rule out FIP1L1-PDGFRA rearrangements. BCR-ABL1, PDGFRB, FGFR1, and t(8;9)/PCM1-JAK2 rearrangements typically are detected with high-quality cytogenetic analysis and thus do not require targeted molecular assays. Although certain gene mutations (eg, SRSF2, TET2, ASXL1, CBL) are commonly detected in CMML, the HMG subcommittee does not recommend sequencing-based mutation panels, as there is insufficient information for testing for prognostic or treatment stratification.

If MDS/MPN with ring sideroblasts and thrombocytosis is suspected on the basis of the clinical and morphologic criteria, molecular tests for the JAK2 (p.V617F) and SF3B1 mutations may be considered in an effort to help confirm the diagnosis.

Atypical CML is a rare MDS/MPN subtype that is now better characterized molecularly with SETBP1 and/or ETNK1 mutations, which are detectable in up to a third of cases. If clinical suspicion is high, sequencing may be diagnostically helpful.

Lymphoid Neoplasms

Chronic Lymphocytic Leukemia

In CLL, recurrent chromosomal abnormalities (eg, deletions of 13q, trisomy 12, deletions of 11q, deletions of 17p) have clear prognostic value and can be detected with FISH. Other prognostic information, such as somatic mutation of immunoglobulin heavy chain variable (IgHV) genes, TP53 mutations, SF3B1, and NOTCH1 mutation, are mostly derived from PCR-based assays. The discovery of recurrently mutated genes in CLL has increased with the use of highly sensitive sequencing methods constructing a more detailed landscape of CLL at genetic, epigenetic, and cellular levels. A recent literature review summarizes the vast heterogeneity of CLL with recurrent pathogenetic findings in MYD88, SF3B1, TP53, ATM, and NOTCH1 signaling pathways.26 The treatment of CLL is rapidly evolving, and many clinical trials are proposing a change from the “watch and wait” paradigm to treatment upon initial presentation based on molecular findings. Additional testing based on new treatment options from current clinical trials will be recommended.

 

 

Flow cytometry and morphology are standard for CLL diagnosis. The HMG subcommittee recommends FISH for del(13q14), del(11q), trisomy 12, and del(17p) at time of diagnosis or immediately before therapy initiation. Zeta-chain (ζ-chain) associated protein 70 (ZAP-70) by flow cytometry and IgHV mutation status are optional (use depends on test availability). For high-risk CLL cases, PCR-based or sequencing-based assays should be used to detect the TP53 mutation, especially in CLL patients who are candidates for treatment with recently approved CLL-targeted therapies such as ibrutinib (irreversible inhibitor of Bruton tyrosine kinase) and idelalisib (PI3Kγ inhibitor). Recent studies have shown that NOTCH1 and SF3B1 mutations may have prognostic significance, but routine testing is not recommended at this time.27-29

Other B-Cell Lymphoproliferative Disorders

Unlike the common molecular changes in CLL, in other mature B-cell lymphomas, chromosomal translocations that juxtapose a variety of different oncogenes next to an Ig gene enhancer usually are—and those that switch regions less commonly are—important initiating events that can be detected with PCR, DNA sequencing, or FISH. In follicular lymphoma (FL), Burkitt lymphoma, marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL), these oncogenes driven by an Ig gene enhancer typically include BCL2, MYC, MALT1, and CCND1 (cyclin D1), respectively. Molecular variants of these lymphomas that lack these classical translocations often activate homologous genes (eg, cyclin D3/CCND3 is activated in variants of MCL).

Morphology, flow cytometry, and IHC are routinely used for diagnosis. In inconclusive cases, Ig gene rearrangement by PCR may be used. The Table summarizes common molecular changes in B-cell lymphomas.

Mantle cell lymphoma. MCL is a non-Hodgkin lymphoma subtype characterized by t(11;14) (q13;q32) translocations that in the majority of cases lead to overexpression of cyclin D1 (BCL1). Recent molecular profiling has identified an MCL variant that is cyclin D1–negative but SOX11-positive and may have a more aggressive clinical course.30SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive MCL.

Lymphoplasmacytic lymphoma. Lymphoplasmacytic lymphoma (LPL), MZL, and CLL/small lymphocytic lymphoma are well-defined clinicopathologic entities. However, distinguishing LPL from MZL and atypical cases of CLL can sometimes be difficult because of overlapping clinical and morphologic features. Recent studies have identified a recurrent L265P mutation in the MYD88 gene in 90% to 95% of LPL cases with IgM paraprotein and in 40% to 50% of the rare non-IgM LPL cases. In contrast, the mutation is much less frequently present in MZL and other low-grade B-cell neoplasms (2%-7%).31 Therefore, testing for this abnormality can be a diagnostic aid in these difficult-to-classify cases. In addition, from a therapeutic perspective, presence or absence of MYD88 mutation may prove more significant than presence of a specific paraprotein or histopathologic features. Ibrutinib has shown efficacy in LPL and demonstrates improved response rates in patients with MYD88 mutation compared with that of their mutation-negative counterparts.32 Several MYD88 inhibitors are in clinical trials. This again indicates the need to more accurately identify and subclassify these non-IgM LPL cases to ensure appropriate molecular evaluation.

Hairy cell leukemia. Flow cytometry and morphology are usually sufficient for a hairy cell leukemia (HCL) diagnosis. However, rare cases are difficult to distinguish variant HCL from other mimics. The BRAF V600E mutation recently was described as a disease-defining molecular marker for HCL—present in nearly all HCL cases but virtually absent in HCL mimics. Therefore, detection of the BRAF mutation by IHC stain with specific antibody or PCR analysis is highly sensitive and specific for the diagnosis of HCL.33

Diffuse large B-cell lymphoma. Recent molecular analysis has created various risk stratification schemata for diffuse large B-cell lymphoma (DLBCL). The HGM subcommittee agrees that well-preserved morphology, IHC, flow cytometry, and FISH-specific markers (BCL2, BCL6, cMYC) are sufficient for diagnostic, prognostic, and therapeutic purposes. Although a wide range of genes have been implicated in the pathogenesis of DLBCL, sequencing and gene expression profiling are not cost-effective at this time and do not add benefit to patient treatment.

The MYD88 L265P mutation has been identified in DLBCL, particularly the activated B-cell-like type and primary central nervous system lymphoma (PCNSL), and may have implications for ibrutinib therapy. PCNSL commonly manifests aggressive clinical behavior and has a poor prognosis. It has been proposed that the MYD88 mutation can be used as a genetic hallmark for PCNSL to distinguish CNS involvement by systemic DLBCL from PCNSL.34

Plasma cell neoplasms. Flow cytometry is acceptable for the diagnosis of plasma cell neoplasms and for residual disease follow-up. Chromosomal karyotype or FISH for IGH/CCND1, IGH/MMSET, and IGH/CMAF dual fusion probes is recommended in conjunction with morphology, IHC, and flow cytometry. In plasma cell myeloma, several genetic mutations can be detected with NGS, including mutations in NRAS, KRAS, TP53, BCL7A, DIS3, and FAM46C.35 Less commonly, BRAF mutations, previously described in melanoma and several other solid tumors, can be detected with DNA sequencing in 4% of multiple myeloma cases, which may prove promising for targeted therapy with BRAF inhibitors. However, current therapeutic decisions are based on genetic and clinical factors, and sequence-based assays are not recommended at this time.

Follicular lymphoma. Cytology, histology, and IHC typically are sufficient for diagnosing FL. In difficult-to-diagnose cases and in cases with scant material, additional tests may help with diagnosis. Eighty to ninety percent of FL cases have t(14;18)(q32;q21), which places the BCL2 gene transcription under the control of the IGH promoter. In addition, about 10% of FL cases have 3q27 aberrancies at the BCL6 gene.36-38 More recently, cases of FL with bulky inguinal disease negative for IGH-BCL2 and BCL6 translocations were found to have 1p36 deletions. These 1p36-deleted FLs typically have a diffuse pattern and a good prognosis.39 For t(14;18), 3q27, or 1p36, FISH is a sensitive means for detecting these translocations, as is PCR for IGH-BCL2.40 There are reports that t(14;18) can be detected in a substantial fraction of otherwise healthy donors at levels and rates that depend on the type of detection test used.41-43 In addition, between one-fourth and one-third of de novo DLBCLs show t(14;18), and about one-third show BCL6 abnormalities at 3q27. Therefore, these genetic changes are not specific for FL and should not be used to subtype a lymphoma as follicular in origin.

Use of IGH-BCL2 as a marker for MRD is still controversial. Some studies have found that a postinduction and posttransplantation IGH-BCL2-positive finding by PCR predicted relapse.44,45 However, others studies have not found significance to postinduction IGH-BCL2 positivity.46 The NCCN guidelines recommend testing for IGH-BCL2 or BCL6 translocations or 1p36 deletion only if this testing is needed for diagnosis. The guidelines do not recommend using these genetic assays in follow-up biopsies, as the importance of treating early relapse has not been definitively demonstrated.

Therefore, if a lymphoma has morphologic, histologic, and IHC findings consistent with FL, then cytogenetic, FISH, or PCR testing is not needed for diagnosis but may be used as confirmation. Follow-up molecular and cytogenetic testing should be avoided if the original cytogenetic abnormality is unknown. That is, IGH-BCL2 FISH should be performed in follow-up samples only if the original lymphoma is known to contain the translocation. As follow-up genetic testing is of disputed clinical significance even in cases in which the original molecular change is known, the NCCN recommendations for therapy are no different. The HMG subcommittee does not recommend molecular or cytogenetic testing in FL beyond what is required for initial diagnosis.

T-Cell Lymphomas

Mature T-Cell Lymphoma and Leukemia

For mature T-cell lymphoma (TCL) and leukemia, the clinical and morphologic criteria have a very important role in the initial workup. However, IHC immunophenotyping is crucial for definitive diagnosis and subclassification. Flow cytometry is routinely used in diagnosing diseases such as T-cell prolymphocytic leukemia (TPLL), T-cell large granular lymphocytic (LGL) leukemia, and Sézary syndrome. T-cell clonality studies, preferably with BIOMED-II–validated primers against targets such as T-cell receptor γ (TCR-γ) and TCR-β, are commonly used as ancillary tests in the evaluation of TCL and T-cell leukemia. Clonality testing, however, comes with an important caveat: A gene rearrangement study is never a substitute for thorough morphologic and immunophenotypic evaluation. Clonality is not proof of malignancy.

Significant advances in TCL classification have led to revisions and the inclusion of new provisional entities in the 2016 World Health Organization classification of lymphoid neoplasms.47 Many of these changes originated in studies of gene expression profiling and the genetic landscape of T-cell neoplasms. Even though subsets of peripheral TCL not otherwise specified (PTCL-NOS) have been recognized on the basis of phenotypic and molecular abnormalities with possible clinical implications, in most cases molecular testing is not part of routine practice. Typically, only a few cytogenetic abnormalities and genetic mutations are used in the evaluation of TCL and T-cell leukemia.

 

 

A group of T-cell lymphoproliferative disorders with expression of T follicular helper cell markers can be identified with IHC. These disorders include angioimmunoblastic TCL; follicular TCL, a new entity that is a PTCL-NOS subset; and primary cutaneous CD4-positive small/medium T-cell lymphoproliferative disorder. The neoplastic cells should express at least 2 or 3 T follicular helper cell–related antigens, including CD279/PD1, CD10, BCL6, CXCL13, ICOS, SAP, and CCR5; the most commonly used are PD1, BCL6, and CD10. Recurrent fusion of ITK-SYK translocation t(5;9) or CTLA4-CD28 is also common in follicular TCL. Although recurrent mutation is found in these entities, conventional karyotyping or IHC should be sufficient for diagnosis.

Cutaneous γ-Δ T-Cell Lymphoma

Among cutaneous TCLs, primary cutaneous γ-Δ TCL is clinically aggressive (median survival, 15 months). By definition, the cells are of the TCR-γ-Δ phenotype. When available, this phenotype is best shown with IHC staining for TCR-γ or TCR-Δ with appropriate detection methods. In routine practice, however, absence of β-F1 expression is sufficient to infer the TCR-γ-Δ phenotype.48

Peripheral T-Cell Lymphoma

Gene expression profiling analysis of PTCLs has identified at least 3 subtypes characterized by overexpression of GATA3, TBX21, and cytotoxic genes and expression of the corresponding proteins with IHC.47 These subtypes are associated with different clinical behavior and therapy responses. The GATA3 subtype has an inferior prognosis and shows a high level of T helper type 2 cytokines, which can be identified with IHC. As IHC-stained GATA3 has been available as a marker of urothelial carcinoma at most IHC laboratories, GATA3 IHC staining also may be considered in the evaluation of PTCLs.

Many monoclonal antibody therapies are being used as primary or secondary regimens in the treatment of TCL. Clinical trials are working to establish their efficacy. If treatment with a monoclonal antibody is being considered, it is appropriate to conduct IHC to demonstrate the presence of the target antigen and at follow-up, to demonstrate the efficacy of treatment. These therapies include alemtuzumab, which targets CD52, and brentuximab, which targets CD30.

T-Cell Large Granular Lymphocytic Leukemia

T-cell LGL leukemia is a complex diagnosis that requires persistent clonal expansion of LGLs and clinically peripheral blood cytopenia. In many cases, the diagnosis is difficult to establish, as benign large granular lymphocytosis with clonal T cells may occur in conjunction with viral infections or autoimmune disorders. Somatic mutations in the STAT3 (signal transducer and activator of transcription 3) gene are found in 40% of patients with T-cell LGL leukemia.49 More recently, somatic mutations in the STAT5B gene were identified in 2% of T-cell LGL leukemia subsets. The clinical course of T-cell LGL leukemia in patients with the STAT5B mutation is aggressive and fatal, clearly different from the relatively favorable course of typical T-cell LGL leukemia.50 The HMG subcommittee recommends considering a STAT3 and STAT5B mutation study for selected cases in which it is difficult to distinguish true T-cell LGL leukemia from its reactive expansions.

T-Cell Prolymphocytic Leukemia

T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive disease and is most commonly associated with a prolymphocytic morphology and expression of CD4. However, since a specific immunophenotypic profile of T-PLL has not been identified, flow cytometry is not adequate in isolation for definitive classification as T-PLL.51 A diagnosis of T-PLL often requires cytogenetics or a FISH study to confirm a suspected case. Most TPLL cases harbor characteristic chromosomal abnormalities involving 14q11.2 (TCR α/Δ), 14q32 (TCL1 gene), or Xq28 (MTCP1 gene); abnormalities of chromosomes 8 and 12p; and deletions of the long arm of chromosomes 5, 6, 11, and 13.52 In routine practice, a TPLL diagnosis should be confirmed with inv(14) (paracentric inversion of chromosome 14) or t(14;14) by conventional cytogenetic studies and/or rearrangement of the TCL1 gene by FISH. In addition, ATM and JAK3 mutations are highly recurrent in TPLL and may aid in the diagnosis of challenging cases.53

Anaplastic Large Cell Lymphoma

The World Health Organization recognizes 3 distinct types of anaplastic large cell lymphoma (ALCL): systemic anaplastic lymphoma kinase (ALK)–positive ALCL, systemic ALK-negative ALCL, and primary cutaneous ALCL. Systemic ALK-positive ALCLs consistently have ALK gene rearrangements and favorable outcomes. The most common translocation is the t(2;5) rearrangement of NPM1 and ALK, though other ALK partners are also possible. In contrast, systemic ALK-negative ALCLs lack ALK gene rearrangements and as a whole have outcomes inferior to those of systemic ALK-positive ALCLs. However, studies have found systemic ALK-negative ALCL to be a genetically and clinically heterogeneous entity.54 About 30% of cases have rearrangements of the DUSP22-IRF4 locus on 6p25.3 (DUSP22 rearrangement), and these cases have favorable outcomes similar to those of systemic ALK-positive ALCL.55 Only 8% of patients have TP63 rearrangements and very poor outcomes. The remaining cases lack ALK, DUSP22, and TP63 rearrangements and have intermediate outcomes. The HMG subcommittee recommends considering DUSP22 rearrangement by FISH in the evaluation of systemic ALK-negative ALCL.

Conclusion

The pathologic diagnosis, classification, and risk stratification of lymphoma and leukemia require an approach that integrates morphology, flow cytometry, cytogenetics, and molecular pathology. Rapidly evolving molecular techniques currently allow for detailed description of the molecular defects in lymphoma and leukemia, including driver mutations, amplification/deletion events, and clonal evolution. Unfortunately, the technical ability to catalogue the molecular defects in lymphoma and leukemia, often at great expense, is outpacing the ability to use this detailed information in treating patients with hematologic malignancies. The challenge, then, is to identify best practices for the diagnosis and classification of lymphoma and leukemia in VHA hospitals that incorporate the most useful molecular tests without wasting financial resources.

In this report, the HMG subcommittee of the MGPW has presented its recommendations for molecular testing in AML, MPN, MDS, and lymphomas in the context of standard morphologic and immunophenotypic approaches to hematopathology diagnosis and classification. Adoption of these recommendations by VHA hospitals and clinics should help ensure that all VA patients with hematologic malignancies benefit from the latest advances in precision medicine.

Within the vast and comprehensive national VHA health care system are multiple centers of expertise in hematopathology. In addition, multiple VA clinical molecular diagnostic laboratories are performing state-of-the-art testing. The HMG subcommittee proposes that, to make best use of these expert resources, the VHA should establish an interfacility hematopathology consultation service. This service would allow any VA pathologist to consult a board-certified hematopathologist regarding use of ancillary molecular genetic testing in the diagnosis of hematologic malignancy.

In addition, the HMG subcommittee recommends consolidating VA molecular diagnostic reference laboratories and having them perform molecular testing for other VA hospitals rather than using commercial reference laboratories, where testing standards are not uniform and results may be difficult to interpret. Several well-established VA clinical laboratories with technical expertise and informatics support are already performing selected molecular diagnostic testing. These laboratories’ resources should be expanded, where practical, to cost-effectively provide VA expertise to all veterans and to improve access to appropriate molecular diagnostic testing.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner , Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

 

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In January 2015, President Obama introduced the Precision Medicine Initiative, a program set up to identify new biomedical discoveries for the development of a personalized knowledge base of disease entities and individualized treatments. Advances in precision medicine typically involve the use of targeted therapies tailored to individual genetic characteristics identified with molecular testing. The goals are to improve survival and reduce adverse effects. With an initial budget of $215 million, this initiative presented a unique opportunity to combine efforts in genomic discovery, bioinformatic analysis, and health information technology to move toward data-driven, evidence-based precision medicine.1

The VHA is the largest comprehensive health care system in the U. S. and has more than 1,700 care sites serving nearly 9 million veterans each year. The budget for this single-payer system is proposed by the President and approved by Congress. As the VHA must treat a diverse and aging veteran population in an environment of rising costs and budget constraints, limited resources must be monitored and appropriated for the most cost-effective health care delivery. Precision medicine offers a model in which physicians can select the most appropriate diagnostic tests in defined clinical settings to direct clinical care. It supports the testing needed to subdivide each disease category into distinct subcategories. Nevertheless, the need for fiscal responsibility in a capitated health care system recommends testing in cases in which it can change therapy or prognosis rather than for purely academic reasons.

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Pathology and Laboratory Medicine Service

Given limited resources and an increasing number of requests for advanced molecular testing, the VA Pathology and Laboratory Medicine Service (P&LMS) formed the Molecular Genetics Pathology Workgroup (MGPW) in September 2013. The charter listed the tasks of the MGPW to “provide recommendations on how to effectively use molecular genetics tests, promote increased quality and availability of testing within the VHA, encourage internal referral testing, provide an organizational structure for Molecular Genetics Testing Consortia, and create a P&LMS policy for molecular genetic testing in general, specifically addressing the issues surrounding laboratory developed testing.” The MGPW has 4 subcommittees: molecular oncology, pharmacogenetics, hematopathology molecular genetics (HMG), and genetic medicine. Since its inception, the HMG subcommittee has had several objectives:

  • Standardize the molecular testing nomenclature for and develop practice guidelines for acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, lymphoma, and plasma cell neoplasms;
  • Develop standardized reporting guidelines for current VA molecular laboratories;
  • Identify new tests as they are being reported in the literature and collaborate with hematology and oncology services to evaluate the clinical utility of these tests for VA patients;
  • Network current VA molecular laboratories, perform fact-finding for these laboratories, and compile test menus; and
  • Assess for the formation of VA-wide interfacility consultation services for hematopathology so that all VA facilities, regardless of their complexity, will be able to access the expertise of hematopathology-trained pathologists (Appendix).

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The HMG subcommittee met monthly and discussed various diagnostic entities in hematopathology. For hematolymphoid malignancies, it was generally agreed that the traditional laboratory tools of morphology, flow cytometry, and immunohistochemistry (IHC) are standard in initial assessment and often in diagnosis. As the clinical molecular and cytogenetic assays of karyotype, fluorescence in situ hybridization (FISH), advanced DNA sequencing, microarray, and highly sensitive polymerase chain reaction (PCR) analysis affect diagnosis, subclassification, minimal residual disease (MRD) monitoring, prognosis, and therapy selection, their use is marked by a high degree of variability. As a result, standardization is needed. As each laboratory develops and reports ancillary testing, the variable reporting formats may generate postanalytic errors.

A detailed description of all molecular methodologies is beyond the scope of this article. For practicing pathologists, challenges remain in overall cost and reimbursement, extensive and time-consuming data analysis, and in some cases, interpretation differences.

Myeloid Neoplasms

Myeloid malignancies were divided into AML, MPN, and MDS. Next-generation sequencing (NGS) information for these malignancies was used to identify various contributory functional categories, including cell signaling (FLT3, KIT, JAK2, MPL, KRAS/NRAS, PTPN11, NF1, CSF3R); transcription (CEBPA, RUNX1, GATA1/GATA2, PHF6, ETV6); splicing (SF3B1, SRSF2, ZRSR2, U2AF1); epigenetics (DNMT3A, TET2, IDH1/IDH2, ASXL1, EZH2, SUZ12, KDM6A); cohesin complex (STAG2, SMC1A, SMC3, RAD21); and cell cycle (TP53, NPM1).2

Acute Myeloid Leukemia

The HMG subcommittee reviewed the literature on prognostically significant genes in myeloid leukemias. Karyotype abnormalities, such as t(8;21) and inv(16), collectively known as the core-binding factor (CBF) leukemias, t(15;17), t(11q23) (KMT2A/MLL), and so forth, are recurrent lesions in AML. Included in the minimum set of genes recommended by the National Comprehensive Cancer Network (NCCN) for AML prognosis evaluation are nucleolar protein nucleophosmin (NPM1), CCAAT/enhancer-binding protein α (CEBPA), and fms-related tyrosine kinase 3 (FLT3).3 Presence of NPM1 and CEBPA mutations generally is thought to confer a favorable prognosis in AML with a normal karyotype. However, FLT3 with or without NPM1 confers an adverse prognosis. Any KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) mutation changes an otherwise better CBF AML prognosis to a poor prognosis. The methods used to detect these gene mutations are based on either PCR analysis or sequencing.

Some of the chromosomal translocations, such as inv(16)/t(16;16) in AML and t(15;17) in acute promyelocytic leukemia, can be monitored with FISH or reverse transcription–PCR (RT-PCR) analysis. As NPM1 mutations tend to be seen in recurrence, they can be used as molecular markers for MRD. Other mutations that provide important prognostic information in AML include:

  • Activating insertions/duplications in the FLT3 receptor tyrosine kinase, which can be detected with PCR sizing assays;
  • Mutations in the KIT receptor tyrosine kinase, which can be detected with DNA sequencing or more limited hotspot PCR;
  • Mutations in the DNA methyltransferase, DNMT3A, a poor prognostic indicator seen in 22% of cases of AML, also detected with gene sequencing or more limited hotspot PCR; and
  • Another set of genes, TET2, IDH1, IDH2, KRAS, NRAS, EZH2, and ASXL1, is mutated in MPN as well as AML and MDS, making a common molecular panel with next-generation sequencing useful in diagnosing and risk-stratifying all myeloid neoplasms.

The HMG subcommittee agreed that, for de novo AML, chromosomal karyotype is the standard of care, necessary in detecting known cytogenetic abnormalities as well as a wide range of lesions that might indicate a diagnosis of AML with myelodysplasia-related changes at time of diagnosis. In addition, molecular analysis of FLT3 is useful in determining prognosis, and CEBPA (biallelic) and NPM1 mutations are good prognostic factors in normal-karyotype AML. KMT2A (MLL) rearrangements should be tested with FISH if the lineage is ambiguous. The PML-RARA fusion gene also should be tested with FISH if morphologic and flow cytometry results suggest acute promyelocytic leukemia (Table). At this time, testing for TP53, DNMT3A, RAS, and other such mutations is not recommended because it is not cost-effective for the VA.

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Myeloproliferative Neoplasms

Myeloproliferative neoplasms are clonal hematopoietic stem cell disorders characterized by proliferation of at least 1 myeloid lineage: granulocytic, erythroid, or megakaryocytic. Myeloproliferative neoplasms show a range of recurrent chromosomal translocations, such as BCR-ABL1 fusion in chronic myelogenous leukemia (CML) that can be detected with RT-PCR analysis as well as FISH. In CML, BCR-ABL1 fusion transcript levels detected by a quantitative PCR (qPCR) method are now used to monitor the course of CML therapy with tyrosine kinase inhibitors (TKIs) and to trigger a treatment change in drug-resistant cases. Given the importance of qPCR in clinical management, significant progress has been made in standardizing both the PCR protocol and the reference materials used to calibrate the BCR-ABL1 PCR assay. BCR-ABL1–negative MPN, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are most commonly associated with mutations in the tyrosine kinase JAK2. Mutations in CALR and MPL are seen in a subset of patients with ET and PMF as well, whereas PV is essentially exclusively a disease of JAK2 mutations.

Chronic myelogenous leukemia is the prototypical MPN. To establish the initial diagnosis, FISH and/or qPCR for BCR-ABL1 fusion should be used. If CML is confirmed, the sample can be reflexed to qPCR BCR-ABL1 on the initial peripheral blood and/or bone marrow sample(s) to establish the patient’s baseline. In addition, a bone marrow sample (aspirate) should be used for a complete karyotype and for morphologic confirmation of disease phase.

 

 

For follow-up assessment of CML patients’ response to TKI treatment, qPCR for BCR-ABL1 should be tested with a peripheral blood sample or a bone marrow sample every 3 months.4 A peripheral blood sample is more commonly used because it is conveniently obtained. Early molecular response as indicated by a BCR-ABL1 transcript ratio of < 10% on the International Scale at 3 months, has a strong prognostic value.5 Major molecular response as indicated by a BCR-ABL1 transcript ratio of < 0.1% on the International Scale at 12 to 18 months is also highly prognostic.5

After the peripheral blood sample becomes negative for BCR-ABL1 by qPCR, testing bone marrow samples may be considered. If important treatment response benchmarks are not achieved, or response is lost with rising BCR-ABL1 levels (TKI resistance), ABL1 kinase domain mutation analysis as well as repeat FISH (to assess for copy number multiplication) should be performed to guide further management. Patients with the ABL1 T315I mutation are resistant to all first-line TKIs but may respond to later third-generation TKIs.6

BCR-ABL1–negative MPNs include PV, ET, and PMF. Bone marrow morphology remains the cornerstone of ET and PMF diagnosis. The discovery of JAK2, CALR, and MPL mutations has contributed to how these disorders are diagnosed.7-12 Besides providing the clonality proof that is crucial for diagnosis, the molecular markers influence the prognosis. The JAK2 (p.V617F) or less common JAK2 exon 12 mutations, which are detected in more than 95% of PV cases, are used as molecular markers to confirm diagnosis.7 Further, the JAK2 (p.V617F), CALR (exon 9), and MPL (exon 10) mutations are detected in ET (~60%, 25%, and 3%-5%, respectively) and PMF (~55%, 30%, and 5%, respectively).12 If ET or PMF is suspected clinically, first JAK2 (p.V617F) mutation analysis should be performed, then CALR mutation analysis, and finally MPL mutation analysis. Although novel gain-of-function JAK2 and MPL mutations were recently discovered in triple-negative ET (negative for canonical mutations in JAK2, CALR, and MPL) and PMF by whole exome sequencing,13 clinical testing is not readily available. Besides its utility in the initial diagnosis of ET and PMF, the JAK2 or CALR mutation assay also may be considered for bone marrow transplantation follow-up (Table).14

Despite the continuing debate on the classification of eosinophilic myeloid disorders, the discovery of the FIP1L1-PDGFRA fusion represents a major milestone in the understanding of these disorders.15,16 Unlike PDGFRB (5q33) and FGFR1 (8p11) rearrangements, which can be detected with routine chromosomal analysis (cytogenetics), the cryptic FIP1L1-PDGFRA fusion must be detected with FISH (for CHIC2 deletion) or RT-PCR analysis. It should be pointed out that, as most eosinophilia is reactive or secondary, molecular testing for FIP1L1-PDGFRA fusion is indicated only when primary hypereosinophilia or hypereosinophilic syndrome (HES) is suspected. This is particularly the case in the following hypereosinophilia accompanying conditions: CML-like morphology, but BCR-ABL1–negative; chronic myelomonocytic leukemia (CMML)–like morphology with a normal karyotype; and new onset of cardiac damage or dysfunction.17

Primary eosinophilic myeloid disorders with PDGFRA or PDGFRB rearrangements can be treated with TKIs (eg, imatinib). Next-generation sequencing may be considered in cases of presumed HES when there is no identifiable karyotypic or FISH abnormality. Recent studies have found that cases of HES with somatic mutations indicating clonality had adverse clinical outcomes similar to those of cases of chronic eosinophilic leukemia.18

The discovery of CSF3R mutations offers a new molecular marker for the diagnosis of chronic neutrophilic leukemia (CNL), an MPN.19 The CSF3R (p.T618I) mutation or another activating CSF3R mutation is now used as a diagnostic criterion for CNL. Identification of specific CSF3R mutations may have therapeutic implications as well. The test should be ordered only for patients with clinical and morphologic findings suggestive of CNL; reactive neutrophilic leukocytosis (eg, infection, inflammation) should be ruled out before the test is ordered.

Myelodysplastic Syndrome

Myelodysplastic syndrome is a group of clonal bone marrow disorders characterized by ineffective hematopoiesis, manifested by morphologic dysplasia in ≥ 1 hematopoietic lineages and peripheral cytopenias (hemoglobin level, < 10 g/dL; platelet count, < 100×103/µL; absolute neutrophil count, < 1.8×103/µL). Diagnosis and classification of MDS depend mainly on the degree of morphologic dysplasia and blast percentages, as determined by examining well-prepared cellular bone marrow aspirate smears and/or biopsy touch preparations and peripheral blood smears.

Conventional karyotyping is an essential part of the diagnostic workup for all presumptive cases of MDS and is of both diagnostic and prognostic importance.20 About 60% of MDS cases have recurrent cytogenetic abnormalities, which can be detected with conventional karyotyping. If a high-quality cytogenetic analysis cannot be performed (eg, the bone marrow sample is inadequate), or if quick turnaround is required, an alternative FISH panel may be used to detect some of the common MDS-associated chromosomal abnormalities (eg, 5q deletion, 7q deletion/monosomy 7, +8, 20q deletion).21 Sequencing with FISH also can be useful for assessing MRD by detecting a previously identified chromosomal abnormality.

Targeted sequencing of a limited number of genes can detect mutations in the vast majority of patients with MDS. The most commonly mutated genes in MDS are SF3B1, TET2, SRSF2, ASXL1, DNMT3A, RUNX1, U2AF1, TP53, and EZH2. Mutations in SRSF2 cause RNA splicing abnormalities. In addition, mutations in TP53, EZH2, RUNX1, and ASXL1 are associated with poor prognosis,22,23 whereas mutations in SF3B1 confer better event-free survival.24 Despite these developments, the HMG subcommittee agreed that NGS-based mutation panels are not cost-effective for the VA population at this time and should not be included in a MDS workup. Only in rare situations and when clinically indicated (to change disease classification or patient management) should evaluation for specific gene mutations be considered—for instance, the SF3B1 mutation for patients with probable MDS with ring sideroblasts, if ring sideroblasts are < 15%.25

Myelodysplastic/Myeloproliferative Neoplasms

Myelodysplastic/myeloproliferative neoplasms are a group of myeloid neoplasms with clinical, laboratory, and morphologic features that overlap both MDS and MPN. In MDS/MPN, the karyotype is often normal or shows abnormalities in common with MDS.

In cases of unexplained monocytosis for which there is clinical concern for CMML, morphologic evaluation and conventional chromosomal karyotyping should be performed after other secondary causes and known myeloproliferative and myelodysplastic entities have been excluded. If concomitant hypereosinophilia is present and the karyotype is normal, FISH or PCR-based assay should be performed to rule out FIP1L1-PDGFRA rearrangements. BCR-ABL1, PDGFRB, FGFR1, and t(8;9)/PCM1-JAK2 rearrangements typically are detected with high-quality cytogenetic analysis and thus do not require targeted molecular assays. Although certain gene mutations (eg, SRSF2, TET2, ASXL1, CBL) are commonly detected in CMML, the HMG subcommittee does not recommend sequencing-based mutation panels, as there is insufficient information for testing for prognostic or treatment stratification.

If MDS/MPN with ring sideroblasts and thrombocytosis is suspected on the basis of the clinical and morphologic criteria, molecular tests for the JAK2 (p.V617F) and SF3B1 mutations may be considered in an effort to help confirm the diagnosis.

Atypical CML is a rare MDS/MPN subtype that is now better characterized molecularly with SETBP1 and/or ETNK1 mutations, which are detectable in up to a third of cases. If clinical suspicion is high, sequencing may be diagnostically helpful.

Lymphoid Neoplasms

Chronic Lymphocytic Leukemia

In CLL, recurrent chromosomal abnormalities (eg, deletions of 13q, trisomy 12, deletions of 11q, deletions of 17p) have clear prognostic value and can be detected with FISH. Other prognostic information, such as somatic mutation of immunoglobulin heavy chain variable (IgHV) genes, TP53 mutations, SF3B1, and NOTCH1 mutation, are mostly derived from PCR-based assays. The discovery of recurrently mutated genes in CLL has increased with the use of highly sensitive sequencing methods constructing a more detailed landscape of CLL at genetic, epigenetic, and cellular levels. A recent literature review summarizes the vast heterogeneity of CLL with recurrent pathogenetic findings in MYD88, SF3B1, TP53, ATM, and NOTCH1 signaling pathways.26 The treatment of CLL is rapidly evolving, and many clinical trials are proposing a change from the “watch and wait” paradigm to treatment upon initial presentation based on molecular findings. Additional testing based on new treatment options from current clinical trials will be recommended.

 

 

Flow cytometry and morphology are standard for CLL diagnosis. The HMG subcommittee recommends FISH for del(13q14), del(11q), trisomy 12, and del(17p) at time of diagnosis or immediately before therapy initiation. Zeta-chain (ζ-chain) associated protein 70 (ZAP-70) by flow cytometry and IgHV mutation status are optional (use depends on test availability). For high-risk CLL cases, PCR-based or sequencing-based assays should be used to detect the TP53 mutation, especially in CLL patients who are candidates for treatment with recently approved CLL-targeted therapies such as ibrutinib (irreversible inhibitor of Bruton tyrosine kinase) and idelalisib (PI3Kγ inhibitor). Recent studies have shown that NOTCH1 and SF3B1 mutations may have prognostic significance, but routine testing is not recommended at this time.27-29

Other B-Cell Lymphoproliferative Disorders

Unlike the common molecular changes in CLL, in other mature B-cell lymphomas, chromosomal translocations that juxtapose a variety of different oncogenes next to an Ig gene enhancer usually are—and those that switch regions less commonly are—important initiating events that can be detected with PCR, DNA sequencing, or FISH. In follicular lymphoma (FL), Burkitt lymphoma, marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL), these oncogenes driven by an Ig gene enhancer typically include BCL2, MYC, MALT1, and CCND1 (cyclin D1), respectively. Molecular variants of these lymphomas that lack these classical translocations often activate homologous genes (eg, cyclin D3/CCND3 is activated in variants of MCL).

Morphology, flow cytometry, and IHC are routinely used for diagnosis. In inconclusive cases, Ig gene rearrangement by PCR may be used. The Table summarizes common molecular changes in B-cell lymphomas.

Mantle cell lymphoma. MCL is a non-Hodgkin lymphoma subtype characterized by t(11;14) (q13;q32) translocations that in the majority of cases lead to overexpression of cyclin D1 (BCL1). Recent molecular profiling has identified an MCL variant that is cyclin D1–negative but SOX11-positive and may have a more aggressive clinical course.30SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive MCL.

Lymphoplasmacytic lymphoma. Lymphoplasmacytic lymphoma (LPL), MZL, and CLL/small lymphocytic lymphoma are well-defined clinicopathologic entities. However, distinguishing LPL from MZL and atypical cases of CLL can sometimes be difficult because of overlapping clinical and morphologic features. Recent studies have identified a recurrent L265P mutation in the MYD88 gene in 90% to 95% of LPL cases with IgM paraprotein and in 40% to 50% of the rare non-IgM LPL cases. In contrast, the mutation is much less frequently present in MZL and other low-grade B-cell neoplasms (2%-7%).31 Therefore, testing for this abnormality can be a diagnostic aid in these difficult-to-classify cases. In addition, from a therapeutic perspective, presence or absence of MYD88 mutation may prove more significant than presence of a specific paraprotein or histopathologic features. Ibrutinib has shown efficacy in LPL and demonstrates improved response rates in patients with MYD88 mutation compared with that of their mutation-negative counterparts.32 Several MYD88 inhibitors are in clinical trials. This again indicates the need to more accurately identify and subclassify these non-IgM LPL cases to ensure appropriate molecular evaluation.

Hairy cell leukemia. Flow cytometry and morphology are usually sufficient for a hairy cell leukemia (HCL) diagnosis. However, rare cases are difficult to distinguish variant HCL from other mimics. The BRAF V600E mutation recently was described as a disease-defining molecular marker for HCL—present in nearly all HCL cases but virtually absent in HCL mimics. Therefore, detection of the BRAF mutation by IHC stain with specific antibody or PCR analysis is highly sensitive and specific for the diagnosis of HCL.33

Diffuse large B-cell lymphoma. Recent molecular analysis has created various risk stratification schemata for diffuse large B-cell lymphoma (DLBCL). The HGM subcommittee agrees that well-preserved morphology, IHC, flow cytometry, and FISH-specific markers (BCL2, BCL6, cMYC) are sufficient for diagnostic, prognostic, and therapeutic purposes. Although a wide range of genes have been implicated in the pathogenesis of DLBCL, sequencing and gene expression profiling are not cost-effective at this time and do not add benefit to patient treatment.

The MYD88 L265P mutation has been identified in DLBCL, particularly the activated B-cell-like type and primary central nervous system lymphoma (PCNSL), and may have implications for ibrutinib therapy. PCNSL commonly manifests aggressive clinical behavior and has a poor prognosis. It has been proposed that the MYD88 mutation can be used as a genetic hallmark for PCNSL to distinguish CNS involvement by systemic DLBCL from PCNSL.34

Plasma cell neoplasms. Flow cytometry is acceptable for the diagnosis of plasma cell neoplasms and for residual disease follow-up. Chromosomal karyotype or FISH for IGH/CCND1, IGH/MMSET, and IGH/CMAF dual fusion probes is recommended in conjunction with morphology, IHC, and flow cytometry. In plasma cell myeloma, several genetic mutations can be detected with NGS, including mutations in NRAS, KRAS, TP53, BCL7A, DIS3, and FAM46C.35 Less commonly, BRAF mutations, previously described in melanoma and several other solid tumors, can be detected with DNA sequencing in 4% of multiple myeloma cases, which may prove promising for targeted therapy with BRAF inhibitors. However, current therapeutic decisions are based on genetic and clinical factors, and sequence-based assays are not recommended at this time.

Follicular lymphoma. Cytology, histology, and IHC typically are sufficient for diagnosing FL. In difficult-to-diagnose cases and in cases with scant material, additional tests may help with diagnosis. Eighty to ninety percent of FL cases have t(14;18)(q32;q21), which places the BCL2 gene transcription under the control of the IGH promoter. In addition, about 10% of FL cases have 3q27 aberrancies at the BCL6 gene.36-38 More recently, cases of FL with bulky inguinal disease negative for IGH-BCL2 and BCL6 translocations were found to have 1p36 deletions. These 1p36-deleted FLs typically have a diffuse pattern and a good prognosis.39 For t(14;18), 3q27, or 1p36, FISH is a sensitive means for detecting these translocations, as is PCR for IGH-BCL2.40 There are reports that t(14;18) can be detected in a substantial fraction of otherwise healthy donors at levels and rates that depend on the type of detection test used.41-43 In addition, between one-fourth and one-third of de novo DLBCLs show t(14;18), and about one-third show BCL6 abnormalities at 3q27. Therefore, these genetic changes are not specific for FL and should not be used to subtype a lymphoma as follicular in origin.

Use of IGH-BCL2 as a marker for MRD is still controversial. Some studies have found that a postinduction and posttransplantation IGH-BCL2-positive finding by PCR predicted relapse.44,45 However, others studies have not found significance to postinduction IGH-BCL2 positivity.46 The NCCN guidelines recommend testing for IGH-BCL2 or BCL6 translocations or 1p36 deletion only if this testing is needed for diagnosis. The guidelines do not recommend using these genetic assays in follow-up biopsies, as the importance of treating early relapse has not been definitively demonstrated.

Therefore, if a lymphoma has morphologic, histologic, and IHC findings consistent with FL, then cytogenetic, FISH, or PCR testing is not needed for diagnosis but may be used as confirmation. Follow-up molecular and cytogenetic testing should be avoided if the original cytogenetic abnormality is unknown. That is, IGH-BCL2 FISH should be performed in follow-up samples only if the original lymphoma is known to contain the translocation. As follow-up genetic testing is of disputed clinical significance even in cases in which the original molecular change is known, the NCCN recommendations for therapy are no different. The HMG subcommittee does not recommend molecular or cytogenetic testing in FL beyond what is required for initial diagnosis.

T-Cell Lymphomas

Mature T-Cell Lymphoma and Leukemia

For mature T-cell lymphoma (TCL) and leukemia, the clinical and morphologic criteria have a very important role in the initial workup. However, IHC immunophenotyping is crucial for definitive diagnosis and subclassification. Flow cytometry is routinely used in diagnosing diseases such as T-cell prolymphocytic leukemia (TPLL), T-cell large granular lymphocytic (LGL) leukemia, and Sézary syndrome. T-cell clonality studies, preferably with BIOMED-II–validated primers against targets such as T-cell receptor γ (TCR-γ) and TCR-β, are commonly used as ancillary tests in the evaluation of TCL and T-cell leukemia. Clonality testing, however, comes with an important caveat: A gene rearrangement study is never a substitute for thorough morphologic and immunophenotypic evaluation. Clonality is not proof of malignancy.

Significant advances in TCL classification have led to revisions and the inclusion of new provisional entities in the 2016 World Health Organization classification of lymphoid neoplasms.47 Many of these changes originated in studies of gene expression profiling and the genetic landscape of T-cell neoplasms. Even though subsets of peripheral TCL not otherwise specified (PTCL-NOS) have been recognized on the basis of phenotypic and molecular abnormalities with possible clinical implications, in most cases molecular testing is not part of routine practice. Typically, only a few cytogenetic abnormalities and genetic mutations are used in the evaluation of TCL and T-cell leukemia.

 

 

A group of T-cell lymphoproliferative disorders with expression of T follicular helper cell markers can be identified with IHC. These disorders include angioimmunoblastic TCL; follicular TCL, a new entity that is a PTCL-NOS subset; and primary cutaneous CD4-positive small/medium T-cell lymphoproliferative disorder. The neoplastic cells should express at least 2 or 3 T follicular helper cell–related antigens, including CD279/PD1, CD10, BCL6, CXCL13, ICOS, SAP, and CCR5; the most commonly used are PD1, BCL6, and CD10. Recurrent fusion of ITK-SYK translocation t(5;9) or CTLA4-CD28 is also common in follicular TCL. Although recurrent mutation is found in these entities, conventional karyotyping or IHC should be sufficient for diagnosis.

Cutaneous γ-Δ T-Cell Lymphoma

Among cutaneous TCLs, primary cutaneous γ-Δ TCL is clinically aggressive (median survival, 15 months). By definition, the cells are of the TCR-γ-Δ phenotype. When available, this phenotype is best shown with IHC staining for TCR-γ or TCR-Δ with appropriate detection methods. In routine practice, however, absence of β-F1 expression is sufficient to infer the TCR-γ-Δ phenotype.48

Peripheral T-Cell Lymphoma

Gene expression profiling analysis of PTCLs has identified at least 3 subtypes characterized by overexpression of GATA3, TBX21, and cytotoxic genes and expression of the corresponding proteins with IHC.47 These subtypes are associated with different clinical behavior and therapy responses. The GATA3 subtype has an inferior prognosis and shows a high level of T helper type 2 cytokines, which can be identified with IHC. As IHC-stained GATA3 has been available as a marker of urothelial carcinoma at most IHC laboratories, GATA3 IHC staining also may be considered in the evaluation of PTCLs.

Many monoclonal antibody therapies are being used as primary or secondary regimens in the treatment of TCL. Clinical trials are working to establish their efficacy. If treatment with a monoclonal antibody is being considered, it is appropriate to conduct IHC to demonstrate the presence of the target antigen and at follow-up, to demonstrate the efficacy of treatment. These therapies include alemtuzumab, which targets CD52, and brentuximab, which targets CD30.

T-Cell Large Granular Lymphocytic Leukemia

T-cell LGL leukemia is a complex diagnosis that requires persistent clonal expansion of LGLs and clinically peripheral blood cytopenia. In many cases, the diagnosis is difficult to establish, as benign large granular lymphocytosis with clonal T cells may occur in conjunction with viral infections or autoimmune disorders. Somatic mutations in the STAT3 (signal transducer and activator of transcription 3) gene are found in 40% of patients with T-cell LGL leukemia.49 More recently, somatic mutations in the STAT5B gene were identified in 2% of T-cell LGL leukemia subsets. The clinical course of T-cell LGL leukemia in patients with the STAT5B mutation is aggressive and fatal, clearly different from the relatively favorable course of typical T-cell LGL leukemia.50 The HMG subcommittee recommends considering a STAT3 and STAT5B mutation study for selected cases in which it is difficult to distinguish true T-cell LGL leukemia from its reactive expansions.

T-Cell Prolymphocytic Leukemia

T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive disease and is most commonly associated with a prolymphocytic morphology and expression of CD4. However, since a specific immunophenotypic profile of T-PLL has not been identified, flow cytometry is not adequate in isolation for definitive classification as T-PLL.51 A diagnosis of T-PLL often requires cytogenetics or a FISH study to confirm a suspected case. Most TPLL cases harbor characteristic chromosomal abnormalities involving 14q11.2 (TCR α/Δ), 14q32 (TCL1 gene), or Xq28 (MTCP1 gene); abnormalities of chromosomes 8 and 12p; and deletions of the long arm of chromosomes 5, 6, 11, and 13.52 In routine practice, a TPLL diagnosis should be confirmed with inv(14) (paracentric inversion of chromosome 14) or t(14;14) by conventional cytogenetic studies and/or rearrangement of the TCL1 gene by FISH. In addition, ATM and JAK3 mutations are highly recurrent in TPLL and may aid in the diagnosis of challenging cases.53

Anaplastic Large Cell Lymphoma

The World Health Organization recognizes 3 distinct types of anaplastic large cell lymphoma (ALCL): systemic anaplastic lymphoma kinase (ALK)–positive ALCL, systemic ALK-negative ALCL, and primary cutaneous ALCL. Systemic ALK-positive ALCLs consistently have ALK gene rearrangements and favorable outcomes. The most common translocation is the t(2;5) rearrangement of NPM1 and ALK, though other ALK partners are also possible. In contrast, systemic ALK-negative ALCLs lack ALK gene rearrangements and as a whole have outcomes inferior to those of systemic ALK-positive ALCLs. However, studies have found systemic ALK-negative ALCL to be a genetically and clinically heterogeneous entity.54 About 30% of cases have rearrangements of the DUSP22-IRF4 locus on 6p25.3 (DUSP22 rearrangement), and these cases have favorable outcomes similar to those of systemic ALK-positive ALCL.55 Only 8% of patients have TP63 rearrangements and very poor outcomes. The remaining cases lack ALK, DUSP22, and TP63 rearrangements and have intermediate outcomes. The HMG subcommittee recommends considering DUSP22 rearrangement by FISH in the evaluation of systemic ALK-negative ALCL.

Conclusion

The pathologic diagnosis, classification, and risk stratification of lymphoma and leukemia require an approach that integrates morphology, flow cytometry, cytogenetics, and molecular pathology. Rapidly evolving molecular techniques currently allow for detailed description of the molecular defects in lymphoma and leukemia, including driver mutations, amplification/deletion events, and clonal evolution. Unfortunately, the technical ability to catalogue the molecular defects in lymphoma and leukemia, often at great expense, is outpacing the ability to use this detailed information in treating patients with hematologic malignancies. The challenge, then, is to identify best practices for the diagnosis and classification of lymphoma and leukemia in VHA hospitals that incorporate the most useful molecular tests without wasting financial resources.

In this report, the HMG subcommittee of the MGPW has presented its recommendations for molecular testing in AML, MPN, MDS, and lymphomas in the context of standard morphologic and immunophenotypic approaches to hematopathology diagnosis and classification. Adoption of these recommendations by VHA hospitals and clinics should help ensure that all VA patients with hematologic malignancies benefit from the latest advances in precision medicine.

Within the vast and comprehensive national VHA health care system are multiple centers of expertise in hematopathology. In addition, multiple VA clinical molecular diagnostic laboratories are performing state-of-the-art testing. The HMG subcommittee proposes that, to make best use of these expert resources, the VHA should establish an interfacility hematopathology consultation service. This service would allow any VA pathologist to consult a board-certified hematopathologist regarding use of ancillary molecular genetic testing in the diagnosis of hematologic malignancy.

In addition, the HMG subcommittee recommends consolidating VA molecular diagnostic reference laboratories and having them perform molecular testing for other VA hospitals rather than using commercial reference laboratories, where testing standards are not uniform and results may be difficult to interpret. Several well-established VA clinical laboratories with technical expertise and informatics support are already performing selected molecular diagnostic testing. These laboratories’ resources should be expanded, where practical, to cost-effectively provide VA expertise to all veterans and to improve access to appropriate molecular diagnostic testing.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner , Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

 

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10. Vannucchi AM, Antonioli E, Guglielmelli P, et al. Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia. Blood. 2008;112(3):844-847.

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12. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379-2390.

13. Harrison CN, Vannucchi AM. Closing the gap: genetic landscape of MPN. Blood. 2016;127(3):276-278.

14. Tefferi A, Barbui T. Essential thrombocythemia and polycythemia vera: focus on clinical practice. Mayo Clin Proc. 2015;90(9):1283-1293.

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20. Schanz J, Tüchler H, Solé F, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. 2012;30(8):820-829.

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27. Jeromin S, Weissmann S, Haferlach C, et al. SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients. Leukemia. 2014;28(1):108-117.

28. Del Giudice I, Rossi D, Chiaretti S, et al. NOTCH1 mutations in +12 chronic lymphocytic leukemia (CLL) confer an unfavorable prognosis, induce a distinctive transcriptional profiling and refine the intermediate prognosis of +12 CLL. Haematologica. 2012;97(3):437-441.

29. Weissmann S, Roller A, Jeromin S, et al. Prognostic impact and landscape of NOTCH1 mutations in chronic lymphocytic leukemia (CLL): a study on 852 patients. Leukemia. 2013;27(12):2393-2396.

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32. Insuasti-Beltran G, Gale JM, Wilson CS, Foucar K, Czuchlewski DR. Significance of MYD88 L265P mutation status in the subclassification of low-grade B-cell lymphoma/leukemia. Arch Pathol Lab Med. 2015;139(8):1035-1041.

33. Wang XJ, Kim A, Li S. Immunohistochemical analysis using a BRAF V600E mutation specific antibody is highly sensitive and specific for the diagnosis of hairy cell leukemia. Int J Clin Exp Pathol. 2014;7(7):4323-4328.

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References

1. Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015;372(9):793-795.

2. Matynia AP, Szankasi P, Shen W, Kelley TW. Molecular genetic biomarkers in myeloid malignancies. Arch Pathol Lab Med. 2015;139(5):594-601.

3. Wang ML, Bailey NG. Acute myeloid leukemia genetics: risk stratification and implications for therapy. Arch Pathol Lab Med. 2015;139(10):1215-1223.

4. Marum JE, Branford S. Current developments in molecular monitoring in chronic myeloid leukemia. Ther Adv Hematol. 2016;7(5):237-251.

5. Hughes TP, Saglio G, Kantarjian HM, et al. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib. Blood. 2014;123(9):1353-1360.

6. Pallera A, Altman JK, Berman E, et al. Guidelines insights: chronic myeloid leukemia, version 1.2017. J Natl Compr Canc Netw. 2016;14:1505-1512.

7. James C, Ugo V, Le Couédic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144-1148.

8. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17):1779-1790.

9. Beer PA, Campbell PJ, Scott LM, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood. 2008;112(1):141-149.

10. Vannucchi AM, Antonioli E, Guglielmelli P, et al. Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia. Blood. 2008;112(3):844-847.

11. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391-2405.

12. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379-2390.

13. Harrison CN, Vannucchi AM. Closing the gap: genetic landscape of MPN. Blood. 2016;127(3):276-278.

14. Tefferi A, Barbui T. Essential thrombocythemia and polycythemia vera: focus on clinical practice. Mayo Clin Proc. 2015;90(9):1283-1293.

15. Cools J, DeAngelo DJ, Gotlib J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003;348(13):1201-1214.

16. Valent P, Klion AD, Horny HP, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol. 2012;130(3):607-612.e609.

17. Bain B, Billiland D, Horny H, Verdiman J. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1. In: Swerdlow S, Campo E, Harris N, et al, eds. WHO Classification of Tumours of the Haematopoietic and Lymphoid Tissues. Vol 2. Lyon, France: IRAC Press; 2008:68-73.

18. Wang SA, Tam W, Tsai AG, et al. Targeted next-generation sequencing identifies a subset of idiopathic hypereosinophilic syndrome with features similar to chronic eosinophilic leukemia, not otherwise specified. Mod Pathol. 2016;29(8):854-864.

19. Maxson JE, Gotlib J, Pollyea DA, et al. Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML. N Engl J Med. 2013;368(19):1781-1790.

20. Schanz J, Tüchler H, Solé F, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. 2012;30(8):820-829.

21. Marshall D, Roboz GJ. Standardizing the initial evaluation for myelodysplastic syndromes. Curr Hematol Malig Rep. 2013;8(4):361-369.

22. Damm F, Chesnais V, Nagata Y, et al. BCOR and BCORL1 mutations in myelodysplastic syndromes and related disorders. Blood. 2013;122(18):3169-3177.

23. Malcovati L, Papaemmanuil E, Ambaglio I, et al. Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia. Blood. 2014;124(9):1513-1521.

24. Papaemmanuil E, Cazzola M, Boultwood J, et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med. 2011;365(15):1384-1395.

25. Patnaik MM, Hanson CA, Sulai NH, et al. Prognostic irrelevance of ring sideroblast percentage in World Health Organization-defined myelodysplastic syndromes without excess blasts. Blood. 2012;119(24):5674-5677.

26. Guièze R, Wu CJ. Genomic and epigenomic heterogeneity in chronic lymphocytic leukemia. Blood. 2015;126(4):445-453.

27. Jeromin S, Weissmann S, Haferlach C, et al. SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients. Leukemia. 2014;28(1):108-117.

28. Del Giudice I, Rossi D, Chiaretti S, et al. NOTCH1 mutations in +12 chronic lymphocytic leukemia (CLL) confer an unfavorable prognosis, induce a distinctive transcriptional profiling and refine the intermediate prognosis of +12 CLL. Haematologica. 2012;97(3):437-441.

29. Weissmann S, Roller A, Jeromin S, et al. Prognostic impact and landscape of NOTCH1 mutations in chronic lymphocytic leukemia (CLL): a study on 852 patients. Leukemia. 2013;27(12):2393-2396.

30. Vegliante MC, Palomero J, Pérez-Galán P, et al. SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma. Blood. 2013;121(12):2175-2185.

31. King RL, Gonsalves WI, Ansell SM, et al. Lymphoplasmacytic lymphoma with a non-IgM paraprotein shows clinical and pathologic heterogeneity and may harbor MYD88 L265P mutations. Am J Clin Pathol. 2016;145(6):843-851.

32. Insuasti-Beltran G, Gale JM, Wilson CS, Foucar K, Czuchlewski DR. Significance of MYD88 L265P mutation status in the subclassification of low-grade B-cell lymphoma/leukemia. Arch Pathol Lab Med. 2015;139(8):1035-1041.

33. Wang XJ, Kim A, Li S. Immunohistochemical analysis using a BRAF V600E mutation specific antibody is highly sensitive and specific for the diagnosis of hairy cell leukemia. Int J Clin Exp Pathol. 2014;7(7):4323-4328.

34. Nakamura T, Tateishi K, Niwa T, et al. Recurrent mutations of CD79B and MYD88 are the hallmark of primary central nervous system lymphomas. Neuropathol Appl Neurobiol. 2016;42(3):279-290.

35. Chapman MA, Lawrence MS, Keats JJ, et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011;471(7339):467-472.

36. Bosga-Bouwer AG, van Imhoff GW, Boonstra R, et al. Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t(14;18), 3q27, or other translocations: t(14;18) and 3q27 are mutually exclusive. Blood. 2003;101(3):1149-1154.

37. Gu K, Fu K, Jain S, et al. t(14;18)-negative follicular lymphomas are associated with a high frequency of BCL6 rearrangement at the alternative breakpoint region. Mod Pathol. 2009;22(9):1251-1257.

38. Katzenberger T, Ott G, Klein T, Kalla J, Müller-Hermelink HK, Ott MM. Cytogenetic alterations affecting BCL6 are predominantly found in follicular lymphomas grade 3B with a diffuse large B-cell component. Am J Pathol. 2004;165(2):481-490.

39. Katzenberger T, Kalla J, Leich E, et al. A distinctive subtype of t(14;18)-negative nodal follicular non-Hodgkin lymphoma characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36. Blood. 2009;113(5):1053-1061.

40. Belaud-Rotureau MA, Parrens M, Carrere N, et al. Interphase fluorescence in situ hybridization is more sensitive than BIOMED-2 polymerase chain reaction protocol in detecting IGH-BCL2 rearrangement in both fixed and frozen lymph node with follicular lymphoma. Hum Pathol. 2007;38(2):365-372.

41. Limpens J, Stad R, Vos C, et al. Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals. Blood. 1995;85(9):2528-2536.

42. Schmitt C, Balogh B, Grundt A, et al. The bcl-2/IgH rearrangement in a population of 204 healthy individuals: occurrence, age and gender distribution, breakpoints, and detection method validity. Leuk Res. 2006;30(6):745-750.

43. Summers KE, Goff LK, Wilson AG, Gupta RK, Lister TA, Fitzgibbon J. Frequency of the Bcl-2/IgH rearrangement in normal individuals: implications for the monitoring of disease in patients with follicular lymphoma. J Clin Oncol. 2001;19(2):420-424.

44. Galimberti S, Luminari S, Ciabatti E, et al. Minimal residual disease after conventional treatment significantly impacts on progression-free survival of patients with follicular lymphoma: the FIL FOLL05 trial. Clin Cancer Res. 2014;20(24):6398-6405.

45. Ladetto M, Lobetti-Bodoni C, Mantoan B, et al; Fondazione Italiana Linfomi. Persistence of minimal residual disease in bone marrow predicts outcome in follicular lymphomas treated with a rituximab-intensive program. Blood. 2013;122(23):3759-3766.

46. van Oers MHJ, Tönnissen E, Van Glabbeke M, et al. BCL-2/IgH polymerase chain reaction status at the end of induction treatment is not predictive for progression-free survival in relapsed/resistant follicular lymphoma: results of a prospective randomized EORTC 20981 phase III intergroup study. J Clin Oncol. 2010;28(13):2246-2252.

47. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-2390.

48. Dewar R, Andea AA, Guitart J, Arber DA, Weiss LM. Best practices in diagnostic immunohistochemistry: workup of cutaneous lymphoid lesions in the diagnosis of primary cutaneous lymphoma. Arch Pathol Lab Med. 2015;139(3):338-350.

49. Koskela HLM, Eldfors S, Ellonen P, et al. Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med. 2012;366(20):1905-1913.

50. Rajala HL, Eldfors S, Kuusanmäki H, et al. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood. 2013;121(22):4541-4550.

51. Chen X, Cherian S. Immunophenotypic characterization of T-cell prolymphocytic leukemia. Am J Clin Pathol. 2013;140(5):727-735.

52. Delgado P, Starshak P, Rao N, Tirado C. A comprehensive update on molecular and cytogenetic abnormalities in T-cell prolymphocytic leukemia (T-PLL). J Assoc Genet Technol. 2012;38(4):193-198.

53. Stengel A, Kern W, Zenger M, et al. Genetic characterization of T-PLL reveals two major biologic subgroups and JAK3 mutations as prognostic marker. Genes Chromosomes Cancer. 2016;55(1):82-94.

54. Thompson MA, Stumph J, Henrickson SE, et al. Differential gene expression in anaplastic lymphoma kinase-positive and anaplastic lymphoma kinase-negative anaplastic large cell lymphomas. Hum Pathol. 2005;36(5):494-504.

55. King R, Dao L, McPhail E, et al. Morphologic features of ALK-negative anaplastic large cell lymphomas with DUSP22 rearrangements. Am J Surg Pathol. 2016;40(1):36-43.

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Nonpathologic Postdeployment Transition Symptoms in Combat National Guard Members and Reservists

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The rigid dichotomy between combat deployment and postdeployment environments necessitates a multitude of cognitive, behavioral, and emotional adjustments for National Guard members and reservists to resume postdeployment civilian lifestyles successfully. Reacclimating to the postdeployment world is not a quick process for these veterans because of the time required to adjust from a deeply ingrained military combat mentality to civilian life. The process of this reintegration into the civilian world is known as postdeployment transition.

More than half of post-9/11 combat veterans report at least some difficulty with postdeployment transition.1,2 Frequently encountered symptoms of this period include impaired sleep, low frustration tolerance, decreased attention, poor concentration, short-term memory deficits, and difficulty with emotional regulation.1,3,4 Veterans will have difficulty reintegrating into the family unit and society without successful coping strategies to address these symptoms. If transition symptoms are prolonged, veterans are at risk for developing chronic adjustment difficulty or mental health issues.

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Although there is significant attention paid to postdeployment adjustment by military family advocacy groups, there is little information in the medical literature on what constitutes common, nonpathologic postdeployment reactions among combat veterans. Frequently, when postdeployment transition symptoms are discussed, the medical literature tends to explain these in the context of a mental health disorder, such posttraumatic stress disorder (PTSD) or a cognitive injury, such as traumatic brain injury.5-8 Without a balanced understanding of normal postdeployment transitions, a health care provider (HCP) inappropriately may equate transition symptoms with the presence of mental health disorders or cognitive injury and medicalize the coping strategies needed to promote healthy adjustment.

The purpose of this article is to promote HCP awareness of common, nonpathologic postdeployment transition symptoms in combat veterans who are National Guard members or reservists. Such knowledge will enable HCPs to evaluate transition symptoms among these combat veterans reentering the civilian world, normalize common transition reactions, and recognize when further intervention is needed. This article reflects the author’s experience as a medical director working in a VA postdeployment clinic combined with data available in the medical literature and lay press.

Postdeployment Transition Symptoms

Dysregulation of emotional expression in returning combat veterans potentially can be present throughout the postdeployment period of adjustment. Although individual experiences vary widely in intensity and frequency, during postdeployment transition veterans often note difficulty in adjusting emotional expression to match that of nonmilitary counterparts.1,9-11 These difficulties usually fall into 2 broad categories: (1) relative emotional neutrality to major life events that cause nonmilitary civilians great joy or sadness; and (2) overreaction to trivial events, causing significant irritation, anger, or sadness that normally would not produce such emotional reactions in nonmilitary civilians. The former is largely overlooked in medical literature to date except in relation to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) categories, and the latter is often described in limited terms as increased irritability, restlessness, and low frustration tolerance. This emotional dysregulation creates confusing paradoxes for veterans. For example, a veteran might feel no strong emotion when notified of the death of a close relative and yet cry uncontrollably while watching a sad scene in a fictional movie.

Sleep difficulties are intrinsic to the postdeployment period.9-12 Sleep-wake cycles often are altered, reflecting residual effects of the rigid schedules required by military duties and poor sleep hygiene in the combat theater. Inadequate, nonrestful sleep is frequently reported on return to the civilian world. Difficulty falling asleep or difficulty staying asleep also commonly occurs. Nightmares may be present.

Transient difficulty with concentration and attention is often prominent within the postdeployment transition period.9-11,13 Manifestations are variable, but problems with focusing on minor tasks are commonly reported. A more intense effort to master new concepts may be required. Learning styles developed during predeployment phases may be altered so that more conscious effort is required to comprehend and retain new information.

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Short-term memory frequently may be affected during postdeployment transition.9-11,13 Veterans often report postdeployment difficulty in recalling appointments or tasks that must be completed even if they had a keen sense of memory during predeployment or deployment. Veterans also may have difficulty recalling the details of specific routines that were done without hesitation during deployment. Compared with predeployment time frames, veterans may exert greater effort to recall newly learned material.

Automatic behaviors necessary for survival in a combat theater still may be prominent in the postdeployment period.10,11,14 Aggressive driving required to avoid deployment ambush may be problematic during the postdeployment transition. Steering clear of any roadside trash may be a residual instinctive drive postdeployment because of the risk of improvised explosive devices concealed by debris in the combat theater. Veterans may avoid sitting with their back to the exit as the result of military safety training. Carrying weapons to ensure safety may be a compelling urge, because being armed and ready at all times was necessary for survival during deployment. Avoiding large crowds may be another strong tendency, because throngs of people were associated with potential danger in the combat theater.

Decision making may be challenging to resume in the postdeployment phase.9-11,15 In the deployment theater, time is relativel structured with rules in place, whereas at home veterans face a myriad of choices and decisions that must be made in order to complete the responsibilities of everyday living. As a result, making decisions about what item to buy, which clothes to wear, or what activities to prioritize, though relatively minor, can be a source of significant frustration. It may be difficult to independently navigate a realm of options available for new employment, schooling, or benefits, especially when there is little or no prior experience with these issues.

 

 

Relationship of Symptoms to Mental Health Diagnoses

Postdeployment transition symptoms do not automatically indicate the presence of an underlying mental health diagnosis. However, persistent and/or severe symptoms of postdeployment transition can overlap with or contribute to the development of mental health concerns (Table 1).14 The effects of the emotional disconnect also can exacerbate underlying mental health diagnoses.

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While postdeployment emotional numbness to major life events, irritability, sleep disturbances, and impaired concentration can be associated with acute stress disorder (ASD) or PTSD, there is a constellation of other symptoms that must be present to diagnose these psychiatric conditions.16 Diagnostic criteria include persistent intrusive symptoms associated with the trauma, persistent avoidance of triggers/reminders associated with the trauma, significant changes in physiologic and cognitive arousal states, and negative changes in mood or cognition related to the trauma.16 The symptoms must cause significant impairment in some aspect of functioning on an individual, social, or occupational level. Acute stress disorder occurs when the symptoms last 30 days or less, whereas PTSD is diagnosed if the symptoms persist longer than a month.

Impaired emotional regulation, sleep disturbances, and decreased concentration also can be associated with depression or anxiety but are insufficient in themselves to make the diagnosis of those disorders.16 At least a 2-week history of depressed mood or inability to experience interest or pleasure in activities must be present as one of the criteria for depression as well as 4 or more other symptoms affecting sleep, appetite, energy, movement, self-esteem, or suicidal thoughts. Anxiety disorders have varying specific diagnostic criteria, but recurrent excessive worrying is a hallmark. Just like ASD or PTSD, the diagnostic symptoms of either depression or anxiety disorders must be causing significant impairment in functioning on an individual, social, or occupational level.

Irritability, sleep disturbances, agitation, memory impairment, and difficulty with concentration and attention can mimic the symptoms associated with mild-to-moderate traumatic brain injury (TBI).17,18 However, symptom onset must have a temporal relationship with a TBI. The presence of other TBI symptoms not associated with normal postdeployment transition usually can be used to differentiate between the diagnoses. Those TBI symptoms include recurrent headaches, poor balance, dizziness, tinnitus, and/or light sensitivity. In the majority of mild TBI cases, the symptoms resolve spontaneously within 3 months of TBI symptom manifestation.16,19 For those with persistent postconcussive syndrome, symptoms usually stabilize or improve over time.18,19 If symptoms worsen, there is often a confounding diagnosis such as PTSD or depression.17,20,21

Some returning combat veterans mistakenly believe postdeployment emotional transition symptoms are always a sign of a mental health disorder. Because there is a significant stigma associated with mental health disorders as well as potential repercussions on their service record if they use mental health resources, many reservists and National Guard members avoid accessing health care services if they are experiencing postdeployment adjustment issues, especially if those symptoms are related to emotional transitions.22-24 Unfortunately, such avoidance carries the risk that stress-inducing symptoms will persist and potentiate adjustment problems.

Course of Symptoms

The range for the postdeployment adjustment period generally falls within 3 to 12 months but can extend longer, depending on individual factors.10,11,25 Factors include presence of significant physical injury or illness, co-occurrence of mental health issues, underlying communication styles, and efficacy of coping strategies chosen. Although there is no clear-cut time frame for transition, ideally transition is complete when the returning veteran successfully enters his or her civilian lifestyle roles and feels a sense of purpose and belonging in society.

Postdeployment transition symptoms occur on a continuum in terms of duration and intensity for reservists and National Guard members. It is difficult to predict how specific transition symptoms will affect a particular veteran. The degree to which those symptoms will complicate reintegration depends on the individual veteran’s ability to adapt within the psychosocial context in which the symptoms occur. For example, minor irritation may be short-lived if a veteran can employ techniques to diffuse that feeling. Alternatively, minor irritation also suddenly may explode into a powerful wave of anger if the veteran has significant underlying emotional tension. Similarly, impaired short-term memory may be limited to forgetting a few appointments or may be so common that the veteran is at risk of losing track of his or her day. The level of memory impairment depends on emotional functioning, co-occurring stressors, and use of adaptive strategies.

In general, as these veterans successfully take on civilian routines, postdeployment transition symptoms will improve. Although such symptom improvement may be a passive process for some veterans, others will need to actively employ strategies to help change the military combat mind-set. The goal is to initiate useful interventions early in transition before symptoms become problematic.14

There are numerous self-help techniques and mobile apps that can be applied to a wide number of symptoms. Viable strategies include exercise, yoga, meditation, mindfulness training, and cognitive reframing. Reaching out for early assistance from various military assistance organizations that are well versed in dealing with postdeployment transition challenges often is helpful for reducing stress and navigating postdeployment obstacles (Table 2).

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Symptom Strain and Exacerbation

Whenever stumbling blocks are encountered during the postdeployment period, any transition symptom can persist and/or worsen.10,11,14 Emotional disconnect and other transition symptoms can be exacerbated by physical, psychological, and social stressors common in the postdeployment period. Insomnia, poor quality sleep, or other sleep impairments that frequently occur as part of postdeployment transition can negatively impact the veteran’s ability to psychologically cope with daytime stressors. Poor concentration and short-term memory impairment noted by many reservists and National Guard members in the postdeployment phase can cause increased difficulty in attention to the moment and complicate completion of routine tasks. These difficulties can compound frustration and irritation to minor events and make it hard to emotionally connect with more serious issues.

Concentration and attention to mundane activities may be further reduced if the veteran feels no connection to the civilian world and/or experiences the surreal sensation that he or she should be attending to more serious life and death matters, such as those experienced in the combat theater. Ongoing psychological adjustment to physical injuries sustained during deployment can limit emotional flexibility when adapting to either minor or major stressors. Insufficient financial resources, work issues, or school problems can potentiate irritation, anger, and sadness and create an overwhelming emotional overload, leading to helplessness and hopelessness.

Perceived irregularities in emotional connection to the civilian world can significantly strain interpersonal relationships and be powerful impediments to successful reintegration.9,11,14 Failure to express emotions to major life events in the civilian world can result in combat veterans being viewed as not empathetic to others’ feelings. Overreaction to trivial events during postdeployment can lead to the veteran being labeled as unreasonable, controlling, and/or unpredictable. Persistent emotional disconnect with civilians engenders a growing sense of emotional isolation from family and friends when there is either incorrect interpretation of emotional transitions or failure to adapt healthy coping strategies. This isolation further enlarges the emotional chasm and may greatly diminish the veteran’s ability to seek assistance and appropriately address stressors in the civilian world.

Transition and the Family

Emotional disconnection may be more acutely felt within the immediate family unit.26 Redistribution of family unit responsibilities during deployment may mean that roles the veteran played during predeployment now may be handled by a partner. On the veteran’s return to the civilian world, such circumstances require active renegotiation of duties. Interactions with loved ones, especially children, may be colored by the family members’ individual perspectives on deployment as well as by the veteran’s transition symptoms. When there is disagreement about role responsibilities and/or underlying family resentment about deployment, conditions are ripe for significant discord between the veteran and family members, vital loss of partner intimacy, and notable loss of psychological safety to express feelings within the family unit. If there are  concerns about infidelity by the veteran or significant other during the period of deployment, postdeployment tensions can further escalate. If unaddressed in the presence of emotional disconnect, any of these situations can raise the risk of domestic violence and destruction of relationships.

Without adequate knowledge of common postdeployment transitions and coping strategies, the postdeployment transition period is often bewildering to returning veterans and their families. They are taken aback by postdeployment behaviors that do not conform to the veteran’s predeployment personality or mannerisms. Families may feel they have “lost” the veteran and view the emotionally distant postdeployment veteran as a stranger. Veterans mistakenly may view the postdeployment emotional disconnect as evidence that they were permanently altered by deployment and no longer can assimilate into the civilian world. Unless veterans and families develop an awareness of the postdeployment transition symptoms and healthy coping strategies,  these perspectives can contribute to a veteran’s persistent feelings of alienation, significant sense of personal failure, and loss of vital social supports.

 

 

When transition symptoms are or have the potential to become significant stressors, veterans would benefit from mental health counseling either individually or with family members. Overcoming the stigma of seeking mental health services can prove challenging. Explaining that these postdeployment symptoms occur commonly, stem from military combat training, can be reversed, and when reversed will empower the individual to control his or her life may help veterans overcome the stigma and seek mental health services.

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The fear of future career impairment with the military reserve or National Guard is another real concern among this cohort who might consider accessing behavioral health care, especially since VA mental health medical records can be accessed by DoD officials through links with the VHA. Fortunately, this concern can be alleviated through the use of Vet Centers, free-standing counseling centers nationwide that offer no-cost individual and family counseling to veterans with combat exposure. Vet Center counseling records are completely confidential, never shared, and are not linked to the VHA electronic health record, the DoD, or any other entity. Although Vet Center providers don’t prescribe medications, the counselors can actively address many issues for veterans and their families. For individuals who do not live near a Vet Center or for those who require psychiatric medications, a frank discussion on the benefits of treatment vs the risk of treatment avoidance must be held.

Assessing Symptoms and Coping Mechanisms

Postdeployment transition symptoms vary, depending on the nature and context of the symptom. Not only must the returning reservist and National Guard member be screened for symptoms, but HCPs also should assess the impact of those symptoms on the veteran and his or her interpersonal relationships. Some veterans will feel that the symptoms have relatively minor impact in their lives, because the veteran can easily compensate for the transient effects. Others may feel that the symptoms are somewhat burdensome because the issues are complicating the smooth transition to civilian roles. Still others will judge the symptoms to be devastating because of the negative effects on personal control, selfesteem, and emotional connection with family and friends.

In addition to screening for symptoms, HCPs should assess these veterans’ current coping adaptations to various transition symptoms. Whereas some activities may be functional and promote reintegration, other short-term coping solutions may cripple the veteran’s ability to successfully resume civilian life. Global avoidance of communication with others and/or retreating from all social situations is a destructive coping pattern that can further alienate veterans from their families and the civilian world. Reacting with anger to all stressful issues is another maladaptive pattern of coping with life’s frustrations. Because of the potential to self-medicate when dealing with social difficulties, depression, anxiety, or other mental health diagnoses, veterans may develop an inappropriate reliance on drugs or alcohol to handle postdeployment stressors.27 Therefore, HCP screening for substance use disorders (SUD) is important so that interventions can be initiated early.

Because of the overlap of postdeployment transition symptoms with mental health disorders and the relative frequency of those mental health disorders among combat veterans, HCPs should have a heightened awareness of the potential for co-occurring mental health difficulties in the postdeployment reservist and National Guard cohort. Health care providers should screen for depression, anxiety, and PTSD. Even if initial screening is done early within the transition period, repeat screening would be of benefit 6 months into the postdeployment period because of the tendency of mental health issues to develop during that time.28,29

By evaluating the impact of the transition symptom and coping strategies on these veterans’ lives, HCPs can better determine which strategies might adequately compensate for symptom effects. In general, informal counseling, even if just to help veterans normalize postdeployment transition symptoms and develop a plan to address such symptoms, can significantly minimize the negative impact of transition symptoms.14,26 Specific symptoms should be targeted by interventions that match the degree of symptom impact.

Symptoms to be aggressively addressed are those that significantly interfere with successful reintegration into the civilian world. For example, persistent sleep difficulties should be dealt with because they can worsen all other transition symptoms. However, the majority of strategies to address sleep do not require medication unless there are confounding factors such as severe nightmares. Minor memory issues attributed to the transition phase can be mitigated by several strategies to improve recall, including use of task lists, digital calendars, or other memory-prodding techniques. However, severe memory issues related to depression or anxiety likely would require pharmaceutical assistance and formal counseling in addition to other nonpharmacologic approaches.

Intermittent irritation or restlessness may be amenable to selfhelp strategies, but significant anger outbursts or aggression will require additional support, such as formal behavioral interventions to help identify the triggers and develop strategic plans to reduce emotional tension. A mild sense of not belonging may resolve without intervention, but a stronger sense of alienation will require further evaluation.

Conclusion

Civilian reintegration after combat deployment is a gradual process rather than a discrete event for reservists and National Guard members. There are common, nonpathologic postdeployment transition symptoms that, if misunderstood or inappropriately addressed, can complicate civilian reintegration. Health care providers are in the unique position to promote a healthy postdeployment transition by assisting veterans to recognize nonpathologic transition symptoms, select appropriate coping strategies, and seek further assistance for more complex problems.

References

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and after military combat deployment. JAMA. 2008;300(6):663-675.

28. Seal KH, Metzler TH, Gima KS, Bertenthal D, Maguen S, Marmar CR. Trends and risk factors for mental health diagnoses among Iraq and Afghanistan veterans Department of Veterans Affairs health care, 2002-2008. Am J Public Health. 2009;99(9):1651-1658.

29. Milliken CS, Auchterlonie JL, Hoge CW. Longitudinal assessment of mental health problems among active and reserve component soldiers returning from the Iraq war. JAMA. 2007;298(18):2141-2148.

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Related Articles

The rigid dichotomy between combat deployment and postdeployment environments necessitates a multitude of cognitive, behavioral, and emotional adjustments for National Guard members and reservists to resume postdeployment civilian lifestyles successfully. Reacclimating to the postdeployment world is not a quick process for these veterans because of the time required to adjust from a deeply ingrained military combat mentality to civilian life. The process of this reintegration into the civilian world is known as postdeployment transition.

More than half of post-9/11 combat veterans report at least some difficulty with postdeployment transition.1,2 Frequently encountered symptoms of this period include impaired sleep, low frustration tolerance, decreased attention, poor concentration, short-term memory deficits, and difficulty with emotional regulation.1,3,4 Veterans will have difficulty reintegrating into the family unit and society without successful coping strategies to address these symptoms. If transition symptoms are prolonged, veterans are at risk for developing chronic adjustment difficulty or mental health issues.

[embed:render:related:node:132641]

Although there is significant attention paid to postdeployment adjustment by military family advocacy groups, there is little information in the medical literature on what constitutes common, nonpathologic postdeployment reactions among combat veterans. Frequently, when postdeployment transition symptoms are discussed, the medical literature tends to explain these in the context of a mental health disorder, such posttraumatic stress disorder (PTSD) or a cognitive injury, such as traumatic brain injury.5-8 Without a balanced understanding of normal postdeployment transitions, a health care provider (HCP) inappropriately may equate transition symptoms with the presence of mental health disorders or cognitive injury and medicalize the coping strategies needed to promote healthy adjustment.

The purpose of this article is to promote HCP awareness of common, nonpathologic postdeployment transition symptoms in combat veterans who are National Guard members or reservists. Such knowledge will enable HCPs to evaluate transition symptoms among these combat veterans reentering the civilian world, normalize common transition reactions, and recognize when further intervention is needed. This article reflects the author’s experience as a medical director working in a VA postdeployment clinic combined with data available in the medical literature and lay press.

Postdeployment Transition Symptoms

Dysregulation of emotional expression in returning combat veterans potentially can be present throughout the postdeployment period of adjustment. Although individual experiences vary widely in intensity and frequency, during postdeployment transition veterans often note difficulty in adjusting emotional expression to match that of nonmilitary counterparts.1,9-11 These difficulties usually fall into 2 broad categories: (1) relative emotional neutrality to major life events that cause nonmilitary civilians great joy or sadness; and (2) overreaction to trivial events, causing significant irritation, anger, or sadness that normally would not produce such emotional reactions in nonmilitary civilians. The former is largely overlooked in medical literature to date except in relation to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) categories, and the latter is often described in limited terms as increased irritability, restlessness, and low frustration tolerance. This emotional dysregulation creates confusing paradoxes for veterans. For example, a veteran might feel no strong emotion when notified of the death of a close relative and yet cry uncontrollably while watching a sad scene in a fictional movie.

Sleep difficulties are intrinsic to the postdeployment period.9-12 Sleep-wake cycles often are altered, reflecting residual effects of the rigid schedules required by military duties and poor sleep hygiene in the combat theater. Inadequate, nonrestful sleep is frequently reported on return to the civilian world. Difficulty falling asleep or difficulty staying asleep also commonly occurs. Nightmares may be present.

Transient difficulty with concentration and attention is often prominent within the postdeployment transition period.9-11,13 Manifestations are variable, but problems with focusing on minor tasks are commonly reported. A more intense effort to master new concepts may be required. Learning styles developed during predeployment phases may be altered so that more conscious effort is required to comprehend and retain new information.

[embed:render:related:node:107864]

Short-term memory frequently may be affected during postdeployment transition.9-11,13 Veterans often report postdeployment difficulty in recalling appointments or tasks that must be completed even if they had a keen sense of memory during predeployment or deployment. Veterans also may have difficulty recalling the details of specific routines that were done without hesitation during deployment. Compared with predeployment time frames, veterans may exert greater effort to recall newly learned material.

Automatic behaviors necessary for survival in a combat theater still may be prominent in the postdeployment period.10,11,14 Aggressive driving required to avoid deployment ambush may be problematic during the postdeployment transition. Steering clear of any roadside trash may be a residual instinctive drive postdeployment because of the risk of improvised explosive devices concealed by debris in the combat theater. Veterans may avoid sitting with their back to the exit as the result of military safety training. Carrying weapons to ensure safety may be a compelling urge, because being armed and ready at all times was necessary for survival during deployment. Avoiding large crowds may be another strong tendency, because throngs of people were associated with potential danger in the combat theater.

Decision making may be challenging to resume in the postdeployment phase.9-11,15 In the deployment theater, time is relativel structured with rules in place, whereas at home veterans face a myriad of choices and decisions that must be made in order to complete the responsibilities of everyday living. As a result, making decisions about what item to buy, which clothes to wear, or what activities to prioritize, though relatively minor, can be a source of significant frustration. It may be difficult to independently navigate a realm of options available for new employment, schooling, or benefits, especially when there is little or no prior experience with these issues.

 

 

Relationship of Symptoms to Mental Health Diagnoses

Postdeployment transition symptoms do not automatically indicate the presence of an underlying mental health diagnosis. However, persistent and/or severe symptoms of postdeployment transition can overlap with or contribute to the development of mental health concerns (Table 1).14 The effects of the emotional disconnect also can exacerbate underlying mental health diagnoses.

fed03407016_t1.png

While postdeployment emotional numbness to major life events, irritability, sleep disturbances, and impaired concentration can be associated with acute stress disorder (ASD) or PTSD, there is a constellation of other symptoms that must be present to diagnose these psychiatric conditions.16 Diagnostic criteria include persistent intrusive symptoms associated with the trauma, persistent avoidance of triggers/reminders associated with the trauma, significant changes in physiologic and cognitive arousal states, and negative changes in mood or cognition related to the trauma.16 The symptoms must cause significant impairment in some aspect of functioning on an individual, social, or occupational level. Acute stress disorder occurs when the symptoms last 30 days or less, whereas PTSD is diagnosed if the symptoms persist longer than a month.

Impaired emotional regulation, sleep disturbances, and decreased concentration also can be associated with depression or anxiety but are insufficient in themselves to make the diagnosis of those disorders.16 At least a 2-week history of depressed mood or inability to experience interest or pleasure in activities must be present as one of the criteria for depression as well as 4 or more other symptoms affecting sleep, appetite, energy, movement, self-esteem, or suicidal thoughts. Anxiety disorders have varying specific diagnostic criteria, but recurrent excessive worrying is a hallmark. Just like ASD or PTSD, the diagnostic symptoms of either depression or anxiety disorders must be causing significant impairment in functioning on an individual, social, or occupational level.

Irritability, sleep disturbances, agitation, memory impairment, and difficulty with concentration and attention can mimic the symptoms associated with mild-to-moderate traumatic brain injury (TBI).17,18 However, symptom onset must have a temporal relationship with a TBI. The presence of other TBI symptoms not associated with normal postdeployment transition usually can be used to differentiate between the diagnoses. Those TBI symptoms include recurrent headaches, poor balance, dizziness, tinnitus, and/or light sensitivity. In the majority of mild TBI cases, the symptoms resolve spontaneously within 3 months of TBI symptom manifestation.16,19 For those with persistent postconcussive syndrome, symptoms usually stabilize or improve over time.18,19 If symptoms worsen, there is often a confounding diagnosis such as PTSD or depression.17,20,21

Some returning combat veterans mistakenly believe postdeployment emotional transition symptoms are always a sign of a mental health disorder. Because there is a significant stigma associated with mental health disorders as well as potential repercussions on their service record if they use mental health resources, many reservists and National Guard members avoid accessing health care services if they are experiencing postdeployment adjustment issues, especially if those symptoms are related to emotional transitions.22-24 Unfortunately, such avoidance carries the risk that stress-inducing symptoms will persist and potentiate adjustment problems.

Course of Symptoms

The range for the postdeployment adjustment period generally falls within 3 to 12 months but can extend longer, depending on individual factors.10,11,25 Factors include presence of significant physical injury or illness, co-occurrence of mental health issues, underlying communication styles, and efficacy of coping strategies chosen. Although there is no clear-cut time frame for transition, ideally transition is complete when the returning veteran successfully enters his or her civilian lifestyle roles and feels a sense of purpose and belonging in society.

Postdeployment transition symptoms occur on a continuum in terms of duration and intensity for reservists and National Guard members. It is difficult to predict how specific transition symptoms will affect a particular veteran. The degree to which those symptoms will complicate reintegration depends on the individual veteran’s ability to adapt within the psychosocial context in which the symptoms occur. For example, minor irritation may be short-lived if a veteran can employ techniques to diffuse that feeling. Alternatively, minor irritation also suddenly may explode into a powerful wave of anger if the veteran has significant underlying emotional tension. Similarly, impaired short-term memory may be limited to forgetting a few appointments or may be so common that the veteran is at risk of losing track of his or her day. The level of memory impairment depends on emotional functioning, co-occurring stressors, and use of adaptive strategies.

In general, as these veterans successfully take on civilian routines, postdeployment transition symptoms will improve. Although such symptom improvement may be a passive process for some veterans, others will need to actively employ strategies to help change the military combat mind-set. The goal is to initiate useful interventions early in transition before symptoms become problematic.14

There are numerous self-help techniques and mobile apps that can be applied to a wide number of symptoms. Viable strategies include exercise, yoga, meditation, mindfulness training, and cognitive reframing. Reaching out for early assistance from various military assistance organizations that are well versed in dealing with postdeployment transition challenges often is helpful for reducing stress and navigating postdeployment obstacles (Table 2).

fed03407016_t2.png

Symptom Strain and Exacerbation

Whenever stumbling blocks are encountered during the postdeployment period, any transition symptom can persist and/or worsen.10,11,14 Emotional disconnect and other transition symptoms can be exacerbated by physical, psychological, and social stressors common in the postdeployment period. Insomnia, poor quality sleep, or other sleep impairments that frequently occur as part of postdeployment transition can negatively impact the veteran’s ability to psychologically cope with daytime stressors. Poor concentration and short-term memory impairment noted by many reservists and National Guard members in the postdeployment phase can cause increased difficulty in attention to the moment and complicate completion of routine tasks. These difficulties can compound frustration and irritation to minor events and make it hard to emotionally connect with more serious issues.

Concentration and attention to mundane activities may be further reduced if the veteran feels no connection to the civilian world and/or experiences the surreal sensation that he or she should be attending to more serious life and death matters, such as those experienced in the combat theater. Ongoing psychological adjustment to physical injuries sustained during deployment can limit emotional flexibility when adapting to either minor or major stressors. Insufficient financial resources, work issues, or school problems can potentiate irritation, anger, and sadness and create an overwhelming emotional overload, leading to helplessness and hopelessness.

Perceived irregularities in emotional connection to the civilian world can significantly strain interpersonal relationships and be powerful impediments to successful reintegration.9,11,14 Failure to express emotions to major life events in the civilian world can result in combat veterans being viewed as not empathetic to others’ feelings. Overreaction to trivial events during postdeployment can lead to the veteran being labeled as unreasonable, controlling, and/or unpredictable. Persistent emotional disconnect with civilians engenders a growing sense of emotional isolation from family and friends when there is either incorrect interpretation of emotional transitions or failure to adapt healthy coping strategies. This isolation further enlarges the emotional chasm and may greatly diminish the veteran’s ability to seek assistance and appropriately address stressors in the civilian world.

Transition and the Family

Emotional disconnection may be more acutely felt within the immediate family unit.26 Redistribution of family unit responsibilities during deployment may mean that roles the veteran played during predeployment now may be handled by a partner. On the veteran’s return to the civilian world, such circumstances require active renegotiation of duties. Interactions with loved ones, especially children, may be colored by the family members’ individual perspectives on deployment as well as by the veteran’s transition symptoms. When there is disagreement about role responsibilities and/or underlying family resentment about deployment, conditions are ripe for significant discord between the veteran and family members, vital loss of partner intimacy, and notable loss of psychological safety to express feelings within the family unit. If there are  concerns about infidelity by the veteran or significant other during the period of deployment, postdeployment tensions can further escalate. If unaddressed in the presence of emotional disconnect, any of these situations can raise the risk of domestic violence and destruction of relationships.

Without adequate knowledge of common postdeployment transitions and coping strategies, the postdeployment transition period is often bewildering to returning veterans and their families. They are taken aback by postdeployment behaviors that do not conform to the veteran’s predeployment personality or mannerisms. Families may feel they have “lost” the veteran and view the emotionally distant postdeployment veteran as a stranger. Veterans mistakenly may view the postdeployment emotional disconnect as evidence that they were permanently altered by deployment and no longer can assimilate into the civilian world. Unless veterans and families develop an awareness of the postdeployment transition symptoms and healthy coping strategies,  these perspectives can contribute to a veteran’s persistent feelings of alienation, significant sense of personal failure, and loss of vital social supports.

 

 

When transition symptoms are or have the potential to become significant stressors, veterans would benefit from mental health counseling either individually or with family members. Overcoming the stigma of seeking mental health services can prove challenging. Explaining that these postdeployment symptoms occur commonly, stem from military combat training, can be reversed, and when reversed will empower the individual to control his or her life may help veterans overcome the stigma and seek mental health services.

[embed:render:related:node:137280]

The fear of future career impairment with the military reserve or National Guard is another real concern among this cohort who might consider accessing behavioral health care, especially since VA mental health medical records can be accessed by DoD officials through links with the VHA. Fortunately, this concern can be alleviated through the use of Vet Centers, free-standing counseling centers nationwide that offer no-cost individual and family counseling to veterans with combat exposure. Vet Center counseling records are completely confidential, never shared, and are not linked to the VHA electronic health record, the DoD, or any other entity. Although Vet Center providers don’t prescribe medications, the counselors can actively address many issues for veterans and their families. For individuals who do not live near a Vet Center or for those who require psychiatric medications, a frank discussion on the benefits of treatment vs the risk of treatment avoidance must be held.

Assessing Symptoms and Coping Mechanisms

Postdeployment transition symptoms vary, depending on the nature and context of the symptom. Not only must the returning reservist and National Guard member be screened for symptoms, but HCPs also should assess the impact of those symptoms on the veteran and his or her interpersonal relationships. Some veterans will feel that the symptoms have relatively minor impact in their lives, because the veteran can easily compensate for the transient effects. Others may feel that the symptoms are somewhat burdensome because the issues are complicating the smooth transition to civilian roles. Still others will judge the symptoms to be devastating because of the negative effects on personal control, selfesteem, and emotional connection with family and friends.

In addition to screening for symptoms, HCPs should assess these veterans’ current coping adaptations to various transition symptoms. Whereas some activities may be functional and promote reintegration, other short-term coping solutions may cripple the veteran’s ability to successfully resume civilian life. Global avoidance of communication with others and/or retreating from all social situations is a destructive coping pattern that can further alienate veterans from their families and the civilian world. Reacting with anger to all stressful issues is another maladaptive pattern of coping with life’s frustrations. Because of the potential to self-medicate when dealing with social difficulties, depression, anxiety, or other mental health diagnoses, veterans may develop an inappropriate reliance on drugs or alcohol to handle postdeployment stressors.27 Therefore, HCP screening for substance use disorders (SUD) is important so that interventions can be initiated early.

Because of the overlap of postdeployment transition symptoms with mental health disorders and the relative frequency of those mental health disorders among combat veterans, HCPs should have a heightened awareness of the potential for co-occurring mental health difficulties in the postdeployment reservist and National Guard cohort. Health care providers should screen for depression, anxiety, and PTSD. Even if initial screening is done early within the transition period, repeat screening would be of benefit 6 months into the postdeployment period because of the tendency of mental health issues to develop during that time.28,29

By evaluating the impact of the transition symptom and coping strategies on these veterans’ lives, HCPs can better determine which strategies might adequately compensate for symptom effects. In general, informal counseling, even if just to help veterans normalize postdeployment transition symptoms and develop a plan to address such symptoms, can significantly minimize the negative impact of transition symptoms.14,26 Specific symptoms should be targeted by interventions that match the degree of symptom impact.

Symptoms to be aggressively addressed are those that significantly interfere with successful reintegration into the civilian world. For example, persistent sleep difficulties should be dealt with because they can worsen all other transition symptoms. However, the majority of strategies to address sleep do not require medication unless there are confounding factors such as severe nightmares. Minor memory issues attributed to the transition phase can be mitigated by several strategies to improve recall, including use of task lists, digital calendars, or other memory-prodding techniques. However, severe memory issues related to depression or anxiety likely would require pharmaceutical assistance and formal counseling in addition to other nonpharmacologic approaches.

Intermittent irritation or restlessness may be amenable to selfhelp strategies, but significant anger outbursts or aggression will require additional support, such as formal behavioral interventions to help identify the triggers and develop strategic plans to reduce emotional tension. A mild sense of not belonging may resolve without intervention, but a stronger sense of alienation will require further evaluation.

Conclusion

Civilian reintegration after combat deployment is a gradual process rather than a discrete event for reservists and National Guard members. There are common, nonpathologic postdeployment transition symptoms that, if misunderstood or inappropriately addressed, can complicate civilian reintegration. Health care providers are in the unique position to promote a healthy postdeployment transition by assisting veterans to recognize nonpathologic transition symptoms, select appropriate coping strategies, and seek further assistance for more complex problems.

The rigid dichotomy between combat deployment and postdeployment environments necessitates a multitude of cognitive, behavioral, and emotional adjustments for National Guard members and reservists to resume postdeployment civilian lifestyles successfully. Reacclimating to the postdeployment world is not a quick process for these veterans because of the time required to adjust from a deeply ingrained military combat mentality to civilian life. The process of this reintegration into the civilian world is known as postdeployment transition.

More than half of post-9/11 combat veterans report at least some difficulty with postdeployment transition.1,2 Frequently encountered symptoms of this period include impaired sleep, low frustration tolerance, decreased attention, poor concentration, short-term memory deficits, and difficulty with emotional regulation.1,3,4 Veterans will have difficulty reintegrating into the family unit and society without successful coping strategies to address these symptoms. If transition symptoms are prolonged, veterans are at risk for developing chronic adjustment difficulty or mental health issues.

[embed:render:related:node:132641]

Although there is significant attention paid to postdeployment adjustment by military family advocacy groups, there is little information in the medical literature on what constitutes common, nonpathologic postdeployment reactions among combat veterans. Frequently, when postdeployment transition symptoms are discussed, the medical literature tends to explain these in the context of a mental health disorder, such posttraumatic stress disorder (PTSD) or a cognitive injury, such as traumatic brain injury.5-8 Without a balanced understanding of normal postdeployment transitions, a health care provider (HCP) inappropriately may equate transition symptoms with the presence of mental health disorders or cognitive injury and medicalize the coping strategies needed to promote healthy adjustment.

The purpose of this article is to promote HCP awareness of common, nonpathologic postdeployment transition symptoms in combat veterans who are National Guard members or reservists. Such knowledge will enable HCPs to evaluate transition symptoms among these combat veterans reentering the civilian world, normalize common transition reactions, and recognize when further intervention is needed. This article reflects the author’s experience as a medical director working in a VA postdeployment clinic combined with data available in the medical literature and lay press.

Postdeployment Transition Symptoms

Dysregulation of emotional expression in returning combat veterans potentially can be present throughout the postdeployment period of adjustment. Although individual experiences vary widely in intensity and frequency, during postdeployment transition veterans often note difficulty in adjusting emotional expression to match that of nonmilitary counterparts.1,9-11 These difficulties usually fall into 2 broad categories: (1) relative emotional neutrality to major life events that cause nonmilitary civilians great joy or sadness; and (2) overreaction to trivial events, causing significant irritation, anger, or sadness that normally would not produce such emotional reactions in nonmilitary civilians. The former is largely overlooked in medical literature to date except in relation to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) categories, and the latter is often described in limited terms as increased irritability, restlessness, and low frustration tolerance. This emotional dysregulation creates confusing paradoxes for veterans. For example, a veteran might feel no strong emotion when notified of the death of a close relative and yet cry uncontrollably while watching a sad scene in a fictional movie.

Sleep difficulties are intrinsic to the postdeployment period.9-12 Sleep-wake cycles often are altered, reflecting residual effects of the rigid schedules required by military duties and poor sleep hygiene in the combat theater. Inadequate, nonrestful sleep is frequently reported on return to the civilian world. Difficulty falling asleep or difficulty staying asleep also commonly occurs. Nightmares may be present.

Transient difficulty with concentration and attention is often prominent within the postdeployment transition period.9-11,13 Manifestations are variable, but problems with focusing on minor tasks are commonly reported. A more intense effort to master new concepts may be required. Learning styles developed during predeployment phases may be altered so that more conscious effort is required to comprehend and retain new information.

[embed:render:related:node:107864]

Short-term memory frequently may be affected during postdeployment transition.9-11,13 Veterans often report postdeployment difficulty in recalling appointments or tasks that must be completed even if they had a keen sense of memory during predeployment or deployment. Veterans also may have difficulty recalling the details of specific routines that were done without hesitation during deployment. Compared with predeployment time frames, veterans may exert greater effort to recall newly learned material.

Automatic behaviors necessary for survival in a combat theater still may be prominent in the postdeployment period.10,11,14 Aggressive driving required to avoid deployment ambush may be problematic during the postdeployment transition. Steering clear of any roadside trash may be a residual instinctive drive postdeployment because of the risk of improvised explosive devices concealed by debris in the combat theater. Veterans may avoid sitting with their back to the exit as the result of military safety training. Carrying weapons to ensure safety may be a compelling urge, because being armed and ready at all times was necessary for survival during deployment. Avoiding large crowds may be another strong tendency, because throngs of people were associated with potential danger in the combat theater.

Decision making may be challenging to resume in the postdeployment phase.9-11,15 In the deployment theater, time is relativel structured with rules in place, whereas at home veterans face a myriad of choices and decisions that must be made in order to complete the responsibilities of everyday living. As a result, making decisions about what item to buy, which clothes to wear, or what activities to prioritize, though relatively minor, can be a source of significant frustration. It may be difficult to independently navigate a realm of options available for new employment, schooling, or benefits, especially when there is little or no prior experience with these issues.

 

 

Relationship of Symptoms to Mental Health Diagnoses

Postdeployment transition symptoms do not automatically indicate the presence of an underlying mental health diagnosis. However, persistent and/or severe symptoms of postdeployment transition can overlap with or contribute to the development of mental health concerns (Table 1).14 The effects of the emotional disconnect also can exacerbate underlying mental health diagnoses.

fed03407016_t1.png

While postdeployment emotional numbness to major life events, irritability, sleep disturbances, and impaired concentration can be associated with acute stress disorder (ASD) or PTSD, there is a constellation of other symptoms that must be present to diagnose these psychiatric conditions.16 Diagnostic criteria include persistent intrusive symptoms associated with the trauma, persistent avoidance of triggers/reminders associated with the trauma, significant changes in physiologic and cognitive arousal states, and negative changes in mood or cognition related to the trauma.16 The symptoms must cause significant impairment in some aspect of functioning on an individual, social, or occupational level. Acute stress disorder occurs when the symptoms last 30 days or less, whereas PTSD is diagnosed if the symptoms persist longer than a month.

Impaired emotional regulation, sleep disturbances, and decreased concentration also can be associated with depression or anxiety but are insufficient in themselves to make the diagnosis of those disorders.16 At least a 2-week history of depressed mood or inability to experience interest or pleasure in activities must be present as one of the criteria for depression as well as 4 or more other symptoms affecting sleep, appetite, energy, movement, self-esteem, or suicidal thoughts. Anxiety disorders have varying specific diagnostic criteria, but recurrent excessive worrying is a hallmark. Just like ASD or PTSD, the diagnostic symptoms of either depression or anxiety disorders must be causing significant impairment in functioning on an individual, social, or occupational level.

Irritability, sleep disturbances, agitation, memory impairment, and difficulty with concentration and attention can mimic the symptoms associated with mild-to-moderate traumatic brain injury (TBI).17,18 However, symptom onset must have a temporal relationship with a TBI. The presence of other TBI symptoms not associated with normal postdeployment transition usually can be used to differentiate between the diagnoses. Those TBI symptoms include recurrent headaches, poor balance, dizziness, tinnitus, and/or light sensitivity. In the majority of mild TBI cases, the symptoms resolve spontaneously within 3 months of TBI symptom manifestation.16,19 For those with persistent postconcussive syndrome, symptoms usually stabilize or improve over time.18,19 If symptoms worsen, there is often a confounding diagnosis such as PTSD or depression.17,20,21

Some returning combat veterans mistakenly believe postdeployment emotional transition symptoms are always a sign of a mental health disorder. Because there is a significant stigma associated with mental health disorders as well as potential repercussions on their service record if they use mental health resources, many reservists and National Guard members avoid accessing health care services if they are experiencing postdeployment adjustment issues, especially if those symptoms are related to emotional transitions.22-24 Unfortunately, such avoidance carries the risk that stress-inducing symptoms will persist and potentiate adjustment problems.

Course of Symptoms

The range for the postdeployment adjustment period generally falls within 3 to 12 months but can extend longer, depending on individual factors.10,11,25 Factors include presence of significant physical injury or illness, co-occurrence of mental health issues, underlying communication styles, and efficacy of coping strategies chosen. Although there is no clear-cut time frame for transition, ideally transition is complete when the returning veteran successfully enters his or her civilian lifestyle roles and feels a sense of purpose and belonging in society.

Postdeployment transition symptoms occur on a continuum in terms of duration and intensity for reservists and National Guard members. It is difficult to predict how specific transition symptoms will affect a particular veteran. The degree to which those symptoms will complicate reintegration depends on the individual veteran’s ability to adapt within the psychosocial context in which the symptoms occur. For example, minor irritation may be short-lived if a veteran can employ techniques to diffuse that feeling. Alternatively, minor irritation also suddenly may explode into a powerful wave of anger if the veteran has significant underlying emotional tension. Similarly, impaired short-term memory may be limited to forgetting a few appointments or may be so common that the veteran is at risk of losing track of his or her day. The level of memory impairment depends on emotional functioning, co-occurring stressors, and use of adaptive strategies.

In general, as these veterans successfully take on civilian routines, postdeployment transition symptoms will improve. Although such symptom improvement may be a passive process for some veterans, others will need to actively employ strategies to help change the military combat mind-set. The goal is to initiate useful interventions early in transition before symptoms become problematic.14

There are numerous self-help techniques and mobile apps that can be applied to a wide number of symptoms. Viable strategies include exercise, yoga, meditation, mindfulness training, and cognitive reframing. Reaching out for early assistance from various military assistance organizations that are well versed in dealing with postdeployment transition challenges often is helpful for reducing stress and navigating postdeployment obstacles (Table 2).

fed03407016_t2.png

Symptom Strain and Exacerbation

Whenever stumbling blocks are encountered during the postdeployment period, any transition symptom can persist and/or worsen.10,11,14 Emotional disconnect and other transition symptoms can be exacerbated by physical, psychological, and social stressors common in the postdeployment period. Insomnia, poor quality sleep, or other sleep impairments that frequently occur as part of postdeployment transition can negatively impact the veteran’s ability to psychologically cope with daytime stressors. Poor concentration and short-term memory impairment noted by many reservists and National Guard members in the postdeployment phase can cause increased difficulty in attention to the moment and complicate completion of routine tasks. These difficulties can compound frustration and irritation to minor events and make it hard to emotionally connect with more serious issues.

Concentration and attention to mundane activities may be further reduced if the veteran feels no connection to the civilian world and/or experiences the surreal sensation that he or she should be attending to more serious life and death matters, such as those experienced in the combat theater. Ongoing psychological adjustment to physical injuries sustained during deployment can limit emotional flexibility when adapting to either minor or major stressors. Insufficient financial resources, work issues, or school problems can potentiate irritation, anger, and sadness and create an overwhelming emotional overload, leading to helplessness and hopelessness.

Perceived irregularities in emotional connection to the civilian world can significantly strain interpersonal relationships and be powerful impediments to successful reintegration.9,11,14 Failure to express emotions to major life events in the civilian world can result in combat veterans being viewed as not empathetic to others’ feelings. Overreaction to trivial events during postdeployment can lead to the veteran being labeled as unreasonable, controlling, and/or unpredictable. Persistent emotional disconnect with civilians engenders a growing sense of emotional isolation from family and friends when there is either incorrect interpretation of emotional transitions or failure to adapt healthy coping strategies. This isolation further enlarges the emotional chasm and may greatly diminish the veteran’s ability to seek assistance and appropriately address stressors in the civilian world.

Transition and the Family

Emotional disconnection may be more acutely felt within the immediate family unit.26 Redistribution of family unit responsibilities during deployment may mean that roles the veteran played during predeployment now may be handled by a partner. On the veteran’s return to the civilian world, such circumstances require active renegotiation of duties. Interactions with loved ones, especially children, may be colored by the family members’ individual perspectives on deployment as well as by the veteran’s transition symptoms. When there is disagreement about role responsibilities and/or underlying family resentment about deployment, conditions are ripe for significant discord between the veteran and family members, vital loss of partner intimacy, and notable loss of psychological safety to express feelings within the family unit. If there are  concerns about infidelity by the veteran or significant other during the period of deployment, postdeployment tensions can further escalate. If unaddressed in the presence of emotional disconnect, any of these situations can raise the risk of domestic violence and destruction of relationships.

Without adequate knowledge of common postdeployment transitions and coping strategies, the postdeployment transition period is often bewildering to returning veterans and their families. They are taken aback by postdeployment behaviors that do not conform to the veteran’s predeployment personality or mannerisms. Families may feel they have “lost” the veteran and view the emotionally distant postdeployment veteran as a stranger. Veterans mistakenly may view the postdeployment emotional disconnect as evidence that they were permanently altered by deployment and no longer can assimilate into the civilian world. Unless veterans and families develop an awareness of the postdeployment transition symptoms and healthy coping strategies,  these perspectives can contribute to a veteran’s persistent feelings of alienation, significant sense of personal failure, and loss of vital social supports.

 

 

When transition symptoms are or have the potential to become significant stressors, veterans would benefit from mental health counseling either individually or with family members. Overcoming the stigma of seeking mental health services can prove challenging. Explaining that these postdeployment symptoms occur commonly, stem from military combat training, can be reversed, and when reversed will empower the individual to control his or her life may help veterans overcome the stigma and seek mental health services.

[embed:render:related:node:137280]

The fear of future career impairment with the military reserve or National Guard is another real concern among this cohort who might consider accessing behavioral health care, especially since VA mental health medical records can be accessed by DoD officials through links with the VHA. Fortunately, this concern can be alleviated through the use of Vet Centers, free-standing counseling centers nationwide that offer no-cost individual and family counseling to veterans with combat exposure. Vet Center counseling records are completely confidential, never shared, and are not linked to the VHA electronic health record, the DoD, or any other entity. Although Vet Center providers don’t prescribe medications, the counselors can actively address many issues for veterans and their families. For individuals who do not live near a Vet Center or for those who require psychiatric medications, a frank discussion on the benefits of treatment vs the risk of treatment avoidance must be held.

Assessing Symptoms and Coping Mechanisms

Postdeployment transition symptoms vary, depending on the nature and context of the symptom. Not only must the returning reservist and National Guard member be screened for symptoms, but HCPs also should assess the impact of those symptoms on the veteran and his or her interpersonal relationships. Some veterans will feel that the symptoms have relatively minor impact in their lives, because the veteran can easily compensate for the transient effects. Others may feel that the symptoms are somewhat burdensome because the issues are complicating the smooth transition to civilian roles. Still others will judge the symptoms to be devastating because of the negative effects on personal control, selfesteem, and emotional connection with family and friends.

In addition to screening for symptoms, HCPs should assess these veterans’ current coping adaptations to various transition symptoms. Whereas some activities may be functional and promote reintegration, other short-term coping solutions may cripple the veteran’s ability to successfully resume civilian life. Global avoidance of communication with others and/or retreating from all social situations is a destructive coping pattern that can further alienate veterans from their families and the civilian world. Reacting with anger to all stressful issues is another maladaptive pattern of coping with life’s frustrations. Because of the potential to self-medicate when dealing with social difficulties, depression, anxiety, or other mental health diagnoses, veterans may develop an inappropriate reliance on drugs or alcohol to handle postdeployment stressors.27 Therefore, HCP screening for substance use disorders (SUD) is important so that interventions can be initiated early.

Because of the overlap of postdeployment transition symptoms with mental health disorders and the relative frequency of those mental health disorders among combat veterans, HCPs should have a heightened awareness of the potential for co-occurring mental health difficulties in the postdeployment reservist and National Guard cohort. Health care providers should screen for depression, anxiety, and PTSD. Even if initial screening is done early within the transition period, repeat screening would be of benefit 6 months into the postdeployment period because of the tendency of mental health issues to develop during that time.28,29

By evaluating the impact of the transition symptom and coping strategies on these veterans’ lives, HCPs can better determine which strategies might adequately compensate for symptom effects. In general, informal counseling, even if just to help veterans normalize postdeployment transition symptoms and develop a plan to address such symptoms, can significantly minimize the negative impact of transition symptoms.14,26 Specific symptoms should be targeted by interventions that match the degree of symptom impact.

Symptoms to be aggressively addressed are those that significantly interfere with successful reintegration into the civilian world. For example, persistent sleep difficulties should be dealt with because they can worsen all other transition symptoms. However, the majority of strategies to address sleep do not require medication unless there are confounding factors such as severe nightmares. Minor memory issues attributed to the transition phase can be mitigated by several strategies to improve recall, including use of task lists, digital calendars, or other memory-prodding techniques. However, severe memory issues related to depression or anxiety likely would require pharmaceutical assistance and formal counseling in addition to other nonpharmacologic approaches.

Intermittent irritation or restlessness may be amenable to selfhelp strategies, but significant anger outbursts or aggression will require additional support, such as formal behavioral interventions to help identify the triggers and develop strategic plans to reduce emotional tension. A mild sense of not belonging may resolve without intervention, but a stronger sense of alienation will require further evaluation.

Conclusion

Civilian reintegration after combat deployment is a gradual process rather than a discrete event for reservists and National Guard members. There are common, nonpathologic postdeployment transition symptoms that, if misunderstood or inappropriately addressed, can complicate civilian reintegration. Health care providers are in the unique position to promote a healthy postdeployment transition by assisting veterans to recognize nonpathologic transition symptoms, select appropriate coping strategies, and seek further assistance for more complex problems.

References

1. Pew Research Center. War and sacrifice in the post 9/11 era: executive summary. http://www
.pewsocialtrends.org/2011/10/05/war-and-sacrifice-in-the-post-911-era. Published October 5, 2011. Accessed June 12, 2017.

2. Interian A, Kline A, Callahan L, Losonczy M. Readjustment stressors and early mental health treatment seeking by returning National Guard soldiers with PTSD. Psychiatr Serv. 2012;63(9):855-861.

3. Spelman JF, Hunt SC, Seal KH, Burgo-Black AL. Post deployment care for returning combat veterans. J Gen Intern Med. 2012;27(9):1200-1209.

4. Vasterling JJ, Daily ES, Friedman MJ. Posttraumatic stress reactions over time: the battlefield, homecoming, and long-term course. In: Ruzek JI, Schnurr PP, Vasterling JJ, Friedman MJ, eds. Caring for Veterans With Deployment-Related Stress Disorders: Iraq, Afghanistan, and Beyond. Washington,DC: American Psychological Association;2011:chap 2.

5. Wilcox SL, Oh H, Redmon SA, Chicas J, Hassan AM, Lee PJ, Ell K. A scope of the problem: Postdeployment reintegration challenges in a National Guard Unit. Work. 2015;50(1):73-83.

6. Griffith J. Homecoming of citizen soldiers: Postdeployment problems and service use among Army National Guard soldiers. Community Ment Health J. 2017. doi:10.1007/s10597-017-0132-9. (Epub ahead of print)

7. Schultz M, Glickman ME, Eisen SV. Predictors of decline in overall mental health, PTSD and alcohol use in OEF/OIF veterans. Comprehensive Psychiatry. 2014;55(7):1654-1664.

8. Polusny MA, Kehle SM, Nelson NW, Erbes CR, Arbisi PA, Thuras P. Longitudinal effects of mild traumatic brain injury and posttraumatic stress disorder comorbidity on postdeployment outcomes in National Guard soldiers deployed to Iraq. Arch Gen Psychiatry. 2011:68(1):79-89.

9. U.S. Department of Veterans Affairs, National Center for PTSD. Returning from the war zone: a guide for military personnel. http://www.ptsd.va.gov/public/reintegration/guide-pdf/SMGuide.pdf. Updated January 2014. Accessed June 12, 2017.

10. Slone LB, Friedman MJ. After the War Zone: A Practical Guide for Returning Troops and their Families. Philadelphia, PA: Da Capo Press; 2008.

11. Ainspan ND, Penk WE, eds. When the Warrior Returns: Making the Transition at Home. Annapolis, MD: Naval Institute Press; 2012.

12. Yosick T, Bates M, Moore M, Crowe C, Phillips J, Davison J. A review of post-deployment reintegration: evidence, challenges, and strategies for program development. http://www.dcoe.mil/files/Review_of_Post-Deployment_Reintegration.pdf. Published February 10, 2012. Accessed June 12, 2017.

13. Vasterling JJ, Proctor SP, Amoroso P, Kane R, Heeren T, White RF. Neuropsychological outcomes of army personnel following deployment to the Iraq war. JAMA. 2006;296(5):519-529.

14. Castro CA, Kintzle S, Hassan AM. The combat veteran paradox: paradoxes and dilemmas encountered with reintegrating combat veterans and the agencies that support them. Traumatology. 2015;21(4):299-310.

15. Rivers FM, Gordon S, Speraw S, Reese S. U.S. Army nurses’ reintegration and homecoming experiences after Iraq and Afghanistan. Mil Med. 2013;178(2):166-173.

16. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington,VA: American Psychiatric Association;2013.

17. Tanielian T, Jaycox LH, eds. Invisible Wounds of War: Psychological and Cognitive Injuries, Their Consequences, and Services to Assist Recovery. Santa Monica, CA: Rand Corporation, 2008.

18. Orff HJ, Hays CC, Heldreth AA, Stein MB, Twamley EW. Clinical considerations in the evaluation and management of patients following traumatic brain injury. Focus. 2013;11(3):328-340.

19. Morissette SB, Woodward M, Kimbrel NA, et al. Deployment-related TBI, persistent postconcussive symptoms, PTSD, and depression in OEF/OIF veterans. Rehabil Psychol. 2011;56(4):340-350.

20. Polusny MA, Kehle SM, Nelson NW, Erbes CR, Arbisi PA, Thuras P. Longitudinal effects of mild traumatic brain injury and posttraumatic stress disorder comorbidity on postdeployment outcomes in national guard soldiers deployed to Iraq. Arch Gen Psychiatry. 2011;68(1):79-89.

21. Wilk JE, Herrell RK, Wynn GH, Riviere LA, Hoge CW. Mild traumatic brain injury (concussion), posttraumatic stress disorder, and depression in U.S. soldiers involved in combat deployments: association with postdeployment symptoms. Psychosom Med. 2012;74(3):249-257.

22. Hoge CW, Grossman SH, Auchterlonie JL, Riviere LA, Milliken CS, Wilk JE. PTSD treatment for soldiers after combat deployment: low utilization of mental health care and reasons for dropout. Psychiatr Serv. 2014;65(8):997-1004.

23. Hines LA, Goodwin L, Jones M, et al. Factors affecting help seeking for mental health problems after deployment to Iraq and Afghanistan. Psychiatr Serv. 2014;65(1):98-105.

24. Gorman LA, Blow AJ, Ames BD, Read PL. National Guard families after combat: mental health, use of mental health services, and perceived treatment barriers. Psychiatr Serv. 2011;62(1):28-34.

25. Marek LI, Hollingsworth WG, D’Aniello C, et al. Returning home: what we know about the reintegration of deployed service members into their families and communities. https://www.ncfr.org/ncfr-report/focus/military-families/returninghome. Published March 1, 2012. Accessed June 13, 2017.

26. Bowling UB, Sherman MD. Welcoming them home: supporting service members and their families in navigating the tasks of reintegration. Prof Psychol Res Pr. 2008;39(4):451-458.

27. Jacobson IG, Ryan MA, Hooper TI, et al. Alcohol use and alcohol-related problems before
and after military combat deployment. JAMA. 2008;300(6):663-675.

28. Seal KH, Metzler TH, Gima KS, Bertenthal D, Maguen S, Marmar CR. Trends and risk factors for mental health diagnoses among Iraq and Afghanistan veterans Department of Veterans Affairs health care, 2002-2008. Am J Public Health. 2009;99(9):1651-1658.

29. Milliken CS, Auchterlonie JL, Hoge CW. Longitudinal assessment of mental health problems among active and reserve component soldiers returning from the Iraq war. JAMA. 2007;298(18):2141-2148.

References

1. Pew Research Center. War and sacrifice in the post 9/11 era: executive summary. http://www
.pewsocialtrends.org/2011/10/05/war-and-sacrifice-in-the-post-911-era. Published October 5, 2011. Accessed June 12, 2017.

2. Interian A, Kline A, Callahan L, Losonczy M. Readjustment stressors and early mental health treatment seeking by returning National Guard soldiers with PTSD. Psychiatr Serv. 2012;63(9):855-861.

3. Spelman JF, Hunt SC, Seal KH, Burgo-Black AL. Post deployment care for returning combat veterans. J Gen Intern Med. 2012;27(9):1200-1209.

4. Vasterling JJ, Daily ES, Friedman MJ. Posttraumatic stress reactions over time: the battlefield, homecoming, and long-term course. In: Ruzek JI, Schnurr PP, Vasterling JJ, Friedman MJ, eds. Caring for Veterans With Deployment-Related Stress Disorders: Iraq, Afghanistan, and Beyond. Washington,DC: American Psychological Association;2011:chap 2.

5. Wilcox SL, Oh H, Redmon SA, Chicas J, Hassan AM, Lee PJ, Ell K. A scope of the problem: Postdeployment reintegration challenges in a National Guard Unit. Work. 2015;50(1):73-83.

6. Griffith J. Homecoming of citizen soldiers: Postdeployment problems and service use among Army National Guard soldiers. Community Ment Health J. 2017. doi:10.1007/s10597-017-0132-9. (Epub ahead of print)

7. Schultz M, Glickman ME, Eisen SV. Predictors of decline in overall mental health, PTSD and alcohol use in OEF/OIF veterans. Comprehensive Psychiatry. 2014;55(7):1654-1664.

8. Polusny MA, Kehle SM, Nelson NW, Erbes CR, Arbisi PA, Thuras P. Longitudinal effects of mild traumatic brain injury and posttraumatic stress disorder comorbidity on postdeployment outcomes in National Guard soldiers deployed to Iraq. Arch Gen Psychiatry. 2011:68(1):79-89.

9. U.S. Department of Veterans Affairs, National Center for PTSD. Returning from the war zone: a guide for military personnel. http://www.ptsd.va.gov/public/reintegration/guide-pdf/SMGuide.pdf. Updated January 2014. Accessed June 12, 2017.

10. Slone LB, Friedman MJ. After the War Zone: A Practical Guide for Returning Troops and their Families. Philadelphia, PA: Da Capo Press; 2008.

11. Ainspan ND, Penk WE, eds. When the Warrior Returns: Making the Transition at Home. Annapolis, MD: Naval Institute Press; 2012.

12. Yosick T, Bates M, Moore M, Crowe C, Phillips J, Davison J. A review of post-deployment reintegration: evidence, challenges, and strategies for program development. http://www.dcoe.mil/files/Review_of_Post-Deployment_Reintegration.pdf. Published February 10, 2012. Accessed June 12, 2017.

13. Vasterling JJ, Proctor SP, Amoroso P, Kane R, Heeren T, White RF. Neuropsychological outcomes of army personnel following deployment to the Iraq war. JAMA. 2006;296(5):519-529.

14. Castro CA, Kintzle S, Hassan AM. The combat veteran paradox: paradoxes and dilemmas encountered with reintegrating combat veterans and the agencies that support them. Traumatology. 2015;21(4):299-310.

15. Rivers FM, Gordon S, Speraw S, Reese S. U.S. Army nurses’ reintegration and homecoming experiences after Iraq and Afghanistan. Mil Med. 2013;178(2):166-173.

16. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington,VA: American Psychiatric Association;2013.

17. Tanielian T, Jaycox LH, eds. Invisible Wounds of War: Psychological and Cognitive Injuries, Their Consequences, and Services to Assist Recovery. Santa Monica, CA: Rand Corporation, 2008.

18. Orff HJ, Hays CC, Heldreth AA, Stein MB, Twamley EW. Clinical considerations in the evaluation and management of patients following traumatic brain injury. Focus. 2013;11(3):328-340.

19. Morissette SB, Woodward M, Kimbrel NA, et al. Deployment-related TBI, persistent postconcussive symptoms, PTSD, and depression in OEF/OIF veterans. Rehabil Psychol. 2011;56(4):340-350.

20. Polusny MA, Kehle SM, Nelson NW, Erbes CR, Arbisi PA, Thuras P. Longitudinal effects of mild traumatic brain injury and posttraumatic stress disorder comorbidity on postdeployment outcomes in national guard soldiers deployed to Iraq. Arch Gen Psychiatry. 2011;68(1):79-89.

21. Wilk JE, Herrell RK, Wynn GH, Riviere LA, Hoge CW. Mild traumatic brain injury (concussion), posttraumatic stress disorder, and depression in U.S. soldiers involved in combat deployments: association with postdeployment symptoms. Psychosom Med. 2012;74(3):249-257.

22. Hoge CW, Grossman SH, Auchterlonie JL, Riviere LA, Milliken CS, Wilk JE. PTSD treatment for soldiers after combat deployment: low utilization of mental health care and reasons for dropout. Psychiatr Serv. 2014;65(8):997-1004.

23. Hines LA, Goodwin L, Jones M, et al. Factors affecting help seeking for mental health problems after deployment to Iraq and Afghanistan. Psychiatr Serv. 2014;65(1):98-105.

24. Gorman LA, Blow AJ, Ames BD, Read PL. National Guard families after combat: mental health, use of mental health services, and perceived treatment barriers. Psychiatr Serv. 2011;62(1):28-34.

25. Marek LI, Hollingsworth WG, D’Aniello C, et al. Returning home: what we know about the reintegration of deployed service members into their families and communities. https://www.ncfr.org/ncfr-report/focus/military-families/returninghome. Published March 1, 2012. Accessed June 13, 2017.

26. Bowling UB, Sherman MD. Welcoming them home: supporting service members and their families in navigating the tasks of reintegration. Prof Psychol Res Pr. 2008;39(4):451-458.

27. Jacobson IG, Ryan MA, Hooper TI, et al. Alcohol use and alcohol-related problems before
and after military combat deployment. JAMA. 2008;300(6):663-675.

28. Seal KH, Metzler TH, Gima KS, Bertenthal D, Maguen S, Marmar CR. Trends and risk factors for mental health diagnoses among Iraq and Afghanistan veterans Department of Veterans Affairs health care, 2002-2008. Am J Public Health. 2009;99(9):1651-1658.

29. Milliken CS, Auchterlonie JL, Hoge CW. Longitudinal assessment of mental health problems among active and reserve component soldiers returning from the Iraq war. JAMA. 2007;298(18):2141-2148.

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