My first exposure to the notion of scarce resources was in medical school. I had to discuss the ethical principles behind the allocation of organs for transplantation, specifically livers and the required abstinence from alcohol ... but this was just an exercise, right?

A few years later, during residency, I heard the anecdotes from one of my internal medicine attendings about the time he spent in Europe as a visiting geriatrics fellow in the 1970s. The health-care districts in the region would be allotted an annual budget, and it was up to those districts how to best allocate those resources to meet, to the best of their abilities, the health-care needs of their population. He vividly recalled that a patient he cared for, an individual over 65 in need of renal replacement therapy for a reversible condition, who was not offered such therapy despite the clear benefit. There was a finite amount of resources, and those resources were thought to be better spent on public health measures like vaccination ... but that was on another continent and in another era, right?

I remember when I first heard of an outbreak of viral pneumonia in China in January of this year. As someone prone to anxiety, my first strategy was to put my head in the sand and wait it out. This strategy didn’t last very long – within a couple of weeks, there were confirmed cases in the United States. It was now apparent that this virus was not going to be contained. In an impressively short amount of time, SARS-CoV 2 has infected over 3.5 million individuals and killed almost a quarter million people worldwide. In the United States, we have seen almost 1.2 million cases and lost over 68 thousand lives. This pandemic has managed to devastate multiple countries, health care systems, and economies. It has also challenged every physician’s ideas of beneficence and justice ... but it’s just a virus, right?

Beneficence, the principle of medical ethics regarding acting in the patient’s best interest, had always seemed to me to be a no-brainer. Not like autonomy, which can get sticky, or justice, which I really had not had to consider much prior to 2020. Of course, I would always do what was best for my patient, I thought, why wouldn’t I?

Justice, the principle that deals with the distribution of scarce health-care resources, is the wrench that has been thrown into the beneficence works in the age of COVID-19. In a country and an era in which I had not dreamed we would ever have to think about how to support multiple people with one ventilator, we have had to do just that (“Joint Statement on Multiple Patients per Ventilator,” CHEST News, Mar 27, 2020). Things that I have taken for granted through all of my training are now worth their weight in gold—from sedative drips and inhalers down to videolaryngoscopy blades and face masks. I can’t just do what is best for my patient because sometimes what is best for my patient is not what is best for my next patient, what is best for my team, or even what is best for me and for my family. COVID-19 has reminded us of the uncomfortable truth that when contemplating justice, the patient in front of us is not the only person we have to consider.

Early on, before things in the United States had surged, I asked the twitter community what I thought would be a hypothetical question: “An employee needs to urgently help a COVID-19 patient. There is no appropriate PPE available due to shortage. What should happen?”

Like the idea of splitting ventilators, it was a thought I had never considered pre-COVID-19. Our instinct as physicians, especially as critical care physicians, is to intervene in emergency situations as quickly as possible. The extensive PPE required to manage COVID-19 patients has slowed that process, but, as many institutions are reaching the ends of their PPE stores, our safety is now placed at odds with that of our patient’s. To stay back violates what we feel is our duty to our patients, to go in violates our duty to ourselves, to our families, and to the rest of our patients. To care adequately for your patient is to put yourself at risk (and vice-versa), and this is a problem that I don’t think we have an answer for.

COVID-19 threatens many good and noble things, and what is worse, it directly puts them at odds with one another. They are paired sliding scales, where more of one means less of the other. If I have enough masks, it means my colleague probably doesn’t. If we have enough ventilators, it means another city doesn’t. If I get a break to be with my family, it means someone else is having to leave theirs to tend to patients who are sicker, lonelier, and more numerous than in any other time in recent memory.

And if these situations and resource limitations don’t provide enough moral injury for health-care workers, there are some specifics of humanity’s response to the pandemic that are exceptionally hurtful.

We as a country had notice, which was squandered. Instead of caution and preparation, we saw the powers that be make light of the serious situation most scientists and clinicians warned was coming. Instead of efforts to find or create PPE, we saw accusations against us of misuse and waste (“Trump comments about hospital mask thefts spark backlash from doctors,” Newsweek, March 30, 2020). Instead of support, we saw our altruism taken advantage of and used against us in unsafe and unfair situations. We have seen physicians in training and full-fledged attendings alike treated unfairly by their supervisors, instead of protected. Every instance of anti-science opinion or action from our friends and families that we once tolerated now feels like a personal affront, as these directly increase our risk and our immediate family’s risk of contracting the illness. We are being touted as heroes and angels, but really, we’re afraid—afraid of our patients, afraid of illness, afraid for our families, and afraid of jobs that we used to love. We don’t want to be praised; we just want to work our regular jobs safely and with adequate support.

I don’t know what health care looks like at the end of all of this. Relationships between physicians and health-care administrations were strained before the pandemic, to say the least. How can health-care workers just go back to business as usual, working for entities that were so ill-prepared, and, in many cases, calloused toward the concerns of their employees?

COVID-19 has revealed the fragility of our health-care system, our public health capabilities, and our economy. The pandemic has forced us to finally acknowledge something that has been true all along—our resources are finite, and tension exists between what is right and what is profitable, and between what is just and what is easy.

But it’s just a virus, right?
 

Dr. Fridenmaker is a Pulmonary and Critical Care Fellow at the University of Kentucky, Lexington.

My first exposure to the notion of scarce resources was in medical school. I had to discuss the ethical principles behind the allocation of organs for transplantation, specifically livers and the required abstinence from alcohol ... but this was just an exercise, right?

A few years later, during residency, I heard the anecdotes from one of my internal medicine attendings about the time he spent in Europe as a visiting geriatrics fellow in the 1970s. The health-care districts in the region would be allotted an annual budget, and it was up to those districts how to best allocate those resources to meet, to the best of their abilities, the health-care needs of their population. He vividly recalled that a patient he cared for, an individual over 65 in need of renal replacement therapy for a reversible condition, who was not offered such therapy despite the clear benefit. There was a finite amount of resources, and those resources were thought to be better spent on public health measures like vaccination ... but that was on another continent and in another era, right?

I remember when I first heard of an outbreak of viral pneumonia in China in January of this year. As someone prone to anxiety, my first strategy was to put my head in the sand and wait it out. This strategy didn’t last very long – within a couple of weeks, there were confirmed cases in the United States. It was now apparent that this virus was not going to be contained. In an impressively short amount of time, SARS-CoV 2 has infected over 3.5 million individuals and killed almost a quarter million people worldwide. In the United States, we have seen almost 1.2 million cases and lost over 68 thousand lives. This pandemic has managed to devastate multiple countries, health care systems, and economies. It has also challenged every physician’s ideas of beneficence and justice ... but it’s just a virus, right?

Beneficence, the principle of medical ethics regarding acting in the patient’s best interest, had always seemed to me to be a no-brainer. Not like autonomy, which can get sticky, or justice, which I really had not had to consider much prior to 2020. Of course, I would always do what was best for my patient, I thought, why wouldn’t I?

Justice, the principle that deals with the distribution of scarce health-care resources, is the wrench that has been thrown into the beneficence works in the age of COVID-19. In a country and an era in which I had not dreamed we would ever have to think about how to support multiple people with one ventilator, we have had to do just that (“Joint Statement on Multiple Patients per Ventilator,” CHEST News, Mar 27, 2020). Things that I have taken for granted through all of my training are now worth their weight in gold—from sedative drips and inhalers down to videolaryngoscopy blades and face masks. I can’t just do what is best for my patient because sometimes what is best for my patient is not what is best for my next patient, what is best for my team, or even what is best for me and for my family. COVID-19 has reminded us of the uncomfortable truth that when contemplating justice, the patient in front of us is not the only person we have to consider.

Early on, before things in the United States had surged, I asked the twitter community what I thought would be a hypothetical question: “An employee needs to urgently help a COVID-19 patient. There is no appropriate PPE available due to shortage. What should happen?”

Like the idea of splitting ventilators, it was a thought I had never considered pre-COVID-19. Our instinct as physicians, especially as critical care physicians, is to intervene in emergency situations as quickly as possible. The extensive PPE required to manage COVID-19 patients has slowed that process, but, as many institutions are reaching the ends of their PPE stores, our safety is now placed at odds with that of our patient’s. To stay back violates what we feel is our duty to our patients, to go in violates our duty to ourselves, to our families, and to the rest of our patients. To care adequately for your patient is to put yourself at risk (and vice-versa), and this is a problem that I don’t think we have an answer for.

COVID-19 threatens many good and noble things, and what is worse, it directly puts them at odds with one another. They are paired sliding scales, where more of one means less of the other. If I have enough masks, it means my colleague probably doesn’t. If we have enough ventilators, it means another city doesn’t. If I get a break to be with my family, it means someone else is having to leave theirs to tend to patients who are sicker, lonelier, and more numerous than in any other time in recent memory.

And if these situations and resource limitations don’t provide enough moral injury for health-care workers, there are some specifics of humanity’s response to the pandemic that are exceptionally hurtful.

We as a country had notice, which was squandered. Instead of caution and preparation, we saw the powers that be make light of the serious situation most scientists and clinicians warned was coming. Instead of efforts to find or create PPE, we saw accusations against us of misuse and waste (“Trump comments about hospital mask thefts spark backlash from doctors,” Newsweek, March 30, 2020). Instead of support, we saw our altruism taken advantage of and used against us in unsafe and unfair situations. We have seen physicians in training and full-fledged attendings alike treated unfairly by their supervisors, instead of protected. Every instance of anti-science opinion or action from our friends and families that we once tolerated now feels like a personal affront, as these directly increase our risk and our immediate family’s risk of contracting the illness. We are being touted as heroes and angels, but really, we’re afraid—afraid of our patients, afraid of illness, afraid for our families, and afraid of jobs that we used to love. We don’t want to be praised; we just want to work our regular jobs safely and with adequate support.

I don’t know what health care looks like at the end of all of this. Relationships between physicians and health-care administrations were strained before the pandemic, to say the least. How can health-care workers just go back to business as usual, working for entities that were so ill-prepared, and, in many cases, calloused toward the concerns of their employees?

COVID-19 has revealed the fragility of our health-care system, our public health capabilities, and our economy. The pandemic has forced us to finally acknowledge something that has been true all along—our resources are finite, and tension exists between what is right and what is profitable, and between what is just and what is easy.

But it’s just a virus, right?
 

Dr. Fridenmaker is a Pulmonary and Critical Care Fellow at the University of Kentucky, Lexington.

My first exposure to the notion of scarce resources was in medical school. I had to discuss the ethical principles behind the allocation of organs for transplantation, specifically livers and the required abstinence from alcohol ... but this was just an exercise, right?

A few years later, during residency, I heard the anecdotes from one of my internal medicine attendings about the time he spent in Europe as a visiting geriatrics fellow in the 1970s. The health-care districts in the region would be allotted an annual budget, and it was up to those districts how to best allocate those resources to meet, to the best of their abilities, the health-care needs of their population. He vividly recalled that a patient he cared for, an individual over 65 in need of renal replacement therapy for a reversible condition, who was not offered such therapy despite the clear benefit. There was a finite amount of resources, and those resources were thought to be better spent on public health measures like vaccination ... but that was on another continent and in another era, right?

I remember when I first heard of an outbreak of viral pneumonia in China in January of this year. As someone prone to anxiety, my first strategy was to put my head in the sand and wait it out. This strategy didn’t last very long – within a couple of weeks, there were confirmed cases in the United States. It was now apparent that this virus was not going to be contained. In an impressively short amount of time, SARS-CoV 2 has infected over 3.5 million individuals and killed almost a quarter million people worldwide. In the United States, we have seen almost 1.2 million cases and lost over 68 thousand lives. This pandemic has managed to devastate multiple countries, health care systems, and economies. It has also challenged every physician’s ideas of beneficence and justice ... but it’s just a virus, right?

Beneficence, the principle of medical ethics regarding acting in the patient’s best interest, had always seemed to me to be a no-brainer. Not like autonomy, which can get sticky, or justice, which I really had not had to consider much prior to 2020. Of course, I would always do what was best for my patient, I thought, why wouldn’t I?

Justice, the principle that deals with the distribution of scarce health-care resources, is the wrench that has been thrown into the beneficence works in the age of COVID-19. In a country and an era in which I had not dreamed we would ever have to think about how to support multiple people with one ventilator, we have had to do just that (“Joint Statement on Multiple Patients per Ventilator,” CHEST News, Mar 27, 2020). Things that I have taken for granted through all of my training are now worth their weight in gold—from sedative drips and inhalers down to videolaryngoscopy blades and face masks. I can’t just do what is best for my patient because sometimes what is best for my patient is not what is best for my next patient, what is best for my team, or even what is best for me and for my family. COVID-19 has reminded us of the uncomfortable truth that when contemplating justice, the patient in front of us is not the only person we have to consider.

Early on, before things in the United States had surged, I asked the twitter community what I thought would be a hypothetical question: “An employee needs to urgently help a COVID-19 patient. There is no appropriate PPE available due to shortage. What should happen?”

Like the idea of splitting ventilators, it was a thought I had never considered pre-COVID-19. Our instinct as physicians, especially as critical care physicians, is to intervene in emergency situations as quickly as possible. The extensive PPE required to manage COVID-19 patients has slowed that process, but, as many institutions are reaching the ends of their PPE stores, our safety is now placed at odds with that of our patient’s. To stay back violates what we feel is our duty to our patients, to go in violates our duty to ourselves, to our families, and to the rest of our patients. To care adequately for your patient is to put yourself at risk (and vice-versa), and this is a problem that I don’t think we have an answer for.

COVID-19 threatens many good and noble things, and what is worse, it directly puts them at odds with one another. They are paired sliding scales, where more of one means less of the other. If I have enough masks, it means my colleague probably doesn’t. If we have enough ventilators, it means another city doesn’t. If I get a break to be with my family, it means someone else is having to leave theirs to tend to patients who are sicker, lonelier, and more numerous than in any other time in recent memory.

And if these situations and resource limitations don’t provide enough moral injury for health-care workers, there are some specifics of humanity’s response to the pandemic that are exceptionally hurtful.

We as a country had notice, which was squandered. Instead of caution and preparation, we saw the powers that be make light of the serious situation most scientists and clinicians warned was coming. Instead of efforts to find or create PPE, we saw accusations against us of misuse and waste (“Trump comments about hospital mask thefts spark backlash from doctors,” Newsweek, March 30, 2020). Instead of support, we saw our altruism taken advantage of and used against us in unsafe and unfair situations. We have seen physicians in training and full-fledged attendings alike treated unfairly by their supervisors, instead of protected. Every instance of anti-science opinion or action from our friends and families that we once tolerated now feels like a personal affront, as these directly increase our risk and our immediate family’s risk of contracting the illness. We are being touted as heroes and angels, but really, we’re afraid—afraid of our patients, afraid of illness, afraid for our families, and afraid of jobs that we used to love. We don’t want to be praised; we just want to work our regular jobs safely and with adequate support.

I don’t know what health care looks like at the end of all of this. Relationships between physicians and health-care administrations were strained before the pandemic, to say the least. How can health-care workers just go back to business as usual, working for entities that were so ill-prepared, and, in many cases, calloused toward the concerns of their employees?

COVID-19 has revealed the fragility of our health-care system, our public health capabilities, and our economy. The pandemic has forced us to finally acknowledge something that has been true all along—our resources are finite, and tension exists between what is right and what is profitable, and between what is just and what is easy.

But it’s just a virus, right?
 

Dr. Fridenmaker is a Pulmonary and Critical Care Fellow at the University of Kentucky, Lexington.

Cardiovascular medicine and surgery

COVID-19 and the cardiovascular system

With the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ongoing, there is increased awareness of the cardiovascular manifestations and implications of COVID-19. Approximately 20% of inpatients with COVID-19 have acute cardiac injury (defined as cardiac troponin elevation) (Shi S, et al. JAMA Cardiol. 2020 Mar 25. doi: 10.1001/jamacardio.2020.0950). Moreover, in one cohort, both acute cardiac injury and preexisting cardiovascular disease (CVD) were associated with COVID-19 hospital mortality: 69% with elevated troponin levels and underlying CVD vs 7.6% with neither (Guo T, et al. JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017). Moreover, case reports suggest COVID-19 may present as myopericarditis, cardiomyopathy, acute on chronic decompensated heart failure, and acute coronary syndrome (Fried JA, et al. Circulation. 2020 Apr 3. doi: 10.1161/circulationaha.120.047164). Adding to this clinical variability, one case series suggests that electrocardiographic ST-segment elevation may not reliably identify obstructive coronary disease (Bangalore S, et al. N Engl J Med. 2020 Apr 17. doi: 10.1056/NEJMc2009020). Intriguingly, the angiotensin-converting enzyme 2 (ACE2) protein is the functional receptor for SARS-CoV-2 cell entry, and ACE2 is highly expressed in pulmonary and cardiac cells (Driggin E, et al. J Am Coll Cardiol. 2020;75[18]:2352). Given the central role of ACE2 and the renin-angiotensin-aldosterone (RAAS) system in cardiovascular pathophysiology and pharmacotherapy, RAAS modulation could have beneficial and/or detrimental effects with COVID-19 (Vaduganathan M, et al. N Engl J Med. 2020;382:1653). Available evidence and societal guidelines support continuing RAAS antagonists in patients per established clinical practice (Mancia G, et al. N Engl J Med. 2020 May 1. doi: 10.1056/NEJMoa2006923); (Mehra MR, et al. N Engl J Med. 2020 May 1. doi: 10.1056/NEJMoa2007621). A better understanding of the direct and indirect effect of SARS-CoV-2 on the cardiovascular system will require additional evidence.

Benjamin B. Kenigsberg, MD

Fellow-in-Training Steering Committee Member

Thrombotic events in COVID-19: Implications and evolving practice recommendations

A startling potential complication of infection with SARS-CoV2 has been the reported predisposition to thrombotic events. Mortality in COVID-19 patients is associated with notable increases in hemostatic parameters such as levels of d-dimer (Bikdeli, et al. J Am Coll Cardiol. 2020 Apr 15. pii: S0735-1097(20)35008-7. doi: 10.1016/j.jacc.2020.04.031. Available autopsy findings suggest that microvascular thrombosis may contribute to development of hypoxemic respiratory failure in COVID-19 (Wichmann, et al. Ann Intern Med. 2020 May 6. doi: 10.7326/M20-2003. Hence, the role of anticoagulation in COVID-19 merits serious discussion.

Vascular societies led by International Society on Thrombosis and Haemostasis (ISTH) have published consensus recommendations for guidance. If no contraindications exist, pharmacologic venous thromboembolism (VTE) prophylaxis with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) is recommended for hospitalized patients with moderate or severe COVID-19 without disseminated intravascular coagulation (DIC). VTE prophylaxis should also be considered for patients with moderate or severe COVID-19 and in DIC but without overt bleeding. There is insufficient evidence to consider routine therapeutic or intermediate-dose parenteral anticoagulation with UFH or LMWH. Many institutions have developed protocols advising therapeutic-intensity anticoagulation when certain thresholds of d-dimer levels are observed, even in the absence of documented VTE. It is unclear how long the prothrombotic milieu in COVID-19 persists after recovery, and consensus recommendations (and some centers) are considering extended prophylaxis (30-45 days) post-discharge after individual VTE risk stratification (Kreuziger LB, et al. American Society of Hematology, April 17, 2020.. Further well-designed research is needed to inform clinicians of anticoagulation strategies in COVID-19 population.

Saiprakash B. Venkateshiah, MD, FCCP,

Chair

Gabriela Magda, MD

Fellow-in-Training Steering Committee Member
 

Interprofessional Team

Quality of interprofessional collaboration in the medical intensive care unit: perceptions by caregivers

A recent study examining caregivers’ perceptions of team interactions and interprofessional collaborative practice (IPCP) behaviors offers new, exciting insights on the importance of interprofessional team functioning in the medical intensive care unit (MICU) (Chen DW, et al. J Gen Intern Med. 2018;33[10]:1708).

Cardiovascular medicine and surgery

COVID-19 and the cardiovascular system

With the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ongoing, there is increased awareness of the cardiovascular manifestations and implications of COVID-19. Approximately 20% of inpatients with COVID-19 have acute cardiac injury (defined as cardiac troponin elevation) (Shi S, et al. JAMA Cardiol. 2020 Mar 25. doi: 10.1001/jamacardio.2020.0950). Moreover, in one cohort, both acute cardiac injury and preexisting cardiovascular disease (CVD) were associated with COVID-19 hospital mortality: 69% with elevated troponin levels and underlying CVD vs 7.6% with neither (Guo T, et al. JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017). Moreover, case reports suggest COVID-19 may present as myopericarditis, cardiomyopathy, acute on chronic decompensated heart failure, and acute coronary syndrome (Fried JA, et al. Circulation. 2020 Apr 3. doi: 10.1161/circulationaha.120.047164). Adding to this clinical variability, one case series suggests that electrocardiographic ST-segment elevation may not reliably identify obstructive coronary disease (Bangalore S, et al. N Engl J Med. 2020 Apr 17. doi: 10.1056/NEJMc2009020). Intriguingly, the angiotensin-converting enzyme 2 (ACE2) protein is the functional receptor for SARS-CoV-2 cell entry, and ACE2 is highly expressed in pulmonary and cardiac cells (Driggin E, et al. J Am Coll Cardiol. 2020;75[18]:2352). Given the central role of ACE2 and the renin-angiotensin-aldosterone (RAAS) system in cardiovascular pathophysiology and pharmacotherapy, RAAS modulation could have beneficial and/or detrimental effects with COVID-19 (Vaduganathan M, et al. N Engl J Med. 2020;382:1653). Available evidence and societal guidelines support continuing RAAS antagonists in patients per established clinical practice (Mancia G, et al. N Engl J Med. 2020 May 1. doi: 10.1056/NEJMoa2006923); (Mehra MR, et al. N Engl J Med. 2020 May 1. doi: 10.1056/NEJMoa2007621). A better understanding of the direct and indirect effect of SARS-CoV-2 on the cardiovascular system will require additional evidence.

Benjamin B. Kenigsberg, MD

Fellow-in-Training Steering Committee Member

Thrombotic events in COVID-19: Implications and evolving practice recommendations

A startling potential complication of infection with SARS-CoV2 has been the reported predisposition to thrombotic events. Mortality in COVID-19 patients is associated with notable increases in hemostatic parameters such as levels of d-dimer (Bikdeli, et al. J Am Coll Cardiol. 2020 Apr 15. pii: S0735-1097(20)35008-7. doi: 10.1016/j.jacc.2020.04.031. Available autopsy findings suggest that microvascular thrombosis may contribute to development of hypoxemic respiratory failure in COVID-19 (Wichmann, et al. Ann Intern Med. 2020 May 6. doi: 10.7326/M20-2003. Hence, the role of anticoagulation in COVID-19 merits serious discussion.

Vascular societies led by International Society on Thrombosis and Haemostasis (ISTH) have published consensus recommendations for guidance. If no contraindications exist, pharmacologic venous thromboembolism (VTE) prophylaxis with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) is recommended for hospitalized patients with moderate or severe COVID-19 without disseminated intravascular coagulation (DIC). VTE prophylaxis should also be considered for patients with moderate or severe COVID-19 and in DIC but without overt bleeding. There is insufficient evidence to consider routine therapeutic or intermediate-dose parenteral anticoagulation with UFH or LMWH. Many institutions have developed protocols advising therapeutic-intensity anticoagulation when certain thresholds of d-dimer levels are observed, even in the absence of documented VTE. It is unclear how long the prothrombotic milieu in COVID-19 persists after recovery, and consensus recommendations (and some centers) are considering extended prophylaxis (30-45 days) post-discharge after individual VTE risk stratification (Kreuziger LB, et al. American Society of Hematology, April 17, 2020.. Further well-designed research is needed to inform clinicians of anticoagulation strategies in COVID-19 population.

Saiprakash B. Venkateshiah, MD, FCCP,

Chair

Gabriela Magda, MD

Fellow-in-Training Steering Committee Member
 

Interprofessional Team

Quality of interprofessional collaboration in the medical intensive care unit: perceptions by caregivers

A recent study examining caregivers’ perceptions of team interactions and interprofessional collaborative practice (IPCP) behaviors offers new, exciting insights on the importance of interprofessional team functioning in the medical intensive care unit (MICU) (Chen DW, et al. J Gen Intern Med. 2018;33[10]:1708).

Cardiovascular medicine and surgery

COVID-19 and the cardiovascular system

With the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ongoing, there is increased awareness of the cardiovascular manifestations and implications of COVID-19. Approximately 20% of inpatients with COVID-19 have acute cardiac injury (defined as cardiac troponin elevation) (Shi S, et al. JAMA Cardiol. 2020 Mar 25. doi: 10.1001/jamacardio.2020.0950). Moreover, in one cohort, both acute cardiac injury and preexisting cardiovascular disease (CVD) were associated with COVID-19 hospital mortality: 69% with elevated troponin levels and underlying CVD vs 7.6% with neither (Guo T, et al. JAMA Cardiol. 2020 Mar 27. doi: 10.1001/jamacardio.2020.1017). Moreover, case reports suggest COVID-19 may present as myopericarditis, cardiomyopathy, acute on chronic decompensated heart failure, and acute coronary syndrome (Fried JA, et al. Circulation. 2020 Apr 3. doi: 10.1161/circulationaha.120.047164). Adding to this clinical variability, one case series suggests that electrocardiographic ST-segment elevation may not reliably identify obstructive coronary disease (Bangalore S, et al. N Engl J Med. 2020 Apr 17. doi: 10.1056/NEJMc2009020). Intriguingly, the angiotensin-converting enzyme 2 (ACE2) protein is the functional receptor for SARS-CoV-2 cell entry, and ACE2 is highly expressed in pulmonary and cardiac cells (Driggin E, et al. J Am Coll Cardiol. 2020;75[18]:2352). Given the central role of ACE2 and the renin-angiotensin-aldosterone (RAAS) system in cardiovascular pathophysiology and pharmacotherapy, RAAS modulation could have beneficial and/or detrimental effects with COVID-19 (Vaduganathan M, et al. N Engl J Med. 2020;382:1653). Available evidence and societal guidelines support continuing RAAS antagonists in patients per established clinical practice (Mancia G, et al. N Engl J Med. 2020 May 1. doi: 10.1056/NEJMoa2006923); (Mehra MR, et al. N Engl J Med. 2020 May 1. doi: 10.1056/NEJMoa2007621). A better understanding of the direct and indirect effect of SARS-CoV-2 on the cardiovascular system will require additional evidence.

Benjamin B. Kenigsberg, MD

Fellow-in-Training Steering Committee Member

Thrombotic events in COVID-19: Implications and evolving practice recommendations

A startling potential complication of infection with SARS-CoV2 has been the reported predisposition to thrombotic events. Mortality in COVID-19 patients is associated with notable increases in hemostatic parameters such as levels of d-dimer (Bikdeli, et al. J Am Coll Cardiol. 2020 Apr 15. pii: S0735-1097(20)35008-7. doi: 10.1016/j.jacc.2020.04.031. Available autopsy findings suggest that microvascular thrombosis may contribute to development of hypoxemic respiratory failure in COVID-19 (Wichmann, et al. Ann Intern Med. 2020 May 6. doi: 10.7326/M20-2003. Hence, the role of anticoagulation in COVID-19 merits serious discussion.

Vascular societies led by International Society on Thrombosis and Haemostasis (ISTH) have published consensus recommendations for guidance. If no contraindications exist, pharmacologic venous thromboembolism (VTE) prophylaxis with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) is recommended for hospitalized patients with moderate or severe COVID-19 without disseminated intravascular coagulation (DIC). VTE prophylaxis should also be considered for patients with moderate or severe COVID-19 and in DIC but without overt bleeding. There is insufficient evidence to consider routine therapeutic or intermediate-dose parenteral anticoagulation with UFH or LMWH. Many institutions have developed protocols advising therapeutic-intensity anticoagulation when certain thresholds of d-dimer levels are observed, even in the absence of documented VTE. It is unclear how long the prothrombotic milieu in COVID-19 persists after recovery, and consensus recommendations (and some centers) are considering extended prophylaxis (30-45 days) post-discharge after individual VTE risk stratification (Kreuziger LB, et al. American Society of Hematology, April 17, 2020.. Further well-designed research is needed to inform clinicians of anticoagulation strategies in COVID-19 population.

Saiprakash B. Venkateshiah, MD, FCCP,

Chair

Gabriela Magda, MD

Fellow-in-Training Steering Committee Member
 

Interprofessional Team

Quality of interprofessional collaboration in the medical intensive care unit: perceptions by caregivers

A recent study examining caregivers’ perceptions of team interactions and interprofessional collaborative practice (IPCP) behaviors offers new, exciting insights on the importance of interprofessional team functioning in the medical intensive care unit (MICU) (Chen DW, et al. J Gen Intern Med. 2018;33[10]:1708).

Preparing for the COVID-19 Pandemic: Our Experience in New York.By Dr. H. Zubair, et al.

The Utility of Electronic Inhaler Monitoring in COPD Management: Promises and Challenges.By Dr. A. H. Attaway, et al.

Patterns of Use of Adjunctive Therapies in Patients With Early Moderate-Severe Acute Respiratory Distress Syndrome: Insights From the LUNG SAFE Study.By Dr. A. Duggal, et al.

Clinical Evaluation of Deployed Military Personnel with Chronic Respiratory Symptoms: STAMPEDE III (Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures). By Dr. M. J. Morris, et al.

Preparing for the COVID-19 Pandemic: Our Experience in New York.By Dr. H. Zubair, et al.

The Utility of Electronic Inhaler Monitoring in COPD Management: Promises and Challenges.By Dr. A. H. Attaway, et al.

Patterns of Use of Adjunctive Therapies in Patients With Early Moderate-Severe Acute Respiratory Distress Syndrome: Insights From the LUNG SAFE Study.By Dr. A. Duggal, et al.

Clinical Evaluation of Deployed Military Personnel with Chronic Respiratory Symptoms: STAMPEDE III (Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures). By Dr. M. J. Morris, et al.

Preparing for the COVID-19 Pandemic: Our Experience in New York.By Dr. H. Zubair, et al.

The Utility of Electronic Inhaler Monitoring in COPD Management: Promises and Challenges.By Dr. A. H. Attaway, et al.

Patterns of Use of Adjunctive Therapies in Patients With Early Moderate-Severe Acute Respiratory Distress Syndrome: Insights From the LUNG SAFE Study.By Dr. A. Duggal, et al.

Clinical Evaluation of Deployed Military Personnel with Chronic Respiratory Symptoms: STAMPEDE III (Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures). By Dr. M. J. Morris, et al.

Cystic fibrosis (CF) is an autosomal recessive disorder affecting thousands of people worldwide. When this genetic disease was first discovered in the first half of the 20th century, the median survival was approximately 5 years of age. Since then, median survival for patients with CF has steadily improved. Today, it is 47.4 years based on Cystic Fibrosis Foundation registry data from 2018. Patients with CF are living longer and staying healthier; the discussion to follow is how patients, researchers, and the CF Foundation reached this point.

In 1938, pediatrician and pathologist Dorothy Anderson observed on the autopsies of children thought to have celiac disease pancreatic lesions she termed “cystic fibrosis of the pancreas.” In addition to the abnormal pancreas, she noted abnormal lungs filled with mucus that obstructed the airways.

Paul Di Sant’Agnese recognized during a heatwave in late 1948 that children with CF were routinely being diagnosed with heatstroke and dehydration. This helped lead to the discovery that these children had elevated salt content in their sweat, paving the way for the development of the sweat chloride test in 1959 by Gibson and Cooke. Not only did Dr. Di Sant’Agnese recognize excess salt in the sweat of patients with CF, but with the help of several concerned parents of children with CF, he established the Cystic Fibrosis Foundation in 1955. The Foundation helped organize the care center model over the next decades, increasing from 30 care centers in 1962 to over 100 in 1978. The care center model also developed a patient registry to track patient care longitudinally.

In June 1989, Francis Collins and Lap-Chee Tsui discovered the location of the CF transmembrane conductance regulator (CFTR) protein using a novel technique called chromosome jumping (Rommens JM, et al. Science. 1989;245[4922]1059). The discovery was a breakthrough in basic science research, but it would take 3 more decades before this discovery could be translated into a medication that could be used by most patients for everyday care.

In the early 1990s, when median survival for patients with CF was 29 years of age, the CF Foundation and Genentech, Inc., coordinated a 24-week multicenter double-blind randomized control trial (RCT) for a new inhaled medication that digested the extracellular DNA from the neutrophils that accumulated in the airways of patients with CF. Inhaled recombinant human DNase in these patients reduced the risk of pulmonary exacerbations and also had a small improvement in pulmonary function in the group compared with the placebo group (Fuchs H, et al. N Engl J Med. 1994;331:637). Five years later, another double-blind RCT demonstrated that inhaled tobramycin in patients with CF whose disease was colonized with Pseudomonas aeruginosa improved pulmonary function and reduced the risk of hospitalizations (Ramsey B, et al. N Engl J Med. 1999;340:23). In 2006, the use of hypertonic saline solution in patients with CF decreased the overall pulmonary exacerbation rate (Elkins MR, et al. N Engl J Med. 2006;354:229). The combination of these inhaled medications, along with inhaled aztreonam, formed the backbone of inhalation therapy for CF care today.

In 1998, even with the ongoing development and approval of new CF medications by the pharmaceutical industry, Robert Beall, CEO of the CF Foundation, realized that he needed to challenge the current drug development paradigm. Instead of trying to convince companies to develop CF medications, he started a concept called venture philanthropy. This concept entailed the CF Foundation financially investing in pharmaceutical companies’ development of new medications. The Foundation first invested in a small company named Aurora Biosciences (known today as Vertex Pharmaceuticals) in 2000. Aurora Biosciences specialized in high throughput screening. This process uses a unique technology allowing one to test the therapeutic reaction of airway cells to thousands of chemical compounds in a single day, instead of using the traditional process of tediously pipetting compounds one by one. Today, the CF Foundation has invested millions of dollars into bioscience research to advance CF care.

In 2011, the results of a study were published in which a small molecule altered defective CFTR protein in patients with CF with the CFTR mutation G551D, thus improving chloride transport at the airway surface. In the original study, after 24 weeks of therapy receiving the medication known as ivacaftor, predicted FEV1 in patients with CF improved 10.6%, and the patients were 55% less likely to have a pulmonary exacerbation compared with those receiving a placebo. This breakthrough provided patients with CF the first medication that could correct the CFTR at the source of the problem (Ramsey BW, et al. N Engl J Med. 2011;365:1663). Ivacaftor was approved by the US FDA in 2012.

Ivacaftor provided proof of concept that using small molecules could improve CFTR function. Ivacaftor was only beneficial to a small percentage of patients and was not effective in patients with CF who had either 1 or 2 F508del CFTR mutations. In 2015, patients with CF with F508del homozygous treated with a combination therapy of lumacaftor/ivacaftor had predicted FEV1% improved 2.6% to 4.0%. More importantly, there was a significant reduction in the number of pulmonary exacerbations per year compared with placebo. Unexpectedly, some of the patients experienced bronchoconstriction while receiving lumacaftor/ivacaftor (Wainwright CE, et al. N Engl J Med. 2015; 373:220). The problem was recognized, and a new small molecule to improve the processing and trafficking of CFTR called tezacaftor was developed. The combination of tezacaftor/ivacaftor in patients with CF who were F508del homozygous demonstrated a similar reduction in pulmonary exacerbations, an absolute improvement of predicted FEV₁ of 4%, and no increased respiratory symptoms compared with the placebo arm (Taylor-Cousar JL, et al. N Engl J Med. 2017;377[21]2013).

CFTR modulators were a major breakthrough for patients with CF, but the efficacy of these therapies was dependent on the patients’ genotype and ranged from mildly to moderately effective. Unfortunately, these therapies were ineffective for the patients who were delta 508 heterozygotes. Starting in the summer of 2018, VX 445-tezacaftor-ivacaftor (ETI) was compared with placebo in patients with CF who were 1 copy of F508del and a second CFTR mutation that has minimal function. The study found an absolute improvement in predicted FEV1 of 14.3% and a 63% reduction in exacerbations at 24 weeks compared with placebo (Middleton PG, et al. N Engl J Med. 2019;381:1809). In late 2019, based on these data, ETI was approved by the FDA for all patients with CF who were F508del heterozygous. This innovation provided effective therapy to 90% of the CF population.

With the discovery of many highly effective therapies beneficial in most patients, the CF Foundation started a program called Path to a Cure to find therapies for the 10% of patients with CF who were not candidates for ETI or other CFTR modulators. This program looks to develop novel methods to restore CFTR protein function and repair or replace the CFTR protein via gene editing or gene transfer. This process creates many challenges that are quite complex, but patients, researchers, physicians, and CF Foundation will not stop working until CF stands for CURE FOUND.

Today, patients with CF are living longer, and many are eligible or have already started ETI therapy. This medication and the many others being developed will hopefully lead to patients with CF living a normal lifespan in the near future.
 

Dr. Finklea is Assistant Professor of Medicine, Division of Pulmonary and Critical Care, University of Texas Southwestern, Dallas, Texas. Dr. Finklea receives grant support from the Cystic Fibrosis Foundation.

Cystic fibrosis (CF) is an autosomal recessive disorder affecting thousands of people worldwide. When this genetic disease was first discovered in the first half of the 20th century, the median survival was approximately 5 years of age. Since then, median survival for patients with CF has steadily improved. Today, it is 47.4 years based on Cystic Fibrosis Foundation registry data from 2018. Patients with CF are living longer and staying healthier; the discussion to follow is how patients, researchers, and the CF Foundation reached this point.

In 1938, pediatrician and pathologist Dorothy Anderson observed on the autopsies of children thought to have celiac disease pancreatic lesions she termed “cystic fibrosis of the pancreas.” In addition to the abnormal pancreas, she noted abnormal lungs filled with mucus that obstructed the airways.

Paul Di Sant’Agnese recognized during a heatwave in late 1948 that children with CF were routinely being diagnosed with heatstroke and dehydration. This helped lead to the discovery that these children had elevated salt content in their sweat, paving the way for the development of the sweat chloride test in 1959 by Gibson and Cooke. Not only did Dr. Di Sant’Agnese recognize excess salt in the sweat of patients with CF, but with the help of several concerned parents of children with CF, he established the Cystic Fibrosis Foundation in 1955. The Foundation helped organize the care center model over the next decades, increasing from 30 care centers in 1962 to over 100 in 1978. The care center model also developed a patient registry to track patient care longitudinally.

In June 1989, Francis Collins and Lap-Chee Tsui discovered the location of the CF transmembrane conductance regulator (CFTR) protein using a novel technique called chromosome jumping (Rommens JM, et al. Science. 1989;245[4922]1059). The discovery was a breakthrough in basic science research, but it would take 3 more decades before this discovery could be translated into a medication that could be used by most patients for everyday care.

In the early 1990s, when median survival for patients with CF was 29 years of age, the CF Foundation and Genentech, Inc., coordinated a 24-week multicenter double-blind randomized control trial (RCT) for a new inhaled medication that digested the extracellular DNA from the neutrophils that accumulated in the airways of patients with CF. Inhaled recombinant human DNase in these patients reduced the risk of pulmonary exacerbations and also had a small improvement in pulmonary function in the group compared with the placebo group (Fuchs H, et al. N Engl J Med. 1994;331:637). Five years later, another double-blind RCT demonstrated that inhaled tobramycin in patients with CF whose disease was colonized with Pseudomonas aeruginosa improved pulmonary function and reduced the risk of hospitalizations (Ramsey B, et al. N Engl J Med. 1999;340:23). In 2006, the use of hypertonic saline solution in patients with CF decreased the overall pulmonary exacerbation rate (Elkins MR, et al. N Engl J Med. 2006;354:229). The combination of these inhaled medications, along with inhaled aztreonam, formed the backbone of inhalation therapy for CF care today.

In 1998, even with the ongoing development and approval of new CF medications by the pharmaceutical industry, Robert Beall, CEO of the CF Foundation, realized that he needed to challenge the current drug development paradigm. Instead of trying to convince companies to develop CF medications, he started a concept called venture philanthropy. This concept entailed the CF Foundation financially investing in pharmaceutical companies’ development of new medications. The Foundation first invested in a small company named Aurora Biosciences (known today as Vertex Pharmaceuticals) in 2000. Aurora Biosciences specialized in high throughput screening. This process uses a unique technology allowing one to test the therapeutic reaction of airway cells to thousands of chemical compounds in a single day, instead of using the traditional process of tediously pipetting compounds one by one. Today, the CF Foundation has invested millions of dollars into bioscience research to advance CF care.

In 2011, the results of a study were published in which a small molecule altered defective CFTR protein in patients with CF with the CFTR mutation G551D, thus improving chloride transport at the airway surface. In the original study, after 24 weeks of therapy receiving the medication known as ivacaftor, predicted FEV1 in patients with CF improved 10.6%, and the patients were 55% less likely to have a pulmonary exacerbation compared with those receiving a placebo. This breakthrough provided patients with CF the first medication that could correct the CFTR at the source of the problem (Ramsey BW, et al. N Engl J Med. 2011;365:1663). Ivacaftor was approved by the US FDA in 2012.

Ivacaftor provided proof of concept that using small molecules could improve CFTR function. Ivacaftor was only beneficial to a small percentage of patients and was not effective in patients with CF who had either 1 or 2 F508del CFTR mutations. In 2015, patients with CF with F508del homozygous treated with a combination therapy of lumacaftor/ivacaftor had predicted FEV1% improved 2.6% to 4.0%. More importantly, there was a significant reduction in the number of pulmonary exacerbations per year compared with placebo. Unexpectedly, some of the patients experienced bronchoconstriction while receiving lumacaftor/ivacaftor (Wainwright CE, et al. N Engl J Med. 2015; 373:220). The problem was recognized, and a new small molecule to improve the processing and trafficking of CFTR called tezacaftor was developed. The combination of tezacaftor/ivacaftor in patients with CF who were F508del homozygous demonstrated a similar reduction in pulmonary exacerbations, an absolute improvement of predicted FEV₁ of 4%, and no increased respiratory symptoms compared with the placebo arm (Taylor-Cousar JL, et al. N Engl J Med. 2017;377[21]2013).

CFTR modulators were a major breakthrough for patients with CF, but the efficacy of these therapies was dependent on the patients’ genotype and ranged from mildly to moderately effective. Unfortunately, these therapies were ineffective for the patients who were delta 508 heterozygotes. Starting in the summer of 2018, VX 445-tezacaftor-ivacaftor (ETI) was compared with placebo in patients with CF who were 1 copy of F508del and a second CFTR mutation that has minimal function. The study found an absolute improvement in predicted FEV1 of 14.3% and a 63% reduction in exacerbations at 24 weeks compared with placebo (Middleton PG, et al. N Engl J Med. 2019;381:1809). In late 2019, based on these data, ETI was approved by the FDA for all patients with CF who were F508del heterozygous. This innovation provided effective therapy to 90% of the CF population.

With the discovery of many highly effective therapies beneficial in most patients, the CF Foundation started a program called Path to a Cure to find therapies for the 10% of patients with CF who were not candidates for ETI or other CFTR modulators. This program looks to develop novel methods to restore CFTR protein function and repair or replace the CFTR protein via gene editing or gene transfer. This process creates many challenges that are quite complex, but patients, researchers, physicians, and CF Foundation will not stop working until CF stands for CURE FOUND.

Today, patients with CF are living longer, and many are eligible or have already started ETI therapy. This medication and the many others being developed will hopefully lead to patients with CF living a normal lifespan in the near future.
 

Dr. Finklea is Assistant Professor of Medicine, Division of Pulmonary and Critical Care, University of Texas Southwestern, Dallas, Texas. Dr. Finklea receives grant support from the Cystic Fibrosis Foundation.

Cystic fibrosis (CF) is an autosomal recessive disorder affecting thousands of people worldwide. When this genetic disease was first discovered in the first half of the 20th century, the median survival was approximately 5 years of age. Since then, median survival for patients with CF has steadily improved. Today, it is 47.4 years based on Cystic Fibrosis Foundation registry data from 2018. Patients with CF are living longer and staying healthier; the discussion to follow is how patients, researchers, and the CF Foundation reached this point.

In 1938, pediatrician and pathologist Dorothy Anderson observed on the autopsies of children thought to have celiac disease pancreatic lesions she termed “cystic fibrosis of the pancreas.” In addition to the abnormal pancreas, she noted abnormal lungs filled with mucus that obstructed the airways.

Paul Di Sant’Agnese recognized during a heatwave in late 1948 that children with CF were routinely being diagnosed with heatstroke and dehydration. This helped lead to the discovery that these children had elevated salt content in their sweat, paving the way for the development of the sweat chloride test in 1959 by Gibson and Cooke. Not only did Dr. Di Sant’Agnese recognize excess salt in the sweat of patients with CF, but with the help of several concerned parents of children with CF, he established the Cystic Fibrosis Foundation in 1955. The Foundation helped organize the care center model over the next decades, increasing from 30 care centers in 1962 to over 100 in 1978. The care center model also developed a patient registry to track patient care longitudinally.

In June 1989, Francis Collins and Lap-Chee Tsui discovered the location of the CF transmembrane conductance regulator (CFTR) protein using a novel technique called chromosome jumping (Rommens JM, et al. Science. 1989;245[4922]1059). The discovery was a breakthrough in basic science research, but it would take 3 more decades before this discovery could be translated into a medication that could be used by most patients for everyday care.

In the early 1990s, when median survival for patients with CF was 29 years of age, the CF Foundation and Genentech, Inc., coordinated a 24-week multicenter double-blind randomized control trial (RCT) for a new inhaled medication that digested the extracellular DNA from the neutrophils that accumulated in the airways of patients with CF. Inhaled recombinant human DNase in these patients reduced the risk of pulmonary exacerbations and also had a small improvement in pulmonary function in the group compared with the placebo group (Fuchs H, et al. N Engl J Med. 1994;331:637). Five years later, another double-blind RCT demonstrated that inhaled tobramycin in patients with CF whose disease was colonized with Pseudomonas aeruginosa improved pulmonary function and reduced the risk of hospitalizations (Ramsey B, et al. N Engl J Med. 1999;340:23). In 2006, the use of hypertonic saline solution in patients with CF decreased the overall pulmonary exacerbation rate (Elkins MR, et al. N Engl J Med. 2006;354:229). The combination of these inhaled medications, along with inhaled aztreonam, formed the backbone of inhalation therapy for CF care today.

In 1998, even with the ongoing development and approval of new CF medications by the pharmaceutical industry, Robert Beall, CEO of the CF Foundation, realized that he needed to challenge the current drug development paradigm. Instead of trying to convince companies to develop CF medications, he started a concept called venture philanthropy. This concept entailed the CF Foundation financially investing in pharmaceutical companies’ development of new medications. The Foundation first invested in a small company named Aurora Biosciences (known today as Vertex Pharmaceuticals) in 2000. Aurora Biosciences specialized in high throughput screening. This process uses a unique technology allowing one to test the therapeutic reaction of airway cells to thousands of chemical compounds in a single day, instead of using the traditional process of tediously pipetting compounds one by one. Today, the CF Foundation has invested millions of dollars into bioscience research to advance CF care.

In 2011, the results of a study were published in which a small molecule altered defective CFTR protein in patients with CF with the CFTR mutation G551D, thus improving chloride transport at the airway surface. In the original study, after 24 weeks of therapy receiving the medication known as ivacaftor, predicted FEV1 in patients with CF improved 10.6%, and the patients were 55% less likely to have a pulmonary exacerbation compared with those receiving a placebo. This breakthrough provided patients with CF the first medication that could correct the CFTR at the source of the problem (Ramsey BW, et al. N Engl J Med. 2011;365:1663). Ivacaftor was approved by the US FDA in 2012.

Ivacaftor provided proof of concept that using small molecules could improve CFTR function. Ivacaftor was only beneficial to a small percentage of patients and was not effective in patients with CF who had either 1 or 2 F508del CFTR mutations. In 2015, patients with CF with F508del homozygous treated with a combination therapy of lumacaftor/ivacaftor had predicted FEV1% improved 2.6% to 4.0%. More importantly, there was a significant reduction in the number of pulmonary exacerbations per year compared with placebo. Unexpectedly, some of the patients experienced bronchoconstriction while receiving lumacaftor/ivacaftor (Wainwright CE, et al. N Engl J Med. 2015; 373:220). The problem was recognized, and a new small molecule to improve the processing and trafficking of CFTR called tezacaftor was developed. The combination of tezacaftor/ivacaftor in patients with CF who were F508del homozygous demonstrated a similar reduction in pulmonary exacerbations, an absolute improvement of predicted FEV₁ of 4%, and no increased respiratory symptoms compared with the placebo arm (Taylor-Cousar JL, et al. N Engl J Med. 2017;377[21]2013).

CFTR modulators were a major breakthrough for patients with CF, but the efficacy of these therapies was dependent on the patients’ genotype and ranged from mildly to moderately effective. Unfortunately, these therapies were ineffective for the patients who were delta 508 heterozygotes. Starting in the summer of 2018, VX 445-tezacaftor-ivacaftor (ETI) was compared with placebo in patients with CF who were 1 copy of F508del and a second CFTR mutation that has minimal function. The study found an absolute improvement in predicted FEV1 of 14.3% and a 63% reduction in exacerbations at 24 weeks compared with placebo (Middleton PG, et al. N Engl J Med. 2019;381:1809). In late 2019, based on these data, ETI was approved by the FDA for all patients with CF who were F508del heterozygous. This innovation provided effective therapy to 90% of the CF population.

With the discovery of many highly effective therapies beneficial in most patients, the CF Foundation started a program called Path to a Cure to find therapies for the 10% of patients with CF who were not candidates for ETI or other CFTR modulators. This program looks to develop novel methods to restore CFTR protein function and repair or replace the CFTR protein via gene editing or gene transfer. This process creates many challenges that are quite complex, but patients, researchers, physicians, and CF Foundation will not stop working until CF stands for CURE FOUND.

Today, patients with CF are living longer, and many are eligible or have already started ETI therapy. This medication and the many others being developed will hopefully lead to patients with CF living a normal lifespan in the near future.
 

Dr. Finklea is Assistant Professor of Medicine, Division of Pulmonary and Critical Care, University of Texas Southwestern, Dallas, Texas. Dr. Finklea receives grant support from the Cystic Fibrosis Foundation.

Approximately one-fifth of patients undergoing hematopoietic stem cell transplantation (HSCT) develop posttraumatic stress disorder (PTSD), based on a retrospective analysis.

Patient factors at time of transplantation, such as low quality of life and high anxiety, predicted PTSD 6 months later, reported lead author Sarah Griffith, MD, of Massachusetts General Hospital, Boston, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“We know that patients admitted for HSCT are often isolated in the hospital for a prolonged period of time, usually about 3-4 weeks, and that they endure substantial toxicities that impact both their physical and psychological well-being,” Dr. Griffith said. “We also know from the literature that HSCT can be considered a traumatic event and that it may lead to clinically significant PTSD symptoms.” But studies evaluating the prevalence and characteristics of PTSD in this patient population have been lacking, she noted.

Dr. Griffith and her colleagues therefore conducted a retrospective analysis involving 250 adults with hematologic malignancies who underwent autologous or allogeneic HSCT during clinical trials conducted from 2014 to 2016. Median patient age was 56 years.

The first objective of the study was to measure the prevalence of PTSD. The second was to characterize features of PTSD such as intrusion, which entails reliving experiences in the form of nightmares or flashbacks, and hypervigilance, which encompasses insomnia, irritability, and hyperarousal for threat. The third objective was to determine risk factors at baseline.

At time of admission for HSCT, after 2 weeks of hospitalization, and again 6 months after transplantation, patients were evaluated using the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT), and the Hospital Anxiety and Depression Scale (HADS), which measured of quality of life, anxiety, and depression. Six months after HSCT, patients also underwent screening for PTSD with the Post-Traumatic Stress Checklist (PTSD-CL). Multivariate regression models were used to determine predictive risk factors.

Six months after HSCT, 18.9% of patients had clinically significant PTSD symptoms; most common were symptoms of avoidance (92.3%), hypervigilance (92.3%), and intrusion (76.9%). Among those who did not have clinically significant PTSD, almost one-quarter (24.5%) demonstrated significant hypervigilance, while 13.7% showed symptoms of avoidance.

“Clinically significant PTSD symptoms are common in the transplant population,” Dr. Griffith said.

Baseline predictors of PTSD included single status and lower quality of life. More severe PTSD was predicted by single status, younger age, higher baseline scores for anxiety or depression, and increased anxiety during hospitalization.

Concluding her presentation, Dr. Griffith said that the findings, while correlative and not causative, should prompt concern and intervention.

“It is very important to be aware of and to manage PTSD symptoms in these patients,” she said. “There are several baseline factors that can be identified prior to HSCT that may illuminate patients at risk for developing worse PTSD symptoms down the road, and these patients may benefit from tailored supportive care interventions.”

Specifically, Dr. Griffith recommended integrating palliative care into hospitalization, as this has been shown to reduce anxiety.

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., highlighted the importance of the findings, while also noting that the impact of palliative care on risk of PTSD has yet to be demonstrated.

Dr. Shah suggested that future research may be improved through use of a formal diagnosis for PTSD, instead of a PTSD checklist, as was used in the present study.

“And certainly long-term follow-up would be important to evaluate the utility of this tool looking at symptoms beyond 6 months,” she said.

Dr. Shah went on to discuss the relevance of the findings for pediatric populations, as children may face unique risk factors and consequences related to PTSD.

“[PTSD in children] may be impacted by family dynamics and structure,” Dr. Shah said. “Children may also have significant neurocognitive implications as a result of their underlying disease or prior therapy. They may experience chronic pain as they go out into adulthood and long-term survivorship, and may also struggle with symptoms of anxiety and depression.”

According to Dr. Shah, one previous study involving more than 6,000 adult survivors of childhood cancer found that PTSD was relatively common, with prevalence rate of 9%, suggesting that interventional work is necessary.

“Applying the data in the study from Griffith et al. suggests that evaluation in the more proximal posttransplant period for children is needed to specifically evaluate PTSD and symptoms thereof, and to try to use this to identify an opportunity for intervention,” Dr. Shah said.

“Pediatric-specific assessments are essential to optimally capture disease and/or age-specific considerations,” she added.

The study was funded by the Lymphoma and Leukemia Society. The investigators disclosed additional relationships with Vector Oncology, Pfizer, AstraZeneca, and Gaido Health/BCG Digital Ventures.

SOURCE: Griffith et al. ASCO 2020. Abstract # 7505.

Approximately one-fifth of patients undergoing hematopoietic stem cell transplantation (HSCT) develop posttraumatic stress disorder (PTSD), based on a retrospective analysis.

Patient factors at time of transplantation, such as low quality of life and high anxiety, predicted PTSD 6 months later, reported lead author Sarah Griffith, MD, of Massachusetts General Hospital, Boston, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“We know that patients admitted for HSCT are often isolated in the hospital for a prolonged period of time, usually about 3-4 weeks, and that they endure substantial toxicities that impact both their physical and psychological well-being,” Dr. Griffith said. “We also know from the literature that HSCT can be considered a traumatic event and that it may lead to clinically significant PTSD symptoms.” But studies evaluating the prevalence and characteristics of PTSD in this patient population have been lacking, she noted.

Dr. Griffith and her colleagues therefore conducted a retrospective analysis involving 250 adults with hematologic malignancies who underwent autologous or allogeneic HSCT during clinical trials conducted from 2014 to 2016. Median patient age was 56 years.

The first objective of the study was to measure the prevalence of PTSD. The second was to characterize features of PTSD such as intrusion, which entails reliving experiences in the form of nightmares or flashbacks, and hypervigilance, which encompasses insomnia, irritability, and hyperarousal for threat. The third objective was to determine risk factors at baseline.

At time of admission for HSCT, after 2 weeks of hospitalization, and again 6 months after transplantation, patients were evaluated using the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT), and the Hospital Anxiety and Depression Scale (HADS), which measured of quality of life, anxiety, and depression. Six months after HSCT, patients also underwent screening for PTSD with the Post-Traumatic Stress Checklist (PTSD-CL). Multivariate regression models were used to determine predictive risk factors.

Six months after HSCT, 18.9% of patients had clinically significant PTSD symptoms; most common were symptoms of avoidance (92.3%), hypervigilance (92.3%), and intrusion (76.9%). Among those who did not have clinically significant PTSD, almost one-quarter (24.5%) demonstrated significant hypervigilance, while 13.7% showed symptoms of avoidance.

“Clinically significant PTSD symptoms are common in the transplant population,” Dr. Griffith said.

Baseline predictors of PTSD included single status and lower quality of life. More severe PTSD was predicted by single status, younger age, higher baseline scores for anxiety or depression, and increased anxiety during hospitalization.

Concluding her presentation, Dr. Griffith said that the findings, while correlative and not causative, should prompt concern and intervention.

“It is very important to be aware of and to manage PTSD symptoms in these patients,” she said. “There are several baseline factors that can be identified prior to HSCT that may illuminate patients at risk for developing worse PTSD symptoms down the road, and these patients may benefit from tailored supportive care interventions.”

Specifically, Dr. Griffith recommended integrating palliative care into hospitalization, as this has been shown to reduce anxiety.

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., highlighted the importance of the findings, while also noting that the impact of palliative care on risk of PTSD has yet to be demonstrated.

Dr. Shah suggested that future research may be improved through use of a formal diagnosis for PTSD, instead of a PTSD checklist, as was used in the present study.

“And certainly long-term follow-up would be important to evaluate the utility of this tool looking at symptoms beyond 6 months,” she said.

Dr. Shah went on to discuss the relevance of the findings for pediatric populations, as children may face unique risk factors and consequences related to PTSD.

“[PTSD in children] may be impacted by family dynamics and structure,” Dr. Shah said. “Children may also have significant neurocognitive implications as a result of their underlying disease or prior therapy. They may experience chronic pain as they go out into adulthood and long-term survivorship, and may also struggle with symptoms of anxiety and depression.”

According to Dr. Shah, one previous study involving more than 6,000 adult survivors of childhood cancer found that PTSD was relatively common, with prevalence rate of 9%, suggesting that interventional work is necessary.

“Applying the data in the study from Griffith et al. suggests that evaluation in the more proximal posttransplant period for children is needed to specifically evaluate PTSD and symptoms thereof, and to try to use this to identify an opportunity for intervention,” Dr. Shah said.

“Pediatric-specific assessments are essential to optimally capture disease and/or age-specific considerations,” she added.

The study was funded by the Lymphoma and Leukemia Society. The investigators disclosed additional relationships with Vector Oncology, Pfizer, AstraZeneca, and Gaido Health/BCG Digital Ventures.

SOURCE: Griffith et al. ASCO 2020. Abstract # 7505.

Approximately one-fifth of patients undergoing hematopoietic stem cell transplantation (HSCT) develop posttraumatic stress disorder (PTSD), based on a retrospective analysis.

Patient factors at time of transplantation, such as low quality of life and high anxiety, predicted PTSD 6 months later, reported lead author Sarah Griffith, MD, of Massachusetts General Hospital, Boston, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“We know that patients admitted for HSCT are often isolated in the hospital for a prolonged period of time, usually about 3-4 weeks, and that they endure substantial toxicities that impact both their physical and psychological well-being,” Dr. Griffith said. “We also know from the literature that HSCT can be considered a traumatic event and that it may lead to clinically significant PTSD symptoms.” But studies evaluating the prevalence and characteristics of PTSD in this patient population have been lacking, she noted.

Dr. Griffith and her colleagues therefore conducted a retrospective analysis involving 250 adults with hematologic malignancies who underwent autologous or allogeneic HSCT during clinical trials conducted from 2014 to 2016. Median patient age was 56 years.

The first objective of the study was to measure the prevalence of PTSD. The second was to characterize features of PTSD such as intrusion, which entails reliving experiences in the form of nightmares or flashbacks, and hypervigilance, which encompasses insomnia, irritability, and hyperarousal for threat. The third objective was to determine risk factors at baseline.

At time of admission for HSCT, after 2 weeks of hospitalization, and again 6 months after transplantation, patients were evaluated using the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT), and the Hospital Anxiety and Depression Scale (HADS), which measured of quality of life, anxiety, and depression. Six months after HSCT, patients also underwent screening for PTSD with the Post-Traumatic Stress Checklist (PTSD-CL). Multivariate regression models were used to determine predictive risk factors.

Six months after HSCT, 18.9% of patients had clinically significant PTSD symptoms; most common were symptoms of avoidance (92.3%), hypervigilance (92.3%), and intrusion (76.9%). Among those who did not have clinically significant PTSD, almost one-quarter (24.5%) demonstrated significant hypervigilance, while 13.7% showed symptoms of avoidance.

“Clinically significant PTSD symptoms are common in the transplant population,” Dr. Griffith said.

Baseline predictors of PTSD included single status and lower quality of life. More severe PTSD was predicted by single status, younger age, higher baseline scores for anxiety or depression, and increased anxiety during hospitalization.

Concluding her presentation, Dr. Griffith said that the findings, while correlative and not causative, should prompt concern and intervention.

“It is very important to be aware of and to manage PTSD symptoms in these patients,” she said. “There are several baseline factors that can be identified prior to HSCT that may illuminate patients at risk for developing worse PTSD symptoms down the road, and these patients may benefit from tailored supportive care interventions.”

Specifically, Dr. Griffith recommended integrating palliative care into hospitalization, as this has been shown to reduce anxiety.

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., highlighted the importance of the findings, while also noting that the impact of palliative care on risk of PTSD has yet to be demonstrated.

Dr. Shah suggested that future research may be improved through use of a formal diagnosis for PTSD, instead of a PTSD checklist, as was used in the present study.

“And certainly long-term follow-up would be important to evaluate the utility of this tool looking at symptoms beyond 6 months,” she said.

Dr. Shah went on to discuss the relevance of the findings for pediatric populations, as children may face unique risk factors and consequences related to PTSD.

“[PTSD in children] may be impacted by family dynamics and structure,” Dr. Shah said. “Children may also have significant neurocognitive implications as a result of their underlying disease or prior therapy. They may experience chronic pain as they go out into adulthood and long-term survivorship, and may also struggle with symptoms of anxiety and depression.”

According to Dr. Shah, one previous study involving more than 6,000 adult survivors of childhood cancer found that PTSD was relatively common, with prevalence rate of 9%, suggesting that interventional work is necessary.

“Applying the data in the study from Griffith et al. suggests that evaluation in the more proximal posttransplant period for children is needed to specifically evaluate PTSD and symptoms thereof, and to try to use this to identify an opportunity for intervention,” Dr. Shah said.

“Pediatric-specific assessments are essential to optimally capture disease and/or age-specific considerations,” she added.

The study was funded by the Lymphoma and Leukemia Society. The investigators disclosed additional relationships with Vector Oncology, Pfizer, AstraZeneca, and Gaido Health/BCG Digital Ventures.

SOURCE: Griffith et al. ASCO 2020. Abstract # 7505.

Here are the stories our MDedge editors across specialties think you need to know about today:

ACS Update: ‘It is best not to drink alcohol’

The American Cancer Society (ACS) is taking its strongest stance yet against drinking. In its updated cancer prevention guidelines, the ACS now recommends that “it is best not to drink alcohol.” Previously, the organizations had suggested that, for those who consume alcoholic beverages, intake should be no more than one drink per day for women or two per day for men. That recommendation is still in place, but is now accompanied by this new, stronger directive. The guidelines also place more emphasis on reducing the consumption of processed and red meat and highly processed foods, and on increasing physical activity. “Individual choice is an important part of a healthy lifestyle, but having the right policies and environmental factors to break down these barriers is also important, and that is something that clinicians can support,” said Laura Makaroff, DO, American Cancer Society senior vice president. The guidelines were published in CA: A Cancer Journal for Clinicians. Read more.

COVID health system changes may be here to stay

The COVID-19 pandemic has forced sudden major changes to the nation’s health care system that are unlikely to be reversed. While there’s some good news, there are also some alarming trends. Experts said there are three trends that are likely to stick around: telehealth for all, an exodus of primary care physicians, and less emphasis on hospital care. “I’ve been trying to raise the alarm about the kind of perilous future of primary care,” said Farzad Mostashari, MD, a top Department of Health & Human Services official in the Obama administration. Dr. Mostashari runs Aledade, a company that helps primary care doctors make the transition from fee-for-service medicine to new payment models. The American Academy of Family Physicians reports that 70% of primary care physicians are reporting declines in patient volume of 50% or more since March, and 40% have laid off or furloughed staff. The AAFP has joined other primary care and insurance groups in asking HHS for an infusion of cash. “This is absolutely essential to effectively treat patients today and to maintain their ongoing operations until we overcome this public health emergency,” the groups wrote. Read more.

Asthma-COPD overlap deaths

Death rates for combined asthma and chronic obstructive pulmonary disease declined during 1999-2016, but the risk remains higher among women, compared with men, and in certain occupations, according to a recent report from the Centers for Disease Control and Prevention. There is also an association between mortality and nonworking status among adults aged 25-64 years, which “suggests that asthma-COPD overlap might be associated with substantial morbidity,” Katelynn E. Dodd, MPH, and associates at the CDC’s National Institute for Occupational Safety and Health said in the Morbidity and Mortality Weekly Report. “These patients have been reported to have worse health outcomes than do those with asthma or COPD alone.” Read more.

Cancer triage in a pandemic: There’s an app for that

Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic. Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help? OncCOVID is a free tool that was launched in May by the University of Michigan. It allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care. “We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine. Read more.
 

For more on COVID-19, visit our Resource Center . All of our latest news is available on MDedge.com .

Here are the stories our MDedge editors across specialties think you need to know about today:

ACS Update: ‘It is best not to drink alcohol’

The American Cancer Society (ACS) is taking its strongest stance yet against drinking. In its updated cancer prevention guidelines, the ACS now recommends that “it is best not to drink alcohol.” Previously, the organizations had suggested that, for those who consume alcoholic beverages, intake should be no more than one drink per day for women or two per day for men. That recommendation is still in place, but is now accompanied by this new, stronger directive. The guidelines also place more emphasis on reducing the consumption of processed and red meat and highly processed foods, and on increasing physical activity. “Individual choice is an important part of a healthy lifestyle, but having the right policies and environmental factors to break down these barriers is also important, and that is something that clinicians can support,” said Laura Makaroff, DO, American Cancer Society senior vice president. The guidelines were published in CA: A Cancer Journal for Clinicians. Read more.

COVID health system changes may be here to stay

The COVID-19 pandemic has forced sudden major changes to the nation’s health care system that are unlikely to be reversed. While there’s some good news, there are also some alarming trends. Experts said there are three trends that are likely to stick around: telehealth for all, an exodus of primary care physicians, and less emphasis on hospital care. “I’ve been trying to raise the alarm about the kind of perilous future of primary care,” said Farzad Mostashari, MD, a top Department of Health & Human Services official in the Obama administration. Dr. Mostashari runs Aledade, a company that helps primary care doctors make the transition from fee-for-service medicine to new payment models. The American Academy of Family Physicians reports that 70% of primary care physicians are reporting declines in patient volume of 50% or more since March, and 40% have laid off or furloughed staff. The AAFP has joined other primary care and insurance groups in asking HHS for an infusion of cash. “This is absolutely essential to effectively treat patients today and to maintain their ongoing operations until we overcome this public health emergency,” the groups wrote. Read more.

Asthma-COPD overlap deaths

Death rates for combined asthma and chronic obstructive pulmonary disease declined during 1999-2016, but the risk remains higher among women, compared with men, and in certain occupations, according to a recent report from the Centers for Disease Control and Prevention. There is also an association between mortality and nonworking status among adults aged 25-64 years, which “suggests that asthma-COPD overlap might be associated with substantial morbidity,” Katelynn E. Dodd, MPH, and associates at the CDC’s National Institute for Occupational Safety and Health said in the Morbidity and Mortality Weekly Report. “These patients have been reported to have worse health outcomes than do those with asthma or COPD alone.” Read more.

Cancer triage in a pandemic: There’s an app for that

Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic. Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help? OncCOVID is a free tool that was launched in May by the University of Michigan. It allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care. “We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine. Read more.
 

For more on COVID-19, visit our Resource Center . All of our latest news is available on MDedge.com .

Here are the stories our MDedge editors across specialties think you need to know about today:

ACS Update: ‘It is best not to drink alcohol’

The American Cancer Society (ACS) is taking its strongest stance yet against drinking. In its updated cancer prevention guidelines, the ACS now recommends that “it is best not to drink alcohol.” Previously, the organizations had suggested that, for those who consume alcoholic beverages, intake should be no more than one drink per day for women or two per day for men. That recommendation is still in place, but is now accompanied by this new, stronger directive. The guidelines also place more emphasis on reducing the consumption of processed and red meat and highly processed foods, and on increasing physical activity. “Individual choice is an important part of a healthy lifestyle, but having the right policies and environmental factors to break down these barriers is also important, and that is something that clinicians can support,” said Laura Makaroff, DO, American Cancer Society senior vice president. The guidelines were published in CA: A Cancer Journal for Clinicians. Read more.

COVID health system changes may be here to stay

The COVID-19 pandemic has forced sudden major changes to the nation’s health care system that are unlikely to be reversed. While there’s some good news, there are also some alarming trends. Experts said there are three trends that are likely to stick around: telehealth for all, an exodus of primary care physicians, and less emphasis on hospital care. “I’ve been trying to raise the alarm about the kind of perilous future of primary care,” said Farzad Mostashari, MD, a top Department of Health & Human Services official in the Obama administration. Dr. Mostashari runs Aledade, a company that helps primary care doctors make the transition from fee-for-service medicine to new payment models. The American Academy of Family Physicians reports that 70% of primary care physicians are reporting declines in patient volume of 50% or more since March, and 40% have laid off or furloughed staff. The AAFP has joined other primary care and insurance groups in asking HHS for an infusion of cash. “This is absolutely essential to effectively treat patients today and to maintain their ongoing operations until we overcome this public health emergency,” the groups wrote. Read more.

Asthma-COPD overlap deaths

Death rates for combined asthma and chronic obstructive pulmonary disease declined during 1999-2016, but the risk remains higher among women, compared with men, and in certain occupations, according to a recent report from the Centers for Disease Control and Prevention. There is also an association between mortality and nonworking status among adults aged 25-64 years, which “suggests that asthma-COPD overlap might be associated with substantial morbidity,” Katelynn E. Dodd, MPH, and associates at the CDC’s National Institute for Occupational Safety and Health said in the Morbidity and Mortality Weekly Report. “These patients have been reported to have worse health outcomes than do those with asthma or COPD alone.” Read more.

Cancer triage in a pandemic: There’s an app for that

Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic. Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help? OncCOVID is a free tool that was launched in May by the University of Michigan. It allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care. “We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine. Read more.
 

For more on COVID-19, visit our Resource Center . All of our latest news is available on MDedge.com .

Irritability in adults with major depressive disorder (MDD) and stimulant use disorder (SUD) is strongly linked to suicidality and should be assessed by clinicians.

Three clinical trials of adults with MDD and one trial of adults with SUD showed that the link between irritability and suicidality was stronger than the association between depression severity and suicidal behaviors.

“Irritability is an important construct that is not often studied in adults with major depressive disorder,” Manish K. Jha, MD, of Icahn School of Medicine at Mount Sinai, New York, said in an interview.

“If you look at current diagnostic convention, irritability is not considered a symptom of major depressive episodes in adults, but below age 18, it is considered one of the two main symptoms,” Dr. Jha said.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2020 annual Meeting.
 

Clinically useful

Irritability is assessed using age-related norms of behavior, Dr. Jha said.

“The best way to conceptualize it is that it is the propensity to get angry easily or more frequently as compared to peers in response to frustration. I have a 2½-year old, and if he throws a tantrum, that is perfectly age appropriate. But if I do the same thing, it would be extreme irritability. The pediatric literature uses the word ‘grouchiness,’ but it is a little bit difficult to define, in part because it hasn’t been studied extensively,” he said.

To better understand the potential association between irritability and suicidality, the investigators reviewed results of three trials involving adults with MDD. These trials were CO-MED (Combining Medications to Enhance Depression Outcomes), which included 665 patients; EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care), which included 296 patients; and SAMS (Suicide Assessment Methodology Study), which included 266 patients.

They also examined the STRIDE (Stimulant Reduction Intervention Using Dosed Exercise) study, which was conducted in 302 adults with SUD.

All studies assessed irritability using the Concise Associated Symptom Tracking scale, a 5-point Likert scale. The trials also assessed suicidality with the Concise Health Risk Tracking Suicidal Thoughts.

The investigators found that irritability and suicidality were positively correlated. The association between irritability and suicidality was 2-11 times stronger than the link to overall depression.

Higher irritability at baseline predicted higher levels of suicidality at week 9 in CO-MED (P = .011), EMBARC (P < .0001), and STRIDE (P = .007), but not in SAMS (P = .21).

Greater reduction in irritability from baseline to week 4 predicted lower levels of suicidality at week 8 in CO-MED (P = .007), EMBARC (P < .0001), and STRIDE (P < .0001), but not in SAMS (P = .065).

Similarly, lower baseline levels and greater reductions in irritability were associated with lower levels of suicidality at week 28 of CO-MED, week 16 of EMBARC, and week 36 of STRIDE.

Dr. Jha speculated that by treating irritability, it may be possible to lower rates of subsequent suicidal ideation, and he believes that measuring irritability in MDD “has clinical utility.”
 

A common and disabling symptom

Commenting on the study, Sanjay J. Mathew, MD, professor of psychiatry and behavioral sciences at Baylor College of Medicine, Houston, said the findings provide further support that irritability is a relatively common and disabling symptom associated with major depression.

“The presence of significant irritability was associated with higher levels of suicidal ideation and is therefore highly relevant for clinicians to assess,” said Dr. Mathew, who was not part of the study.

“Early improvements in irritability are associated with better longer-term outcomes with antidepressant treatments, and this highlights the need for careful clinical evaluation early on in the course of antidepressant therapy, ideally within the first 2 weeks,” he said.

Dr. Jha reports financial relationships with Acadia Pharmaceuticals and Janssen Research & Development. Dr. Mathew reports financial relationships with Allergan, Vistagen, Janssen, Clexio, and Biohaven.
 

A version of this article originally appeared on Medscape.com.

Irritability in adults with major depressive disorder (MDD) and stimulant use disorder (SUD) is strongly linked to suicidality and should be assessed by clinicians.

Three clinical trials of adults with MDD and one trial of adults with SUD showed that the link between irritability and suicidality was stronger than the association between depression severity and suicidal behaviors.

“Irritability is an important construct that is not often studied in adults with major depressive disorder,” Manish K. Jha, MD, of Icahn School of Medicine at Mount Sinai, New York, said in an interview.

“If you look at current diagnostic convention, irritability is not considered a symptom of major depressive episodes in adults, but below age 18, it is considered one of the two main symptoms,” Dr. Jha said.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2020 annual Meeting.
 

Clinically useful

Irritability is assessed using age-related norms of behavior, Dr. Jha said.

“The best way to conceptualize it is that it is the propensity to get angry easily or more frequently as compared to peers in response to frustration. I have a 2½-year old, and if he throws a tantrum, that is perfectly age appropriate. But if I do the same thing, it would be extreme irritability. The pediatric literature uses the word ‘grouchiness,’ but it is a little bit difficult to define, in part because it hasn’t been studied extensively,” he said.

To better understand the potential association between irritability and suicidality, the investigators reviewed results of three trials involving adults with MDD. These trials were CO-MED (Combining Medications to Enhance Depression Outcomes), which included 665 patients; EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care), which included 296 patients; and SAMS (Suicide Assessment Methodology Study), which included 266 patients.

They also examined the STRIDE (Stimulant Reduction Intervention Using Dosed Exercise) study, which was conducted in 302 adults with SUD.

All studies assessed irritability using the Concise Associated Symptom Tracking scale, a 5-point Likert scale. The trials also assessed suicidality with the Concise Health Risk Tracking Suicidal Thoughts.

The investigators found that irritability and suicidality were positively correlated. The association between irritability and suicidality was 2-11 times stronger than the link to overall depression.

Higher irritability at baseline predicted higher levels of suicidality at week 9 in CO-MED (P = .011), EMBARC (P < .0001), and STRIDE (P = .007), but not in SAMS (P = .21).

Greater reduction in irritability from baseline to week 4 predicted lower levels of suicidality at week 8 in CO-MED (P = .007), EMBARC (P < .0001), and STRIDE (P < .0001), but not in SAMS (P = .065).

Similarly, lower baseline levels and greater reductions in irritability were associated with lower levels of suicidality at week 28 of CO-MED, week 16 of EMBARC, and week 36 of STRIDE.

Dr. Jha speculated that by treating irritability, it may be possible to lower rates of subsequent suicidal ideation, and he believes that measuring irritability in MDD “has clinical utility.”
 

A common and disabling symptom

Commenting on the study, Sanjay J. Mathew, MD, professor of psychiatry and behavioral sciences at Baylor College of Medicine, Houston, said the findings provide further support that irritability is a relatively common and disabling symptom associated with major depression.

“The presence of significant irritability was associated with higher levels of suicidal ideation and is therefore highly relevant for clinicians to assess,” said Dr. Mathew, who was not part of the study.

“Early improvements in irritability are associated with better longer-term outcomes with antidepressant treatments, and this highlights the need for careful clinical evaluation early on in the course of antidepressant therapy, ideally within the first 2 weeks,” he said.

Dr. Jha reports financial relationships with Acadia Pharmaceuticals and Janssen Research & Development. Dr. Mathew reports financial relationships with Allergan, Vistagen, Janssen, Clexio, and Biohaven.
 

A version of this article originally appeared on Medscape.com.

Irritability in adults with major depressive disorder (MDD) and stimulant use disorder (SUD) is strongly linked to suicidality and should be assessed by clinicians.

Three clinical trials of adults with MDD and one trial of adults with SUD showed that the link between irritability and suicidality was stronger than the association between depression severity and suicidal behaviors.

“Irritability is an important construct that is not often studied in adults with major depressive disorder,” Manish K. Jha, MD, of Icahn School of Medicine at Mount Sinai, New York, said in an interview.

“If you look at current diagnostic convention, irritability is not considered a symptom of major depressive episodes in adults, but below age 18, it is considered one of the two main symptoms,” Dr. Jha said.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2020 annual Meeting.
 

Clinically useful

Irritability is assessed using age-related norms of behavior, Dr. Jha said.

“The best way to conceptualize it is that it is the propensity to get angry easily or more frequently as compared to peers in response to frustration. I have a 2½-year old, and if he throws a tantrum, that is perfectly age appropriate. But if I do the same thing, it would be extreme irritability. The pediatric literature uses the word ‘grouchiness,’ but it is a little bit difficult to define, in part because it hasn’t been studied extensively,” he said.

To better understand the potential association between irritability and suicidality, the investigators reviewed results of three trials involving adults with MDD. These trials were CO-MED (Combining Medications to Enhance Depression Outcomes), which included 665 patients; EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care), which included 296 patients; and SAMS (Suicide Assessment Methodology Study), which included 266 patients.

They also examined the STRIDE (Stimulant Reduction Intervention Using Dosed Exercise) study, which was conducted in 302 adults with SUD.

All studies assessed irritability using the Concise Associated Symptom Tracking scale, a 5-point Likert scale. The trials also assessed suicidality with the Concise Health Risk Tracking Suicidal Thoughts.

The investigators found that irritability and suicidality were positively correlated. The association between irritability and suicidality was 2-11 times stronger than the link to overall depression.

Higher irritability at baseline predicted higher levels of suicidality at week 9 in CO-MED (P = .011), EMBARC (P < .0001), and STRIDE (P = .007), but not in SAMS (P = .21).

Greater reduction in irritability from baseline to week 4 predicted lower levels of suicidality at week 8 in CO-MED (P = .007), EMBARC (P < .0001), and STRIDE (P < .0001), but not in SAMS (P = .065).

Similarly, lower baseline levels and greater reductions in irritability were associated with lower levels of suicidality at week 28 of CO-MED, week 16 of EMBARC, and week 36 of STRIDE.

Dr. Jha speculated that by treating irritability, it may be possible to lower rates of subsequent suicidal ideation, and he believes that measuring irritability in MDD “has clinical utility.”
 

A common and disabling symptom

Commenting on the study, Sanjay J. Mathew, MD, professor of psychiatry and behavioral sciences at Baylor College of Medicine, Houston, said the findings provide further support that irritability is a relatively common and disabling symptom associated with major depression.

“The presence of significant irritability was associated with higher levels of suicidal ideation and is therefore highly relevant for clinicians to assess,” said Dr. Mathew, who was not part of the study.

“Early improvements in irritability are associated with better longer-term outcomes with antidepressant treatments, and this highlights the need for careful clinical evaluation early on in the course of antidepressant therapy, ideally within the first 2 weeks,” he said.

Dr. Jha reports financial relationships with Acadia Pharmaceuticals and Janssen Research & Development. Dr. Mathew reports financial relationships with Allergan, Vistagen, Janssen, Clexio, and Biohaven.
 

A version of this article originally appeared on Medscape.com.

I am writing this commentary to bring to readers’ attention a medical and ethical complexity related to human sitters for presumably suicidal, COVID-19–positive hospitalized patients.

To shape and bundle the ethics issues addressed here into a single question, I offer the following: Should policies and practices requiring that patients in presumed need of a sitter because of assessed suicidality change when the patient is COVID-19–positive? Although the analysis might be similar when a sitter is monitoring a Patient Under Investigation (PUI), here I focus only on COVID-19–positive patients. Similarly, there are other reasons for sitters, of course, such as to prevent elopement, or, if a patient is in restraints, to prevent the patient from pulling out lines or tubes. Again, discussion of some of these ethical complications is beyond the scope of this piece. Just considering the matter of potential suicidality and sitters is complex enough. And so, to start, I sought out existing sources for guidance.

In looking for such sources, I first turned to the Centers for Medicare and Medicaid Services before COVID-19. CMS has required that there be a sitter for a patient who is suicidal and that the sitter remain in the room so that the sitter can intervene expeditiously if the patient tries to hurt himself or herself. There has been no change in this guidance since the COVID-19 pandemic in the United States. To the best of my knowledge, there is no substantive guidance for protecting sitters from contagion other than PPE. Given this, it begs the question: Shouldn’t the CMS guidance be changed to allow for hospitals to study different approaches to contagion reduction for sitters?

In my hospital, I already have begun discussing the potential risks of harm and potential benefits to our suicidal patients of having a sitter directly outside the patient’s room. I also have considered whether to have one sitter watching several room cameras at once, commonly referred to as “telehealth strategies.”

To be sure, sitting for hours in the room of a COVID-19–positive patient is onerous. The sitter is required to be in full PPE (N-95 mask, gown, and gloves), which is hot and uncomfortable. Current practice is resource intensive in other ways. It requires changing out the sitter every 2 hours, which uses substantial amounts of PPE and multiple sitters.

Regardless, however, there are really no data upon which to base any sound ethics judgment about what should or should not be tried. We just have no information on how to attempt to balance potential risks and prospects for the benefit of whom and when. And, given that good clinical ethics always begin with the facts, I write this piece to see whether readers have thought about these issues before – and whether any of clinicians have started collecting the valuable data needed to begin making sound ethical judgments about how to care for our presumably suicidal COVID-19–positive patients and the sitters who watch over them.
 

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington. She has no disclosures and can be reached at cpnews@mdedge.com.

This column is an outcome of a discussion that occurred during Psych/Ethics rounds on June 5, and does not represent any official statements of Medstar Washington Hospital Center or any entity of the MedStar Corp. Dr. Ritchie would like to thank Evan G. DeRenzo, PhD, of the John J. Lynch Center for Ethics, for her thoughtful review of a previous draft of this commentary.

I am writing this commentary to bring to readers’ attention a medical and ethical complexity related to human sitters for presumably suicidal, COVID-19–positive hospitalized patients.

To shape and bundle the ethics issues addressed here into a single question, I offer the following: Should policies and practices requiring that patients in presumed need of a sitter because of assessed suicidality change when the patient is COVID-19–positive? Although the analysis might be similar when a sitter is monitoring a Patient Under Investigation (PUI), here I focus only on COVID-19–positive patients. Similarly, there are other reasons for sitters, of course, such as to prevent elopement, or, if a patient is in restraints, to prevent the patient from pulling out lines or tubes. Again, discussion of some of these ethical complications is beyond the scope of this piece. Just considering the matter of potential suicidality and sitters is complex enough. And so, to start, I sought out existing sources for guidance.

In looking for such sources, I first turned to the Centers for Medicare and Medicaid Services before COVID-19. CMS has required that there be a sitter for a patient who is suicidal and that the sitter remain in the room so that the sitter can intervene expeditiously if the patient tries to hurt himself or herself. There has been no change in this guidance since the COVID-19 pandemic in the United States. To the best of my knowledge, there is no substantive guidance for protecting sitters from contagion other than PPE. Given this, it begs the question: Shouldn’t the CMS guidance be changed to allow for hospitals to study different approaches to contagion reduction for sitters?

In my hospital, I already have begun discussing the potential risks of harm and potential benefits to our suicidal patients of having a sitter directly outside the patient’s room. I also have considered whether to have one sitter watching several room cameras at once, commonly referred to as “telehealth strategies.”

To be sure, sitting for hours in the room of a COVID-19–positive patient is onerous. The sitter is required to be in full PPE (N-95 mask, gown, and gloves), which is hot and uncomfortable. Current practice is resource intensive in other ways. It requires changing out the sitter every 2 hours, which uses substantial amounts of PPE and multiple sitters.

Regardless, however, there are really no data upon which to base any sound ethics judgment about what should or should not be tried. We just have no information on how to attempt to balance potential risks and prospects for the benefit of whom and when. And, given that good clinical ethics always begin with the facts, I write this piece to see whether readers have thought about these issues before – and whether any of clinicians have started collecting the valuable data needed to begin making sound ethical judgments about how to care for our presumably suicidal COVID-19–positive patients and the sitters who watch over them.
 

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington. She has no disclosures and can be reached at cpnews@mdedge.com.

This column is an outcome of a discussion that occurred during Psych/Ethics rounds on June 5, and does not represent any official statements of Medstar Washington Hospital Center or any entity of the MedStar Corp. Dr. Ritchie would like to thank Evan G. DeRenzo, PhD, of the John J. Lynch Center for Ethics, for her thoughtful review of a previous draft of this commentary.

I am writing this commentary to bring to readers’ attention a medical and ethical complexity related to human sitters for presumably suicidal, COVID-19–positive hospitalized patients.

To shape and bundle the ethics issues addressed here into a single question, I offer the following: Should policies and practices requiring that patients in presumed need of a sitter because of assessed suicidality change when the patient is COVID-19–positive? Although the analysis might be similar when a sitter is monitoring a Patient Under Investigation (PUI), here I focus only on COVID-19–positive patients. Similarly, there are other reasons for sitters, of course, such as to prevent elopement, or, if a patient is in restraints, to prevent the patient from pulling out lines or tubes. Again, discussion of some of these ethical complications is beyond the scope of this piece. Just considering the matter of potential suicidality and sitters is complex enough. And so, to start, I sought out existing sources for guidance.

In looking for such sources, I first turned to the Centers for Medicare and Medicaid Services before COVID-19. CMS has required that there be a sitter for a patient who is suicidal and that the sitter remain in the room so that the sitter can intervene expeditiously if the patient tries to hurt himself or herself. There has been no change in this guidance since the COVID-19 pandemic in the United States. To the best of my knowledge, there is no substantive guidance for protecting sitters from contagion other than PPE. Given this, it begs the question: Shouldn’t the CMS guidance be changed to allow for hospitals to study different approaches to contagion reduction for sitters?

In my hospital, I already have begun discussing the potential risks of harm and potential benefits to our suicidal patients of having a sitter directly outside the patient’s room. I also have considered whether to have one sitter watching several room cameras at once, commonly referred to as “telehealth strategies.”

To be sure, sitting for hours in the room of a COVID-19–positive patient is onerous. The sitter is required to be in full PPE (N-95 mask, gown, and gloves), which is hot and uncomfortable. Current practice is resource intensive in other ways. It requires changing out the sitter every 2 hours, which uses substantial amounts of PPE and multiple sitters.

Regardless, however, there are really no data upon which to base any sound ethics judgment about what should or should not be tried. We just have no information on how to attempt to balance potential risks and prospects for the benefit of whom and when. And, given that good clinical ethics always begin with the facts, I write this piece to see whether readers have thought about these issues before – and whether any of clinicians have started collecting the valuable data needed to begin making sound ethical judgments about how to care for our presumably suicidal COVID-19–positive patients and the sitters who watch over them.
 

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington. She has no disclosures and can be reached at cpnews@mdedge.com.

This column is an outcome of a discussion that occurred during Psych/Ethics rounds on June 5, and does not represent any official statements of Medstar Washington Hospital Center or any entity of the MedStar Corp. Dr. Ritchie would like to thank Evan G. DeRenzo, PhD, of the John J. Lynch Center for Ethics, for her thoughtful review of a previous draft of this commentary.

The Diagnosis: Disseminated Strongyloidiasis  

Strongyloidiasis is a parasitic infection caused by Strongyloides stercoralis. In the United States it is most prevalent in the Appalachian region. During the filariform larval stage of the parasite's life cycle, larvae from contaminated soil infect the human skin and spread to the intestinal epithelium,¹ then the larvae mature into adult female worms that can produce eggs asexually. Rhabditiform larvae hatch from the eggs and are either excreted in the stool or develop into infectious filariform larvae. The latter can cause autoinfection of the intestinal mucosa or nearby skin; in addition, if the larvae enter the bloodstream, they can spread throughout the body and lead to disseminated strongyloidiasis and hyperinfection syndrome.² This often fatal progression most commonly occurs in immunosuppressed individuals.³ The mortality rate has been reported to be up to 87%.^2,4  

Fever, abdominal pain, nausea, and diarrhea are clinically common in disseminated strongyloidiasis and hyperinfection syndrome.⁵ Patients also may exhibit dyspnea, cough, wheezing, and hemoptysis.² Cutaneous manifestations are rare and typically include pruritus and petechiae.⁶ Eosinophilia may be present but is not a reliable indicator.¹  

Our patient displayed several risk factors and an early clinical presentation for disseminated strongyloidiasis and hyperinfection syndrome, which evolved over the course of hospitalization. Clues to the diagnosis included an immunosuppressed state; erythematous pruritic macules at presentation that later developed into reticulated petechial patches; and fever, general abdominal symptoms, and dyspnea. However, the patient's overall physical examination findings were subtle and nonspecific. Additionally, the patient did not display the classic larva currens for strongyloidiasis or the pathognomonic periumbilical thumbprint purpura of disseminated infection,^6,7 which may indicate that the latter is a later-stage finding. Although graft-vs-host disease initially was suspected, a third skin biopsy revealed basophilic Strongyloides larvae, extravasated erythrocytes, and mild perivascular inflammation (Figure).

Subsequent gastric aspirates and stool cultures revealed S stercoralis. A bronchoalveolar lavage specimen and serum enzyme-linked immunosorbent assay for Strongyloides antibody were negative. The patient was treated with an extended 16-day course of ivermectin 12 mg daily until gastric aspirates and stool cultures were negative for the parasite. The rash receded by the end of the patient's 32-day hospital stay.  

Because of the high mortality rate of untreated disseminated strongyloidiasis and hyperinfection syndrome, early diagnosis and initiation of anthelmintic treatment is vital in improving patient outcomes. As such, the diagnosis of disseminated strongyloidiasis should be considered in any immunosuppressed patient with multisystemic symptoms and/or petechiae. The differential diagnosis includes graft-vs-host disease, drug-induced urticaria, disseminated intravascular coagulation, and other opportunistic parasites.^6,8,9

The Diagnosis: Disseminated Strongyloidiasis  

Strongyloidiasis is a parasitic infection caused by Strongyloides stercoralis. In the United States it is most prevalent in the Appalachian region. During the filariform larval stage of the parasite's life cycle, larvae from contaminated soil infect the human skin and spread to the intestinal epithelium,¹ then the larvae mature into adult female worms that can produce eggs asexually. Rhabditiform larvae hatch from the eggs and are either excreted in the stool or develop into infectious filariform larvae. The latter can cause autoinfection of the intestinal mucosa or nearby skin; in addition, if the larvae enter the bloodstream, they can spread throughout the body and lead to disseminated strongyloidiasis and hyperinfection syndrome.² This often fatal progression most commonly occurs in immunosuppressed individuals.³ The mortality rate has been reported to be up to 87%.^2,4  

Fever, abdominal pain, nausea, and diarrhea are clinically common in disseminated strongyloidiasis and hyperinfection syndrome.⁵ Patients also may exhibit dyspnea, cough, wheezing, and hemoptysis.² Cutaneous manifestations are rare and typically include pruritus and petechiae.⁶ Eosinophilia may be present but is not a reliable indicator.¹  

Our patient displayed several risk factors and an early clinical presentation for disseminated strongyloidiasis and hyperinfection syndrome, which evolved over the course of hospitalization. Clues to the diagnosis included an immunosuppressed state; erythematous pruritic macules at presentation that later developed into reticulated petechial patches; and fever, general abdominal symptoms, and dyspnea. However, the patient's overall physical examination findings were subtle and nonspecific. Additionally, the patient did not display the classic larva currens for strongyloidiasis or the pathognomonic periumbilical thumbprint purpura of disseminated infection,^6,7 which may indicate that the latter is a later-stage finding. Although graft-vs-host disease initially was suspected, a third skin biopsy revealed basophilic Strongyloides larvae, extravasated erythrocytes, and mild perivascular inflammation (Figure).

Subsequent gastric aspirates and stool cultures revealed S stercoralis. A bronchoalveolar lavage specimen and serum enzyme-linked immunosorbent assay for Strongyloides antibody were negative. The patient was treated with an extended 16-day course of ivermectin 12 mg daily until gastric aspirates and stool cultures were negative for the parasite. The rash receded by the end of the patient's 32-day hospital stay.  

Because of the high mortality rate of untreated disseminated strongyloidiasis and hyperinfection syndrome, early diagnosis and initiation of anthelmintic treatment is vital in improving patient outcomes. As such, the diagnosis of disseminated strongyloidiasis should be considered in any immunosuppressed patient with multisystemic symptoms and/or petechiae. The differential diagnosis includes graft-vs-host disease, drug-induced urticaria, disseminated intravascular coagulation, and other opportunistic parasites.^6,8,9

The Diagnosis: Disseminated Strongyloidiasis  

Strongyloidiasis is a parasitic infection caused by Strongyloides stercoralis. In the United States it is most prevalent in the Appalachian region. During the filariform larval stage of the parasite's life cycle, larvae from contaminated soil infect the human skin and spread to the intestinal epithelium,¹ then the larvae mature into adult female worms that can produce eggs asexually. Rhabditiform larvae hatch from the eggs and are either excreted in the stool or develop into infectious filariform larvae. The latter can cause autoinfection of the intestinal mucosa or nearby skin; in addition, if the larvae enter the bloodstream, they can spread throughout the body and lead to disseminated strongyloidiasis and hyperinfection syndrome.² This often fatal progression most commonly occurs in immunosuppressed individuals.³ The mortality rate has been reported to be up to 87%.^2,4  

Fever, abdominal pain, nausea, and diarrhea are clinically common in disseminated strongyloidiasis and hyperinfection syndrome.⁵ Patients also may exhibit dyspnea, cough, wheezing, and hemoptysis.² Cutaneous manifestations are rare and typically include pruritus and petechiae.⁶ Eosinophilia may be present but is not a reliable indicator.¹  

Our patient displayed several risk factors and an early clinical presentation for disseminated strongyloidiasis and hyperinfection syndrome, which evolved over the course of hospitalization. Clues to the diagnosis included an immunosuppressed state; erythematous pruritic macules at presentation that later developed into reticulated petechial patches; and fever, general abdominal symptoms, and dyspnea. However, the patient's overall physical examination findings were subtle and nonspecific. Additionally, the patient did not display the classic larva currens for strongyloidiasis or the pathognomonic periumbilical thumbprint purpura of disseminated infection,^6,7 which may indicate that the latter is a later-stage finding. Although graft-vs-host disease initially was suspected, a third skin biopsy revealed basophilic Strongyloides larvae, extravasated erythrocytes, and mild perivascular inflammation (Figure).

Subsequent gastric aspirates and stool cultures revealed S stercoralis. A bronchoalveolar lavage specimen and serum enzyme-linked immunosorbent assay for Strongyloides antibody were negative. The patient was treated with an extended 16-day course of ivermectin 12 mg daily until gastric aspirates and stool cultures were negative for the parasite. The rash receded by the end of the patient's 32-day hospital stay.  

Because of the high mortality rate of untreated disseminated strongyloidiasis and hyperinfection syndrome, early diagnosis and initiation of anthelmintic treatment is vital in improving patient outcomes. As such, the diagnosis of disseminated strongyloidiasis should be considered in any immunosuppressed patient with multisystemic symptoms and/or petechiae. The differential diagnosis includes graft-vs-host disease, drug-induced urticaria, disseminated intravascular coagulation, and other opportunistic parasites.^6,8,9