Jeannette Guerrasio, MD

Dr. Pyke

PRO

Hospitalists’ moral obligation is to protect the patient

In this era of historic budget deficits, wars, and political strife surrounding healthcare reform, one might ask if we can afford to spend valuable time and energy on the issue of reporting physicians who abuse substances.

At first glance, I certainly had skepticism about the subject, but then I dug deeper. To my surprise (and likely yours), studies indicate that physicians develop substance-abuse problems as often or more than the general population does.¹ Recent reports detail horrific patient outcomes at the hands of health providers whose actions are compromised by drug use. With data showing the prevalence of substance abuse among physicians hovering around 10% to 12%, we must accept the reality that hospitalists are not exempt.^2,3,4,5

As medical doctors, our promise to our patients is to provide care in an ethical manner. Even if we try to live in denial, most of us would agree that with great blessing (or power) comes great responsibility. So when the question of reporting a fellow hospitalist who is abusing substances was asked, my response was unequivocally yes.

In my opinion, this discussion can be limited to two overarching principles: First, we are compelled to put our patients first. As hospitalists, we are blessed to be caring for some of the most frail and vulnerable in our society. Fortunately, an overwhelming number of us do so with pride, skill, and integrity.

The task of providing high-quality care to an empowered patient population is difficult enough with us being physically, emotionally, and mentally exhausted. But to add substance abuse to this is just a complete and utter violation of our patients’ trust. We must agree that putting our patients’ well-being beyond reproach requires us to report any colleague who is compromised.

Second, delayed help for a colleague in trouble with substance-abuse issues could be fatal—and for more than just that single colleague. At some point, we are compelled to do more than just raise an eyebrow and shake our head. Usually at the time of discovery, months if not years of substance abuse already have gone by undetected. Deferring to the next person is just not an option. There is too much at stake. It is our moral duty to help our colleagues who are unable to realize the danger they are posing to themselves, the team, and, most importantly, the patients.

Certainly, physicians do not need another lecture about the perils of substance abuse. Whether discussing prescription drugs, alcohol, marijuana, cocaine, or the like, we all have witnessed the devastating effects of abuse. The fact is, any substance that alters our ability to perform our trusted duty must be avoided.

Colleagues, the algorithm is simple: Be vigilant, observe, confirm, and report. It is our moral and ethical imperative.

Dr. Pyke is chief medical officer of Medicus Consulting, LLC.

Dr. Guerrasio

CON

Responsible, helpful action doesn’t always mean official involvement

Recognizing impairment in our colleagues is both difficult and ethically challenging. Despite national trends, medicine remains a largely self-regulated profession, and we have an ethical obligation to report impaired, incompetent, or unethical colleagues. Rarely are the indications for reporting or identifying a colleague clear.

As trained clinicians, we know the signs of substance abuse:⁶

• Frequent tardiness and absences;
• Unexplained disappearances during working hours;
• Inappropriate behavior;
• Affective lability or irritability;
• Interpersonal conflict;
• Avoidance of peers or supervisors;
• Keeping odd hours;
• Disorganized and forgetful;
• Incomplete charts and work performance;
• Heavy drinking at social functions;
• Unexplained changes in weight or energy level;
• Diminished personal hygiene;
• Slurred or rapid speech;
• Frequently dilated pupils or red, watery eyes and a runny nose;
• Defensiveness, anxiety, apathy, and manipulative behaviors; and
• Withdrawal from long-standing relationships.

Yet when it is a colleague, we are often in denial about their substance abuse. Certainly, simple seasonal allergies and allergy medications can cause a number of the above symptoms. We also are aware of and fear the potential impact of licensing board notification on a physician’s career. In fact, in a national survey of physicians, 45% of respondents who had encountered impaired or incompetent physicians had not reported them, even though 96% of those surveyed agreed that physicians should report impaired or incompetent colleagues.⁷

Similar to reporting child or elder abuse, you don’t want to be wrong.

At the same time, impaired physicians are disruptive. They negatively impact the lives of their patients, colleagues, and hospital staff.

It is possible to do both the responsible thing and not go directly to the licensing board. You are not responsible for diagnosing your colleagues, but rather recognizing possible impairment.

Check out the Federation of State Physician Health Programs’ website (www.fsphp.org) to identify a local physician health program. Call them and place a report of concern identifying your impaired colleague. While it’s possibly new to you, they have years of experience working with this situation. Trust these organizations, many of which are independent from licensing, to intervene responsibly and confidentially. They can evaluate your colleague and provide a treatment plan and monitoring, as needed. Their approach is rehabilitative rather than punitive, and they resist reporting to the medical board unless the physician-patient is noncompliant.

Physicians have better outcomes than the general population, with reported abstinence rates of 70% to 90% for those who complete treatment.^8,9 Between 75% and 85% of physicians who complete rehabilitation and comply with close monitoring and follow-up care are able to return to work.^9,10

There is hope for your impaired colleague. Contact your local physician health program.

Dr. Guerrasio is a hospitalist and director of resident and medical student remediation at the University of Colorado Denver.

References

1. Hughes PH, Brandenburg N, Baldwin DC Jr., et al. Prevalence of substance use among US physicians. JAMA. 1992;267:2333-2339.
2. Gold KB, Teitelbaum SA. Physicians impaired by substance abuse disorders. The Journal of Global Drug Policy and Practice website. Available at: http://www.globaldrugpolicy.org/2/2/3.php. Accessed June 27, 2011.
3. Wolfgang AP. Substance abuse potential and job stress: a study of pharmacists, physicians, and nurses. J Pharm Mark Manage. 1989;3(4):97-110.
4. Cicala RS. Substance abuse among physicians: What you need to know. Hosp Phys. 2003:39-46.
5. Berge KH, Seppala MD, Schipper AM. Chemical dependency and the physician. Mayo Clin Proc. 2009;84(7):625-631.
6. Bright RP, Krahn L. Impaired physicians: How to recognize, when to report, and where to refer. Curr Psy. 2010;9(6):11-20.
7. Campbell EG, Regan S, Gruen RL, et al. Professionalism in medicine: results of a national survey of physicians. Ann Intern Med. 2007;147:795-802.
8. Femino J, Nirenberg TD. Treatment outcome studies on physician impairment: a review of the literature. R I Med. 1994;77:345-350.
9. Alpern F, Correnti CE, Dolan TE, Llufrio MC, Sill A. A survey of recovering Maryland physicians. Md Med J. 1992;41:301-303.
10. Gallegos KV, Lubin BH, Bowers C, Blevins JW, Talbott GD, Wilson PO. Relapse and recovery: five to ten year follow-up study of chemically dependent physicians—the Georgia experience. Md Med J. 1992;41:315-319.

Dr. Pyke

PRO

Hospitalists’ moral obligation is to protect the patient

In this era of historic budget deficits, wars, and political strife surrounding healthcare reform, one might ask if we can afford to spend valuable time and energy on the issue of reporting physicians who abuse substances.

At first glance, I certainly had skepticism about the subject, but then I dug deeper. To my surprise (and likely yours), studies indicate that physicians develop substance-abuse problems as often or more than the general population does.¹ Recent reports detail horrific patient outcomes at the hands of health providers whose actions are compromised by drug use. With data showing the prevalence of substance abuse among physicians hovering around 10% to 12%, we must accept the reality that hospitalists are not exempt.^2,3,4,5

As medical doctors, our promise to our patients is to provide care in an ethical manner. Even if we try to live in denial, most of us would agree that with great blessing (or power) comes great responsibility. So when the question of reporting a fellow hospitalist who is abusing substances was asked, my response was unequivocally yes.

In my opinion, this discussion can be limited to two overarching principles: First, we are compelled to put our patients first. As hospitalists, we are blessed to be caring for some of the most frail and vulnerable in our society. Fortunately, an overwhelming number of us do so with pride, skill, and integrity.

The task of providing high-quality care to an empowered patient population is difficult enough with us being physically, emotionally, and mentally exhausted. But to add substance abuse to this is just a complete and utter violation of our patients’ trust. We must agree that putting our patients’ well-being beyond reproach requires us to report any colleague who is compromised.

Second, delayed help for a colleague in trouble with substance-abuse issues could be fatal—and for more than just that single colleague. At some point, we are compelled to do more than just raise an eyebrow and shake our head. Usually at the time of discovery, months if not years of substance abuse already have gone by undetected. Deferring to the next person is just not an option. There is too much at stake. It is our moral duty to help our colleagues who are unable to realize the danger they are posing to themselves, the team, and, most importantly, the patients.

Certainly, physicians do not need another lecture about the perils of substance abuse. Whether discussing prescription drugs, alcohol, marijuana, cocaine, or the like, we all have witnessed the devastating effects of abuse. The fact is, any substance that alters our ability to perform our trusted duty must be avoided.

Colleagues, the algorithm is simple: Be vigilant, observe, confirm, and report. It is our moral and ethical imperative.

Dr. Pyke is chief medical officer of Medicus Consulting, LLC.

Dr. Guerrasio

CON

Responsible, helpful action doesn’t always mean official involvement

Recognizing impairment in our colleagues is both difficult and ethically challenging. Despite national trends, medicine remains a largely self-regulated profession, and we have an ethical obligation to report impaired, incompetent, or unethical colleagues. Rarely are the indications for reporting or identifying a colleague clear.

As trained clinicians, we know the signs of substance abuse:⁶

• Frequent tardiness and absences;
• Unexplained disappearances during working hours;
• Inappropriate behavior;
• Affective lability or irritability;
• Interpersonal conflict;
• Avoidance of peers or supervisors;
• Keeping odd hours;
• Disorganized and forgetful;
• Incomplete charts and work performance;
• Heavy drinking at social functions;
• Unexplained changes in weight or energy level;
• Diminished personal hygiene;
• Slurred or rapid speech;
• Frequently dilated pupils or red, watery eyes and a runny nose;
• Defensiveness, anxiety, apathy, and manipulative behaviors; and
• Withdrawal from long-standing relationships.

Yet when it is a colleague, we are often in denial about their substance abuse. Certainly, simple seasonal allergies and allergy medications can cause a number of the above symptoms. We also are aware of and fear the potential impact of licensing board notification on a physician’s career. In fact, in a national survey of physicians, 45% of respondents who had encountered impaired or incompetent physicians had not reported them, even though 96% of those surveyed agreed that physicians should report impaired or incompetent colleagues.⁷

Similar to reporting child or elder abuse, you don’t want to be wrong.

At the same time, impaired physicians are disruptive. They negatively impact the lives of their patients, colleagues, and hospital staff.

It is possible to do both the responsible thing and not go directly to the licensing board. You are not responsible for diagnosing your colleagues, but rather recognizing possible impairment.

Check out the Federation of State Physician Health Programs’ website (www.fsphp.org) to identify a local physician health program. Call them and place a report of concern identifying your impaired colleague. While it’s possibly new to you, they have years of experience working with this situation. Trust these organizations, many of which are independent from licensing, to intervene responsibly and confidentially. They can evaluate your colleague and provide a treatment plan and monitoring, as needed. Their approach is rehabilitative rather than punitive, and they resist reporting to the medical board unless the physician-patient is noncompliant.

Physicians have better outcomes than the general population, with reported abstinence rates of 70% to 90% for those who complete treatment.^8,9 Between 75% and 85% of physicians who complete rehabilitation and comply with close monitoring and follow-up care are able to return to work.^9,10

There is hope for your impaired colleague. Contact your local physician health program.

Dr. Guerrasio is a hospitalist and director of resident and medical student remediation at the University of Colorado Denver.

References

1. Hughes PH, Brandenburg N, Baldwin DC Jr., et al. Prevalence of substance use among US physicians. JAMA. 1992;267:2333-2339.
2. Gold KB, Teitelbaum SA. Physicians impaired by substance abuse disorders. The Journal of Global Drug Policy and Practice website. Available at: http://www.globaldrugpolicy.org/2/2/3.php. Accessed June 27, 2011.
3. Wolfgang AP. Substance abuse potential and job stress: a study of pharmacists, physicians, and nurses. J Pharm Mark Manage. 1989;3(4):97-110.
4. Cicala RS. Substance abuse among physicians: What you need to know. Hosp Phys. 2003:39-46.
5. Berge KH, Seppala MD, Schipper AM. Chemical dependency and the physician. Mayo Clin Proc. 2009;84(7):625-631.
6. Bright RP, Krahn L. Impaired physicians: How to recognize, when to report, and where to refer. Curr Psy. 2010;9(6):11-20.
7. Campbell EG, Regan S, Gruen RL, et al. Professionalism in medicine: results of a national survey of physicians. Ann Intern Med. 2007;147:795-802.
8. Femino J, Nirenberg TD. Treatment outcome studies on physician impairment: a review of the literature. R I Med. 1994;77:345-350.
9. Alpern F, Correnti CE, Dolan TE, Llufrio MC, Sill A. A survey of recovering Maryland physicians. Md Med J. 1992;41:301-303.
10. Gallegos KV, Lubin BH, Bowers C, Blevins JW, Talbott GD, Wilson PO. Relapse and recovery: five to ten year follow-up study of chemically dependent physicians—the Georgia experience. Md Med J. 1992;41:315-319.

Dr. Pyke

PRO

Hospitalists’ moral obligation is to protect the patient

In this era of historic budget deficits, wars, and political strife surrounding healthcare reform, one might ask if we can afford to spend valuable time and energy on the issue of reporting physicians who abuse substances.

At first glance, I certainly had skepticism about the subject, but then I dug deeper. To my surprise (and likely yours), studies indicate that physicians develop substance-abuse problems as often or more than the general population does.¹ Recent reports detail horrific patient outcomes at the hands of health providers whose actions are compromised by drug use. With data showing the prevalence of substance abuse among physicians hovering around 10% to 12%, we must accept the reality that hospitalists are not exempt.^2,3,4,5

As medical doctors, our promise to our patients is to provide care in an ethical manner. Even if we try to live in denial, most of us would agree that with great blessing (or power) comes great responsibility. So when the question of reporting a fellow hospitalist who is abusing substances was asked, my response was unequivocally yes.

In my opinion, this discussion can be limited to two overarching principles: First, we are compelled to put our patients first. As hospitalists, we are blessed to be caring for some of the most frail and vulnerable in our society. Fortunately, an overwhelming number of us do so with pride, skill, and integrity.

The task of providing high-quality care to an empowered patient population is difficult enough with us being physically, emotionally, and mentally exhausted. But to add substance abuse to this is just a complete and utter violation of our patients’ trust. We must agree that putting our patients’ well-being beyond reproach requires us to report any colleague who is compromised.

Second, delayed help for a colleague in trouble with substance-abuse issues could be fatal—and for more than just that single colleague. At some point, we are compelled to do more than just raise an eyebrow and shake our head. Usually at the time of discovery, months if not years of substance abuse already have gone by undetected. Deferring to the next person is just not an option. There is too much at stake. It is our moral duty to help our colleagues who are unable to realize the danger they are posing to themselves, the team, and, most importantly, the patients.

Certainly, physicians do not need another lecture about the perils of substance abuse. Whether discussing prescription drugs, alcohol, marijuana, cocaine, or the like, we all have witnessed the devastating effects of abuse. The fact is, any substance that alters our ability to perform our trusted duty must be avoided.

Colleagues, the algorithm is simple: Be vigilant, observe, confirm, and report. It is our moral and ethical imperative.

Dr. Pyke is chief medical officer of Medicus Consulting, LLC.

Dr. Guerrasio

CON

Responsible, helpful action doesn’t always mean official involvement

Recognizing impairment in our colleagues is both difficult and ethically challenging. Despite national trends, medicine remains a largely self-regulated profession, and we have an ethical obligation to report impaired, incompetent, or unethical colleagues. Rarely are the indications for reporting or identifying a colleague clear.

As trained clinicians, we know the signs of substance abuse:⁶

• Frequent tardiness and absences;
• Unexplained disappearances during working hours;
• Inappropriate behavior;
• Affective lability or irritability;
• Interpersonal conflict;
• Avoidance of peers or supervisors;
• Keeping odd hours;
• Disorganized and forgetful;
• Incomplete charts and work performance;
• Heavy drinking at social functions;
• Unexplained changes in weight or energy level;
• Diminished personal hygiene;
• Slurred or rapid speech;
• Frequently dilated pupils or red, watery eyes and a runny nose;
• Defensiveness, anxiety, apathy, and manipulative behaviors; and
• Withdrawal from long-standing relationships.

Yet when it is a colleague, we are often in denial about their substance abuse. Certainly, simple seasonal allergies and allergy medications can cause a number of the above symptoms. We also are aware of and fear the potential impact of licensing board notification on a physician’s career. In fact, in a national survey of physicians, 45% of respondents who had encountered impaired or incompetent physicians had not reported them, even though 96% of those surveyed agreed that physicians should report impaired or incompetent colleagues.⁷

Similar to reporting child or elder abuse, you don’t want to be wrong.

At the same time, impaired physicians are disruptive. They negatively impact the lives of their patients, colleagues, and hospital staff.

It is possible to do both the responsible thing and not go directly to the licensing board. You are not responsible for diagnosing your colleagues, but rather recognizing possible impairment.

Check out the Federation of State Physician Health Programs’ website (www.fsphp.org) to identify a local physician health program. Call them and place a report of concern identifying your impaired colleague. While it’s possibly new to you, they have years of experience working with this situation. Trust these organizations, many of which are independent from licensing, to intervene responsibly and confidentially. They can evaluate your colleague and provide a treatment plan and monitoring, as needed. Their approach is rehabilitative rather than punitive, and they resist reporting to the medical board unless the physician-patient is noncompliant.

Physicians have better outcomes than the general population, with reported abstinence rates of 70% to 90% for those who complete treatment.^8,9 Between 75% and 85% of physicians who complete rehabilitation and comply with close monitoring and follow-up care are able to return to work.^9,10

There is hope for your impaired colleague. Contact your local physician health program.

Dr. Guerrasio is a hospitalist and director of resident and medical student remediation at the University of Colorado Denver.

References

1. Hughes PH, Brandenburg N, Baldwin DC Jr., et al. Prevalence of substance use among US physicians. JAMA. 1992;267:2333-2339.
2. Gold KB, Teitelbaum SA. Physicians impaired by substance abuse disorders. The Journal of Global Drug Policy and Practice website. Available at: http://www.globaldrugpolicy.org/2/2/3.php. Accessed June 27, 2011.
3. Wolfgang AP. Substance abuse potential and job stress: a study of pharmacists, physicians, and nurses. J Pharm Mark Manage. 1989;3(4):97-110.
4. Cicala RS. Substance abuse among physicians: What you need to know. Hosp Phys. 2003:39-46.
5. Berge KH, Seppala MD, Schipper AM. Chemical dependency and the physician. Mayo Clin Proc. 2009;84(7):625-631.
6. Bright RP, Krahn L. Impaired physicians: How to recognize, when to report, and where to refer. Curr Psy. 2010;9(6):11-20.
7. Campbell EG, Regan S, Gruen RL, et al. Professionalism in medicine: results of a national survey of physicians. Ann Intern Med. 2007;147:795-802.
8. Femino J, Nirenberg TD. Treatment outcome studies on physician impairment: a review of the literature. R I Med. 1994;77:345-350.
9. Alpern F, Correnti CE, Dolan TE, Llufrio MC, Sill A. A survey of recovering Maryland physicians. Md Med J. 1992;41:301-303.
10. Gallegos KV, Lubin BH, Bowers C, Blevins JW, Talbott GD, Wilson PO. Relapse and recovery: five to ten year follow-up study of chemically dependent physicians—the Georgia experience. Md Med J. 1992;41:315-319.

In This Edition

Literature at a Glance

A guide to this month’s studies

• PE and COPD exacerbations.
• Care bundles and readmission rates.
• Family history and VTE risk.
• Vasopressor choice and mortality in sepsis.
• Vitamin K use in overanticoagulation.
• Appropriate treatment of asymptomatic bacteriuria.
• Guideline adherence in thrombocytopenia.

Pulmonary Embolism Frequently Complicates COPD Exacerbations

Clinical question: What percentage of patients with acute chronic obstructive pulmonary disease (COPD) exacerbations has pulmonary emboli?

Background: As many as 30% of COPD exacerbations have no apparent precipitating event. Even in patients with evidence of a precipitating event, such as an upper-respiratory illness or increased environmental irritants, pulmonary emboli (PE) may coexist and warrant evaluation.

Study design: Literature review.

Setting: Multiple studies in Europe and the U.S.

Synopsis: This literature review included five studies to estimate the rate of PE in patients with a COPD exacerbation. Overall incidence of PE in COPD exacerbations was 19.9%, but of those patients requiring hospitalization, the incidence was as high as 25.5%. Incidence estimates varied based on interpretation of data that were missing or inconsistent between studies. Patients most commonly present with dyspnea, chest pain, hemoptysis, cough, and palpitations. Six percent of PE patients presented with syncope; no patients with an exacerbation without a PE presented with syncope.

Risk of mortality from PE is almost twice as high in patients with a COPD exacerbation compared with PE in other settings. A significant number of patients have PE without history or evidence of DVT, so in situ thrombosis is a significant factor. The interpretation of these results is limited by the heterogeneity of the study designs, and by the relatively low number of cases. Larger trials are necessary.

Bottom line: Pulmonary emboli are present in as many as 25% of all COPD exacerbations. Delay in diagnosis of PE in COPD patients affects morbidity and mortality. PE should be a consideration in many COPD exacerbations.

Citation: Rizkallah J, Man SF, Din DD. Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2009;135(3):786-793.

Targeted-Care Bundle Can Reduce ED Visits and Readmission Rates in High-Risk Elderly Patients

Clinical question: Can a care coordination bundle reduce length of stay (LOS), ED visits, or readmissions within 30 days of a hospital admission?

Background: Hospital-based care coordination interventions have shown mixed results in affecting LOS, post-discharge ED visits, and readmission rates. Although there has been some success with particular interventions, no consistent benefit has been demonstrated. Most notably, a recent meta-analysis of several different interventions showed no improvement in mortality, LOS, or readmission rates.

Study design: A randomized, controlled trial of select high-risk elderly patients.

Setting: A large teaching hospital at Baylor University Medical Center.

Synopsis: A “targeted-care bundle” was implemented with high-risk elderly patients to try to reduce LOS, readmissions, and ED visits. High-risk patients were identified by age, diagnosis-related group (DRG), number of medications at admission, comorbid conditions, and need for assistance in activities of daily living. Subjects were randomized to usual care or to receive a targeted-care bundle. The targeted-care bundle included multiple interventions. A study care coordinator provided daily patient education, including condition-specific teaching, discharge teaching and planning, and a follow-up phone call at five to seven days after discharge. A clinical pharmacist intervened for medication reconciliation at admission and discharge, medication teaching, and a follow-up phone call at five to seven days after discharge. Structured documents, including a personal health record and supplemental discharge form, were implemented.

The study had low enrollment, largely due to the requirement to obtain informed consent from all participants. Therefore, the study was underpowered to detect such target endpoints as LOS. A significant decrease in 30-day readmission rates/ED visits was noticed, but there was no persistent effect at 60 days.

The intervention was designed to use existing hospital staff in order to be practical for broad utilization. Future studies need to focus on increased enrollment to demonstrate beneficial effect.

Bottom line: Targeted health interventions focusing on education and coordination of care might effect some significant outcomes, most notably readmissions or ED visits within 30 days, but the nature of the clinical problem makes rigorous testing of interventions a challenge.

Citation: Kohler BE, Richter KM, Youngblood L, et al. Reduction of 30-day postdischarge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4(4):211-218.

Family History Is a Risk Factor for Venous Thrombosis

Clinical question: Is family history of additional value in predicting an individual’s risk of venous thrombosis once a genetic risk factor is identified?

Background: A positive family history of venous thrombosis might suggest the presence of genetic risk factors in a given family. However, it is not known whether family history is of additional significance—once a risk factor is identified—in predicting an individual’s risk for venous thrombosis.

Study design: Population-based, case-control study.

Setting: Participants in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study.

Synopsis: Recruitment, data collection, and blood samples were obtained from individuals in the MEGA study. Participants completed a questionnaire about risk factors for venous thrombosis and family history. A positive family history more than doubled the risk of venous thrombosis, and when more than one family member was affected, the risk increased fourfold. The risk for venous thrombosis increased 64 times for individuals who had a family history, genetic risk factor, and environmental risk factor when compared with those with a negative family history and no known risk factors.

The underreporting or overestimation of the prevalence of a positive family history might limit this study.

Bottom line: Family history is a risk indictor for a first venous thrombosis, despite the presence of other risk factors.

Citation: Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The value of family history as a risk indicator for venous thrombosis. Arch Intern Med. 2009;169(6):610-615.

Vasopressor Choice Predicts Mortality in Septic Shock

Clinical question: Does vasopressor choice affect mortality in patients with community-acquired septic shock?

Background: Community-acquired septic shock is a common illness and, despite aggressive care, a leading cause of death. Randomized clinical control trials evaluating the efficacy and safety of different adrenergic supportive agents are lacking. Thus, both norepinephrine and dopamine are recommended as first-line agents in the treatment of septic shock by the Surviving Sepsis Campaign guidelines.

Study design: Multicenter, cohort observational study.

Setting: Seventeen intensive-care units in Portugal.

Synopsis: In adjusted analysis controlling for Simplified Acute Physiology Score (SAPS) II, use of norepinephrine in community-acquired septic shock was associated with higher hospital mortality and lower 28-day survival when compared with dopamine. Specifically, patients treated with norepinephrine had a statistically significant higher hospital mortality rate than those treated with dopamine (52% and 38.5%, respectively, P=0.002) and a lower 28-day survival (log rank=22.6; P<0.001). While this data is valuable, the nonrandomized, observational study design limits firm conclusions regarding vasopressor choice. Further results from three large trials comparing vasopressor use in septic shock should continue to shed light on this debate.

Bottom line: Norepinephrine administration is associated with higher hospital mortality and lower 28-day survival when compared with dopamine in patients with community-acquired septic shock.

Citation: Póvoa PR, Carneiro AH, Ribeiro OS, Pereira AC, Portuguese Community-Acquired Sepsis Study Group. Influence of vasopressor agent in septic shock mortality. Results from the Portuguese Community-Acquired Sepsis Study (SACiUCI study). Crit Care Med. 2009;37(2):410-416.

Oral Vitamin K Versus Placebo to Correct Excess Anticoagulation in Warfarin Patients

Clinical question: In nonbleeding patients with warfarin-associated coagulopathy, does oral vitamin K reduce bleeding events when compared to placebo?

Background: Warfarin is a common drug for primary and secondary prevention of thromboembolism, but it requires continued monitoring of the international normalized ratio (INR) value. INR values >4.0 are associated with an increase in bleeding complications, with specific concern for intracranial bleeding when INR values exceed 4.5. Small, randomized trials have shown that single, low-dose administration of oral vitamin K effectively reduces the INR in nonbleeding, overanticoagulated patients.

However, these studies have not shown if vitamin K reduces risk for bleeding without increasing the risk for thromboembolism.

Study design: Randomized, placebo-controlled trial.

Setting: Fourteen anticoagulation clinics in Canada, Italy, and the U.S.

Synopsis: Nonbleeding patients with supratherapeutic INR values between 4.5 and 10.0 were randomly assigned to receive 1.25 mg of oral vitamin K or placebo, then evaluated for all forms of bleeding for 90 days. Bleeding events were defined as “major bleeding,” “minor bleeding,” and “trivial bleeding.”

Though patients who received oral vitamin K had a significantly more rapid INR decrease, there were no differences between the two groups with regard to all bleeding events, thromboembolism, or death. The study was underpowered to detect differences in major bleeding.

Bottom line: Low-dose oral vitamin K leads to more rapid correction of the INR in overanticoagulated patients on warfarin therapy, but has little effect on clinical outcomes at 90 days.

Citation: Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med. 2009;150(5):293-300.

Inappropriate Treatment of Catheter-Associated Asymptomatic Bacteriuria

Clinical question: Are hospitalized patients with urinary catheters inappropriately treated with antibiotics for asymptomatic bacteriuria?

Background: Persons with catheters acquire bacteriuria at the rate of 3% to 10% per day, but in the majority of cases, no symptoms or secondary complications occur. Evidenced-based guidelines state that asymptomatic bacteriuria is not a clinically significant infection, and numerous studies have shown that treatment is unlikely to confer clinical benefit.

Study design: Retrospective cohort study.

Setting: A single-site Veterans Affairs hospital.

Synopsis: Using urine culture results over a three-month period from a single VA medical center, 280 cases were analyzed: 164 catheter-associated asymptomatic bacteriuria and 116 catheter-associated urinary tract infections (UTIs). A UTI was defined as having one or more of these symptoms: fever, urgency, frequency, dysuria, suprapubic tenderness, altered mental status, or hypotension in a patient without another recognized infection and a positive urine culture. Of the asymptomatic bacteriuria cases, 68% were managed appropriately with no antibiotic treatment; 32% were inappropriately treated with antibiotics.

In multivariate analysis, older patient age, predominance of gram-negative bacteria, and higher urine white blood cell count were significantly associated with inappropriate treatment.

This study highlights the fact that antibiotics continue to be used inappropriately in patients with catheters. Current guidelines do not distinguish well between asymptomatic bacteriuria and UTI, so there might be a knowledge gap. This study was based on urine culture data, not urinalysis of all patients with a catheter, so the symptomatic patients were likely over-represented.

An associated editorial observes that the study extrapolates data from studies that involved patients with uncomplicated UTIs and, therefore, might reach erroneous conclusions. Further, viewing catheter-associated symptomatic UTIs and catheter-associated asymptomatic bactiuria as dichotomous and warranting inherently different management fails to encompass a number of clinical factors, including co-infection, and further fails to acknowledge that removal of the catheter is the first step in treatment. However, the finding that antibiotics continue to be used inappropriately is useful.

Bottom line: A clinical determination of whether a patient with a catheter really has a symptomatic UTI/urosepsis or only has asymptomatic bacteriuria should precede starting antibiotics in hospitalized patients.

Citations: Cope M, Cevallos ME, Cadle RM, Darouiche RO, Musher DM, Trautner BW. Inappropriate treatment of catheter-associated asymptomatic bateriuria in a tertiary care hospital. Clin Infect Dis. 2009;48(9):1182-1188.

Kunin CM. Catheter-associated urinary tract infections: a syllogism compounded by a questionable dichotomy. Clin Infect Dis. 2009;48:1189-1190.

Current Practices in the Evaluation and Management of Thrombocytopenia in Heparin Patients

Clinical question: Are the current American College of Chest Physicians (ACCP) guidelines for the recognition, treatment, and prevention of heparin-induced thrombocytopenia (HIT) being followed?

Background: Heparin-based anticoagulation is frequently given to hospitalized patients, and approximately 1% to 5% of these patients develop HIT. In 2004, the ACCP published a consensus statement on the evaluation, management, and prevention of HIT.

Study design: Prospective, observational study.

Setting: Forty-eight U.S. hospitals in the Complications After Thrombocytopenia Caused by Heparin (CATCH) registry.

Synopsis: The CATCH trial enrolled patients receiving any form of heparin for >96 hours (n=2,420), cardiac-care-unit patients treated with heparin (n=1,090), and patients who had an HIT antibody assay performed (n=449), for a total of 3,536 total patients. The study included patients on unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Thrombocytopenia was defined at a platelet count <150,000, or a decrease of 50% when compared with admission.

In the prolonged heparin group, 36.4% of patients developed thrombocytopenia; however, HIT was suspected in only 19.8% of these high-risk patients. While physicians were more likely to consider HIT in the cardiac-care patients (37.6%), the diagnosis was considered>24 hours after the thrombocytopenia developed. Physicians often waited until after a thromboembolic complication occurred before evaluating for HIT. More often than not, preventive measures were missed (e.g., failing to check for HIT antibodies, continuing heparin after HIT was suspected).

Bottom line: Thrombocytopenia is a common occurrence in patients receiving heparin and, despite the risk of devastating complications from HIT, treatment infrequently conforms to the established guidelines.

Citation: Crespo EM, Oliveira GBF, Honeycutt EF, et al. Evaluation and management of thrombocytopenia and suspected heparin-induced thrombocytopenia in hospitalized patients: The Complications After Thrombocytopenia Caused by Heparin (CATCH) registry. Am Heart J. 2009;157(4):651-657. TH

PEDIATRIC HM LITerature

Epinephrine and Dexamethasone Alone Do Not Reduce Hospital Admissions in Infants with Bronchiolitis

By Mark Shen, MD

Clinical question: Does nebulized epinephrine, oral dexamethasone, or a combination of the two result in a decrease in hospital admissions when given in the ED to infants with bronchiolitis?

Background: Bronchiolitis is the most common lower-respiratory-tract infection of infancy. Rates of admission have climbed in the past two decades. Bronchodilators and corticosteroids are not routinely recommended, and the evidence surrounding epinephrine and dexamethasone has shown varying results.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Eight Canadian pediatric EDs.

Synopsis: Eight hundred infants ages six weeks to 12 months with a first episode of bronchiolitis were randomized to nebulized epinephrine and oral dexamethasone, epinephrine and oral placebo, dexamethasone and nebulized placebo, or oral and nebulized placebo. Epinephrine was delivered as two nebulizations 30 minutes apart, and dexamethasone was given as a 1 mg/kg oral dose, followed by five once-daily doses of 0.6 mg/kg. In unadjusted analysis, only the infants who received epinephrine and dexamethasone were less likely to be admitted to the hospital by day seven.

Limitations of this study include a small effect size and a non-statistically-significant difference between the epinephrine/dexamethasone group and placebo after statistical adjustment for multiple comparisons. Given that admission rates did not decrease in the epinephrine/placebo group and the dexamethasone/placebo group, this study supports national guidelines that do not recommend the routine use of these agents in bronchiolitis. The authors suggest that synergy between epinephrine and dexamethasone in bronchiolitis be further studied.

Bottom line: When given alone, epinephrine and dexamethasone do not reduce hospital admissions in infants with bronchiolitis.

Citation: Plint AC, Johnson DW, Patel H, et al. Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360(20):2079-2089.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

In This Edition

Literature at a Glance

A guide to this month’s studies

• PE and COPD exacerbations.
• Care bundles and readmission rates.
• Family history and VTE risk.
• Vasopressor choice and mortality in sepsis.
• Vitamin K use in overanticoagulation.
• Appropriate treatment of asymptomatic bacteriuria.
• Guideline adherence in thrombocytopenia.

Pulmonary Embolism Frequently Complicates COPD Exacerbations

Clinical question: What percentage of patients with acute chronic obstructive pulmonary disease (COPD) exacerbations has pulmonary emboli?

Background: As many as 30% of COPD exacerbations have no apparent precipitating event. Even in patients with evidence of a precipitating event, such as an upper-respiratory illness or increased environmental irritants, pulmonary emboli (PE) may coexist and warrant evaluation.

Study design: Literature review.

Setting: Multiple studies in Europe and the U.S.

Synopsis: This literature review included five studies to estimate the rate of PE in patients with a COPD exacerbation. Overall incidence of PE in COPD exacerbations was 19.9%, but of those patients requiring hospitalization, the incidence was as high as 25.5%. Incidence estimates varied based on interpretation of data that were missing or inconsistent between studies. Patients most commonly present with dyspnea, chest pain, hemoptysis, cough, and palpitations. Six percent of PE patients presented with syncope; no patients with an exacerbation without a PE presented with syncope.

Risk of mortality from PE is almost twice as high in patients with a COPD exacerbation compared with PE in other settings. A significant number of patients have PE without history or evidence of DVT, so in situ thrombosis is a significant factor. The interpretation of these results is limited by the heterogeneity of the study designs, and by the relatively low number of cases. Larger trials are necessary.

Bottom line: Pulmonary emboli are present in as many as 25% of all COPD exacerbations. Delay in diagnosis of PE in COPD patients affects morbidity and mortality. PE should be a consideration in many COPD exacerbations.

Citation: Rizkallah J, Man SF, Din DD. Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2009;135(3):786-793.

Targeted-Care Bundle Can Reduce ED Visits and Readmission Rates in High-Risk Elderly Patients

Clinical question: Can a care coordination bundle reduce length of stay (LOS), ED visits, or readmissions within 30 days of a hospital admission?

Background: Hospital-based care coordination interventions have shown mixed results in affecting LOS, post-discharge ED visits, and readmission rates. Although there has been some success with particular interventions, no consistent benefit has been demonstrated. Most notably, a recent meta-analysis of several different interventions showed no improvement in mortality, LOS, or readmission rates.

Study design: A randomized, controlled trial of select high-risk elderly patients.

Setting: A large teaching hospital at Baylor University Medical Center.

Synopsis: A “targeted-care bundle” was implemented with high-risk elderly patients to try to reduce LOS, readmissions, and ED visits. High-risk patients were identified by age, diagnosis-related group (DRG), number of medications at admission, comorbid conditions, and need for assistance in activities of daily living. Subjects were randomized to usual care or to receive a targeted-care bundle. The targeted-care bundle included multiple interventions. A study care coordinator provided daily patient education, including condition-specific teaching, discharge teaching and planning, and a follow-up phone call at five to seven days after discharge. A clinical pharmacist intervened for medication reconciliation at admission and discharge, medication teaching, and a follow-up phone call at five to seven days after discharge. Structured documents, including a personal health record and supplemental discharge form, were implemented.

The study had low enrollment, largely due to the requirement to obtain informed consent from all participants. Therefore, the study was underpowered to detect such target endpoints as LOS. A significant decrease in 30-day readmission rates/ED visits was noticed, but there was no persistent effect at 60 days.

The intervention was designed to use existing hospital staff in order to be practical for broad utilization. Future studies need to focus on increased enrollment to demonstrate beneficial effect.

Bottom line: Targeted health interventions focusing on education and coordination of care might effect some significant outcomes, most notably readmissions or ED visits within 30 days, but the nature of the clinical problem makes rigorous testing of interventions a challenge.

Citation: Kohler BE, Richter KM, Youngblood L, et al. Reduction of 30-day postdischarge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4(4):211-218.

Family History Is a Risk Factor for Venous Thrombosis

Clinical question: Is family history of additional value in predicting an individual’s risk of venous thrombosis once a genetic risk factor is identified?

Background: A positive family history of venous thrombosis might suggest the presence of genetic risk factors in a given family. However, it is not known whether family history is of additional significance—once a risk factor is identified—in predicting an individual’s risk for venous thrombosis.

Study design: Population-based, case-control study.

Setting: Participants in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study.

Synopsis: Recruitment, data collection, and blood samples were obtained from individuals in the MEGA study. Participants completed a questionnaire about risk factors for venous thrombosis and family history. A positive family history more than doubled the risk of venous thrombosis, and when more than one family member was affected, the risk increased fourfold. The risk for venous thrombosis increased 64 times for individuals who had a family history, genetic risk factor, and environmental risk factor when compared with those with a negative family history and no known risk factors.

The underreporting or overestimation of the prevalence of a positive family history might limit this study.

Bottom line: Family history is a risk indictor for a first venous thrombosis, despite the presence of other risk factors.

Citation: Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The value of family history as a risk indicator for venous thrombosis. Arch Intern Med. 2009;169(6):610-615.

Vasopressor Choice Predicts Mortality in Septic Shock

Clinical question: Does vasopressor choice affect mortality in patients with community-acquired septic shock?

Background: Community-acquired septic shock is a common illness and, despite aggressive care, a leading cause of death. Randomized clinical control trials evaluating the efficacy and safety of different adrenergic supportive agents are lacking. Thus, both norepinephrine and dopamine are recommended as first-line agents in the treatment of septic shock by the Surviving Sepsis Campaign guidelines.

Study design: Multicenter, cohort observational study.

Setting: Seventeen intensive-care units in Portugal.

Synopsis: In adjusted analysis controlling for Simplified Acute Physiology Score (SAPS) II, use of norepinephrine in community-acquired septic shock was associated with higher hospital mortality and lower 28-day survival when compared with dopamine. Specifically, patients treated with norepinephrine had a statistically significant higher hospital mortality rate than those treated with dopamine (52% and 38.5%, respectively, P=0.002) and a lower 28-day survival (log rank=22.6; P<0.001). While this data is valuable, the nonrandomized, observational study design limits firm conclusions regarding vasopressor choice. Further results from three large trials comparing vasopressor use in septic shock should continue to shed light on this debate.

Bottom line: Norepinephrine administration is associated with higher hospital mortality and lower 28-day survival when compared with dopamine in patients with community-acquired septic shock.

Citation: Póvoa PR, Carneiro AH, Ribeiro OS, Pereira AC, Portuguese Community-Acquired Sepsis Study Group. Influence of vasopressor agent in septic shock mortality. Results from the Portuguese Community-Acquired Sepsis Study (SACiUCI study). Crit Care Med. 2009;37(2):410-416.

Oral Vitamin K Versus Placebo to Correct Excess Anticoagulation in Warfarin Patients

Clinical question: In nonbleeding patients with warfarin-associated coagulopathy, does oral vitamin K reduce bleeding events when compared to placebo?

Background: Warfarin is a common drug for primary and secondary prevention of thromboembolism, but it requires continued monitoring of the international normalized ratio (INR) value. INR values >4.0 are associated with an increase in bleeding complications, with specific concern for intracranial bleeding when INR values exceed 4.5. Small, randomized trials have shown that single, low-dose administration of oral vitamin K effectively reduces the INR in nonbleeding, overanticoagulated patients.

However, these studies have not shown if vitamin K reduces risk for bleeding without increasing the risk for thromboembolism.

Study design: Randomized, placebo-controlled trial.

Setting: Fourteen anticoagulation clinics in Canada, Italy, and the U.S.

Synopsis: Nonbleeding patients with supratherapeutic INR values between 4.5 and 10.0 were randomly assigned to receive 1.25 mg of oral vitamin K or placebo, then evaluated for all forms of bleeding for 90 days. Bleeding events were defined as “major bleeding,” “minor bleeding,” and “trivial bleeding.”

Though patients who received oral vitamin K had a significantly more rapid INR decrease, there were no differences between the two groups with regard to all bleeding events, thromboembolism, or death. The study was underpowered to detect differences in major bleeding.

Bottom line: Low-dose oral vitamin K leads to more rapid correction of the INR in overanticoagulated patients on warfarin therapy, but has little effect on clinical outcomes at 90 days.

Citation: Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med. 2009;150(5):293-300.

Inappropriate Treatment of Catheter-Associated Asymptomatic Bacteriuria

Clinical question: Are hospitalized patients with urinary catheters inappropriately treated with antibiotics for asymptomatic bacteriuria?

Background: Persons with catheters acquire bacteriuria at the rate of 3% to 10% per day, but in the majority of cases, no symptoms or secondary complications occur. Evidenced-based guidelines state that asymptomatic bacteriuria is not a clinically significant infection, and numerous studies have shown that treatment is unlikely to confer clinical benefit.

Study design: Retrospective cohort study.

Setting: A single-site Veterans Affairs hospital.

Synopsis: Using urine culture results over a three-month period from a single VA medical center, 280 cases were analyzed: 164 catheter-associated asymptomatic bacteriuria and 116 catheter-associated urinary tract infections (UTIs). A UTI was defined as having one or more of these symptoms: fever, urgency, frequency, dysuria, suprapubic tenderness, altered mental status, or hypotension in a patient without another recognized infection and a positive urine culture. Of the asymptomatic bacteriuria cases, 68% were managed appropriately with no antibiotic treatment; 32% were inappropriately treated with antibiotics.

In multivariate analysis, older patient age, predominance of gram-negative bacteria, and higher urine white blood cell count were significantly associated with inappropriate treatment.

This study highlights the fact that antibiotics continue to be used inappropriately in patients with catheters. Current guidelines do not distinguish well between asymptomatic bacteriuria and UTI, so there might be a knowledge gap. This study was based on urine culture data, not urinalysis of all patients with a catheter, so the symptomatic patients were likely over-represented.

An associated editorial observes that the study extrapolates data from studies that involved patients with uncomplicated UTIs and, therefore, might reach erroneous conclusions. Further, viewing catheter-associated symptomatic UTIs and catheter-associated asymptomatic bactiuria as dichotomous and warranting inherently different management fails to encompass a number of clinical factors, including co-infection, and further fails to acknowledge that removal of the catheter is the first step in treatment. However, the finding that antibiotics continue to be used inappropriately is useful.

Bottom line: A clinical determination of whether a patient with a catheter really has a symptomatic UTI/urosepsis or only has asymptomatic bacteriuria should precede starting antibiotics in hospitalized patients.

Citations: Cope M, Cevallos ME, Cadle RM, Darouiche RO, Musher DM, Trautner BW. Inappropriate treatment of catheter-associated asymptomatic bateriuria in a tertiary care hospital. Clin Infect Dis. 2009;48(9):1182-1188.

Kunin CM. Catheter-associated urinary tract infections: a syllogism compounded by a questionable dichotomy. Clin Infect Dis. 2009;48:1189-1190.

Current Practices in the Evaluation and Management of Thrombocytopenia in Heparin Patients

Clinical question: Are the current American College of Chest Physicians (ACCP) guidelines for the recognition, treatment, and prevention of heparin-induced thrombocytopenia (HIT) being followed?

Background: Heparin-based anticoagulation is frequently given to hospitalized patients, and approximately 1% to 5% of these patients develop HIT. In 2004, the ACCP published a consensus statement on the evaluation, management, and prevention of HIT.

Study design: Prospective, observational study.

Setting: Forty-eight U.S. hospitals in the Complications After Thrombocytopenia Caused by Heparin (CATCH) registry.

Synopsis: The CATCH trial enrolled patients receiving any form of heparin for >96 hours (n=2,420), cardiac-care-unit patients treated with heparin (n=1,090), and patients who had an HIT antibody assay performed (n=449), for a total of 3,536 total patients. The study included patients on unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Thrombocytopenia was defined at a platelet count <150,000, or a decrease of 50% when compared with admission.

In the prolonged heparin group, 36.4% of patients developed thrombocytopenia; however, HIT was suspected in only 19.8% of these high-risk patients. While physicians were more likely to consider HIT in the cardiac-care patients (37.6%), the diagnosis was considered>24 hours after the thrombocytopenia developed. Physicians often waited until after a thromboembolic complication occurred before evaluating for HIT. More often than not, preventive measures were missed (e.g., failing to check for HIT antibodies, continuing heparin after HIT was suspected).

Bottom line: Thrombocytopenia is a common occurrence in patients receiving heparin and, despite the risk of devastating complications from HIT, treatment infrequently conforms to the established guidelines.

Citation: Crespo EM, Oliveira GBF, Honeycutt EF, et al. Evaluation and management of thrombocytopenia and suspected heparin-induced thrombocytopenia in hospitalized patients: The Complications After Thrombocytopenia Caused by Heparin (CATCH) registry. Am Heart J. 2009;157(4):651-657. TH

PEDIATRIC HM LITerature

Epinephrine and Dexamethasone Alone Do Not Reduce Hospital Admissions in Infants with Bronchiolitis

By Mark Shen, MD

Clinical question: Does nebulized epinephrine, oral dexamethasone, or a combination of the two result in a decrease in hospital admissions when given in the ED to infants with bronchiolitis?

Background: Bronchiolitis is the most common lower-respiratory-tract infection of infancy. Rates of admission have climbed in the past two decades. Bronchodilators and corticosteroids are not routinely recommended, and the evidence surrounding epinephrine and dexamethasone has shown varying results.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Eight Canadian pediatric EDs.

Synopsis: Eight hundred infants ages six weeks to 12 months with a first episode of bronchiolitis were randomized to nebulized epinephrine and oral dexamethasone, epinephrine and oral placebo, dexamethasone and nebulized placebo, or oral and nebulized placebo. Epinephrine was delivered as two nebulizations 30 minutes apart, and dexamethasone was given as a 1 mg/kg oral dose, followed by five once-daily doses of 0.6 mg/kg. In unadjusted analysis, only the infants who received epinephrine and dexamethasone were less likely to be admitted to the hospital by day seven.

Limitations of this study include a small effect size and a non-statistically-significant difference between the epinephrine/dexamethasone group and placebo after statistical adjustment for multiple comparisons. Given that admission rates did not decrease in the epinephrine/placebo group and the dexamethasone/placebo group, this study supports national guidelines that do not recommend the routine use of these agents in bronchiolitis. The authors suggest that synergy between epinephrine and dexamethasone in bronchiolitis be further studied.

Bottom line: When given alone, epinephrine and dexamethasone do not reduce hospital admissions in infants with bronchiolitis.

Citation: Plint AC, Johnson DW, Patel H, et al. Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360(20):2079-2089.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

In This Edition

Literature at a Glance

A guide to this month’s studies

• PE and COPD exacerbations.
• Care bundles and readmission rates.
• Family history and VTE risk.
• Vasopressor choice and mortality in sepsis.
• Vitamin K use in overanticoagulation.
• Appropriate treatment of asymptomatic bacteriuria.
• Guideline adherence in thrombocytopenia.

Pulmonary Embolism Frequently Complicates COPD Exacerbations

Clinical question: What percentage of patients with acute chronic obstructive pulmonary disease (COPD) exacerbations has pulmonary emboli?

Background: As many as 30% of COPD exacerbations have no apparent precipitating event. Even in patients with evidence of a precipitating event, such as an upper-respiratory illness or increased environmental irritants, pulmonary emboli (PE) may coexist and warrant evaluation.

Study design: Literature review.

Setting: Multiple studies in Europe and the U.S.

Synopsis: This literature review included five studies to estimate the rate of PE in patients with a COPD exacerbation. Overall incidence of PE in COPD exacerbations was 19.9%, but of those patients requiring hospitalization, the incidence was as high as 25.5%. Incidence estimates varied based on interpretation of data that were missing or inconsistent between studies. Patients most commonly present with dyspnea, chest pain, hemoptysis, cough, and palpitations. Six percent of PE patients presented with syncope; no patients with an exacerbation without a PE presented with syncope.

Risk of mortality from PE is almost twice as high in patients with a COPD exacerbation compared with PE in other settings. A significant number of patients have PE without history or evidence of DVT, so in situ thrombosis is a significant factor. The interpretation of these results is limited by the heterogeneity of the study designs, and by the relatively low number of cases. Larger trials are necessary.

Bottom line: Pulmonary emboli are present in as many as 25% of all COPD exacerbations. Delay in diagnosis of PE in COPD patients affects morbidity and mortality. PE should be a consideration in many COPD exacerbations.

Citation: Rizkallah J, Man SF, Din DD. Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2009;135(3):786-793.

Targeted-Care Bundle Can Reduce ED Visits and Readmission Rates in High-Risk Elderly Patients

Clinical question: Can a care coordination bundle reduce length of stay (LOS), ED visits, or readmissions within 30 days of a hospital admission?

Background: Hospital-based care coordination interventions have shown mixed results in affecting LOS, post-discharge ED visits, and readmission rates. Although there has been some success with particular interventions, no consistent benefit has been demonstrated. Most notably, a recent meta-analysis of several different interventions showed no improvement in mortality, LOS, or readmission rates.

Study design: A randomized, controlled trial of select high-risk elderly patients.

Setting: A large teaching hospital at Baylor University Medical Center.

Synopsis: A “targeted-care bundle” was implemented with high-risk elderly patients to try to reduce LOS, readmissions, and ED visits. High-risk patients were identified by age, diagnosis-related group (DRG), number of medications at admission, comorbid conditions, and need for assistance in activities of daily living. Subjects were randomized to usual care or to receive a targeted-care bundle. The targeted-care bundle included multiple interventions. A study care coordinator provided daily patient education, including condition-specific teaching, discharge teaching and planning, and a follow-up phone call at five to seven days after discharge. A clinical pharmacist intervened for medication reconciliation at admission and discharge, medication teaching, and a follow-up phone call at five to seven days after discharge. Structured documents, including a personal health record and supplemental discharge form, were implemented.

The study had low enrollment, largely due to the requirement to obtain informed consent from all participants. Therefore, the study was underpowered to detect such target endpoints as LOS. A significant decrease in 30-day readmission rates/ED visits was noticed, but there was no persistent effect at 60 days.

The intervention was designed to use existing hospital staff in order to be practical for broad utilization. Future studies need to focus on increased enrollment to demonstrate beneficial effect.

Bottom line: Targeted health interventions focusing on education and coordination of care might effect some significant outcomes, most notably readmissions or ED visits within 30 days, but the nature of the clinical problem makes rigorous testing of interventions a challenge.

Citation: Kohler BE, Richter KM, Youngblood L, et al. Reduction of 30-day postdischarge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4(4):211-218.

Family History Is a Risk Factor for Venous Thrombosis

Clinical question: Is family history of additional value in predicting an individual’s risk of venous thrombosis once a genetic risk factor is identified?

Background: A positive family history of venous thrombosis might suggest the presence of genetic risk factors in a given family. However, it is not known whether family history is of additional significance—once a risk factor is identified—in predicting an individual’s risk for venous thrombosis.

Study design: Population-based, case-control study.

Setting: Participants in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study.

Synopsis: Recruitment, data collection, and blood samples were obtained from individuals in the MEGA study. Participants completed a questionnaire about risk factors for venous thrombosis and family history. A positive family history more than doubled the risk of venous thrombosis, and when more than one family member was affected, the risk increased fourfold. The risk for venous thrombosis increased 64 times for individuals who had a family history, genetic risk factor, and environmental risk factor when compared with those with a negative family history and no known risk factors.

The underreporting or overestimation of the prevalence of a positive family history might limit this study.

Bottom line: Family history is a risk indictor for a first venous thrombosis, despite the presence of other risk factors.

Citation: Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The value of family history as a risk indicator for venous thrombosis. Arch Intern Med. 2009;169(6):610-615.

Vasopressor Choice Predicts Mortality in Septic Shock

Clinical question: Does vasopressor choice affect mortality in patients with community-acquired septic shock?

Background: Community-acquired septic shock is a common illness and, despite aggressive care, a leading cause of death. Randomized clinical control trials evaluating the efficacy and safety of different adrenergic supportive agents are lacking. Thus, both norepinephrine and dopamine are recommended as first-line agents in the treatment of septic shock by the Surviving Sepsis Campaign guidelines.

Study design: Multicenter, cohort observational study.

Setting: Seventeen intensive-care units in Portugal.

Synopsis: In adjusted analysis controlling for Simplified Acute Physiology Score (SAPS) II, use of norepinephrine in community-acquired septic shock was associated with higher hospital mortality and lower 28-day survival when compared with dopamine. Specifically, patients treated with norepinephrine had a statistically significant higher hospital mortality rate than those treated with dopamine (52% and 38.5%, respectively, P=0.002) and a lower 28-day survival (log rank=22.6; P<0.001). While this data is valuable, the nonrandomized, observational study design limits firm conclusions regarding vasopressor choice. Further results from three large trials comparing vasopressor use in septic shock should continue to shed light on this debate.

Bottom line: Norepinephrine administration is associated with higher hospital mortality and lower 28-day survival when compared with dopamine in patients with community-acquired septic shock.

Citation: Póvoa PR, Carneiro AH, Ribeiro OS, Pereira AC, Portuguese Community-Acquired Sepsis Study Group. Influence of vasopressor agent in septic shock mortality. Results from the Portuguese Community-Acquired Sepsis Study (SACiUCI study). Crit Care Med. 2009;37(2):410-416.

Oral Vitamin K Versus Placebo to Correct Excess Anticoagulation in Warfarin Patients

Clinical question: In nonbleeding patients with warfarin-associated coagulopathy, does oral vitamin K reduce bleeding events when compared to placebo?

Background: Warfarin is a common drug for primary and secondary prevention of thromboembolism, but it requires continued monitoring of the international normalized ratio (INR) value. INR values >4.0 are associated with an increase in bleeding complications, with specific concern for intracranial bleeding when INR values exceed 4.5. Small, randomized trials have shown that single, low-dose administration of oral vitamin K effectively reduces the INR in nonbleeding, overanticoagulated patients.

However, these studies have not shown if vitamin K reduces risk for bleeding without increasing the risk for thromboembolism.

Study design: Randomized, placebo-controlled trial.

Setting: Fourteen anticoagulation clinics in Canada, Italy, and the U.S.

Synopsis: Nonbleeding patients with supratherapeutic INR values between 4.5 and 10.0 were randomly assigned to receive 1.25 mg of oral vitamin K or placebo, then evaluated for all forms of bleeding for 90 days. Bleeding events were defined as “major bleeding,” “minor bleeding,” and “trivial bleeding.”

Though patients who received oral vitamin K had a significantly more rapid INR decrease, there were no differences between the two groups with regard to all bleeding events, thromboembolism, or death. The study was underpowered to detect differences in major bleeding.

Bottom line: Low-dose oral vitamin K leads to more rapid correction of the INR in overanticoagulated patients on warfarin therapy, but has little effect on clinical outcomes at 90 days.

Citation: Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med. 2009;150(5):293-300.

Inappropriate Treatment of Catheter-Associated Asymptomatic Bacteriuria

Clinical question: Are hospitalized patients with urinary catheters inappropriately treated with antibiotics for asymptomatic bacteriuria?

Background: Persons with catheters acquire bacteriuria at the rate of 3% to 10% per day, but in the majority of cases, no symptoms or secondary complications occur. Evidenced-based guidelines state that asymptomatic bacteriuria is not a clinically significant infection, and numerous studies have shown that treatment is unlikely to confer clinical benefit.

Study design: Retrospective cohort study.

Setting: A single-site Veterans Affairs hospital.

Synopsis: Using urine culture results over a three-month period from a single VA medical center, 280 cases were analyzed: 164 catheter-associated asymptomatic bacteriuria and 116 catheter-associated urinary tract infections (UTIs). A UTI was defined as having one or more of these symptoms: fever, urgency, frequency, dysuria, suprapubic tenderness, altered mental status, or hypotension in a patient without another recognized infection and a positive urine culture. Of the asymptomatic bacteriuria cases, 68% were managed appropriately with no antibiotic treatment; 32% were inappropriately treated with antibiotics.

In multivariate analysis, older patient age, predominance of gram-negative bacteria, and higher urine white blood cell count were significantly associated with inappropriate treatment.

This study highlights the fact that antibiotics continue to be used inappropriately in patients with catheters. Current guidelines do not distinguish well between asymptomatic bacteriuria and UTI, so there might be a knowledge gap. This study was based on urine culture data, not urinalysis of all patients with a catheter, so the symptomatic patients were likely over-represented.

An associated editorial observes that the study extrapolates data from studies that involved patients with uncomplicated UTIs and, therefore, might reach erroneous conclusions. Further, viewing catheter-associated symptomatic UTIs and catheter-associated asymptomatic bactiuria as dichotomous and warranting inherently different management fails to encompass a number of clinical factors, including co-infection, and further fails to acknowledge that removal of the catheter is the first step in treatment. However, the finding that antibiotics continue to be used inappropriately is useful.

Bottom line: A clinical determination of whether a patient with a catheter really has a symptomatic UTI/urosepsis or only has asymptomatic bacteriuria should precede starting antibiotics in hospitalized patients.

Citations: Cope M, Cevallos ME, Cadle RM, Darouiche RO, Musher DM, Trautner BW. Inappropriate treatment of catheter-associated asymptomatic bateriuria in a tertiary care hospital. Clin Infect Dis. 2009;48(9):1182-1188.

Kunin CM. Catheter-associated urinary tract infections: a syllogism compounded by a questionable dichotomy. Clin Infect Dis. 2009;48:1189-1190.

Current Practices in the Evaluation and Management of Thrombocytopenia in Heparin Patients

Clinical question: Are the current American College of Chest Physicians (ACCP) guidelines for the recognition, treatment, and prevention of heparin-induced thrombocytopenia (HIT) being followed?

Background: Heparin-based anticoagulation is frequently given to hospitalized patients, and approximately 1% to 5% of these patients develop HIT. In 2004, the ACCP published a consensus statement on the evaluation, management, and prevention of HIT.

Study design: Prospective, observational study.

Setting: Forty-eight U.S. hospitals in the Complications After Thrombocytopenia Caused by Heparin (CATCH) registry.

Synopsis: The CATCH trial enrolled patients receiving any form of heparin for >96 hours (n=2,420), cardiac-care-unit patients treated with heparin (n=1,090), and patients who had an HIT antibody assay performed (n=449), for a total of 3,536 total patients. The study included patients on unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Thrombocytopenia was defined at a platelet count <150,000, or a decrease of 50% when compared with admission.

In the prolonged heparin group, 36.4% of patients developed thrombocytopenia; however, HIT was suspected in only 19.8% of these high-risk patients. While physicians were more likely to consider HIT in the cardiac-care patients (37.6%), the diagnosis was considered>24 hours after the thrombocytopenia developed. Physicians often waited until after a thromboembolic complication occurred before evaluating for HIT. More often than not, preventive measures were missed (e.g., failing to check for HIT antibodies, continuing heparin after HIT was suspected).

Bottom line: Thrombocytopenia is a common occurrence in patients receiving heparin and, despite the risk of devastating complications from HIT, treatment infrequently conforms to the established guidelines.

Citation: Crespo EM, Oliveira GBF, Honeycutt EF, et al. Evaluation and management of thrombocytopenia and suspected heparin-induced thrombocytopenia in hospitalized patients: The Complications After Thrombocytopenia Caused by Heparin (CATCH) registry. Am Heart J. 2009;157(4):651-657. TH

PEDIATRIC HM LITerature

Epinephrine and Dexamethasone Alone Do Not Reduce Hospital Admissions in Infants with Bronchiolitis

By Mark Shen, MD

Clinical question: Does nebulized epinephrine, oral dexamethasone, or a combination of the two result in a decrease in hospital admissions when given in the ED to infants with bronchiolitis?

Background: Bronchiolitis is the most common lower-respiratory-tract infection of infancy. Rates of admission have climbed in the past two decades. Bronchodilators and corticosteroids are not routinely recommended, and the evidence surrounding epinephrine and dexamethasone has shown varying results.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Eight Canadian pediatric EDs.

Synopsis: Eight hundred infants ages six weeks to 12 months with a first episode of bronchiolitis were randomized to nebulized epinephrine and oral dexamethasone, epinephrine and oral placebo, dexamethasone and nebulized placebo, or oral and nebulized placebo. Epinephrine was delivered as two nebulizations 30 minutes apart, and dexamethasone was given as a 1 mg/kg oral dose, followed by five once-daily doses of 0.6 mg/kg. In unadjusted analysis, only the infants who received epinephrine and dexamethasone were less likely to be admitted to the hospital by day seven.

Limitations of this study include a small effect size and a non-statistically-significant difference between the epinephrine/dexamethasone group and placebo after statistical adjustment for multiple comparisons. Given that admission rates did not decrease in the epinephrine/placebo group and the dexamethasone/placebo group, this study supports national guidelines that do not recommend the routine use of these agents in bronchiolitis. The authors suggest that synergy between epinephrine and dexamethasone in bronchiolitis be further studied.

Bottom line: When given alone, epinephrine and dexamethasone do not reduce hospital admissions in infants with bronchiolitis.

Citation: Plint AC, Johnson DW, Patel H, et al. Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360(20):2079-2089.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

In This Edition

• Cost sharing for prescription medications increases consumption of more costly healthcare services
• Community-acquired pneumonia core measures can lead to unintended consequences
• Prophylactic revascularization has no clear benefit for high-risk patients undergoing vascular surgery
• Aspirin resistance correlates with adverse clinical events
• Low-molecular-weight heparin appears to have greater efficacy as a prophylactic agent against deep-vein thrombosis and pulmonary embolism
• Antipsychotic medications appear to be associated with increased risk of death in demented patients
• Anticoagulation plus antiplatelet therapy fails to show benefit for peripheral arterial disease
• Transient atrial fibrillation following myocardial infarction increases the risk of recurrence and stroke

Do Incentives to Encourage Use of Certain Medications Affect Care?

Background: Insurers are increasingly using financial mechanisms to affect pharmaceutical usage. These practices may affect medication use and health outcomes in ways that are poorly defined and difficult to detect.

Study design: Literature review

Synopsis: There are numerous structures for drug-cost sharing, and this study evaluated co-payments, tiers/co-insurance, benefit caps, formulary limitations, and reference pricing strategies for their effect on prescription drug usage and healthcare outcomes.

Included articles varied widely in study design, making generalizable results difficult to isolate, and insurers may have instituted more than one cost-sharing mechanism simultaneously. Overall, for every 10% increase in cost sharing (via copayments or co-insurance) there was an associated 2%-6% decrease in prescription drug spending. Increasing consumer costs for medications clearly decreases usage.

Some studies demonstrated that the decrease in medication utilization was more pronounced for “nonessential” medications over “essential” medications. However, in specific chronic illnesses this is clearly associated with greater usage of inpatient and emergency medical services.

Cost sharing was also more likely to have adverse health consequences in vulnerable populations, particularly the elderly and poor. One in four Medicaid patients couldn’t fill at least one prescription in the past year, as opposed to one in 10 privately insured patients who couldn’t purchase one or more medications.

Further impact on healthcare consumption and outcomes may be masked because it is difficult to determine individual disease severity, and the effect on the more severely ill would be expected to be greater. These authors attempted to sort out a complex interaction between cost, consumption, and health, and they found important trends.

The goal of cost sharing is to align consumption more clearly with appropriate and economic products, thereby using cost sharing as a public health tool. The consequence of creating the incentives for ill patients to forego necessary treatments is a counterbalancing concern that is supported in some, but not all, of the literature.

Bottom line: Cost sharing for prescription medications decreases medication spending and utilization but disproportionately affects the disadvantaged and increases consumption of more costly healthcare services in patients with some chronic illnesses.

Citation: Goldman DP, Joyce GF, Zheng Y. Prescription drug cost sharing: associations with medication and medical utilization and spending and health. JAMA. 2007;298(1):61-69.

Does Antibiotic Requirement for Suspected CAP Increase Misdiagnosis?

Background: Early administration of antibiotics in community-acquired pneumonia (CAP) improves patient outcomes. The Infectious Disease Society of America instituted guidelines that recommend initiation of antibiotics to all patients with suspected CAP within four hours of triage, and some payors are using this as a quality measure affecting reimbursement. However, this incentive may cause premature diagnosis of CAP and overuse of antibiotics.

Study design: Retrospective chart review

Setting: A large, high-volume teaching hospital with more than 500 beds and more than 112,000 annual emergency department (ED) visits

Synopsis: Charts of all patients with an admitting diagnosis of CAP were reviewed over two six-month periods. The initial review was prior to initiation of a four-hour antibiotics rule; the second was after a financial incentive to initiate antibiotics within four hours of triage was initiated.

After initiation of the four-hour rule, of the patients with an admitting diagnosis of CAP, significantly more patients received antibiotics within four hours of triage (66% versus 54%). However, the number of patients with abnormal chest X-ray findings associated with the diagnosis of CAP decreased from 28.5% to 20.6%, and the proportion of patients with a discharge diagnosis of CAP decreased from 75.9% to 58.9%.

The authors also used two diagnostic paradigms to make an independent diagnosis of CAP based on chart data. With the less rigorous independent analysis 44.7% of patients actually had CAP prior to the four-hour rule, and this fell to 36% after the four-hour rule. Using a more rigorous definition, only 32.7% of patients actually had CAP prior to initiation of the four-hour rule, and this fell to 27%.

There was no difference in length of stay or ICU transfers between the two analysis periods. The authors concluded that a four-hour rule increases premature diagnosis of CAP, presumably because providers felt compelled to initiate antibiotics before they had complete clinical data.

This tendency was associated with misuse and overuse of antibiotics, and increased laboratory testing, such as blood cultures, which had to be obtained before antibiotics were initiated. The authors emphasized the importance of reimbursement-associated quality measures creating incentives to treat the right patients for the correct diagnosis, and the potential harmful consequences of applying a quality-driven protocol to the wrong patient.

They suggest a six-hour rule would decrease the misdiagnosis of CAP. They also feel eliminating a mandatory time frame and requiring only that the first dose of antibiotics be administered in the ED will further ameliorate these effects.

Bottom line: Mandatory administration of antibiotics to patients with suspected CAP within four hours of triage increases the percentage of patients who receive antibiotics within four hours, but also increases the rate of misdiagnosis of CAP, inappropriate administration of antibiotics, and increased use of some laboratory services.

Citation: Kanwar M, Brar N, Khatib R, et al. Misdiagnosis of community-acquired pneumonia and inappropriate utilization of antibiotics: side effects of the 4-hour antibiotic administration rule. Chest. 2007 Jun;131(6):1865-1869.

Does prophylactic cardiac revascularization benefit patients undergoing vascular surgery?

Background: American College of Cardiology/American Heart Association Guidelines recommend referral for patients with multiple cardiac risk factors for non-invasive cardiac stress testing prior to surgery and prophylactic revascularization in high-risk patients. The authors performed a pilot analysis to determine how many patients would be needed to prospectively validate this recommendation in those with more significant ischemic cardiac disease.

Study design: Randomized controlled pilot study of 1,880 consecutive patients undergoing elective vascular surgery

Setting: Brazil, Belgium, the Netherlands, Italy, Serbia, and Montenegro

Synopsis: This was a pilot study to determine the necessary power to prove or disprove the benefit of the recommendation for cardiac revascularization in high-risk patients before major vascular surgery.

Prior research had shown that prophylactic revascularization is not of demonstrable benefit in this cohort. However, the majority of the patients in this previous trial had two-vessel disease and preserved left ventricular function. This study examined a sicker cohort of patients with more significant coronary artery disease and depressed left ventricular function.

This pilot screened all patients undergoing high-risk vascular surgery. All patients with three or more risk factors underwent non-invasive evaluation for cardiac ischemia. Patients with extensive ischemia were randomized to invasive evaluation and revascularization as appropriate or non-invasive management. Both arms received optimal medical management.

Prophylactic revascularization did not improve 30-day outcome after vascular surgery, demonstrated no difference in perioperative cardiac events, and found no difference in all-cause mortality or nonfatal myocardial infarction. Similarly, there was no evidence of long-term (at one year) difference between groups. The sample size needed to definitively establish that coronary revascularization is superior to medical therapy would be 300 patients per arm. That would require screening 9,000 patients.

Bottom line: Prophylactic revascularization has no clear benefit for high-risk patients undergoing vascular surgery, but a much larger sample size would be required to definitively prove or disprove benefit.

Citation: Poldermans D, Schouten O, Vidakovic R, et al. Clinical randomized trial to evaluate the safety of a noninvasive approach in high-risk patients undergoing major vascular surgery: the DECREASE-V pilot study. J. Am Coll Cardiol. 2007;49(17):1763-1769.

How Does Aspirin Resistance Affect Patients with Coronary Artery Disease?

Background: Although aspirin is used to decrease the risk of ischemic events, up to 45% of patients do not derive adequate anti-platelet activity. Few prospective studies have used laboratory-measured aspirin resistance to assess clinical outcomes.

Study design: Blinded cohort

Setting: Patients affiliated with Queen Mary Hospital, the University of Hong Kong.

Synopsis: Aspirin-induced platelet inhibition was measured quantitatively on 468 patients with stable coronary artery disease who take 80-325 mg of aspirin per day. The study found 128 patients were aspirin resistant. Aspirin resistance was more prevalent with increased age, female gender, renal insufficiency, anemia, and with use of low-dose aspirin. At follow up, aspirin-resistant patients were more likely to develop a primary outcome event: cardiovascular deaths, myocardial infarction, stroke, transient ischemic attack, and unstable angina. Aspirin resistance was an independent risk factor for developing the aforementioned outcomes, as are diabetes, prior myocardial infarction, and low hemoglobin.

Bottom line: Aspirin resistance, as defined by an aggregation-based assay, is associated with adverse outcomes in patients with stable coronary artery disease.

Citation: Chen W, Cheng X, Lee PY, et al. Aspirin resistance and adverse clinical events in patients with coronary artery disease. Am J Med. 2007 Jul;120(7):631-635.

Which Agents Best Prevent Venous Thromboembolism?

Background: Pulmonary emboli have been linked to 10% of in-hospital deaths. There continues to be a strong emphasis on prevention. Unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and selective factor Xa inhibitors are used for prophylaxis.

Study design: A meta-analysis of randomized controlled trials

Synopsis: The meta-analysis included 36 studies of hospitalized medical patients that compared UFH with control, LMWH with control, LMWH with UFH, and a selective factor Xa inhibitor with a placebo.

When each was compared with a control, UFH and LMWH were associated with a decreased risk of deep venous thrombosis (DVT) (risk ratio=0.33; 0.56) and pulmonary embolism (PE) (risk ratio=0.64; 0.37). Compared with control, LMWH three times daily was more effective than twice-daily dosing (risk ratio=0.27, 0.52). Through direct comparison of UFH and LMWH, LMWH was shown to have decreased DVT risk (risk ratio=0.68) and fewer injection site hematomas (risk ratio=0.47).

Neither UFH nor LMWH reduced mortality. LMWH and UFH were associated with significantly more bleeding events than control, but this increased risk was significant only for minor bleeding.

Bottom line: LMWH appears to have greater efficacy than UFH as a prophylactic agent against DVT/PE. If UFH is used, three times daily dosing is preferred.

Citation: Wein L, Wein S, Haas SJ, et al. Pharmacological venous thromboembolism prophylaxis in hospitalized medical patients. Arch Intern Med. 2007;167(14):1476-1486.

What Is the Association Between Antipsychotic Drugs and Mortality?

Background: Atypical antipsychotics prescribed off-label for problematic behaviors in dementia have been associated with risks including diabetes, stroke, and increased mortality. This resulted in the FDA placing a “black box” warning on atypical antipsychotics used for dementia. Subsequent studies have suggested that conventional antipsychotics are perhaps even more problematic.

Study Design: Retrospective cohort study

Synopsis: This trial found a small but significant increase in the risk of death in patients taking an antipsychotic medication.

The adjusted hazard ratio for death with the use of atypical antipsychotics in community dwelling patients with dementia was 1.3 (confidence interval 1.02-1.70). Similar to prior research, the authors found that conventional antipsychotics carried a higher risk than atypical agents.

Patients in long-term care settings also suffered increased risk compared with community dwelling patients. Interestingly, the increased risk of death was apparent after as little as a month of treatment.

As with all retrospective observational cohort trials, there remains the risk that an unanticipated confounding factor could skew the data and create a false association. However, the findings of this research support prior concerns that antipsychotics carry risk of increased mortality. This research bolsters the argument that these agents should not be used lightly or without full discussion of risks and benefits with the patient and/or proxy.

Bottom line: Antipsychotic agents used in patients with dementia may create increased risk of death. Potential benefit needs to be carefully weighted against this serious harm.

Citation: Gill S, Bronskill SE, Normand SL, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007 June 5;146(11):775-786.

Does Combination Therapy Help Prevent Serious Vascular Ischemic Events?

Background: Peripheral arterial disease (PAD) manifests as claudication and limb ischemia affecting 8.5 million Americans. Atherosclerotic disease in the periphery also reflects increased risk for ischemic events in the coronary and cranial circulations. Both antiplatelet agents and anticoagulation will decrease the probability of thrombus formation, although this must be weighed against bleeding risk.

Study design: Randomized, open-label, multicenter trial

Setting: Eighty centers in Europe, Asia, Australia, and North America

Synopsis: This trial randomized more than 2,000 patients with PAD to treatment with antiplatelet therapy (aspirin, ticlopidine, or clopidogrel) with or without additional anticoagulation.

During the next 3.5 years serious vascular events occurred at approximately the same rate in both combination and monotherapy groups (15.9% versus 17.4%, p=0.37). There was no significant difference between the occurrence of the composite ischemic endpoints or any of the individual endpoints. There was, however, a significantly higher rate of both moderate and life-threatening bleeding in the combination therapy group.

The 4% risk of life-threatening hemorrhage in the combination group exceeded the 1.2% rate of the monotherapy group creating a relative risk for bleeding of 3.4.

This trial demonstrates that for patients with PAD on antiplatelet therapy, the increased rate of bleeding without significant added benefit makes addition of warfarin inadvisable.1 Evidence of utility of combination therapy from studies in other arterial systems provides mixed results.2-4 Based on the results of this study, combination therapy cannot be advocated if the primary symptoms are from PAD.

Bottom line: This study provides further evidence that more is not always better when it comes to preventing thrombosis and ischemia in the peripheral arterial system. Antiplatelet agents are preferable for PAD to combination antiplatelet plus anticoagulation.

Citations:

1. The Warfarin Antiplatelet Vascular Evaluation Trial Investigators. Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med. 2007 Jul 19;357(3):217-227.
2. Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002 Sep 26;347(13):969-974.
3. Mohr JP, Thompson JL, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001 Nov 15;345(20):1444-1451.
4. The ESPRIT Study Group. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a ran­dom­ised controlled trial. Lancet Neurol. 2007 Feb;6:115-124.

Does Transient Atrial Fibrillation Increase Stroke Risk After ST-Elevation Myocardial Infarction?

Background: Prior research has demonstrated that 2.1% of patients will suffer a stroke in the year following a heart attack. Persistent and paroxysmal atrial fibrillation (AF) are well recognized as risk factors for stroke, but the significance of transient ischemia-induced AF is less clear.

Study design: Retrospective cohort study

Setting: Queen Mary Hospital, Hong Kong

Synopsis: The study involved patients admitted for acute inferior ST-segment-elevation myocardial infarction (MI) with preserved left ventricular ejection fraction.

Transient AF that had converted back to normal sinus rhythm by discharge was observed in 14% of patients after the MI. Over the next three years the transient AF patients were 15 times more likely than those who remained in sinus rhythm during the index hospitalization to have recurrent AF (34% versus 2%). Despite antiplatelet therapy in both groups, ischemic stroke developed in 22% of patients who had transient AF following their MI, compared with only 4% in patients who did not (HR 5.1, confidence interval 2.4-11.2). Cerebrovascular accidents generally occurred simultaneously with recurrence of paroxysmal AF.1-2

The finding that patients with transient-ischemia-induced AF represents a group with markedly higher risk of ischemic stroke is compelling. It suggests that these patients may be candidates for combined antiplatelet and anticoagulant therapy. Trials of combined therapy following MI demonstrate that this strategy reduces the rate of recurrent cardiac ischemia, stroke, or death but does carry significantly increased risk of bleeding.3-4

Bottom line: The presence of transient AF following MI represents a significant risk factor for the development of subsequent paroxysmal AF. These patients have a five-fold increased risk of ischemic stroke over the next three years and should be considered for combined antiplatelet and anticoagulant therapy.

Citations:

1. Chung-Wah S, Man-Hong J, Hee-Hwa H, et al. Transient atrial fibrillation complicating acute inferior myocardial infarction: implications for future risk of ischemic stroke. Chest. 2007 Mar 30;132(1):44-49.
2. Witt BJ, Ballman KV, Brown RD Jr., Meverden RA, Jacobsen SJ, Roger VL. The incidence of stroke after myocardial infarction: a meta-analysis. Am J. Med. 2006;119(4):354 e1-9.
3. Van Es RF, Jonker J, Verheugt F, et al. Aspirin and Coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet. 2002 Jul 13;360(9327):109-113.
4. Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002 Sep 26;347(13):969-974. TH

In This Edition

• Cost sharing for prescription medications increases consumption of more costly healthcare services
• Community-acquired pneumonia core measures can lead to unintended consequences
• Prophylactic revascularization has no clear benefit for high-risk patients undergoing vascular surgery
• Aspirin resistance correlates with adverse clinical events
• Low-molecular-weight heparin appears to have greater efficacy as a prophylactic agent against deep-vein thrombosis and pulmonary embolism
• Antipsychotic medications appear to be associated with increased risk of death in demented patients
• Anticoagulation plus antiplatelet therapy fails to show benefit for peripheral arterial disease
• Transient atrial fibrillation following myocardial infarction increases the risk of recurrence and stroke

Do Incentives to Encourage Use of Certain Medications Affect Care?

Background: Insurers are increasingly using financial mechanisms to affect pharmaceutical usage. These practices may affect medication use and health outcomes in ways that are poorly defined and difficult to detect.

Study design: Literature review

Synopsis: There are numerous structures for drug-cost sharing, and this study evaluated co-payments, tiers/co-insurance, benefit caps, formulary limitations, and reference pricing strategies for their effect on prescription drug usage and healthcare outcomes.

Included articles varied widely in study design, making generalizable results difficult to isolate, and insurers may have instituted more than one cost-sharing mechanism simultaneously. Overall, for every 10% increase in cost sharing (via copayments or co-insurance) there was an associated 2%-6% decrease in prescription drug spending. Increasing consumer costs for medications clearly decreases usage.

Some studies demonstrated that the decrease in medication utilization was more pronounced for “nonessential” medications over “essential” medications. However, in specific chronic illnesses this is clearly associated with greater usage of inpatient and emergency medical services.

Cost sharing was also more likely to have adverse health consequences in vulnerable populations, particularly the elderly and poor. One in four Medicaid patients couldn’t fill at least one prescription in the past year, as opposed to one in 10 privately insured patients who couldn’t purchase one or more medications.

Further impact on healthcare consumption and outcomes may be masked because it is difficult to determine individual disease severity, and the effect on the more severely ill would be expected to be greater. These authors attempted to sort out a complex interaction between cost, consumption, and health, and they found important trends.

The goal of cost sharing is to align consumption more clearly with appropriate and economic products, thereby using cost sharing as a public health tool. The consequence of creating the incentives for ill patients to forego necessary treatments is a counterbalancing concern that is supported in some, but not all, of the literature.

Bottom line: Cost sharing for prescription medications decreases medication spending and utilization but disproportionately affects the disadvantaged and increases consumption of more costly healthcare services in patients with some chronic illnesses.

Citation: Goldman DP, Joyce GF, Zheng Y. Prescription drug cost sharing: associations with medication and medical utilization and spending and health. JAMA. 2007;298(1):61-69.

Does Antibiotic Requirement for Suspected CAP Increase Misdiagnosis?

Background: Early administration of antibiotics in community-acquired pneumonia (CAP) improves patient outcomes. The Infectious Disease Society of America instituted guidelines that recommend initiation of antibiotics to all patients with suspected CAP within four hours of triage, and some payors are using this as a quality measure affecting reimbursement. However, this incentive may cause premature diagnosis of CAP and overuse of antibiotics.

Study design: Retrospective chart review

Setting: A large, high-volume teaching hospital with more than 500 beds and more than 112,000 annual emergency department (ED) visits

Synopsis: Charts of all patients with an admitting diagnosis of CAP were reviewed over two six-month periods. The initial review was prior to initiation of a four-hour antibiotics rule; the second was after a financial incentive to initiate antibiotics within four hours of triage was initiated.

After initiation of the four-hour rule, of the patients with an admitting diagnosis of CAP, significantly more patients received antibiotics within four hours of triage (66% versus 54%). However, the number of patients with abnormal chest X-ray findings associated with the diagnosis of CAP decreased from 28.5% to 20.6%, and the proportion of patients with a discharge diagnosis of CAP decreased from 75.9% to 58.9%.

The authors also used two diagnostic paradigms to make an independent diagnosis of CAP based on chart data. With the less rigorous independent analysis 44.7% of patients actually had CAP prior to the four-hour rule, and this fell to 36% after the four-hour rule. Using a more rigorous definition, only 32.7% of patients actually had CAP prior to initiation of the four-hour rule, and this fell to 27%.

There was no difference in length of stay or ICU transfers between the two analysis periods. The authors concluded that a four-hour rule increases premature diagnosis of CAP, presumably because providers felt compelled to initiate antibiotics before they had complete clinical data.

This tendency was associated with misuse and overuse of antibiotics, and increased laboratory testing, such as blood cultures, which had to be obtained before antibiotics were initiated. The authors emphasized the importance of reimbursement-associated quality measures creating incentives to treat the right patients for the correct diagnosis, and the potential harmful consequences of applying a quality-driven protocol to the wrong patient.

They suggest a six-hour rule would decrease the misdiagnosis of CAP. They also feel eliminating a mandatory time frame and requiring only that the first dose of antibiotics be administered in the ED will further ameliorate these effects.

Bottom line: Mandatory administration of antibiotics to patients with suspected CAP within four hours of triage increases the percentage of patients who receive antibiotics within four hours, but also increases the rate of misdiagnosis of CAP, inappropriate administration of antibiotics, and increased use of some laboratory services.

Citation: Kanwar M, Brar N, Khatib R, et al. Misdiagnosis of community-acquired pneumonia and inappropriate utilization of antibiotics: side effects of the 4-hour antibiotic administration rule. Chest. 2007 Jun;131(6):1865-1869.

Does prophylactic cardiac revascularization benefit patients undergoing vascular surgery?

Background: American College of Cardiology/American Heart Association Guidelines recommend referral for patients with multiple cardiac risk factors for non-invasive cardiac stress testing prior to surgery and prophylactic revascularization in high-risk patients. The authors performed a pilot analysis to determine how many patients would be needed to prospectively validate this recommendation in those with more significant ischemic cardiac disease.

Study design: Randomized controlled pilot study of 1,880 consecutive patients undergoing elective vascular surgery

Setting: Brazil, Belgium, the Netherlands, Italy, Serbia, and Montenegro

Synopsis: This was a pilot study to determine the necessary power to prove or disprove the benefit of the recommendation for cardiac revascularization in high-risk patients before major vascular surgery.

Prior research had shown that prophylactic revascularization is not of demonstrable benefit in this cohort. However, the majority of the patients in this previous trial had two-vessel disease and preserved left ventricular function. This study examined a sicker cohort of patients with more significant coronary artery disease and depressed left ventricular function.

This pilot screened all patients undergoing high-risk vascular surgery. All patients with three or more risk factors underwent non-invasive evaluation for cardiac ischemia. Patients with extensive ischemia were randomized to invasive evaluation and revascularization as appropriate or non-invasive management. Both arms received optimal medical management.

Prophylactic revascularization did not improve 30-day outcome after vascular surgery, demonstrated no difference in perioperative cardiac events, and found no difference in all-cause mortality or nonfatal myocardial infarction. Similarly, there was no evidence of long-term (at one year) difference between groups. The sample size needed to definitively establish that coronary revascularization is superior to medical therapy would be 300 patients per arm. That would require screening 9,000 patients.

Bottom line: Prophylactic revascularization has no clear benefit for high-risk patients undergoing vascular surgery, but a much larger sample size would be required to definitively prove or disprove benefit.

Citation: Poldermans D, Schouten O, Vidakovic R, et al. Clinical randomized trial to evaluate the safety of a noninvasive approach in high-risk patients undergoing major vascular surgery: the DECREASE-V pilot study. J. Am Coll Cardiol. 2007;49(17):1763-1769.

How Does Aspirin Resistance Affect Patients with Coronary Artery Disease?

Background: Although aspirin is used to decrease the risk of ischemic events, up to 45% of patients do not derive adequate anti-platelet activity. Few prospective studies have used laboratory-measured aspirin resistance to assess clinical outcomes.

Study design: Blinded cohort

Setting: Patients affiliated with Queen Mary Hospital, the University of Hong Kong.

Synopsis: Aspirin-induced platelet inhibition was measured quantitatively on 468 patients with stable coronary artery disease who take 80-325 mg of aspirin per day. The study found 128 patients were aspirin resistant. Aspirin resistance was more prevalent with increased age, female gender, renal insufficiency, anemia, and with use of low-dose aspirin. At follow up, aspirin-resistant patients were more likely to develop a primary outcome event: cardiovascular deaths, myocardial infarction, stroke, transient ischemic attack, and unstable angina. Aspirin resistance was an independent risk factor for developing the aforementioned outcomes, as are diabetes, prior myocardial infarction, and low hemoglobin.

Bottom line: Aspirin resistance, as defined by an aggregation-based assay, is associated with adverse outcomes in patients with stable coronary artery disease.

Citation: Chen W, Cheng X, Lee PY, et al. Aspirin resistance and adverse clinical events in patients with coronary artery disease. Am J Med. 2007 Jul;120(7):631-635.

Which Agents Best Prevent Venous Thromboembolism?

Background: Pulmonary emboli have been linked to 10% of in-hospital deaths. There continues to be a strong emphasis on prevention. Unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and selective factor Xa inhibitors are used for prophylaxis.

Study design: A meta-analysis of randomized controlled trials

Synopsis: The meta-analysis included 36 studies of hospitalized medical patients that compared UFH with control, LMWH with control, LMWH with UFH, and a selective factor Xa inhibitor with a placebo.

When each was compared with a control, UFH and LMWH were associated with a decreased risk of deep venous thrombosis (DVT) (risk ratio=0.33; 0.56) and pulmonary embolism (PE) (risk ratio=0.64; 0.37). Compared with control, LMWH three times daily was more effective than twice-daily dosing (risk ratio=0.27, 0.52). Through direct comparison of UFH and LMWH, LMWH was shown to have decreased DVT risk (risk ratio=0.68) and fewer injection site hematomas (risk ratio=0.47).

Neither UFH nor LMWH reduced mortality. LMWH and UFH were associated with significantly more bleeding events than control, but this increased risk was significant only for minor bleeding.

Bottom line: LMWH appears to have greater efficacy than UFH as a prophylactic agent against DVT/PE. If UFH is used, three times daily dosing is preferred.

Citation: Wein L, Wein S, Haas SJ, et al. Pharmacological venous thromboembolism prophylaxis in hospitalized medical patients. Arch Intern Med. 2007;167(14):1476-1486.

What Is the Association Between Antipsychotic Drugs and Mortality?

Background: Atypical antipsychotics prescribed off-label for problematic behaviors in dementia have been associated with risks including diabetes, stroke, and increased mortality. This resulted in the FDA placing a “black box” warning on atypical antipsychotics used for dementia. Subsequent studies have suggested that conventional antipsychotics are perhaps even more problematic.

Study Design: Retrospective cohort study

Synopsis: This trial found a small but significant increase in the risk of death in patients taking an antipsychotic medication.

The adjusted hazard ratio for death with the use of atypical antipsychotics in community dwelling patients with dementia was 1.3 (confidence interval 1.02-1.70). Similar to prior research, the authors found that conventional antipsychotics carried a higher risk than atypical agents.

Patients in long-term care settings also suffered increased risk compared with community dwelling patients. Interestingly, the increased risk of death was apparent after as little as a month of treatment.

As with all retrospective observational cohort trials, there remains the risk that an unanticipated confounding factor could skew the data and create a false association. However, the findings of this research support prior concerns that antipsychotics carry risk of increased mortality. This research bolsters the argument that these agents should not be used lightly or without full discussion of risks and benefits with the patient and/or proxy.

Bottom line: Antipsychotic agents used in patients with dementia may create increased risk of death. Potential benefit needs to be carefully weighted against this serious harm.

Citation: Gill S, Bronskill SE, Normand SL, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007 June 5;146(11):775-786.

Does Combination Therapy Help Prevent Serious Vascular Ischemic Events?

Background: Peripheral arterial disease (PAD) manifests as claudication and limb ischemia affecting 8.5 million Americans. Atherosclerotic disease in the periphery also reflects increased risk for ischemic events in the coronary and cranial circulations. Both antiplatelet agents and anticoagulation will decrease the probability of thrombus formation, although this must be weighed against bleeding risk.

Study design: Randomized, open-label, multicenter trial

Setting: Eighty centers in Europe, Asia, Australia, and North America

Synopsis: This trial randomized more than 2,000 patients with PAD to treatment with antiplatelet therapy (aspirin, ticlopidine, or clopidogrel) with or without additional anticoagulation.

During the next 3.5 years serious vascular events occurred at approximately the same rate in both combination and monotherapy groups (15.9% versus 17.4%, p=0.37). There was no significant difference between the occurrence of the composite ischemic endpoints or any of the individual endpoints. There was, however, a significantly higher rate of both moderate and life-threatening bleeding in the combination therapy group.

The 4% risk of life-threatening hemorrhage in the combination group exceeded the 1.2% rate of the monotherapy group creating a relative risk for bleeding of 3.4.

This trial demonstrates that for patients with PAD on antiplatelet therapy, the increased rate of bleeding without significant added benefit makes addition of warfarin inadvisable.1 Evidence of utility of combination therapy from studies in other arterial systems provides mixed results.2-4 Based on the results of this study, combination therapy cannot be advocated if the primary symptoms are from PAD.

Bottom line: This study provides further evidence that more is not always better when it comes to preventing thrombosis and ischemia in the peripheral arterial system. Antiplatelet agents are preferable for PAD to combination antiplatelet plus anticoagulation.

Citations:

1. The Warfarin Antiplatelet Vascular Evaluation Trial Investigators. Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med. 2007 Jul 19;357(3):217-227.
2. Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002 Sep 26;347(13):969-974.
3. Mohr JP, Thompson JL, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001 Nov 15;345(20):1444-1451.
4. The ESPRIT Study Group. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a ran­dom­ised controlled trial. Lancet Neurol. 2007 Feb;6:115-124.

Does Transient Atrial Fibrillation Increase Stroke Risk After ST-Elevation Myocardial Infarction?

Background: Prior research has demonstrated that 2.1% of patients will suffer a stroke in the year following a heart attack. Persistent and paroxysmal atrial fibrillation (AF) are well recognized as risk factors for stroke, but the significance of transient ischemia-induced AF is less clear.

Study design: Retrospective cohort study

Setting: Queen Mary Hospital, Hong Kong

Synopsis: The study involved patients admitted for acute inferior ST-segment-elevation myocardial infarction (MI) with preserved left ventricular ejection fraction.

Transient AF that had converted back to normal sinus rhythm by discharge was observed in 14% of patients after the MI. Over the next three years the transient AF patients were 15 times more likely than those who remained in sinus rhythm during the index hospitalization to have recurrent AF (34% versus 2%). Despite antiplatelet therapy in both groups, ischemic stroke developed in 22% of patients who had transient AF following their MI, compared with only 4% in patients who did not (HR 5.1, confidence interval 2.4-11.2). Cerebrovascular accidents generally occurred simultaneously with recurrence of paroxysmal AF.1-2

The finding that patients with transient-ischemia-induced AF represents a group with markedly higher risk of ischemic stroke is compelling. It suggests that these patients may be candidates for combined antiplatelet and anticoagulant therapy. Trials of combined therapy following MI demonstrate that this strategy reduces the rate of recurrent cardiac ischemia, stroke, or death but does carry significantly increased risk of bleeding.3-4

Bottom line: The presence of transient AF following MI represents a significant risk factor for the development of subsequent paroxysmal AF. These patients have a five-fold increased risk of ischemic stroke over the next three years and should be considered for combined antiplatelet and anticoagulant therapy.

Citations:

1. Chung-Wah S, Man-Hong J, Hee-Hwa H, et al. Transient atrial fibrillation complicating acute inferior myocardial infarction: implications for future risk of ischemic stroke. Chest. 2007 Mar 30;132(1):44-49.
2. Witt BJ, Ballman KV, Brown RD Jr., Meverden RA, Jacobsen SJ, Roger VL. The incidence of stroke after myocardial infarction: a meta-analysis. Am J. Med. 2006;119(4):354 e1-9.
3. Van Es RF, Jonker J, Verheugt F, et al. Aspirin and Coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet. 2002 Jul 13;360(9327):109-113.
4. Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002 Sep 26;347(13):969-974. TH

In This Edition

• Cost sharing for prescription medications increases consumption of more costly healthcare services
• Community-acquired pneumonia core measures can lead to unintended consequences
• Prophylactic revascularization has no clear benefit for high-risk patients undergoing vascular surgery
• Aspirin resistance correlates with adverse clinical events
• Low-molecular-weight heparin appears to have greater efficacy as a prophylactic agent against deep-vein thrombosis and pulmonary embolism
• Antipsychotic medications appear to be associated with increased risk of death in demented patients
• Anticoagulation plus antiplatelet therapy fails to show benefit for peripheral arterial disease
• Transient atrial fibrillation following myocardial infarction increases the risk of recurrence and stroke

Do Incentives to Encourage Use of Certain Medications Affect Care?

Background: Insurers are increasingly using financial mechanisms to affect pharmaceutical usage. These practices may affect medication use and health outcomes in ways that are poorly defined and difficult to detect.

Study design: Literature review

Synopsis: There are numerous structures for drug-cost sharing, and this study evaluated co-payments, tiers/co-insurance, benefit caps, formulary limitations, and reference pricing strategies for their effect on prescription drug usage and healthcare outcomes.

Included articles varied widely in study design, making generalizable results difficult to isolate, and insurers may have instituted more than one cost-sharing mechanism simultaneously. Overall, for every 10% increase in cost sharing (via copayments or co-insurance) there was an associated 2%-6% decrease in prescription drug spending. Increasing consumer costs for medications clearly decreases usage.

Some studies demonstrated that the decrease in medication utilization was more pronounced for “nonessential” medications over “essential” medications. However, in specific chronic illnesses this is clearly associated with greater usage of inpatient and emergency medical services.

Cost sharing was also more likely to have adverse health consequences in vulnerable populations, particularly the elderly and poor. One in four Medicaid patients couldn’t fill at least one prescription in the past year, as opposed to one in 10 privately insured patients who couldn’t purchase one or more medications.

Further impact on healthcare consumption and outcomes may be masked because it is difficult to determine individual disease severity, and the effect on the more severely ill would be expected to be greater. These authors attempted to sort out a complex interaction between cost, consumption, and health, and they found important trends.

The goal of cost sharing is to align consumption more clearly with appropriate and economic products, thereby using cost sharing as a public health tool. The consequence of creating the incentives for ill patients to forego necessary treatments is a counterbalancing concern that is supported in some, but not all, of the literature.

Bottom line: Cost sharing for prescription medications decreases medication spending and utilization but disproportionately affects the disadvantaged and increases consumption of more costly healthcare services in patients with some chronic illnesses.

Citation: Goldman DP, Joyce GF, Zheng Y. Prescription drug cost sharing: associations with medication and medical utilization and spending and health. JAMA. 2007;298(1):61-69.

Does Antibiotic Requirement for Suspected CAP Increase Misdiagnosis?

Background: Early administration of antibiotics in community-acquired pneumonia (CAP) improves patient outcomes. The Infectious Disease Society of America instituted guidelines that recommend initiation of antibiotics to all patients with suspected CAP within four hours of triage, and some payors are using this as a quality measure affecting reimbursement. However, this incentive may cause premature diagnosis of CAP and overuse of antibiotics.

Study design: Retrospective chart review

Setting: A large, high-volume teaching hospital with more than 500 beds and more than 112,000 annual emergency department (ED) visits

Synopsis: Charts of all patients with an admitting diagnosis of CAP were reviewed over two six-month periods. The initial review was prior to initiation of a four-hour antibiotics rule; the second was after a financial incentive to initiate antibiotics within four hours of triage was initiated.

After initiation of the four-hour rule, of the patients with an admitting diagnosis of CAP, significantly more patients received antibiotics within four hours of triage (66% versus 54%). However, the number of patients with abnormal chest X-ray findings associated with the diagnosis of CAP decreased from 28.5% to 20.6%, and the proportion of patients with a discharge diagnosis of CAP decreased from 75.9% to 58.9%.

The authors also used two diagnostic paradigms to make an independent diagnosis of CAP based on chart data. With the less rigorous independent analysis 44.7% of patients actually had CAP prior to the four-hour rule, and this fell to 36% after the four-hour rule. Using a more rigorous definition, only 32.7% of patients actually had CAP prior to initiation of the four-hour rule, and this fell to 27%.

There was no difference in length of stay or ICU transfers between the two analysis periods. The authors concluded that a four-hour rule increases premature diagnosis of CAP, presumably because providers felt compelled to initiate antibiotics before they had complete clinical data.

This tendency was associated with misuse and overuse of antibiotics, and increased laboratory testing, such as blood cultures, which had to be obtained before antibiotics were initiated. The authors emphasized the importance of reimbursement-associated quality measures creating incentives to treat the right patients for the correct diagnosis, and the potential harmful consequences of applying a quality-driven protocol to the wrong patient.

They suggest a six-hour rule would decrease the misdiagnosis of CAP. They also feel eliminating a mandatory time frame and requiring only that the first dose of antibiotics be administered in the ED will further ameliorate these effects.

Bottom line: Mandatory administration of antibiotics to patients with suspected CAP within four hours of triage increases the percentage of patients who receive antibiotics within four hours, but also increases the rate of misdiagnosis of CAP, inappropriate administration of antibiotics, and increased use of some laboratory services.

Citation: Kanwar M, Brar N, Khatib R, et al. Misdiagnosis of community-acquired pneumonia and inappropriate utilization of antibiotics: side effects of the 4-hour antibiotic administration rule. Chest. 2007 Jun;131(6):1865-1869.

Does prophylactic cardiac revascularization benefit patients undergoing vascular surgery?

Background: American College of Cardiology/American Heart Association Guidelines recommend referral for patients with multiple cardiac risk factors for non-invasive cardiac stress testing prior to surgery and prophylactic revascularization in high-risk patients. The authors performed a pilot analysis to determine how many patients would be needed to prospectively validate this recommendation in those with more significant ischemic cardiac disease.

Study design: Randomized controlled pilot study of 1,880 consecutive patients undergoing elective vascular surgery

Setting: Brazil, Belgium, the Netherlands, Italy, Serbia, and Montenegro

Synopsis: This was a pilot study to determine the necessary power to prove or disprove the benefit of the recommendation for cardiac revascularization in high-risk patients before major vascular surgery.

Prior research had shown that prophylactic revascularization is not of demonstrable benefit in this cohort. However, the majority of the patients in this previous trial had two-vessel disease and preserved left ventricular function. This study examined a sicker cohort of patients with more significant coronary artery disease and depressed left ventricular function.

This pilot screened all patients undergoing high-risk vascular surgery. All patients with three or more risk factors underwent non-invasive evaluation for cardiac ischemia. Patients with extensive ischemia were randomized to invasive evaluation and revascularization as appropriate or non-invasive management. Both arms received optimal medical management.

Prophylactic revascularization did not improve 30-day outcome after vascular surgery, demonstrated no difference in perioperative cardiac events, and found no difference in all-cause mortality or nonfatal myocardial infarction. Similarly, there was no evidence of long-term (at one year) difference between groups. The sample size needed to definitively establish that coronary revascularization is superior to medical therapy would be 300 patients per arm. That would require screening 9,000 patients.

Bottom line: Prophylactic revascularization has no clear benefit for high-risk patients undergoing vascular surgery, but a much larger sample size would be required to definitively prove or disprove benefit.

Citation: Poldermans D, Schouten O, Vidakovic R, et al. Clinical randomized trial to evaluate the safety of a noninvasive approach in high-risk patients undergoing major vascular surgery: the DECREASE-V pilot study. J. Am Coll Cardiol. 2007;49(17):1763-1769.

How Does Aspirin Resistance Affect Patients with Coronary Artery Disease?

Background: Although aspirin is used to decrease the risk of ischemic events, up to 45% of patients do not derive adequate anti-platelet activity. Few prospective studies have used laboratory-measured aspirin resistance to assess clinical outcomes.

Study design: Blinded cohort

Setting: Patients affiliated with Queen Mary Hospital, the University of Hong Kong.

Synopsis: Aspirin-induced platelet inhibition was measured quantitatively on 468 patients with stable coronary artery disease who take 80-325 mg of aspirin per day. The study found 128 patients were aspirin resistant. Aspirin resistance was more prevalent with increased age, female gender, renal insufficiency, anemia, and with use of low-dose aspirin. At follow up, aspirin-resistant patients were more likely to develop a primary outcome event: cardiovascular deaths, myocardial infarction, stroke, transient ischemic attack, and unstable angina. Aspirin resistance was an independent risk factor for developing the aforementioned outcomes, as are diabetes, prior myocardial infarction, and low hemoglobin.

Bottom line: Aspirin resistance, as defined by an aggregation-based assay, is associated with adverse outcomes in patients with stable coronary artery disease.

Citation: Chen W, Cheng X, Lee PY, et al. Aspirin resistance and adverse clinical events in patients with coronary artery disease. Am J Med. 2007 Jul;120(7):631-635.

Which Agents Best Prevent Venous Thromboembolism?

Background: Pulmonary emboli have been linked to 10% of in-hospital deaths. There continues to be a strong emphasis on prevention. Unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and selective factor Xa inhibitors are used for prophylaxis.

Study design: A meta-analysis of randomized controlled trials

Synopsis: The meta-analysis included 36 studies of hospitalized medical patients that compared UFH with control, LMWH with control, LMWH with UFH, and a selective factor Xa inhibitor with a placebo.

When each was compared with a control, UFH and LMWH were associated with a decreased risk of deep venous thrombosis (DVT) (risk ratio=0.33; 0.56) and pulmonary embolism (PE) (risk ratio=0.64; 0.37). Compared with control, LMWH three times daily was more effective than twice-daily dosing (risk ratio=0.27, 0.52). Through direct comparison of UFH and LMWH, LMWH was shown to have decreased DVT risk (risk ratio=0.68) and fewer injection site hematomas (risk ratio=0.47).

Neither UFH nor LMWH reduced mortality. LMWH and UFH were associated with significantly more bleeding events than control, but this increased risk was significant only for minor bleeding.

Bottom line: LMWH appears to have greater efficacy than UFH as a prophylactic agent against DVT/PE. If UFH is used, three times daily dosing is preferred.

Citation: Wein L, Wein S, Haas SJ, et al. Pharmacological venous thromboembolism prophylaxis in hospitalized medical patients. Arch Intern Med. 2007;167(14):1476-1486.

What Is the Association Between Antipsychotic Drugs and Mortality?

Background: Atypical antipsychotics prescribed off-label for problematic behaviors in dementia have been associated with risks including diabetes, stroke, and increased mortality. This resulted in the FDA placing a “black box” warning on atypical antipsychotics used for dementia. Subsequent studies have suggested that conventional antipsychotics are perhaps even more problematic.

Study Design: Retrospective cohort study

Synopsis: This trial found a small but significant increase in the risk of death in patients taking an antipsychotic medication.

The adjusted hazard ratio for death with the use of atypical antipsychotics in community dwelling patients with dementia was 1.3 (confidence interval 1.02-1.70). Similar to prior research, the authors found that conventional antipsychotics carried a higher risk than atypical agents.

Patients in long-term care settings also suffered increased risk compared with community dwelling patients. Interestingly, the increased risk of death was apparent after as little as a month of treatment.

As with all retrospective observational cohort trials, there remains the risk that an unanticipated confounding factor could skew the data and create a false association. However, the findings of this research support prior concerns that antipsychotics carry risk of increased mortality. This research bolsters the argument that these agents should not be used lightly or without full discussion of risks and benefits with the patient and/or proxy.

Bottom line: Antipsychotic agents used in patients with dementia may create increased risk of death. Potential benefit needs to be carefully weighted against this serious harm.

Citation: Gill S, Bronskill SE, Normand SL, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007 June 5;146(11):775-786.

Does Combination Therapy Help Prevent Serious Vascular Ischemic Events?

Background: Peripheral arterial disease (PAD) manifests as claudication and limb ischemia affecting 8.5 million Americans. Atherosclerotic disease in the periphery also reflects increased risk for ischemic events in the coronary and cranial circulations. Both antiplatelet agents and anticoagulation will decrease the probability of thrombus formation, although this must be weighed against bleeding risk.

Study design: Randomized, open-label, multicenter trial

Setting: Eighty centers in Europe, Asia, Australia, and North America

Synopsis: This trial randomized more than 2,000 patients with PAD to treatment with antiplatelet therapy (aspirin, ticlopidine, or clopidogrel) with or without additional anticoagulation.

During the next 3.5 years serious vascular events occurred at approximately the same rate in both combination and monotherapy groups (15.9% versus 17.4%, p=0.37). There was no significant difference between the occurrence of the composite ischemic endpoints or any of the individual endpoints. There was, however, a significantly higher rate of both moderate and life-threatening bleeding in the combination therapy group.

The 4% risk of life-threatening hemorrhage in the combination group exceeded the 1.2% rate of the monotherapy group creating a relative risk for bleeding of 3.4.

This trial demonstrates that for patients with PAD on antiplatelet therapy, the increased rate of bleeding without significant added benefit makes addition of warfarin inadvisable.1 Evidence of utility of combination therapy from studies in other arterial systems provides mixed results.2-4 Based on the results of this study, combination therapy cannot be advocated if the primary symptoms are from PAD.

Bottom line: This study provides further evidence that more is not always better when it comes to preventing thrombosis and ischemia in the peripheral arterial system. Antiplatelet agents are preferable for PAD to combination antiplatelet plus anticoagulation.

Citations:

1. The Warfarin Antiplatelet Vascular Evaluation Trial Investigators. Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med. 2007 Jul 19;357(3):217-227.
2. Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002 Sep 26;347(13):969-974.
3. Mohr JP, Thompson JL, Lazar RM, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med. 2001 Nov 15;345(20):1444-1451.
4. The ESPRIT Study Group. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a ran­dom­ised controlled trial. Lancet Neurol. 2007 Feb;6:115-124.

Does Transient Atrial Fibrillation Increase Stroke Risk After ST-Elevation Myocardial Infarction?

Background: Prior research has demonstrated that 2.1% of patients will suffer a stroke in the year following a heart attack. Persistent and paroxysmal atrial fibrillation (AF) are well recognized as risk factors for stroke, but the significance of transient ischemia-induced AF is less clear.

Study design: Retrospective cohort study

Setting: Queen Mary Hospital, Hong Kong

Synopsis: The study involved patients admitted for acute inferior ST-segment-elevation myocardial infarction (MI) with preserved left ventricular ejection fraction.

Transient AF that had converted back to normal sinus rhythm by discharge was observed in 14% of patients after the MI. Over the next three years the transient AF patients were 15 times more likely than those who remained in sinus rhythm during the index hospitalization to have recurrent AF (34% versus 2%). Despite antiplatelet therapy in both groups, ischemic stroke developed in 22% of patients who had transient AF following their MI, compared with only 4% in patients who did not (HR 5.1, confidence interval 2.4-11.2). Cerebrovascular accidents generally occurred simultaneously with recurrence of paroxysmal AF.1-2

The finding that patients with transient-ischemia-induced AF represents a group with markedly higher risk of ischemic stroke is compelling. It suggests that these patients may be candidates for combined antiplatelet and anticoagulant therapy. Trials of combined therapy following MI demonstrate that this strategy reduces the rate of recurrent cardiac ischemia, stroke, or death but does carry significantly increased risk of bleeding.3-4

Bottom line: The presence of transient AF following MI represents a significant risk factor for the development of subsequent paroxysmal AF. These patients have a five-fold increased risk of ischemic stroke over the next three years and should be considered for combined antiplatelet and anticoagulant therapy.

Citations:

1. Chung-Wah S, Man-Hong J, Hee-Hwa H, et al. Transient atrial fibrillation complicating acute inferior myocardial infarction: implications for future risk of ischemic stroke. Chest. 2007 Mar 30;132(1):44-49.
2. Witt BJ, Ballman KV, Brown RD Jr., Meverden RA, Jacobsen SJ, Roger VL. The incidence of stroke after myocardial infarction: a meta-analysis. Am J. Med. 2006;119(4):354 e1-9.
3. Van Es RF, Jonker J, Verheugt F, et al. Aspirin and Coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet. 2002 Jul 13;360(9327):109-113.
4. Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002 Sep 26;347(13):969-974. TH