Hospitalist News (Archived)

Levosimendan does not reduce the likelihood of severe organ dysfunction in adults with sepsis, nor does it lower the mortality rate, according to research presented at the annual congress of the European Society of Intensive Care Medicine and published in the New England Journal of Medicine.

Levosimendan is a calcium-sensitizing drug with inotropic and vasodilatory properties, which is commonly used to treat decompensated heart failure. “Small studies that have investigated the use of levosimendan in patients with septic shock have shown improvements in hemodynamic variables, microcirculatory flow, and renal and hepatic function, as compared with dobutamine,” wrote Anthony C. Gordon, MD, of Imperial College London and Imperial College Healthcare NHS Trust and his coauthors.

©invisioner/thinkstockphotos.com

Levosimendan does not reduce the likelihood of severe organ dysfunction in adults with sepsis, nor does it lower the mortality rate, according to research presented at the annual congress of the European Society of Intensive Care Medicine and published in the New England Journal of Medicine.

Levosimendan is a calcium-sensitizing drug with inotropic and vasodilatory properties, which is commonly used to treat decompensated heart failure. “Small studies that have investigated the use of levosimendan in patients with septic shock have shown improvements in hemodynamic variables, microcirculatory flow, and renal and hepatic function, as compared with dobutamine,” wrote Anthony C. Gordon, MD, of Imperial College London and Imperial College Healthcare NHS Trust and his coauthors.

©invisioner/thinkstockphotos.com

Levosimendan does not reduce the likelihood of severe organ dysfunction in adults with sepsis, nor does it lower the mortality rate, according to research presented at the annual congress of the European Society of Intensive Care Medicine and published in the New England Journal of Medicine.

Levosimendan is a calcium-sensitizing drug with inotropic and vasodilatory properties, which is commonly used to treat decompensated heart failure. “Small studies that have investigated the use of levosimendan in patients with septic shock have shown improvements in hemodynamic variables, microcirculatory flow, and renal and hepatic function, as compared with dobutamine,” wrote Anthony C. Gordon, MD, of Imperial College London and Imperial College Healthcare NHS Trust and his coauthors.

©invisioner/thinkstockphotos.com

Carbapenem-resistant Enterobacteriaceae (CRE) are extremely drug-resistant organisms. According to the Centers for Disease Control and Prevention’s National Healthcare Safety Network, in 2014 in the United States, 3.6% of Enterobacteriaceae causing hospital-acquired infections were resistant to carbapenems.¹ Antibiotic treatment options for CRE infections are severely limited, and mortality for invasive infections can be as high as 40%-50%.²

Resistance to carbapenems can be mediated by several mechanisms. From an epidemiologic standpoint, production of carbapenemases is the most-threatening mechanism because Enterobacteriaceae-harboring carbapenemases are highly transmissible.

Carbapenemase-producing CRE (CP-CRE) have caused large outbreaks throughout the world. Israel experienced a nationwide outbreak of CP-CRE, primarily Klebsiella pneumoniae carbapenemase–producing Klebsiella pneumoniae, in the mid-2000s. At the peak of the outbreak in 2007, there were 185 new cases per month (55.5/100,000 patient-days). A successful intervention at the national level dramatically decreased the incidence to 4.8/100,000 patient days in 2012.³

One component of the intervention (which is still ongoing) is active surveillance of high-risk groups using rectal swabs. Upon admission to the hospital, we screen patients who were recently in other hospitals or long-term care facilities. In addition, when a patient is newly diagnosed with CP-CRE (either asymptomatic carriage or clinical infection), we screen patients who had contact with that index case before isolation measures were implemented.

We recently published a study in Infection Control and Hospital Epidemiology that draws on our experience with CP-CRE screening of contacts at Tel Aviv Sourasky Medical Center.⁴ Both Israeli and International guidelines do not precisely define which contacts of a CP-CRE index case warrant screening. For example, should only roommates of index cases be screened or should we screen all patients on the same ward as the index case? Likewise, is there a minimum time of contact that should trigger screening?

Identifying which contacts are at high risk of acquiring CP-CRE is important for two reasons: We want to detect contacts who acquired CP-CRE so that they can be isolated before further transmission occurs, and we don’t want to waste resources and screen those at low risk. In our hospital, the criteria for being a contact are staying in the same ward and being treated by the same nursing staff as a newly identified CP-CRE patient.

This strategy appears to lead to overscreening, as we found that from October 2008 to June 2012, 3,158 screening tests were performed to detect 53 positive contacts (a yield of less than 2%). In order to screen more efficiently, our study aimed to determine risk factors for CP-CRE acquisition among patients exposed to a CP-CRE index patient.

We used a matched case-control design. The case group consisted of the 53 contacts who screened positive for CP-CRE. For each case we chose 2 controls: contacts who screened negative for CP-CRE. The basis for matching between the case and the 2 controls was that they were exposed to the same index patient. The benefit of matching this way was that it eliminated the question of whether a contact became positive because the index patient was more likely to transmit CP-CRE (e.g., because of diarrhea), and not because of characteristics of the contact patients themselves.

We found three factors that increased the risk that a contact would screen positive:

• Contact period of at least 3 days with the index case.

• Being on mechanical ventilation.

• Having a history of carriage or infection with another multidrug-resistant organism (such as methicillin-resistant Staphylococcus aureus).

Unexpectedly, sharing a room with the index patient or being debilitated did not significantly increase the risk of acquiring CP-CRE.

Many studies have identified antibiotic use as a risk factor for acquiring CP-CRE. In our study, no class of antibiotic increased the risk of CP-CRE acquisition, probably because only a small number of patients received each class. We were surprised to find that contacts who had taken cephalosporins were less likely to acquire CP-CRE. On further examination, when we compared patients who received only cephalosporins with patients who received no antibiotic, this protective effect disappeared. Nevertheless, compared with other antibiotics, it appears that cephalosporins might pose less of a risk for CP-CRE acquisition. More studies are needed to confirm our findings.

Our findings have practical implications for infection control. Using the risk factors we identified could help us to avoid excessive screening. We calculated that selective screening, based on our three risk factors, would have decreased the number of contacts screened by 30%, but 2 out of 53 positive contacts would have been missed. Institutions need to decide whether that is a trade-off they are willing to make.

Another way to apply our findings could be to add an additional layer of infection control by preemptively implementing contact precautions for patients at highest risk, for example, those with more than one risk factor.
 

1. Weiner LM, Fridkin SK, Aponte-Torres Z, Avery L, Coffin N, Dudeck MA, Edwards JR, Jernigan JA, Konnor R, Soe MM, Peterson K, Clifford McDonald L. Vital signs: preventing antibiotic-resistant infections in hospitals - United States, 2014. Am J Transplant. 2016 Jul;16(7):2224-30.

2. Centers for Disease Control and Prevention. Facility guidance for control of carbapenem-resistant Enterobacteriaceae (CRE): November 2015 update – CRE Toolkit.

3. Schwaber MJ, Carmeli Y. An ongoing national intervention to contain the spread of carbapenem-resistant enterobacteriaceae. Clin Infect Dis. 2014 Mar;58(5):697-703.

Schwartz-Neiderman A, Braun T, Fallach N, Schwartz D, Carmeli Y, Schechner V. Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients. Infect Control Hosp Epidemiol. 2016 Jul 25:1-7.
 

Vered Schechner, MD, MSc, is an infection control physician in the department of epidemiology at Tel Aviv Sourasky Medical Center.

Carbapenem-resistant Enterobacteriaceae (CRE) are extremely drug-resistant organisms. According to the Centers for Disease Control and Prevention’s National Healthcare Safety Network, in 2014 in the United States, 3.6% of Enterobacteriaceae causing hospital-acquired infections were resistant to carbapenems.¹ Antibiotic treatment options for CRE infections are severely limited, and mortality for invasive infections can be as high as 40%-50%.²

Resistance to carbapenems can be mediated by several mechanisms. From an epidemiologic standpoint, production of carbapenemases is the most-threatening mechanism because Enterobacteriaceae-harboring carbapenemases are highly transmissible.

Carbapenemase-producing CRE (CP-CRE) have caused large outbreaks throughout the world. Israel experienced a nationwide outbreak of CP-CRE, primarily Klebsiella pneumoniae carbapenemase–producing Klebsiella pneumoniae, in the mid-2000s. At the peak of the outbreak in 2007, there were 185 new cases per month (55.5/100,000 patient-days). A successful intervention at the national level dramatically decreased the incidence to 4.8/100,000 patient days in 2012.³

One component of the intervention (which is still ongoing) is active surveillance of high-risk groups using rectal swabs. Upon admission to the hospital, we screen patients who were recently in other hospitals or long-term care facilities. In addition, when a patient is newly diagnosed with CP-CRE (either asymptomatic carriage or clinical infection), we screen patients who had contact with that index case before isolation measures were implemented.

We recently published a study in Infection Control and Hospital Epidemiology that draws on our experience with CP-CRE screening of contacts at Tel Aviv Sourasky Medical Center.⁴ Both Israeli and International guidelines do not precisely define which contacts of a CP-CRE index case warrant screening. For example, should only roommates of index cases be screened or should we screen all patients on the same ward as the index case? Likewise, is there a minimum time of contact that should trigger screening?

Identifying which contacts are at high risk of acquiring CP-CRE is important for two reasons: We want to detect contacts who acquired CP-CRE so that they can be isolated before further transmission occurs, and we don’t want to waste resources and screen those at low risk. In our hospital, the criteria for being a contact are staying in the same ward and being treated by the same nursing staff as a newly identified CP-CRE patient.

This strategy appears to lead to overscreening, as we found that from October 2008 to June 2012, 3,158 screening tests were performed to detect 53 positive contacts (a yield of less than 2%). In order to screen more efficiently, our study aimed to determine risk factors for CP-CRE acquisition among patients exposed to a CP-CRE index patient.

We used a matched case-control design. The case group consisted of the 53 contacts who screened positive for CP-CRE. For each case we chose 2 controls: contacts who screened negative for CP-CRE. The basis for matching between the case and the 2 controls was that they were exposed to the same index patient. The benefit of matching this way was that it eliminated the question of whether a contact became positive because the index patient was more likely to transmit CP-CRE (e.g., because of diarrhea), and not because of characteristics of the contact patients themselves.

We found three factors that increased the risk that a contact would screen positive:

• Contact period of at least 3 days with the index case.

• Being on mechanical ventilation.

• Having a history of carriage or infection with another multidrug-resistant organism (such as methicillin-resistant Staphylococcus aureus).

Unexpectedly, sharing a room with the index patient or being debilitated did not significantly increase the risk of acquiring CP-CRE.

Many studies have identified antibiotic use as a risk factor for acquiring CP-CRE. In our study, no class of antibiotic increased the risk of CP-CRE acquisition, probably because only a small number of patients received each class. We were surprised to find that contacts who had taken cephalosporins were less likely to acquire CP-CRE. On further examination, when we compared patients who received only cephalosporins with patients who received no antibiotic, this protective effect disappeared. Nevertheless, compared with other antibiotics, it appears that cephalosporins might pose less of a risk for CP-CRE acquisition. More studies are needed to confirm our findings.

Our findings have practical implications for infection control. Using the risk factors we identified could help us to avoid excessive screening. We calculated that selective screening, based on our three risk factors, would have decreased the number of contacts screened by 30%, but 2 out of 53 positive contacts would have been missed. Institutions need to decide whether that is a trade-off they are willing to make.

Another way to apply our findings could be to add an additional layer of infection control by preemptively implementing contact precautions for patients at highest risk, for example, those with more than one risk factor.
 

1. Weiner LM, Fridkin SK, Aponte-Torres Z, Avery L, Coffin N, Dudeck MA, Edwards JR, Jernigan JA, Konnor R, Soe MM, Peterson K, Clifford McDonald L. Vital signs: preventing antibiotic-resistant infections in hospitals - United States, 2014. Am J Transplant. 2016 Jul;16(7):2224-30.

2. Centers for Disease Control and Prevention. Facility guidance for control of carbapenem-resistant Enterobacteriaceae (CRE): November 2015 update – CRE Toolkit.

3. Schwaber MJ, Carmeli Y. An ongoing national intervention to contain the spread of carbapenem-resistant enterobacteriaceae. Clin Infect Dis. 2014 Mar;58(5):697-703.

Schwartz-Neiderman A, Braun T, Fallach N, Schwartz D, Carmeli Y, Schechner V. Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients. Infect Control Hosp Epidemiol. 2016 Jul 25:1-7.
 

Vered Schechner, MD, MSc, is an infection control physician in the department of epidemiology at Tel Aviv Sourasky Medical Center.

Carbapenem-resistant Enterobacteriaceae (CRE) are extremely drug-resistant organisms. According to the Centers for Disease Control and Prevention’s National Healthcare Safety Network, in 2014 in the United States, 3.6% of Enterobacteriaceae causing hospital-acquired infections were resistant to carbapenems.¹ Antibiotic treatment options for CRE infections are severely limited, and mortality for invasive infections can be as high as 40%-50%.²

Resistance to carbapenems can be mediated by several mechanisms. From an epidemiologic standpoint, production of carbapenemases is the most-threatening mechanism because Enterobacteriaceae-harboring carbapenemases are highly transmissible.

Carbapenemase-producing CRE (CP-CRE) have caused large outbreaks throughout the world. Israel experienced a nationwide outbreak of CP-CRE, primarily Klebsiella pneumoniae carbapenemase–producing Klebsiella pneumoniae, in the mid-2000s. At the peak of the outbreak in 2007, there were 185 new cases per month (55.5/100,000 patient-days). A successful intervention at the national level dramatically decreased the incidence to 4.8/100,000 patient days in 2012.³

One component of the intervention (which is still ongoing) is active surveillance of high-risk groups using rectal swabs. Upon admission to the hospital, we screen patients who were recently in other hospitals or long-term care facilities. In addition, when a patient is newly diagnosed with CP-CRE (either asymptomatic carriage or clinical infection), we screen patients who had contact with that index case before isolation measures were implemented.

We recently published a study in Infection Control and Hospital Epidemiology that draws on our experience with CP-CRE screening of contacts at Tel Aviv Sourasky Medical Center.⁴ Both Israeli and International guidelines do not precisely define which contacts of a CP-CRE index case warrant screening. For example, should only roommates of index cases be screened or should we screen all patients on the same ward as the index case? Likewise, is there a minimum time of contact that should trigger screening?

Identifying which contacts are at high risk of acquiring CP-CRE is important for two reasons: We want to detect contacts who acquired CP-CRE so that they can be isolated before further transmission occurs, and we don’t want to waste resources and screen those at low risk. In our hospital, the criteria for being a contact are staying in the same ward and being treated by the same nursing staff as a newly identified CP-CRE patient.

This strategy appears to lead to overscreening, as we found that from October 2008 to June 2012, 3,158 screening tests were performed to detect 53 positive contacts (a yield of less than 2%). In order to screen more efficiently, our study aimed to determine risk factors for CP-CRE acquisition among patients exposed to a CP-CRE index patient.

We used a matched case-control design. The case group consisted of the 53 contacts who screened positive for CP-CRE. For each case we chose 2 controls: contacts who screened negative for CP-CRE. The basis for matching between the case and the 2 controls was that they were exposed to the same index patient. The benefit of matching this way was that it eliminated the question of whether a contact became positive because the index patient was more likely to transmit CP-CRE (e.g., because of diarrhea), and not because of characteristics of the contact patients themselves.

We found three factors that increased the risk that a contact would screen positive:

• Contact period of at least 3 days with the index case.

• Being on mechanical ventilation.

• Having a history of carriage or infection with another multidrug-resistant organism (such as methicillin-resistant Staphylococcus aureus).

Unexpectedly, sharing a room with the index patient or being debilitated did not significantly increase the risk of acquiring CP-CRE.

Many studies have identified antibiotic use as a risk factor for acquiring CP-CRE. In our study, no class of antibiotic increased the risk of CP-CRE acquisition, probably because only a small number of patients received each class. We were surprised to find that contacts who had taken cephalosporins were less likely to acquire CP-CRE. On further examination, when we compared patients who received only cephalosporins with patients who received no antibiotic, this protective effect disappeared. Nevertheless, compared with other antibiotics, it appears that cephalosporins might pose less of a risk for CP-CRE acquisition. More studies are needed to confirm our findings.

Our findings have practical implications for infection control. Using the risk factors we identified could help us to avoid excessive screening. We calculated that selective screening, based on our three risk factors, would have decreased the number of contacts screened by 30%, but 2 out of 53 positive contacts would have been missed. Institutions need to decide whether that is a trade-off they are willing to make.

Another way to apply our findings could be to add an additional layer of infection control by preemptively implementing contact precautions for patients at highest risk, for example, those with more than one risk factor.
 

1. Weiner LM, Fridkin SK, Aponte-Torres Z, Avery L, Coffin N, Dudeck MA, Edwards JR, Jernigan JA, Konnor R, Soe MM, Peterson K, Clifford McDonald L. Vital signs: preventing antibiotic-resistant infections in hospitals - United States, 2014. Am J Transplant. 2016 Jul;16(7):2224-30.

2. Centers for Disease Control and Prevention. Facility guidance for control of carbapenem-resistant Enterobacteriaceae (CRE): November 2015 update – CRE Toolkit.

3. Schwaber MJ, Carmeli Y. An ongoing national intervention to contain the spread of carbapenem-resistant enterobacteriaceae. Clin Infect Dis. 2014 Mar;58(5):697-703.

Schwartz-Neiderman A, Braun T, Fallach N, Schwartz D, Carmeli Y, Schechner V. Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients. Infect Control Hosp Epidemiol. 2016 Jul 25:1-7.
 

Vered Schechner, MD, MSc, is an infection control physician in the department of epidemiology at Tel Aviv Sourasky Medical Center.

Switching between generic versions of the same antiepileptic drug made by different manufacturers does not appear to change the risk of seizure-related events in patients with epilepsy, according to a population-based, case-crossover study of generic antiepileptic drug users.

Instead, the study indicates that delays and complications of the medication refilling process might increase a patient’s risk for a seizure, said first author Aaron Kesselheim, MD, and his associates from Brigham and Women’s Hospital and Harvard Medical School, Boston (Neurology. 2016 Sep 28. doi: 10.1212/WNL.0000000000003259).

The study was not supported by any specific targeted funding. The investigators reported receiving support from various foundations and from programs within Harvard University and grants from the Agency for Healthcare Research and Quality and the Food and Drug Administration; the investigators also disclosed acting in a research support role for and/or receiving financial compensation from several pharmaceutical companies and other organizations.

[email protected]

On Twitter @jessnicolecraig

Switching between generic versions of the same antiepileptic drug made by different manufacturers does not appear to change the risk of seizure-related events in patients with epilepsy, according to a population-based, case-crossover study of generic antiepileptic drug users.

Instead, the study indicates that delays and complications of the medication refilling process might increase a patient’s risk for a seizure, said first author Aaron Kesselheim, MD, and his associates from Brigham and Women’s Hospital and Harvard Medical School, Boston (Neurology. 2016 Sep 28. doi: 10.1212/WNL.0000000000003259).

The study was not supported by any specific targeted funding. The investigators reported receiving support from various foundations and from programs within Harvard University and grants from the Agency for Healthcare Research and Quality and the Food and Drug Administration; the investigators also disclosed acting in a research support role for and/or receiving financial compensation from several pharmaceutical companies and other organizations.

[email protected]

On Twitter @jessnicolecraig

Switching between generic versions of the same antiepileptic drug made by different manufacturers does not appear to change the risk of seizure-related events in patients with epilepsy, according to a population-based, case-crossover study of generic antiepileptic drug users.

Instead, the study indicates that delays and complications of the medication refilling process might increase a patient’s risk for a seizure, said first author Aaron Kesselheim, MD, and his associates from Brigham and Women’s Hospital and Harvard Medical School, Boston (Neurology. 2016 Sep 28. doi: 10.1212/WNL.0000000000003259).

The study was not supported by any specific targeted funding. The investigators reported receiving support from various foundations and from programs within Harvard University and grants from the Agency for Healthcare Research and Quality and the Food and Drug Administration; the investigators also disclosed acting in a research support role for and/or receiving financial compensation from several pharmaceutical companies and other organizations.

[email protected]

On Twitter @jessnicolecraig

Sometimes it seems like cardiac troponin testing has become nearly as ubiquitous as the CBC and the BMP. Concern over atypical presentations of MI has contributed to widespread use in emergency departments and hospitalized patients. But once the test comes back elevated, what do you do with that information?

Typically, the next step is to consult Cardiology, which is a reasonable request with or without a suspicion of MI. Frequently, invasive management is not an option; or perhaps the diagnosis is “type 2 MI.”¹

Courtesy University of Florida

1. Thygesen K, Alpert JS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60:1581-98.

2. Alcalai R, Planer D, Culhaoglu A, Osman A, Pollak A and Lotan C. Acute coronary syndrome vs nonspecific troponin elevation: clinical predictors and survival analysis. Arch Intern Med. 2007;167:276-81.

3. Winchester DE, Burke L, Agarwal N, Schmalfuss C and Pepine CJ. Predictors of short- and long-term mortality in hospitalized veterans with elevated troponin. J Hosp Med. 2016 Jun 3. doi: 10.1002/jhm.2619.

David Winchester, MD, is assistant professor in the division of cardiovascular medicine at the University of Florida (Gainesville), and practices general cardiology at the Malcom Randall VA Medical Center, Gainesville.

Sometimes it seems like cardiac troponin testing has become nearly as ubiquitous as the CBC and the BMP. Concern over atypical presentations of MI has contributed to widespread use in emergency departments and hospitalized patients. But once the test comes back elevated, what do you do with that information?

Typically, the next step is to consult Cardiology, which is a reasonable request with or without a suspicion of MI. Frequently, invasive management is not an option; or perhaps the diagnosis is “type 2 MI.”¹

Courtesy University of Florida

1. Thygesen K, Alpert JS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60:1581-98.

2. Alcalai R, Planer D, Culhaoglu A, Osman A, Pollak A and Lotan C. Acute coronary syndrome vs nonspecific troponin elevation: clinical predictors and survival analysis. Arch Intern Med. 2007;167:276-81.

3. Winchester DE, Burke L, Agarwal N, Schmalfuss C and Pepine CJ. Predictors of short- and long-term mortality in hospitalized veterans with elevated troponin. J Hosp Med. 2016 Jun 3. doi: 10.1002/jhm.2619.

David Winchester, MD, is assistant professor in the division of cardiovascular medicine at the University of Florida (Gainesville), and practices general cardiology at the Malcom Randall VA Medical Center, Gainesville.

Sometimes it seems like cardiac troponin testing has become nearly as ubiquitous as the CBC and the BMP. Concern over atypical presentations of MI has contributed to widespread use in emergency departments and hospitalized patients. But once the test comes back elevated, what do you do with that information?

Typically, the next step is to consult Cardiology, which is a reasonable request with or without a suspicion of MI. Frequently, invasive management is not an option; or perhaps the diagnosis is “type 2 MI.”¹

Courtesy University of Florida

1. Thygesen K, Alpert JS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60:1581-98.

2. Alcalai R, Planer D, Culhaoglu A, Osman A, Pollak A and Lotan C. Acute coronary syndrome vs nonspecific troponin elevation: clinical predictors and survival analysis. Arch Intern Med. 2007;167:276-81.

3. Winchester DE, Burke L, Agarwal N, Schmalfuss C and Pepine CJ. Predictors of short- and long-term mortality in hospitalized veterans with elevated troponin. J Hosp Med. 2016 Jun 3. doi: 10.1002/jhm.2619.

David Winchester, MD, is assistant professor in the division of cardiovascular medicine at the University of Florida (Gainesville), and practices general cardiology at the Malcom Randall VA Medical Center, Gainesville.

Patients with chronic obstructive pulmonary disease or interstitial lung disease have longer stays in the intensive care unit, yet are less likely than patients with metastatic cancer to receive comprehensive palliative care.

This finding, reported in Annals of the American Thoracic Society, underscores the need to expand palliative care programs, incorporate elements of palliative care into routine ICU practices, and identify the most effective components of palliative care, said several experts who were not involved in the study.

“Patients with metastatic cancer are more likely to discuss goals of therapy and code status with their inpatient physician and then receive referrals to palliative care,” said Dr. Michael J. Waxman, medical director of the intensive care unit at Research Medical Center in Kansas City. “I can share many anecdotes over the years where a patient is admitted to my ICU with metastatic cancer, or severe COPD [chronic obstructive pulmonary disease] or IPF [idiopathic pulmonary fibrosis],” he added. “The cognition of these patients in some cases may have been normal, but I learned during my review that they did not receive a good discussion of desires regarding resuscitation or intensity of care. It was regularly assumed that there would be no limits on intensity of care.”

Palliative care historically has focused on patients with cancer, even though mortality rates can be high in noncancer lung disease, Dr. Crystal Brown and her associates at the University of Washington in Seattle wrote in their article (Ann Am Thorac Soc. 2016;13:684-9.). Their secondary analysis of the randomized Integrating Palliative and Critical Care trial examined medical chart data for 592 patients with COPD, 158 patients with metastatic cancer, and 79 patients with interstitial lung disease (ILD) who died in the ICUs of 15 Seattle-area hospitals between 2003 and 2008. The investigators performed regression modeling to test associations between diagnosis and eight elements of palliative care – avoidance of cardiopulmonary resuscitation during the hour before death, pain assessment during the 24 hours before death, the presence of a do-not-resuscitate order at the time of death, discussion of prognosis within 72 hours of ICU admission, withdrawal of life support measures before death, involvement of a spiritual care provider, consultation with a palliative care specialist, and the presence of an advance directive. The statistical models controlled for many potential confounders, including age, sex, race and ethnicity, education level, hospital, and whether patients died before or after hospitals implemented a palliative care quality improvement intervention.

Even though median lengths of ICU stay were significantly longer for ILD patients (4.2 days) and COPD patients (2.9 days) than for metastatic cancer patients (2.3 days), patients with COPD were significantly less likely to avoid CPR in the hour before death (adjusted odds ratio, 0.43; 95% confidence interval, 0.20-0.90), while ILD patients were less likely to have a documented pain assessment in the 24 hours before death (OR, 0.43; 95% CI, 0.19-0.97), compared with metastatic cancer patients. Patients with ILD or COPD also were significantly less likely to have a do-not-resuscitate order in place or documentation of a discussion of their prognosis, Dr. Brown and her associates reported.

The findings raise several concerns. “Clearly, this points to both intensivists and palliative care consultants needing to do more to target patients with nonmalignant end-stage chronic lung diseases, such as some patients with COPD and ILD,” said Dr. Robert Hyzy, director of the critical care medicine unit at the University of Michigan Hospital, Ann Arbor. The difference in length of stay also suggests a need to recognize earlier when critically ill patients have not responded to an appropriate time period of treatment (sometimes called a “time-limited trial”), “which signals the transition from cure to comfort,” he added.

Vera De Palo, MD, MBA, FCCP, who is chief of medicine at Signature Healthcare Brockton (Mass.) Hospital, agreed. “While treatment plans for patients with end-stage ILD and COPD do at times include palliative care, the study points out what is often the experience for most patients,” she said. “Our oncology colleagues have better understood the time line of transition between curative care and palliative care than those of us who also manage noncancer chronic diseases. They are more likely to participate in the development of palliative care programs, ensuring that this avenue of care is also available to their patients.”

This is not the only study to reveal gaps in palliative care for advanced nonmalignant lung disease. In a recent analysis of the Nationwide Inpatient Sample, only 2.6% of COPD patients who were home on oxygen and then were hospitalized with an exacerbation received a palliative care referral (CHEST. 2016 Jul 4. doi:10.1016/j.chest.2016.06.023). Such findings belie the most recent palliative care guidelines from the American Thoracic Society for patients with respiratory diseases and critical illnesses, which not only emphasize most of the same palliative care elements as the study by Dr. Brown and her colleagues, but also recommend “early consultation” with palliative care experts to help manage difficult end-of-life discussions (Am J Respir Crit Care Med. 2008;177:912-27).

Oncology palliative care includes both primary and secondary (specialty-level) services, Dr. Arif Kamal of Duke Cancer Institute at Duke University Medical Center, Durham, N.C., and his associates wrote in a viewpoint published in JAMA. Primary services, such as assessing and managing symptoms, discussing priorities and what to expect, and ensuring continuity of care, are usually left to the oncology team. Secondary services are reserved for more complex or time-consuming cases and are provided by palliative care consultants. “This ‘manage first, refer second’ practice reflects the ethos of the oncology profession – the notion that ‘this is our job’ – while also reflecting a practical humility – ‘It’s hard to be everything to everyone all the time,’ ” Dr. Kamal and his associates wrote.

When it comes to palliative care for advanced nonmalignant lung disease, Dr. De Palo said, patients and families may not feel ready to discuss end-of-life issues, and providers may find it difficult to initiate these conversations. “From the moment of diagnosis, the focus of a patient’s care for providers is curative care.” Including a palliative focus can be difficult.

Nonmalignant pulmonary diseases often carry an “uncertain short-term prognosis,” the ATS guidelines stated, and experts echoed that point. “I believe our confidence in determination of prognosis is a key factor in hesitation or delay in engaging palliative care,” said David Bowton, MD, a professor specializing in critical care at Wake Forest School of Medicine, Winston-Salem, N.C. Oncology patients needing ICU care usually have “considerably higher” mortality than the rates of 20%-45% and 15%-30% that are cited for ILD and COPD patients, respectively, he said. Furthermore, there are seemingly accurate scoring systems for predicting short-term mortality in critically ill cancer patients, which is not the case for ILD or COPD, he added.

Such factors point to differences in disease trajectory. “In this study, it is likely that the patients with cancer diagnoses more often received the elements of palliative care in the ICU because it was clearly communicated to the intensive care providers that the opportunities for curative care were exhausted,” Dr. De Palo said. “With care for end-stage chronic respiratory diseases, ICU care can usually optimize breathing enough to get the patient off the vent and stabilized at their previous functional plateau or, more often, at a lower functional plateau, until the next shortness of breath episode.”

Given these challenges and uncertainties, how can clinicians improve palliative care for patients with advanced nonmalignant lung diseases? “Simple. Have a discussion with everyone about what their expectations are,” said Dr. Waxman. “Find out what is important to them and what their goals of therapy are. Help them understand the reality of what actually will be possible to accomplish in a hospitalization, a surgery, or a therapy.”

Dr. De Palo agreed. “For my patients with end-stage respiratory disease, we often discuss whether a sustaining therapy of mechanical ventilation would offer any benefit, and what role cardiopulmonary resuscitation should play in the context of their wishes for care as their disease progresses,” she said. “I believe that providers and health care organizations should offer patients the spectrum of curative and palliative care, and work together to develop a palliative care program where one does not exist,” she stressed. Access to “the full spectrum of care – from curative to palliative – will provide the compassion and quality of life at each stage of their chronic disease.”

Intensivists should also ensure that all ICU patients receive consultations with providers “who can look more at the big picture of their health care, not just at their admission diagnosis and the specific treatment they are receiving,” Dr. Waxman said. And Dr. Bowton offered a final caveat. “While it appears obvious that providing palliative care consultation or integrating elements of palliative care into our routine ICU care will improve the experience for our patients and their families, this has been difficult to demonstrate in well-designed studies,” he said. “Thus, rather than focusing solely on our apparent shortcomings in providing palliative care to our ICU patients with ILD and COPD, we should vigorously support efforts to ascertain what components of palliative care and what ‘dose’ are most effective in alleviating physical and emotional distress.”

The National Institute of Nursing Research funded the study by Dr. Brown and her associates, who reported no relevant financial conflicts of interest.

Patients with chronic obstructive pulmonary disease or interstitial lung disease have longer stays in the intensive care unit, yet are less likely than patients with metastatic cancer to receive comprehensive palliative care.

This finding, reported in Annals of the American Thoracic Society, underscores the need to expand palliative care programs, incorporate elements of palliative care into routine ICU practices, and identify the most effective components of palliative care, said several experts who were not involved in the study.

“Patients with metastatic cancer are more likely to discuss goals of therapy and code status with their inpatient physician and then receive referrals to palliative care,” said Dr. Michael J. Waxman, medical director of the intensive care unit at Research Medical Center in Kansas City. “I can share many anecdotes over the years where a patient is admitted to my ICU with metastatic cancer, or severe COPD [chronic obstructive pulmonary disease] or IPF [idiopathic pulmonary fibrosis],” he added. “The cognition of these patients in some cases may have been normal, but I learned during my review that they did not receive a good discussion of desires regarding resuscitation or intensity of care. It was regularly assumed that there would be no limits on intensity of care.”

Palliative care historically has focused on patients with cancer, even though mortality rates can be high in noncancer lung disease, Dr. Crystal Brown and her associates at the University of Washington in Seattle wrote in their article (Ann Am Thorac Soc. 2016;13:684-9.). Their secondary analysis of the randomized Integrating Palliative and Critical Care trial examined medical chart data for 592 patients with COPD, 158 patients with metastatic cancer, and 79 patients with interstitial lung disease (ILD) who died in the ICUs of 15 Seattle-area hospitals between 2003 and 2008. The investigators performed regression modeling to test associations between diagnosis and eight elements of palliative care – avoidance of cardiopulmonary resuscitation during the hour before death, pain assessment during the 24 hours before death, the presence of a do-not-resuscitate order at the time of death, discussion of prognosis within 72 hours of ICU admission, withdrawal of life support measures before death, involvement of a spiritual care provider, consultation with a palliative care specialist, and the presence of an advance directive. The statistical models controlled for many potential confounders, including age, sex, race and ethnicity, education level, hospital, and whether patients died before or after hospitals implemented a palliative care quality improvement intervention.

Even though median lengths of ICU stay were significantly longer for ILD patients (4.2 days) and COPD patients (2.9 days) than for metastatic cancer patients (2.3 days), patients with COPD were significantly less likely to avoid CPR in the hour before death (adjusted odds ratio, 0.43; 95% confidence interval, 0.20-0.90), while ILD patients were less likely to have a documented pain assessment in the 24 hours before death (OR, 0.43; 95% CI, 0.19-0.97), compared with metastatic cancer patients. Patients with ILD or COPD also were significantly less likely to have a do-not-resuscitate order in place or documentation of a discussion of their prognosis, Dr. Brown and her associates reported.

The findings raise several concerns. “Clearly, this points to both intensivists and palliative care consultants needing to do more to target patients with nonmalignant end-stage chronic lung diseases, such as some patients with COPD and ILD,” said Dr. Robert Hyzy, director of the critical care medicine unit at the University of Michigan Hospital, Ann Arbor. The difference in length of stay also suggests a need to recognize earlier when critically ill patients have not responded to an appropriate time period of treatment (sometimes called a “time-limited trial”), “which signals the transition from cure to comfort,” he added.

Vera De Palo, MD, MBA, FCCP, who is chief of medicine at Signature Healthcare Brockton (Mass.) Hospital, agreed. “While treatment plans for patients with end-stage ILD and COPD do at times include palliative care, the study points out what is often the experience for most patients,” she said. “Our oncology colleagues have better understood the time line of transition between curative care and palliative care than those of us who also manage noncancer chronic diseases. They are more likely to participate in the development of palliative care programs, ensuring that this avenue of care is also available to their patients.”

This is not the only study to reveal gaps in palliative care for advanced nonmalignant lung disease. In a recent analysis of the Nationwide Inpatient Sample, only 2.6% of COPD patients who were home on oxygen and then were hospitalized with an exacerbation received a palliative care referral (CHEST. 2016 Jul 4. doi:10.1016/j.chest.2016.06.023). Such findings belie the most recent palliative care guidelines from the American Thoracic Society for patients with respiratory diseases and critical illnesses, which not only emphasize most of the same palliative care elements as the study by Dr. Brown and her colleagues, but also recommend “early consultation” with palliative care experts to help manage difficult end-of-life discussions (Am J Respir Crit Care Med. 2008;177:912-27).

Oncology palliative care includes both primary and secondary (specialty-level) services, Dr. Arif Kamal of Duke Cancer Institute at Duke University Medical Center, Durham, N.C., and his associates wrote in a viewpoint published in JAMA. Primary services, such as assessing and managing symptoms, discussing priorities and what to expect, and ensuring continuity of care, are usually left to the oncology team. Secondary services are reserved for more complex or time-consuming cases and are provided by palliative care consultants. “This ‘manage first, refer second’ practice reflects the ethos of the oncology profession – the notion that ‘this is our job’ – while also reflecting a practical humility – ‘It’s hard to be everything to everyone all the time,’ ” Dr. Kamal and his associates wrote.

When it comes to palliative care for advanced nonmalignant lung disease, Dr. De Palo said, patients and families may not feel ready to discuss end-of-life issues, and providers may find it difficult to initiate these conversations. “From the moment of diagnosis, the focus of a patient’s care for providers is curative care.” Including a palliative focus can be difficult.

Nonmalignant pulmonary diseases often carry an “uncertain short-term prognosis,” the ATS guidelines stated, and experts echoed that point. “I believe our confidence in determination of prognosis is a key factor in hesitation or delay in engaging palliative care,” said David Bowton, MD, a professor specializing in critical care at Wake Forest School of Medicine, Winston-Salem, N.C. Oncology patients needing ICU care usually have “considerably higher” mortality than the rates of 20%-45% and 15%-30% that are cited for ILD and COPD patients, respectively, he said. Furthermore, there are seemingly accurate scoring systems for predicting short-term mortality in critically ill cancer patients, which is not the case for ILD or COPD, he added.

Such factors point to differences in disease trajectory. “In this study, it is likely that the patients with cancer diagnoses more often received the elements of palliative care in the ICU because it was clearly communicated to the intensive care providers that the opportunities for curative care were exhausted,” Dr. De Palo said. “With care for end-stage chronic respiratory diseases, ICU care can usually optimize breathing enough to get the patient off the vent and stabilized at their previous functional plateau or, more often, at a lower functional plateau, until the next shortness of breath episode.”

Given these challenges and uncertainties, how can clinicians improve palliative care for patients with advanced nonmalignant lung diseases? “Simple. Have a discussion with everyone about what their expectations are,” said Dr. Waxman. “Find out what is important to them and what their goals of therapy are. Help them understand the reality of what actually will be possible to accomplish in a hospitalization, a surgery, or a therapy.”

Dr. De Palo agreed. “For my patients with end-stage respiratory disease, we often discuss whether a sustaining therapy of mechanical ventilation would offer any benefit, and what role cardiopulmonary resuscitation should play in the context of their wishes for care as their disease progresses,” she said. “I believe that providers and health care organizations should offer patients the spectrum of curative and palliative care, and work together to develop a palliative care program where one does not exist,” she stressed. Access to “the full spectrum of care – from curative to palliative – will provide the compassion and quality of life at each stage of their chronic disease.”

Intensivists should also ensure that all ICU patients receive consultations with providers “who can look more at the big picture of their health care, not just at their admission diagnosis and the specific treatment they are receiving,” Dr. Waxman said. And Dr. Bowton offered a final caveat. “While it appears obvious that providing palliative care consultation or integrating elements of palliative care into our routine ICU care will improve the experience for our patients and their families, this has been difficult to demonstrate in well-designed studies,” he said. “Thus, rather than focusing solely on our apparent shortcomings in providing palliative care to our ICU patients with ILD and COPD, we should vigorously support efforts to ascertain what components of palliative care and what ‘dose’ are most effective in alleviating physical and emotional distress.”

The National Institute of Nursing Research funded the study by Dr. Brown and her associates, who reported no relevant financial conflicts of interest.

Patients with chronic obstructive pulmonary disease or interstitial lung disease have longer stays in the intensive care unit, yet are less likely than patients with metastatic cancer to receive comprehensive palliative care.

This finding, reported in Annals of the American Thoracic Society, underscores the need to expand palliative care programs, incorporate elements of palliative care into routine ICU practices, and identify the most effective components of palliative care, said several experts who were not involved in the study.

“Patients with metastatic cancer are more likely to discuss goals of therapy and code status with their inpatient physician and then receive referrals to palliative care,” said Dr. Michael J. Waxman, medical director of the intensive care unit at Research Medical Center in Kansas City. “I can share many anecdotes over the years where a patient is admitted to my ICU with metastatic cancer, or severe COPD [chronic obstructive pulmonary disease] or IPF [idiopathic pulmonary fibrosis],” he added. “The cognition of these patients in some cases may have been normal, but I learned during my review that they did not receive a good discussion of desires regarding resuscitation or intensity of care. It was regularly assumed that there would be no limits on intensity of care.”

Palliative care historically has focused on patients with cancer, even though mortality rates can be high in noncancer lung disease, Dr. Crystal Brown and her associates at the University of Washington in Seattle wrote in their article (Ann Am Thorac Soc. 2016;13:684-9.). Their secondary analysis of the randomized Integrating Palliative and Critical Care trial examined medical chart data for 592 patients with COPD, 158 patients with metastatic cancer, and 79 patients with interstitial lung disease (ILD) who died in the ICUs of 15 Seattle-area hospitals between 2003 and 2008. The investigators performed regression modeling to test associations between diagnosis and eight elements of palliative care – avoidance of cardiopulmonary resuscitation during the hour before death, pain assessment during the 24 hours before death, the presence of a do-not-resuscitate order at the time of death, discussion of prognosis within 72 hours of ICU admission, withdrawal of life support measures before death, involvement of a spiritual care provider, consultation with a palliative care specialist, and the presence of an advance directive. The statistical models controlled for many potential confounders, including age, sex, race and ethnicity, education level, hospital, and whether patients died before or after hospitals implemented a palliative care quality improvement intervention.

Even though median lengths of ICU stay were significantly longer for ILD patients (4.2 days) and COPD patients (2.9 days) than for metastatic cancer patients (2.3 days), patients with COPD were significantly less likely to avoid CPR in the hour before death (adjusted odds ratio, 0.43; 95% confidence interval, 0.20-0.90), while ILD patients were less likely to have a documented pain assessment in the 24 hours before death (OR, 0.43; 95% CI, 0.19-0.97), compared with metastatic cancer patients. Patients with ILD or COPD also were significantly less likely to have a do-not-resuscitate order in place or documentation of a discussion of their prognosis, Dr. Brown and her associates reported.

The findings raise several concerns. “Clearly, this points to both intensivists and palliative care consultants needing to do more to target patients with nonmalignant end-stage chronic lung diseases, such as some patients with COPD and ILD,” said Dr. Robert Hyzy, director of the critical care medicine unit at the University of Michigan Hospital, Ann Arbor. The difference in length of stay also suggests a need to recognize earlier when critically ill patients have not responded to an appropriate time period of treatment (sometimes called a “time-limited trial”), “which signals the transition from cure to comfort,” he added.

Vera De Palo, MD, MBA, FCCP, who is chief of medicine at Signature Healthcare Brockton (Mass.) Hospital, agreed. “While treatment plans for patients with end-stage ILD and COPD do at times include palliative care, the study points out what is often the experience for most patients,” she said. “Our oncology colleagues have better understood the time line of transition between curative care and palliative care than those of us who also manage noncancer chronic diseases. They are more likely to participate in the development of palliative care programs, ensuring that this avenue of care is also available to their patients.”

This is not the only study to reveal gaps in palliative care for advanced nonmalignant lung disease. In a recent analysis of the Nationwide Inpatient Sample, only 2.6% of COPD patients who were home on oxygen and then were hospitalized with an exacerbation received a palliative care referral (CHEST. 2016 Jul 4. doi:10.1016/j.chest.2016.06.023). Such findings belie the most recent palliative care guidelines from the American Thoracic Society for patients with respiratory diseases and critical illnesses, which not only emphasize most of the same palliative care elements as the study by Dr. Brown and her colleagues, but also recommend “early consultation” with palliative care experts to help manage difficult end-of-life discussions (Am J Respir Crit Care Med. 2008;177:912-27).

Oncology palliative care includes both primary and secondary (specialty-level) services, Dr. Arif Kamal of Duke Cancer Institute at Duke University Medical Center, Durham, N.C., and his associates wrote in a viewpoint published in JAMA. Primary services, such as assessing and managing symptoms, discussing priorities and what to expect, and ensuring continuity of care, are usually left to the oncology team. Secondary services are reserved for more complex or time-consuming cases and are provided by palliative care consultants. “This ‘manage first, refer second’ practice reflects the ethos of the oncology profession – the notion that ‘this is our job’ – while also reflecting a practical humility – ‘It’s hard to be everything to everyone all the time,’ ” Dr. Kamal and his associates wrote.

When it comes to palliative care for advanced nonmalignant lung disease, Dr. De Palo said, patients and families may not feel ready to discuss end-of-life issues, and providers may find it difficult to initiate these conversations. “From the moment of diagnosis, the focus of a patient’s care for providers is curative care.” Including a palliative focus can be difficult.

Nonmalignant pulmonary diseases often carry an “uncertain short-term prognosis,” the ATS guidelines stated, and experts echoed that point. “I believe our confidence in determination of prognosis is a key factor in hesitation or delay in engaging palliative care,” said David Bowton, MD, a professor specializing in critical care at Wake Forest School of Medicine, Winston-Salem, N.C. Oncology patients needing ICU care usually have “considerably higher” mortality than the rates of 20%-45% and 15%-30% that are cited for ILD and COPD patients, respectively, he said. Furthermore, there are seemingly accurate scoring systems for predicting short-term mortality in critically ill cancer patients, which is not the case for ILD or COPD, he added.

Such factors point to differences in disease trajectory. “In this study, it is likely that the patients with cancer diagnoses more often received the elements of palliative care in the ICU because it was clearly communicated to the intensive care providers that the opportunities for curative care were exhausted,” Dr. De Palo said. “With care for end-stage chronic respiratory diseases, ICU care can usually optimize breathing enough to get the patient off the vent and stabilized at their previous functional plateau or, more often, at a lower functional plateau, until the next shortness of breath episode.”

Given these challenges and uncertainties, how can clinicians improve palliative care for patients with advanced nonmalignant lung diseases? “Simple. Have a discussion with everyone about what their expectations are,” said Dr. Waxman. “Find out what is important to them and what their goals of therapy are. Help them understand the reality of what actually will be possible to accomplish in a hospitalization, a surgery, or a therapy.”

Dr. De Palo agreed. “For my patients with end-stage respiratory disease, we often discuss whether a sustaining therapy of mechanical ventilation would offer any benefit, and what role cardiopulmonary resuscitation should play in the context of their wishes for care as their disease progresses,” she said. “I believe that providers and health care organizations should offer patients the spectrum of curative and palliative care, and work together to develop a palliative care program where one does not exist,” she stressed. Access to “the full spectrum of care – from curative to palliative – will provide the compassion and quality of life at each stage of their chronic disease.”

Intensivists should also ensure that all ICU patients receive consultations with providers “who can look more at the big picture of their health care, not just at their admission diagnosis and the specific treatment they are receiving,” Dr. Waxman said. And Dr. Bowton offered a final caveat. “While it appears obvious that providing palliative care consultation or integrating elements of palliative care into our routine ICU care will improve the experience for our patients and their families, this has been difficult to demonstrate in well-designed studies,” he said. “Thus, rather than focusing solely on our apparent shortcomings in providing palliative care to our ICU patients with ILD and COPD, we should vigorously support efforts to ascertain what components of palliative care and what ‘dose’ are most effective in alleviating physical and emotional distress.”

The National Institute of Nursing Research funded the study by Dr. Brown and her associates, who reported no relevant financial conflicts of interest.

Patients treated for acute MI at high-performing hospitals – those with the best performance on 30-day mortality quality measures assessed by the Centers for Medicare & Medicaid Services – had longer life expectancies than did patients treated at low-performing hospitals, according to a report published online Oct. 6 in the New England Journal of Medicine.

This survival benefit persisted through 17 years of follow-up, said Emily Bucholz, MD, of Boston Children’s Hospital, and her associates.

Until now, researchers didn’t know whether the short-term survival benefit at high-performing hospitals would wane over time, which “would lend support to the theory that these hospitals discharge more patients alive but with higher subsequent mortality.” The results of this secondary analysis of data from a nationally representative cohort study indicate that, instead, the superior quality of care delivered at high-performing hospitals appears to “produce an early benefit that endures over time,” Dr. Bucholz and her associates noted. The investigators assessed long-term life expectancy using data from the Cooperative Cardiovascular Project, which enrolled Medicare beneficiaries aged 65 years and older treated for acute MI in 1994-1996. They focused on 119,735 patients admitted to 1,824 hospitals. They grouped the hospitals according to their case mixes (a measure of patients’ severity of illness) and calculated risk-standardized mortality rates according to CMS criteria.

“We found that patients treated at high-performing hospitals ... lived, on average, between 0.74 and 1.14 years longer after acute MI than [did] those treated at low-performing hospitals. These findings were consistent across case-mix strata, which indicates that the relationship between hospital performance and long-term patient outcomes is independent of hospital case mix,” Dr. Bucholz and her associates said (N Engl J Med. 2016 Oct 6. doi: 10.1056/NEJMoa1513223).

These findings show that the early survival advantage achieved by high-performing hospitals is durable, and that “investing in initiatives to improve short-term hospital performance may also improve patient outcomes over the long term,” they added.

Patients treated for acute MI at high-performing hospitals – those with the best performance on 30-day mortality quality measures assessed by the Centers for Medicare & Medicaid Services – had longer life expectancies than did patients treated at low-performing hospitals, according to a report published online Oct. 6 in the New England Journal of Medicine.

This survival benefit persisted through 17 years of follow-up, said Emily Bucholz, MD, of Boston Children’s Hospital, and her associates.

Until now, researchers didn’t know whether the short-term survival benefit at high-performing hospitals would wane over time, which “would lend support to the theory that these hospitals discharge more patients alive but with higher subsequent mortality.” The results of this secondary analysis of data from a nationally representative cohort study indicate that, instead, the superior quality of care delivered at high-performing hospitals appears to “produce an early benefit that endures over time,” Dr. Bucholz and her associates noted. The investigators assessed long-term life expectancy using data from the Cooperative Cardiovascular Project, which enrolled Medicare beneficiaries aged 65 years and older treated for acute MI in 1994-1996. They focused on 119,735 patients admitted to 1,824 hospitals. They grouped the hospitals according to their case mixes (a measure of patients’ severity of illness) and calculated risk-standardized mortality rates according to CMS criteria.

“We found that patients treated at high-performing hospitals ... lived, on average, between 0.74 and 1.14 years longer after acute MI than [did] those treated at low-performing hospitals. These findings were consistent across case-mix strata, which indicates that the relationship between hospital performance and long-term patient outcomes is independent of hospital case mix,” Dr. Bucholz and her associates said (N Engl J Med. 2016 Oct 6. doi: 10.1056/NEJMoa1513223).

These findings show that the early survival advantage achieved by high-performing hospitals is durable, and that “investing in initiatives to improve short-term hospital performance may also improve patient outcomes over the long term,” they added.

Patients treated for acute MI at high-performing hospitals – those with the best performance on 30-day mortality quality measures assessed by the Centers for Medicare & Medicaid Services – had longer life expectancies than did patients treated at low-performing hospitals, according to a report published online Oct. 6 in the New England Journal of Medicine.

This survival benefit persisted through 17 years of follow-up, said Emily Bucholz, MD, of Boston Children’s Hospital, and her associates.

Until now, researchers didn’t know whether the short-term survival benefit at high-performing hospitals would wane over time, which “would lend support to the theory that these hospitals discharge more patients alive but with higher subsequent mortality.” The results of this secondary analysis of data from a nationally representative cohort study indicate that, instead, the superior quality of care delivered at high-performing hospitals appears to “produce an early benefit that endures over time,” Dr. Bucholz and her associates noted. The investigators assessed long-term life expectancy using data from the Cooperative Cardiovascular Project, which enrolled Medicare beneficiaries aged 65 years and older treated for acute MI in 1994-1996. They focused on 119,735 patients admitted to 1,824 hospitals. They grouped the hospitals according to their case mixes (a measure of patients’ severity of illness) and calculated risk-standardized mortality rates according to CMS criteria.

“We found that patients treated at high-performing hospitals ... lived, on average, between 0.74 and 1.14 years longer after acute MI than [did] those treated at low-performing hospitals. These findings were consistent across case-mix strata, which indicates that the relationship between hospital performance and long-term patient outcomes is independent of hospital case mix,” Dr. Bucholz and her associates said (N Engl J Med. 2016 Oct 6. doi: 10.1056/NEJMoa1513223).

These findings show that the early survival advantage achieved by high-performing hospitals is durable, and that “investing in initiatives to improve short-term hospital performance may also improve patient outcomes over the long term,” they added.

Influenza vaccine coverage among U.S. health care personnel increased very slightly during the 2015-2016 flu season, with 79% reporting that they received the shot, compared with 77% in 2014-2015.

Hospital personnel were most likely to be covered (91%) and long-term care personnel least likely to be covered (69%), Carla L. Black, PhD, wrote in the Sept. 30 issue of Morbidity and Mortality Weekly Report (2016;65:1026-31). Coverage among health care personnel working in long-term care settings did increase, however, from 64% in the 2014-2015 seasons to 69% in the 2015-2016 season, Dr. Black and colleagues noted.

“Although low, this is the only setting with an appreciable increase in coverage, compared with last season. Influenza vaccination among health care personnel in long-term care settings is especially important because influenza vaccine effectiveness is generally lowest in the elderly,” according to Dr Black, an epidemiologist with the Centers for Disease Control and Prevention.

CDC conducted the Internet survey of 2,258 health care workers from March to April, 2016.

Physicians had the highest level of coverage (95.6%), while health care assistants and aides had the lowest (64.5%). Employers also exerted an influence on coverage. Most respondents (73%) were vaccinated at work. Coverage was highest (96.5%) at facilities where vaccination was required and lowest (45%) where vaccination was not required, promoted, or offered on site.

“Employer vaccination requirements likely contributed to the observed gradual increase in vaccination among health care personnel working in settings with the lowest coverage,” the investigators noted. “In the absence of vaccination requirements, expanding the number of health care locations offering vaccination on site, over multiple days, and at no cost might help sustain and improve influenza vaccination coverage among health care personnel, including in long-term care settings.”

As a CDC employee, Dr. Black has no financial conflicts.

[email protected]

Influenza vaccine coverage among U.S. health care personnel increased very slightly during the 2015-2016 flu season, with 79% reporting that they received the shot, compared with 77% in 2014-2015.

Hospital personnel were most likely to be covered (91%) and long-term care personnel least likely to be covered (69%), Carla L. Black, PhD, wrote in the Sept. 30 issue of Morbidity and Mortality Weekly Report (2016;65:1026-31). Coverage among health care personnel working in long-term care settings did increase, however, from 64% in the 2014-2015 seasons to 69% in the 2015-2016 season, Dr. Black and colleagues noted.

“Although low, this is the only setting with an appreciable increase in coverage, compared with last season. Influenza vaccination among health care personnel in long-term care settings is especially important because influenza vaccine effectiveness is generally lowest in the elderly,” according to Dr Black, an epidemiologist with the Centers for Disease Control and Prevention.

CDC conducted the Internet survey of 2,258 health care workers from March to April, 2016.

Physicians had the highest level of coverage (95.6%), while health care assistants and aides had the lowest (64.5%). Employers also exerted an influence on coverage. Most respondents (73%) were vaccinated at work. Coverage was highest (96.5%) at facilities where vaccination was required and lowest (45%) where vaccination was not required, promoted, or offered on site.

“Employer vaccination requirements likely contributed to the observed gradual increase in vaccination among health care personnel working in settings with the lowest coverage,” the investigators noted. “In the absence of vaccination requirements, expanding the number of health care locations offering vaccination on site, over multiple days, and at no cost might help sustain and improve influenza vaccination coverage among health care personnel, including in long-term care settings.”

As a CDC employee, Dr. Black has no financial conflicts.

[email protected]

Influenza vaccine coverage among U.S. health care personnel increased very slightly during the 2015-2016 flu season, with 79% reporting that they received the shot, compared with 77% in 2014-2015.

Hospital personnel were most likely to be covered (91%) and long-term care personnel least likely to be covered (69%), Carla L. Black, PhD, wrote in the Sept. 30 issue of Morbidity and Mortality Weekly Report (2016;65:1026-31). Coverage among health care personnel working in long-term care settings did increase, however, from 64% in the 2014-2015 seasons to 69% in the 2015-2016 season, Dr. Black and colleagues noted.

“Although low, this is the only setting with an appreciable increase in coverage, compared with last season. Influenza vaccination among health care personnel in long-term care settings is especially important because influenza vaccine effectiveness is generally lowest in the elderly,” according to Dr Black, an epidemiologist with the Centers for Disease Control and Prevention.

CDC conducted the Internet survey of 2,258 health care workers from March to April, 2016.

Physicians had the highest level of coverage (95.6%), while health care assistants and aides had the lowest (64.5%). Employers also exerted an influence on coverage. Most respondents (73%) were vaccinated at work. Coverage was highest (96.5%) at facilities where vaccination was required and lowest (45%) where vaccination was not required, promoted, or offered on site.

“Employer vaccination requirements likely contributed to the observed gradual increase in vaccination among health care personnel working in settings with the lowest coverage,” the investigators noted. “In the absence of vaccination requirements, expanding the number of health care locations offering vaccination on site, over multiple days, and at no cost might help sustain and improve influenza vaccination coverage among health care personnel, including in long-term care settings.”

As a CDC employee, Dr. Black has no financial conflicts.

[email protected]

Tuberculosis patients admitted to intensive care units with acute respiratory failure had significantly better survival at 90 days after treatment with corticosteroids and anti-TB drugs, compared with patients not treated with the steroids, according to a retrospective study.

An adjusted inverse probability of treatment weighted analysis using propensity scores revealed corticosteroid use to be independently associated with a significantly reduced 90-day mortality rate (OR = 0.47; 95% CI, 0.22-0.98). This statistical approach was used because it reduces selection bias and other potential confounding factors in a way that a multivariate analysis cannot, wrote Ji Young Yang, MD, of Busan (South Korea) Paik Hospital and Inje University College of Medicine in Busan.

Zerbor/Thinkstock

Tuberculosis patients admitted to intensive care units with acute respiratory failure had significantly better survival at 90 days after treatment with corticosteroids and anti-TB drugs, compared with patients not treated with the steroids, according to a retrospective study.

An adjusted inverse probability of treatment weighted analysis using propensity scores revealed corticosteroid use to be independently associated with a significantly reduced 90-day mortality rate (OR = 0.47; 95% CI, 0.22-0.98). This statistical approach was used because it reduces selection bias and other potential confounding factors in a way that a multivariate analysis cannot, wrote Ji Young Yang, MD, of Busan (South Korea) Paik Hospital and Inje University College of Medicine in Busan.

Zerbor/Thinkstock

Tuberculosis patients admitted to intensive care units with acute respiratory failure had significantly better survival at 90 days after treatment with corticosteroids and anti-TB drugs, compared with patients not treated with the steroids, according to a retrospective study.

An adjusted inverse probability of treatment weighted analysis using propensity scores revealed corticosteroid use to be independently associated with a significantly reduced 90-day mortality rate (OR = 0.47; 95% CI, 0.22-0.98). This statistical approach was used because it reduces selection bias and other potential confounding factors in a way that a multivariate analysis cannot, wrote Ji Young Yang, MD, of Busan (South Korea) Paik Hospital and Inje University College of Medicine in Busan.

Zerbor/Thinkstock

ORLANDO – Early experience with extended half-life clotting factor concentrates suggests these products are generally safe and effective, at least in the short term, according to hemophilia experts.

“In adolescent and adult patients, the extended half-life clotting factor concentrates demonstrate efficacy and safety in a variety of clinical settings, including prophylaxis, treatment of bleeds, and perisurgical hemostasis,” said Johnny Mahlangu, MD, director of the Haemophilia Comprehensive Care Centre in Johannesburg, South Africa.

The X factor

Extended half-life products currently available or in development include those created through fusion technology, including factor VIII products for treatment of hemophilia A, factor IX for treating hemophilia B, and factor VII products for treating factor VII deficiency (Alexander’s Disease).

More recent products created through pegylation technology include recombinant FVIII products.

Factor IX EHL CFCs

The three recombinant factor IX (rFIX) products that have completed phase III clinical trials are: nonacog beta pegol (N9-GP), rFIXFc (Alprolix), and rFIX-FP (Idelvion). The latter two are approved by the U.S. Food and Drug Administration; the former is waiting European and U.S. approval.

In clinical trials in adolescents and adults, these agents were associated with low median annualized bleeding rates, as follows:

• rFIXFc: 3.0 for a 50 IU/kg dose given every 7 days, and 1.4 for a 100 IU/kg dose given every 10 days

• rFIX-FP: 0.0 for a 40 IU/kg dose given every 7 days, and 1.08 for a 75 IU/kg dose given every 14 days

• Nonacog beta pegol: 2.93 for a 10 IU/kg dose and 1.0 for a 40 IU/kg dose, each given every 7 days.

All of these agents effectively treated bleeding episodes after one or two doses, Dr. Mahlangu said. The respective overall hemostatic efficacy rates were 97.2%, 96.7%, and 97.1%.

Safety analyses from published studies showed that no patients exposed to any of these agents developed inhibiting antibodies, although three patients treated with rFIXFc and nonacog beta pegol each developed noninhibitory antibodies.

There were no deaths from thromboembolic episodes and no drug-related serious adverse events.

Data are more limited for children treated with rFIX products, Dr. Young noted. In studies thus far, no children developed inhibitors, although this population had been heavily pretreated, he noted. Median annualized bleeding rates ranged from 1 to 3 and did not differ significantly between the products.

Factor VIII EHL CFCs

Four factor VIII EHL products are available or in development: rFVIIIFc (Eloctate); antihemophilic factor, pegylated (Adynovate); turoctocog alfa pegol (N8-GP); and BAY 94-9027. The former two agents are approved in the United States.

In adults and adolescents, these products have half-lives comparatively shorter than those seen with Factor IX products, the researchers noted.

Annualized bleeding rates for patients on prophylaxis with these agents were less than 4 bleeds per year, ranging from 1.3 to 3.6. In all, 96% of bleeds that did occur could be resolved with one or two injections of the extended half-life rFVIII products.

All patients had at least 50 exposures to these products, and none have developed inhibitors to date.

Only one study has been published to date of factor VIII products in children, comparing a standard half-life product with rFVIIIFc, Dr. Young said.

In this study, the patients were treated with a twice weekly, split-dose regimen. No patients developed inhibitors, and the mean annualized bleeding rate was a low 1.96.

Dr. Mahlangu disclosed research grants from Bayer, Biogen, CSL Behring, Novo Nordisk, and Roche, and speakers bureau participation for Amgen, Biotest, Biogen, CSL Behring, Novo Nordisk, and Sobi. Dr. Young disclosed honoraria and consulting fees from Baxalta, Bayer, Biogen, CSL Behring, and Novo Nordisk. Ellis J. Neufeld, MD, PhD, the invited discussant of the presentation, disclosed institutional grants from Baxalta, Novo Nordisk, and Octapharma, consulting/advising for those companies and for CSL Behring, Genentech, Hema Biologics, and Pfizer.

ORLANDO – Early experience with extended half-life clotting factor concentrates suggests these products are generally safe and effective, at least in the short term, according to hemophilia experts.

“In adolescent and adult patients, the extended half-life clotting factor concentrates demonstrate efficacy and safety in a variety of clinical settings, including prophylaxis, treatment of bleeds, and perisurgical hemostasis,” said Johnny Mahlangu, MD, director of the Haemophilia Comprehensive Care Centre in Johannesburg, South Africa.

The X factor

Extended half-life products currently available or in development include those created through fusion technology, including factor VIII products for treatment of hemophilia A, factor IX for treating hemophilia B, and factor VII products for treating factor VII deficiency (Alexander’s Disease).

More recent products created through pegylation technology include recombinant FVIII products.

Factor IX EHL CFCs

The three recombinant factor IX (rFIX) products that have completed phase III clinical trials are: nonacog beta pegol (N9-GP), rFIXFc (Alprolix), and rFIX-FP (Idelvion). The latter two are approved by the U.S. Food and Drug Administration; the former is waiting European and U.S. approval.

In clinical trials in adolescents and adults, these agents were associated with low median annualized bleeding rates, as follows:

• rFIXFc: 3.0 for a 50 IU/kg dose given every 7 days, and 1.4 for a 100 IU/kg dose given every 10 days

• rFIX-FP: 0.0 for a 40 IU/kg dose given every 7 days, and 1.08 for a 75 IU/kg dose given every 14 days

• Nonacog beta pegol: 2.93 for a 10 IU/kg dose and 1.0 for a 40 IU/kg dose, each given every 7 days.

All of these agents effectively treated bleeding episodes after one or two doses, Dr. Mahlangu said. The respective overall hemostatic efficacy rates were 97.2%, 96.7%, and 97.1%.

Safety analyses from published studies showed that no patients exposed to any of these agents developed inhibiting antibodies, although three patients treated with rFIXFc and nonacog beta pegol each developed noninhibitory antibodies.

There were no deaths from thromboembolic episodes and no drug-related serious adverse events.

Data are more limited for children treated with rFIX products, Dr. Young noted. In studies thus far, no children developed inhibitors, although this population had been heavily pretreated, he noted. Median annualized bleeding rates ranged from 1 to 3 and did not differ significantly between the products.

Factor VIII EHL CFCs

Four factor VIII EHL products are available or in development: rFVIIIFc (Eloctate); antihemophilic factor, pegylated (Adynovate); turoctocog alfa pegol (N8-GP); and BAY 94-9027. The former two agents are approved in the United States.

In adults and adolescents, these products have half-lives comparatively shorter than those seen with Factor IX products, the researchers noted.

Annualized bleeding rates for patients on prophylaxis with these agents were less than 4 bleeds per year, ranging from 1.3 to 3.6. In all, 96% of bleeds that did occur could be resolved with one or two injections of the extended half-life rFVIII products.

All patients had at least 50 exposures to these products, and none have developed inhibitors to date.

Only one study has been published to date of factor VIII products in children, comparing a standard half-life product with rFVIIIFc, Dr. Young said.

In this study, the patients were treated with a twice weekly, split-dose regimen. No patients developed inhibitors, and the mean annualized bleeding rate was a low 1.96.

Dr. Mahlangu disclosed research grants from Bayer, Biogen, CSL Behring, Novo Nordisk, and Roche, and speakers bureau participation for Amgen, Biotest, Biogen, CSL Behring, Novo Nordisk, and Sobi. Dr. Young disclosed honoraria and consulting fees from Baxalta, Bayer, Biogen, CSL Behring, and Novo Nordisk. Ellis J. Neufeld, MD, PhD, the invited discussant of the presentation, disclosed institutional grants from Baxalta, Novo Nordisk, and Octapharma, consulting/advising for those companies and for CSL Behring, Genentech, Hema Biologics, and Pfizer.

ORLANDO – Early experience with extended half-life clotting factor concentrates suggests these products are generally safe and effective, at least in the short term, according to hemophilia experts.

“In adolescent and adult patients, the extended half-life clotting factor concentrates demonstrate efficacy and safety in a variety of clinical settings, including prophylaxis, treatment of bleeds, and perisurgical hemostasis,” said Johnny Mahlangu, MD, director of the Haemophilia Comprehensive Care Centre in Johannesburg, South Africa.

The X factor

Extended half-life products currently available or in development include those created through fusion technology, including factor VIII products for treatment of hemophilia A, factor IX for treating hemophilia B, and factor VII products for treating factor VII deficiency (Alexander’s Disease).

More recent products created through pegylation technology include recombinant FVIII products.

Factor IX EHL CFCs

The three recombinant factor IX (rFIX) products that have completed phase III clinical trials are: nonacog beta pegol (N9-GP), rFIXFc (Alprolix), and rFIX-FP (Idelvion). The latter two are approved by the U.S. Food and Drug Administration; the former is waiting European and U.S. approval.

In clinical trials in adolescents and adults, these agents were associated with low median annualized bleeding rates, as follows:

• rFIXFc: 3.0 for a 50 IU/kg dose given every 7 days, and 1.4 for a 100 IU/kg dose given every 10 days

• rFIX-FP: 0.0 for a 40 IU/kg dose given every 7 days, and 1.08 for a 75 IU/kg dose given every 14 days

• Nonacog beta pegol: 2.93 for a 10 IU/kg dose and 1.0 for a 40 IU/kg dose, each given every 7 days.

All of these agents effectively treated bleeding episodes after one or two doses, Dr. Mahlangu said. The respective overall hemostatic efficacy rates were 97.2%, 96.7%, and 97.1%.

Safety analyses from published studies showed that no patients exposed to any of these agents developed inhibiting antibodies, although three patients treated with rFIXFc and nonacog beta pegol each developed noninhibitory antibodies.

There were no deaths from thromboembolic episodes and no drug-related serious adverse events.

Data are more limited for children treated with rFIX products, Dr. Young noted. In studies thus far, no children developed inhibitors, although this population had been heavily pretreated, he noted. Median annualized bleeding rates ranged from 1 to 3 and did not differ significantly between the products.

Factor VIII EHL CFCs

Four factor VIII EHL products are available or in development: rFVIIIFc (Eloctate); antihemophilic factor, pegylated (Adynovate); turoctocog alfa pegol (N8-GP); and BAY 94-9027. The former two agents are approved in the United States.

In adults and adolescents, these products have half-lives comparatively shorter than those seen with Factor IX products, the researchers noted.

Annualized bleeding rates for patients on prophylaxis with these agents were less than 4 bleeds per year, ranging from 1.3 to 3.6. In all, 96% of bleeds that did occur could be resolved with one or two injections of the extended half-life rFVIII products.

All patients had at least 50 exposures to these products, and none have developed inhibitors to date.

Only one study has been published to date of factor VIII products in children, comparing a standard half-life product with rFVIIIFc, Dr. Young said.

In this study, the patients were treated with a twice weekly, split-dose regimen. No patients developed inhibitors, and the mean annualized bleeding rate was a low 1.96.

Dr. Mahlangu disclosed research grants from Bayer, Biogen, CSL Behring, Novo Nordisk, and Roche, and speakers bureau participation for Amgen, Biotest, Biogen, CSL Behring, Novo Nordisk, and Sobi. Dr. Young disclosed honoraria and consulting fees from Baxalta, Bayer, Biogen, CSL Behring, and Novo Nordisk. Ellis J. Neufeld, MD, PhD, the invited discussant of the presentation, disclosed institutional grants from Baxalta, Novo Nordisk, and Octapharma, consulting/advising for those companies and for CSL Behring, Genentech, Hema Biologics, and Pfizer.

Rivaroxaban is associated with significantly more intra- and extracranial bleeding than is dabigatran in older patients who have nonvalvular atrial fibrillation, according to a report published online Oct. 3 in JAMA Internal Medicine.

This is the principal finding of a retrospective cohort study – the only study to directly compare the two oral non–vitamin-K-antagonists – that involved more than 118,000 patients who initiated anticoagulation treatment during a 2.5-year period. The Centers for Medicare & Medicaid Services and the Food and Drug Administration jointly conducted the study.

During the study period, rivaroxaban was used 2-3 times more often than was dabigatran in AF patients in the United States, “perhaps partly because of prescriber misperceptions about bleeding risks with dabigatran, arising from FDA receipt of a large number of postmarketing case reports following its approval. Ironically, we [now find] substantially higher bleeding risks with use of rivaroxaban than dabigatran,” said David J. Graham, MD, of the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA, Silver Spring, Md., and his associates.

The researchers assessed Medicare beneficiaries who initiated standard oral doses of rivaroxaban (66,651 patients) or dabigatran (52,240 patients) and were followed for a mean of 110 days.

The primary outcome measure – a composite of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding events including GI bleeding, and mortality – occurred in significantly more patients taking rivaroxaban than in those taking dabigatran. When the individual components of this composite outcome were considered, rivaroxaban was associated with significant increases in intracranial hemorrhage (HR, 1.65), major extracranial bleeding (HR, 1.48), and major GI bleeding (HR, 1.40); a nonsignificant decrease in thromboembolic stroke (HR, 0.81); and a nonsignificant increase in mortality (HR, 1.15).

In a further analysis of the data, rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment. In addition, rivaroxaban was associated with a significantly increased risk of death in two subgroups of patients: those aged 75 and older and those whose CHADS-2 scores indicated higher bleeding risk, Dr. Graham and his associates said (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.5954).

Of note, “the net increase in intracranial hemorrhage, the outcome with the highest case fatality rate, exceeded the net reduction in thromboembolic stroke” with rivaroxaban treatment, they added.

Rivaroxaban is associated with significantly more intra- and extracranial bleeding than is dabigatran in older patients who have nonvalvular atrial fibrillation, according to a report published online Oct. 3 in JAMA Internal Medicine.

This is the principal finding of a retrospective cohort study – the only study to directly compare the two oral non–vitamin-K-antagonists – that involved more than 118,000 patients who initiated anticoagulation treatment during a 2.5-year period. The Centers for Medicare & Medicaid Services and the Food and Drug Administration jointly conducted the study.

During the study period, rivaroxaban was used 2-3 times more often than was dabigatran in AF patients in the United States, “perhaps partly because of prescriber misperceptions about bleeding risks with dabigatran, arising from FDA receipt of a large number of postmarketing case reports following its approval. Ironically, we [now find] substantially higher bleeding risks with use of rivaroxaban than dabigatran,” said David J. Graham, MD, of the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA, Silver Spring, Md., and his associates.

The researchers assessed Medicare beneficiaries who initiated standard oral doses of rivaroxaban (66,651 patients) or dabigatran (52,240 patients) and were followed for a mean of 110 days.

The primary outcome measure – a composite of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding events including GI bleeding, and mortality – occurred in significantly more patients taking rivaroxaban than in those taking dabigatran. When the individual components of this composite outcome were considered, rivaroxaban was associated with significant increases in intracranial hemorrhage (HR, 1.65), major extracranial bleeding (HR, 1.48), and major GI bleeding (HR, 1.40); a nonsignificant decrease in thromboembolic stroke (HR, 0.81); and a nonsignificant increase in mortality (HR, 1.15).

In a further analysis of the data, rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment. In addition, rivaroxaban was associated with a significantly increased risk of death in two subgroups of patients: those aged 75 and older and those whose CHADS-2 scores indicated higher bleeding risk, Dr. Graham and his associates said (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.5954).

Of note, “the net increase in intracranial hemorrhage, the outcome with the highest case fatality rate, exceeded the net reduction in thromboembolic stroke” with rivaroxaban treatment, they added.

Rivaroxaban is associated with significantly more intra- and extracranial bleeding than is dabigatran in older patients who have nonvalvular atrial fibrillation, according to a report published online Oct. 3 in JAMA Internal Medicine.

This is the principal finding of a retrospective cohort study – the only study to directly compare the two oral non–vitamin-K-antagonists – that involved more than 118,000 patients who initiated anticoagulation treatment during a 2.5-year period. The Centers for Medicare & Medicaid Services and the Food and Drug Administration jointly conducted the study.

During the study period, rivaroxaban was used 2-3 times more often than was dabigatran in AF patients in the United States, “perhaps partly because of prescriber misperceptions about bleeding risks with dabigatran, arising from FDA receipt of a large number of postmarketing case reports following its approval. Ironically, we [now find] substantially higher bleeding risks with use of rivaroxaban than dabigatran,” said David J. Graham, MD, of the Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, FDA, Silver Spring, Md., and his associates.

The researchers assessed Medicare beneficiaries who initiated standard oral doses of rivaroxaban (66,651 patients) or dabigatran (52,240 patients) and were followed for a mean of 110 days.

The primary outcome measure – a composite of thromboembolic stroke, intracranial hemorrhage, major extracranial bleeding events including GI bleeding, and mortality – occurred in significantly more patients taking rivaroxaban than in those taking dabigatran. When the individual components of this composite outcome were considered, rivaroxaban was associated with significant increases in intracranial hemorrhage (HR, 1.65), major extracranial bleeding (HR, 1.48), and major GI bleeding (HR, 1.40); a nonsignificant decrease in thromboembolic stroke (HR, 0.81); and a nonsignificant increase in mortality (HR, 1.15).

In a further analysis of the data, rivaroxaban was linked to 2.3 excess cases of intracranial hemorrhage, 13 excess cases of major extracranial bleeding, 9.4 excess cases of major GI bleeding, and 3.1 excess deaths per 1,000 person-years of treatment. In addition, rivaroxaban was associated with a significantly increased risk of death in two subgroups of patients: those aged 75 and older and those whose CHADS-2 scores indicated higher bleeding risk, Dr. Graham and his associates said (JAMA Intern. Med. 2016 Oct 3. doi: 10.1001/jamainternmed.2016.5954).

Of note, “the net increase in intracranial hemorrhage, the outcome with the highest case fatality rate, exceeded the net reduction in thromboembolic stroke” with rivaroxaban treatment, they added.