Targeting insulin resistance (IR) may be an important strategy to reduce cardiovascular events in patients infected with HIV, say researchers from Johns Hopkins University in Baltimore, Maryland, and Northwestern University in Chicago, Illinois.

Related: Homelessness, HIV, and HCV

To find out whether IR was greater in men infected with HIV and, consequently, whether coronary artery disease would be amplified in those patients, the researchers analyzed data collected over 10 years from 448 men infected with HIV and 306 uninfected men in the Multicenter AIDS Cohort Study. They measured fasting serum insulin and glucose and computed the homeostatic model assessment of IR. At the end of the study, they assessed atherosclerotic disease with computed tomographic angiography (CTA).

Insulin resistance was higher in men infected with HIV when averaged over the course of the study and when measured with CTA. The prevalence of coronary stenosis ≥ 50% was similar between both groups. Men with mean IR values in the highest tertile had nearly 3 times the odds of coronary stenosis than men in the lowest tertile.

Men infected with HIV (of whom about 11% also had hepatitis C infection) were more insulin resistant than those without HIV. Insulin resistance was associated in all the study participants with common cardiovascular disease (CVD) risk factors, such as hypertension, but also with hepatitis C infection. The association between IR and coronary artery stenosis remained after adjustment for multiple CVD risk factors as well as HIV-related variables. That may mean the association is independent of the severity of immune suppression or HIV control.

Related: HIV Antibody Infusion Safely Reduces Viral Load

Coronary artery stenosis was associated with IR in both groups, particularly when IR values were assessed over the 10 years rather than at the time of the angiography. The researchers say this suggests that long-standing IR is an important contributor to CVD in patients infected with HIV.

Source: Brener MI, Post WS, Haberlen SA, et al. Am J Cardiol. 2016;117(6):993-1000.doi: 10.1016/j.amjcard.2015.12.037. 

Targeting insulin resistance (IR) may be an important strategy to reduce cardiovascular events in patients infected with HIV, say researchers from Johns Hopkins University in Baltimore, Maryland, and Northwestern University in Chicago, Illinois.

Related: Homelessness, HIV, and HCV

To find out whether IR was greater in men infected with HIV and, consequently, whether coronary artery disease would be amplified in those patients, the researchers analyzed data collected over 10 years from 448 men infected with HIV and 306 uninfected men in the Multicenter AIDS Cohort Study. They measured fasting serum insulin and glucose and computed the homeostatic model assessment of IR. At the end of the study, they assessed atherosclerotic disease with computed tomographic angiography (CTA).

Insulin resistance was higher in men infected with HIV when averaged over the course of the study and when measured with CTA. The prevalence of coronary stenosis ≥ 50% was similar between both groups. Men with mean IR values in the highest tertile had nearly 3 times the odds of coronary stenosis than men in the lowest tertile.

Men infected with HIV (of whom about 11% also had hepatitis C infection) were more insulin resistant than those without HIV. Insulin resistance was associated in all the study participants with common cardiovascular disease (CVD) risk factors, such as hypertension, but also with hepatitis C infection. The association between IR and coronary artery stenosis remained after adjustment for multiple CVD risk factors as well as HIV-related variables. That may mean the association is independent of the severity of immune suppression or HIV control.

Related: HIV Antibody Infusion Safely Reduces Viral Load

Coronary artery stenosis was associated with IR in both groups, particularly when IR values were assessed over the 10 years rather than at the time of the angiography. The researchers say this suggests that long-standing IR is an important contributor to CVD in patients infected with HIV.

Source: Brener MI, Post WS, Haberlen SA, et al. Am J Cardiol. 2016;117(6):993-1000.doi: 10.1016/j.amjcard.2015.12.037. 

Targeting insulin resistance (IR) may be an important strategy to reduce cardiovascular events in patients infected with HIV, say researchers from Johns Hopkins University in Baltimore, Maryland, and Northwestern University in Chicago, Illinois.

Related: Homelessness, HIV, and HCV

To find out whether IR was greater in men infected with HIV and, consequently, whether coronary artery disease would be amplified in those patients, the researchers analyzed data collected over 10 years from 448 men infected with HIV and 306 uninfected men in the Multicenter AIDS Cohort Study. They measured fasting serum insulin and glucose and computed the homeostatic model assessment of IR. At the end of the study, they assessed atherosclerotic disease with computed tomographic angiography (CTA).

Insulin resistance was higher in men infected with HIV when averaged over the course of the study and when measured with CTA. The prevalence of coronary stenosis ≥ 50% was similar between both groups. Men with mean IR values in the highest tertile had nearly 3 times the odds of coronary stenosis than men in the lowest tertile.

Men infected with HIV (of whom about 11% also had hepatitis C infection) were more insulin resistant than those without HIV. Insulin resistance was associated in all the study participants with common cardiovascular disease (CVD) risk factors, such as hypertension, but also with hepatitis C infection. The association between IR and coronary artery stenosis remained after adjustment for multiple CVD risk factors as well as HIV-related variables. That may mean the association is independent of the severity of immune suppression or HIV control.

Related: HIV Antibody Infusion Safely Reduces Viral Load

Coronary artery stenosis was associated with IR in both groups, particularly when IR values were assessed over the 10 years rather than at the time of the angiography. The researchers say this suggests that long-standing IR is an important contributor to CVD in patients infected with HIV.

Source: Brener MI, Post WS, Haberlen SA, et al. Am J Cardiol. 2016;117(6):993-1000.doi: 10.1016/j.amjcard.2015.12.037. 

Headache worsening after treatment with IV dihydroergotamine (DHE) does not predict poor headache outcome in the medium term among patients with chronic migraine, according to research published March 1 in Neurology. Headache exacerbation thus is not a sufficient reason to stop treatment. Instead, neurologists should focus on controlling nausea, which is the most important modifiable factor in achieving a good headache outcome, according to the researchers.

Neurologists have used IV DHE to treat patients with migraine for decades. After receiving this therapy, some patients have transient headache worsening, and this development may be interpreted as a reason to stop the infusions. Michael Eller, MD, Assistant Clinical Professor of Neurology at the University of California, San Francisco (UCSF), and colleagues performed a retrospective chart review to determine whether transient headache worsening after IV DHE infusion predicts medium-term headache outcome in patients with chronic migraine.

The investigators included all patients with chronic migraine admitted by the UCSF Headache Service between January 1, 2008, and December 31, 2012, in their analysis. All patients received IV DHE according to a standard protocol, which included 1-mg doses administered over five days to a typical target dose of 11.25 mg. In addition, patients were premedicated with ondansetron, domperidone, or both. Participants with medication overuse (approximately 30% of the population) also received IV aspirin before receiving IV DHE.

Dr. Eller and colleagues retrospectively analyzed the prospectively collected inpatient headache diaries, progress notes, and discharge summaries. Physicians did not routinely ask patients whether they had headache exacerbation. The researchers defined DHE worsening as headache (typically, exacerbation of the underlying phenotype) or nausea increase within 30 minutes of the infusion. The treating clinician assessed and recorded medium-term headache outcome at follow-up approximately six weeks after discharge.

During the study period, 274 patients with chronic migraine had inpatient treatment with DHE. Mean age was 44, and 77% of the population was female. In all, 153 patients had been receiving migraine preventives. Headache outcome information was available for 214 patients, and patients with missing outcome data did not differ from the others in terms of age, sex, or likelihood of having nausea or medication overuse. Approximately 78% of patients with follow-up data had medium-term headache benefit following IV DHE.

Forty-one participants (19%) had headache worsening with DHE infusions. Of these patients, 66% had medium-term headache benefit, compared with 82% of patients who did not have headache exacerbation. A univariate analysis indicated that headache exacerbation with DHE infusion was associated with reduced odds of medium-term headache benefit. Multivariate logistic regression analysis adjusted for nausea, leg cramping, medication overuse, sex, and age, however, indicated that headache exacerbation with DHE was not an independent predictor of medium-term headache benefit.

Nausea was the modifiable risk factor with the greatest effect on headache outcome. In an adjusted model, nausea was significantly associated with headache exacerbation with DHE infusion. Nausea also was an independent predictor of decreased likelihood of medium-term headache benefit in the fully adjusted model, as was medication overuse. Older age was strongly associated with increased odds of headache benefit.

The results suggest that adequate nausea control might help prevent headache exacerbation, said the authors. “Clinicians in all settings should focus their efforts on aggressive nausea control during a course of IV DHE for chronic migraine,” they added. Younger patients with chronic migraine were less likely to benefit from an inpatient course of IV DHE, and this finding “highlights an even greater need for nausea control in that population.”

The study’s retrospective design was a limitation, said Dr. Eller. Some exacerbations of headache may have gone unreported, and future studies should systematically query patients for this symptom, he added.

Data Improve the Understanding of DHE

The investigation by Dr. Eller and colleagues improves our current understanding of the effects of DHE, said Andrew Charles, MD, Director of the Headache Research and Treatment Program at the University of California, Los Angeles, in an accompanying editorial. The careful documentation and systematic reporting of patient experience, although retrospective, can be valuable in characterizing common patient-management issues, he added.

In population studies, persistent frequent nausea has been associated with increased risk of progression from episodic migraine to chronic migraine. “Whether or not treatment of nausea as a ‘modifiable risk factor’ actually changes the clinical course of migraine remains unclear,” said Dr. Charles. “What is clear, however, is that nausea is a frequently disabling component of migraine that warrants aggressive therapy.” Various therapeutic options exist, but no evidence clearly supports one option over the others. “This study underscores the importance of optimizing therapy of migraine-related nausea, and of coming to a better understanding of the role of nausea and its treatment in the short- and long-term outcomes of patients with migraine,” Dr. Charles concluded.

—Erik Greb

Headache worsening after treatment with IV dihydroergotamine (DHE) does not predict poor headache outcome in the medium term among patients with chronic migraine, according to research published March 1 in Neurology. Headache exacerbation thus is not a sufficient reason to stop treatment. Instead, neurologists should focus on controlling nausea, which is the most important modifiable factor in achieving a good headache outcome, according to the researchers.

Neurologists have used IV DHE to treat patients with migraine for decades. After receiving this therapy, some patients have transient headache worsening, and this development may be interpreted as a reason to stop the infusions. Michael Eller, MD, Assistant Clinical Professor of Neurology at the University of California, San Francisco (UCSF), and colleagues performed a retrospective chart review to determine whether transient headache worsening after IV DHE infusion predicts medium-term headache outcome in patients with chronic migraine.

The investigators included all patients with chronic migraine admitted by the UCSF Headache Service between January 1, 2008, and December 31, 2012, in their analysis. All patients received IV DHE according to a standard protocol, which included 1-mg doses administered over five days to a typical target dose of 11.25 mg. In addition, patients were premedicated with ondansetron, domperidone, or both. Participants with medication overuse (approximately 30% of the population) also received IV aspirin before receiving IV DHE.

Dr. Eller and colleagues retrospectively analyzed the prospectively collected inpatient headache diaries, progress notes, and discharge summaries. Physicians did not routinely ask patients whether they had headache exacerbation. The researchers defined DHE worsening as headache (typically, exacerbation of the underlying phenotype) or nausea increase within 30 minutes of the infusion. The treating clinician assessed and recorded medium-term headache outcome at follow-up approximately six weeks after discharge.

During the study period, 274 patients with chronic migraine had inpatient treatment with DHE. Mean age was 44, and 77% of the population was female. In all, 153 patients had been receiving migraine preventives. Headache outcome information was available for 214 patients, and patients with missing outcome data did not differ from the others in terms of age, sex, or likelihood of having nausea or medication overuse. Approximately 78% of patients with follow-up data had medium-term headache benefit following IV DHE.

Forty-one participants (19%) had headache worsening with DHE infusions. Of these patients, 66% had medium-term headache benefit, compared with 82% of patients who did not have headache exacerbation. A univariate analysis indicated that headache exacerbation with DHE infusion was associated with reduced odds of medium-term headache benefit. Multivariate logistic regression analysis adjusted for nausea, leg cramping, medication overuse, sex, and age, however, indicated that headache exacerbation with DHE was not an independent predictor of medium-term headache benefit.

Nausea was the modifiable risk factor with the greatest effect on headache outcome. In an adjusted model, nausea was significantly associated with headache exacerbation with DHE infusion. Nausea also was an independent predictor of decreased likelihood of medium-term headache benefit in the fully adjusted model, as was medication overuse. Older age was strongly associated with increased odds of headache benefit.

The results suggest that adequate nausea control might help prevent headache exacerbation, said the authors. “Clinicians in all settings should focus their efforts on aggressive nausea control during a course of IV DHE for chronic migraine,” they added. Younger patients with chronic migraine were less likely to benefit from an inpatient course of IV DHE, and this finding “highlights an even greater need for nausea control in that population.”

The study’s retrospective design was a limitation, said Dr. Eller. Some exacerbations of headache may have gone unreported, and future studies should systematically query patients for this symptom, he added.

Data Improve the Understanding of DHE

The investigation by Dr. Eller and colleagues improves our current understanding of the effects of DHE, said Andrew Charles, MD, Director of the Headache Research and Treatment Program at the University of California, Los Angeles, in an accompanying editorial. The careful documentation and systematic reporting of patient experience, although retrospective, can be valuable in characterizing common patient-management issues, he added.

In population studies, persistent frequent nausea has been associated with increased risk of progression from episodic migraine to chronic migraine. “Whether or not treatment of nausea as a ‘modifiable risk factor’ actually changes the clinical course of migraine remains unclear,” said Dr. Charles. “What is clear, however, is that nausea is a frequently disabling component of migraine that warrants aggressive therapy.” Various therapeutic options exist, but no evidence clearly supports one option over the others. “This study underscores the importance of optimizing therapy of migraine-related nausea, and of coming to a better understanding of the role of nausea and its treatment in the short- and long-term outcomes of patients with migraine,” Dr. Charles concluded.

—Erik Greb

Headache worsening after treatment with IV dihydroergotamine (DHE) does not predict poor headache outcome in the medium term among patients with chronic migraine, according to research published March 1 in Neurology. Headache exacerbation thus is not a sufficient reason to stop treatment. Instead, neurologists should focus on controlling nausea, which is the most important modifiable factor in achieving a good headache outcome, according to the researchers.

Neurologists have used IV DHE to treat patients with migraine for decades. After receiving this therapy, some patients have transient headache worsening, and this development may be interpreted as a reason to stop the infusions. Michael Eller, MD, Assistant Clinical Professor of Neurology at the University of California, San Francisco (UCSF), and colleagues performed a retrospective chart review to determine whether transient headache worsening after IV DHE infusion predicts medium-term headache outcome in patients with chronic migraine.

The investigators included all patients with chronic migraine admitted by the UCSF Headache Service between January 1, 2008, and December 31, 2012, in their analysis. All patients received IV DHE according to a standard protocol, which included 1-mg doses administered over five days to a typical target dose of 11.25 mg. In addition, patients were premedicated with ondansetron, domperidone, or both. Participants with medication overuse (approximately 30% of the population) also received IV aspirin before receiving IV DHE.

Dr. Eller and colleagues retrospectively analyzed the prospectively collected inpatient headache diaries, progress notes, and discharge summaries. Physicians did not routinely ask patients whether they had headache exacerbation. The researchers defined DHE worsening as headache (typically, exacerbation of the underlying phenotype) or nausea increase within 30 minutes of the infusion. The treating clinician assessed and recorded medium-term headache outcome at follow-up approximately six weeks after discharge.

During the study period, 274 patients with chronic migraine had inpatient treatment with DHE. Mean age was 44, and 77% of the population was female. In all, 153 patients had been receiving migraine preventives. Headache outcome information was available for 214 patients, and patients with missing outcome data did not differ from the others in terms of age, sex, or likelihood of having nausea or medication overuse. Approximately 78% of patients with follow-up data had medium-term headache benefit following IV DHE.

Forty-one participants (19%) had headache worsening with DHE infusions. Of these patients, 66% had medium-term headache benefit, compared with 82% of patients who did not have headache exacerbation. A univariate analysis indicated that headache exacerbation with DHE infusion was associated with reduced odds of medium-term headache benefit. Multivariate logistic regression analysis adjusted for nausea, leg cramping, medication overuse, sex, and age, however, indicated that headache exacerbation with DHE was not an independent predictor of medium-term headache benefit.

Nausea was the modifiable risk factor with the greatest effect on headache outcome. In an adjusted model, nausea was significantly associated with headache exacerbation with DHE infusion. Nausea also was an independent predictor of decreased likelihood of medium-term headache benefit in the fully adjusted model, as was medication overuse. Older age was strongly associated with increased odds of headache benefit.

The results suggest that adequate nausea control might help prevent headache exacerbation, said the authors. “Clinicians in all settings should focus their efforts on aggressive nausea control during a course of IV DHE for chronic migraine,” they added. Younger patients with chronic migraine were less likely to benefit from an inpatient course of IV DHE, and this finding “highlights an even greater need for nausea control in that population.”

The study’s retrospective design was a limitation, said Dr. Eller. Some exacerbations of headache may have gone unreported, and future studies should systematically query patients for this symptom, he added.

Data Improve the Understanding of DHE

The investigation by Dr. Eller and colleagues improves our current understanding of the effects of DHE, said Andrew Charles, MD, Director of the Headache Research and Treatment Program at the University of California, Los Angeles, in an accompanying editorial. The careful documentation and systematic reporting of patient experience, although retrospective, can be valuable in characterizing common patient-management issues, he added.

In population studies, persistent frequent nausea has been associated with increased risk of progression from episodic migraine to chronic migraine. “Whether or not treatment of nausea as a ‘modifiable risk factor’ actually changes the clinical course of migraine remains unclear,” said Dr. Charles. “What is clear, however, is that nausea is a frequently disabling component of migraine that warrants aggressive therapy.” Various therapeutic options exist, but no evidence clearly supports one option over the others. “This study underscores the importance of optimizing therapy of migraine-related nausea, and of coming to a better understanding of the role of nausea and its treatment in the short- and long-term outcomes of patients with migraine,” Dr. Charles concluded.

—Erik Greb

Engaged hospitalists drive quality care, and SHM has the tools to help you assess the level of engagement of hospitalists in your hospital medicine group. SHM offered a Hospitalist Engagement Benchmarking Service in 2015 and analyzed engagement of approximately 1,500 hospitalists. Organizational climate, care quality, autonomy, effective motivation, and burnout risk are just a few of the domains that were benchmarked.

“The engagement survey opened conversations about everything from how we relate to the C-suite to what we can do to sustain teamwork,” says Erin Stucky Fisher, MD, MHM, pediatric hospitalist at Rady Children’s Hospital-San Diego. “[It] highlighted what was working well and identified what needs work.”

More than 80% of respondents indicated that they will utilize the service again and plan to recommend it to a colleague. Help ensure hospitalists are engaged in your hospital medicine group by registering now for the next cohort at www.hospitalmedicine.org/engage. TH

Brett Radler is SHM’s communications coordinator.

Engaged hospitalists drive quality care, and SHM has the tools to help you assess the level of engagement of hospitalists in your hospital medicine group. SHM offered a Hospitalist Engagement Benchmarking Service in 2015 and analyzed engagement of approximately 1,500 hospitalists. Organizational climate, care quality, autonomy, effective motivation, and burnout risk are just a few of the domains that were benchmarked.

“The engagement survey opened conversations about everything from how we relate to the C-suite to what we can do to sustain teamwork,” says Erin Stucky Fisher, MD, MHM, pediatric hospitalist at Rady Children’s Hospital-San Diego. “[It] highlighted what was working well and identified what needs work.”

More than 80% of respondents indicated that they will utilize the service again and plan to recommend it to a colleague. Help ensure hospitalists are engaged in your hospital medicine group by registering now for the next cohort at www.hospitalmedicine.org/engage. TH

Brett Radler is SHM’s communications coordinator.

Engaged hospitalists drive quality care, and SHM has the tools to help you assess the level of engagement of hospitalists in your hospital medicine group. SHM offered a Hospitalist Engagement Benchmarking Service in 2015 and analyzed engagement of approximately 1,500 hospitalists. Organizational climate, care quality, autonomy, effective motivation, and burnout risk are just a few of the domains that were benchmarked.

“The engagement survey opened conversations about everything from how we relate to the C-suite to what we can do to sustain teamwork,” says Erin Stucky Fisher, MD, MHM, pediatric hospitalist at Rady Children’s Hospital-San Diego. “[It] highlighted what was working well and identified what needs work.”

More than 80% of respondents indicated that they will utilize the service again and plan to recommend it to a colleague. Help ensure hospitalists are engaged in your hospital medicine group by registering now for the next cohort at www.hospitalmedicine.org/engage. TH

Brett Radler is SHM’s communications coordinator.

Ever wish you had more leadership training in medical school or your residency programs? Feel a bit overwhelmed when developing operational plans for your hospital or negotiating important contracts? Join SHM in sunny Lake Buena Vista, Fla., October 24–27, for its esteemed Leadership Academy (www.shmleadershipacademy.org). SHM Leadership Academy prepares clinicians, academicians, and administrators with vital leadership skills traditionally not taught throughout the course of medical training, tailored specifically to hospital medicine.

“SHM’s Leadership Academy teaches leadership skills for individuals all across the spectrum of the hospital team. My experience helped me to raise the bar not only to benefit myself but also my institution and especially my patients,” says Ron Greeno, MD, MHM. “I highly recommend this experience to any hospital medicine professionals who aspire to take their leadership skills to the next level.”

All three courses run concurrently over the span of the four days and are led by world-renowned faculty. This expanded meeting will provide attendees with unprecedented networking opportunities with hundreds of colleagues and enhanced career development.

Available Leadership Academy courses include:

• Leadership Foundations, a four-day course that serves as the first step in your leadership journey. Attendees learn how to evaluate personal leadership strengths and weaknesses, create and execute a communication strategy for key team members, understand key hospital drivers, examine how hospital metrics are derived, and much more. Attendees are divided into smaller moderated groups to ensure meaningful, relevant application of concepts to hands-on activities.
• Advanced Leadership: Influential Management, a course that builds skills around driving culture change through specific leadership behaviors and actions, financial storytelling, engaging in effective professional negotiation activities with proven techniques, and more through world-renowned faculty and applied exercises.

  (Prerequisite: Leadership Foundations or an advanced management degree upon course director approval)

• Advanced Leadership: Mastering Teamwork, a course developed in response to high demand from previous Leadership Academy attendees. Participants learn how to critically assess program growth opportunities and develop operational plans; utilize the principles of SWARM intelligence; lead, manage, and motivate teams in complex hospital environments; and develop effective communication strategies.

  (Prerequisite: Leadership Foundations or an advanced management degree upon course director approval.)

SHM members receive reduced rates for course tuition. For more information on how to register, visit www.SHMLeadershipAcademy.org.

Ever wish you had more leadership training in medical school or your residency programs? Feel a bit overwhelmed when developing operational plans for your hospital or negotiating important contracts? Join SHM in sunny Lake Buena Vista, Fla., October 24–27, for its esteemed Leadership Academy (www.shmleadershipacademy.org). SHM Leadership Academy prepares clinicians, academicians, and administrators with vital leadership skills traditionally not taught throughout the course of medical training, tailored specifically to hospital medicine.

“SHM’s Leadership Academy teaches leadership skills for individuals all across the spectrum of the hospital team. My experience helped me to raise the bar not only to benefit myself but also my institution and especially my patients,” says Ron Greeno, MD, MHM. “I highly recommend this experience to any hospital medicine professionals who aspire to take their leadership skills to the next level.”

All three courses run concurrently over the span of the four days and are led by world-renowned faculty. This expanded meeting will provide attendees with unprecedented networking opportunities with hundreds of colleagues and enhanced career development.

Available Leadership Academy courses include:

• Leadership Foundations, a four-day course that serves as the first step in your leadership journey. Attendees learn how to evaluate personal leadership strengths and weaknesses, create and execute a communication strategy for key team members, understand key hospital drivers, examine how hospital metrics are derived, and much more. Attendees are divided into smaller moderated groups to ensure meaningful, relevant application of concepts to hands-on activities.
• Advanced Leadership: Influential Management, a course that builds skills around driving culture change through specific leadership behaviors and actions, financial storytelling, engaging in effective professional negotiation activities with proven techniques, and more through world-renowned faculty and applied exercises.

  (Prerequisite: Leadership Foundations or an advanced management degree upon course director approval)

• Advanced Leadership: Mastering Teamwork, a course developed in response to high demand from previous Leadership Academy attendees. Participants learn how to critically assess program growth opportunities and develop operational plans; utilize the principles of SWARM intelligence; lead, manage, and motivate teams in complex hospital environments; and develop effective communication strategies.

  (Prerequisite: Leadership Foundations or an advanced management degree upon course director approval.)

SHM members receive reduced rates for course tuition. For more information on how to register, visit www.SHMLeadershipAcademy.org.

Ever wish you had more leadership training in medical school or your residency programs? Feel a bit overwhelmed when developing operational plans for your hospital or negotiating important contracts? Join SHM in sunny Lake Buena Vista, Fla., October 24–27, for its esteemed Leadership Academy (www.shmleadershipacademy.org). SHM Leadership Academy prepares clinicians, academicians, and administrators with vital leadership skills traditionally not taught throughout the course of medical training, tailored specifically to hospital medicine.

“SHM’s Leadership Academy teaches leadership skills for individuals all across the spectrum of the hospital team. My experience helped me to raise the bar not only to benefit myself but also my institution and especially my patients,” says Ron Greeno, MD, MHM. “I highly recommend this experience to any hospital medicine professionals who aspire to take their leadership skills to the next level.”

All three courses run concurrently over the span of the four days and are led by world-renowned faculty. This expanded meeting will provide attendees with unprecedented networking opportunities with hundreds of colleagues and enhanced career development.

Available Leadership Academy courses include:

• Leadership Foundations, a four-day course that serves as the first step in your leadership journey. Attendees learn how to evaluate personal leadership strengths and weaknesses, create and execute a communication strategy for key team members, understand key hospital drivers, examine how hospital metrics are derived, and much more. Attendees are divided into smaller moderated groups to ensure meaningful, relevant application of concepts to hands-on activities.
• Advanced Leadership: Influential Management, a course that builds skills around driving culture change through specific leadership behaviors and actions, financial storytelling, engaging in effective professional negotiation activities with proven techniques, and more through world-renowned faculty and applied exercises.

  (Prerequisite: Leadership Foundations or an advanced management degree upon course director approval)

• Advanced Leadership: Mastering Teamwork, a course developed in response to high demand from previous Leadership Academy attendees. Participants learn how to critically assess program growth opportunities and develop operational plans; utilize the principles of SWARM intelligence; lead, manage, and motivate teams in complex hospital environments; and develop effective communication strategies.

  (Prerequisite: Leadership Foundations or an advanced management degree upon course director approval.)

SHM members receive reduced rates for course tuition. For more information on how to register, visit www.SHMLeadershipAcademy.org.

NEW YORK (Reuters Health) - Use of the marker procalcitonin to guide antibacterial therapy in the critically ill is associated with shorter treatment and reduced mortality, according to Dutch researchers.

As Dr. Evelien de Jong told Reuters Health by email, "Antibiotic overconsumption is one of the largest threats to medicine in the near future. Our study is the largest randomized controlled trial of antibiotic reduction in intensive care units (ICUs) and will, hopefully, contribute to a more individualized antibiotic duration per patient and an overall reduction of antibiotic use."

In a February 29 online paper in the Lancet Infectious Diseases, Dr. de Jong, of VU University Medical Center, Amsterdam, and colleagues noted that a "drop in procalcitonin concentration might help (clinicians) to discontinue antibiotic use in a more timely fashion" than reliance on biomarkers such as C-reactive protein.

To investigate, the researchers studied 1,575 ICU patients who received antibiotics and were randomized to procalcitonin-guided antibiotic discontinuation or standard of care. Fifteen were excluded from the procalcitonin group and 14 were excluded from the standard care group.

"In the procalcitonin-guided group, a non-binding advice to discontinue antibiotics was provided if procalcitonin concentration had decreased by 80% or more of its peak value or to 0.5 ug/L or lower," the authors reported.

In all, 538 (71%) of 761 patients in the procalcitonin-guided group and 457 (58%) of 785 patients in the standard-of-care group completed their antibiotic treatment in the ICU.

Median consumption of antibiotics was 7.5 daily defined doses in the procalcitonin group, significantly less than the 9.3 daily defined doses in the standard-of-care group, for a mean group absolute difference of 2.69 (p<0.0001).

Median duration of treatment was also significantly shorter in the procalcitonin-guided group (five versus seven days), for a mean group absolute difference of 1.22 (p<0.0001).

Mortality at 28 days was also significantly less than in the standard-of-care group. This was 20% versus 27% in intention-to-treat analysis. At one year, corresponding per protocol proportions were 36% and 43%.

Overall, the researchers concluded, "Procalcitonin concentrations might help physicians in deciding whether or not the presumed infection is truly bacterial, leading to more adequate diagnosis and treatment, the cornerstones of antibiotic stewardship."

Commenting by email, Dr. Philipp Schuetz, coauthor of an accompanying editorial, told Reuters Health, "This well-done and large landmark trial proves that procalcitonin-guided care reduces unnecessary antibiotic courses in critical care patients with assumed or proven infection and thereby improves patient outcomes, namely overall survival."

Dr. Schuetz, of the University of Basel, Switzerland, concluded, "We should now adapt our guidelines and start to (adopt) more widespread use of procalcitonin protocols in clinical practice to slow emergence of bacterial resistance and improve sepsis care."

NEW YORK (Reuters Health) - Use of the marker procalcitonin to guide antibacterial therapy in the critically ill is associated with shorter treatment and reduced mortality, according to Dutch researchers.

As Dr. Evelien de Jong told Reuters Health by email, "Antibiotic overconsumption is one of the largest threats to medicine in the near future. Our study is the largest randomized controlled trial of antibiotic reduction in intensive care units (ICUs) and will, hopefully, contribute to a more individualized antibiotic duration per patient and an overall reduction of antibiotic use."

In a February 29 online paper in the Lancet Infectious Diseases, Dr. de Jong, of VU University Medical Center, Amsterdam, and colleagues noted that a "drop in procalcitonin concentration might help (clinicians) to discontinue antibiotic use in a more timely fashion" than reliance on biomarkers such as C-reactive protein.

To investigate, the researchers studied 1,575 ICU patients who received antibiotics and were randomized to procalcitonin-guided antibiotic discontinuation or standard of care. Fifteen were excluded from the procalcitonin group and 14 were excluded from the standard care group.

"In the procalcitonin-guided group, a non-binding advice to discontinue antibiotics was provided if procalcitonin concentration had decreased by 80% or more of its peak value or to 0.5 ug/L or lower," the authors reported.

In all, 538 (71%) of 761 patients in the procalcitonin-guided group and 457 (58%) of 785 patients in the standard-of-care group completed their antibiotic treatment in the ICU.

Median consumption of antibiotics was 7.5 daily defined doses in the procalcitonin group, significantly less than the 9.3 daily defined doses in the standard-of-care group, for a mean group absolute difference of 2.69 (p<0.0001).

Median duration of treatment was also significantly shorter in the procalcitonin-guided group (five versus seven days), for a mean group absolute difference of 1.22 (p<0.0001).

Mortality at 28 days was also significantly less than in the standard-of-care group. This was 20% versus 27% in intention-to-treat analysis. At one year, corresponding per protocol proportions were 36% and 43%.

Overall, the researchers concluded, "Procalcitonin concentrations might help physicians in deciding whether or not the presumed infection is truly bacterial, leading to more adequate diagnosis and treatment, the cornerstones of antibiotic stewardship."

Commenting by email, Dr. Philipp Schuetz, coauthor of an accompanying editorial, told Reuters Health, "This well-done and large landmark trial proves that procalcitonin-guided care reduces unnecessary antibiotic courses in critical care patients with assumed or proven infection and thereby improves patient outcomes, namely overall survival."

Dr. Schuetz, of the University of Basel, Switzerland, concluded, "We should now adapt our guidelines and start to (adopt) more widespread use of procalcitonin protocols in clinical practice to slow emergence of bacterial resistance and improve sepsis care."

NEW YORK (Reuters Health) - Use of the marker procalcitonin to guide antibacterial therapy in the critically ill is associated with shorter treatment and reduced mortality, according to Dutch researchers.

As Dr. Evelien de Jong told Reuters Health by email, "Antibiotic overconsumption is one of the largest threats to medicine in the near future. Our study is the largest randomized controlled trial of antibiotic reduction in intensive care units (ICUs) and will, hopefully, contribute to a more individualized antibiotic duration per patient and an overall reduction of antibiotic use."

In a February 29 online paper in the Lancet Infectious Diseases, Dr. de Jong, of VU University Medical Center, Amsterdam, and colleagues noted that a "drop in procalcitonin concentration might help (clinicians) to discontinue antibiotic use in a more timely fashion" than reliance on biomarkers such as C-reactive protein.

To investigate, the researchers studied 1,575 ICU patients who received antibiotics and were randomized to procalcitonin-guided antibiotic discontinuation or standard of care. Fifteen were excluded from the procalcitonin group and 14 were excluded from the standard care group.

"In the procalcitonin-guided group, a non-binding advice to discontinue antibiotics was provided if procalcitonin concentration had decreased by 80% or more of its peak value or to 0.5 ug/L or lower," the authors reported.

In all, 538 (71%) of 761 patients in the procalcitonin-guided group and 457 (58%) of 785 patients in the standard-of-care group completed their antibiotic treatment in the ICU.

Median consumption of antibiotics was 7.5 daily defined doses in the procalcitonin group, significantly less than the 9.3 daily defined doses in the standard-of-care group, for a mean group absolute difference of 2.69 (p<0.0001).

Median duration of treatment was also significantly shorter in the procalcitonin-guided group (five versus seven days), for a mean group absolute difference of 1.22 (p<0.0001).

Mortality at 28 days was also significantly less than in the standard-of-care group. This was 20% versus 27% in intention-to-treat analysis. At one year, corresponding per protocol proportions were 36% and 43%.

Overall, the researchers concluded, "Procalcitonin concentrations might help physicians in deciding whether or not the presumed infection is truly bacterial, leading to more adequate diagnosis and treatment, the cornerstones of antibiotic stewardship."

Commenting by email, Dr. Philipp Schuetz, coauthor of an accompanying editorial, told Reuters Health, "This well-done and large landmark trial proves that procalcitonin-guided care reduces unnecessary antibiotic courses in critical care patients with assumed or proven infection and thereby improves patient outcomes, namely overall survival."

Dr. Schuetz, of the University of Basel, Switzerland, concluded, "We should now adapt our guidelines and start to (adopt) more widespread use of procalcitonin protocols in clinical practice to slow emergence of bacterial resistance and improve sepsis care."

Lab mice

Photo by Aaron Logan

Increasing levels of a gut microbiome-derived metabolite could help prevent graft-versus-host disease (GVHD) after hematopoietic stem cell transplant (HSCT), according to preclinical research published in Nature Immunology.

For this study, researchers searched for alterations in the gut microbiome to see whether metabolites could impact outcomes after HSCT.

They found that levels of a metabolite called butyrate were significantly reduced in the intestinal tract of mice that received a transplant.

When the researchers increased butyrate levels in these mice, they saw a decrease in the incidence and severity of GVHD.

“Our findings suggest we can prevent graft-vs-host disease by bolstering the amount of the microbiome-derived metabolite butyrate,” said study author Pavan Reddy, MD, of the University of Michigan Comprehensive Cancer Center in Ann Arbor.

He and his colleagues found they could mitigate GVHD by administering butyrate to mice or by altering the composition of indigenous gastrointestinal microbiota so they produced high levels of butyrate.

The team noted that diet is another way to control butyrate production by the gut microbiome—specifically, through resistant starch such as that found in potatoes.

The researchers hope to begin a clinical trial later this year in which they will combine resistant starch with current methods of preventing GVHD to assess whether they can increase butyrate and reduce the incidence and severity of GVHD in HSCT recipients.

“This is a whole new approach,” Dr Reddy said. “The idea is to make the host cells stronger, to be able to withstand the assault of the donor immune cells while reducing the risk of infection or [disease] relapse.” 

Lab mice

Photo by Aaron Logan

Increasing levels of a gut microbiome-derived metabolite could help prevent graft-versus-host disease (GVHD) after hematopoietic stem cell transplant (HSCT), according to preclinical research published in Nature Immunology.

For this study, researchers searched for alterations in the gut microbiome to see whether metabolites could impact outcomes after HSCT.

They found that levels of a metabolite called butyrate were significantly reduced in the intestinal tract of mice that received a transplant.

When the researchers increased butyrate levels in these mice, they saw a decrease in the incidence and severity of GVHD.

“Our findings suggest we can prevent graft-vs-host disease by bolstering the amount of the microbiome-derived metabolite butyrate,” said study author Pavan Reddy, MD, of the University of Michigan Comprehensive Cancer Center in Ann Arbor.

He and his colleagues found they could mitigate GVHD by administering butyrate to mice or by altering the composition of indigenous gastrointestinal microbiota so they produced high levels of butyrate.

The team noted that diet is another way to control butyrate production by the gut microbiome—specifically, through resistant starch such as that found in potatoes.

The researchers hope to begin a clinical trial later this year in which they will combine resistant starch with current methods of preventing GVHD to assess whether they can increase butyrate and reduce the incidence and severity of GVHD in HSCT recipients.

“This is a whole new approach,” Dr Reddy said. “The idea is to make the host cells stronger, to be able to withstand the assault of the donor immune cells while reducing the risk of infection or [disease] relapse.” 

Lab mice

Photo by Aaron Logan

Increasing levels of a gut microbiome-derived metabolite could help prevent graft-versus-host disease (GVHD) after hematopoietic stem cell transplant (HSCT), according to preclinical research published in Nature Immunology.

For this study, researchers searched for alterations in the gut microbiome to see whether metabolites could impact outcomes after HSCT.

They found that levels of a metabolite called butyrate were significantly reduced in the intestinal tract of mice that received a transplant.

When the researchers increased butyrate levels in these mice, they saw a decrease in the incidence and severity of GVHD.

“Our findings suggest we can prevent graft-vs-host disease by bolstering the amount of the microbiome-derived metabolite butyrate,” said study author Pavan Reddy, MD, of the University of Michigan Comprehensive Cancer Center in Ann Arbor.

He and his colleagues found they could mitigate GVHD by administering butyrate to mice or by altering the composition of indigenous gastrointestinal microbiota so they produced high levels of butyrate.

The team noted that diet is another way to control butyrate production by the gut microbiome—specifically, through resistant starch such as that found in potatoes.

The researchers hope to begin a clinical trial later this year in which they will combine resistant starch with current methods of preventing GVHD to assess whether they can increase butyrate and reduce the incidence and severity of GVHD in HSCT recipients.

“This is a whole new approach,” Dr Reddy said. “The idea is to make the host cells stronger, to be able to withstand the assault of the donor immune cells while reducing the risk of infection or [disease] relapse.” 

 

 

Idelalisib (Zydelig)

Photo courtesy of

Gilead Sciences, Inc.

 

In light of recently reported safety concerns, the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has issued provisional advice for doctors and patients using idelalisib (Zydelig).

The EMA recently began reviewing the safety of idelalisib because of serious adverse events, most of which were infection-related, that were reported in 3 clinical trials investigating idelalisib in combination with other drugs.

These trials have since been stopped.

Now, the PRAC is making provisional recommendations to ensure idelalisib is used as safely as possible outside of clinical trials.

These recommendations will be forwarded to the European Commission, which will issue a provisional legally binding decision applicable in all European Union (EU) member states.

In the EU, idelalisib is approved as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

Idelalisib is also approved for use in combination with rituximab to treat adults with chronic lymphocytic leukemia (CLL) who have received at least 1 prior therapy or as first-line treatment in the presence of 17p deletion or TP53 mutation in CLL patients considered unsuitable for chemo-immunotherapy.

Recommendations

The PRAC is recommending that previously untreated CLL patients with 17p deletion or TP53 mutation do not begin treatment with idelalisib. In addition, doctors should re-evaluate each patient taking idelalisib as first-line treatment for CLL and only continue treatment if the benefits outweigh the risks.

Idelalisib can continue to be used in combination, only with rituximab, in CLL patients who have received at least 1 prior therapy and as monotherapy in patients with follicular lymphoma that is refractory to 2 lines of treatment.

Patients with any evidence of ongoing systemic infection should not be started on treatment with idelalisib.

And patients should be informed about the risk of serious infections with idelalisib.

All patients who do receive idelalisib should take antibiotics to prevent Pneumocystis jirovecii pneumonia, and they should be monitored for respiratory signs and symptoms. Regular clinical and laboratory monitoring for cytomegalovirus infection is also recommended.

Patients should have regular blood tests to detect neutropenia. In case a patient has moderate or severe neutropenia, treatment with idelalisib may have to be interrupted, in line with the updated summary of product characteristics.

The EMA said further details on these provisional measures will be provided in writing to healthcare professionals, and the product information will be updated accordingly.

Likewise, further information on the review of idelalisib will be provided as necessary and once the review is finished.

About the review

The EMA’s review of idelalisib started after a higher rate of serious adverse events, including deaths, was seen in 3 clinical trials evaluating the addition of idelalisib to standard therapy in first-line CLL and relapsed indolent non-Hodgkin lymphoma (NHL).

Most of the deaths were related to infections such as Pneumocystis jirovecii pneumonia and cytomegalovirus infection. Other excess deaths were related mainly to respiratory events.

The NHL studies (NCT01732926 and NCT01732913) included patients with disease characteristics different from those covered by the currently approved indication for idelalisib and investigated combinations of drugs that are not currently approved in the EU—idelalisib plus rituximab for NHL and idelalisib plus bendamustine and rituximab for NHL.

The CLL trial (NCT01980888) involved patients who had not received previous treatment, some of whom had the 17p deletion or TP53 mutation. However, the trial also investigated a combination of drugs not currently approved in the EU—idelalisib plus bendamustine and rituximab.

At present, the PRAC is conducting the review. Once the PRAC is finished, its recommendations will be forwarded to the EMA’s Committee for Medicinal Products for Human Use, which will adopt a final opinion.

The European Commission will take this opinion into account and adopt a legally binding decision that is applicable in all EU member states.

 

 

Idelalisib (Zydelig)

Photo courtesy of

Gilead Sciences, Inc.

 

In light of recently reported safety concerns, the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has issued provisional advice for doctors and patients using idelalisib (Zydelig).

The EMA recently began reviewing the safety of idelalisib because of serious adverse events, most of which were infection-related, that were reported in 3 clinical trials investigating idelalisib in combination with other drugs.

These trials have since been stopped.

Now, the PRAC is making provisional recommendations to ensure idelalisib is used as safely as possible outside of clinical trials.

These recommendations will be forwarded to the European Commission, which will issue a provisional legally binding decision applicable in all European Union (EU) member states.

In the EU, idelalisib is approved as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

Idelalisib is also approved for use in combination with rituximab to treat adults with chronic lymphocytic leukemia (CLL) who have received at least 1 prior therapy or as first-line treatment in the presence of 17p deletion or TP53 mutation in CLL patients considered unsuitable for chemo-immunotherapy.

Recommendations

The PRAC is recommending that previously untreated CLL patients with 17p deletion or TP53 mutation do not begin treatment with idelalisib. In addition, doctors should re-evaluate each patient taking idelalisib as first-line treatment for CLL and only continue treatment if the benefits outweigh the risks.

Idelalisib can continue to be used in combination, only with rituximab, in CLL patients who have received at least 1 prior therapy and as monotherapy in patients with follicular lymphoma that is refractory to 2 lines of treatment.

Patients with any evidence of ongoing systemic infection should not be started on treatment with idelalisib.

And patients should be informed about the risk of serious infections with idelalisib.

All patients who do receive idelalisib should take antibiotics to prevent Pneumocystis jirovecii pneumonia, and they should be monitored for respiratory signs and symptoms. Regular clinical and laboratory monitoring for cytomegalovirus infection is also recommended.

Patients should have regular blood tests to detect neutropenia. In case a patient has moderate or severe neutropenia, treatment with idelalisib may have to be interrupted, in line with the updated summary of product characteristics.

The EMA said further details on these provisional measures will be provided in writing to healthcare professionals, and the product information will be updated accordingly.

Likewise, further information on the review of idelalisib will be provided as necessary and once the review is finished.

About the review

The EMA’s review of idelalisib started after a higher rate of serious adverse events, including deaths, was seen in 3 clinical trials evaluating the addition of idelalisib to standard therapy in first-line CLL and relapsed indolent non-Hodgkin lymphoma (NHL).

Most of the deaths were related to infections such as Pneumocystis jirovecii pneumonia and cytomegalovirus infection. Other excess deaths were related mainly to respiratory events.

The NHL studies (NCT01732926 and NCT01732913) included patients with disease characteristics different from those covered by the currently approved indication for idelalisib and investigated combinations of drugs that are not currently approved in the EU—idelalisib plus rituximab for NHL and idelalisib plus bendamustine and rituximab for NHL.

The CLL trial (NCT01980888) involved patients who had not received previous treatment, some of whom had the 17p deletion or TP53 mutation. However, the trial also investigated a combination of drugs not currently approved in the EU—idelalisib plus bendamustine and rituximab.

At present, the PRAC is conducting the review. Once the PRAC is finished, its recommendations will be forwarded to the EMA’s Committee for Medicinal Products for Human Use, which will adopt a final opinion.

The European Commission will take this opinion into account and adopt a legally binding decision that is applicable in all EU member states.

 

 

Idelalisib (Zydelig)

Photo courtesy of

Gilead Sciences, Inc.

 

In light of recently reported safety concerns, the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has issued provisional advice for doctors and patients using idelalisib (Zydelig).

The EMA recently began reviewing the safety of idelalisib because of serious adverse events, most of which were infection-related, that were reported in 3 clinical trials investigating idelalisib in combination with other drugs.

These trials have since been stopped.

Now, the PRAC is making provisional recommendations to ensure idelalisib is used as safely as possible outside of clinical trials.

These recommendations will be forwarded to the European Commission, which will issue a provisional legally binding decision applicable in all European Union (EU) member states.

In the EU, idelalisib is approved as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

Idelalisib is also approved for use in combination with rituximab to treat adults with chronic lymphocytic leukemia (CLL) who have received at least 1 prior therapy or as first-line treatment in the presence of 17p deletion or TP53 mutation in CLL patients considered unsuitable for chemo-immunotherapy.

Recommendations

The PRAC is recommending that previously untreated CLL patients with 17p deletion or TP53 mutation do not begin treatment with idelalisib. In addition, doctors should re-evaluate each patient taking idelalisib as first-line treatment for CLL and only continue treatment if the benefits outweigh the risks.

Idelalisib can continue to be used in combination, only with rituximab, in CLL patients who have received at least 1 prior therapy and as monotherapy in patients with follicular lymphoma that is refractory to 2 lines of treatment.

Patients with any evidence of ongoing systemic infection should not be started on treatment with idelalisib.

And patients should be informed about the risk of serious infections with idelalisib.

All patients who do receive idelalisib should take antibiotics to prevent Pneumocystis jirovecii pneumonia, and they should be monitored for respiratory signs and symptoms. Regular clinical and laboratory monitoring for cytomegalovirus infection is also recommended.

Patients should have regular blood tests to detect neutropenia. In case a patient has moderate or severe neutropenia, treatment with idelalisib may have to be interrupted, in line with the updated summary of product characteristics.

The EMA said further details on these provisional measures will be provided in writing to healthcare professionals, and the product information will be updated accordingly.

Likewise, further information on the review of idelalisib will be provided as necessary and once the review is finished.

About the review

The EMA’s review of idelalisib started after a higher rate of serious adverse events, including deaths, was seen in 3 clinical trials evaluating the addition of idelalisib to standard therapy in first-line CLL and relapsed indolent non-Hodgkin lymphoma (NHL).

Most of the deaths were related to infections such as Pneumocystis jirovecii pneumonia and cytomegalovirus infection. Other excess deaths were related mainly to respiratory events.

The NHL studies (NCT01732926 and NCT01732913) included patients with disease characteristics different from those covered by the currently approved indication for idelalisib and investigated combinations of drugs that are not currently approved in the EU—idelalisib plus rituximab for NHL and idelalisib plus bendamustine and rituximab for NHL.

The CLL trial (NCT01980888) involved patients who had not received previous treatment, some of whom had the 17p deletion or TP53 mutation. However, the trial also investigated a combination of drugs not currently approved in the EU—idelalisib plus bendamustine and rituximab.

At present, the PRAC is conducting the review. Once the PRAC is finished, its recommendations will be forwarded to the EMA’s Committee for Medicinal Products for Human Use, which will adopt a final opinion.

The European Commission will take this opinion into account and adopt a legally binding decision that is applicable in all EU member states.

Powdered gloves

Photo by Chonion Antoine

The US Food and Drug Administration (FDA) is proposing a ban on most powdered gloves in the US.

The proposed ban applies to powdered surgeon’s gloves, powdered patient examination gloves, and absorbable powder for lubricating a surgeon’s glove.

The FDA said these gloves pose an unreasonable and substantial risk of illness or injury to healthcare providers, patients, and other individuals who are exposed to them, which cannot be corrected through new or updated labeling.

“This ban is about protecting patients and healthcare professionals from a danger they might not even be aware of,” said Jeffrey Shuren, MD, director of FDA’s Center for Devices and Radiological Health.

“We take bans very seriously and only take this action when we feel it’s necessary to protect the public health.”

The FDA said powdered gloves are dangerous for a variety of reasons. In particular, aerosolized glove powder on natural rubber latex gloves, but not on synthetic powdered gloves, can carry proteins that may cause respiratory allergic reactions.

Although powdered synthetic gloves do not present the risk of allergic reactions, these gloves are associated with an extensive list of potentially serious adverse events, including severe airway inflammation, wound inflammation, and post-surgical adhesions. These side effects have been attributed to the use of glove powder with all types of gloves.

As these risks cannot be corrected through new or updated labeling, the FDA is moving forward with the proposal to ban these products, which—if finalized—would ultimately remove them from the marketplace completely.

In making the determination that these products are dangerous and present an unreasonable and substantial risk, the FDA considered all available evidence, which included a thorough review of the scientific literature and comments received on a February 2011 Federal Register Notice.

The FDA also conducted an economic analysis that showed a powdered glove ban would not cause a glove shortage, and the economic impact of a ban would not be significant. The ban is also not likely to impact medical practice, because many non-powdered protective glove options are currently available.

The FDA has determined that the banning standard would not apply to powdered radiographic protection gloves. The agency is not aware of any powdered radiographic protection gloves that are currently on the market.

Non-powdered surgeon gloves and non-powdered patient examination gloves will not be included in the ban and will remain Class I medical devices. Therefore, the FDA is also proposing amendments to their classification regulations to clarify that they apply only to non-powdered gloves.

The proposed rule is available online at www.regulations.gov for public comment for 90 days.

Powdered gloves

Photo by Chonion Antoine

The US Food and Drug Administration (FDA) is proposing a ban on most powdered gloves in the US.

The proposed ban applies to powdered surgeon’s gloves, powdered patient examination gloves, and absorbable powder for lubricating a surgeon’s glove.

The FDA said these gloves pose an unreasonable and substantial risk of illness or injury to healthcare providers, patients, and other individuals who are exposed to them, which cannot be corrected through new or updated labeling.

“This ban is about protecting patients and healthcare professionals from a danger they might not even be aware of,” said Jeffrey Shuren, MD, director of FDA’s Center for Devices and Radiological Health.

“We take bans very seriously and only take this action when we feel it’s necessary to protect the public health.”

The FDA said powdered gloves are dangerous for a variety of reasons. In particular, aerosolized glove powder on natural rubber latex gloves, but not on synthetic powdered gloves, can carry proteins that may cause respiratory allergic reactions.

Although powdered synthetic gloves do not present the risk of allergic reactions, these gloves are associated with an extensive list of potentially serious adverse events, including severe airway inflammation, wound inflammation, and post-surgical adhesions. These side effects have been attributed to the use of glove powder with all types of gloves.

As these risks cannot be corrected through new or updated labeling, the FDA is moving forward with the proposal to ban these products, which—if finalized—would ultimately remove them from the marketplace completely.

In making the determination that these products are dangerous and present an unreasonable and substantial risk, the FDA considered all available evidence, which included a thorough review of the scientific literature and comments received on a February 2011 Federal Register Notice.

The FDA also conducted an economic analysis that showed a powdered glove ban would not cause a glove shortage, and the economic impact of a ban would not be significant. The ban is also not likely to impact medical practice, because many non-powdered protective glove options are currently available.

The FDA has determined that the banning standard would not apply to powdered radiographic protection gloves. The agency is not aware of any powdered radiographic protection gloves that are currently on the market.

Non-powdered surgeon gloves and non-powdered patient examination gloves will not be included in the ban and will remain Class I medical devices. Therefore, the FDA is also proposing amendments to their classification regulations to clarify that they apply only to non-powdered gloves.

The proposed rule is available online at www.regulations.gov for public comment for 90 days.

Powdered gloves

Photo by Chonion Antoine

The US Food and Drug Administration (FDA) is proposing a ban on most powdered gloves in the US.

The proposed ban applies to powdered surgeon’s gloves, powdered patient examination gloves, and absorbable powder for lubricating a surgeon’s glove.

The FDA said these gloves pose an unreasonable and substantial risk of illness or injury to healthcare providers, patients, and other individuals who are exposed to them, which cannot be corrected through new or updated labeling.

“This ban is about protecting patients and healthcare professionals from a danger they might not even be aware of,” said Jeffrey Shuren, MD, director of FDA’s Center for Devices and Radiological Health.

“We take bans very seriously and only take this action when we feel it’s necessary to protect the public health.”

The FDA said powdered gloves are dangerous for a variety of reasons. In particular, aerosolized glove powder on natural rubber latex gloves, but not on synthetic powdered gloves, can carry proteins that may cause respiratory allergic reactions.

Although powdered synthetic gloves do not present the risk of allergic reactions, these gloves are associated with an extensive list of potentially serious adverse events, including severe airway inflammation, wound inflammation, and post-surgical adhesions. These side effects have been attributed to the use of glove powder with all types of gloves.

As these risks cannot be corrected through new or updated labeling, the FDA is moving forward with the proposal to ban these products, which—if finalized—would ultimately remove them from the marketplace completely.

In making the determination that these products are dangerous and present an unreasonable and substantial risk, the FDA considered all available evidence, which included a thorough review of the scientific literature and comments received on a February 2011 Federal Register Notice.

The FDA also conducted an economic analysis that showed a powdered glove ban would not cause a glove shortage, and the economic impact of a ban would not be significant. The ban is also not likely to impact medical practice, because many non-powdered protective glove options are currently available.

The FDA has determined that the banning standard would not apply to powdered radiographic protection gloves. The agency is not aware of any powdered radiographic protection gloves that are currently on the market.

Non-powdered surgeon gloves and non-powdered patient examination gloves will not be included in the ban and will remain Class I medical devices. Therefore, the FDA is also proposing amendments to their classification regulations to clarify that they apply only to non-powdered gloves.

The proposed rule is available online at www.regulations.gov for public comment for 90 days.

Proliferating HSCs

Image by John Perry

Four genes govern the growth and multiplication of hematopoietic stem cells (HSCs), according to a study published in Cell Reports.

Investigators conducted a genome-wide RNA interference screen in cells derived from human cord blood, looking for genes whose knockdown maintained the HSC phenotype during culture.

This revealed the 4 genes—STAG2, RAD21, STAG1, and SMC3—which are all members of the cohesin complex.

“The discovery showed that this protein complex is crucial and has an overarching function in the growth of the blood stem cells,” said study author Jonas Larsson, MD, PhD, of Lund University in Sweden.

Dr Larsson and his colleagues screened 15,000 genes for this study and found 20 candidates with a strong capacity to affect the balance of growth in HSCs.

Four of the genes—STAG2, RAD21, STAG1, and SMC3—were physically connected through cooperation in the cohesin complex. This complex forms a sort of brace that holds different parts of the DNA strand together in the cell.

The researchers believe this allows the cohesin complex to control access to the “on/off switches” in the DNA and to change the impulses that HSCs receive from various genes, thereby affecting whether an HSC multiplies or matures.

“Clarifying what regulates the balance between multiplication and maturation of blood stem cells could provide the right keys to expanding them outside the body,” said Roman Galeev, a doctoral student at Lund University.

“In addition, it would enable the identification of new points of attack for the treatment of blood cancer, which is precisely a disruption of the balance between multiplication and maturation.”

Galeev noted that research by other groups has revealed mutations in the cohesin complex genes in patients with hematologic malignancies (Mazumdar C, Cell Stem Cell 2015; Mullenders J, J Exp Med 2015; and Viny AD, J Exp Med 2015).

“This is incredibly exciting,” Galeev said. “Together with the results from our study, this indicates that the cohesin genes are directly and crucially significant in the development of blood cancer.”

“Our findings entail a new understanding of how the expansion of blood stem cells is controlled. Eventually, this can lead to new ways of affecting the process, either to prevent the development of cancer or to expand the stem cells for transplant.”

Proliferating HSCs

Image by John Perry

Four genes govern the growth and multiplication of hematopoietic stem cells (HSCs), according to a study published in Cell Reports.

Investigators conducted a genome-wide RNA interference screen in cells derived from human cord blood, looking for genes whose knockdown maintained the HSC phenotype during culture.

This revealed the 4 genes—STAG2, RAD21, STAG1, and SMC3—which are all members of the cohesin complex.

“The discovery showed that this protein complex is crucial and has an overarching function in the growth of the blood stem cells,” said study author Jonas Larsson, MD, PhD, of Lund University in Sweden.

Dr Larsson and his colleagues screened 15,000 genes for this study and found 20 candidates with a strong capacity to affect the balance of growth in HSCs.

Four of the genes—STAG2, RAD21, STAG1, and SMC3—were physically connected through cooperation in the cohesin complex. This complex forms a sort of brace that holds different parts of the DNA strand together in the cell.

The researchers believe this allows the cohesin complex to control access to the “on/off switches” in the DNA and to change the impulses that HSCs receive from various genes, thereby affecting whether an HSC multiplies or matures.

“Clarifying what regulates the balance between multiplication and maturation of blood stem cells could provide the right keys to expanding them outside the body,” said Roman Galeev, a doctoral student at Lund University.

“In addition, it would enable the identification of new points of attack for the treatment of blood cancer, which is precisely a disruption of the balance between multiplication and maturation.”

Galeev noted that research by other groups has revealed mutations in the cohesin complex genes in patients with hematologic malignancies (Mazumdar C, Cell Stem Cell 2015; Mullenders J, J Exp Med 2015; and Viny AD, J Exp Med 2015).

“This is incredibly exciting,” Galeev said. “Together with the results from our study, this indicates that the cohesin genes are directly and crucially significant in the development of blood cancer.”

“Our findings entail a new understanding of how the expansion of blood stem cells is controlled. Eventually, this can lead to new ways of affecting the process, either to prevent the development of cancer or to expand the stem cells for transplant.”

Proliferating HSCs

Image by John Perry

Four genes govern the growth and multiplication of hematopoietic stem cells (HSCs), according to a study published in Cell Reports.

Investigators conducted a genome-wide RNA interference screen in cells derived from human cord blood, looking for genes whose knockdown maintained the HSC phenotype during culture.

This revealed the 4 genes—STAG2, RAD21, STAG1, and SMC3—which are all members of the cohesin complex.

“The discovery showed that this protein complex is crucial and has an overarching function in the growth of the blood stem cells,” said study author Jonas Larsson, MD, PhD, of Lund University in Sweden.

Dr Larsson and his colleagues screened 15,000 genes for this study and found 20 candidates with a strong capacity to affect the balance of growth in HSCs.

Four of the genes—STAG2, RAD21, STAG1, and SMC3—were physically connected through cooperation in the cohesin complex. This complex forms a sort of brace that holds different parts of the DNA strand together in the cell.

The researchers believe this allows the cohesin complex to control access to the “on/off switches” in the DNA and to change the impulses that HSCs receive from various genes, thereby affecting whether an HSC multiplies or matures.

“Clarifying what regulates the balance between multiplication and maturation of blood stem cells could provide the right keys to expanding them outside the body,” said Roman Galeev, a doctoral student at Lund University.

“In addition, it would enable the identification of new points of attack for the treatment of blood cancer, which is precisely a disruption of the balance between multiplication and maturation.”

Galeev noted that research by other groups has revealed mutations in the cohesin complex genes in patients with hematologic malignancies (Mazumdar C, Cell Stem Cell 2015; Mullenders J, J Exp Med 2015; and Viny AD, J Exp Med 2015).

“This is incredibly exciting,” Galeev said. “Together with the results from our study, this indicates that the cohesin genes are directly and crucially significant in the development of blood cancer.”

“Our findings entail a new understanding of how the expansion of blood stem cells is controlled. Eventually, this can lead to new ways of affecting the process, either to prevent the development of cancer or to expand the stem cells for transplant.”

As dermatology residents, the telephone calls we get at 2 am usually are the toughest for 2 reasons: (1) we rarely get calls at 2 am, and (2) it usually means there is a case to rule out Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Stevens-Johnson syndrome and TEN are severe mucocutaneous eruptions that usually develop due to drug reactions and involve a continuum of conjunctivitis, mucocutaneous sloughing, keratinocyte death, and bullae development. Body surface area (BSA) coverage determines the distinction between SJS and TEN; less than 10% BSA affected indicates SJS, 10% to 30% BSA affected indicates overlap between SJS and TEN, and greater than 30% BSA affected indicates TEN.¹ The mortality rates for these conditions range from 1% to 5% in SJS versus 25% to 30% in TEN.²

Being driven and dedicated residents, we rise to the challenge by arranging appropriate consultations, obtaining frozen section biopsies, providing recommendations to remove unnecessary medications, and offering skin care management. However, what comes next? Intravenous immunoglobulin (IVIG)? Cyclosporine? Or is it appropriate to allow the reaction to continue its course? Dermatology programs have a varying standard of care due to the limited number of studies conducted on SJS/TEN patients. Few studies have relayed the efficacy of cyclosporine; however, published results have shown that cyclosporine can decrease the overall mortality risk and minimize disease progression.^2-5 In this article, I will review some of the key studies conducted in the last 5 years regarding the use of cyclosporine in the therapeutic plan for SJS/TEN.

In one retrospective analysis conducted by Kirchhof et al¹ in 2014, 35 patients with SJS/TEN who were treated with IVIG and 15 who were treated with cyclosporine were evaluated for mortality benefit. Two patients were treated with both cyclosporine and IVIG and were included in both arms of the study. Overall, the evaluation indicated that cyclosporine can potentially have a better overall advantage in treatment of SJS/TEN over IVIG.¹ Although this study had an uneven number of patients treated with IVIG versus cyclosporine, a nonstandardized way of comparing patients with early SJS to TEN patients, and no double-blind randomized trial, cyclosporine may still show benefit over IVIG.

Singh et al⁶ conducted an uncontrolled open study in a tertiary care center (July 2011–June 2012) that showed a similar result of benefit with cyclosporine in SJS, SJS/TEN, and TEN patients. Eleven participants were included in the study based on SCORTEN (Score of Toxic Epidermal Necrosis) criteria (age, >40 years; heart rate, >120 BPM; serum blood urea nitrogen level, >28 mg/dL; body surface area affected, >10%; serum bicarbonate, >20 mEq/L; serum glucose, >252 mg/dL). They were treated with cyclosporine 3 mg/kg for 7 days and then tapered over another 7 days. Six participants were treated with corticosteroids. Participants treated with cyclosporine reepithelialized in 16.7 days compared to 23 days with corticosteroids. The hospital stay was 18.09 days in participants treated with cyclosporine versus 26 days in those treated with corticosteroids. Lastly, 2 participants who were treated with corticosteroids died as opposed to none with cyclosporine.⁶ Although the power of this study also was limited and it was not a randomized, double-blind, controlled trial, it provides more evidence that cyclosporine can be efficacious in SJS/TEN patients.

A phase 2 open trial conducted by Valeyrie-Allanore et al⁷ evaluated the benefit and efficacy of cyclosporine in SJS/TEN patients. There were 29 participants at the start of the study (SJS, n=10; SJS/TEN, n=12; TEN, n=7) and 26 completed treatment. Cyclosporine was administered orally at 3 mg/kg for 10 days and tapered over the following month. This study noted 3 basic principles: First, patients tolerated cyclosporine well; second, limited disease progression was noted in 62% (18/29) of participants around day 3 and in only about 35% (11/29) of IVIG patients; and third, no deaths were noted in all participants.⁷

Final Thoughts

Case reports have indicated that cyclosporine may be effective in limiting progression of SJS/TEN; however, a double-blind study has not validated this finding. Hence, patients should be evaluated on a case-by-case basis to determine if they should be treated with cyclosporine or IVIG or simply complete the course of the disease process with supportive care.

As dermatology residents, the telephone calls we get at 2 am usually are the toughest for 2 reasons: (1) we rarely get calls at 2 am, and (2) it usually means there is a case to rule out Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Stevens-Johnson syndrome and TEN are severe mucocutaneous eruptions that usually develop due to drug reactions and involve a continuum of conjunctivitis, mucocutaneous sloughing, keratinocyte death, and bullae development. Body surface area (BSA) coverage determines the distinction between SJS and TEN; less than 10% BSA affected indicates SJS, 10% to 30% BSA affected indicates overlap between SJS and TEN, and greater than 30% BSA affected indicates TEN.¹ The mortality rates for these conditions range from 1% to 5% in SJS versus 25% to 30% in TEN.²

Being driven and dedicated residents, we rise to the challenge by arranging appropriate consultations, obtaining frozen section biopsies, providing recommendations to remove unnecessary medications, and offering skin care management. However, what comes next? Intravenous immunoglobulin (IVIG)? Cyclosporine? Or is it appropriate to allow the reaction to continue its course? Dermatology programs have a varying standard of care due to the limited number of studies conducted on SJS/TEN patients. Few studies have relayed the efficacy of cyclosporine; however, published results have shown that cyclosporine can decrease the overall mortality risk and minimize disease progression.^2-5 In this article, I will review some of the key studies conducted in the last 5 years regarding the use of cyclosporine in the therapeutic plan for SJS/TEN.

In one retrospective analysis conducted by Kirchhof et al¹ in 2014, 35 patients with SJS/TEN who were treated with IVIG and 15 who were treated with cyclosporine were evaluated for mortality benefit. Two patients were treated with both cyclosporine and IVIG and were included in both arms of the study. Overall, the evaluation indicated that cyclosporine can potentially have a better overall advantage in treatment of SJS/TEN over IVIG.¹ Although this study had an uneven number of patients treated with IVIG versus cyclosporine, a nonstandardized way of comparing patients with early SJS to TEN patients, and no double-blind randomized trial, cyclosporine may still show benefit over IVIG.

Singh et al⁶ conducted an uncontrolled open study in a tertiary care center (July 2011–June 2012) that showed a similar result of benefit with cyclosporine in SJS, SJS/TEN, and TEN patients. Eleven participants were included in the study based on SCORTEN (Score of Toxic Epidermal Necrosis) criteria (age, >40 years; heart rate, >120 BPM; serum blood urea nitrogen level, >28 mg/dL; body surface area affected, >10%; serum bicarbonate, >20 mEq/L; serum glucose, >252 mg/dL). They were treated with cyclosporine 3 mg/kg for 7 days and then tapered over another 7 days. Six participants were treated with corticosteroids. Participants treated with cyclosporine reepithelialized in 16.7 days compared to 23 days with corticosteroids. The hospital stay was 18.09 days in participants treated with cyclosporine versus 26 days in those treated with corticosteroids. Lastly, 2 participants who were treated with corticosteroids died as opposed to none with cyclosporine.⁶ Although the power of this study also was limited and it was not a randomized, double-blind, controlled trial, it provides more evidence that cyclosporine can be efficacious in SJS/TEN patients.

A phase 2 open trial conducted by Valeyrie-Allanore et al⁷ evaluated the benefit and efficacy of cyclosporine in SJS/TEN patients. There were 29 participants at the start of the study (SJS, n=10; SJS/TEN, n=12; TEN, n=7) and 26 completed treatment. Cyclosporine was administered orally at 3 mg/kg for 10 days and tapered over the following month. This study noted 3 basic principles: First, patients tolerated cyclosporine well; second, limited disease progression was noted in 62% (18/29) of participants around day 3 and in only about 35% (11/29) of IVIG patients; and third, no deaths were noted in all participants.⁷

Final Thoughts

Case reports have indicated that cyclosporine may be effective in limiting progression of SJS/TEN; however, a double-blind study has not validated this finding. Hence, patients should be evaluated on a case-by-case basis to determine if they should be treated with cyclosporine or IVIG or simply complete the course of the disease process with supportive care.

As dermatology residents, the telephone calls we get at 2 am usually are the toughest for 2 reasons: (1) we rarely get calls at 2 am, and (2) it usually means there is a case to rule out Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Stevens-Johnson syndrome and TEN are severe mucocutaneous eruptions that usually develop due to drug reactions and involve a continuum of conjunctivitis, mucocutaneous sloughing, keratinocyte death, and bullae development. Body surface area (BSA) coverage determines the distinction between SJS and TEN; less than 10% BSA affected indicates SJS, 10% to 30% BSA affected indicates overlap between SJS and TEN, and greater than 30% BSA affected indicates TEN.¹ The mortality rates for these conditions range from 1% to 5% in SJS versus 25% to 30% in TEN.²

Being driven and dedicated residents, we rise to the challenge by arranging appropriate consultations, obtaining frozen section biopsies, providing recommendations to remove unnecessary medications, and offering skin care management. However, what comes next? Intravenous immunoglobulin (IVIG)? Cyclosporine? Or is it appropriate to allow the reaction to continue its course? Dermatology programs have a varying standard of care due to the limited number of studies conducted on SJS/TEN patients. Few studies have relayed the efficacy of cyclosporine; however, published results have shown that cyclosporine can decrease the overall mortality risk and minimize disease progression.^2-5 In this article, I will review some of the key studies conducted in the last 5 years regarding the use of cyclosporine in the therapeutic plan for SJS/TEN.

In one retrospective analysis conducted by Kirchhof et al¹ in 2014, 35 patients with SJS/TEN who were treated with IVIG and 15 who were treated with cyclosporine were evaluated for mortality benefit. Two patients were treated with both cyclosporine and IVIG and were included in both arms of the study. Overall, the evaluation indicated that cyclosporine can potentially have a better overall advantage in treatment of SJS/TEN over IVIG.¹ Although this study had an uneven number of patients treated with IVIG versus cyclosporine, a nonstandardized way of comparing patients with early SJS to TEN patients, and no double-blind randomized trial, cyclosporine may still show benefit over IVIG.

Singh et al⁶ conducted an uncontrolled open study in a tertiary care center (July 2011–June 2012) that showed a similar result of benefit with cyclosporine in SJS, SJS/TEN, and TEN patients. Eleven participants were included in the study based on SCORTEN (Score of Toxic Epidermal Necrosis) criteria (age, >40 years; heart rate, >120 BPM; serum blood urea nitrogen level, >28 mg/dL; body surface area affected, >10%; serum bicarbonate, >20 mEq/L; serum glucose, >252 mg/dL). They were treated with cyclosporine 3 mg/kg for 7 days and then tapered over another 7 days. Six participants were treated with corticosteroids. Participants treated with cyclosporine reepithelialized in 16.7 days compared to 23 days with corticosteroids. The hospital stay was 18.09 days in participants treated with cyclosporine versus 26 days in those treated with corticosteroids. Lastly, 2 participants who were treated with corticosteroids died as opposed to none with cyclosporine.⁶ Although the power of this study also was limited and it was not a randomized, double-blind, controlled trial, it provides more evidence that cyclosporine can be efficacious in SJS/TEN patients.

A phase 2 open trial conducted by Valeyrie-Allanore et al⁷ evaluated the benefit and efficacy of cyclosporine in SJS/TEN patients. There were 29 participants at the start of the study (SJS, n=10; SJS/TEN, n=12; TEN, n=7) and 26 completed treatment. Cyclosporine was administered orally at 3 mg/kg for 10 days and tapered over the following month. This study noted 3 basic principles: First, patients tolerated cyclosporine well; second, limited disease progression was noted in 62% (18/29) of participants around day 3 and in only about 35% (11/29) of IVIG patients; and third, no deaths were noted in all participants.⁷

Final Thoughts

Case reports have indicated that cyclosporine may be effective in limiting progression of SJS/TEN; however, a double-blind study has not validated this finding. Hence, patients should be evaluated on a case-by-case basis to determine if they should be treated with cyclosporine or IVIG or simply complete the course of the disease process with supportive care.