Hospitalist News (Archived)

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

TORONTO – A scratch-and-sniff test that asks subjects to identify 40 odors and ranks olfaction is almost as powerful a predictor of Alzheimer’s disease as is a positive test for amyloid.

Low scores on the University of Pennsylvania Smell Identification Test (UPSIT) are linked to a thinning of the entorhinal cortex – the brain region where amyloid plaques are thought to first appear as Alzheimer’s disease takes hold, Seonjoo Lee, PhD, reported at the Alzheimer’s Association International Conference.

“The findings indirectly suggest that impairment in odor identification may precede thinning in the entorhinal cortex in the early clinical stage of AD,” she concluded.

According to William Kriesl, MD, poor UPSIT sores are also related to brain levels of amyloid beta and are almost as predictive of cognitive decline.

These sensory changes appear to be one of the earliest manifestations of Alzheimer’s disease, the researchers said at the Alzheimer’s Association International Conference. Their studies also suggest that the test has a place in the clinic as an easy and inexpensive screening tool for patients with memory complaints, Dr. Kreisl said at the Alzheimer’s Association International Conference.

The amyloid biomarker tests currently available are not suitable for wide dissemination. Amyloid brain scans are currently investigative; they are also invasive, expensive, and not covered by Medicare or any private insurance. Lumbar punctures are also invasive and expensive, and almost universally disliked by patients. Additionally, there is little consensus on how to interpret CSF amyloid levels.

“We need easy, noninvasive biomarkers that can be deployed in the clinic for patients who are concerned about their risk of memory decline,” said Dr. Kreisl of Columbia University Medical Center, New York. “Odor identification testing may provide to be a useful tool in helping physicians counsel patients who are concerned about this.”

His study concluded that the UPSIT predicted Alzheimer’s disease almost as well as invasive amyloid biomarkers. The scratch-and-sniff test asks subjects to identify 40 odors and ranks olfaction as normal, or mildly, moderately or severely impaired.

Dr. Kreisl examined the relationship between UPSIT and brain amyloid beta in 84 subjects, 58 of whom had mild cognitive impairment (MCI) at baseline. All of these subjects had either an amyloid brain scan or a lumbar puncture to measure amyloid in cerebrospinal fluid. They were followed for at least 6 months.

At follow-up, 67% of the group of participants showed cognitive decline. After correcting for age, gender, and education, patients who were amyloid-positive on imaging or in CSF were more than 7 times as likely to have experienced cognitive decline [Odds Ratio (OR) 7.3]. Overall, UPSIT score alone didn’t predict cognitive decline, Dr. Kreisl said. However, when it was imputed as a continuous variable, patients with a score of less than 35 on the 40-item test were four times more likely to show cognitive decline than those with a score of 35 or higher (OR 4).

In fact, these low UPSIT scores were much more common among amyloid-positive patients. Of the 38 patients who were positive for amyloid beta on either diagnostic test, 32 had an UPSIT score of less than 35 while six had a score of 35 or higher. Among the 46 amyloid-negative patients, 28 had low UPSIT scores and 18 had normal UPSIT scores.

Combining amyloid status and UPSIT in a single predictive model didn’t increase accuracy above that of either variable alone, which suggests olfactory dysfunction is not being completely driven by amyloid brain pathology.

“This makes sense because other factors like neurofibrillary tangle burden and other neurodegeneration are also involved in influencing how the UPSIT score predicts memory decline,” he said.

In a separate study, Dr. Lee examined the relationship of UPSIT performance to entorhinal cortical thickness in 397 cognitively normal subjects who were involved in the Washington Heights-Inwood Columbia Aging Project. These subjects took the UPSIT and had magnetic resonance brain imaging both at baseline and at 4 years’ follow-up. Over that time, 50 transitioned to dementia, and 49 of them were diagnosed with Alzheimer’s disease. Another 79 subjects experienced cognitive decline, which was defined as a decline of at least one standard deviation in the average of the three cognitive composite scores of memory, language and visuospatial domains.

In comparing the groups with and without dementia, Dr. Lee found significant differences in the follow-up UPSIT score (23 vs. 27) and entorhinal cortical thickness (2.9 vs. 3.1 mm).

One standard deviation in performance on the UPSIT score was associated with a significant 47% increase in the risk of dementia, while one standard deviation in entorhinal cortical thickness was associated with a 22% increase in the risk. However, Dr. Lee said, the interaction of entorhinal thickness and UPSIT score was only significant in the group of subjects who transitioned to dementia.

Dr. Richard Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz., commented on the limited clinical utility of the UPSIT in a video interview.

Neither Dr. Lee nor Dr. Kreisl had any financial declarations.

[email protected]

On Twitter @alz_gal

TORONTO – A scratch-and-sniff test that asks subjects to identify 40 odors and ranks olfaction is almost as powerful a predictor of Alzheimer’s disease as is a positive test for amyloid.

Low scores on the University of Pennsylvania Smell Identification Test (UPSIT) are linked to a thinning of the entorhinal cortex – the brain region where amyloid plaques are thought to first appear as Alzheimer’s disease takes hold, Seonjoo Lee, PhD, reported at the Alzheimer’s Association International Conference.

“The findings indirectly suggest that impairment in odor identification may precede thinning in the entorhinal cortex in the early clinical stage of AD,” she concluded.

According to William Kriesl, MD, poor UPSIT sores are also related to brain levels of amyloid beta and are almost as predictive of cognitive decline.

These sensory changes appear to be one of the earliest manifestations of Alzheimer’s disease, the researchers said at the Alzheimer’s Association International Conference. Their studies also suggest that the test has a place in the clinic as an easy and inexpensive screening tool for patients with memory complaints, Dr. Kreisl said at the Alzheimer’s Association International Conference.

The amyloid biomarker tests currently available are not suitable for wide dissemination. Amyloid brain scans are currently investigative; they are also invasive, expensive, and not covered by Medicare or any private insurance. Lumbar punctures are also invasive and expensive, and almost universally disliked by patients. Additionally, there is little consensus on how to interpret CSF amyloid levels.

“We need easy, noninvasive biomarkers that can be deployed in the clinic for patients who are concerned about their risk of memory decline,” said Dr. Kreisl of Columbia University Medical Center, New York. “Odor identification testing may provide to be a useful tool in helping physicians counsel patients who are concerned about this.”

His study concluded that the UPSIT predicted Alzheimer’s disease almost as well as invasive amyloid biomarkers. The scratch-and-sniff test asks subjects to identify 40 odors and ranks olfaction as normal, or mildly, moderately or severely impaired.

Dr. Kreisl examined the relationship between UPSIT and brain amyloid beta in 84 subjects, 58 of whom had mild cognitive impairment (MCI) at baseline. All of these subjects had either an amyloid brain scan or a lumbar puncture to measure amyloid in cerebrospinal fluid. They were followed for at least 6 months.

At follow-up, 67% of the group of participants showed cognitive decline. After correcting for age, gender, and education, patients who were amyloid-positive on imaging or in CSF were more than 7 times as likely to have experienced cognitive decline [Odds Ratio (OR) 7.3]. Overall, UPSIT score alone didn’t predict cognitive decline, Dr. Kreisl said. However, when it was imputed as a continuous variable, patients with a score of less than 35 on the 40-item test were four times more likely to show cognitive decline than those with a score of 35 or higher (OR 4).

In fact, these low UPSIT scores were much more common among amyloid-positive patients. Of the 38 patients who were positive for amyloid beta on either diagnostic test, 32 had an UPSIT score of less than 35 while six had a score of 35 or higher. Among the 46 amyloid-negative patients, 28 had low UPSIT scores and 18 had normal UPSIT scores.

Combining amyloid status and UPSIT in a single predictive model didn’t increase accuracy above that of either variable alone, which suggests olfactory dysfunction is not being completely driven by amyloid brain pathology.

“This makes sense because other factors like neurofibrillary tangle burden and other neurodegeneration are also involved in influencing how the UPSIT score predicts memory decline,” he said.

In a separate study, Dr. Lee examined the relationship of UPSIT performance to entorhinal cortical thickness in 397 cognitively normal subjects who were involved in the Washington Heights-Inwood Columbia Aging Project. These subjects took the UPSIT and had magnetic resonance brain imaging both at baseline and at 4 years’ follow-up. Over that time, 50 transitioned to dementia, and 49 of them were diagnosed with Alzheimer’s disease. Another 79 subjects experienced cognitive decline, which was defined as a decline of at least one standard deviation in the average of the three cognitive composite scores of memory, language and visuospatial domains.

In comparing the groups with and without dementia, Dr. Lee found significant differences in the follow-up UPSIT score (23 vs. 27) and entorhinal cortical thickness (2.9 vs. 3.1 mm).

One standard deviation in performance on the UPSIT score was associated with a significant 47% increase in the risk of dementia, while one standard deviation in entorhinal cortical thickness was associated with a 22% increase in the risk. However, Dr. Lee said, the interaction of entorhinal thickness and UPSIT score was only significant in the group of subjects who transitioned to dementia.

Dr. Richard Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz., commented on the limited clinical utility of the UPSIT in a video interview.

Neither Dr. Lee nor Dr. Kreisl had any financial declarations.

[email protected]

On Twitter @alz_gal

TORONTO – A scratch-and-sniff test that asks subjects to identify 40 odors and ranks olfaction is almost as powerful a predictor of Alzheimer’s disease as is a positive test for amyloid.

Low scores on the University of Pennsylvania Smell Identification Test (UPSIT) are linked to a thinning of the entorhinal cortex – the brain region where amyloid plaques are thought to first appear as Alzheimer’s disease takes hold, Seonjoo Lee, PhD, reported at the Alzheimer’s Association International Conference.

“The findings indirectly suggest that impairment in odor identification may precede thinning in the entorhinal cortex in the early clinical stage of AD,” she concluded.

According to William Kriesl, MD, poor UPSIT sores are also related to brain levels of amyloid beta and are almost as predictive of cognitive decline.

These sensory changes appear to be one of the earliest manifestations of Alzheimer’s disease, the researchers said at the Alzheimer’s Association International Conference. Their studies also suggest that the test has a place in the clinic as an easy and inexpensive screening tool for patients with memory complaints, Dr. Kreisl said at the Alzheimer’s Association International Conference.

The amyloid biomarker tests currently available are not suitable for wide dissemination. Amyloid brain scans are currently investigative; they are also invasive, expensive, and not covered by Medicare or any private insurance. Lumbar punctures are also invasive and expensive, and almost universally disliked by patients. Additionally, there is little consensus on how to interpret CSF amyloid levels.

“We need easy, noninvasive biomarkers that can be deployed in the clinic for patients who are concerned about their risk of memory decline,” said Dr. Kreisl of Columbia University Medical Center, New York. “Odor identification testing may provide to be a useful tool in helping physicians counsel patients who are concerned about this.”

His study concluded that the UPSIT predicted Alzheimer’s disease almost as well as invasive amyloid biomarkers. The scratch-and-sniff test asks subjects to identify 40 odors and ranks olfaction as normal, or mildly, moderately or severely impaired.

Dr. Kreisl examined the relationship between UPSIT and brain amyloid beta in 84 subjects, 58 of whom had mild cognitive impairment (MCI) at baseline. All of these subjects had either an amyloid brain scan or a lumbar puncture to measure amyloid in cerebrospinal fluid. They were followed for at least 6 months.

At follow-up, 67% of the group of participants showed cognitive decline. After correcting for age, gender, and education, patients who were amyloid-positive on imaging or in CSF were more than 7 times as likely to have experienced cognitive decline [Odds Ratio (OR) 7.3]. Overall, UPSIT score alone didn’t predict cognitive decline, Dr. Kreisl said. However, when it was imputed as a continuous variable, patients with a score of less than 35 on the 40-item test were four times more likely to show cognitive decline than those with a score of 35 or higher (OR 4).

In fact, these low UPSIT scores were much more common among amyloid-positive patients. Of the 38 patients who were positive for amyloid beta on either diagnostic test, 32 had an UPSIT score of less than 35 while six had a score of 35 or higher. Among the 46 amyloid-negative patients, 28 had low UPSIT scores and 18 had normal UPSIT scores.

Combining amyloid status and UPSIT in a single predictive model didn’t increase accuracy above that of either variable alone, which suggests olfactory dysfunction is not being completely driven by amyloid brain pathology.

“This makes sense because other factors like neurofibrillary tangle burden and other neurodegeneration are also involved in influencing how the UPSIT score predicts memory decline,” he said.

In a separate study, Dr. Lee examined the relationship of UPSIT performance to entorhinal cortical thickness in 397 cognitively normal subjects who were involved in the Washington Heights-Inwood Columbia Aging Project. These subjects took the UPSIT and had magnetic resonance brain imaging both at baseline and at 4 years’ follow-up. Over that time, 50 transitioned to dementia, and 49 of them were diagnosed with Alzheimer’s disease. Another 79 subjects experienced cognitive decline, which was defined as a decline of at least one standard deviation in the average of the three cognitive composite scores of memory, language and visuospatial domains.

In comparing the groups with and without dementia, Dr. Lee found significant differences in the follow-up UPSIT score (23 vs. 27) and entorhinal cortical thickness (2.9 vs. 3.1 mm).

One standard deviation in performance on the UPSIT score was associated with a significant 47% increase in the risk of dementia, while one standard deviation in entorhinal cortical thickness was associated with a 22% increase in the risk. However, Dr. Lee said, the interaction of entorhinal thickness and UPSIT score was only significant in the group of subjects who transitioned to dementia.

Dr. Richard Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz., commented on the limited clinical utility of the UPSIT in a video interview.

Neither Dr. Lee nor Dr. Kreisl had any financial declarations.

[email protected]

On Twitter @alz_gal

ROME – Combined exposure to low LDL cholesterol and systolic blood pressure is associated with multiplicative and cumulative effects over time, Brian A. Ference, MD, said in a video interview at the annual congress of the European Society of Cardiology.

Indeed, long-term exposure to a combined 1-mmol/L lower LDL cholesterol and 10-mm Hg lower systolic BP was associated with up to a 90% lower risk of major cardiovascular events in the “naturally randomized” study he presented. The investigators used the 102,000 participants’ genetic LDL and BP scores in a Mendelian design.

If these lower LDL and blood pressure levels are sustained over decades, “those cumulative effects multiply, resulting in potentially dramatic reductions in the lifetime risk of cardiovascular events from even modestly lower levels of LDL and systolic blood pressure,” Dr. Ference of Wayne State University, Detroit, told reporter Bruce Jancin.

[email protected]

ROME – Combined exposure to low LDL cholesterol and systolic blood pressure is associated with multiplicative and cumulative effects over time, Brian A. Ference, MD, said in a video interview at the annual congress of the European Society of Cardiology.

Indeed, long-term exposure to a combined 1-mmol/L lower LDL cholesterol and 10-mm Hg lower systolic BP was associated with up to a 90% lower risk of major cardiovascular events in the “naturally randomized” study he presented. The investigators used the 102,000 participants’ genetic LDL and BP scores in a Mendelian design.

If these lower LDL and blood pressure levels are sustained over decades, “those cumulative effects multiply, resulting in potentially dramatic reductions in the lifetime risk of cardiovascular events from even modestly lower levels of LDL and systolic blood pressure,” Dr. Ference of Wayne State University, Detroit, told reporter Bruce Jancin.

[email protected]

ROME – Combined exposure to low LDL cholesterol and systolic blood pressure is associated with multiplicative and cumulative effects over time, Brian A. Ference, MD, said in a video interview at the annual congress of the European Society of Cardiology.

Indeed, long-term exposure to a combined 1-mmol/L lower LDL cholesterol and 10-mm Hg lower systolic BP was associated with up to a 90% lower risk of major cardiovascular events in the “naturally randomized” study he presented. The investigators used the 102,000 participants’ genetic LDL and BP scores in a Mendelian design.

If these lower LDL and blood pressure levels are sustained over decades, “those cumulative effects multiply, resulting in potentially dramatic reductions in the lifetime risk of cardiovascular events from even modestly lower levels of LDL and systolic blood pressure,” Dr. Ference of Wayne State University, Detroit, told reporter Bruce Jancin.

[email protected]

ROME – Implantable cardioverter-defibrillators failed to significantly cut total mortality in patients with nonischemic systolic heart failure in the first large, randomized trial designed specifically to test the treatment in this setting. But the devices did show significant efficacy for doing what thy are specifically designed to do: prevent sudden cardiac death.

Results from the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) also highlighted the importance of targeting implantable cardioverter-defibrillator (ICD) treatment to the patients with nonischemic systolic heart failure who are most likely to benefit from it, younger patients who can be expected to live substantially longer than 1 year after they receive the device.

Mitchel L. Zoler/Frontline Medical News

As a consequence, although the DANISH outcome was neutral for the study’s primary endpoint of decreased all-cause mortality several experts who commented on the findings as well as its lead investigator saw the overall results as providing important new evidence that ICDs are beneficial as long as they get placed in relative young nonischemic heart failure patients who don’t have comorbidities that threaten a quick demise.

The DANISH results “tell us ICDs can benefit patients if we can be a little better in selecting the right patients,” said Lars Køber, MD, while presenting the results at the annual congress of the European Society of Cardiology.

He noted that “for us [in Denmark] the results actually mean we’ll implant more ICDs. We had not been using ICDs [in patients with nonischemic systolic heart failure] because we were not convinced we should use them on everyone,” said Dr. Køber, a professor of cardiology at the University of Copenhagen.

“The primary outcome was neutral, but the reduction in sudden cardiac death, the primary objective of an ICD, was significant, so placing an ICD should be taken into consideration,” commented Michel Komajda, MD, professor of cardiology at Pierre and Marie Curie University in Paris.

“This is the first trial to look at ICDs in the setting of modern therapy. Most of the ICD trials are very old now,” commented Mariell L. Jessup, MD, a heart failure specialist and professor of medicine at the University of Pennsylvania in Philadelphia. “In DANISH the ICDs significantly reduced the incidence of sudden cardiac death; that is what ICDs do.”

DANISH randomized 1,116 patients with nonischemic systolic heart failure at any of five Danish hospitals to either receive or not receive an ICD on top of optimal medical therapy and, when judged appropriate, placement of a cardiac resynchronization therapy (CRT) device. The patients averaged about 64 years of age, they all had New York Heart Association class II or III heart failure, and their maximum left ventricular ejection fraction was 35%. The researchers followed patients for a median of about 68 months (5.7 years).

The study’s primary endpoint, death from any cause, occurred in 22% of the ICD recipients and in 23% of control patients, a nonsignificant difference. The two prespecified secondary endpoints were cardiovascular death, which was a relative 23% lower in the ICD patients and also not statistically significant, but the rate of sudden cardiac death during follow-up was 4% in the ICD patients and 8% in the controls, a statistically significant 50% relative risk reduction. Concurrent with Dr. Køber’s report of these results at the meeting they also appeared online (N Engl J Med. 2016 Aug 28;doi: 10.1056/NEJMoa1608029).

The study design also included a set of prespecified subset analyses, and one of these showed a statistically significant interaction: When the analysis stratified patients into tertiles by age, those younger than 59 years old had a statistically significant 49% cut in all-cause mortality with ICD use, and patients 59-67 years old had a nonsignificant 25% reduction in all cause mortality when on ICD treatment. A second analysis that included all these patients less than 68 years old showed that ICD use linked with a statistically significant 36% relative cut in all-cause death, compared with the patients who did not receive an ICD. Older patients, those at least age 68 years, had a relative 20% increased rate of all-cause mortality with ICD use but not a statistically significant difference.

Mitchel L. Zoler/Frontline Medical News

The results also showed a downside to ICD use. Among the 42% of patients who did not receive a CRT device, the rate of serious infection was 2.6% in the ICD recipients and 0.8% in the control. Serious infection rates with and without ICD placement were similar in the subgroup of patients who received a CRT device.

The results underscored the ability of ICDs to provide a substantial benefit to well-selected patients based on factors such as age. “Clearly we need more accurate selection of nonischemic systolic heart failure patients before implanting ICDs,” said Christophe Leclerqc, MD, designated discussant for the study and professor of cardiology at Central University Hospital of Rennes, France.

“It’s all about patient selection,” agreed Dr. Jessup, who added that currently many nonischemic heart failure patients worldwide who could benefit from an ICD and have a life expectancy beyond 1 year do not receive a device.

[email protected]

On Twitter @mitchelzoler

ROME – Implantable cardioverter-defibrillators failed to significantly cut total mortality in patients with nonischemic systolic heart failure in the first large, randomized trial designed specifically to test the treatment in this setting. But the devices did show significant efficacy for doing what thy are specifically designed to do: prevent sudden cardiac death.

Results from the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) also highlighted the importance of targeting implantable cardioverter-defibrillator (ICD) treatment to the patients with nonischemic systolic heart failure who are most likely to benefit from it, younger patients who can be expected to live substantially longer than 1 year after they receive the device.

Mitchel L. Zoler/Frontline Medical News

As a consequence, although the DANISH outcome was neutral for the study’s primary endpoint of decreased all-cause mortality several experts who commented on the findings as well as its lead investigator saw the overall results as providing important new evidence that ICDs are beneficial as long as they get placed in relative young nonischemic heart failure patients who don’t have comorbidities that threaten a quick demise.

The DANISH results “tell us ICDs can benefit patients if we can be a little better in selecting the right patients,” said Lars Køber, MD, while presenting the results at the annual congress of the European Society of Cardiology.

He noted that “for us [in Denmark] the results actually mean we’ll implant more ICDs. We had not been using ICDs [in patients with nonischemic systolic heart failure] because we were not convinced we should use them on everyone,” said Dr. Køber, a professor of cardiology at the University of Copenhagen.

“The primary outcome was neutral, but the reduction in sudden cardiac death, the primary objective of an ICD, was significant, so placing an ICD should be taken into consideration,” commented Michel Komajda, MD, professor of cardiology at Pierre and Marie Curie University in Paris.

“This is the first trial to look at ICDs in the setting of modern therapy. Most of the ICD trials are very old now,” commented Mariell L. Jessup, MD, a heart failure specialist and professor of medicine at the University of Pennsylvania in Philadelphia. “In DANISH the ICDs significantly reduced the incidence of sudden cardiac death; that is what ICDs do.”

DANISH randomized 1,116 patients with nonischemic systolic heart failure at any of five Danish hospitals to either receive or not receive an ICD on top of optimal medical therapy and, when judged appropriate, placement of a cardiac resynchronization therapy (CRT) device. The patients averaged about 64 years of age, they all had New York Heart Association class II or III heart failure, and their maximum left ventricular ejection fraction was 35%. The researchers followed patients for a median of about 68 months (5.7 years).

The study’s primary endpoint, death from any cause, occurred in 22% of the ICD recipients and in 23% of control patients, a nonsignificant difference. The two prespecified secondary endpoints were cardiovascular death, which was a relative 23% lower in the ICD patients and also not statistically significant, but the rate of sudden cardiac death during follow-up was 4% in the ICD patients and 8% in the controls, a statistically significant 50% relative risk reduction. Concurrent with Dr. Køber’s report of these results at the meeting they also appeared online (N Engl J Med. 2016 Aug 28;doi: 10.1056/NEJMoa1608029).

The study design also included a set of prespecified subset analyses, and one of these showed a statistically significant interaction: When the analysis stratified patients into tertiles by age, those younger than 59 years old had a statistically significant 49% cut in all-cause mortality with ICD use, and patients 59-67 years old had a nonsignificant 25% reduction in all cause mortality when on ICD treatment. A second analysis that included all these patients less than 68 years old showed that ICD use linked with a statistically significant 36% relative cut in all-cause death, compared with the patients who did not receive an ICD. Older patients, those at least age 68 years, had a relative 20% increased rate of all-cause mortality with ICD use but not a statistically significant difference.

Mitchel L. Zoler/Frontline Medical News

The results also showed a downside to ICD use. Among the 42% of patients who did not receive a CRT device, the rate of serious infection was 2.6% in the ICD recipients and 0.8% in the control. Serious infection rates with and without ICD placement were similar in the subgroup of patients who received a CRT device.

The results underscored the ability of ICDs to provide a substantial benefit to well-selected patients based on factors such as age. “Clearly we need more accurate selection of nonischemic systolic heart failure patients before implanting ICDs,” said Christophe Leclerqc, MD, designated discussant for the study and professor of cardiology at Central University Hospital of Rennes, France.

“It’s all about patient selection,” agreed Dr. Jessup, who added that currently many nonischemic heart failure patients worldwide who could benefit from an ICD and have a life expectancy beyond 1 year do not receive a device.

[email protected]

On Twitter @mitchelzoler

ROME – Implantable cardioverter-defibrillators failed to significantly cut total mortality in patients with nonischemic systolic heart failure in the first large, randomized trial designed specifically to test the treatment in this setting. But the devices did show significant efficacy for doing what thy are specifically designed to do: prevent sudden cardiac death.

Results from the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) also highlighted the importance of targeting implantable cardioverter-defibrillator (ICD) treatment to the patients with nonischemic systolic heart failure who are most likely to benefit from it, younger patients who can be expected to live substantially longer than 1 year after they receive the device.

Mitchel L. Zoler/Frontline Medical News

As a consequence, although the DANISH outcome was neutral for the study’s primary endpoint of decreased all-cause mortality several experts who commented on the findings as well as its lead investigator saw the overall results as providing important new evidence that ICDs are beneficial as long as they get placed in relative young nonischemic heart failure patients who don’t have comorbidities that threaten a quick demise.

The DANISH results “tell us ICDs can benefit patients if we can be a little better in selecting the right patients,” said Lars Køber, MD, while presenting the results at the annual congress of the European Society of Cardiology.

He noted that “for us [in Denmark] the results actually mean we’ll implant more ICDs. We had not been using ICDs [in patients with nonischemic systolic heart failure] because we were not convinced we should use them on everyone,” said Dr. Køber, a professor of cardiology at the University of Copenhagen.

“The primary outcome was neutral, but the reduction in sudden cardiac death, the primary objective of an ICD, was significant, so placing an ICD should be taken into consideration,” commented Michel Komajda, MD, professor of cardiology at Pierre and Marie Curie University in Paris.

“This is the first trial to look at ICDs in the setting of modern therapy. Most of the ICD trials are very old now,” commented Mariell L. Jessup, MD, a heart failure specialist and professor of medicine at the University of Pennsylvania in Philadelphia. “In DANISH the ICDs significantly reduced the incidence of sudden cardiac death; that is what ICDs do.”

DANISH randomized 1,116 patients with nonischemic systolic heart failure at any of five Danish hospitals to either receive or not receive an ICD on top of optimal medical therapy and, when judged appropriate, placement of a cardiac resynchronization therapy (CRT) device. The patients averaged about 64 years of age, they all had New York Heart Association class II or III heart failure, and their maximum left ventricular ejection fraction was 35%. The researchers followed patients for a median of about 68 months (5.7 years).

The study’s primary endpoint, death from any cause, occurred in 22% of the ICD recipients and in 23% of control patients, a nonsignificant difference. The two prespecified secondary endpoints were cardiovascular death, which was a relative 23% lower in the ICD patients and also not statistically significant, but the rate of sudden cardiac death during follow-up was 4% in the ICD patients and 8% in the controls, a statistically significant 50% relative risk reduction. Concurrent with Dr. Køber’s report of these results at the meeting they also appeared online (N Engl J Med. 2016 Aug 28;doi: 10.1056/NEJMoa1608029).

The study design also included a set of prespecified subset analyses, and one of these showed a statistically significant interaction: When the analysis stratified patients into tertiles by age, those younger than 59 years old had a statistically significant 49% cut in all-cause mortality with ICD use, and patients 59-67 years old had a nonsignificant 25% reduction in all cause mortality when on ICD treatment. A second analysis that included all these patients less than 68 years old showed that ICD use linked with a statistically significant 36% relative cut in all-cause death, compared with the patients who did not receive an ICD. Older patients, those at least age 68 years, had a relative 20% increased rate of all-cause mortality with ICD use but not a statistically significant difference.

Mitchel L. Zoler/Frontline Medical News

The results also showed a downside to ICD use. Among the 42% of patients who did not receive a CRT device, the rate of serious infection was 2.6% in the ICD recipients and 0.8% in the control. Serious infection rates with and without ICD placement were similar in the subgroup of patients who received a CRT device.

The results underscored the ability of ICDs to provide a substantial benefit to well-selected patients based on factors such as age. “Clearly we need more accurate selection of nonischemic systolic heart failure patients before implanting ICDs,” said Christophe Leclerqc, MD, designated discussant for the study and professor of cardiology at Central University Hospital of Rennes, France.

“It’s all about patient selection,” agreed Dr. Jessup, who added that currently many nonischemic heart failure patients worldwide who could benefit from an ICD and have a life expectancy beyond 1 year do not receive a device.

[email protected]

On Twitter @mitchelzoler

ROME – Early administration of high-dose N-acetylcysteine and low-dose glyceryl trinitrate in ST-segment elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) achieved a 30% reduction in myocardial infarct size, compared with placebo in a randomized, double-blind, multicenter clinical trial, Sivabaskari Pasupathy reported at the annual congress of the European Society of Cardiology.

The adjunctive regimen also resulted in a doubling of myocardial salvage, the secondary endpoint in the NACIAM (N-acetylcysteine in acute myocardial infarction) trial, said Ms. Pasupathy of the University of Adelaide, Australia.

Bruce Jancin/Frontline Medical News

NACIAM, which she stressed was a pilot study, included 75 randomized STEMI patients with follow-up cardiac MRIs obtained at about 5 days post-PCI, most of whom had another MRI at about 8 months.

All participants received IV glycerol trinitrate at a rate of 25 mcg/min for 48 hours starting in the emergency department. Patients in the active treatment arm received IV N-acetylcysteine (NAC) at 20 mg/min for the first hour and 10 mg/min for the next 47 hours. Controls got placebo at 40 mL/hour for the first hour and 20 mL/hour thereafter.

Cardiac MRI at 5 days showed a myocardial infarct size of 16.5% in the control group and 11% with active treatment. This absolute 5.5% reduction in infarct size in NAC recipients was achieved despite no difference between the two groups in myocardial area at risk by MRI, which was roughly 24%. Nor did the groups differ in rates of anterior MI or microvascular obstruction. The myocardial salvage rate was 60% in the NAC group and just 27% in controls.

Creatine kinase levels, measured hourly during the first 24 hours of hospitalization, were consistently lower in the NAC group, although the difference didn’t reach statistical significance.

In-hospital rates of hypotension, bleeding, or renal dysfunction were similar in the two study arms. However, at 2 years of follow-up the composite rate of death or cardiac rehospitalization was 27% in the control group, compared with 6% in patients who got NAC.

A key to the demonstrable success of the adjunctive NAC/nitrate treatment strategy was that it began early, in the emergency department, when patients initially presented with STEMI. The mean total ischemia time for study participants was 2.4 hours, and the shorter the duration of ischemia, the larger the reduction seen in infarct size, according to Ms. Pasupathy.

The rationale for this therapy is that NAC is thought to reduce oxidative stress by scavenging reactive oxygen species and inhibiting their release, thereby minimizing reperfusion injury. The Australian investigators also believe that NAC potentiates the effects of glycerol trinitrate in improving tissue reperfusion through enhanced vasodilation, inhibition of platelet aggregation, and dampening of inflammation. A reduction in reperfusion injury accompanied by increased tissue reperfusion could result in reduced infarct size, she explained.

Bruce Jancin/Frontline Medical News

John F. Beltrame, MD, lead investigator in the NACIAM study, noted that infarct size and myocardial salvage are surrogate endpoints. The investigators plan to conduct a larger trial with hard clinical outcomes.

“The key thing we need to do before we start using this in widespread fashion and changing practice guidelines is to look at clinical endpoints,” said Dr. Beltrame, professor of medicine at the University of Adelaide.

Nonetheless, he added, this therapy is given routinely in the setting of primary PCI for STEMI where he practices. That has been the case for 20 years because he and colleagues in his department did some of the early studies suggesting NAC was beneficial.

“Hospitals have different practices, and this is one of our particular practices,” the cardiologist said.

It all sounded pretty good to Jorge A. Belardi, MD, who co-chaired a press conference devoted to the NACIAM trial and other hotline presentations.

“It’s a very benign combination of medicines to use. So why not use it? We already use it to prevent contrast nephropathy. And there are no contraindications, to my knowledge,” said Dr. Belardi, director of the department of cardiology at the Buenos Aires Cardiovascular Institute.

Michel Ovize, MD, of the University of Lyon (France), the formal discussant designated for NACIAM, took a more flinty eyed view, noting that the study was small and previous studies of NAC during the past 2 decades have yielded conflicting results.

Ms. Pasupathy responded that a likely explanation for the disparate results is the fact that other investigators didn’t start NAC at the soonest possible time in the ED.

The NACIAM trial was funded by the Australian National Heart Foundation. Ms. Pasupathy and Dr. Beltrame reported having no financial conflicts of interest.

[email protected]

ROME – Early administration of high-dose N-acetylcysteine and low-dose glyceryl trinitrate in ST-segment elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) achieved a 30% reduction in myocardial infarct size, compared with placebo in a randomized, double-blind, multicenter clinical trial, Sivabaskari Pasupathy reported at the annual congress of the European Society of Cardiology.

The adjunctive regimen also resulted in a doubling of myocardial salvage, the secondary endpoint in the NACIAM (N-acetylcysteine in acute myocardial infarction) trial, said Ms. Pasupathy of the University of Adelaide, Australia.

Bruce Jancin/Frontline Medical News

NACIAM, which she stressed was a pilot study, included 75 randomized STEMI patients with follow-up cardiac MRIs obtained at about 5 days post-PCI, most of whom had another MRI at about 8 months.

All participants received IV glycerol trinitrate at a rate of 25 mcg/min for 48 hours starting in the emergency department. Patients in the active treatment arm received IV N-acetylcysteine (NAC) at 20 mg/min for the first hour and 10 mg/min for the next 47 hours. Controls got placebo at 40 mL/hour for the first hour and 20 mL/hour thereafter.

Cardiac MRI at 5 days showed a myocardial infarct size of 16.5% in the control group and 11% with active treatment. This absolute 5.5% reduction in infarct size in NAC recipients was achieved despite no difference between the two groups in myocardial area at risk by MRI, which was roughly 24%. Nor did the groups differ in rates of anterior MI or microvascular obstruction. The myocardial salvage rate was 60% in the NAC group and just 27% in controls.

Creatine kinase levels, measured hourly during the first 24 hours of hospitalization, were consistently lower in the NAC group, although the difference didn’t reach statistical significance.

In-hospital rates of hypotension, bleeding, or renal dysfunction were similar in the two study arms. However, at 2 years of follow-up the composite rate of death or cardiac rehospitalization was 27% in the control group, compared with 6% in patients who got NAC.

A key to the demonstrable success of the adjunctive NAC/nitrate treatment strategy was that it began early, in the emergency department, when patients initially presented with STEMI. The mean total ischemia time for study participants was 2.4 hours, and the shorter the duration of ischemia, the larger the reduction seen in infarct size, according to Ms. Pasupathy.

The rationale for this therapy is that NAC is thought to reduce oxidative stress by scavenging reactive oxygen species and inhibiting their release, thereby minimizing reperfusion injury. The Australian investigators also believe that NAC potentiates the effects of glycerol trinitrate in improving tissue reperfusion through enhanced vasodilation, inhibition of platelet aggregation, and dampening of inflammation. A reduction in reperfusion injury accompanied by increased tissue reperfusion could result in reduced infarct size, she explained.

Bruce Jancin/Frontline Medical News

John F. Beltrame, MD, lead investigator in the NACIAM study, noted that infarct size and myocardial salvage are surrogate endpoints. The investigators plan to conduct a larger trial with hard clinical outcomes.

“The key thing we need to do before we start using this in widespread fashion and changing practice guidelines is to look at clinical endpoints,” said Dr. Beltrame, professor of medicine at the University of Adelaide.

Nonetheless, he added, this therapy is given routinely in the setting of primary PCI for STEMI where he practices. That has been the case for 20 years because he and colleagues in his department did some of the early studies suggesting NAC was beneficial.

“Hospitals have different practices, and this is one of our particular practices,” the cardiologist said.

It all sounded pretty good to Jorge A. Belardi, MD, who co-chaired a press conference devoted to the NACIAM trial and other hotline presentations.

“It’s a very benign combination of medicines to use. So why not use it? We already use it to prevent contrast nephropathy. And there are no contraindications, to my knowledge,” said Dr. Belardi, director of the department of cardiology at the Buenos Aires Cardiovascular Institute.

Michel Ovize, MD, of the University of Lyon (France), the formal discussant designated for NACIAM, took a more flinty eyed view, noting that the study was small and previous studies of NAC during the past 2 decades have yielded conflicting results.

Ms. Pasupathy responded that a likely explanation for the disparate results is the fact that other investigators didn’t start NAC at the soonest possible time in the ED.

The NACIAM trial was funded by the Australian National Heart Foundation. Ms. Pasupathy and Dr. Beltrame reported having no financial conflicts of interest.

[email protected]

ROME – Early administration of high-dose N-acetylcysteine and low-dose glyceryl trinitrate in ST-segment elevation acute myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) achieved a 30% reduction in myocardial infarct size, compared with placebo in a randomized, double-blind, multicenter clinical trial, Sivabaskari Pasupathy reported at the annual congress of the European Society of Cardiology.

The adjunctive regimen also resulted in a doubling of myocardial salvage, the secondary endpoint in the NACIAM (N-acetylcysteine in acute myocardial infarction) trial, said Ms. Pasupathy of the University of Adelaide, Australia.

Bruce Jancin/Frontline Medical News

NACIAM, which she stressed was a pilot study, included 75 randomized STEMI patients with follow-up cardiac MRIs obtained at about 5 days post-PCI, most of whom had another MRI at about 8 months.

All participants received IV glycerol trinitrate at a rate of 25 mcg/min for 48 hours starting in the emergency department. Patients in the active treatment arm received IV N-acetylcysteine (NAC) at 20 mg/min for the first hour and 10 mg/min for the next 47 hours. Controls got placebo at 40 mL/hour for the first hour and 20 mL/hour thereafter.

Cardiac MRI at 5 days showed a myocardial infarct size of 16.5% in the control group and 11% with active treatment. This absolute 5.5% reduction in infarct size in NAC recipients was achieved despite no difference between the two groups in myocardial area at risk by MRI, which was roughly 24%. Nor did the groups differ in rates of anterior MI or microvascular obstruction. The myocardial salvage rate was 60% in the NAC group and just 27% in controls.

Creatine kinase levels, measured hourly during the first 24 hours of hospitalization, were consistently lower in the NAC group, although the difference didn’t reach statistical significance.

In-hospital rates of hypotension, bleeding, or renal dysfunction were similar in the two study arms. However, at 2 years of follow-up the composite rate of death or cardiac rehospitalization was 27% in the control group, compared with 6% in patients who got NAC.

A key to the demonstrable success of the adjunctive NAC/nitrate treatment strategy was that it began early, in the emergency department, when patients initially presented with STEMI. The mean total ischemia time for study participants was 2.4 hours, and the shorter the duration of ischemia, the larger the reduction seen in infarct size, according to Ms. Pasupathy.

The rationale for this therapy is that NAC is thought to reduce oxidative stress by scavenging reactive oxygen species and inhibiting their release, thereby minimizing reperfusion injury. The Australian investigators also believe that NAC potentiates the effects of glycerol trinitrate in improving tissue reperfusion through enhanced vasodilation, inhibition of platelet aggregation, and dampening of inflammation. A reduction in reperfusion injury accompanied by increased tissue reperfusion could result in reduced infarct size, she explained.

Bruce Jancin/Frontline Medical News

John F. Beltrame, MD, lead investigator in the NACIAM study, noted that infarct size and myocardial salvage are surrogate endpoints. The investigators plan to conduct a larger trial with hard clinical outcomes.

“The key thing we need to do before we start using this in widespread fashion and changing practice guidelines is to look at clinical endpoints,” said Dr. Beltrame, professor of medicine at the University of Adelaide.

Nonetheless, he added, this therapy is given routinely in the setting of primary PCI for STEMI where he practices. That has been the case for 20 years because he and colleagues in his department did some of the early studies suggesting NAC was beneficial.

“Hospitals have different practices, and this is one of our particular practices,” the cardiologist said.

It all sounded pretty good to Jorge A. Belardi, MD, who co-chaired a press conference devoted to the NACIAM trial and other hotline presentations.

“It’s a very benign combination of medicines to use. So why not use it? We already use it to prevent contrast nephropathy. And there are no contraindications, to my knowledge,” said Dr. Belardi, director of the department of cardiology at the Buenos Aires Cardiovascular Institute.

Michel Ovize, MD, of the University of Lyon (France), the formal discussant designated for NACIAM, took a more flinty eyed view, noting that the study was small and previous studies of NAC during the past 2 decades have yielded conflicting results.

Ms. Pasupathy responded that a likely explanation for the disparate results is the fact that other investigators didn’t start NAC at the soonest possible time in the ED.

The NACIAM trial was funded by the Australian National Heart Foundation. Ms. Pasupathy and Dr. Beltrame reported having no financial conflicts of interest.

[email protected]

Antibiotics are overprescribed in asthma-related hospitalizations, even though guidelines recommend against prescribing antibiotics during exacerbations of asthma in the absence of concurrent infection, reported Peter K. Lindenauer, MD, MSc, of Baystate Medical Center in Springfield, Mass., and his colleagues.

They examined the hospitalization records of 51,951 individuals admitted to 577 hospitals in the United States between 2013 and 2014 with a principal diagnosis of either asthma or acute respiratory failure combined with asthma as a secondary diagnosis. Each patient type and the timing of antibiotic therapy was noted.

A total of 30,226 of the 51,951 patients (58.2%) were prescribed antibiotics at some point during their hospitalization, while 21,248 (40.9%) were prescribed antibiotics on the first day of hospitalization, without “documentation of an indication for antibiotic therapy.”

Macrolides were most commonly prescribed, given to 9,633 (18.5%) of patients, followed by quinolones (8,632, 16.1%), third-generation cephalosporins (4,420, 8.5%), and tetracyclines (1,858, 3.6%). After adjustment for risk variables, chronic obstructive asthma hospitalizations were found to be those most highly associated with receiving antibiotics (odds ratio 1.6, 95% confidence interval 1.5-1.7).

“Possible explanations for this high rate of potentially inappropriate treatment include the challenge of differentiating bacterial from nonbacterial infections, distinguishing asthma from chronic obstructive pulmonary disease in the acute care setting, and gaps in knowledge about the benefits of antibiotic therapy,” the authors posited, adding that these findings “suggest a significant opportunity to improve patient safety, reduce the spread of resistance, and lower spending through greater adherence to guideline recommendations.”

The National Heart, Lung, and Blood Institute and Veterans Affairs Health Services Research and Development funded the study. Dr. Lindenauer and his coauthors did not report any relevant financial disclosures.

[email protected]

Antibiotics are overprescribed in asthma-related hospitalizations, even though guidelines recommend against prescribing antibiotics during exacerbations of asthma in the absence of concurrent infection, reported Peter K. Lindenauer, MD, MSc, of Baystate Medical Center in Springfield, Mass., and his colleagues.

They examined the hospitalization records of 51,951 individuals admitted to 577 hospitals in the United States between 2013 and 2014 with a principal diagnosis of either asthma or acute respiratory failure combined with asthma as a secondary diagnosis. Each patient type and the timing of antibiotic therapy was noted.

A total of 30,226 of the 51,951 patients (58.2%) were prescribed antibiotics at some point during their hospitalization, while 21,248 (40.9%) were prescribed antibiotics on the first day of hospitalization, without “documentation of an indication for antibiotic therapy.”

Macrolides were most commonly prescribed, given to 9,633 (18.5%) of patients, followed by quinolones (8,632, 16.1%), third-generation cephalosporins (4,420, 8.5%), and tetracyclines (1,858, 3.6%). After adjustment for risk variables, chronic obstructive asthma hospitalizations were found to be those most highly associated with receiving antibiotics (odds ratio 1.6, 95% confidence interval 1.5-1.7).

“Possible explanations for this high rate of potentially inappropriate treatment include the challenge of differentiating bacterial from nonbacterial infections, distinguishing asthma from chronic obstructive pulmonary disease in the acute care setting, and gaps in knowledge about the benefits of antibiotic therapy,” the authors posited, adding that these findings “suggest a significant opportunity to improve patient safety, reduce the spread of resistance, and lower spending through greater adherence to guideline recommendations.”

The National Heart, Lung, and Blood Institute and Veterans Affairs Health Services Research and Development funded the study. Dr. Lindenauer and his coauthors did not report any relevant financial disclosures.

[email protected]

Antibiotics are overprescribed in asthma-related hospitalizations, even though guidelines recommend against prescribing antibiotics during exacerbations of asthma in the absence of concurrent infection, reported Peter K. Lindenauer, MD, MSc, of Baystate Medical Center in Springfield, Mass., and his colleagues.

They examined the hospitalization records of 51,951 individuals admitted to 577 hospitals in the United States between 2013 and 2014 with a principal diagnosis of either asthma or acute respiratory failure combined with asthma as a secondary diagnosis. Each patient type and the timing of antibiotic therapy was noted.

A total of 30,226 of the 51,951 patients (58.2%) were prescribed antibiotics at some point during their hospitalization, while 21,248 (40.9%) were prescribed antibiotics on the first day of hospitalization, without “documentation of an indication for antibiotic therapy.”

Macrolides were most commonly prescribed, given to 9,633 (18.5%) of patients, followed by quinolones (8,632, 16.1%), third-generation cephalosporins (4,420, 8.5%), and tetracyclines (1,858, 3.6%). After adjustment for risk variables, chronic obstructive asthma hospitalizations were found to be those most highly associated with receiving antibiotics (odds ratio 1.6, 95% confidence interval 1.5-1.7).

“Possible explanations for this high rate of potentially inappropriate treatment include the challenge of differentiating bacterial from nonbacterial infections, distinguishing asthma from chronic obstructive pulmonary disease in the acute care setting, and gaps in knowledge about the benefits of antibiotic therapy,” the authors posited, adding that these findings “suggest a significant opportunity to improve patient safety, reduce the spread of resistance, and lower spending through greater adherence to guideline recommendations.”

The National Heart, Lung, and Blood Institute and Veterans Affairs Health Services Research and Development funded the study. Dr. Lindenauer and his coauthors did not report any relevant financial disclosures.

[email protected]

RNA-expression biosignatures derived from the patient’s peripheral blood distinguish bacterial from viral causes of fever in young children, according to two separate preliminary studies published online Aug. 23 in JAMA.

Several studies have suggested that the source of infection in febrile children might be identified by examining the pattern of host genes that are either activated or suppressed during the body’s inflammatory response. Distinguishing the relatively few but potentially life-threatening bacterial infections from the more common but milder, self-resolving viral infections is difficult, and current practice is to admit “ill-appearing” febrile children to the hospital and administer parenteral antibiotics while awaiting the results of blood and tissue cultures. Those results are often ambiguous, and the whole process represents a large burden on health care resources as well as contributing to inappropriate antibiotic treatment.

Two multinational research groups developed different techniques for detecting RNA biosignatures in patients’ blood samples, then assessed the accuracy of those tests in validation cohorts. One group focused on ruling out bacterial infection as the source of fever in young children (median age, 19 months), while the other investigated whether the host responses of the youngest children (aged 60 days and younger), who have immature immune systems, are robust enough to allow detection of RNA biosignatures.

In the discovery phase of the first study, analysis of RNA gene expression was performed on blood samples obtained from 240 children at admission to hospitals in the United Kingdom, Spain, and the United States during a 4-year period. A total of 8,565 RNA transcript signatures were identified as potential biomarkers to discriminate between viral and bacterial infection. This was narrowed down to 38 transcript signatures, and then to only 2 – IFI44L and FAM89A – that were used to devise a Disease Risk Score (DRS) for each patient, said Jethro A. Herberg, PhD, of the division of infectious diseases, Imperial College London, and his associates.

IFI44L expression was increased in patients who had viral infection, while FAM89A expression was increased in those who had bacterial infection, as compared with healthy children. (In previous studies, IFI44L was reported to be up-regulated in interferon-mediated antiviral responses and FAM89A was reported to be elevated among children with septic shock.)

The DRS showed 90% sensitivity in distinguishing viral from bacterial infection in the discovery cohort. It then showed 96.4% sensitivity in a validation cohort of 130 febrile children (mean age, 17 months). The DRS also identified bacterial infection in a validation cohort of 24 children with meningococcal infection (91.7% sensitivity and 96.0% specificity), and distinguished it from inflammatory conditions in another cohort of 30 children with juvenile idiopathic arthritis and 18 with Henoch-Schönlein purpura (90.0% sensitivity and 95.8% specificity).

The DRS discriminated among viral, bacterial, and inflammatory diseases including systemic lupus erythematosus in a further validation cohort, a published dataset from children and adults who had all three types of illness. It was accurate regardless of the severity of infection and regardless of the duration of infection, as well as in cases where patients were coinfected with both virus and bacteria, the investigators said (JAMA. 2016 Aug 23. doi:10.1001/jama.2016.11236).

“The DRS signature, distinguishing viral from bacterial infections with only two transcripts, has potential to be translated into a clinically applicable test using current technology. Furthermore, new methods for rapid detection of nucleic acids, including nanoparticles and electrical impedance, have potential for low-cost, rapid analysis of multitranscript signatures,” Dr. Herberg and his associates noted.

Further research is needed to assess the accuracy and clinical utility of this technique in different settings, they added.

In the second study, RNA gene expression was analyzed from blood samples from 1,883 febrile infants (median age, 37 days) “who posed diagnostic quandaries” at admission to 22 emergency departments during a 2-year period. The discovery phase involved 89 of these infants who ultimately were found to have bacterial infections (bacteremia or UTIs), 190 who didn’t have bacterial infections (enterovirus, influenza, or other viruses), and 19 healthy control infants, said Prashant Mahajan, MD, division chief and research director, pediatric emergency medicine, Children’s Hospital of Michigan, Detroit, and his associates.

The investigators identified 3,753 RNA transcript signatures that could potentially identify or rule out bacterial sources of infection, which they then narrowed down to 66. This set of 66 signatures showed 82% sensitivity and 88% specificity in the discovery cohort and 87% sensitivity and 89% specificity in a validation cohort.

“The bacterial RNA biosignature was notably more predictive of bacterial infection than clinical examination” and use of the Yale Observation Score, and it “added significantly to prediction beyond the YOS alone,” Dr. Mahajan and his associates said (JAMA. 2016 Aug 23. doi: 10.1001/jama.2016.9207).

“Despite the young age of the febrile infants evaluated, they carried robust RNA biosignatures and demonstrated that regardless of the etiology of the infections, their immune systems are programed to respond not only with shared elements induced by common microbes but also with specific patterns that allow discrimination by class of pathogen,” they noted.

Further research is needed to confirm and refine these preliminary results. “As technology advances, RNA biosignatures may prove to be an alternative and accurate method to identify infants with bacterial infections. This would help clinicians target evaluation and therapy when they are needed and avoid invasive procedures, antibiotics, and hospitalizations when they are not,” Dr. Mahajan and his associates said.

Dr. Herberg’s study was supported by the Imperial College Comprehensive Biomedical Research Center, the National Institutes of Health, the European Union’s Seventh Framework Program, and numerous other groups. Dr. Herberg reported having no relevant financial disclosures. Dr. Mahajan’s study was supported by the Health Resources and Services Administration, Emergency Services for Children, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institutes of Health. Dr. Mahajan reported having no relevant financial disclosures.

RNA-expression biosignatures derived from the patient’s peripheral blood distinguish bacterial from viral causes of fever in young children, according to two separate preliminary studies published online Aug. 23 in JAMA.

Several studies have suggested that the source of infection in febrile children might be identified by examining the pattern of host genes that are either activated or suppressed during the body’s inflammatory response. Distinguishing the relatively few but potentially life-threatening bacterial infections from the more common but milder, self-resolving viral infections is difficult, and current practice is to admit “ill-appearing” febrile children to the hospital and administer parenteral antibiotics while awaiting the results of blood and tissue cultures. Those results are often ambiguous, and the whole process represents a large burden on health care resources as well as contributing to inappropriate antibiotic treatment.

Two multinational research groups developed different techniques for detecting RNA biosignatures in patients’ blood samples, then assessed the accuracy of those tests in validation cohorts. One group focused on ruling out bacterial infection as the source of fever in young children (median age, 19 months), while the other investigated whether the host responses of the youngest children (aged 60 days and younger), who have immature immune systems, are robust enough to allow detection of RNA biosignatures.

In the discovery phase of the first study, analysis of RNA gene expression was performed on blood samples obtained from 240 children at admission to hospitals in the United Kingdom, Spain, and the United States during a 4-year period. A total of 8,565 RNA transcript signatures were identified as potential biomarkers to discriminate between viral and bacterial infection. This was narrowed down to 38 transcript signatures, and then to only 2 – IFI44L and FAM89A – that were used to devise a Disease Risk Score (DRS) for each patient, said Jethro A. Herberg, PhD, of the division of infectious diseases, Imperial College London, and his associates.

IFI44L expression was increased in patients who had viral infection, while FAM89A expression was increased in those who had bacterial infection, as compared with healthy children. (In previous studies, IFI44L was reported to be up-regulated in interferon-mediated antiviral responses and FAM89A was reported to be elevated among children with septic shock.)

The DRS showed 90% sensitivity in distinguishing viral from bacterial infection in the discovery cohort. It then showed 96.4% sensitivity in a validation cohort of 130 febrile children (mean age, 17 months). The DRS also identified bacterial infection in a validation cohort of 24 children with meningococcal infection (91.7% sensitivity and 96.0% specificity), and distinguished it from inflammatory conditions in another cohort of 30 children with juvenile idiopathic arthritis and 18 with Henoch-Schönlein purpura (90.0% sensitivity and 95.8% specificity).

The DRS discriminated among viral, bacterial, and inflammatory diseases including systemic lupus erythematosus in a further validation cohort, a published dataset from children and adults who had all three types of illness. It was accurate regardless of the severity of infection and regardless of the duration of infection, as well as in cases where patients were coinfected with both virus and bacteria, the investigators said (JAMA. 2016 Aug 23. doi:10.1001/jama.2016.11236).

“The DRS signature, distinguishing viral from bacterial infections with only two transcripts, has potential to be translated into a clinically applicable test using current technology. Furthermore, new methods for rapid detection of nucleic acids, including nanoparticles and electrical impedance, have potential for low-cost, rapid analysis of multitranscript signatures,” Dr. Herberg and his associates noted.

Further research is needed to assess the accuracy and clinical utility of this technique in different settings, they added.

In the second study, RNA gene expression was analyzed from blood samples from 1,883 febrile infants (median age, 37 days) “who posed diagnostic quandaries” at admission to 22 emergency departments during a 2-year period. The discovery phase involved 89 of these infants who ultimately were found to have bacterial infections (bacteremia or UTIs), 190 who didn’t have bacterial infections (enterovirus, influenza, or other viruses), and 19 healthy control infants, said Prashant Mahajan, MD, division chief and research director, pediatric emergency medicine, Children’s Hospital of Michigan, Detroit, and his associates.

The investigators identified 3,753 RNA transcript signatures that could potentially identify or rule out bacterial sources of infection, which they then narrowed down to 66. This set of 66 signatures showed 82% sensitivity and 88% specificity in the discovery cohort and 87% sensitivity and 89% specificity in a validation cohort.

“The bacterial RNA biosignature was notably more predictive of bacterial infection than clinical examination” and use of the Yale Observation Score, and it “added significantly to prediction beyond the YOS alone,” Dr. Mahajan and his associates said (JAMA. 2016 Aug 23. doi: 10.1001/jama.2016.9207).

“Despite the young age of the febrile infants evaluated, they carried robust RNA biosignatures and demonstrated that regardless of the etiology of the infections, their immune systems are programed to respond not only with shared elements induced by common microbes but also with specific patterns that allow discrimination by class of pathogen,” they noted.

Further research is needed to confirm and refine these preliminary results. “As technology advances, RNA biosignatures may prove to be an alternative and accurate method to identify infants with bacterial infections. This would help clinicians target evaluation and therapy when they are needed and avoid invasive procedures, antibiotics, and hospitalizations when they are not,” Dr. Mahajan and his associates said.

Dr. Herberg’s study was supported by the Imperial College Comprehensive Biomedical Research Center, the National Institutes of Health, the European Union’s Seventh Framework Program, and numerous other groups. Dr. Herberg reported having no relevant financial disclosures. Dr. Mahajan’s study was supported by the Health Resources and Services Administration, Emergency Services for Children, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institutes of Health. Dr. Mahajan reported having no relevant financial disclosures.

RNA-expression biosignatures derived from the patient’s peripheral blood distinguish bacterial from viral causes of fever in young children, according to two separate preliminary studies published online Aug. 23 in JAMA.

Several studies have suggested that the source of infection in febrile children might be identified by examining the pattern of host genes that are either activated or suppressed during the body’s inflammatory response. Distinguishing the relatively few but potentially life-threatening bacterial infections from the more common but milder, self-resolving viral infections is difficult, and current practice is to admit “ill-appearing” febrile children to the hospital and administer parenteral antibiotics while awaiting the results of blood and tissue cultures. Those results are often ambiguous, and the whole process represents a large burden on health care resources as well as contributing to inappropriate antibiotic treatment.

Two multinational research groups developed different techniques for detecting RNA biosignatures in patients’ blood samples, then assessed the accuracy of those tests in validation cohorts. One group focused on ruling out bacterial infection as the source of fever in young children (median age, 19 months), while the other investigated whether the host responses of the youngest children (aged 60 days and younger), who have immature immune systems, are robust enough to allow detection of RNA biosignatures.

In the discovery phase of the first study, analysis of RNA gene expression was performed on blood samples obtained from 240 children at admission to hospitals in the United Kingdom, Spain, and the United States during a 4-year period. A total of 8,565 RNA transcript signatures were identified as potential biomarkers to discriminate between viral and bacterial infection. This was narrowed down to 38 transcript signatures, and then to only 2 – IFI44L and FAM89A – that were used to devise a Disease Risk Score (DRS) for each patient, said Jethro A. Herberg, PhD, of the division of infectious diseases, Imperial College London, and his associates.

IFI44L expression was increased in patients who had viral infection, while FAM89A expression was increased in those who had bacterial infection, as compared with healthy children. (In previous studies, IFI44L was reported to be up-regulated in interferon-mediated antiviral responses and FAM89A was reported to be elevated among children with septic shock.)

The DRS showed 90% sensitivity in distinguishing viral from bacterial infection in the discovery cohort. It then showed 96.4% sensitivity in a validation cohort of 130 febrile children (mean age, 17 months). The DRS also identified bacterial infection in a validation cohort of 24 children with meningococcal infection (91.7% sensitivity and 96.0% specificity), and distinguished it from inflammatory conditions in another cohort of 30 children with juvenile idiopathic arthritis and 18 with Henoch-Schönlein purpura (90.0% sensitivity and 95.8% specificity).

The DRS discriminated among viral, bacterial, and inflammatory diseases including systemic lupus erythematosus in a further validation cohort, a published dataset from children and adults who had all three types of illness. It was accurate regardless of the severity of infection and regardless of the duration of infection, as well as in cases where patients were coinfected with both virus and bacteria, the investigators said (JAMA. 2016 Aug 23. doi:10.1001/jama.2016.11236).

“The DRS signature, distinguishing viral from bacterial infections with only two transcripts, has potential to be translated into a clinically applicable test using current technology. Furthermore, new methods for rapid detection of nucleic acids, including nanoparticles and electrical impedance, have potential for low-cost, rapid analysis of multitranscript signatures,” Dr. Herberg and his associates noted.

Further research is needed to assess the accuracy and clinical utility of this technique in different settings, they added.

In the second study, RNA gene expression was analyzed from blood samples from 1,883 febrile infants (median age, 37 days) “who posed diagnostic quandaries” at admission to 22 emergency departments during a 2-year period. The discovery phase involved 89 of these infants who ultimately were found to have bacterial infections (bacteremia or UTIs), 190 who didn’t have bacterial infections (enterovirus, influenza, or other viruses), and 19 healthy control infants, said Prashant Mahajan, MD, division chief and research director, pediatric emergency medicine, Children’s Hospital of Michigan, Detroit, and his associates.

The investigators identified 3,753 RNA transcript signatures that could potentially identify or rule out bacterial sources of infection, which they then narrowed down to 66. This set of 66 signatures showed 82% sensitivity and 88% specificity in the discovery cohort and 87% sensitivity and 89% specificity in a validation cohort.

“The bacterial RNA biosignature was notably more predictive of bacterial infection than clinical examination” and use of the Yale Observation Score, and it “added significantly to prediction beyond the YOS alone,” Dr. Mahajan and his associates said (JAMA. 2016 Aug 23. doi: 10.1001/jama.2016.9207).

“Despite the young age of the febrile infants evaluated, they carried robust RNA biosignatures and demonstrated that regardless of the etiology of the infections, their immune systems are programed to respond not only with shared elements induced by common microbes but also with specific patterns that allow discrimination by class of pathogen,” they noted.

Further research is needed to confirm and refine these preliminary results. “As technology advances, RNA biosignatures may prove to be an alternative and accurate method to identify infants with bacterial infections. This would help clinicians target evaluation and therapy when they are needed and avoid invasive procedures, antibiotics, and hospitalizations when they are not,” Dr. Mahajan and his associates said.

Dr. Herberg’s study was supported by the Imperial College Comprehensive Biomedical Research Center, the National Institutes of Health, the European Union’s Seventh Framework Program, and numerous other groups. Dr. Herberg reported having no relevant financial disclosures. Dr. Mahajan’s study was supported by the Health Resources and Services Administration, Emergency Services for Children, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institutes of Health. Dr. Mahajan reported having no relevant financial disclosures.

ORLANDO – In patients with hemophilia who have therapeutic factor levels at the time of joint replacement surgery, prophylaxis against venous thromboembolism (VTE) may be unnecessary.

In a cohort study of patients with hemophilia A or B who underwent total joint replacement surgery while being in proper hemostasis with therapeutic factor levels, there were no clinically evident episodes of venous thromboembolism, even though none of the patients had received perioperative anticoagulant prophylaxis, reported investigators from the National Hemophilia Center and Institute of Thrombosis and Hemostasis at the Sheba Medical Center in Tel Hashomer, Israel.

© pavlen/iStockphoto

The data should be reassuring to clinicians whose patients with hemophilia require major orthopedic procedures, said lead author Dr. Anna Seltser, an orthopedic resident at Sheba Medical Center, in an interview.

“We have a lot of hemophilia patients who are not well treated because they live in the desert or distant communities, and we also sometimes treat patients from the Palestinian side of the Gaza Strip who don’t have access to care and need this type of surgery,” she said.

“We collected what I think is the biggest series of patients until now, we didn’t give any of them VTE prophylaxis, and none of them had any DVT [deep vein thrombosis], PE [pulmonary embolism], or similar complication,” she said.

Skip the heparin?

VTE prophylaxis with low-molecular-weight heparin, warfarin, or other anticoagulant agents is a common practice following orthopedic surgery in patients without bleeding disorders. But for patients with severe hemophilia, who often require major joint replacement surgery following years of bleeding-induced arthropathy, it’s unclear whether perioperative anticoagulation is beneficial, the investigators noted in a scientific poster at the World Federation of Hemophilia World Congress.

Dr. Seltser and colleagues therefore conducted a prospective cohort study of 50 patients with hemophilia A or B treated with major joint surgery and subsequent revisions from 1988 through 2015 at their center. In all, 47 patients had severe hemophilia A, 2 had mild hemophilia A, and 1 had hemophilia B.

The authors analyzed data on demographics, comorbidities, type of surgery, use of factor concentrates therapy around the time of surgery, and complications during follow-up, including massive hemorrhage, infections, implant loosening, DVT, and PE.

The patients underwent a total of 74 primary joint replacements (16 hips, 52 knees, and 6 ankles) and 23 revision surgeries.

As noted, there were no episodes of either DVT or PE among any of the patients. All but one complication occurred among patients undergoing total knee replacement. These included three cases of hemarthrosis, three limited-range-of-motion cases requiring closed manipulations, four soft-tissue hematomas, and one case each of superficial wound infection, urinary tract infection, pneumonia, and Candida infection of the tongue.

The only other complication was a case of disseminated intravascular coagulation, sepsis, and hemorrhagic shock in a patient who had undergone a revision (original procedure unspecified).

“Despite the concern that proper replacement factor therapy, applied before and after the surgery, may increase the risk for thromboembolic complications in patients with hemophilia undergoing joint replacement, our data show that prophylactic anticoagulation in this group of patients is not necessary,” the investigators concluded.

The study was internally funded. The investigators reported no conflicts of interest.

[email protected]

ORLANDO – In patients with hemophilia who have therapeutic factor levels at the time of joint replacement surgery, prophylaxis against venous thromboembolism (VTE) may be unnecessary.

In a cohort study of patients with hemophilia A or B who underwent total joint replacement surgery while being in proper hemostasis with therapeutic factor levels, there were no clinically evident episodes of venous thromboembolism, even though none of the patients had received perioperative anticoagulant prophylaxis, reported investigators from the National Hemophilia Center and Institute of Thrombosis and Hemostasis at the Sheba Medical Center in Tel Hashomer, Israel.

© pavlen/iStockphoto

The data should be reassuring to clinicians whose patients with hemophilia require major orthopedic procedures, said lead author Dr. Anna Seltser, an orthopedic resident at Sheba Medical Center, in an interview.

“We have a lot of hemophilia patients who are not well treated because they live in the desert or distant communities, and we also sometimes treat patients from the Palestinian side of the Gaza Strip who don’t have access to care and need this type of surgery,” she said.

“We collected what I think is the biggest series of patients until now, we didn’t give any of them VTE prophylaxis, and none of them had any DVT [deep vein thrombosis], PE [pulmonary embolism], or similar complication,” she said.

Skip the heparin?

VTE prophylaxis with low-molecular-weight heparin, warfarin, or other anticoagulant agents is a common practice following orthopedic surgery in patients without bleeding disorders. But for patients with severe hemophilia, who often require major joint replacement surgery following years of bleeding-induced arthropathy, it’s unclear whether perioperative anticoagulation is beneficial, the investigators noted in a scientific poster at the World Federation of Hemophilia World Congress.

Dr. Seltser and colleagues therefore conducted a prospective cohort study of 50 patients with hemophilia A or B treated with major joint surgery and subsequent revisions from 1988 through 2015 at their center. In all, 47 patients had severe hemophilia A, 2 had mild hemophilia A, and 1 had hemophilia B.

The authors analyzed data on demographics, comorbidities, type of surgery, use of factor concentrates therapy around the time of surgery, and complications during follow-up, including massive hemorrhage, infections, implant loosening, DVT, and PE.

The patients underwent a total of 74 primary joint replacements (16 hips, 52 knees, and 6 ankles) and 23 revision surgeries.

As noted, there were no episodes of either DVT or PE among any of the patients. All but one complication occurred among patients undergoing total knee replacement. These included three cases of hemarthrosis, three limited-range-of-motion cases requiring closed manipulations, four soft-tissue hematomas, and one case each of superficial wound infection, urinary tract infection, pneumonia, and Candida infection of the tongue.

The only other complication was a case of disseminated intravascular coagulation, sepsis, and hemorrhagic shock in a patient who had undergone a revision (original procedure unspecified).

“Despite the concern that proper replacement factor therapy, applied before and after the surgery, may increase the risk for thromboembolic complications in patients with hemophilia undergoing joint replacement, our data show that prophylactic anticoagulation in this group of patients is not necessary,” the investigators concluded.

The study was internally funded. The investigators reported no conflicts of interest.

[email protected]

ORLANDO – In patients with hemophilia who have therapeutic factor levels at the time of joint replacement surgery, prophylaxis against venous thromboembolism (VTE) may be unnecessary.

In a cohort study of patients with hemophilia A or B who underwent total joint replacement surgery while being in proper hemostasis with therapeutic factor levels, there were no clinically evident episodes of venous thromboembolism, even though none of the patients had received perioperative anticoagulant prophylaxis, reported investigators from the National Hemophilia Center and Institute of Thrombosis and Hemostasis at the Sheba Medical Center in Tel Hashomer, Israel.

© pavlen/iStockphoto

The data should be reassuring to clinicians whose patients with hemophilia require major orthopedic procedures, said lead author Dr. Anna Seltser, an orthopedic resident at Sheba Medical Center, in an interview.

“We have a lot of hemophilia patients who are not well treated because they live in the desert or distant communities, and we also sometimes treat patients from the Palestinian side of the Gaza Strip who don’t have access to care and need this type of surgery,” she said.

“We collected what I think is the biggest series of patients until now, we didn’t give any of them VTE prophylaxis, and none of them had any DVT [deep vein thrombosis], PE [pulmonary embolism], or similar complication,” she said.

Skip the heparin?

VTE prophylaxis with low-molecular-weight heparin, warfarin, or other anticoagulant agents is a common practice following orthopedic surgery in patients without bleeding disorders. But for patients with severe hemophilia, who often require major joint replacement surgery following years of bleeding-induced arthropathy, it’s unclear whether perioperative anticoagulation is beneficial, the investigators noted in a scientific poster at the World Federation of Hemophilia World Congress.

Dr. Seltser and colleagues therefore conducted a prospective cohort study of 50 patients with hemophilia A or B treated with major joint surgery and subsequent revisions from 1988 through 2015 at their center. In all, 47 patients had severe hemophilia A, 2 had mild hemophilia A, and 1 had hemophilia B.

The authors analyzed data on demographics, comorbidities, type of surgery, use of factor concentrates therapy around the time of surgery, and complications during follow-up, including massive hemorrhage, infections, implant loosening, DVT, and PE.

The patients underwent a total of 74 primary joint replacements (16 hips, 52 knees, and 6 ankles) and 23 revision surgeries.

As noted, there were no episodes of either DVT or PE among any of the patients. All but one complication occurred among patients undergoing total knee replacement. These included three cases of hemarthrosis, three limited-range-of-motion cases requiring closed manipulations, four soft-tissue hematomas, and one case each of superficial wound infection, urinary tract infection, pneumonia, and Candida infection of the tongue.

The only other complication was a case of disseminated intravascular coagulation, sepsis, and hemorrhagic shock in a patient who had undergone a revision (original procedure unspecified).

“Despite the concern that proper replacement factor therapy, applied before and after the surgery, may increase the risk for thromboembolic complications in patients with hemophilia undergoing joint replacement, our data show that prophylactic anticoagulation in this group of patients is not necessary,” the investigators concluded.

The study was internally funded. The investigators reported no conflicts of interest.

[email protected]

The seasonal influenza vaccination reduced flu-related hospitalizations by 56.8% among people aged 50 and older during a recent flu season, according to a report published in Clinical Infectious Diseases.

Even in the oldest age group – the population with the highest risk of developing flu complications and perhaps the weakest immune response – influenza vaccination prevented serious complications, said Fiona P. Havers, MD, of the influenza division, Centers for Disease Control and Prevention, Atlanta, and her associates.

Data on vaccine efficacy in older adults are sparse, and randomized, placebo-controlled trials to gather evidence would be unethical. Dr. Havers and her colleagues studied the issue using a case-control design, focusing on community-dwelling adults aged 50 years and older during the 2010-2011 flu season. They identified 368 patients across 10 states who were hospitalized for polymerase chain reaction–confirmed influenza and matched them for age and county of residence with 773 control subjects.

Hospitalized case-patients were less likely to have been vaccinated (55%) than were control subjects (63%). Thus, the flu vaccine reduced the risk of hospitalization for influenza by 56.8% overall.

©Wavebreakmedia/Thinkstock

Vaccination reduced hospitalization for influenza by 63.9% in the youngest age group (50-64 years), by 61.0% in the intermediate age group (65-74 years), and by 57.3% in the oldest age group (75 years and older).

These results are similar to those reported in other studies assessing the same time period, including one that evaluated vaccine efficacy in ambulatory adults in the United States and Europe. They also are consistent with the results of observational studies performed during different flu seasons, the investigators said (Clin Infect Dis. 2016 Aug 2. doi: 10.1093/cid/ciw512).

Compared with control subjects, case-patients were more likely to be of nonwhite race, to be of Hispanic ethnicity, to have a lower income, to have had fewer years of education, to have two or more chronic health conditions, to have required recent hospitalization for respiratory problems, to have impaired mobility, and to have lower functional status.

“These findings support current U.S. recommendations for annual influenza vaccination in older adults, especially in adults aged 65 and older who are at higher risk of influenza-associated complications,” Dr. Havers and her associates said.

The Centers for Disease Control and Prevention supported the study. Dr. Havers reported having no relevant financial disclosures; one of her associates reported ties to Genentech, Merck, Novavax, and Pfizer.

The seasonal influenza vaccination reduced flu-related hospitalizations by 56.8% among people aged 50 and older during a recent flu season, according to a report published in Clinical Infectious Diseases.

Even in the oldest age group – the population with the highest risk of developing flu complications and perhaps the weakest immune response – influenza vaccination prevented serious complications, said Fiona P. Havers, MD, of the influenza division, Centers for Disease Control and Prevention, Atlanta, and her associates.

Data on vaccine efficacy in older adults are sparse, and randomized, placebo-controlled trials to gather evidence would be unethical. Dr. Havers and her colleagues studied the issue using a case-control design, focusing on community-dwelling adults aged 50 years and older during the 2010-2011 flu season. They identified 368 patients across 10 states who were hospitalized for polymerase chain reaction–confirmed influenza and matched them for age and county of residence with 773 control subjects.

Hospitalized case-patients were less likely to have been vaccinated (55%) than were control subjects (63%). Thus, the flu vaccine reduced the risk of hospitalization for influenza by 56.8% overall.

©Wavebreakmedia/Thinkstock

Vaccination reduced hospitalization for influenza by 63.9% in the youngest age group (50-64 years), by 61.0% in the intermediate age group (65-74 years), and by 57.3% in the oldest age group (75 years and older).

These results are similar to those reported in other studies assessing the same time period, including one that evaluated vaccine efficacy in ambulatory adults in the United States and Europe. They also are consistent with the results of observational studies performed during different flu seasons, the investigators said (Clin Infect Dis. 2016 Aug 2. doi: 10.1093/cid/ciw512).

Compared with control subjects, case-patients were more likely to be of nonwhite race, to be of Hispanic ethnicity, to have a lower income, to have had fewer years of education, to have two or more chronic health conditions, to have required recent hospitalization for respiratory problems, to have impaired mobility, and to have lower functional status.

“These findings support current U.S. recommendations for annual influenza vaccination in older adults, especially in adults aged 65 and older who are at higher risk of influenza-associated complications,” Dr. Havers and her associates said.

The Centers for Disease Control and Prevention supported the study. Dr. Havers reported having no relevant financial disclosures; one of her associates reported ties to Genentech, Merck, Novavax, and Pfizer.

The seasonal influenza vaccination reduced flu-related hospitalizations by 56.8% among people aged 50 and older during a recent flu season, according to a report published in Clinical Infectious Diseases.

Even in the oldest age group – the population with the highest risk of developing flu complications and perhaps the weakest immune response – influenza vaccination prevented serious complications, said Fiona P. Havers, MD, of the influenza division, Centers for Disease Control and Prevention, Atlanta, and her associates.

Data on vaccine efficacy in older adults are sparse, and randomized, placebo-controlled trials to gather evidence would be unethical. Dr. Havers and her colleagues studied the issue using a case-control design, focusing on community-dwelling adults aged 50 years and older during the 2010-2011 flu season. They identified 368 patients across 10 states who were hospitalized for polymerase chain reaction–confirmed influenza and matched them for age and county of residence with 773 control subjects.

Hospitalized case-patients were less likely to have been vaccinated (55%) than were control subjects (63%). Thus, the flu vaccine reduced the risk of hospitalization for influenza by 56.8% overall.

©Wavebreakmedia/Thinkstock

Vaccination reduced hospitalization for influenza by 63.9% in the youngest age group (50-64 years), by 61.0% in the intermediate age group (65-74 years), and by 57.3% in the oldest age group (75 years and older).

These results are similar to those reported in other studies assessing the same time period, including one that evaluated vaccine efficacy in ambulatory adults in the United States and Europe. They also are consistent with the results of observational studies performed during different flu seasons, the investigators said (Clin Infect Dis. 2016 Aug 2. doi: 10.1093/cid/ciw512).

Compared with control subjects, case-patients were more likely to be of nonwhite race, to be of Hispanic ethnicity, to have a lower income, to have had fewer years of education, to have two or more chronic health conditions, to have required recent hospitalization for respiratory problems, to have impaired mobility, and to have lower functional status.

“These findings support current U.S. recommendations for annual influenza vaccination in older adults, especially in adults aged 65 and older who are at higher risk of influenza-associated complications,” Dr. Havers and her associates said.

The Centers for Disease Control and Prevention supported the study. Dr. Havers reported having no relevant financial disclosures; one of her associates reported ties to Genentech, Merck, Novavax, and Pfizer.

NEWPORT BEACH, CALIF. – In medical school you may have been taught that herpes zoster infection primarily impacts elderly patients, but the burden of disease is shifting – along with the understanding of herpes zoster itself.

“Herpes zoster is a disease that can lull us into a false sense of security because we see it all the time,” Iris Ahronowitz, MD, said at the annual meeting of the Pacific Dermatologic Association. “But our understanding of how to manage this disease is still very much a work in progress.”

She noted that while 50% of people will acquire herpes zoster by the time they reach 85 years of age due to diminishing cell-mediated immunity, the major burden of disease impacts immunocompromised patients of all ages. HIV patients and solid-organ transplant recipients are well known to face an increased risk of acquiring herpes zoster, but the most overwhelming risk is seen in leukemia patients, who have rates as high as 100-fold that of the general population.

“More recent data on stem cell transplant patients show that about 50% of them will get zoster,” added Dr. Ahronowitz, a dermatologist at the University of Southern California, Los Angeles. “Most of that’s happening within the first year and a half after their transplant.”

Several recent epidemiologic studies in the medical literature have reported herpes zoster in patients who are not traditionally believed to be immunosuppressed, such as those with lupus, dermatomyositis, rheumatoid arthritis, asthma, and atopic dermatitis. “It begs the question: is it the disease or is it the treatment?” Dr. Ahronowitz said. “We don’t know the answer to that yet. In dermatomyositis and lupus, use of antimalarials has been found to be most associated with the risk of herpes zoster. Other studies looking at one disease are so heterogeneous, some saying that it’s one medication, some saying that it’s another. There’s no cohesive message yet about which medications cause the highest risk of zoster.”

Herpes zoster was originally believed to be far less transmissible than varicella. “Later it was thought that the only way that you can get VZV [varicella zoster virus] from a zoster patient was by direct contact with vesicle fluid,” Dr. Ahronowitz said. “That turns out to be wrong as well.” One study of pediatric patients found similar rates of secondary varicella cases from varicella and herpes zoster cases (15% vs. 9%, respectively), regardless of anatomic location of zoster (J Infect Dis. 2012; 205[9]:1336-41).

Another report that called into question prevailing beliefs about the disease involved an immunocompetent patient in a long-term care facility who developed localized herpes zoster (J Infect Dis. 2008;197[5]:646-53). That individual turned out to be “patient zero” in a varicella outbreak in the facility, even though the person’s lesions had been covered by gauze and clothing at all times. “The next patient who got infected was one of the health care workers who had never been in the room at the same time as the patient but who had changed the patient’s bed linens,” said Dr. Ahronowitz, who was not involved with the study. “Environmental samples were collected from the patient’s room and were contaminated with VZV DNA.”

She went on to note that VZV DNA has been found in vesicle fluid, serum, peripheral blood mononuclear cells, and saliva. One randomized, controlled trial found that hydrocolloid dressings are superior to traditional gauze and paper dressings in preventing the excretion of aerosolized VZV DNA from skin lesions of patients with localized herpes zoster (J Infect Dis. 2004;189[6]:1009-12). Using hydrocolloid dressings to cover lesions “does seem to make a difference,” she said. “Because of all this new data coming out, I think it’s time to reconsider isolation precautions in all hospitalized patients with herpes zoster, because the consequences of VZV transmission within a hospital where there are other patients nearby who have low immune systems could be absolutely devastating.”

The impact of herpes zoster infection on the central nervous system can be significant, including cranial nerve palsy, encephalitis, encephalopathy, and aseptic meningitis. “Patients can have long-lasting residual neurologic deficits from this at 6 months or longer despite appropriate treatment,” she said. “No correlation between CSF viral load and neurologic sequelae has been found at 3 months.”

More recent research has found an association between herpes zoster infection and an increased risk of stroke – up to threefold in some cases. “That risk doesn’t normalize until 6 months after the infection,” Dr. Ahronowitz said. “We’re even seeing it in kids, who have two times the risk of stroke in the first 6 months after VZV infection.” MI risk also seems to be elevated as a secondary outcome (a 1.7-fold increase in the first week of infection).

“There have also been recent reports of VZV antigen/DNA found in the vessel wall of patients with giant cell arteritis and granulomatous arteritis of the aorta,” she said. “This is an evolving story about zoster that we never knew about.”

Drug-induced hypersensitivity syndrome (DIHS) is also associated with CNS manifestations, but they resolve much faster, unlike those of CNS zoster. “As long as you take away the offending medication and put them on steroids they will recover very quickly,” she said. At least one case in the medical literature to date has reported DIHS in association with VZV (Acta Derm Venereol. 2015;95[4]:503-4).

The zoster vaccine (Zostavax, Merck & Co.) is currently indicated in patients aged 60 years and older, but since it is a live attenuated vaccine, it is contraindicated in many patients who could most benefit from it, including those with primary immunodeficiency disorders, those with a hematologic malignancy, those who have had a hematopoietic stem cell transplant within the last 2 years, pregnant patients, and patients taking high-dose steroids or anti–tumor necrosis factor biologics.

“There is an inactivated vaccine in the works being tested, and that is showing good efficacy,” Dr. Ahronowitz said. “Hopefully we’ll be able to prevaccinate patients, even young patients, prior to immune suppression.”

She reported having no relevant disclosures.

[email protected]

NEWPORT BEACH, CALIF. – In medical school you may have been taught that herpes zoster infection primarily impacts elderly patients, but the burden of disease is shifting – along with the understanding of herpes zoster itself.

“Herpes zoster is a disease that can lull us into a false sense of security because we see it all the time,” Iris Ahronowitz, MD, said at the annual meeting of the Pacific Dermatologic Association. “But our understanding of how to manage this disease is still very much a work in progress.”

She noted that while 50% of people will acquire herpes zoster by the time they reach 85 years of age due to diminishing cell-mediated immunity, the major burden of disease impacts immunocompromised patients of all ages. HIV patients and solid-organ transplant recipients are well known to face an increased risk of acquiring herpes zoster, but the most overwhelming risk is seen in leukemia patients, who have rates as high as 100-fold that of the general population.

“More recent data on stem cell transplant patients show that about 50% of them will get zoster,” added Dr. Ahronowitz, a dermatologist at the University of Southern California, Los Angeles. “Most of that’s happening within the first year and a half after their transplant.”

Several recent epidemiologic studies in the medical literature have reported herpes zoster in patients who are not traditionally believed to be immunosuppressed, such as those with lupus, dermatomyositis, rheumatoid arthritis, asthma, and atopic dermatitis. “It begs the question: is it the disease or is it the treatment?” Dr. Ahronowitz said. “We don’t know the answer to that yet. In dermatomyositis and lupus, use of antimalarials has been found to be most associated with the risk of herpes zoster. Other studies looking at one disease are so heterogeneous, some saying that it’s one medication, some saying that it’s another. There’s no cohesive message yet about which medications cause the highest risk of zoster.”

Herpes zoster was originally believed to be far less transmissible than varicella. “Later it was thought that the only way that you can get VZV [varicella zoster virus] from a zoster patient was by direct contact with vesicle fluid,” Dr. Ahronowitz said. “That turns out to be wrong as well.” One study of pediatric patients found similar rates of secondary varicella cases from varicella and herpes zoster cases (15% vs. 9%, respectively), regardless of anatomic location of zoster (J Infect Dis. 2012; 205[9]:1336-41).

Another report that called into question prevailing beliefs about the disease involved an immunocompetent patient in a long-term care facility who developed localized herpes zoster (J Infect Dis. 2008;197[5]:646-53). That individual turned out to be “patient zero” in a varicella outbreak in the facility, even though the person’s lesions had been covered by gauze and clothing at all times. “The next patient who got infected was one of the health care workers who had never been in the room at the same time as the patient but who had changed the patient’s bed linens,” said Dr. Ahronowitz, who was not involved with the study. “Environmental samples were collected from the patient’s room and were contaminated with VZV DNA.”

She went on to note that VZV DNA has been found in vesicle fluid, serum, peripheral blood mononuclear cells, and saliva. One randomized, controlled trial found that hydrocolloid dressings are superior to traditional gauze and paper dressings in preventing the excretion of aerosolized VZV DNA from skin lesions of patients with localized herpes zoster (J Infect Dis. 2004;189[6]:1009-12). Using hydrocolloid dressings to cover lesions “does seem to make a difference,” she said. “Because of all this new data coming out, I think it’s time to reconsider isolation precautions in all hospitalized patients with herpes zoster, because the consequences of VZV transmission within a hospital where there are other patients nearby who have low immune systems could be absolutely devastating.”

The impact of herpes zoster infection on the central nervous system can be significant, including cranial nerve palsy, encephalitis, encephalopathy, and aseptic meningitis. “Patients can have long-lasting residual neurologic deficits from this at 6 months or longer despite appropriate treatment,” she said. “No correlation between CSF viral load and neurologic sequelae has been found at 3 months.”

More recent research has found an association between herpes zoster infection and an increased risk of stroke – up to threefold in some cases. “That risk doesn’t normalize until 6 months after the infection,” Dr. Ahronowitz said. “We’re even seeing it in kids, who have two times the risk of stroke in the first 6 months after VZV infection.” MI risk also seems to be elevated as a secondary outcome (a 1.7-fold increase in the first week of infection).

“There have also been recent reports of VZV antigen/DNA found in the vessel wall of patients with giant cell arteritis and granulomatous arteritis of the aorta,” she said. “This is an evolving story about zoster that we never knew about.”

Drug-induced hypersensitivity syndrome (DIHS) is also associated with CNS manifestations, but they resolve much faster, unlike those of CNS zoster. “As long as you take away the offending medication and put them on steroids they will recover very quickly,” she said. At least one case in the medical literature to date has reported DIHS in association with VZV (Acta Derm Venereol. 2015;95[4]:503-4).

The zoster vaccine (Zostavax, Merck & Co.) is currently indicated in patients aged 60 years and older, but since it is a live attenuated vaccine, it is contraindicated in many patients who could most benefit from it, including those with primary immunodeficiency disorders, those with a hematologic malignancy, those who have had a hematopoietic stem cell transplant within the last 2 years, pregnant patients, and patients taking high-dose steroids or anti–tumor necrosis factor biologics.

“There is an inactivated vaccine in the works being tested, and that is showing good efficacy,” Dr. Ahronowitz said. “Hopefully we’ll be able to prevaccinate patients, even young patients, prior to immune suppression.”

She reported having no relevant disclosures.

[email protected]

NEWPORT BEACH, CALIF. – In medical school you may have been taught that herpes zoster infection primarily impacts elderly patients, but the burden of disease is shifting – along with the understanding of herpes zoster itself.

“Herpes zoster is a disease that can lull us into a false sense of security because we see it all the time,” Iris Ahronowitz, MD, said at the annual meeting of the Pacific Dermatologic Association. “But our understanding of how to manage this disease is still very much a work in progress.”

She noted that while 50% of people will acquire herpes zoster by the time they reach 85 years of age due to diminishing cell-mediated immunity, the major burden of disease impacts immunocompromised patients of all ages. HIV patients and solid-organ transplant recipients are well known to face an increased risk of acquiring herpes zoster, but the most overwhelming risk is seen in leukemia patients, who have rates as high as 100-fold that of the general population.

“More recent data on stem cell transplant patients show that about 50% of them will get zoster,” added Dr. Ahronowitz, a dermatologist at the University of Southern California, Los Angeles. “Most of that’s happening within the first year and a half after their transplant.”

Several recent epidemiologic studies in the medical literature have reported herpes zoster in patients who are not traditionally believed to be immunosuppressed, such as those with lupus, dermatomyositis, rheumatoid arthritis, asthma, and atopic dermatitis. “It begs the question: is it the disease or is it the treatment?” Dr. Ahronowitz said. “We don’t know the answer to that yet. In dermatomyositis and lupus, use of antimalarials has been found to be most associated with the risk of herpes zoster. Other studies looking at one disease are so heterogeneous, some saying that it’s one medication, some saying that it’s another. There’s no cohesive message yet about which medications cause the highest risk of zoster.”

Herpes zoster was originally believed to be far less transmissible than varicella. “Later it was thought that the only way that you can get VZV [varicella zoster virus] from a zoster patient was by direct contact with vesicle fluid,” Dr. Ahronowitz said. “That turns out to be wrong as well.” One study of pediatric patients found similar rates of secondary varicella cases from varicella and herpes zoster cases (15% vs. 9%, respectively), regardless of anatomic location of zoster (J Infect Dis. 2012; 205[9]:1336-41).

Another report that called into question prevailing beliefs about the disease involved an immunocompetent patient in a long-term care facility who developed localized herpes zoster (J Infect Dis. 2008;197[5]:646-53). That individual turned out to be “patient zero” in a varicella outbreak in the facility, even though the person’s lesions had been covered by gauze and clothing at all times. “The next patient who got infected was one of the health care workers who had never been in the room at the same time as the patient but who had changed the patient’s bed linens,” said Dr. Ahronowitz, who was not involved with the study. “Environmental samples were collected from the patient’s room and were contaminated with VZV DNA.”

She went on to note that VZV DNA has been found in vesicle fluid, serum, peripheral blood mononuclear cells, and saliva. One randomized, controlled trial found that hydrocolloid dressings are superior to traditional gauze and paper dressings in preventing the excretion of aerosolized VZV DNA from skin lesions of patients with localized herpes zoster (J Infect Dis. 2004;189[6]:1009-12). Using hydrocolloid dressings to cover lesions “does seem to make a difference,” she said. “Because of all this new data coming out, I think it’s time to reconsider isolation precautions in all hospitalized patients with herpes zoster, because the consequences of VZV transmission within a hospital where there are other patients nearby who have low immune systems could be absolutely devastating.”

The impact of herpes zoster infection on the central nervous system can be significant, including cranial nerve palsy, encephalitis, encephalopathy, and aseptic meningitis. “Patients can have long-lasting residual neurologic deficits from this at 6 months or longer despite appropriate treatment,” she said. “No correlation between CSF viral load and neurologic sequelae has been found at 3 months.”

More recent research has found an association between herpes zoster infection and an increased risk of stroke – up to threefold in some cases. “That risk doesn’t normalize until 6 months after the infection,” Dr. Ahronowitz said. “We’re even seeing it in kids, who have two times the risk of stroke in the first 6 months after VZV infection.” MI risk also seems to be elevated as a secondary outcome (a 1.7-fold increase in the first week of infection).

“There have also been recent reports of VZV antigen/DNA found in the vessel wall of patients with giant cell arteritis and granulomatous arteritis of the aorta,” she said. “This is an evolving story about zoster that we never knew about.”

Drug-induced hypersensitivity syndrome (DIHS) is also associated with CNS manifestations, but they resolve much faster, unlike those of CNS zoster. “As long as you take away the offending medication and put them on steroids they will recover very quickly,” she said. At least one case in the medical literature to date has reported DIHS in association with VZV (Acta Derm Venereol. 2015;95[4]:503-4).

The zoster vaccine (Zostavax, Merck & Co.) is currently indicated in patients aged 60 years and older, but since it is a live attenuated vaccine, it is contraindicated in many patients who could most benefit from it, including those with primary immunodeficiency disorders, those with a hematologic malignancy, those who have had a hematopoietic stem cell transplant within the last 2 years, pregnant patients, and patients taking high-dose steroids or anti–tumor necrosis factor biologics.

“There is an inactivated vaccine in the works being tested, and that is showing good efficacy,” Dr. Ahronowitz said. “Hopefully we’ll be able to prevaccinate patients, even young patients, prior to immune suppression.”

She reported having no relevant disclosures.

[email protected]