Mary Ann Moon

An oral inhibitor of respiratory syncytial virus replication, currently called ALS-008176, significantly reduced total viral load, peak viral load, duration of viral shedding, and clinical symptoms in a small proof-of-concept study funded by the drug’s manufacturer and published online Nov. 18 in the New England Journal of Medicine.

These findings are particularly encouraging because at present, the standard of care for RSV infection is limited to supportive care only, said Dr. John P. DeVincenzo of the departments of pediatrics, microbiology, immunology, and biochemistry, University of Tennessee, and the Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, both in Memphis.

©Dr. Craig Lyerla/CDC

Dr. DeVincenzo and his colleagues performed this randomized, double-blind trial during three separate study periods in which up to 22 healthy adults were confined to a special quarantine unit for 2 weeks at a time. All 62 participants were inoculated intranasally with a clinical strain of RSV and monitored twice daily for the development of RSV infection via assays of fresh nasal washings. The participants were randomly assigned to receive the first dose of ALS-008176 or a matching placebo about 12 hours after the detection of RSV, or on the morning of day 6, whichever came first.

The active drug or the placebo were administered orally every 12 hours for 5 days, for a total of 10 doses. Three dosing regimens were assessed: In the first study period, participants were given a single loading dose of 750 mg followed by nine maintenance doses of 500 mg; in the second period, participants were given a single loading dose of 750 mg followed by nine maintenance doses of 150 mg; and in the third period, participants were given 10 doses of 375 mg each. A total of 35 study participants developed RSV infection.

Compared with placebo, all three dosing regimens significantly reduced viral load within 12 hours of starting treatment: by 88.0% in the first study period, by 85.3% in the second, and by 73.4% in the third. The mean interval until RSV RNA became undetectable ranged from 1.3 to 2.3 days for the three active-treatment groups, compared with 7.2 days for placebo. RSV RNA became undetectable within 4.5 days for all participants who received ALS-0081, compared with 11 days for those who received placebo.

In addition, mean peak viral loads were lower for all three dosing regimens than for placebo. “At the time that the peak viral load occurred in the placebo group, the mean viral load in each of the 3 ALS-008176 treatment groups was more than 1,000 times as low,” wrote Dr. DeVincenzo and his associates (N Engl J Med. 2015 Nov 19;373:2048-58. doi:10.1056/NEJMoa1413275).

As important, RSV symptoms were much less severe in all three active-treatment groups than in the placebo group, as assessed subjectively via symptom scores and objectively via the quantity of nasal mucus produced.

The small study population limited the ability to detect potential safety concerns. Nevertheless, “no serious adverse events, premature discontinuation of the study drug, or clinically significant, treatment-related adverse events were observed in any participants in the intention-to-treat population,” the investigators added.

They noted that people who are infected with RSV under natural circumstances, particularly infants, typically present later in the course of the disease, only after patients or caregivers realize that the illness is not due to a simple cold. Thus, their disease severity would be worse than that of these study participants by the time ALS-008176 could be administered. “Therefore, it may be inappropriate to directly extrapolate the results of this study to a clinical setting,” Dr. DeVincenzo and his associates said.

Alios BioPharma, maker of ALS-008176, funded the study. Dr. DeVincenzo disclosed ties with Alios BioPharma, Gilead Sciences, Alnylam Pharmaceuticals, Microdose Therapeutx–Teva, Janssen, ADMA Biologics, and MedImmune/AstraZeneca. His associates reported ties to Alios and Retroscreen Virology.

An oral inhibitor of respiratory syncytial virus replication, currently called ALS-008176, significantly reduced total viral load, peak viral load, duration of viral shedding, and clinical symptoms in a small proof-of-concept study funded by the drug’s manufacturer and published online Nov. 18 in the New England Journal of Medicine.

These findings are particularly encouraging because at present, the standard of care for RSV infection is limited to supportive care only, said Dr. John P. DeVincenzo of the departments of pediatrics, microbiology, immunology, and biochemistry, University of Tennessee, and the Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, both in Memphis.

©Dr. Craig Lyerla/CDC

Dr. DeVincenzo and his colleagues performed this randomized, double-blind trial during three separate study periods in which up to 22 healthy adults were confined to a special quarantine unit for 2 weeks at a time. All 62 participants were inoculated intranasally with a clinical strain of RSV and monitored twice daily for the development of RSV infection via assays of fresh nasal washings. The participants were randomly assigned to receive the first dose of ALS-008176 or a matching placebo about 12 hours after the detection of RSV, or on the morning of day 6, whichever came first.

The active drug or the placebo were administered orally every 12 hours for 5 days, for a total of 10 doses. Three dosing regimens were assessed: In the first study period, participants were given a single loading dose of 750 mg followed by nine maintenance doses of 500 mg; in the second period, participants were given a single loading dose of 750 mg followed by nine maintenance doses of 150 mg; and in the third period, participants were given 10 doses of 375 mg each. A total of 35 study participants developed RSV infection.

Compared with placebo, all three dosing regimens significantly reduced viral load within 12 hours of starting treatment: by 88.0% in the first study period, by 85.3% in the second, and by 73.4% in the third. The mean interval until RSV RNA became undetectable ranged from 1.3 to 2.3 days for the three active-treatment groups, compared with 7.2 days for placebo. RSV RNA became undetectable within 4.5 days for all participants who received ALS-0081, compared with 11 days for those who received placebo.

In addition, mean peak viral loads were lower for all three dosing regimens than for placebo. “At the time that the peak viral load occurred in the placebo group, the mean viral load in each of the 3 ALS-008176 treatment groups was more than 1,000 times as low,” wrote Dr. DeVincenzo and his associates (N Engl J Med. 2015 Nov 19;373:2048-58. doi:10.1056/NEJMoa1413275).

As important, RSV symptoms were much less severe in all three active-treatment groups than in the placebo group, as assessed subjectively via symptom scores and objectively via the quantity of nasal mucus produced.

The small study population limited the ability to detect potential safety concerns. Nevertheless, “no serious adverse events, premature discontinuation of the study drug, or clinically significant, treatment-related adverse events were observed in any participants in the intention-to-treat population,” the investigators added.

They noted that people who are infected with RSV under natural circumstances, particularly infants, typically present later in the course of the disease, only after patients or caregivers realize that the illness is not due to a simple cold. Thus, their disease severity would be worse than that of these study participants by the time ALS-008176 could be administered. “Therefore, it may be inappropriate to directly extrapolate the results of this study to a clinical setting,” Dr. DeVincenzo and his associates said.

Alios BioPharma, maker of ALS-008176, funded the study. Dr. DeVincenzo disclosed ties with Alios BioPharma, Gilead Sciences, Alnylam Pharmaceuticals, Microdose Therapeutx–Teva, Janssen, ADMA Biologics, and MedImmune/AstraZeneca. His associates reported ties to Alios and Retroscreen Virology.

An oral inhibitor of respiratory syncytial virus replication, currently called ALS-008176, significantly reduced total viral load, peak viral load, duration of viral shedding, and clinical symptoms in a small proof-of-concept study funded by the drug’s manufacturer and published online Nov. 18 in the New England Journal of Medicine.

These findings are particularly encouraging because at present, the standard of care for RSV infection is limited to supportive care only, said Dr. John P. DeVincenzo of the departments of pediatrics, microbiology, immunology, and biochemistry, University of Tennessee, and the Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, both in Memphis.

©Dr. Craig Lyerla/CDC

Dr. DeVincenzo and his colleagues performed this randomized, double-blind trial during three separate study periods in which up to 22 healthy adults were confined to a special quarantine unit for 2 weeks at a time. All 62 participants were inoculated intranasally with a clinical strain of RSV and monitored twice daily for the development of RSV infection via assays of fresh nasal washings. The participants were randomly assigned to receive the first dose of ALS-008176 or a matching placebo about 12 hours after the detection of RSV, or on the morning of day 6, whichever came first.

The active drug or the placebo were administered orally every 12 hours for 5 days, for a total of 10 doses. Three dosing regimens were assessed: In the first study period, participants were given a single loading dose of 750 mg followed by nine maintenance doses of 500 mg; in the second period, participants were given a single loading dose of 750 mg followed by nine maintenance doses of 150 mg; and in the third period, participants were given 10 doses of 375 mg each. A total of 35 study participants developed RSV infection.

Compared with placebo, all three dosing regimens significantly reduced viral load within 12 hours of starting treatment: by 88.0% in the first study period, by 85.3% in the second, and by 73.4% in the third. The mean interval until RSV RNA became undetectable ranged from 1.3 to 2.3 days for the three active-treatment groups, compared with 7.2 days for placebo. RSV RNA became undetectable within 4.5 days for all participants who received ALS-0081, compared with 11 days for those who received placebo.

In addition, mean peak viral loads were lower for all three dosing regimens than for placebo. “At the time that the peak viral load occurred in the placebo group, the mean viral load in each of the 3 ALS-008176 treatment groups was more than 1,000 times as low,” wrote Dr. DeVincenzo and his associates (N Engl J Med. 2015 Nov 19;373:2048-58. doi:10.1056/NEJMoa1413275).

As important, RSV symptoms were much less severe in all three active-treatment groups than in the placebo group, as assessed subjectively via symptom scores and objectively via the quantity of nasal mucus produced.

The small study population limited the ability to detect potential safety concerns. Nevertheless, “no serious adverse events, premature discontinuation of the study drug, or clinically significant, treatment-related adverse events were observed in any participants in the intention-to-treat population,” the investigators added.

They noted that people who are infected with RSV under natural circumstances, particularly infants, typically present later in the course of the disease, only after patients or caregivers realize that the illness is not due to a simple cold. Thus, their disease severity would be worse than that of these study participants by the time ALS-008176 could be administered. “Therefore, it may be inappropriate to directly extrapolate the results of this study to a clinical setting,” Dr. DeVincenzo and his associates said.

Alios BioPharma, maker of ALS-008176, funded the study. Dr. DeVincenzo disclosed ties with Alios BioPharma, Gilead Sciences, Alnylam Pharmaceuticals, Microdose Therapeutx–Teva, Janssen, ADMA Biologics, and MedImmune/AstraZeneca. His associates reported ties to Alios and Retroscreen Virology.

Adding pioglitazone, an insulin-sensitizing agent with anti-inflammatory properties, to usual antidepressant treatment relieved unremitting depression in a small clinical trial, but only in patients who had insulin resistance, a report published online Nov. 18 shows.

The association between insulin resistance and depressive symptoms has been well documented but remains poorly understood. “A better understanding of the reciprocal links between depression and insulin resistance may lead to a dramatic shift in the way in which depression is conceptualized and treated, with a greater focus on treating and/or preventing metabolic dysfunction,” said Kathleen Watson Lin of the department of psychiatry and behavioral sciences, Stanford (Calif.) University, and her associates.

The investigators previously found that rosiglitazone, a related insulin-sensitizing agent, improved depression severity in an open-label pilot study. Now they report the results of a double-blind randomized trial involving 37 men and women aged 23-71 years (mean age, 43-49 years) who had unremitting depression despite receiving a variety of standard treatments. These study participants had a range of insulin sensitivities, including 20 who had insulin resistance, but none had frank diabetes. Nineteen were randomly assigned to receive pioglitazone and 18 to receive a matching placebo pill for 12 weeks.

Pioglitazone improved depressive symptoms only in the subgroup of patients who had insulin resistance. Their scores on the Hamilton Depression Rating Scale-21 declined an average of 7.15 points more than did the scores of patients with insulin resistance who received placebo. In contrast, among patients who did not have insulin resistance, there was no difference in the decline of HDRS-21 scores between those who received pioglitazone and those who received placebo, the investigators said (Psychiatry Res. 2015 Nov 18).

This treatment response was the most pronounced in younger patients.

The study findings suggest that pioglitazone may be an effective adjuvant therapy for unremitting depression, at least in patients who have insulin resistance and especially in those who are younger. However, given the small size of this study population, larger clinical trials are needed to examine this possibility, Ms. Watson Lin and her associates said.

This study was funded by the National Institutes of Health. Ms. Watson Lin reported having no financial disclosures. One of her associates reported serving as a consultant to Shire and Sunovion, and receiving research support from Magceutics and Corcept.

Adding pioglitazone, an insulin-sensitizing agent with anti-inflammatory properties, to usual antidepressant treatment relieved unremitting depression in a small clinical trial, but only in patients who had insulin resistance, a report published online Nov. 18 shows.

The association between insulin resistance and depressive symptoms has been well documented but remains poorly understood. “A better understanding of the reciprocal links between depression and insulin resistance may lead to a dramatic shift in the way in which depression is conceptualized and treated, with a greater focus on treating and/or preventing metabolic dysfunction,” said Kathleen Watson Lin of the department of psychiatry and behavioral sciences, Stanford (Calif.) University, and her associates.

The investigators previously found that rosiglitazone, a related insulin-sensitizing agent, improved depression severity in an open-label pilot study. Now they report the results of a double-blind randomized trial involving 37 men and women aged 23-71 years (mean age, 43-49 years) who had unremitting depression despite receiving a variety of standard treatments. These study participants had a range of insulin sensitivities, including 20 who had insulin resistance, but none had frank diabetes. Nineteen were randomly assigned to receive pioglitazone and 18 to receive a matching placebo pill for 12 weeks.

Pioglitazone improved depressive symptoms only in the subgroup of patients who had insulin resistance. Their scores on the Hamilton Depression Rating Scale-21 declined an average of 7.15 points more than did the scores of patients with insulin resistance who received placebo. In contrast, among patients who did not have insulin resistance, there was no difference in the decline of HDRS-21 scores between those who received pioglitazone and those who received placebo, the investigators said (Psychiatry Res. 2015 Nov 18).

This treatment response was the most pronounced in younger patients.

The study findings suggest that pioglitazone may be an effective adjuvant therapy for unremitting depression, at least in patients who have insulin resistance and especially in those who are younger. However, given the small size of this study population, larger clinical trials are needed to examine this possibility, Ms. Watson Lin and her associates said.

This study was funded by the National Institutes of Health. Ms. Watson Lin reported having no financial disclosures. One of her associates reported serving as a consultant to Shire and Sunovion, and receiving research support from Magceutics and Corcept.

Adding pioglitazone, an insulin-sensitizing agent with anti-inflammatory properties, to usual antidepressant treatment relieved unremitting depression in a small clinical trial, but only in patients who had insulin resistance, a report published online Nov. 18 shows.

The association between insulin resistance and depressive symptoms has been well documented but remains poorly understood. “A better understanding of the reciprocal links between depression and insulin resistance may lead to a dramatic shift in the way in which depression is conceptualized and treated, with a greater focus on treating and/or preventing metabolic dysfunction,” said Kathleen Watson Lin of the department of psychiatry and behavioral sciences, Stanford (Calif.) University, and her associates.

The investigators previously found that rosiglitazone, a related insulin-sensitizing agent, improved depression severity in an open-label pilot study. Now they report the results of a double-blind randomized trial involving 37 men and women aged 23-71 years (mean age, 43-49 years) who had unremitting depression despite receiving a variety of standard treatments. These study participants had a range of insulin sensitivities, including 20 who had insulin resistance, but none had frank diabetes. Nineteen were randomly assigned to receive pioglitazone and 18 to receive a matching placebo pill for 12 weeks.

Pioglitazone improved depressive symptoms only in the subgroup of patients who had insulin resistance. Their scores on the Hamilton Depression Rating Scale-21 declined an average of 7.15 points more than did the scores of patients with insulin resistance who received placebo. In contrast, among patients who did not have insulin resistance, there was no difference in the decline of HDRS-21 scores between those who received pioglitazone and those who received placebo, the investigators said (Psychiatry Res. 2015 Nov 18).

This treatment response was the most pronounced in younger patients.

The study findings suggest that pioglitazone may be an effective adjuvant therapy for unremitting depression, at least in patients who have insulin resistance and especially in those who are younger. However, given the small size of this study population, larger clinical trials are needed to examine this possibility, Ms. Watson Lin and her associates said.

This study was funded by the National Institutes of Health. Ms. Watson Lin reported having no financial disclosures. One of her associates reported serving as a consultant to Shire and Sunovion, and receiving research support from Magceutics and Corcept.

The rate of routine prostate-specific antigen screening among men aged 50 years and older declined 18% during the first year after the 2012 U.S. Preventive Services Task Force recommendation against it, according to two separate reports published online Nov. 17 in JAMA.

Alternative explanations for the substantial decrease in screening rates between 2011 and 2013 are unlikely. Similar changes occurred following new screening recommendations for other cancers, said Dr. Ahmedin Jemal of Surveillance and Health Services Research, American Cancer Society, Atlanta, and his associates.

They assessed temporal trends in both self-reported PSA screening and prostate cancer incidence using nationally representative data on 446,009 men from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program and National Health Interview Surveys from 2005 through 2013, the most recent year for which complete data are available.

Routine PSA screening in this age group increased to a high of 40.6% in 2008, the year in which the USPSTF guidelines first questioned the benefit-to-harm ratio of this clinical practice. The screening rate then showed a nonsignificant decrease to 37.8% in 2010, then a significant drop to 30.8% in 2013. That decline represents a relative decrease of 18% in routine PSA screening across all races and age groups in 2013, Dr. Jemal and his associates noted (JAMA. 2015 Nov 17;314[19]:2054-61).

At the same time, 33,519 fewer men across the country received a diagnosis of prostate cancer in 2012 than in 2011.

“On one hand, overdiagnosis and overtreatment may be reduced in view of the substantial proportion of prostate cancer cases detected through PSA testing that would not cause harm if left undetected,” the study authors noted. “On the other hand, less screening ... may lead to missed opportunities for detecting biologically important lesions at an early stage and preventing deaths from prostate cancer, the ultimate goal of screening.”

Given prostate cancer’s slow progression and long natural history, “any increase in mortality may not be seen for several years after the discontinuation of screening,” the investigators added. “Future studies should examine temporal trends in advanced-stage diagnoses and prostate cancer mortality to assess the long-term effects of changes in PSA-based screening practices at the population level.”

In a separate report, investigators analyzed PSA screening data from 20,757 men participating in National Health Interview Surveys from 2000 through 2013 and reported their findings in a research letter to the editor.

Like Dr. Jemal’s research group, Dr. Jesse D. Sammon of Brigham and Women’s Hospital, Boston, and his associates found that routine PSA screening among men aged 50 years and older was approximately 34% in the early 2000s and approximately 36% in 2010. After the USPSTF recommended against routine PSA screening in 2012, such screening declined to approximately 30%.

In a further analysis of the data, compared with 2010, survey year 2013 was associated with a significantly lower likelihood of PSA screening (odds ratio, 0.79).

The decrease occurred primarily among men younger than 75 years. Routine PSA screening declined from 23% to 18% (OR, 0.71) among men aged 50-54 years, and from 45% to 35% (OR, 0.69) among men aged 60-64 years (JAMA. 2015 Nov 17;314[19]:2077-9).

The findings “suggest that younger men may be altering health care behavior at a higher rate than older men following the new USPSTF recommendations, changes in clinician PSA practices, or both,” Dr. Sammon and his associates said.

Dr. Jemal’s study was supported by the American Cancer Society. Dr. Jemal and his associates reported having no financial disclosures. Dr. Sammon’s study was supported by the Vattikuti Urology Institute and the Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women’s Hospital. Dr. Sammon and his associates reported having no financial disclosures.

The rate of routine prostate-specific antigen screening among men aged 50 years and older declined 18% during the first year after the 2012 U.S. Preventive Services Task Force recommendation against it, according to two separate reports published online Nov. 17 in JAMA.

Alternative explanations for the substantial decrease in screening rates between 2011 and 2013 are unlikely. Similar changes occurred following new screening recommendations for other cancers, said Dr. Ahmedin Jemal of Surveillance and Health Services Research, American Cancer Society, Atlanta, and his associates.

They assessed temporal trends in both self-reported PSA screening and prostate cancer incidence using nationally representative data on 446,009 men from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program and National Health Interview Surveys from 2005 through 2013, the most recent year for which complete data are available.

Routine PSA screening in this age group increased to a high of 40.6% in 2008, the year in which the USPSTF guidelines first questioned the benefit-to-harm ratio of this clinical practice. The screening rate then showed a nonsignificant decrease to 37.8% in 2010, then a significant drop to 30.8% in 2013. That decline represents a relative decrease of 18% in routine PSA screening across all races and age groups in 2013, Dr. Jemal and his associates noted (JAMA. 2015 Nov 17;314[19]:2054-61).

At the same time, 33,519 fewer men across the country received a diagnosis of prostate cancer in 2012 than in 2011.

“On one hand, overdiagnosis and overtreatment may be reduced in view of the substantial proportion of prostate cancer cases detected through PSA testing that would not cause harm if left undetected,” the study authors noted. “On the other hand, less screening ... may lead to missed opportunities for detecting biologically important lesions at an early stage and preventing deaths from prostate cancer, the ultimate goal of screening.”

Given prostate cancer’s slow progression and long natural history, “any increase in mortality may not be seen for several years after the discontinuation of screening,” the investigators added. “Future studies should examine temporal trends in advanced-stage diagnoses and prostate cancer mortality to assess the long-term effects of changes in PSA-based screening practices at the population level.”

In a separate report, investigators analyzed PSA screening data from 20,757 men participating in National Health Interview Surveys from 2000 through 2013 and reported their findings in a research letter to the editor.

Like Dr. Jemal’s research group, Dr. Jesse D. Sammon of Brigham and Women’s Hospital, Boston, and his associates found that routine PSA screening among men aged 50 years and older was approximately 34% in the early 2000s and approximately 36% in 2010. After the USPSTF recommended against routine PSA screening in 2012, such screening declined to approximately 30%.

In a further analysis of the data, compared with 2010, survey year 2013 was associated with a significantly lower likelihood of PSA screening (odds ratio, 0.79).

The decrease occurred primarily among men younger than 75 years. Routine PSA screening declined from 23% to 18% (OR, 0.71) among men aged 50-54 years, and from 45% to 35% (OR, 0.69) among men aged 60-64 years (JAMA. 2015 Nov 17;314[19]:2077-9).

The findings “suggest that younger men may be altering health care behavior at a higher rate than older men following the new USPSTF recommendations, changes in clinician PSA practices, or both,” Dr. Sammon and his associates said.

Dr. Jemal’s study was supported by the American Cancer Society. Dr. Jemal and his associates reported having no financial disclosures. Dr. Sammon’s study was supported by the Vattikuti Urology Institute and the Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women’s Hospital. Dr. Sammon and his associates reported having no financial disclosures.

The rate of routine prostate-specific antigen screening among men aged 50 years and older declined 18% during the first year after the 2012 U.S. Preventive Services Task Force recommendation against it, according to two separate reports published online Nov. 17 in JAMA.

Alternative explanations for the substantial decrease in screening rates between 2011 and 2013 are unlikely. Similar changes occurred following new screening recommendations for other cancers, said Dr. Ahmedin Jemal of Surveillance and Health Services Research, American Cancer Society, Atlanta, and his associates.

They assessed temporal trends in both self-reported PSA screening and prostate cancer incidence using nationally representative data on 446,009 men from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program and National Health Interview Surveys from 2005 through 2013, the most recent year for which complete data are available.

Routine PSA screening in this age group increased to a high of 40.6% in 2008, the year in which the USPSTF guidelines first questioned the benefit-to-harm ratio of this clinical practice. The screening rate then showed a nonsignificant decrease to 37.8% in 2010, then a significant drop to 30.8% in 2013. That decline represents a relative decrease of 18% in routine PSA screening across all races and age groups in 2013, Dr. Jemal and his associates noted (JAMA. 2015 Nov 17;314[19]:2054-61).

At the same time, 33,519 fewer men across the country received a diagnosis of prostate cancer in 2012 than in 2011.

“On one hand, overdiagnosis and overtreatment may be reduced in view of the substantial proportion of prostate cancer cases detected through PSA testing that would not cause harm if left undetected,” the study authors noted. “On the other hand, less screening ... may lead to missed opportunities for detecting biologically important lesions at an early stage and preventing deaths from prostate cancer, the ultimate goal of screening.”

Given prostate cancer’s slow progression and long natural history, “any increase in mortality may not be seen for several years after the discontinuation of screening,” the investigators added. “Future studies should examine temporal trends in advanced-stage diagnoses and prostate cancer mortality to assess the long-term effects of changes in PSA-based screening practices at the population level.”

In a separate report, investigators analyzed PSA screening data from 20,757 men participating in National Health Interview Surveys from 2000 through 2013 and reported their findings in a research letter to the editor.

Like Dr. Jemal’s research group, Dr. Jesse D. Sammon of Brigham and Women’s Hospital, Boston, and his associates found that routine PSA screening among men aged 50 years and older was approximately 34% in the early 2000s and approximately 36% in 2010. After the USPSTF recommended against routine PSA screening in 2012, such screening declined to approximately 30%.

In a further analysis of the data, compared with 2010, survey year 2013 was associated with a significantly lower likelihood of PSA screening (odds ratio, 0.79).

The decrease occurred primarily among men younger than 75 years. Routine PSA screening declined from 23% to 18% (OR, 0.71) among men aged 50-54 years, and from 45% to 35% (OR, 0.69) among men aged 60-64 years (JAMA. 2015 Nov 17;314[19]:2077-9).

The findings “suggest that younger men may be altering health care behavior at a higher rate than older men following the new USPSTF recommendations, changes in clinician PSA practices, or both,” Dr. Sammon and his associates said.

Dr. Jemal’s study was supported by the American Cancer Society. Dr. Jemal and his associates reported having no financial disclosures. Dr. Sammon’s study was supported by the Vattikuti Urology Institute and the Professor Walter Morris-Hale Distinguished Chair in Urologic Oncology at Brigham and Women’s Hospital. Dr. Sammon and his associates reported having no financial disclosures.

Therapeutic hypothermia significantly raises the rate of survival with a good neurologic outcome among patients who are comatose after a cardiac arrest with a nonshockable initial rhythm, according to a report published online November 16 in Circulation.

Many observational and retrospective cohort studies have examined the possible benefits of therapeutic hypothermia in this patient population, but they have produced conflicting results. No prospective randomized clinical trials have been published as yet. This has led to controversy. Some clinicians insist the treatment should be reserved only for patients who meet the narrow criteria for which there is good supportive evidence; others, eager for any clinical strategy that can improve the outcomes of these critically ill patients, routinely expand its use to comatose patients regardless of their initial heart rhythm or the location of the cardiac arrest, wrote Dr. Sarah M. Perman of the department of emergency medicine, University of Colorado, Aurora, and her associates.

They studied the issue using data from a national registry of patients treated at 16 medical centers that sometimes use therapeutic hypothermia after cardiac arrest. They assessed the records of 519 adults during a 3-year period who had a nontraumatic cardiac arrest and initially registered either pulseless electrical activity or asystole, then had a return of spontaneous circulation but remained comatose. Approximately half of these comatose survivors (262 patients) were treated with therapeutic hypothermia according to their hospital’s usual protocols, and the other half (257 control subjects) received standard care without therapeutic hypothermia.

Patients who received the intervention were significantly younger (62 vs 69 years), had a longer duration of cardiac arrest (23 vs 13 minutes), had a higher incidence of asystole as their primary cardiac rhythm (45% vs 35%), and were much more likely to have a an out-of-hospital cardiac arrest (82% vs 39%). To account for these marked differences and to control for confounding by indication, the investigators used propensity matching and identified 200 matched pairs of patients.

In the propensity-matched cohort, the rate of survival to hospital discharge was significantly higher with therapeutic hypothermia (29%) than without it (15%), as was the rate of survival with a favorable neurologic outcome (21% vs 10%). And in a multivariate analysis of factors contributing to positive patient outcomes, the intervention was associated with a 3.5-fold increase in favorable neurologic outcomes. A further analysis of the data showed that therapeutic hypothermia was associated with improved survival, with an OR of 2.8, the investigators said.

In addition, an analysis of outcomes across various subgroups of patients showed that regardless of the location of their cardiac arrest, patients were consistently more likely to survive to hospital discharge neurologically intact if they received therapeutic hypothermia (OR, 2.1 for out-of-hospital and OR, 4.2 for in-hospital cardiac arrest).

“These results lend support to a broadening of indications for therapeutic hypothermia in comatose post-arrest patients with initial nonshockable rhythms,” Dr. Perman and her associates said.

Therapeutic hypothermia significantly raises the rate of survival with a good neurologic outcome among patients who are comatose after a cardiac arrest with a nonshockable initial rhythm, according to a report published online November 16 in Circulation.

Many observational and retrospective cohort studies have examined the possible benefits of therapeutic hypothermia in this patient population, but they have produced conflicting results. No prospective randomized clinical trials have been published as yet. This has led to controversy. Some clinicians insist the treatment should be reserved only for patients who meet the narrow criteria for which there is good supportive evidence; others, eager for any clinical strategy that can improve the outcomes of these critically ill patients, routinely expand its use to comatose patients regardless of their initial heart rhythm or the location of the cardiac arrest, wrote Dr. Sarah M. Perman of the department of emergency medicine, University of Colorado, Aurora, and her associates.

They studied the issue using data from a national registry of patients treated at 16 medical centers that sometimes use therapeutic hypothermia after cardiac arrest. They assessed the records of 519 adults during a 3-year period who had a nontraumatic cardiac arrest and initially registered either pulseless electrical activity or asystole, then had a return of spontaneous circulation but remained comatose. Approximately half of these comatose survivors (262 patients) were treated with therapeutic hypothermia according to their hospital’s usual protocols, and the other half (257 control subjects) received standard care without therapeutic hypothermia.

Patients who received the intervention were significantly younger (62 vs 69 years), had a longer duration of cardiac arrest (23 vs 13 minutes), had a higher incidence of asystole as their primary cardiac rhythm (45% vs 35%), and were much more likely to have a an out-of-hospital cardiac arrest (82% vs 39%). To account for these marked differences and to control for confounding by indication, the investigators used propensity matching and identified 200 matched pairs of patients.

In the propensity-matched cohort, the rate of survival to hospital discharge was significantly higher with therapeutic hypothermia (29%) than without it (15%), as was the rate of survival with a favorable neurologic outcome (21% vs 10%). And in a multivariate analysis of factors contributing to positive patient outcomes, the intervention was associated with a 3.5-fold increase in favorable neurologic outcomes. A further analysis of the data showed that therapeutic hypothermia was associated with improved survival, with an OR of 2.8, the investigators said.

In addition, an analysis of outcomes across various subgroups of patients showed that regardless of the location of their cardiac arrest, patients were consistently more likely to survive to hospital discharge neurologically intact if they received therapeutic hypothermia (OR, 2.1 for out-of-hospital and OR, 4.2 for in-hospital cardiac arrest).

“These results lend support to a broadening of indications for therapeutic hypothermia in comatose post-arrest patients with initial nonshockable rhythms,” Dr. Perman and her associates said.

Therapeutic hypothermia significantly raises the rate of survival with a good neurologic outcome among patients who are comatose after a cardiac arrest with a nonshockable initial rhythm, according to a report published online November 16 in Circulation.

Many observational and retrospective cohort studies have examined the possible benefits of therapeutic hypothermia in this patient population, but they have produced conflicting results. No prospective randomized clinical trials have been published as yet. This has led to controversy. Some clinicians insist the treatment should be reserved only for patients who meet the narrow criteria for which there is good supportive evidence; others, eager for any clinical strategy that can improve the outcomes of these critically ill patients, routinely expand its use to comatose patients regardless of their initial heart rhythm or the location of the cardiac arrest, wrote Dr. Sarah M. Perman of the department of emergency medicine, University of Colorado, Aurora, and her associates.

They studied the issue using data from a national registry of patients treated at 16 medical centers that sometimes use therapeutic hypothermia after cardiac arrest. They assessed the records of 519 adults during a 3-year period who had a nontraumatic cardiac arrest and initially registered either pulseless electrical activity or asystole, then had a return of spontaneous circulation but remained comatose. Approximately half of these comatose survivors (262 patients) were treated with therapeutic hypothermia according to their hospital’s usual protocols, and the other half (257 control subjects) received standard care without therapeutic hypothermia.

Patients who received the intervention were significantly younger (62 vs 69 years), had a longer duration of cardiac arrest (23 vs 13 minutes), had a higher incidence of asystole as their primary cardiac rhythm (45% vs 35%), and were much more likely to have a an out-of-hospital cardiac arrest (82% vs 39%). To account for these marked differences and to control for confounding by indication, the investigators used propensity matching and identified 200 matched pairs of patients.

In the propensity-matched cohort, the rate of survival to hospital discharge was significantly higher with therapeutic hypothermia (29%) than without it (15%), as was the rate of survival with a favorable neurologic outcome (21% vs 10%). And in a multivariate analysis of factors contributing to positive patient outcomes, the intervention was associated with a 3.5-fold increase in favorable neurologic outcomes. A further analysis of the data showed that therapeutic hypothermia was associated with improved survival, with an OR of 2.8, the investigators said.

In addition, an analysis of outcomes across various subgroups of patients showed that regardless of the location of their cardiac arrest, patients were consistently more likely to survive to hospital discharge neurologically intact if they received therapeutic hypothermia (OR, 2.1 for out-of-hospital and OR, 4.2 for in-hospital cardiac arrest).

“These results lend support to a broadening of indications for therapeutic hypothermia in comatose post-arrest patients with initial nonshockable rhythms,” Dr. Perman and her associates said.

Oral melatonin improves both sleep disturbance and skin symptoms in children and adolescents who have atopic dermatitis, according to a report published online November 16 in JAMA Pediatrics.

“Although the magnitude of the benefit is not great, many patients might benefit from this dual effect. Sleep disturbance is highly prevalent in children with AD and . . . leads to impaired quality of life for the patients and their families,” said Dr. Yung-Sen Chang of

© Wjeger/Thinkstockphotos.com

Taipei (Taiwan) City Hospital Renal Branch and associates.

The investigators showed in a previous study that children with AD have longer sleep-onset latency, more sleep fragmentation, less REM sleep, and reduced sleep efficiency than healthy control subjects and that these sleep disturbances are associated with scratching movements, more severe dermatitis, and decreased melatonin secretion. “Worse sleep increases the likelihood that these children will scratch, which will further exacerbate the skin inflammation. . . . We hypothesized that melatonin, with its sleep-promoting and antiinflammatory properties, could break this vicious cycle,” they noted.

Dr. Chang and associates performed a single-center randomized double-blind crossover trial involving 38 patients aged 1-18 years who had AD involving at least 5% of their body surface area and sleep problems that occurred more than 3 days per week. These study participants were randomly assigned to receive oral melatonin (3 mg/day) or a matching placebo at bedtime for 4 weeks, then crossed over to the alternate assignment for a further 4 weeks.

The primary efficacy outcome — AD severity as measured on the Scoring Atopic Dermatitis index — improved with melatonin by a mean of 9.1 points out of a possible 103 points, compared with placebo. Melatonin also significantly reduced sleep-onset latency by more than half (23.4 minutes), compared with placebo, according to objective sleep actigraphy results (JAMA Ped. 2015 November 16 [doi:10.1001/jamapediatrics.2015.3092]).

In addition, more patients and families subjectively reported that dermatitis improved when taking melatonin compared with placebo (47% vs 32%), and more reported that sleep improved when taking melatonin compared with placebo (46% vs 34%).

No adverse effects were reported. Melatonin’s good safety profile is particularly important given that all other medications used for sleep problems in patients with AD, such as antihistamines, benzodiazepines, chloral hydrate, and clonidine, are of limited benefit and carry negative adverse effects.

“We recommend melatonin supplementation for these patients, because it is a potentially safe and effective way to improve their sleep and skin condition simultaneously,” Dr. Chang and associates said.

Oral melatonin improves both sleep disturbance and skin symptoms in children and adolescents who have atopic dermatitis, according to a report published online November 16 in JAMA Pediatrics.

“Although the magnitude of the benefit is not great, many patients might benefit from this dual effect. Sleep disturbance is highly prevalent in children with AD and . . . leads to impaired quality of life for the patients and their families,” said Dr. Yung-Sen Chang of

© Wjeger/Thinkstockphotos.com

Taipei (Taiwan) City Hospital Renal Branch and associates.

The investigators showed in a previous study that children with AD have longer sleep-onset latency, more sleep fragmentation, less REM sleep, and reduced sleep efficiency than healthy control subjects and that these sleep disturbances are associated with scratching movements, more severe dermatitis, and decreased melatonin secretion. “Worse sleep increases the likelihood that these children will scratch, which will further exacerbate the skin inflammation. . . . We hypothesized that melatonin, with its sleep-promoting and antiinflammatory properties, could break this vicious cycle,” they noted.

Dr. Chang and associates performed a single-center randomized double-blind crossover trial involving 38 patients aged 1-18 years who had AD involving at least 5% of their body surface area and sleep problems that occurred more than 3 days per week. These study participants were randomly assigned to receive oral melatonin (3 mg/day) or a matching placebo at bedtime for 4 weeks, then crossed over to the alternate assignment for a further 4 weeks.

The primary efficacy outcome — AD severity as measured on the Scoring Atopic Dermatitis index — improved with melatonin by a mean of 9.1 points out of a possible 103 points, compared with placebo. Melatonin also significantly reduced sleep-onset latency by more than half (23.4 minutes), compared with placebo, according to objective sleep actigraphy results (JAMA Ped. 2015 November 16 [doi:10.1001/jamapediatrics.2015.3092]).

In addition, more patients and families subjectively reported that dermatitis improved when taking melatonin compared with placebo (47% vs 32%), and more reported that sleep improved when taking melatonin compared with placebo (46% vs 34%).

No adverse effects were reported. Melatonin’s good safety profile is particularly important given that all other medications used for sleep problems in patients with AD, such as antihistamines, benzodiazepines, chloral hydrate, and clonidine, are of limited benefit and carry negative adverse effects.

“We recommend melatonin supplementation for these patients, because it is a potentially safe and effective way to improve their sleep and skin condition simultaneously,” Dr. Chang and associates said.

Oral melatonin improves both sleep disturbance and skin symptoms in children and adolescents who have atopic dermatitis, according to a report published online November 16 in JAMA Pediatrics.

“Although the magnitude of the benefit is not great, many patients might benefit from this dual effect. Sleep disturbance is highly prevalent in children with AD and . . . leads to impaired quality of life for the patients and their families,” said Dr. Yung-Sen Chang of

© Wjeger/Thinkstockphotos.com

Taipei (Taiwan) City Hospital Renal Branch and associates.

The investigators showed in a previous study that children with AD have longer sleep-onset latency, more sleep fragmentation, less REM sleep, and reduced sleep efficiency than healthy control subjects and that these sleep disturbances are associated with scratching movements, more severe dermatitis, and decreased melatonin secretion. “Worse sleep increases the likelihood that these children will scratch, which will further exacerbate the skin inflammation. . . . We hypothesized that melatonin, with its sleep-promoting and antiinflammatory properties, could break this vicious cycle,” they noted.

Dr. Chang and associates performed a single-center randomized double-blind crossover trial involving 38 patients aged 1-18 years who had AD involving at least 5% of their body surface area and sleep problems that occurred more than 3 days per week. These study participants were randomly assigned to receive oral melatonin (3 mg/day) or a matching placebo at bedtime for 4 weeks, then crossed over to the alternate assignment for a further 4 weeks.

The primary efficacy outcome — AD severity as measured on the Scoring Atopic Dermatitis index — improved with melatonin by a mean of 9.1 points out of a possible 103 points, compared with placebo. Melatonin also significantly reduced sleep-onset latency by more than half (23.4 minutes), compared with placebo, according to objective sleep actigraphy results (JAMA Ped. 2015 November 16 [doi:10.1001/jamapediatrics.2015.3092]).

In addition, more patients and families subjectively reported that dermatitis improved when taking melatonin compared with placebo (47% vs 32%), and more reported that sleep improved when taking melatonin compared with placebo (46% vs 34%).

No adverse effects were reported. Melatonin’s good safety profile is particularly important given that all other medications used for sleep problems in patients with AD, such as antihistamines, benzodiazepines, chloral hydrate, and clonidine, are of limited benefit and carry negative adverse effects.

“We recommend melatonin supplementation for these patients, because it is a potentially safe and effective way to improve their sleep and skin condition simultaneously,” Dr. Chang and associates said.

Oral melatonin improves both sleep disturbance and skin symptoms in children and adolescents who have atopic dermatitis, according to a report published online November 16 in JAMA Pediatrics.

“Although the magnitude of the benefit is not great, many patients might benefit from this dual effect. Sleep disturbance is highly prevalent in children with AD and . . . leads to impaired quality of life for the patients and their families,” said Dr. Yung-Sen Chang of

© Wjeger/Thinkstockphotos.com

Taipei (Taiwan) City Hospital Renal Branch and associates.

The investigators showed in a previous study that children with AD have longer sleep-onset latency, more sleep fragmentation, less REM sleep, and reduced sleep efficiency than healthy control subjects and that these sleep disturbances are associated with scratching movements, more severe dermatitis, and decreased melatonin secretion. “Worse sleep increases the likelihood that these children will scratch, which will further exacerbate the skin inflammation. . . . We hypothesized that melatonin, with its sleep-promoting and antiinflammatory properties, could break this vicious cycle,” they noted.

Dr. Chang and associates performed a single-center randomized double-blind crossover trial involving 38 patients aged 1-18 years who had AD involving at least 5% of their body surface area and sleep problems that occurred more than 3 days per week. These study participants were randomly assigned to receive oral melatonin (3 mg/day) or a matching placebo at bedtime for 4 weeks, then crossed over to the alternate assignment for a further 4 weeks.

The primary efficacy outcome — AD severity as measured on the Scoring Atopic Dermatitis index — improved with melatonin by a mean of 9.1 points out of a possible 103 points, compared with placebo. Melatonin also significantly reduced sleep-onset latency by more than half (23.4 minutes), compared with placebo, according to objective sleep actigraphy results (JAMA Ped. 2015 November 16 [doi:10.1001/jamapediatrics.2015.3092]).

In addition, more patients and families subjectively reported that dermatitis improved when taking melatonin compared with placebo (47% vs 32%), and more reported that sleep improved when taking melatonin compared with placebo (46% vs 34%).

No adverse effects were reported. Melatonin’s good safety profile is particularly important given that all other medications used for sleep problems in patients with AD, such as antihistamines, benzodiazepines, chloral hydrate, and clonidine, are of limited benefit and carry negative adverse effects.

“We recommend melatonin supplementation for these patients, because it is a potentially safe and effective way to improve their sleep and skin condition simultaneously,” Dr. Chang and associates said.

Oral melatonin improves both sleep disturbance and skin symptoms in children and adolescents who have atopic dermatitis, according to a report published online November 16 in JAMA Pediatrics.

“Although the magnitude of the benefit is not great, many patients might benefit from this dual effect. Sleep disturbance is highly prevalent in children with AD and . . . leads to impaired quality of life for the patients and their families,” said Dr. Yung-Sen Chang of

© Wjeger/Thinkstockphotos.com

Taipei (Taiwan) City Hospital Renal Branch and associates.

The investigators showed in a previous study that children with AD have longer sleep-onset latency, more sleep fragmentation, less REM sleep, and reduced sleep efficiency than healthy control subjects and that these sleep disturbances are associated with scratching movements, more severe dermatitis, and decreased melatonin secretion. “Worse sleep increases the likelihood that these children will scratch, which will further exacerbate the skin inflammation. . . . We hypothesized that melatonin, with its sleep-promoting and antiinflammatory properties, could break this vicious cycle,” they noted.

Dr. Chang and associates performed a single-center randomized double-blind crossover trial involving 38 patients aged 1-18 years who had AD involving at least 5% of their body surface area and sleep problems that occurred more than 3 days per week. These study participants were randomly assigned to receive oral melatonin (3 mg/day) or a matching placebo at bedtime for 4 weeks, then crossed over to the alternate assignment for a further 4 weeks.

The primary efficacy outcome — AD severity as measured on the Scoring Atopic Dermatitis index — improved with melatonin by a mean of 9.1 points out of a possible 103 points, compared with placebo. Melatonin also significantly reduced sleep-onset latency by more than half (23.4 minutes), compared with placebo, according to objective sleep actigraphy results (JAMA Ped. 2015 November 16 [doi:10.1001/jamapediatrics.2015.3092]).

In addition, more patients and families subjectively reported that dermatitis improved when taking melatonin compared with placebo (47% vs 32%), and more reported that sleep improved when taking melatonin compared with placebo (46% vs 34%).

No adverse effects were reported. Melatonin’s good safety profile is particularly important given that all other medications used for sleep problems in patients with AD, such as antihistamines, benzodiazepines, chloral hydrate, and clonidine, are of limited benefit and carry negative adverse effects.

“We recommend melatonin supplementation for these patients, because it is a potentially safe and effective way to improve their sleep and skin condition simultaneously,” Dr. Chang and associates said.

Oral melatonin improves both sleep disturbance and skin symptoms in children and adolescents who have atopic dermatitis, according to a report published online November 16 in JAMA Pediatrics.

“Although the magnitude of the benefit is not great, many patients might benefit from this dual effect. Sleep disturbance is highly prevalent in children with AD and . . . leads to impaired quality of life for the patients and their families,” said Dr. Yung-Sen Chang of

© Wjeger/Thinkstockphotos.com

Taipei (Taiwan) City Hospital Renal Branch and associates.

The investigators showed in a previous study that children with AD have longer sleep-onset latency, more sleep fragmentation, less REM sleep, and reduced sleep efficiency than healthy control subjects and that these sleep disturbances are associated with scratching movements, more severe dermatitis, and decreased melatonin secretion. “Worse sleep increases the likelihood that these children will scratch, which will further exacerbate the skin inflammation. . . . We hypothesized that melatonin, with its sleep-promoting and antiinflammatory properties, could break this vicious cycle,” they noted.

Dr. Chang and associates performed a single-center randomized double-blind crossover trial involving 38 patients aged 1-18 years who had AD involving at least 5% of their body surface area and sleep problems that occurred more than 3 days per week. These study participants were randomly assigned to receive oral melatonin (3 mg/day) or a matching placebo at bedtime for 4 weeks, then crossed over to the alternate assignment for a further 4 weeks.

The primary efficacy outcome — AD severity as measured on the Scoring Atopic Dermatitis index — improved with melatonin by a mean of 9.1 points out of a possible 103 points, compared with placebo. Melatonin also significantly reduced sleep-onset latency by more than half (23.4 minutes), compared with placebo, according to objective sleep actigraphy results (JAMA Ped. 2015 November 16 [doi:10.1001/jamapediatrics.2015.3092]).

In addition, more patients and families subjectively reported that dermatitis improved when taking melatonin compared with placebo (47% vs 32%), and more reported that sleep improved when taking melatonin compared with placebo (46% vs 34%).

No adverse effects were reported. Melatonin’s good safety profile is particularly important given that all other medications used for sleep problems in patients with AD, such as antihistamines, benzodiazepines, chloral hydrate, and clonidine, are of limited benefit and carry negative adverse effects.

“We recommend melatonin supplementation for these patients, because it is a potentially safe and effective way to improve their sleep and skin condition simultaneously,” Dr. Chang and associates said.

Prophylactic antibiotics don’t prevent poststroke pneumonia or reduce mortality, even in patients who have stroke-induced dysphagia and are at high risk of aspiration, according to a report published in the Lancet.

In a prospective open-label cluster-randomized clinical trial, researchers randomly assigned 37 stroke units in the United Kingdom to give new patients either prophylactic antibiotics for 7 days plus standard stroke care (564 patients) or standard stroke care alone (524 patients). All study participants were considered “unsafe to swallow” because they had impaired consciousness, they failed a bedside swallow test, or they had a nasogastric tube, said Lalit Kalra, Ph.D., of the department of basic and clinical neurosciences and the Institute of Psychiatry, Psychology, and Neuroscience at King’s College, London, and his associates.

Each hospital was allowed to choose which prophylactic antibiotics to use according to their local guidelines, as well as which dosage and route of administration. The primary outcome was the incidence of post-stroke pneumonia within 2 weeks of hospitalization, which was assessed by two separate methods: a statistician masked to treatment assignment diagnosed pneumonia according to a criteria-based hierarchical algorithm, and a local treating physician diagnosed pneumonia according to clinical findings.

According to the algorithm, poststroke pneumonia developed in 13% of patients given prophylactic antibiotics and 10% of the control group, for an OR of 1.21. According to the clinical findings, poststroke pneumonia developed in 16% of the intervention group and 15% of the control group, for an OR of 1.01. By either definition, prophylactic antibiotics failed to reduce the incidence of poststroke pneumonia, the investigators said (Lancet 2015;386:1835-44).

In addition, all-cause mortality at 14 days (10%) and at 90 days (39%) was not significantly different between the two study groups. And there was no significant difference in the percentage of patients with good functional outcomes. Prophylactic antibiotics were associated with longer hospital stays than standard treatment.

On the positive side, prophylactic antibiotics did reduce the number of nonpneumonia infections, especially urosepsis.

Adverse effects, including cases of Clostridium difficile-positive diarrhea and MRSA colonization, were rare and occurred in equal numbers across the two study groups.

The findings indicate that routine use of antibiotics to prevent poststroke pneumonia “cannot be recommended and should be used judiciously ... in patients after stroke who are managed on stroke units, even if they are at high risk of aspiration,” Dr. Kalra and associates said.

The most likely explanation for this study’s negative findings is that prophylactic antibiotics “do not add to existing preventive measures such as positioning, regular suction, swallowing techniques, modified diets, and early initiation of antibiotics” if patients are suspected of developing pneumonia. It also is possible that poststroke pneumonia is not just a straightforward infection but a complex respiratory syndrome stemming from multiple bacterial, chemical, and immunologic causes that might not respond to antibiotics alone, they added.

This study was funded by the U.K. National Institute for Health Research. Dr. Kalra and associates reported having no relevant financial disclosures.

Prophylactic antibiotics don’t prevent poststroke pneumonia or reduce mortality, even in patients who have stroke-induced dysphagia and are at high risk of aspiration, according to a report published in the Lancet.

In a prospective open-label cluster-randomized clinical trial, researchers randomly assigned 37 stroke units in the United Kingdom to give new patients either prophylactic antibiotics for 7 days plus standard stroke care (564 patients) or standard stroke care alone (524 patients). All study participants were considered “unsafe to swallow” because they had impaired consciousness, they failed a bedside swallow test, or they had a nasogastric tube, said Lalit Kalra, Ph.D., of the department of basic and clinical neurosciences and the Institute of Psychiatry, Psychology, and Neuroscience at King’s College, London, and his associates.

Each hospital was allowed to choose which prophylactic antibiotics to use according to their local guidelines, as well as which dosage and route of administration. The primary outcome was the incidence of post-stroke pneumonia within 2 weeks of hospitalization, which was assessed by two separate methods: a statistician masked to treatment assignment diagnosed pneumonia according to a criteria-based hierarchical algorithm, and a local treating physician diagnosed pneumonia according to clinical findings.

According to the algorithm, poststroke pneumonia developed in 13% of patients given prophylactic antibiotics and 10% of the control group, for an OR of 1.21. According to the clinical findings, poststroke pneumonia developed in 16% of the intervention group and 15% of the control group, for an OR of 1.01. By either definition, prophylactic antibiotics failed to reduce the incidence of poststroke pneumonia, the investigators said (Lancet 2015;386:1835-44).

In addition, all-cause mortality at 14 days (10%) and at 90 days (39%) was not significantly different between the two study groups. And there was no significant difference in the percentage of patients with good functional outcomes. Prophylactic antibiotics were associated with longer hospital stays than standard treatment.

On the positive side, prophylactic antibiotics did reduce the number of nonpneumonia infections, especially urosepsis.

Adverse effects, including cases of Clostridium difficile-positive diarrhea and MRSA colonization, were rare and occurred in equal numbers across the two study groups.

The findings indicate that routine use of antibiotics to prevent poststroke pneumonia “cannot be recommended and should be used judiciously ... in patients after stroke who are managed on stroke units, even if they are at high risk of aspiration,” Dr. Kalra and associates said.

The most likely explanation for this study’s negative findings is that prophylactic antibiotics “do not add to existing preventive measures such as positioning, regular suction, swallowing techniques, modified diets, and early initiation of antibiotics” if patients are suspected of developing pneumonia. It also is possible that poststroke pneumonia is not just a straightforward infection but a complex respiratory syndrome stemming from multiple bacterial, chemical, and immunologic causes that might not respond to antibiotics alone, they added.

This study was funded by the U.K. National Institute for Health Research. Dr. Kalra and associates reported having no relevant financial disclosures.

Prophylactic antibiotics don’t prevent poststroke pneumonia or reduce mortality, even in patients who have stroke-induced dysphagia and are at high risk of aspiration, according to a report published in the Lancet.

In a prospective open-label cluster-randomized clinical trial, researchers randomly assigned 37 stroke units in the United Kingdom to give new patients either prophylactic antibiotics for 7 days plus standard stroke care (564 patients) or standard stroke care alone (524 patients). All study participants were considered “unsafe to swallow” because they had impaired consciousness, they failed a bedside swallow test, or they had a nasogastric tube, said Lalit Kalra, Ph.D., of the department of basic and clinical neurosciences and the Institute of Psychiatry, Psychology, and Neuroscience at King’s College, London, and his associates.

Each hospital was allowed to choose which prophylactic antibiotics to use according to their local guidelines, as well as which dosage and route of administration. The primary outcome was the incidence of post-stroke pneumonia within 2 weeks of hospitalization, which was assessed by two separate methods: a statistician masked to treatment assignment diagnosed pneumonia according to a criteria-based hierarchical algorithm, and a local treating physician diagnosed pneumonia according to clinical findings.

According to the algorithm, poststroke pneumonia developed in 13% of patients given prophylactic antibiotics and 10% of the control group, for an OR of 1.21. According to the clinical findings, poststroke pneumonia developed in 16% of the intervention group and 15% of the control group, for an OR of 1.01. By either definition, prophylactic antibiotics failed to reduce the incidence of poststroke pneumonia, the investigators said (Lancet 2015;386:1835-44).

In addition, all-cause mortality at 14 days (10%) and at 90 days (39%) was not significantly different between the two study groups. And there was no significant difference in the percentage of patients with good functional outcomes. Prophylactic antibiotics were associated with longer hospital stays than standard treatment.

On the positive side, prophylactic antibiotics did reduce the number of nonpneumonia infections, especially urosepsis.

Adverse effects, including cases of Clostridium difficile-positive diarrhea and MRSA colonization, were rare and occurred in equal numbers across the two study groups.

The findings indicate that routine use of antibiotics to prevent poststroke pneumonia “cannot be recommended and should be used judiciously ... in patients after stroke who are managed on stroke units, even if they are at high risk of aspiration,” Dr. Kalra and associates said.

The most likely explanation for this study’s negative findings is that prophylactic antibiotics “do not add to existing preventive measures such as positioning, regular suction, swallowing techniques, modified diets, and early initiation of antibiotics” if patients are suspected of developing pneumonia. It also is possible that poststroke pneumonia is not just a straightforward infection but a complex respiratory syndrome stemming from multiple bacterial, chemical, and immunologic causes that might not respond to antibiotics alone, they added.

This study was funded by the U.K. National Institute for Health Research. Dr. Kalra and associates reported having no relevant financial disclosures.

Prophylactic antibiotics don’t prevent poststroke pneumonia or reduce mortality, even in patients who have stroke-induced dysphagia and are at high risk of aspiration, according to a report published in the Lancet.

In a prospective open-label cluster-randomized clinical trial, researchers randomly assigned 37 stroke units in the United Kingdom to give new patients either prophylactic antibiotics for 7 days plus standard stroke care (564 patients) or standard stroke care alone (524 patients). All study participants were considered “unsafe to swallow” because they had impaired consciousness, they failed a bedside swallow test, or they had a nasogastric tube, said Lalit Kalra, Ph.D., of the department of basic and clinical neurosciences and the Institute of Psychiatry, Psychology, and Neuroscience at King’s College, London, and his associates.

Each hospital was allowed to choose which prophylactic antibiotics to use according to their local guidelines, as well as which dosage and route of administration. The primary outcome was the incidence of post-stroke pneumonia within 2 weeks of hospitalization, which was assessed by two separate methods: a statistician masked to treatment assignment diagnosed pneumonia according to a criteria-based hierarchical algorithm, and a local treating physician diagnosed pneumonia according to clinical findings.

According to the algorithm, poststroke pneumonia developed in 13% of patients given prophylactic antibiotics and 10% of the control group, for an OR of 1.21. According to the clinical findings, poststroke pneumonia developed in 16% of the intervention group and 15% of the control group, for an OR of 1.01. By either definition, prophylactic antibiotics failed to reduce the incidence of poststroke pneumonia, the investigators said (Lancet 2015;386:1835-44).

In addition, all-cause mortality at 14 days (10%) and at 90 days (39%) was not significantly different between the two study groups. And there was no significant difference in the percentage of patients with good functional outcomes. Prophylactic antibiotics were associated with longer hospital stays than standard treatment.

On the positive side, prophylactic antibiotics did reduce the number of nonpneumonia infections, especially urosepsis.

Adverse effects, including cases of Clostridium difficile-positive diarrhea and MRSA colonization, were rare and occurred in equal numbers across the two study groups.

The findings indicate that routine use of antibiotics to prevent poststroke pneumonia “cannot be recommended and should be used judiciously ... in patients after stroke who are managed on stroke units, even if they are at high risk of aspiration,” Dr. Kalra and associates said.

The most likely explanation for this study’s negative findings is that prophylactic antibiotics “do not add to existing preventive measures such as positioning, regular suction, swallowing techniques, modified diets, and early initiation of antibiotics” if patients are suspected of developing pneumonia. It also is possible that poststroke pneumonia is not just a straightforward infection but a complex respiratory syndrome stemming from multiple bacterial, chemical, and immunologic causes that might not respond to antibiotics alone, they added.

This study was funded by the U.K. National Institute for Health Research. Dr. Kalra and associates reported having no relevant financial disclosures.

Prophylactic antibiotics don’t prevent poststroke pneumonia or reduce mortality, even in patients who have stroke-induced dysphagia and are at high risk of aspiration, according to a report published in the Lancet.

In a prospective open-label cluster-randomized clinical trial, researchers randomly assigned 37 stroke units in the United Kingdom to give new patients either prophylactic antibiotics for 7 days plus standard stroke care (564 patients) or standard stroke care alone (524 patients). All study participants were considered “unsafe to swallow” because they had impaired consciousness, they failed a bedside swallow test, or they had a nasogastric tube, said Lalit Kalra, Ph.D., of the department of basic and clinical neurosciences and the Institute of Psychiatry, Psychology, and Neuroscience at King’s College, London, and his associates.

Each hospital was allowed to choose which prophylactic antibiotics to use according to their local guidelines, as well as which dosage and route of administration. The primary outcome was the incidence of post-stroke pneumonia within 2 weeks of hospitalization, which was assessed by two separate methods: a statistician masked to treatment assignment diagnosed pneumonia according to a criteria-based hierarchical algorithm, and a local treating physician diagnosed pneumonia according to clinical findings.

According to the algorithm, poststroke pneumonia developed in 13% of patients given prophylactic antibiotics and 10% of the control group, for an OR of 1.21. According to the clinical findings, poststroke pneumonia developed in 16% of the intervention group and 15% of the control group, for an OR of 1.01. By either definition, prophylactic antibiotics failed to reduce the incidence of poststroke pneumonia, the investigators said (Lancet 2015;386:1835-44).

In addition, all-cause mortality at 14 days (10%) and at 90 days (39%) was not significantly different between the two study groups. And there was no significant difference in the percentage of patients with good functional outcomes. Prophylactic antibiotics were associated with longer hospital stays than standard treatment.

On the positive side, prophylactic antibiotics did reduce the number of nonpneumonia infections, especially urosepsis.

Adverse effects, including cases of Clostridium difficile-positive diarrhea and MRSA colonization, were rare and occurred in equal numbers across the two study groups.

The findings indicate that routine use of antibiotics to prevent poststroke pneumonia “cannot be recommended and should be used judiciously ... in patients after stroke who are managed on stroke units, even if they are at high risk of aspiration,” Dr. Kalra and associates said.

The most likely explanation for this study’s negative findings is that prophylactic antibiotics “do not add to existing preventive measures such as positioning, regular suction, swallowing techniques, modified diets, and early initiation of antibiotics” if patients are suspected of developing pneumonia. It also is possible that poststroke pneumonia is not just a straightforward infection but a complex respiratory syndrome stemming from multiple bacterial, chemical, and immunologic causes that might not respond to antibiotics alone, they added.

This study was funded by the U.K. National Institute for Health Research. Dr. Kalra and associates reported having no relevant financial disclosures.

Prophylactic antibiotics don’t prevent poststroke pneumonia or reduce mortality, even in patients who have stroke-induced dysphagia and are at high risk of aspiration, according to a report published in the Lancet.

In a prospective open-label cluster-randomized clinical trial, researchers randomly assigned 37 stroke units in the United Kingdom to give new patients either prophylactic antibiotics for 7 days plus standard stroke care (564 patients) or standard stroke care alone (524 patients). All study participants were considered “unsafe to swallow” because they had impaired consciousness, they failed a bedside swallow test, or they had a nasogastric tube, said Lalit Kalra, Ph.D., of the department of basic and clinical neurosciences and the Institute of Psychiatry, Psychology, and Neuroscience at King’s College, London, and his associates.

Each hospital was allowed to choose which prophylactic antibiotics to use according to their local guidelines, as well as which dosage and route of administration. The primary outcome was the incidence of post-stroke pneumonia within 2 weeks of hospitalization, which was assessed by two separate methods: a statistician masked to treatment assignment diagnosed pneumonia according to a criteria-based hierarchical algorithm, and a local treating physician diagnosed pneumonia according to clinical findings.

According to the algorithm, poststroke pneumonia developed in 13% of patients given prophylactic antibiotics and 10% of the control group, for an OR of 1.21. According to the clinical findings, poststroke pneumonia developed in 16% of the intervention group and 15% of the control group, for an OR of 1.01. By either definition, prophylactic antibiotics failed to reduce the incidence of poststroke pneumonia, the investigators said (Lancet 2015;386:1835-44).

In addition, all-cause mortality at 14 days (10%) and at 90 days (39%) was not significantly different between the two study groups. And there was no significant difference in the percentage of patients with good functional outcomes. Prophylactic antibiotics were associated with longer hospital stays than standard treatment.

On the positive side, prophylactic antibiotics did reduce the number of nonpneumonia infections, especially urosepsis.

Adverse effects, including cases of Clostridium difficile-positive diarrhea and MRSA colonization, were rare and occurred in equal numbers across the two study groups.

The findings indicate that routine use of antibiotics to prevent poststroke pneumonia “cannot be recommended and should be used judiciously ... in patients after stroke who are managed on stroke units, even if they are at high risk of aspiration,” Dr. Kalra and associates said.

The most likely explanation for this study’s negative findings is that prophylactic antibiotics “do not add to existing preventive measures such as positioning, regular suction, swallowing techniques, modified diets, and early initiation of antibiotics” if patients are suspected of developing pneumonia. It also is possible that poststroke pneumonia is not just a straightforward infection but a complex respiratory syndrome stemming from multiple bacterial, chemical, and immunologic causes that might not respond to antibiotics alone, they added.

This study was funded by the U.K. National Institute for Health Research. Dr. Kalra and associates reported having no relevant financial disclosures.

Several successive genetic alterations have been identified that underlie the progression of melanoma from benign nevus to invasive malignancy, with different melanoma subtypes showing distinct evolutionary trajectories, according to a report published online Nov. 12 in the New England Journal of Medicine.

This discovery can serve as the basis for formulating refined criteria for diagnosing melanoma and predicting its clinical course. It also “revealed an intermediate category of melanocytic neoplasia, characterized by the presence of more than one pathogenic genetic alteration – a finding that helps to resolve the decades-long controversy about dysplastic nevi,” wrote A. Hunter Shain, Ph.D., of the departments of dermatology and pathology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, and his associates.

©Christian Jasiuk/Thinkstock

Many of the pathogenic mutations in melanoma have already been catalogued, but the order in which they occur has never been defined before. “An individual tumor cannot be readily studied as it progresses from benign to malignant,” the investigators explained.

They approached the problem by comparing tissue samples from individual melanomas and melanoma precursor lesions across a spectrum of pathologic levels in different patients. They analyzed 37 melanocytic neoplasms archived at UCSF, St.John’s Hospital in London, and University Hospital Zurich, microdissecting 150 distinct areas of these samples for genetic sequencing. Eight dermatopathologists independently categorized the samples histologically as probably benign, intermediate but probably benign, intermediate but probably malignant, or malignant melanoma.

The investigators discovered “a more or less consistent pattern of genetic changes.” In every case, a single mutation was identified as the putative initiating oncogene. These were always mutations already known to activate the MAPK signaling pathway, usually in the BRAF or NRAS genes.

More advanced lesions harbored a broader spectrum of additional mutations that contributed to progression. Often these mutations affected the TERT promoter region, the CDKN2A gene and similar genes encoding particular protein subunits, or the tumor-suppressor ARID1A gene. A total of 77% of the areas examined in these intermediate tumors and melanomas in situ harbored TERT promoter mutations, which indicates that these mutations occur “at an unexpectedly early stage of the neoplastic progression,” Dr. Shain and his associates said (N Engl J Med. 2015 Nov 12. doi: 10.1056/NEJMoa1502583).

Only invasive melanomas were characterized by loss of both copies of the CDKN2A gene. Similarly, mutations in the SWI/SNF chromatin remodeling genes emerged primarily at the invasive stage. And losses in the PTEN and TP53 genes occurred exclusively in the thickest invasive melanomas, implying that these mutations occur late in the process of tumor progression. In addition, melanocytic neoplasms transitioned from linear to branched evolution only at later stages of progression, they said.

The investigators noted that “the existence of a category of lesions residing between clearly benign and clearly malignant states has long been proposed, but has remained controversial.” This study demonstrates that these intermediate neoplasms not only exist, but also carry discrete genetic alterations. “Detailed follow-up studies will be necessary to specifically delineate their histopathological characteristics and determine whether genetic or morphologic features can be identified that determine the risk of their progression to melanoma,” they added.

This study was supported by the National Institutes of Health and the Gerson and Barbara Bass Bakar Distinguished Professorship in Cancer Research. Dr. Shain reported having no relevant financial disclosures; one of his associates reported receiving grant support and personal fees from Novartis, Bristol-Myers Squibb, Roche, GlaxoSmithKline, Merck Sharp & Dohme, and Amgen.

Several successive genetic alterations have been identified that underlie the progression of melanoma from benign nevus to invasive malignancy, with different melanoma subtypes showing distinct evolutionary trajectories, according to a report published online Nov. 12 in the New England Journal of Medicine.

This discovery can serve as the basis for formulating refined criteria for diagnosing melanoma and predicting its clinical course. It also “revealed an intermediate category of melanocytic neoplasia, characterized by the presence of more than one pathogenic genetic alteration – a finding that helps to resolve the decades-long controversy about dysplastic nevi,” wrote A. Hunter Shain, Ph.D., of the departments of dermatology and pathology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, and his associates.

©Christian Jasiuk/Thinkstock

Many of the pathogenic mutations in melanoma have already been catalogued, but the order in which they occur has never been defined before. “An individual tumor cannot be readily studied as it progresses from benign to malignant,” the investigators explained.

They approached the problem by comparing tissue samples from individual melanomas and melanoma precursor lesions across a spectrum of pathologic levels in different patients. They analyzed 37 melanocytic neoplasms archived at UCSF, St.John’s Hospital in London, and University Hospital Zurich, microdissecting 150 distinct areas of these samples for genetic sequencing. Eight dermatopathologists independently categorized the samples histologically as probably benign, intermediate but probably benign, intermediate but probably malignant, or malignant melanoma.

The investigators discovered “a more or less consistent pattern of genetic changes.” In every case, a single mutation was identified as the putative initiating oncogene. These were always mutations already known to activate the MAPK signaling pathway, usually in the BRAF or NRAS genes.

More advanced lesions harbored a broader spectrum of additional mutations that contributed to progression. Often these mutations affected the TERT promoter region, the CDKN2A gene and similar genes encoding particular protein subunits, or the tumor-suppressor ARID1A gene. A total of 77% of the areas examined in these intermediate tumors and melanomas in situ harbored TERT promoter mutations, which indicates that these mutations occur “at an unexpectedly early stage of the neoplastic progression,” Dr. Shain and his associates said (N Engl J Med. 2015 Nov 12. doi: 10.1056/NEJMoa1502583).

Only invasive melanomas were characterized by loss of both copies of the CDKN2A gene. Similarly, mutations in the SWI/SNF chromatin remodeling genes emerged primarily at the invasive stage. And losses in the PTEN and TP53 genes occurred exclusively in the thickest invasive melanomas, implying that these mutations occur late in the process of tumor progression. In addition, melanocytic neoplasms transitioned from linear to branched evolution only at later stages of progression, they said.

The investigators noted that “the existence of a category of lesions residing between clearly benign and clearly malignant states has long been proposed, but has remained controversial.” This study demonstrates that these intermediate neoplasms not only exist, but also carry discrete genetic alterations. “Detailed follow-up studies will be necessary to specifically delineate their histopathological characteristics and determine whether genetic or morphologic features can be identified that determine the risk of their progression to melanoma,” they added.

This study was supported by the National Institutes of Health and the Gerson and Barbara Bass Bakar Distinguished Professorship in Cancer Research. Dr. Shain reported having no relevant financial disclosures; one of his associates reported receiving grant support and personal fees from Novartis, Bristol-Myers Squibb, Roche, GlaxoSmithKline, Merck Sharp & Dohme, and Amgen.

Several successive genetic alterations have been identified that underlie the progression of melanoma from benign nevus to invasive malignancy, with different melanoma subtypes showing distinct evolutionary trajectories, according to a report published online Nov. 12 in the New England Journal of Medicine.

This discovery can serve as the basis for formulating refined criteria for diagnosing melanoma and predicting its clinical course. It also “revealed an intermediate category of melanocytic neoplasia, characterized by the presence of more than one pathogenic genetic alteration – a finding that helps to resolve the decades-long controversy about dysplastic nevi,” wrote A. Hunter Shain, Ph.D., of the departments of dermatology and pathology and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, and his associates.

©Christian Jasiuk/Thinkstock

Many of the pathogenic mutations in melanoma have already been catalogued, but the order in which they occur has never been defined before. “An individual tumor cannot be readily studied as it progresses from benign to malignant,” the investigators explained.

They approached the problem by comparing tissue samples from individual melanomas and melanoma precursor lesions across a spectrum of pathologic levels in different patients. They analyzed 37 melanocytic neoplasms archived at UCSF, St.John’s Hospital in London, and University Hospital Zurich, microdissecting 150 distinct areas of these samples for genetic sequencing. Eight dermatopathologists independently categorized the samples histologically as probably benign, intermediate but probably benign, intermediate but probably malignant, or malignant melanoma.

The investigators discovered “a more or less consistent pattern of genetic changes.” In every case, a single mutation was identified as the putative initiating oncogene. These were always mutations already known to activate the MAPK signaling pathway, usually in the BRAF or NRAS genes.

More advanced lesions harbored a broader spectrum of additional mutations that contributed to progression. Often these mutations affected the TERT promoter region, the CDKN2A gene and similar genes encoding particular protein subunits, or the tumor-suppressor ARID1A gene. A total of 77% of the areas examined in these intermediate tumors and melanomas in situ harbored TERT promoter mutations, which indicates that these mutations occur “at an unexpectedly early stage of the neoplastic progression,” Dr. Shain and his associates said (N Engl J Med. 2015 Nov 12. doi: 10.1056/NEJMoa1502583).

Only invasive melanomas were characterized by loss of both copies of the CDKN2A gene. Similarly, mutations in the SWI/SNF chromatin remodeling genes emerged primarily at the invasive stage. And losses in the PTEN and TP53 genes occurred exclusively in the thickest invasive melanomas, implying that these mutations occur late in the process of tumor progression. In addition, melanocytic neoplasms transitioned from linear to branched evolution only at later stages of progression, they said.

The investigators noted that “the existence of a category of lesions residing between clearly benign and clearly malignant states has long been proposed, but has remained controversial.” This study demonstrates that these intermediate neoplasms not only exist, but also carry discrete genetic alterations. “Detailed follow-up studies will be necessary to specifically delineate their histopathological characteristics and determine whether genetic or morphologic features can be identified that determine the risk of their progression to melanoma,” they added.

This study was supported by the National Institutes of Health and the Gerson and Barbara Bass Bakar Distinguished Professorship in Cancer Research. Dr. Shain reported having no relevant financial disclosures; one of his associates reported receiving grant support and personal fees from Novartis, Bristol-Myers Squibb, Roche, GlaxoSmithKline, Merck Sharp & Dohme, and Amgen.

Coronary stent implantation guided by intravascular ultrasound reduces the 1-year rate of major adverse cardiac events in patients who have long lesions, compared with standard angiography-guided stent implantation, Dr. Sung-Jin Hong reported at the American Heart Association annual scientific sessions, a presentation that was simultaneously published online Nov. 10 in JAMA.

Even though four meta-analyses have demonstrated the superiority of IVUS-guided implantation and recent guidelines recommend IVUS guidance for select patients to optimize results, “the effect of IVUS-guided drug-eluting stent implantation on clinical outcomes remains uncertain because of the limited number of properly powered randomized clinical trials,” said Dr. Hong of Sanggye Paik Hospital at Inje University and of Severance Cardiovascular Hospital at Yonsei University, both in Seoul, South Korea.

Dr. Hong and his associates performed a 4-year industry-sponsored randomized trial comparing the two techniques in 1,400 patients who had typical chest pain or evidence of myocardial ischemia and were eligible to receive an everolimus-eluting stent of 28 mm or more in length. The study participants were randomly assigned to undergo either IVUS-guided (700 patients) or angiography-guided (700 patients) stent implantation at 20 Korean medical centers and were followed up for 1 year. The mean patient age was 64 years, and 69% of the participants were men. The mean stent length of the targeted lesions was 39.3 mm.

The primary endpoint – a composite of major adverse cardiac events such as death, target-lesion-related MI, or ischemia-driven revascularization of the target lesion at 1 year – occurred in 2.9% of the IVUS group and 5.8% of the angiography group. This is a significant difference, with the IVUS group showing a 2.9% absolute reduction and a 48% relative reduction in the primary endpoint, the investigators said (JAMA 2015 Nov 10. doi: 10.1001/jama.2015.15454).

The superiority of IVUS-guided stent implantation was attributable primarily to a marked decrease in target-lesion revascularization in that group (2.5% of patients) compared with the angiography-guided group (5.0%). This in turn was likely due to the fact that adjunctive poststent balloon dilation was done more frequently in the IVUS group (76% vs 57%) and that the mean final balloon size was larger. Consequently, the minimum lumen diameter was greater in the IVUS-guided stent group than in the angiography-guided stent group.

“To our knowledge, [this] is the first demonstration of the clinical benefit of IVUS guidance in second-generation drug-eluting stent implantation in an adequately powered randomized clinical trial,” the investigators added.

Coronary stent implantation guided by intravascular ultrasound reduces the 1-year rate of major adverse cardiac events in patients who have long lesions, compared with standard angiography-guided stent implantation, Dr. Sung-Jin Hong reported at the American Heart Association annual scientific sessions, a presentation that was simultaneously published online Nov. 10 in JAMA.

Even though four meta-analyses have demonstrated the superiority of IVUS-guided implantation and recent guidelines recommend IVUS guidance for select patients to optimize results, “the effect of IVUS-guided drug-eluting stent implantation on clinical outcomes remains uncertain because of the limited number of properly powered randomized clinical trials,” said Dr. Hong of Sanggye Paik Hospital at Inje University and of Severance Cardiovascular Hospital at Yonsei University, both in Seoul, South Korea.

Dr. Hong and his associates performed a 4-year industry-sponsored randomized trial comparing the two techniques in 1,400 patients who had typical chest pain or evidence of myocardial ischemia and were eligible to receive an everolimus-eluting stent of 28 mm or more in length. The study participants were randomly assigned to undergo either IVUS-guided (700 patients) or angiography-guided (700 patients) stent implantation at 20 Korean medical centers and were followed up for 1 year. The mean patient age was 64 years, and 69% of the participants were men. The mean stent length of the targeted lesions was 39.3 mm.

The primary endpoint – a composite of major adverse cardiac events such as death, target-lesion-related MI, or ischemia-driven revascularization of the target lesion at 1 year – occurred in 2.9% of the IVUS group and 5.8% of the angiography group. This is a significant difference, with the IVUS group showing a 2.9% absolute reduction and a 48% relative reduction in the primary endpoint, the investigators said (JAMA 2015 Nov 10. doi: 10.1001/jama.2015.15454).

The superiority of IVUS-guided stent implantation was attributable primarily to a marked decrease in target-lesion revascularization in that group (2.5% of patients) compared with the angiography-guided group (5.0%). This in turn was likely due to the fact that adjunctive poststent balloon dilation was done more frequently in the IVUS group (76% vs 57%) and that the mean final balloon size was larger. Consequently, the minimum lumen diameter was greater in the IVUS-guided stent group than in the angiography-guided stent group.

“To our knowledge, [this] is the first demonstration of the clinical benefit of IVUS guidance in second-generation drug-eluting stent implantation in an adequately powered randomized clinical trial,” the investigators added.

Coronary stent implantation guided by intravascular ultrasound reduces the 1-year rate of major adverse cardiac events in patients who have long lesions, compared with standard angiography-guided stent implantation, Dr. Sung-Jin Hong reported at the American Heart Association annual scientific sessions, a presentation that was simultaneously published online Nov. 10 in JAMA.

Even though four meta-analyses have demonstrated the superiority of IVUS-guided implantation and recent guidelines recommend IVUS guidance for select patients to optimize results, “the effect of IVUS-guided drug-eluting stent implantation on clinical outcomes remains uncertain because of the limited number of properly powered randomized clinical trials,” said Dr. Hong of Sanggye Paik Hospital at Inje University and of Severance Cardiovascular Hospital at Yonsei University, both in Seoul, South Korea.

Dr. Hong and his associates performed a 4-year industry-sponsored randomized trial comparing the two techniques in 1,400 patients who had typical chest pain or evidence of myocardial ischemia and were eligible to receive an everolimus-eluting stent of 28 mm or more in length. The study participants were randomly assigned to undergo either IVUS-guided (700 patients) or angiography-guided (700 patients) stent implantation at 20 Korean medical centers and were followed up for 1 year. The mean patient age was 64 years, and 69% of the participants were men. The mean stent length of the targeted lesions was 39.3 mm.

The primary endpoint – a composite of major adverse cardiac events such as death, target-lesion-related MI, or ischemia-driven revascularization of the target lesion at 1 year – occurred in 2.9% of the IVUS group and 5.8% of the angiography group. This is a significant difference, with the IVUS group showing a 2.9% absolute reduction and a 48% relative reduction in the primary endpoint, the investigators said (JAMA 2015 Nov 10. doi: 10.1001/jama.2015.15454).

The superiority of IVUS-guided stent implantation was attributable primarily to a marked decrease in target-lesion revascularization in that group (2.5% of patients) compared with the angiography-guided group (5.0%). This in turn was likely due to the fact that adjunctive poststent balloon dilation was done more frequently in the IVUS group (76% vs 57%) and that the mean final balloon size was larger. Consequently, the minimum lumen diameter was greater in the IVUS-guided stent group than in the angiography-guided stent group.

“To our knowledge, [this] is the first demonstration of the clinical benefit of IVUS guidance in second-generation drug-eluting stent implantation in an adequately powered randomized clinical trial,” the investigators added.