Adjunctive azithromycin cuts postcesarean infection

Is azithromycin especially beneficial in obese mothers?
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Adjunctive azithromycin cuts postcesarean infection

Adding a single intravenous dose of azithromycin to standard antibiotic prophylaxis further reduces maternal infections without increasing neonatal adverse outcomes after nonelective cesarean delivery, according to a report published in the New England Journal of Medicine.

The adjunctive azithromycin also significantly decreased rates of postpartum fever and of readmission or unscheduled office visits, wrote Alan T.N. Tita, MD, PhD, of the University of Alabama at Birmingham, and his colleagues.

Dr. Alan T.N. Tita

Recent studies have suggested that extended-spectrum prophylaxis using azithromycin, when added to standard cephalosporin prophylaxis, would further reduce the incidence of post-cesarean infection, chiefly because of azithromycin’s coverage of ureaplasma species that are frequently associated with these infections. The C/SOAP (Cesarean Section Optimal Antibiotic Prophylaxis) trial tested this hypothesis in 2,013 women who underwent nonelective cesarean delivery of singleton neonates at 14 U.S. hospitals during a 3.5-year period.

All the women received standard antibiotic prophylaxis (usually with cefazolin) and were randomly assigned to receive either a 500-mg dose of azithromycin (1,019 participants) or a matching placebo (994 participants) before surgical incision.

The primary outcome measure – a composite of endometritis; wound infection; or other infections such as abdominopelvic abscess, maternal sepsis, pelvic septic thrombophlebitis, pyelonephritis, pneumonia, or meningitis occurring up to 6 weeks after surgery – developed in half as many women in the azithromycin group (6.1%) as in the placebo group (12.0%). The relative risk (RR) was 0.51 (P less than .001).

Azithromycin, in particular, was associated with significantly lower rates of endometritis (3.8% vs. 6.1%; RR, 0.62; P = .02) and wound infection (2.4% vs. 6.6%; RR, 0.35; P less than .001). This benefit extended across all subgroups of patients regardless of study site, maternal obesity status, the presence or absence of membrane rupture at randomization, preterm or term delivery, or maternal diabetes status.

The number of patients who would need to be treated to prevent one study outcome was 17 for the primary outcome, 43 for endometritis, and 24 for wound infections, the researchers reported (N Engl J Med. 2016 Sep 29;375:1231-41).

Serious maternal adverse events also were less common with azithromycin (1.5%) than with placebo (2.9%). Neonatal outcomes did not differ between the study groups. The rate of combined neonatal death or complications was 14.3% with azithromycin and 13.6% with placebo, a nonsignificant difference.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Pfizer donated the azithromycin used in the trial. Dr. Tita reported having no relevant financial disclosures; his colleagues reported ties to numerous industry sources.

References

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This well-designed, pragmatic, multicenter trial shows that a single adjunctive dose of azithromycin likely would reduce the number of infectious complications for women undergoing nonelective cesarean section.

The addition of azithromycin may have been particularly effective for the 73% of this study population who had a body mass index of 30 kg/m2 or more. Obesity is known to double the risk of infectious complications, and previous studies have suggested that cefazolin may be underdosed in women with increased BMI values. It appears that azithromycin improved outcomes on the basis of the additive effects of the two drugs against common surgical pathogens, such as staphylococcus species. Information provided in the Supplementary Appendix accompanying the article indicates that routine bacterial cultures, when done, were much-less-frequently positive in the azithromycin group.

Robert A. Weinstein, MD, and Kenneth M. Boyer, MD, are at Rush University Medical Center and Cook County Health and Hospital System, both in Chicago. Dr. Weinstein reported receiving support from Merck outside of this work, and Dr. Boyer reported having no relevant financial disclosures. These remarks are adapted from an accompanying editorial (N Engl J Med. 2016 Sept 29. doi: 10.1056/NEJMe1610010).

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This well-designed, pragmatic, multicenter trial shows that a single adjunctive dose of azithromycin likely would reduce the number of infectious complications for women undergoing nonelective cesarean section.

The addition of azithromycin may have been particularly effective for the 73% of this study population who had a body mass index of 30 kg/m2 or more. Obesity is known to double the risk of infectious complications, and previous studies have suggested that cefazolin may be underdosed in women with increased BMI values. It appears that azithromycin improved outcomes on the basis of the additive effects of the two drugs against common surgical pathogens, such as staphylococcus species. Information provided in the Supplementary Appendix accompanying the article indicates that routine bacterial cultures, when done, were much-less-frequently positive in the azithromycin group.

Robert A. Weinstein, MD, and Kenneth M. Boyer, MD, are at Rush University Medical Center and Cook County Health and Hospital System, both in Chicago. Dr. Weinstein reported receiving support from Merck outside of this work, and Dr. Boyer reported having no relevant financial disclosures. These remarks are adapted from an accompanying editorial (N Engl J Med. 2016 Sept 29. doi: 10.1056/NEJMe1610010).

Body

This well-designed, pragmatic, multicenter trial shows that a single adjunctive dose of azithromycin likely would reduce the number of infectious complications for women undergoing nonelective cesarean section.

The addition of azithromycin may have been particularly effective for the 73% of this study population who had a body mass index of 30 kg/m2 or more. Obesity is known to double the risk of infectious complications, and previous studies have suggested that cefazolin may be underdosed in women with increased BMI values. It appears that azithromycin improved outcomes on the basis of the additive effects of the two drugs against common surgical pathogens, such as staphylococcus species. Information provided in the Supplementary Appendix accompanying the article indicates that routine bacterial cultures, when done, were much-less-frequently positive in the azithromycin group.

Robert A. Weinstein, MD, and Kenneth M. Boyer, MD, are at Rush University Medical Center and Cook County Health and Hospital System, both in Chicago. Dr. Weinstein reported receiving support from Merck outside of this work, and Dr. Boyer reported having no relevant financial disclosures. These remarks are adapted from an accompanying editorial (N Engl J Med. 2016 Sept 29. doi: 10.1056/NEJMe1610010).

Title
Is azithromycin especially beneficial in obese mothers?
Is azithromycin especially beneficial in obese mothers?

Adding a single intravenous dose of azithromycin to standard antibiotic prophylaxis further reduces maternal infections without increasing neonatal adverse outcomes after nonelective cesarean delivery, according to a report published in the New England Journal of Medicine.

The adjunctive azithromycin also significantly decreased rates of postpartum fever and of readmission or unscheduled office visits, wrote Alan T.N. Tita, MD, PhD, of the University of Alabama at Birmingham, and his colleagues.

Dr. Alan T.N. Tita

Recent studies have suggested that extended-spectrum prophylaxis using azithromycin, when added to standard cephalosporin prophylaxis, would further reduce the incidence of post-cesarean infection, chiefly because of azithromycin’s coverage of ureaplasma species that are frequently associated with these infections. The C/SOAP (Cesarean Section Optimal Antibiotic Prophylaxis) trial tested this hypothesis in 2,013 women who underwent nonelective cesarean delivery of singleton neonates at 14 U.S. hospitals during a 3.5-year period.

All the women received standard antibiotic prophylaxis (usually with cefazolin) and were randomly assigned to receive either a 500-mg dose of azithromycin (1,019 participants) or a matching placebo (994 participants) before surgical incision.

The primary outcome measure – a composite of endometritis; wound infection; or other infections such as abdominopelvic abscess, maternal sepsis, pelvic septic thrombophlebitis, pyelonephritis, pneumonia, or meningitis occurring up to 6 weeks after surgery – developed in half as many women in the azithromycin group (6.1%) as in the placebo group (12.0%). The relative risk (RR) was 0.51 (P less than .001).

Azithromycin, in particular, was associated with significantly lower rates of endometritis (3.8% vs. 6.1%; RR, 0.62; P = .02) and wound infection (2.4% vs. 6.6%; RR, 0.35; P less than .001). This benefit extended across all subgroups of patients regardless of study site, maternal obesity status, the presence or absence of membrane rupture at randomization, preterm or term delivery, or maternal diabetes status.

The number of patients who would need to be treated to prevent one study outcome was 17 for the primary outcome, 43 for endometritis, and 24 for wound infections, the researchers reported (N Engl J Med. 2016 Sep 29;375:1231-41).

Serious maternal adverse events also were less common with azithromycin (1.5%) than with placebo (2.9%). Neonatal outcomes did not differ between the study groups. The rate of combined neonatal death or complications was 14.3% with azithromycin and 13.6% with placebo, a nonsignificant difference.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Pfizer donated the azithromycin used in the trial. Dr. Tita reported having no relevant financial disclosures; his colleagues reported ties to numerous industry sources.

Adding a single intravenous dose of azithromycin to standard antibiotic prophylaxis further reduces maternal infections without increasing neonatal adverse outcomes after nonelective cesarean delivery, according to a report published in the New England Journal of Medicine.

The adjunctive azithromycin also significantly decreased rates of postpartum fever and of readmission or unscheduled office visits, wrote Alan T.N. Tita, MD, PhD, of the University of Alabama at Birmingham, and his colleagues.

Dr. Alan T.N. Tita

Recent studies have suggested that extended-spectrum prophylaxis using azithromycin, when added to standard cephalosporin prophylaxis, would further reduce the incidence of post-cesarean infection, chiefly because of azithromycin’s coverage of ureaplasma species that are frequently associated with these infections. The C/SOAP (Cesarean Section Optimal Antibiotic Prophylaxis) trial tested this hypothesis in 2,013 women who underwent nonelective cesarean delivery of singleton neonates at 14 U.S. hospitals during a 3.5-year period.

All the women received standard antibiotic prophylaxis (usually with cefazolin) and were randomly assigned to receive either a 500-mg dose of azithromycin (1,019 participants) or a matching placebo (994 participants) before surgical incision.

The primary outcome measure – a composite of endometritis; wound infection; or other infections such as abdominopelvic abscess, maternal sepsis, pelvic septic thrombophlebitis, pyelonephritis, pneumonia, or meningitis occurring up to 6 weeks after surgery – developed in half as many women in the azithromycin group (6.1%) as in the placebo group (12.0%). The relative risk (RR) was 0.51 (P less than .001).

Azithromycin, in particular, was associated with significantly lower rates of endometritis (3.8% vs. 6.1%; RR, 0.62; P = .02) and wound infection (2.4% vs. 6.6%; RR, 0.35; P less than .001). This benefit extended across all subgroups of patients regardless of study site, maternal obesity status, the presence or absence of membrane rupture at randomization, preterm or term delivery, or maternal diabetes status.

The number of patients who would need to be treated to prevent one study outcome was 17 for the primary outcome, 43 for endometritis, and 24 for wound infections, the researchers reported (N Engl J Med. 2016 Sep 29;375:1231-41).

Serious maternal adverse events also were less common with azithromycin (1.5%) than with placebo (2.9%). Neonatal outcomes did not differ between the study groups. The rate of combined neonatal death or complications was 14.3% with azithromycin and 13.6% with placebo, a nonsignificant difference.

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Pfizer donated the azithromycin used in the trial. Dr. Tita reported having no relevant financial disclosures; his colleagues reported ties to numerous industry sources.

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CSF2RB mutation, common in Ashkenazim, linked to Crohn’s

Discovery could pave way to studies on Crohn’s disease development
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CSF2RB mutation, common in Ashkenazim, linked to Crohn’s

A frameshift mutation in the CSF2RB gene that is common in Ashkenazi Jews has been linked to Crohn’s disease, according to a report in Gastroenterology.

The Ashkenazi Jewish population has a four- to sevenfold higher prevalence of Crohn’s disease than does the general population. To identify possible genetic mutations associated with the disease, researchers performed exome sequencing of samples from 1,477 Ashkenazi Jewish patients with Crohn’s disease and 2,614 Ashkenazi Jewish control subjects who didn’t have the disorder. All the study participants were enrolled at medical centers throughout North America, Europe, and Israel, noted Ling-Shiang Chuang, PhD, a postdoctoral fellow in genetics and genomic sciences, Mount Sinai Medical Center, New York, and his associates.

They genotyped 224 frameshift mutations and identified one in the colony-stimulating factor 2–receptor beta common subunit (CSF2RB) gene that was significantly associated with Crohn’s disease. They validated this association in a replication cohort of 1,515 Ashkenazi Jewish patients with Crohn’s disease and 7,052 health Ashkenazi control subjects, observing nearly identical allele frequencies and odds ratios as in the discovery cohort.

 

©SilverV/Thinkstock.com

Since the CSF2RB gene encodes for the receptor for GM-CSF (granulocyte-macrophage colony-stimulating factor) cytokines, the mutation would be expected to reduce GM-CSF signaling in monocytes obtained from carriers. The investigators found this was true when they examined monocytes taken from intestinal-tissue samples and peripheral-blood samples from affected patients.

“The present findings of a loss-of-function frameshift variant in the CSF2RB gene argue for a primary pathogenic role of decreased GM-CSF signaling in driving a subset of Crohn’s disease cases. As many as 30% of cases have increased levels of anti-GM-CSF antibodies, which can neutralize GM-CSF activity, indicating that impaired GM-CSF signaling plays a major role in Crohn’s disease,” Dr. Chuang and his associates wrote (Gastroenterol. 2016;151:710-23.e2. doi: 10.1053/j.gastro.2016.06.045).

Future research may identify subgroups of Crohn’s patients in which treatments that target GM-CSF signaling may be effective, and it may also point the way to novel therapies for the broader population of patients with Crohn’s disease, they added.

This study was supported by the National Institutes of Health, the Inflammatory Bowel Disease Genetics Consortium, the Genetic Research Center at Mount Sinai Medical Center, New York’s Crohn’s Foundation, and several others. Dr. Chuang and his associates reported having no relevant financial disclosures.

Body

Genome-wide association studies (GWASs) have identified over 200 DNA mutations (mainly single nucleotide polymorphisms, SNPs) contributing to inflammatory bowel disease. However, their causality in IBD remains unknown. In the post-GWAS era, functional characterization and mechanistic elucidation of these SNPs is a major challenge. SNPs impacting the protein-coding genes can drastically alter protein function and play an important role in molecular pathogenesis. However, most SNPs are in noncoding genes and their impact on gene regulation and disease outcome remains largely unknown. This study reveals a frameshift mutation in the CSF2RB gene associated with Crohn’s disease in an Ashkenazi Jewish population. A frameshift mutation results in the deletion or insertion in a DNA sequence that shifts the way the sequence is transcribed into RNA. The most well described frameshift mutation in Crohn’s disease with clinical relevance is in the NOD2 gene, which results in impaired immune response to microbial stimuli. Because GWASs show association not causality, the biological consequence of the CSF2RB frameshift mutation in intestinal macrophages leads to a decrease in its response to granulocyte-monocyte stimulating factor (GM-CSF) providing a potential mechanistic role for the mutation in Crohn’s disease pathogenesis in a disease-relevant cell and site. This study will pave the way for future important studies that reveal the impact of SNPs on Crohn’s disease development, prognosis, and eventually response to therapy.

Shehzad Z. Sheikh MD, PhD, assistant professor of medicine, department of medicine, division of gastroenterology and hepatology, University of North Carolina, Chapel Hill.

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Genome-wide association studies (GWASs) have identified over 200 DNA mutations (mainly single nucleotide polymorphisms, SNPs) contributing to inflammatory bowel disease. However, their causality in IBD remains unknown. In the post-GWAS era, functional characterization and mechanistic elucidation of these SNPs is a major challenge. SNPs impacting the protein-coding genes can drastically alter protein function and play an important role in molecular pathogenesis. However, most SNPs are in noncoding genes and their impact on gene regulation and disease outcome remains largely unknown. This study reveals a frameshift mutation in the CSF2RB gene associated with Crohn’s disease in an Ashkenazi Jewish population. A frameshift mutation results in the deletion or insertion in a DNA sequence that shifts the way the sequence is transcribed into RNA. The most well described frameshift mutation in Crohn’s disease with clinical relevance is in the NOD2 gene, which results in impaired immune response to microbial stimuli. Because GWASs show association not causality, the biological consequence of the CSF2RB frameshift mutation in intestinal macrophages leads to a decrease in its response to granulocyte-monocyte stimulating factor (GM-CSF) providing a potential mechanistic role for the mutation in Crohn’s disease pathogenesis in a disease-relevant cell and site. This study will pave the way for future important studies that reveal the impact of SNPs on Crohn’s disease development, prognosis, and eventually response to therapy.

Shehzad Z. Sheikh MD, PhD, assistant professor of medicine, department of medicine, division of gastroenterology and hepatology, University of North Carolina, Chapel Hill.

Body

Genome-wide association studies (GWASs) have identified over 200 DNA mutations (mainly single nucleotide polymorphisms, SNPs) contributing to inflammatory bowel disease. However, their causality in IBD remains unknown. In the post-GWAS era, functional characterization and mechanistic elucidation of these SNPs is a major challenge. SNPs impacting the protein-coding genes can drastically alter protein function and play an important role in molecular pathogenesis. However, most SNPs are in noncoding genes and their impact on gene regulation and disease outcome remains largely unknown. This study reveals a frameshift mutation in the CSF2RB gene associated with Crohn’s disease in an Ashkenazi Jewish population. A frameshift mutation results in the deletion or insertion in a DNA sequence that shifts the way the sequence is transcribed into RNA. The most well described frameshift mutation in Crohn’s disease with clinical relevance is in the NOD2 gene, which results in impaired immune response to microbial stimuli. Because GWASs show association not causality, the biological consequence of the CSF2RB frameshift mutation in intestinal macrophages leads to a decrease in its response to granulocyte-monocyte stimulating factor (GM-CSF) providing a potential mechanistic role for the mutation in Crohn’s disease pathogenesis in a disease-relevant cell and site. This study will pave the way for future important studies that reveal the impact of SNPs on Crohn’s disease development, prognosis, and eventually response to therapy.

Shehzad Z. Sheikh MD, PhD, assistant professor of medicine, department of medicine, division of gastroenterology and hepatology, University of North Carolina, Chapel Hill.

Title
Discovery could pave way to studies on Crohn’s disease development
Discovery could pave way to studies on Crohn’s disease development

A frameshift mutation in the CSF2RB gene that is common in Ashkenazi Jews has been linked to Crohn’s disease, according to a report in Gastroenterology.

The Ashkenazi Jewish population has a four- to sevenfold higher prevalence of Crohn’s disease than does the general population. To identify possible genetic mutations associated with the disease, researchers performed exome sequencing of samples from 1,477 Ashkenazi Jewish patients with Crohn’s disease and 2,614 Ashkenazi Jewish control subjects who didn’t have the disorder. All the study participants were enrolled at medical centers throughout North America, Europe, and Israel, noted Ling-Shiang Chuang, PhD, a postdoctoral fellow in genetics and genomic sciences, Mount Sinai Medical Center, New York, and his associates.

They genotyped 224 frameshift mutations and identified one in the colony-stimulating factor 2–receptor beta common subunit (CSF2RB) gene that was significantly associated with Crohn’s disease. They validated this association in a replication cohort of 1,515 Ashkenazi Jewish patients with Crohn’s disease and 7,052 health Ashkenazi control subjects, observing nearly identical allele frequencies and odds ratios as in the discovery cohort.

 

©SilverV/Thinkstock.com

Since the CSF2RB gene encodes for the receptor for GM-CSF (granulocyte-macrophage colony-stimulating factor) cytokines, the mutation would be expected to reduce GM-CSF signaling in monocytes obtained from carriers. The investigators found this was true when they examined monocytes taken from intestinal-tissue samples and peripheral-blood samples from affected patients.

“The present findings of a loss-of-function frameshift variant in the CSF2RB gene argue for a primary pathogenic role of decreased GM-CSF signaling in driving a subset of Crohn’s disease cases. As many as 30% of cases have increased levels of anti-GM-CSF antibodies, which can neutralize GM-CSF activity, indicating that impaired GM-CSF signaling plays a major role in Crohn’s disease,” Dr. Chuang and his associates wrote (Gastroenterol. 2016;151:710-23.e2. doi: 10.1053/j.gastro.2016.06.045).

Future research may identify subgroups of Crohn’s patients in which treatments that target GM-CSF signaling may be effective, and it may also point the way to novel therapies for the broader population of patients with Crohn’s disease, they added.

This study was supported by the National Institutes of Health, the Inflammatory Bowel Disease Genetics Consortium, the Genetic Research Center at Mount Sinai Medical Center, New York’s Crohn’s Foundation, and several others. Dr. Chuang and his associates reported having no relevant financial disclosures.

A frameshift mutation in the CSF2RB gene that is common in Ashkenazi Jews has been linked to Crohn’s disease, according to a report in Gastroenterology.

The Ashkenazi Jewish population has a four- to sevenfold higher prevalence of Crohn’s disease than does the general population. To identify possible genetic mutations associated with the disease, researchers performed exome sequencing of samples from 1,477 Ashkenazi Jewish patients with Crohn’s disease and 2,614 Ashkenazi Jewish control subjects who didn’t have the disorder. All the study participants were enrolled at medical centers throughout North America, Europe, and Israel, noted Ling-Shiang Chuang, PhD, a postdoctoral fellow in genetics and genomic sciences, Mount Sinai Medical Center, New York, and his associates.

They genotyped 224 frameshift mutations and identified one in the colony-stimulating factor 2–receptor beta common subunit (CSF2RB) gene that was significantly associated with Crohn’s disease. They validated this association in a replication cohort of 1,515 Ashkenazi Jewish patients with Crohn’s disease and 7,052 health Ashkenazi control subjects, observing nearly identical allele frequencies and odds ratios as in the discovery cohort.

 

©SilverV/Thinkstock.com

Since the CSF2RB gene encodes for the receptor for GM-CSF (granulocyte-macrophage colony-stimulating factor) cytokines, the mutation would be expected to reduce GM-CSF signaling in monocytes obtained from carriers. The investigators found this was true when they examined monocytes taken from intestinal-tissue samples and peripheral-blood samples from affected patients.

“The present findings of a loss-of-function frameshift variant in the CSF2RB gene argue for a primary pathogenic role of decreased GM-CSF signaling in driving a subset of Crohn’s disease cases. As many as 30% of cases have increased levels of anti-GM-CSF antibodies, which can neutralize GM-CSF activity, indicating that impaired GM-CSF signaling plays a major role in Crohn’s disease,” Dr. Chuang and his associates wrote (Gastroenterol. 2016;151:710-23.e2. doi: 10.1053/j.gastro.2016.06.045).

Future research may identify subgroups of Crohn’s patients in which treatments that target GM-CSF signaling may be effective, and it may also point the way to novel therapies for the broader population of patients with Crohn’s disease, they added.

This study was supported by the National Institutes of Health, the Inflammatory Bowel Disease Genetics Consortium, the Genetic Research Center at Mount Sinai Medical Center, New York’s Crohn’s Foundation, and several others. Dr. Chuang and his associates reported having no relevant financial disclosures.

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Key clinical point: A frameshift mutation in the CSF2RB gene that is common in Ashkenazi Jews has been linked to Crohn’s disease.

Major finding: Genotyping of 224 frameshift mutations identified one in the colony-stimulating factor 2–receptor common subunit (CSF2RB) gene that was significantly associated with Crohn’s disease.

Data source: Exome sequencing and genotype analyses of samples from 1,477 Ashkenazi Jewish people with Crohn’s disease and 2,614 without it.

Disclosures: This study was supported by the National Institutes of Health, the Inflammatory Bowel Disease Genetics Consortium, the Genetic Research Center at Mount Sinai Medical Center, New York’s Crohn’s Foundation, and several others. Dr. Chuang and his associates reported having no relevant financial disclosures.

Simple interventions markedly improve hepatitis care

Interventions can be adopted widely
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Simple interventions markedly improve hepatitis care

Several simple, inexpensive operational interventions substantially improve care for viral hepatitis, according to a report published in the Lancet.

Recent advances in treatment for chronic hepatitis B and chronic hepatitis C have the potential to halt or even reverse the progression of associated liver disease and to reduce related mortality, reported Kali Zhou, MD, of the division of gastroenterology, University of California, San Francisco, and her associates. But they can do so only if affected individuals are engaged and retained in the relatively long continuum of care, from diagnosis through viral suppression or cure.

To assess the usefulness of interventions that promote such patient engagement and retention, Dr. Zhou and her colleagues reviewed the scientific literature and performed a meta-analysis of 56 studies. They examined 15 studies on HBV care, 38 on HCV care, and 3 on both types of hepatitis (Lancet Infect Dis. 2016 Sep 5. doi: 10.1016/S1473-3099[16]30208-0).

Among their findings:

• Educating a single lay health worker to improve knowledge about the disease in his or her community and to promote diagnostic testing nearly tripled the testing rate (relative risk, 2.68), compared with no such intervention.

• Clinician reminders during regular office visits to consider hepatitis testing – such as prompts in the patients’ electronic medical records or stickers on their charts – nearly quadrupled the testing rate (RR, 3.70), compared with no clinician reminders.

• Providing guided referral to a hepatitis specialist for people at risk for the disorder markedly improved the rate of visits to such specialists (RR, 1.57), compared with no such referrals.

• Providing psychological counseling and motivational therapy for mental health and/or substance misuse problems along with medical care for hepatitis dramatically increased the number of patients treated (OR, 3.42) and raised the rate of treatment completion (RR, 1.14).

• Combining mental health, substance misuse, and hepatitis treatment services at one location increased the rate of treatment initiation (RR, 1.36), treatment adherence (RR, 1.22), and cure as measured by sustained virologic response rate (RR, 1.21), compared with usual care.

These interventions might be useful in augmenting hepatitis treatment programs worldwide, Dr. Zhou and her associates said.

The World Health Organization and the U.S. Fulbright Program supported the study. Dr. Zhou and her associates reported having no relevant financial disclosures.

Body

This meta-analysis identified proven strategies that can be adopted widely and can become standard components of a package of health care services for viral hepatitis.

But it also revealed the need for additional high-quality data to guide the development of even more such strategies. Reducing the burden of hepatitis depends on helping patients navigate through diagnosis; referral to specialist care; completion of complex, long-term treatment; and linkages to related clinical services such as mental health or substance misuse counseling.

John W. Ward, MD, is director of the division of viral hepatitis at the Centers for Disease Control and Prevention, Atlanta. He reported having no relevant financial disclosures. Dr. Ward made these remarks in a comment accompanying Dr. Zhou’s report (Lancet. 2016 Sep 5; doi: 10.1016/S1473-3099[16]30272-9).

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This meta-analysis identified proven strategies that can be adopted widely and can become standard components of a package of health care services for viral hepatitis.

But it also revealed the need for additional high-quality data to guide the development of even more such strategies. Reducing the burden of hepatitis depends on helping patients navigate through diagnosis; referral to specialist care; completion of complex, long-term treatment; and linkages to related clinical services such as mental health or substance misuse counseling.

John W. Ward, MD, is director of the division of viral hepatitis at the Centers for Disease Control and Prevention, Atlanta. He reported having no relevant financial disclosures. Dr. Ward made these remarks in a comment accompanying Dr. Zhou’s report (Lancet. 2016 Sep 5; doi: 10.1016/S1473-3099[16]30272-9).

Body

This meta-analysis identified proven strategies that can be adopted widely and can become standard components of a package of health care services for viral hepatitis.

But it also revealed the need for additional high-quality data to guide the development of even more such strategies. Reducing the burden of hepatitis depends on helping patients navigate through diagnosis; referral to specialist care; completion of complex, long-term treatment; and linkages to related clinical services such as mental health or substance misuse counseling.

John W. Ward, MD, is director of the division of viral hepatitis at the Centers for Disease Control and Prevention, Atlanta. He reported having no relevant financial disclosures. Dr. Ward made these remarks in a comment accompanying Dr. Zhou’s report (Lancet. 2016 Sep 5; doi: 10.1016/S1473-3099[16]30272-9).

Title
Interventions can be adopted widely
Interventions can be adopted widely

Several simple, inexpensive operational interventions substantially improve care for viral hepatitis, according to a report published in the Lancet.

Recent advances in treatment for chronic hepatitis B and chronic hepatitis C have the potential to halt or even reverse the progression of associated liver disease and to reduce related mortality, reported Kali Zhou, MD, of the division of gastroenterology, University of California, San Francisco, and her associates. But they can do so only if affected individuals are engaged and retained in the relatively long continuum of care, from diagnosis through viral suppression or cure.

To assess the usefulness of interventions that promote such patient engagement and retention, Dr. Zhou and her colleagues reviewed the scientific literature and performed a meta-analysis of 56 studies. They examined 15 studies on HBV care, 38 on HCV care, and 3 on both types of hepatitis (Lancet Infect Dis. 2016 Sep 5. doi: 10.1016/S1473-3099[16]30208-0).

Among their findings:

• Educating a single lay health worker to improve knowledge about the disease in his or her community and to promote diagnostic testing nearly tripled the testing rate (relative risk, 2.68), compared with no such intervention.

• Clinician reminders during regular office visits to consider hepatitis testing – such as prompts in the patients’ electronic medical records or stickers on their charts – nearly quadrupled the testing rate (RR, 3.70), compared with no clinician reminders.

• Providing guided referral to a hepatitis specialist for people at risk for the disorder markedly improved the rate of visits to such specialists (RR, 1.57), compared with no such referrals.

• Providing psychological counseling and motivational therapy for mental health and/or substance misuse problems along with medical care for hepatitis dramatically increased the number of patients treated (OR, 3.42) and raised the rate of treatment completion (RR, 1.14).

• Combining mental health, substance misuse, and hepatitis treatment services at one location increased the rate of treatment initiation (RR, 1.36), treatment adherence (RR, 1.22), and cure as measured by sustained virologic response rate (RR, 1.21), compared with usual care.

These interventions might be useful in augmenting hepatitis treatment programs worldwide, Dr. Zhou and her associates said.

The World Health Organization and the U.S. Fulbright Program supported the study. Dr. Zhou and her associates reported having no relevant financial disclosures.

Several simple, inexpensive operational interventions substantially improve care for viral hepatitis, according to a report published in the Lancet.

Recent advances in treatment for chronic hepatitis B and chronic hepatitis C have the potential to halt or even reverse the progression of associated liver disease and to reduce related mortality, reported Kali Zhou, MD, of the division of gastroenterology, University of California, San Francisco, and her associates. But they can do so only if affected individuals are engaged and retained in the relatively long continuum of care, from diagnosis through viral suppression or cure.

To assess the usefulness of interventions that promote such patient engagement and retention, Dr. Zhou and her colleagues reviewed the scientific literature and performed a meta-analysis of 56 studies. They examined 15 studies on HBV care, 38 on HCV care, and 3 on both types of hepatitis (Lancet Infect Dis. 2016 Sep 5. doi: 10.1016/S1473-3099[16]30208-0).

Among their findings:

• Educating a single lay health worker to improve knowledge about the disease in his or her community and to promote diagnostic testing nearly tripled the testing rate (relative risk, 2.68), compared with no such intervention.

• Clinician reminders during regular office visits to consider hepatitis testing – such as prompts in the patients’ electronic medical records or stickers on their charts – nearly quadrupled the testing rate (RR, 3.70), compared with no clinician reminders.

• Providing guided referral to a hepatitis specialist for people at risk for the disorder markedly improved the rate of visits to such specialists (RR, 1.57), compared with no such referrals.

• Providing psychological counseling and motivational therapy for mental health and/or substance misuse problems along with medical care for hepatitis dramatically increased the number of patients treated (OR, 3.42) and raised the rate of treatment completion (RR, 1.14).

• Combining mental health, substance misuse, and hepatitis treatment services at one location increased the rate of treatment initiation (RR, 1.36), treatment adherence (RR, 1.22), and cure as measured by sustained virologic response rate (RR, 1.21), compared with usual care.

These interventions might be useful in augmenting hepatitis treatment programs worldwide, Dr. Zhou and her associates said.

The World Health Organization and the U.S. Fulbright Program supported the study. Dr. Zhou and her associates reported having no relevant financial disclosures.

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Key clinical point: Several simple, inexpensive operational interventions substantially improve care for viral hepatitis.

Major finding: Clinician reminders during regular office visits to consider hepatitis testing – such as prompts in the patients’ electronic medical records or stickers on their charts – nearly quadrupled the testing rate (relative risk, 3.70).

Data source: A meta-analysis of 56 studies worldwide assessing interventions to improve HBV and HCV care.

Disclosures: The World Health Organization and the U.S. Fulbright Program supported the study. Dr. Zhou and her associates reported having no relevant financial disclosures.

Benefits of early endovascular thrombectomy outlined in five trials

Investigate approaches to shorten times further
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Mon, 01/07/2019 - 12:44
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Benefits of early endovascular thrombectomy outlined in five trials

For patients with large-vessel ischemic stroke, endovascular thrombectomy produces better functional outcomes at 90 days than does optimal medical therapy, as long as the procedure is started within 7.3 hours of symptom onset, according to a report published online Sept. 27 in JAMA.

The benefit of thrombectomy was greatest when the procedure was begun under 2 hours from symptom onset, and it became nonsignificant after 7 hours and 18 minutes elapsed. This emphasizes “the importance of programs to enhance patient awareness, out-of-hospital care, and in-hospital management to shorten symptom onset-to-treatment times,” wrote Jeffrey L. Saver, MD, of the University of California, Los Angeles, and his associates.

Dr. Jeffrey L. Saver

Five major randomized trials have demonstrated the benefit of second-generation endovascular recanalization therapies over medical therapy in this patient population, but uncertainties persist regarding the timing of the intervention. For example, practice guidelines in the United States recommend thrombectomy until 6 hours after symptom onset, but the Food and Drug Administration allows thrombectomy devices to be used up to 8 hours after symptom onset and Canadian guidelines recommend the procedure for selected patients up to 12 hours after symptom onset.

The investigators for the five trials formed the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration to pool their individual patient data and perform a meta-analysis to clarify the issue of timing. They assessed patients’ functional independence at 90 days using the modified Rankin Score (mRS). The study participants included 634 patients who had been randomly assigned to endovascular thrombectomy and 653 randomly assigned to medical therapy.

The intervention correlated with a substantially lower degree of patient disability at 90 days than did medical therapy: the mean mRS was 2.9 in the thrombectomy group and 3.6 in the medical therapy group. In addition, increasing delays in treatment were associated with higher levels of residual disability in the thrombectomy group but not in the medical therapy group, the investigators reported.

“Based on the current study, and assuming the findings are generalizable to the population of patients with acute ischemic stroke due to large-vessel occlusion, among every 1,000 patients achieving substantial endovascular reperfusion, for every 15-minute faster ED door-to-reperfusion time, an estimated 39 patients would have a less-disabled outcome at 3 months, including 25 more who would achieve functional independence (mRS 0-2),” Dr. Saver and his associates wrote (JAMA. 2016;316[12]:1279-88).

These findings reinforce current recommendations to attempt endovascular thrombectomy when the procedure can be initiated within 6 hours of symptom onset, and they also “provide evidence that potentially supports strengthening of the recommendation for treatment from 6 through 7.3 hours after symptom onset,” they added.

No specific sponsor of this study was cited. Dr. Saver reported ties to Medtronic, Stryker, Cognition Medical, Covidien, Neuravi, BrainsGate, Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, ZZ Biotech, St. Jude Medical, and Genentech. His associates reported ties to numerous industry sources.

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Earlier thrombectomy has such a profound effect on stroke patients’ outcomes that substantial changes in the current medical system are warranted to shorten these times even further. In this study, median time from symptom onset to randomization was approximately 3 hours, median time to arterial puncture was approximately 4 hours, and median time to reperfusion was nearly 5 hours.

Reducing the number of patients who are transferred from community hospitals to facilities with stroke centers would shorten door-to-reperfusion time a great deal. It is estimated that direct transport to stroke centers would allow endovascular thrombectomy for an additional 13% of stroke patients. Telemedicine, mobile stroke units, and out-of-hospital administration of tissue plasminogen activator are other possibilities that should be investigated.

Steven Warach, MD, PhD, and S. Claiborne Johnston, MD, PhD, are with the University of Texas at Austin. They reported having no relevant financial disclosures. Dr. Warach and Dr. Johnston made these remarks in an editorial (JAMA. 2016;316[12]:1265-6) accompanying Dr. Saver’s report.

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Earlier thrombectomy has such a profound effect on stroke patients’ outcomes that substantial changes in the current medical system are warranted to shorten these times even further. In this study, median time from symptom onset to randomization was approximately 3 hours, median time to arterial puncture was approximately 4 hours, and median time to reperfusion was nearly 5 hours.

Reducing the number of patients who are transferred from community hospitals to facilities with stroke centers would shorten door-to-reperfusion time a great deal. It is estimated that direct transport to stroke centers would allow endovascular thrombectomy for an additional 13% of stroke patients. Telemedicine, mobile stroke units, and out-of-hospital administration of tissue plasminogen activator are other possibilities that should be investigated.

Steven Warach, MD, PhD, and S. Claiborne Johnston, MD, PhD, are with the University of Texas at Austin. They reported having no relevant financial disclosures. Dr. Warach and Dr. Johnston made these remarks in an editorial (JAMA. 2016;316[12]:1265-6) accompanying Dr. Saver’s report.

Body

Earlier thrombectomy has such a profound effect on stroke patients’ outcomes that substantial changes in the current medical system are warranted to shorten these times even further. In this study, median time from symptom onset to randomization was approximately 3 hours, median time to arterial puncture was approximately 4 hours, and median time to reperfusion was nearly 5 hours.

Reducing the number of patients who are transferred from community hospitals to facilities with stroke centers would shorten door-to-reperfusion time a great deal. It is estimated that direct transport to stroke centers would allow endovascular thrombectomy for an additional 13% of stroke patients. Telemedicine, mobile stroke units, and out-of-hospital administration of tissue plasminogen activator are other possibilities that should be investigated.

Steven Warach, MD, PhD, and S. Claiborne Johnston, MD, PhD, are with the University of Texas at Austin. They reported having no relevant financial disclosures. Dr. Warach and Dr. Johnston made these remarks in an editorial (JAMA. 2016;316[12]:1265-6) accompanying Dr. Saver’s report.

Title
Investigate approaches to shorten times further
Investigate approaches to shorten times further

For patients with large-vessel ischemic stroke, endovascular thrombectomy produces better functional outcomes at 90 days than does optimal medical therapy, as long as the procedure is started within 7.3 hours of symptom onset, according to a report published online Sept. 27 in JAMA.

The benefit of thrombectomy was greatest when the procedure was begun under 2 hours from symptom onset, and it became nonsignificant after 7 hours and 18 minutes elapsed. This emphasizes “the importance of programs to enhance patient awareness, out-of-hospital care, and in-hospital management to shorten symptom onset-to-treatment times,” wrote Jeffrey L. Saver, MD, of the University of California, Los Angeles, and his associates.

Dr. Jeffrey L. Saver

Five major randomized trials have demonstrated the benefit of second-generation endovascular recanalization therapies over medical therapy in this patient population, but uncertainties persist regarding the timing of the intervention. For example, practice guidelines in the United States recommend thrombectomy until 6 hours after symptom onset, but the Food and Drug Administration allows thrombectomy devices to be used up to 8 hours after symptom onset and Canadian guidelines recommend the procedure for selected patients up to 12 hours after symptom onset.

The investigators for the five trials formed the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration to pool their individual patient data and perform a meta-analysis to clarify the issue of timing. They assessed patients’ functional independence at 90 days using the modified Rankin Score (mRS). The study participants included 634 patients who had been randomly assigned to endovascular thrombectomy and 653 randomly assigned to medical therapy.

The intervention correlated with a substantially lower degree of patient disability at 90 days than did medical therapy: the mean mRS was 2.9 in the thrombectomy group and 3.6 in the medical therapy group. In addition, increasing delays in treatment were associated with higher levels of residual disability in the thrombectomy group but not in the medical therapy group, the investigators reported.

“Based on the current study, and assuming the findings are generalizable to the population of patients with acute ischemic stroke due to large-vessel occlusion, among every 1,000 patients achieving substantial endovascular reperfusion, for every 15-minute faster ED door-to-reperfusion time, an estimated 39 patients would have a less-disabled outcome at 3 months, including 25 more who would achieve functional independence (mRS 0-2),” Dr. Saver and his associates wrote (JAMA. 2016;316[12]:1279-88).

These findings reinforce current recommendations to attempt endovascular thrombectomy when the procedure can be initiated within 6 hours of symptom onset, and they also “provide evidence that potentially supports strengthening of the recommendation for treatment from 6 through 7.3 hours after symptom onset,” they added.

No specific sponsor of this study was cited. Dr. Saver reported ties to Medtronic, Stryker, Cognition Medical, Covidien, Neuravi, BrainsGate, Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, ZZ Biotech, St. Jude Medical, and Genentech. His associates reported ties to numerous industry sources.

For patients with large-vessel ischemic stroke, endovascular thrombectomy produces better functional outcomes at 90 days than does optimal medical therapy, as long as the procedure is started within 7.3 hours of symptom onset, according to a report published online Sept. 27 in JAMA.

The benefit of thrombectomy was greatest when the procedure was begun under 2 hours from symptom onset, and it became nonsignificant after 7 hours and 18 minutes elapsed. This emphasizes “the importance of programs to enhance patient awareness, out-of-hospital care, and in-hospital management to shorten symptom onset-to-treatment times,” wrote Jeffrey L. Saver, MD, of the University of California, Los Angeles, and his associates.

Dr. Jeffrey L. Saver

Five major randomized trials have demonstrated the benefit of second-generation endovascular recanalization therapies over medical therapy in this patient population, but uncertainties persist regarding the timing of the intervention. For example, practice guidelines in the United States recommend thrombectomy until 6 hours after symptom onset, but the Food and Drug Administration allows thrombectomy devices to be used up to 8 hours after symptom onset and Canadian guidelines recommend the procedure for selected patients up to 12 hours after symptom onset.

The investigators for the five trials formed the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration to pool their individual patient data and perform a meta-analysis to clarify the issue of timing. They assessed patients’ functional independence at 90 days using the modified Rankin Score (mRS). The study participants included 634 patients who had been randomly assigned to endovascular thrombectomy and 653 randomly assigned to medical therapy.

The intervention correlated with a substantially lower degree of patient disability at 90 days than did medical therapy: the mean mRS was 2.9 in the thrombectomy group and 3.6 in the medical therapy group. In addition, increasing delays in treatment were associated with higher levels of residual disability in the thrombectomy group but not in the medical therapy group, the investigators reported.

“Based on the current study, and assuming the findings are generalizable to the population of patients with acute ischemic stroke due to large-vessel occlusion, among every 1,000 patients achieving substantial endovascular reperfusion, for every 15-minute faster ED door-to-reperfusion time, an estimated 39 patients would have a less-disabled outcome at 3 months, including 25 more who would achieve functional independence (mRS 0-2),” Dr. Saver and his associates wrote (JAMA. 2016;316[12]:1279-88).

These findings reinforce current recommendations to attempt endovascular thrombectomy when the procedure can be initiated within 6 hours of symptom onset, and they also “provide evidence that potentially supports strengthening of the recommendation for treatment from 6 through 7.3 hours after symptom onset,” they added.

No specific sponsor of this study was cited. Dr. Saver reported ties to Medtronic, Stryker, Cognition Medical, Covidien, Neuravi, BrainsGate, Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, ZZ Biotech, St. Jude Medical, and Genentech. His associates reported ties to numerous industry sources.

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Benefits of early endovascular thrombectomy outlined in five trials
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Key clinical point: Endovascular thrombectomy started within 7.3 hours of symptom onset for large-vessel ischemic stroke produces better outcomes than does optimal medical therapy.

Major finding: For every 15-minute shorter door-to-reperfusion time, an estimated 39 patients would have a less-disabled outcome at 3 months, including 25 more who would achieve functional independence.

Data source: A meta-analysis of pooled data from five randomized clinical trials involving 1,287 patients.

Disclosures: No specific sponsor of this study was cited. Dr. Saver reported ties to Medtronic, Stryker, Cognition Medical, Covidien, Neuravi, BrainsGate, Pfizer, Bristol Myers Squibb, Boehringer Ingelheim, ZZ Biotech, St. Jude Medical, and Genentech. His associates reported ties to numerous industry sources.

10-year follow-up: Localized prostate cancer treatments offer similar efficacy

More metastasis with active monitoring
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Fri, 01/18/2019 - 16:13
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10-year follow-up: Localized prostate cancer treatments offer similar efficacy

The three main approaches for treating localized prostate cancer – surgery, radiotherapy, or active monitoring – yield similar efficacy outcomes but different quality-of-life outcomes, according to two reports published on the New England Journal of Medicine.

Both reports present the findings of the ongoing Protect (Prostate Testing for Cancer and Treatment) trial, a large prospective, randomized trial in the United Kingdom comparing mortality and other health outcomes in men with PSA-detected localized disease. The trial involved 82,429 men aged 50-69 years who had a PSA test between 1999 and 2009, of whom 2,664 were found to have localized prostate cancer. A total of 1,643 of these participants agreed to be randomly assigned to radical prostatectomy (553 men), radical radiotherapy (545 men), or active monitoring (545 men).

©Mark Kostich/Thinkstock

“Active monitoring” involved avoiding any immediate therapy and regularly monitoring disease progression so that radical treatment with curative intent could be given if the need arose. Patients were monitored every 3 months for the first year, then every 6-12 months thereafter. This differs from “watchful waiting,” which doesn’t involve any plan for curative radical treatment if disease progresses.

The first report focused on mortality and disease progression in these 1,643 participants at a median of 10 years of follow-up. The primary outcome measure, prostate cancer–specific survival, was 98.8% or greater across all three study groups, and there was no significant difference among them. Thus, all three approaches yielded the same efficacy: prostate cancer–specific mortality of approximately 1%, said Freddie C. Hamdy, MD, of the Nuffield Department of Surgical Sciences, University of Oxford, and his associates.

However, the rate of disease progression among men assigned to surgery (8.9/1,000 person-years) or to radiotherapy (9.0/1,000 person-years) was less than half the rate among men assigned to active monitoring (22.9/1,000 person-years). The rate of metastasis followed this same pattern (2.4, 3.0, and 6.3 per 1,000 person-years, respectively).

“These differences show the effectiveness of immediate radical therapy over active monitoring, but they have not translated into significant differences – nor have they ruled out equivalence – in disease-specific or all-cause mortality; thus, longer-term follow-up is necessary,” Dr. Hamdy and his associates said (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606220).

The trade-off was that 44% of the men assigned to active monitoring were able to forgo both radical surgery and radical radiotherapy, avoiding the adverse effects of those treatments. These included nine thromboembolic or cardiovascular events, 14 transfusions, one rectal injury, and nine anastomotic problems requiring intervention, they noted.

It is important to remember that approximately one-fourth of the men assigned to active monitoring went on to undergo radical treatment within 3 years, and that more than half did so by the 10-year follow-up date, the investigators added.

The second report focused on patient-reported outcomes concerning urinary, bowel, sexual, and quality-of-life issues in the 1,643 participants at 6 years of follow-up. These differed markedly among the three study groups, said Jenny L. Donovan, PhD, of the School of Social and Community Medicine, University of Bristol, U.K., and her associates.

Prostatectomy had a clear negative effect on urinary continence and sexual function, particularly erectile function, compared with radiotherapy and active monitoring. This peaked at 6 months after surgery, and though some patients recovered some function over time, urinary incontinence remained worse in the prostatectomy group than in the other two groups throughout follow-up. The use of absorbent pads rose from 1% at baseline to 46% at 6 months in the prostatectomy group. In comparison, the 6-month rate in the radiotherapy group rose to only 5% and that in the active-monitoring group to only 4%.

Radiotherapy plus neoadjuvant androgen-deprivation therapy had more of a negative effect on bowel function, urinary voiding, and nocturia than did the other two treatment approaches. However, many patients eventually showed considerable recovery on most of these measures, except that they continued to have bloody stools more frequently than did men who had prostatectomy or active monitoring.

Men in the active-monitoring group had substantially less difficulty with urinary, sexual, and bowel function, as expected. However, this gradually worsened over time as increasing numbers of these men eventually underwent radical treatments, Dr. Donovan and her associates wrote (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606221).

Quality-of-life measures generally reflected these differences among the three study groups, “with some evidence of accommodation to changes over time.” General mental and physical health, cancer-specific quality of life, and anxiety and depression all were similar across the three groups at 6 years.

“Follow-up for an additional 5-10 years is required to fully inform decisions involving the trade-off between the shorter-term effects of the management strategies shown here and the longer course of progression and treatment of prostate cancer in the context of other life-threatening conditions,” they said.

 

 

The Protect trial was supported by the U.K. National Institute for Health Research Health Technology Assessment Programme, the University of Oxford, University Hospitals Bristol, the Oxford NIHR Biomedical Research Centre, and the Cancer Research U.K. Oxford Centre. Dr. Hamdy and Dr. Donovan and their associates reported having no relevant financial disclosures.

References

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As both groups of researchers noted, longer follow-up is needed to definitively assess outcomes in the Protect trial. For now, however, we can conclude that active monitoring leads to increased metastasis, compared with either surgery or radiotherapy.

So if a man wants to avoid metastatic prostate cancer and the adverse effects of its treatment, active monitoring should be considered only if he has life-shortening, coexisting disease and his life expectancy is less than the 10-year median follow-up of this study.

Men who have low- or intermediate-risk prostate cancer should feel free to select either surgery or radiotherapy on the basis of the treatments’ QOL profiles, since the mortality profiles are equivalent.

Anthony V. D’Amico, MD, is in the department of radiation oncology at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, both in Boston. He reported having no relevant financial disclosures. Dr. D’Amico made these remarks in an editorial accompanying the two reports on the Protect trial (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEHMe1610395).

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Body

As both groups of researchers noted, longer follow-up is needed to definitively assess outcomes in the Protect trial. For now, however, we can conclude that active monitoring leads to increased metastasis, compared with either surgery or radiotherapy.

So if a man wants to avoid metastatic prostate cancer and the adverse effects of its treatment, active monitoring should be considered only if he has life-shortening, coexisting disease and his life expectancy is less than the 10-year median follow-up of this study.

Men who have low- or intermediate-risk prostate cancer should feel free to select either surgery or radiotherapy on the basis of the treatments’ QOL profiles, since the mortality profiles are equivalent.

Anthony V. D’Amico, MD, is in the department of radiation oncology at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, both in Boston. He reported having no relevant financial disclosures. Dr. D’Amico made these remarks in an editorial accompanying the two reports on the Protect trial (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEHMe1610395).

Body

As both groups of researchers noted, longer follow-up is needed to definitively assess outcomes in the Protect trial. For now, however, we can conclude that active monitoring leads to increased metastasis, compared with either surgery or radiotherapy.

So if a man wants to avoid metastatic prostate cancer and the adverse effects of its treatment, active monitoring should be considered only if he has life-shortening, coexisting disease and his life expectancy is less than the 10-year median follow-up of this study.

Men who have low- or intermediate-risk prostate cancer should feel free to select either surgery or radiotherapy on the basis of the treatments’ QOL profiles, since the mortality profiles are equivalent.

Anthony V. D’Amico, MD, is in the department of radiation oncology at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, both in Boston. He reported having no relevant financial disclosures. Dr. D’Amico made these remarks in an editorial accompanying the two reports on the Protect trial (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEHMe1610395).

Title
More metastasis with active monitoring
More metastasis with active monitoring

The three main approaches for treating localized prostate cancer – surgery, radiotherapy, or active monitoring – yield similar efficacy outcomes but different quality-of-life outcomes, according to two reports published on the New England Journal of Medicine.

Both reports present the findings of the ongoing Protect (Prostate Testing for Cancer and Treatment) trial, a large prospective, randomized trial in the United Kingdom comparing mortality and other health outcomes in men with PSA-detected localized disease. The trial involved 82,429 men aged 50-69 years who had a PSA test between 1999 and 2009, of whom 2,664 were found to have localized prostate cancer. A total of 1,643 of these participants agreed to be randomly assigned to radical prostatectomy (553 men), radical radiotherapy (545 men), or active monitoring (545 men).

©Mark Kostich/Thinkstock

“Active monitoring” involved avoiding any immediate therapy and regularly monitoring disease progression so that radical treatment with curative intent could be given if the need arose. Patients were monitored every 3 months for the first year, then every 6-12 months thereafter. This differs from “watchful waiting,” which doesn’t involve any plan for curative radical treatment if disease progresses.

The first report focused on mortality and disease progression in these 1,643 participants at a median of 10 years of follow-up. The primary outcome measure, prostate cancer–specific survival, was 98.8% or greater across all three study groups, and there was no significant difference among them. Thus, all three approaches yielded the same efficacy: prostate cancer–specific mortality of approximately 1%, said Freddie C. Hamdy, MD, of the Nuffield Department of Surgical Sciences, University of Oxford, and his associates.

However, the rate of disease progression among men assigned to surgery (8.9/1,000 person-years) or to radiotherapy (9.0/1,000 person-years) was less than half the rate among men assigned to active monitoring (22.9/1,000 person-years). The rate of metastasis followed this same pattern (2.4, 3.0, and 6.3 per 1,000 person-years, respectively).

“These differences show the effectiveness of immediate radical therapy over active monitoring, but they have not translated into significant differences – nor have they ruled out equivalence – in disease-specific or all-cause mortality; thus, longer-term follow-up is necessary,” Dr. Hamdy and his associates said (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606220).

The trade-off was that 44% of the men assigned to active monitoring were able to forgo both radical surgery and radical radiotherapy, avoiding the adverse effects of those treatments. These included nine thromboembolic or cardiovascular events, 14 transfusions, one rectal injury, and nine anastomotic problems requiring intervention, they noted.

It is important to remember that approximately one-fourth of the men assigned to active monitoring went on to undergo radical treatment within 3 years, and that more than half did so by the 10-year follow-up date, the investigators added.

The second report focused on patient-reported outcomes concerning urinary, bowel, sexual, and quality-of-life issues in the 1,643 participants at 6 years of follow-up. These differed markedly among the three study groups, said Jenny L. Donovan, PhD, of the School of Social and Community Medicine, University of Bristol, U.K., and her associates.

Prostatectomy had a clear negative effect on urinary continence and sexual function, particularly erectile function, compared with radiotherapy and active monitoring. This peaked at 6 months after surgery, and though some patients recovered some function over time, urinary incontinence remained worse in the prostatectomy group than in the other two groups throughout follow-up. The use of absorbent pads rose from 1% at baseline to 46% at 6 months in the prostatectomy group. In comparison, the 6-month rate in the radiotherapy group rose to only 5% and that in the active-monitoring group to only 4%.

Radiotherapy plus neoadjuvant androgen-deprivation therapy had more of a negative effect on bowel function, urinary voiding, and nocturia than did the other two treatment approaches. However, many patients eventually showed considerable recovery on most of these measures, except that they continued to have bloody stools more frequently than did men who had prostatectomy or active monitoring.

Men in the active-monitoring group had substantially less difficulty with urinary, sexual, and bowel function, as expected. However, this gradually worsened over time as increasing numbers of these men eventually underwent radical treatments, Dr. Donovan and her associates wrote (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606221).

Quality-of-life measures generally reflected these differences among the three study groups, “with some evidence of accommodation to changes over time.” General mental and physical health, cancer-specific quality of life, and anxiety and depression all were similar across the three groups at 6 years.

“Follow-up for an additional 5-10 years is required to fully inform decisions involving the trade-off between the shorter-term effects of the management strategies shown here and the longer course of progression and treatment of prostate cancer in the context of other life-threatening conditions,” they said.

 

 

The Protect trial was supported by the U.K. National Institute for Health Research Health Technology Assessment Programme, the University of Oxford, University Hospitals Bristol, the Oxford NIHR Biomedical Research Centre, and the Cancer Research U.K. Oxford Centre. Dr. Hamdy and Dr. Donovan and their associates reported having no relevant financial disclosures.

The three main approaches for treating localized prostate cancer – surgery, radiotherapy, or active monitoring – yield similar efficacy outcomes but different quality-of-life outcomes, according to two reports published on the New England Journal of Medicine.

Both reports present the findings of the ongoing Protect (Prostate Testing for Cancer and Treatment) trial, a large prospective, randomized trial in the United Kingdom comparing mortality and other health outcomes in men with PSA-detected localized disease. The trial involved 82,429 men aged 50-69 years who had a PSA test between 1999 and 2009, of whom 2,664 were found to have localized prostate cancer. A total of 1,643 of these participants agreed to be randomly assigned to radical prostatectomy (553 men), radical radiotherapy (545 men), or active monitoring (545 men).

©Mark Kostich/Thinkstock

“Active monitoring” involved avoiding any immediate therapy and regularly monitoring disease progression so that radical treatment with curative intent could be given if the need arose. Patients were monitored every 3 months for the first year, then every 6-12 months thereafter. This differs from “watchful waiting,” which doesn’t involve any plan for curative radical treatment if disease progresses.

The first report focused on mortality and disease progression in these 1,643 participants at a median of 10 years of follow-up. The primary outcome measure, prostate cancer–specific survival, was 98.8% or greater across all three study groups, and there was no significant difference among them. Thus, all three approaches yielded the same efficacy: prostate cancer–specific mortality of approximately 1%, said Freddie C. Hamdy, MD, of the Nuffield Department of Surgical Sciences, University of Oxford, and his associates.

However, the rate of disease progression among men assigned to surgery (8.9/1,000 person-years) or to radiotherapy (9.0/1,000 person-years) was less than half the rate among men assigned to active monitoring (22.9/1,000 person-years). The rate of metastasis followed this same pattern (2.4, 3.0, and 6.3 per 1,000 person-years, respectively).

“These differences show the effectiveness of immediate radical therapy over active monitoring, but they have not translated into significant differences – nor have they ruled out equivalence – in disease-specific or all-cause mortality; thus, longer-term follow-up is necessary,” Dr. Hamdy and his associates said (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606220).

The trade-off was that 44% of the men assigned to active monitoring were able to forgo both radical surgery and radical radiotherapy, avoiding the adverse effects of those treatments. These included nine thromboembolic or cardiovascular events, 14 transfusions, one rectal injury, and nine anastomotic problems requiring intervention, they noted.

It is important to remember that approximately one-fourth of the men assigned to active monitoring went on to undergo radical treatment within 3 years, and that more than half did so by the 10-year follow-up date, the investigators added.

The second report focused on patient-reported outcomes concerning urinary, bowel, sexual, and quality-of-life issues in the 1,643 participants at 6 years of follow-up. These differed markedly among the three study groups, said Jenny L. Donovan, PhD, of the School of Social and Community Medicine, University of Bristol, U.K., and her associates.

Prostatectomy had a clear negative effect on urinary continence and sexual function, particularly erectile function, compared with radiotherapy and active monitoring. This peaked at 6 months after surgery, and though some patients recovered some function over time, urinary incontinence remained worse in the prostatectomy group than in the other two groups throughout follow-up. The use of absorbent pads rose from 1% at baseline to 46% at 6 months in the prostatectomy group. In comparison, the 6-month rate in the radiotherapy group rose to only 5% and that in the active-monitoring group to only 4%.

Radiotherapy plus neoadjuvant androgen-deprivation therapy had more of a negative effect on bowel function, urinary voiding, and nocturia than did the other two treatment approaches. However, many patients eventually showed considerable recovery on most of these measures, except that they continued to have bloody stools more frequently than did men who had prostatectomy or active monitoring.

Men in the active-monitoring group had substantially less difficulty with urinary, sexual, and bowel function, as expected. However, this gradually worsened over time as increasing numbers of these men eventually underwent radical treatments, Dr. Donovan and her associates wrote (N Engl J Med. 2016 Sep 14. doi: 10.1056/NEJMoa1606221).

Quality-of-life measures generally reflected these differences among the three study groups, “with some evidence of accommodation to changes over time.” General mental and physical health, cancer-specific quality of life, and anxiety and depression all were similar across the three groups at 6 years.

“Follow-up for an additional 5-10 years is required to fully inform decisions involving the trade-off between the shorter-term effects of the management strategies shown here and the longer course of progression and treatment of prostate cancer in the context of other life-threatening conditions,” they said.

 

 

The Protect trial was supported by the U.K. National Institute for Health Research Health Technology Assessment Programme, the University of Oxford, University Hospitals Bristol, the Oxford NIHR Biomedical Research Centre, and the Cancer Research U.K. Oxford Centre. Dr. Hamdy and Dr. Donovan and their associates reported having no relevant financial disclosures.

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10-year follow-up: Localized prostate cancer treatments offer similar efficacy
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Key clinical point: The three main approaches for treating localized prostate cancer yield similar efficacy outcomes but different quality-of-life outcomes.

Major finding: All three treatment approaches – surgery, radiotherapy, and active monitoring – yielded the same efficacy: 10-year prostate cancer–specific mortality of approximately 1%.

Data source: The Protect trial, a prospective randomized study involving 1,643 prostate cancer patients in the U.K. followed for 10 years.

Disclosures: The Protect trial was supported by the U.K. National Institute for Health Research Health Technology Assessment Programme, the University of Oxford, University Hospitals Bristol, the Oxford NIHR Biomedical Research Centre, and the Cancer Research U.K. Oxford Centre. Dr. Hamdy and Dr. Donovan and their associates reported having no relevant financial disclosures.

CSF lactate concentration identifies postneurosurgical bacterial meningitis

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CSF lactate concentration identifies postneurosurgical bacterial meningitis

The concentration of lactate in the cerebrospinal fluid accurately identifies bacterial meningitis that develops after neurosurgery, distinguishing it from other conditions, according to a report published in BMC Infectious Diseases.

In patients who have undergone neurosurgery, failure to promptly identify and treat bacterial meningitis is associated with patient mortality as high as 50%, reported Xiong Xiao of the department of neurosurgery and the China National Clinical Research Center for Neurological Diseases at Beijing Tiantan Hospital and Capital Medical University, Beijing, and associates.

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Neisseria meningitidis colonies are shown on a blood agar plate.

A recent small study suggested that cerebrospinal fluid (CSF) lactate was accurate at differentiating postoperative bacterial meningitis from aseptic meningitis. To examine this possibility in a larger patient population, Dr. Xiao and associates reviewed 1,672 articles in the medical literature. They found few high-quality studies of this topic, but were able to perform a meta-analysis and pool the data from five studies involving 404 postneurosurgical patients treated during a 15-year period.

CSF lactate concentration identified bacterial meningitis with a pooled sensitivity of 92% and a pooled specificity of 88%. “Moreover, this test is fast, simple, objective, and affordable, and can be widely applied in hospitals,” the investigators wrote (BMC Infect Dis. 2016;16:483. doi: 10.1186/s12879-016-1818-2).Larger prospective studies are needed to confirm this finding and to provide a more thorough understanding of the indicators of postneurosurgical meningitis, Dr. Xiao and associates added.

This study was supported by Beijing Tiantan Hospital Funds for Young Scholars, the Ministry of Science and Technology of China, and the Beijing Talents Fund. Dr. Xiao and associates reported having no relevant financial disclosures.

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The concentration of lactate in the cerebrospinal fluid accurately identifies bacterial meningitis that develops after neurosurgery, distinguishing it from other conditions, according to a report published in BMC Infectious Diseases.

In patients who have undergone neurosurgery, failure to promptly identify and treat bacterial meningitis is associated with patient mortality as high as 50%, reported Xiong Xiao of the department of neurosurgery and the China National Clinical Research Center for Neurological Diseases at Beijing Tiantan Hospital and Capital Medical University, Beijing, and associates.

Courtesy CDC
Neisseria meningitidis colonies are shown on a blood agar plate.

A recent small study suggested that cerebrospinal fluid (CSF) lactate was accurate at differentiating postoperative bacterial meningitis from aseptic meningitis. To examine this possibility in a larger patient population, Dr. Xiao and associates reviewed 1,672 articles in the medical literature. They found few high-quality studies of this topic, but were able to perform a meta-analysis and pool the data from five studies involving 404 postneurosurgical patients treated during a 15-year period.

CSF lactate concentration identified bacterial meningitis with a pooled sensitivity of 92% and a pooled specificity of 88%. “Moreover, this test is fast, simple, objective, and affordable, and can be widely applied in hospitals,” the investigators wrote (BMC Infect Dis. 2016;16:483. doi: 10.1186/s12879-016-1818-2).Larger prospective studies are needed to confirm this finding and to provide a more thorough understanding of the indicators of postneurosurgical meningitis, Dr. Xiao and associates added.

This study was supported by Beijing Tiantan Hospital Funds for Young Scholars, the Ministry of Science and Technology of China, and the Beijing Talents Fund. Dr. Xiao and associates reported having no relevant financial disclosures.

The concentration of lactate in the cerebrospinal fluid accurately identifies bacterial meningitis that develops after neurosurgery, distinguishing it from other conditions, according to a report published in BMC Infectious Diseases.

In patients who have undergone neurosurgery, failure to promptly identify and treat bacterial meningitis is associated with patient mortality as high as 50%, reported Xiong Xiao of the department of neurosurgery and the China National Clinical Research Center for Neurological Diseases at Beijing Tiantan Hospital and Capital Medical University, Beijing, and associates.

Courtesy CDC
Neisseria meningitidis colonies are shown on a blood agar plate.

A recent small study suggested that cerebrospinal fluid (CSF) lactate was accurate at differentiating postoperative bacterial meningitis from aseptic meningitis. To examine this possibility in a larger patient population, Dr. Xiao and associates reviewed 1,672 articles in the medical literature. They found few high-quality studies of this topic, but were able to perform a meta-analysis and pool the data from five studies involving 404 postneurosurgical patients treated during a 15-year period.

CSF lactate concentration identified bacterial meningitis with a pooled sensitivity of 92% and a pooled specificity of 88%. “Moreover, this test is fast, simple, objective, and affordable, and can be widely applied in hospitals,” the investigators wrote (BMC Infect Dis. 2016;16:483. doi: 10.1186/s12879-016-1818-2).Larger prospective studies are needed to confirm this finding and to provide a more thorough understanding of the indicators of postneurosurgical meningitis, Dr. Xiao and associates added.

This study was supported by Beijing Tiantan Hospital Funds for Young Scholars, the Ministry of Science and Technology of China, and the Beijing Talents Fund. Dr. Xiao and associates reported having no relevant financial disclosures.

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CSF lactate concentration identifies postneurosurgical bacterial meningitis
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Key clinical point: CSF lactate concentration accurately identifies bacterial meningitis that develops after neurosurgery.

Major finding: CSF lactate concentration identified bacterial meningitis with a pooled sensitivity of 92% and a pooled specificity of 88%.

Data source: A meta-analysis of five published studies involving 404 patients during a 15-year period.

Disclosures: This study was supported by Beijing Tiantan Hospital Funds for Young Scholars, the Ministry of Science and Technology of China, and the Beijing Talents Fund. Dr. Xiao and associates reported having no relevant financial disclosures.

Buprenorphine restrictions don’t hinder addiction therapy

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Buprenorphine restrictions don’t hinder addiction therapy

Restrictions on the number of buprenorphine prescriptions a physician can write in a given year do not hinder addiction treatment, as some had feared, according to a Research Letter published online Sept. 20 in JAMA.

Physicians who wish to treat opioid use disorders using buprenorphine are allowed to prescribe the drug to up to 30 patients during the first year they offer the treatment, and after that, they may request that the limit be increased to 100 patients. Some experts have expressed concern that this requirement may pose a barrier to buprenorphine therapy. To examine this possibility, researchers analyzed information in a database of prescriptions filled at retail pharmacies across the United States.

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The investigators focused on buprenorphine prescriptions filled during a 3-year period in seven states with the highest rates of addiction therapy: California, Florida, Massachusetts, Michigan, New York, Pennsylvania, and Texas. They identified 3,234 physician prescribers and 245,016 patients receiving a new buprenorphine prescription during the study period, said Bradley D. Stein, MD, PhD, of the RAND Corporation, Pittsburgh, and his associates.

A substantial proportion of the physician prescribers – 20% – treated only 1-3 patients, and an additional 49% treated fewer than the 30-patient limit. Only 9% of physician prescribers treated more than 75 patients. So the restrictions on the number of concurrent prescriptions do not appear to pose a barrier to buprenorphine therapy, Dr. Stein and his associates said (JAMA. 2016 Sep 20;316[11]:1211-2).

An unexpected finding was that the median duration of buprenorphine therapy was only 53 days, even though clinical recommendations specify that up to 12 months of treatment is beneficial, and longer duration of therapy is associated with better outcomes.

These findings indicate that strategies for improving access to addiction therapy may not need to target prescription limits, the investigators said.

Dr. Stein and his associates said their research was supported by the National Institute on Drug Abuse. He reported having served on the advisory board of Otsuka Pharmaceuticals, and the other investigators reported receiving royalties from Cambridge University Press and UpToDate.

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Restrictions on the number of buprenorphine prescriptions a physician can write in a given year do not hinder addiction treatment, as some had feared, according to a Research Letter published online Sept. 20 in JAMA.

Physicians who wish to treat opioid use disorders using buprenorphine are allowed to prescribe the drug to up to 30 patients during the first year they offer the treatment, and after that, they may request that the limit be increased to 100 patients. Some experts have expressed concern that this requirement may pose a barrier to buprenorphine therapy. To examine this possibility, researchers analyzed information in a database of prescriptions filled at retail pharmacies across the United States.

©Fuse/Thinkstock

The investigators focused on buprenorphine prescriptions filled during a 3-year period in seven states with the highest rates of addiction therapy: California, Florida, Massachusetts, Michigan, New York, Pennsylvania, and Texas. They identified 3,234 physician prescribers and 245,016 patients receiving a new buprenorphine prescription during the study period, said Bradley D. Stein, MD, PhD, of the RAND Corporation, Pittsburgh, and his associates.

A substantial proportion of the physician prescribers – 20% – treated only 1-3 patients, and an additional 49% treated fewer than the 30-patient limit. Only 9% of physician prescribers treated more than 75 patients. So the restrictions on the number of concurrent prescriptions do not appear to pose a barrier to buprenorphine therapy, Dr. Stein and his associates said (JAMA. 2016 Sep 20;316[11]:1211-2).

An unexpected finding was that the median duration of buprenorphine therapy was only 53 days, even though clinical recommendations specify that up to 12 months of treatment is beneficial, and longer duration of therapy is associated with better outcomes.

These findings indicate that strategies for improving access to addiction therapy may not need to target prescription limits, the investigators said.

Dr. Stein and his associates said their research was supported by the National Institute on Drug Abuse. He reported having served on the advisory board of Otsuka Pharmaceuticals, and the other investigators reported receiving royalties from Cambridge University Press and UpToDate.

Restrictions on the number of buprenorphine prescriptions a physician can write in a given year do not hinder addiction treatment, as some had feared, according to a Research Letter published online Sept. 20 in JAMA.

Physicians who wish to treat opioid use disorders using buprenorphine are allowed to prescribe the drug to up to 30 patients during the first year they offer the treatment, and after that, they may request that the limit be increased to 100 patients. Some experts have expressed concern that this requirement may pose a barrier to buprenorphine therapy. To examine this possibility, researchers analyzed information in a database of prescriptions filled at retail pharmacies across the United States.

©Fuse/Thinkstock

The investigators focused on buprenorphine prescriptions filled during a 3-year period in seven states with the highest rates of addiction therapy: California, Florida, Massachusetts, Michigan, New York, Pennsylvania, and Texas. They identified 3,234 physician prescribers and 245,016 patients receiving a new buprenorphine prescription during the study period, said Bradley D. Stein, MD, PhD, of the RAND Corporation, Pittsburgh, and his associates.

A substantial proportion of the physician prescribers – 20% – treated only 1-3 patients, and an additional 49% treated fewer than the 30-patient limit. Only 9% of physician prescribers treated more than 75 patients. So the restrictions on the number of concurrent prescriptions do not appear to pose a barrier to buprenorphine therapy, Dr. Stein and his associates said (JAMA. 2016 Sep 20;316[11]:1211-2).

An unexpected finding was that the median duration of buprenorphine therapy was only 53 days, even though clinical recommendations specify that up to 12 months of treatment is beneficial, and longer duration of therapy is associated with better outcomes.

These findings indicate that strategies for improving access to addiction therapy may not need to target prescription limits, the investigators said.

Dr. Stein and his associates said their research was supported by the National Institute on Drug Abuse. He reported having served on the advisory board of Otsuka Pharmaceuticals, and the other investigators reported receiving royalties from Cambridge University Press and UpToDate.

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Buprenorphine restrictions don’t hinder addiction therapy
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Key clinical point: Restrictions on the number of buprenorphine prescriptions a physician can write in a given year do not hinder addiction treatment.

Major finding: Most (69%) of physician prescribers treated fewer than the 30-patient limit for buprenorphine prescriptions in a given year

Data source: An analysis of pharmacy data regarding 3,234 buprenorphine prescribers in seven states during a 3-year period.

Disclosures: This work was supported by the National Institute on Drug Abuse. Dr. Stein reported having served on an advisory board of Otsuka Pharmaceuticals; the other investigators reported receiving royalties from Cambridge University Press and UpToDate.

ASCO updates postmastectomy radiotherapy guideline

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ASCO updates postmastectomy radiotherapy guideline

The 2001 American Society of Clinical Oncology clinical practice guideline on postmastectomy radiotherapy has been updated to help clinicians and patients decide which cases of T1-T2 breast cancer with one-three positive axillary lymph nodes will not benefit from the treatment. Recent evidence suggests that some subsets of this patient group are likely to have such a low risk of locoregional recurrence that the potential adverse effects of radiotherapy would outweigh its benefit.

“We still don’t have a single, validated formula that can determine who needs postmastectomy radiotherapy, but we hope that the research evidence summarized in this guideline update will help doctors and patients make more informed decisions,” Abram Recht, MD, cochair of the expert panel that developed the update, said in a press statement.

“Thanks to advances in systemic therapy, fewer women need radiation therapy after a mastectomy. This means we can be more selective when recommending this treatment to our patients,” said Dr. Recht of Beth Israel Deaconess Medical Center, Boston.

ASCO, in collaboration with the American Society for Radiation Oncology and the Society of Surgical Oncology, reviewed the literature since 2001, including a meta-analysis of 22 clinical trials involving 8,135 patients who were randomly assigned to receive or not receive postmastectomy radiotherapy. “Our panel focused on the results for the 3,786 women who underwent axillary dissection.” The 10-year rate of locoregional treatment failure was only 4.3% with irradiation, compared with 21.0% without irradiation. The 10-year rate of local or distant treatment failure was 33.8% with irradiation and 45.5% without it, and the 20-year rates of breast cancer mortality were 41.5% and 49.4%, respectively.

“The panel unanimously agreed that the available evidence shows that postmastectomy radiotherapy reduces the risks of locoregional failure, any recurrence, and breast cancer mortality for patients with T1-T2 breast cancer and one-three positive lymph nodes,” according to the guideline.

However, clinicians and patients “should consider factors that may decrease the risk of locoregional failure, attenuate the benefit of reduced breast cancer–specific mortality, and/or increase the risk of complications.” These include older patient age, limited life expectancy, coexisting conditions that affect the risk of complications, small tumor size, absence of lymphovascular invasion, small nodal metastases, substantial response to neoadjuvant systemic therapy, low tumor grade, or strong tumor sensitivity to hormonal therapy, Dr. Recht and his associates said (J Clin Oncol. 2016 Sep 19. doi: 10.1200/JCO.2016.69.1188).

The guideline also addressed other areas of controversy.

Some clinicians now omit performing axillary lymph node dissection if one-two sentinel nodes are positive, “primarily based on extrapolation of data from randomized trials of patients treated exclusively or predominantly with breast-conserving surgery.” In such cases, the updated guideline “recommends that these patients receive postmastectomy radiotherapy only if there is already sufficient information to justify its use without needing to know that additional axillary nodes are involved.”

Many clinicians are uncertain whether to pursue postmastectomy radiotherapy in patients who have received neoadjuvant systemic therapy, because observational studies suggest the risk of locoregional recurrence is low for those who either have clinically negative nodes before undergoing the treatment or have a complete pathologic response to it in the lymph nodes. The panel decided that current evidence is insufficient to recommend whether radiotherapy should be administered or can be omitted in these groups.

The guideline also recommends that regional nodal irradiation generally should target both the internal mammary and the supraclavicular-axillary apical nodes, in addition to the chest wall or reconstructed breast. “There may be subgroups that will experience limited, if any, benefits from treating both these nodal areas, compared with treating only one or perhaps treating only the chest wall or reconstructed breast. [However,] there is insufficient evidence at this time to define such subgroups in detail.”

Copies of the updated guideline, as well as additional information such as details regarding the panel’s methodology, evidence tables, and clinical tools, are avail at www.asco.org/pmrt-guideline and www.asco.org/guidelineswiki.

This work was supported by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. Dr. Recht reported serving as a consultant or advisor to CareCore and U.S. Oncology and receiving research funding from Genomic Health; his associates reported ties to numerous industry sources.

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The 2001 American Society of Clinical Oncology clinical practice guideline on postmastectomy radiotherapy has been updated to help clinicians and patients decide which cases of T1-T2 breast cancer with one-three positive axillary lymph nodes will not benefit from the treatment. Recent evidence suggests that some subsets of this patient group are likely to have such a low risk of locoregional recurrence that the potential adverse effects of radiotherapy would outweigh its benefit.

“We still don’t have a single, validated formula that can determine who needs postmastectomy radiotherapy, but we hope that the research evidence summarized in this guideline update will help doctors and patients make more informed decisions,” Abram Recht, MD, cochair of the expert panel that developed the update, said in a press statement.

“Thanks to advances in systemic therapy, fewer women need radiation therapy after a mastectomy. This means we can be more selective when recommending this treatment to our patients,” said Dr. Recht of Beth Israel Deaconess Medical Center, Boston.

ASCO, in collaboration with the American Society for Radiation Oncology and the Society of Surgical Oncology, reviewed the literature since 2001, including a meta-analysis of 22 clinical trials involving 8,135 patients who were randomly assigned to receive or not receive postmastectomy radiotherapy. “Our panel focused on the results for the 3,786 women who underwent axillary dissection.” The 10-year rate of locoregional treatment failure was only 4.3% with irradiation, compared with 21.0% without irradiation. The 10-year rate of local or distant treatment failure was 33.8% with irradiation and 45.5% without it, and the 20-year rates of breast cancer mortality were 41.5% and 49.4%, respectively.

“The panel unanimously agreed that the available evidence shows that postmastectomy radiotherapy reduces the risks of locoregional failure, any recurrence, and breast cancer mortality for patients with T1-T2 breast cancer and one-three positive lymph nodes,” according to the guideline.

However, clinicians and patients “should consider factors that may decrease the risk of locoregional failure, attenuate the benefit of reduced breast cancer–specific mortality, and/or increase the risk of complications.” These include older patient age, limited life expectancy, coexisting conditions that affect the risk of complications, small tumor size, absence of lymphovascular invasion, small nodal metastases, substantial response to neoadjuvant systemic therapy, low tumor grade, or strong tumor sensitivity to hormonal therapy, Dr. Recht and his associates said (J Clin Oncol. 2016 Sep 19. doi: 10.1200/JCO.2016.69.1188).

The guideline also addressed other areas of controversy.

Some clinicians now omit performing axillary lymph node dissection if one-two sentinel nodes are positive, “primarily based on extrapolation of data from randomized trials of patients treated exclusively or predominantly with breast-conserving surgery.” In such cases, the updated guideline “recommends that these patients receive postmastectomy radiotherapy only if there is already sufficient information to justify its use without needing to know that additional axillary nodes are involved.”

Many clinicians are uncertain whether to pursue postmastectomy radiotherapy in patients who have received neoadjuvant systemic therapy, because observational studies suggest the risk of locoregional recurrence is low for those who either have clinically negative nodes before undergoing the treatment or have a complete pathologic response to it in the lymph nodes. The panel decided that current evidence is insufficient to recommend whether radiotherapy should be administered or can be omitted in these groups.

The guideline also recommends that regional nodal irradiation generally should target both the internal mammary and the supraclavicular-axillary apical nodes, in addition to the chest wall or reconstructed breast. “There may be subgroups that will experience limited, if any, benefits from treating both these nodal areas, compared with treating only one or perhaps treating only the chest wall or reconstructed breast. [However,] there is insufficient evidence at this time to define such subgroups in detail.”

Copies of the updated guideline, as well as additional information such as details regarding the panel’s methodology, evidence tables, and clinical tools, are avail at www.asco.org/pmrt-guideline and www.asco.org/guidelineswiki.

This work was supported by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. Dr. Recht reported serving as a consultant or advisor to CareCore and U.S. Oncology and receiving research funding from Genomic Health; his associates reported ties to numerous industry sources.

[email protected]

The 2001 American Society of Clinical Oncology clinical practice guideline on postmastectomy radiotherapy has been updated to help clinicians and patients decide which cases of T1-T2 breast cancer with one-three positive axillary lymph nodes will not benefit from the treatment. Recent evidence suggests that some subsets of this patient group are likely to have such a low risk of locoregional recurrence that the potential adverse effects of radiotherapy would outweigh its benefit.

“We still don’t have a single, validated formula that can determine who needs postmastectomy radiotherapy, but we hope that the research evidence summarized in this guideline update will help doctors and patients make more informed decisions,” Abram Recht, MD, cochair of the expert panel that developed the update, said in a press statement.

“Thanks to advances in systemic therapy, fewer women need radiation therapy after a mastectomy. This means we can be more selective when recommending this treatment to our patients,” said Dr. Recht of Beth Israel Deaconess Medical Center, Boston.

ASCO, in collaboration with the American Society for Radiation Oncology and the Society of Surgical Oncology, reviewed the literature since 2001, including a meta-analysis of 22 clinical trials involving 8,135 patients who were randomly assigned to receive or not receive postmastectomy radiotherapy. “Our panel focused on the results for the 3,786 women who underwent axillary dissection.” The 10-year rate of locoregional treatment failure was only 4.3% with irradiation, compared with 21.0% without irradiation. The 10-year rate of local or distant treatment failure was 33.8% with irradiation and 45.5% without it, and the 20-year rates of breast cancer mortality were 41.5% and 49.4%, respectively.

“The panel unanimously agreed that the available evidence shows that postmastectomy radiotherapy reduces the risks of locoregional failure, any recurrence, and breast cancer mortality for patients with T1-T2 breast cancer and one-three positive lymph nodes,” according to the guideline.

However, clinicians and patients “should consider factors that may decrease the risk of locoregional failure, attenuate the benefit of reduced breast cancer–specific mortality, and/or increase the risk of complications.” These include older patient age, limited life expectancy, coexisting conditions that affect the risk of complications, small tumor size, absence of lymphovascular invasion, small nodal metastases, substantial response to neoadjuvant systemic therapy, low tumor grade, or strong tumor sensitivity to hormonal therapy, Dr. Recht and his associates said (J Clin Oncol. 2016 Sep 19. doi: 10.1200/JCO.2016.69.1188).

The guideline also addressed other areas of controversy.

Some clinicians now omit performing axillary lymph node dissection if one-two sentinel nodes are positive, “primarily based on extrapolation of data from randomized trials of patients treated exclusively or predominantly with breast-conserving surgery.” In such cases, the updated guideline “recommends that these patients receive postmastectomy radiotherapy only if there is already sufficient information to justify its use without needing to know that additional axillary nodes are involved.”

Many clinicians are uncertain whether to pursue postmastectomy radiotherapy in patients who have received neoadjuvant systemic therapy, because observational studies suggest the risk of locoregional recurrence is low for those who either have clinically negative nodes before undergoing the treatment or have a complete pathologic response to it in the lymph nodes. The panel decided that current evidence is insufficient to recommend whether radiotherapy should be administered or can be omitted in these groups.

The guideline also recommends that regional nodal irradiation generally should target both the internal mammary and the supraclavicular-axillary apical nodes, in addition to the chest wall or reconstructed breast. “There may be subgroups that will experience limited, if any, benefits from treating both these nodal areas, compared with treating only one or perhaps treating only the chest wall or reconstructed breast. [However,] there is insufficient evidence at this time to define such subgroups in detail.”

Copies of the updated guideline, as well as additional information such as details regarding the panel’s methodology, evidence tables, and clinical tools, are avail at www.asco.org/pmrt-guideline and www.asco.org/guidelineswiki.

This work was supported by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. Dr. Recht reported serving as a consultant or advisor to CareCore and U.S. Oncology and receiving research funding from Genomic Health; his associates reported ties to numerous industry sources.

[email protected]

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Key clinical point: The ASCO clinical practice guideline on postmastectomy radiotherapy has been updated to help clinicians decide which patients who have T1-T2 breast cancer with one-three positive axillary lymph nodes will not benefit from the treatment.

Major finding: The 10-year rate of locoregional treatment failure was only 4.3% with irradiation, compared with 21.0% without irradiation, and the 10-year rate of local or distant treatment failure was 33.8% with irradiation and 45.5% without it.

Data source: A review of the literature and compilation of several treatment recommendations.

Disclosures: This work was supported by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. Dr. Recht reported serving as a consultant or advisor to CareCore and U.S. Oncology and receiving research funding from Genomic Health; his associates reported ties to numerous industry sources.

Four factors raise risk of post-TAVR endocarditis

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Four factors raise risk of post-TAVR endocarditis

Four factors – younger patient age, male sex, diabetes, and moderate to severe residual aortic regurgitation – are associated with a significantly increased risk of infective endocarditis after transcatheter aortic valve replacement, according to a report published online Sept. 13 in JAMA.

Until now, data pertaining to endocarditis following TAVR “have been limited to case reports and relatively small series with limited follow-up,” said Ander Regueiro, MD, of Laval University, Quebec City, and his associates.

They performed a retrospective analysis of data in a large international registry of TAVR cases to better characterize post-TAVR endocarditis.

Dr. Regueiro and his colleagues focused on 20,006 TAVR procedures done at 47 medical centers in Europe, North America, and South America during a 10-year period. The median time to symptom onset was 5.3 months after the procedure.

Infective endocarditis was definitively diagnosed in 250 of these cases. This incidence is similar to that reported for endocarditis following surgical aortic valve replacement, indicating that TAVR is no less predisposing to endocarditis despite being a less invasive approach.

The mean age of patients who developed post-TAVR endocarditis was 78.9 years, compared with 81.8 years for those who did not (HR, 0.97). The reason for this association is unclear, but it is possible that younger patients chosen for TAVR because of their prohibitive surgical risk carry a higher burden of comorbidity than do older patients. Similarly, 62% of endocarditis cases arose in men (HR, 1.69), and sex differences in comorbid conditions may explain the higher risk among men.

More patients who developed endocarditis had diabetes (41.7%), compared with those who did not develop endocarditis (30%), for an HR of 1.52. And patients who had moderate to severe residual aortic regurgitation after TAVR also were at much higher risk for endocarditis than were those who did not (HR, 2.05), the investigators noted (JAMA. 2016 Sep 13;316[10]:1083-92).

In contrast, factors that were not associated with endocarditis risk included chronic pulmonary disease, type of valve (self-expandable or balloon-expandable), and setting of the procedure (catheterization lab vs. operating room).

The bacteria that most commonly caused infective endocarditis were Enterococci species (24.6% of cases), Staphylococcus aureus (23.8%), and coagulase-negative staphylococci (16.8%). This should be taken into consideration when selecting antibiotics for prophylaxis before TAVR and when choosing empirical antibiotics for treatment while waiting for blood culture results, wrote Dr. Regueiro and his associates.

“This information may help clinicians identify patients at higher risk [for endocarditis] and aid in implementing appropriate preventive measures,” they noted.

This study was supported by a grant from the Alfonso Martin Escudero Foundation. Dr. Regueiro reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.

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Four factors – younger patient age, male sex, diabetes, and moderate to severe residual aortic regurgitation – are associated with a significantly increased risk of infective endocarditis after transcatheter aortic valve replacement, according to a report published online Sept. 13 in JAMA.

Until now, data pertaining to endocarditis following TAVR “have been limited to case reports and relatively small series with limited follow-up,” said Ander Regueiro, MD, of Laval University, Quebec City, and his associates.

They performed a retrospective analysis of data in a large international registry of TAVR cases to better characterize post-TAVR endocarditis.

Dr. Regueiro and his colleagues focused on 20,006 TAVR procedures done at 47 medical centers in Europe, North America, and South America during a 10-year period. The median time to symptom onset was 5.3 months after the procedure.

Infective endocarditis was definitively diagnosed in 250 of these cases. This incidence is similar to that reported for endocarditis following surgical aortic valve replacement, indicating that TAVR is no less predisposing to endocarditis despite being a less invasive approach.

The mean age of patients who developed post-TAVR endocarditis was 78.9 years, compared with 81.8 years for those who did not (HR, 0.97). The reason for this association is unclear, but it is possible that younger patients chosen for TAVR because of their prohibitive surgical risk carry a higher burden of comorbidity than do older patients. Similarly, 62% of endocarditis cases arose in men (HR, 1.69), and sex differences in comorbid conditions may explain the higher risk among men.

More patients who developed endocarditis had diabetes (41.7%), compared with those who did not develop endocarditis (30%), for an HR of 1.52. And patients who had moderate to severe residual aortic regurgitation after TAVR also were at much higher risk for endocarditis than were those who did not (HR, 2.05), the investigators noted (JAMA. 2016 Sep 13;316[10]:1083-92).

In contrast, factors that were not associated with endocarditis risk included chronic pulmonary disease, type of valve (self-expandable or balloon-expandable), and setting of the procedure (catheterization lab vs. operating room).

The bacteria that most commonly caused infective endocarditis were Enterococci species (24.6% of cases), Staphylococcus aureus (23.8%), and coagulase-negative staphylococci (16.8%). This should be taken into consideration when selecting antibiotics for prophylaxis before TAVR and when choosing empirical antibiotics for treatment while waiting for blood culture results, wrote Dr. Regueiro and his associates.

“This information may help clinicians identify patients at higher risk [for endocarditis] and aid in implementing appropriate preventive measures,” they noted.

This study was supported by a grant from the Alfonso Martin Escudero Foundation. Dr. Regueiro reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.

Four factors – younger patient age, male sex, diabetes, and moderate to severe residual aortic regurgitation – are associated with a significantly increased risk of infective endocarditis after transcatheter aortic valve replacement, according to a report published online Sept. 13 in JAMA.

Until now, data pertaining to endocarditis following TAVR “have been limited to case reports and relatively small series with limited follow-up,” said Ander Regueiro, MD, of Laval University, Quebec City, and his associates.

They performed a retrospective analysis of data in a large international registry of TAVR cases to better characterize post-TAVR endocarditis.

Dr. Regueiro and his colleagues focused on 20,006 TAVR procedures done at 47 medical centers in Europe, North America, and South America during a 10-year period. The median time to symptom onset was 5.3 months after the procedure.

Infective endocarditis was definitively diagnosed in 250 of these cases. This incidence is similar to that reported for endocarditis following surgical aortic valve replacement, indicating that TAVR is no less predisposing to endocarditis despite being a less invasive approach.

The mean age of patients who developed post-TAVR endocarditis was 78.9 years, compared with 81.8 years for those who did not (HR, 0.97). The reason for this association is unclear, but it is possible that younger patients chosen for TAVR because of their prohibitive surgical risk carry a higher burden of comorbidity than do older patients. Similarly, 62% of endocarditis cases arose in men (HR, 1.69), and sex differences in comorbid conditions may explain the higher risk among men.

More patients who developed endocarditis had diabetes (41.7%), compared with those who did not develop endocarditis (30%), for an HR of 1.52. And patients who had moderate to severe residual aortic regurgitation after TAVR also were at much higher risk for endocarditis than were those who did not (HR, 2.05), the investigators noted (JAMA. 2016 Sep 13;316[10]:1083-92).

In contrast, factors that were not associated with endocarditis risk included chronic pulmonary disease, type of valve (self-expandable or balloon-expandable), and setting of the procedure (catheterization lab vs. operating room).

The bacteria that most commonly caused infective endocarditis were Enterococci species (24.6% of cases), Staphylococcus aureus (23.8%), and coagulase-negative staphylococci (16.8%). This should be taken into consideration when selecting antibiotics for prophylaxis before TAVR and when choosing empirical antibiotics for treatment while waiting for blood culture results, wrote Dr. Regueiro and his associates.

“This information may help clinicians identify patients at higher risk [for endocarditis] and aid in implementing appropriate preventive measures,” they noted.

This study was supported by a grant from the Alfonso Martin Escudero Foundation. Dr. Regueiro reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.

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Key clinical point: Four factors raise the risk that patients undergoing transcatheter aortic valve replacement will develop infective endocarditis.

Major finding: The mean age of patients who developed post-TAVR endocarditis was 78.9 years, compared with 81.8 years for those who didn’t (HR, 0.97).

Data source: A retrospective analysis of data in an international registry involving 20,006 patients who underwent TAVR at 47 medical centers during a 10-year period.

Disclosures: This study was supported by a grant from the Alfonso Martin Escudero Foundation. Dr. Regueiro reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.

Smoking thickens LV wall, worsens function

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Smoking thickens LV wall, worsens function

Current smoking, as well as higher levels of cumulative cigarette exposure from past smoking, were both associated with higher left ventricular mass, a higher LV mass-to-volume ratio, and worse diastolic function in an elderly community-based population with no overt indications of coronary artery disease or heart failure, according to a report published online Sept. 13 in Circulation: Cardiovascular Imaging.

“These findings suggest that smoking is associated with subtle alterations in LV structure and function, which might help explain the higher risk of heart failure [HF] reported for smokers, independent of coronary artery disease [CAD],” said Wilson Nadruz Jr., MD, of the cardiovascular division, Brigham and Women’s Hospital, Boston, and his associates.

©Zoonar/A.Mijatovic/Thinkstock.com

They analyzed links between smoking and echocardiographic features using data from the Atherosclerosis Risk in Communities (ARIC) study, an ongoing prospective observational study involving community-dwelling adults who were aged 45-64 years at baseline in 1987-1989. For their study, Dr. Nadruz and his colleagues assessed echocardiographic images taken for 4,580 ARIC participants at follow-up roughly 25 years later. None of these adults had any indication of CAD or HF; 287 (6.3%) were current smokers, 2,316 (50.5%) were former smokers, and 1,977 (43.2%) never smoked.

Compared with never smokers, current smokers showed a greater LV mass index (80.4 vs. 76.7), a greater LV mass-to-volume ratio (1.93 vs. 1.83), and a higher prevalence of LV hypertrophy (15% vs. 9%), as well as a higher prevalence of concentric LV hypertrophy and worse LV diastolic function. The same association was found between never smokers and former smokers who had higher levels of cumulative cigarette exposure, the investigators said (Circ Cardiovasc Imag. 2016 Sep 13. doi: 10.1161/circimaging.116.004950).

Dr. Scott D. Solomon

This association between smoking and altered LV structure and function remained robust after the data were adjusted to account for numerous cardiac risk factors such as older age, higher BMI, diabetes, hypertension, greater alcohol consumption, and higher heart rate. It also didn’t vary by patient sex, race, or income level. In contrast, there was no association between smoking and right ventricular structure or function.

“These data suggest that smoking can independently lead to thickening of the heart and worsening of heart function, which may lead to a higher risk for heart failure, even in people who don’t have heart attacks,” Dr. Nadruz said in a statement.

Looking at the results in a more positive light, senior author Scott D. Solomon, MD, professor of medicine at Harvard University, Boston, said “The good news is that former smokers had similar heart structure and function, compared with never smokers,” suggesting that “the potential effects of tobacco on the myocardium might be reversible after smoking cessation.”

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Current smoking, as well as higher levels of cumulative cigarette exposure from past smoking, were both associated with higher left ventricular mass, a higher LV mass-to-volume ratio, and worse diastolic function in an elderly community-based population with no overt indications of coronary artery disease or heart failure, according to a report published online Sept. 13 in Circulation: Cardiovascular Imaging.

“These findings suggest that smoking is associated with subtle alterations in LV structure and function, which might help explain the higher risk of heart failure [HF] reported for smokers, independent of coronary artery disease [CAD],” said Wilson Nadruz Jr., MD, of the cardiovascular division, Brigham and Women’s Hospital, Boston, and his associates.

©Zoonar/A.Mijatovic/Thinkstock.com

They analyzed links between smoking and echocardiographic features using data from the Atherosclerosis Risk in Communities (ARIC) study, an ongoing prospective observational study involving community-dwelling adults who were aged 45-64 years at baseline in 1987-1989. For their study, Dr. Nadruz and his colleagues assessed echocardiographic images taken for 4,580 ARIC participants at follow-up roughly 25 years later. None of these adults had any indication of CAD or HF; 287 (6.3%) were current smokers, 2,316 (50.5%) were former smokers, and 1,977 (43.2%) never smoked.

Compared with never smokers, current smokers showed a greater LV mass index (80.4 vs. 76.7), a greater LV mass-to-volume ratio (1.93 vs. 1.83), and a higher prevalence of LV hypertrophy (15% vs. 9%), as well as a higher prevalence of concentric LV hypertrophy and worse LV diastolic function. The same association was found between never smokers and former smokers who had higher levels of cumulative cigarette exposure, the investigators said (Circ Cardiovasc Imag. 2016 Sep 13. doi: 10.1161/circimaging.116.004950).

Dr. Scott D. Solomon

This association between smoking and altered LV structure and function remained robust after the data were adjusted to account for numerous cardiac risk factors such as older age, higher BMI, diabetes, hypertension, greater alcohol consumption, and higher heart rate. It also didn’t vary by patient sex, race, or income level. In contrast, there was no association between smoking and right ventricular structure or function.

“These data suggest that smoking can independently lead to thickening of the heart and worsening of heart function, which may lead to a higher risk for heart failure, even in people who don’t have heart attacks,” Dr. Nadruz said in a statement.

Looking at the results in a more positive light, senior author Scott D. Solomon, MD, professor of medicine at Harvard University, Boston, said “The good news is that former smokers had similar heart structure and function, compared with never smokers,” suggesting that “the potential effects of tobacco on the myocardium might be reversible after smoking cessation.”

Current smoking, as well as higher levels of cumulative cigarette exposure from past smoking, were both associated with higher left ventricular mass, a higher LV mass-to-volume ratio, and worse diastolic function in an elderly community-based population with no overt indications of coronary artery disease or heart failure, according to a report published online Sept. 13 in Circulation: Cardiovascular Imaging.

“These findings suggest that smoking is associated with subtle alterations in LV structure and function, which might help explain the higher risk of heart failure [HF] reported for smokers, independent of coronary artery disease [CAD],” said Wilson Nadruz Jr., MD, of the cardiovascular division, Brigham and Women’s Hospital, Boston, and his associates.

©Zoonar/A.Mijatovic/Thinkstock.com

They analyzed links between smoking and echocardiographic features using data from the Atherosclerosis Risk in Communities (ARIC) study, an ongoing prospective observational study involving community-dwelling adults who were aged 45-64 years at baseline in 1987-1989. For their study, Dr. Nadruz and his colleagues assessed echocardiographic images taken for 4,580 ARIC participants at follow-up roughly 25 years later. None of these adults had any indication of CAD or HF; 287 (6.3%) were current smokers, 2,316 (50.5%) were former smokers, and 1,977 (43.2%) never smoked.

Compared with never smokers, current smokers showed a greater LV mass index (80.4 vs. 76.7), a greater LV mass-to-volume ratio (1.93 vs. 1.83), and a higher prevalence of LV hypertrophy (15% vs. 9%), as well as a higher prevalence of concentric LV hypertrophy and worse LV diastolic function. The same association was found between never smokers and former smokers who had higher levels of cumulative cigarette exposure, the investigators said (Circ Cardiovasc Imag. 2016 Sep 13. doi: 10.1161/circimaging.116.004950).

Dr. Scott D. Solomon

This association between smoking and altered LV structure and function remained robust after the data were adjusted to account for numerous cardiac risk factors such as older age, higher BMI, diabetes, hypertension, greater alcohol consumption, and higher heart rate. It also didn’t vary by patient sex, race, or income level. In contrast, there was no association between smoking and right ventricular structure or function.

“These data suggest that smoking can independently lead to thickening of the heart and worsening of heart function, which may lead to a higher risk for heart failure, even in people who don’t have heart attacks,” Dr. Nadruz said in a statement.

Looking at the results in a more positive light, senior author Scott D. Solomon, MD, professor of medicine at Harvard University, Boston, said “The good news is that former smokers had similar heart structure and function, compared with never smokers,” suggesting that “the potential effects of tobacco on the myocardium might be reversible after smoking cessation.”

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Key clinical point: Current smoking was associated with higher left ventricular mass, a higher LV mass-to-volume ratio, and worse diastolic function.

Major finding: Compared with never smokers, current smokers showed a greater LV mass index (80.4 vs. 76.7), a greater LV mass-to-volume ratio (1.93 vs. 1.83), and a higher prevalence of LV hypertrophy (15% vs. 9%).

Data source: A secondary analysis of data for 4,580 elderly participants in ARIC, a large community-based cohort.

Disclosures: This study was supported by Brigham and Women’s Hospital, Boston. Dr. Nadruz and his associates reported having no relevant financial disclosures.