EMBARGOED FOR EARLY RELEASE: 10:00 A.M. (CT) MONDAY, NOVEMBER 4, 2013

Media Advisory: To contact Anita P. Courcoulas, M.D., M.P.H., call Andréa Stanford at 412-647-6190 or email Stanfordac@upmc.edu.

In 3-year follow-up after bariatric surgery, substantial weight loss was observed among individuals who were severely obese, with most of the change occurring during the first year; however, there was variability in the amount of weight loss, as well as in diabetes, blood pressure, and lipid outcomes, according to a study published online by JAMA.

“Bariatric surgery results in large, sustained weight loss in severely obese [body mass index (BMI) ≥ 35] populations. Although generally accepted as the most effective means for inducing weight loss in very heavy patients, few studies exist reporting outcomes longer than 2 years after the surgery was performed,” according to background information in the article.

Anita P. Courcoulas, M.D., M.P.H., of the University of Pittsburgh Medical Center, and colleagues used Longitudinal Assessment of Bariatric Surgery (LABS) Consortium data to study change in weight and selected health parameters after common bariatric surgical procedures. The Longitudinal Assessment of Bariatric Surgery (LABS) Consortium is a multicenter observational cohort study at 10 hospitals in 6 clinical centers in the United States. Their study included adults undergoing a first-time bariatric surgical procedure as part of routine clinical care by participating surgeons between 2006 and 2009 and followed until September 2012. Participants (n = 2,458) completed research assessments using standardized and detailed data collection prior to surgery and at 6 months, 12 months, and annually after surgery. At baseline, 774 participants (33 percent) had diabetes, 1,252 (63 percent) dyslipidemia, and 1,601 (68 percent) hypertension.

Three years after Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB), the researchers assessed percent weight change from baseline and the percentage of patients with diabetes who achieved certain measures without pharmacologic therapy. Dyslipidemia or hypertension resolution at 3 years was also assessed.

At the beginning of the study, median (midpoint) BMI was 45.9, and median baseline weight was 284 lbs.; 1,738 participants underwent RYGB, 610 LAGB, and 110 other procedures. Three years after surgery, median percent weight loss was 31.5% of baseline (90 lbs.) for participants who underwent RYGB and 15.9 percent (44 lbs.) for LAGB. As a group, participants experienced most of their total weight change the first year after surgery.

The authors write that variability in weight change “indicates a potential opportunity to improve patient selection and education prior to operation as well as enhance support for continued adherence to lifestyle adjustments in the postoperative years.”

Three years after surgery, the percentages of participants experiencing at least partial diabetes remission were 67.5 percent for RYGB and 28.6 percent for LAGB. Dyslipidemia was in remission for 61.9 percent of RYGB participants and 27.1 percent of LAGB participants at 3 years. Changes in hyperlipidemia were similar. Hypertension was in remission at 3 years in 38.2 percent of RYGB and 17.4 percent of LAGB participants.

“Longer-term follow-up of this cohort will determine the durability of these improvements over time and factors associated with variability in effect.”

(doi:10.l001/jama.2013.280928; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, NOVEMBER 5, 2013

Media Advisory: To contact corresponding author Gunnel Henriksson, M.D., Ph.D., email Gunnel.Henriksson@med.lu.se.

Autoantibodies are present many years before symptom onset in patients with primary Sjögren syndrome, an autoimmune disease, according to a Research Letter published in the November 6 issue of JAMA.

Primary Sjögren syndrome is a disease in which immune cells attack and destroy glands that produce tears and saliva. Autoantibodies are characteristic of this syndrome and may be involved in its development. Roland Jonsson, D.M.D., Ph.D., of the University of Bergen, Norway, and colleagues measured autoantibodies before symptom onset in these patients.

All patients with primary Sjögren syndrome at Malmo University Hospital in Malmo, Sweden, have been included in a registry since 1984. Controls were randomly selected from biobanks and matched by sex, age, and date of earliest sampling (within 60 days before or after) to each case.

Of 360 cases in the registry, 44 (41 women and 3 men) provided 64 presymptomatic serum samples obtained an average of 7 years before symptom onset. In 29 cases (66 percent), autoantibodies were detected before symptom onset. All 29 cases had autoantibodies in their earliest available serum sample, as early as 18 years before symptom onset.

“To our knowledge, this is the first systematic investigation of presymptomatic autoantibodies in Sjögren syndrome. Most cases produced autoantibodies many years before clinical onset of the disease; the median [midpoint] time of 4 to 6 years is an underestimate because all seropositive cases had autoantibodies in their earliest available serum sample,” the authors write.

“Autoantibody profiling may identify individuals at risk many years before disease onset. However, the significance of these presymptomatic autoantibodies for determining prognosis and treatment remains to be determined.”

(doi:10.l001/jama.2013.278448; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, NOVEMBER 5, 2013

Media Advisory: To contact Richard L. Kravitz, M.D., M.S.P.H., call Charles Casey at 916-734-9048 or email  charles.casey@ucdmc.ucdavis.edu.

Chicago — Among depressed patients evaluated in a primary care setting, use of an interactive multimedia computer program immediately prior to a primary care visit resulted in the increased receipt of antidepressant prescription recommendation, mental health referral, or both; however, it did not result in improvement in mental health at 12-week follow-up, according to a study in the November 6 issue of JAMA.

“Despite progress, depression in primary care remains underrecognized and undertreated. Barriers to improvement include system, clinician, and patient factors. System-level interventions are effective in increasing recognition and treatment of depression, but these interventions are difficult to disseminate,” according to background information in the article.

Richard L. Kravitz, M.D., M.S.P.H., of the University of California, Davis, and colleagues examined whether targeted and tailored communication strategies could enhance patient engagement and initial care for patients with depression and the extent to which the interventions promoted prescribing or recommendation of antidepressant medication, depression-related discussion, and antidepressant requests among patients who were not depressed. The trial compared a depression engagement video (DEV), tailored interactive multimedia computer program (IMCP) and control among 925 adult patients treated by 135 primary care clinicians (603 patients with depression and 322 patients without depression) conducted from June 2010 through March 2012 at 7 primary care clinical sites in California. Patients were randomized to a DEV targeted to sex and income, an IMCP tailored to individual patient characteristics, and a sleep hygiene (recommendations for improving sleep) video (control).

Of the 925 eligible patients, 867 were included in the primary analysis (depressed, 559; nondepressed, 308). The researchers found that among depressed patients, rates of achieving the primary outcome (a composite measure of receiving an antidepressant recommendation, a mental health referral, or both during the initial visit) were 17.5 percent for DEV, 26 percent for IMCP, and 16.3 percent for control. Both the DEV and the IMCP increased patient-reported requests for information about depression. However, there were no improvements in mental health (as gauged by a questionnaire) at the 12-week follow-up in response to either intervention.

Among nondepressed patients, no evidence of harm was observed from either intervention for the outcome of clinician-reported antidepressant prescribing, but the authors could not exclude harm (defined as a higher rate of antidepressant prescriptions for nondepressed patients associated with each intervention) based on patient-reported antidepressant recommendation.

“Further research is needed to determine effects on clinical outcomes and whether the benefits outweigh possible harms,” the authors conclude.

(doi:10.l001/jama.2013.280038; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This work was supported by grants from the National Institute of Mental Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, NOVEMBER 5, 2013

Media Advisory: To contact Christopher Vinden, M.D., call Julia Capaldi at 519-685-8500, ext. 75616 or email Julia.Capaldi@LawsonResearch.Com. To contact editorial co-author Michael J. Zinner, M.D., call Tom Langford at 617-525-6375 or email tlangford@partners.org.

Chicago — Surgeons who had operated the night before an elective daytime gallbladder surgery did not have a higher rate of complications, according to a study in the November 6 issue of JAMA.

“Lack of sleep is associated with impaired performance in many situations. To theoretically prevent medical errors, work-hour restrictions on surgeons in training were imposed. There are now proposals for similar work-hour restrictions on practicing surgeons. Several studies found no association between surgeon sleep deprivation as assessed by operating the night prior to an operation or when surgeons report few hours of sleep and patient outcomes. Prior studies were limited because of small sample sizes and being from single academic institutions. Consequently, there is insufficient evidence to conclude that surgeon performance is compromised by insufficient sleep the night prior to performing surgery,” according to background information in the article.

Christopher Vinden, M.D., of Western University, London, Ontario, Canada, and colleagues examined if there was any association between operating the night before performing an elective cholecystectomy (gallbladder removal) and complications. The analysis was conducted using administrative health care databases in Ontario. Participants were 2,078 patients (across 102 community hospitals) who underwent elective laparoscopic cholecystectomies performed by surgeons (n = 331) who operated the overnight before (between midnight and 7 a.m.). Each of these patients was matched with 4 other elective laparoscopic cholecystectomy recipients (n = 8,312), performed by the same surgeon when there was no evidence that surgeon having operated the overnight before.

The primary outcome was conversion of a planned laparoscopic cholecystectomy (removing the gallbladder using a camera and tiny incisions) to an open cholecystectomy (large incision of the abdomen to remove the gallbladder) during the procedure. Although not always considered a complication, conversion to open cholecystectomy may serve as an aggregate end point for many complications, and patients view conversion as an unwanted outcome. Secondary outcomes included evidence of iatrogenic injures (injuries caused by the surgery) or death.

The researchers found no association between conversion rates to open operations and whether or not surgeons operated the night before (2.2 percent with vs. 1.9 percent without overnight operation); or to the risk of iatrogenic injuries (0.7 percent vs. 0.9 percent); or death (≤ 0.2 percent vs. 0.1 percent). These proportions were not statistically different.

The authors write that policies limiting attending surgeon work hours are controversial. “Critics suggest such policies reduce continuity in care, increase communication errors, and introduce the potential for a bystander effect (in which one surgeon may expect another to bear the burden for authority and responsibility). Restructuring health care delivery to prevent surgeons operating during the day after they operated the previous night would have important cost, staffing, and resource implications.”

“These findings do not support safety concerns related to surgeons operating the night before performing elective surgery.”

(doi:10.l001/jama.2013.280372; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Please Note: An author podcast on this study will be available post-embargo on the JAMA website.

Editorial: Surgeons, Sleep, and Patient Safety

Michael J. Zinner, M.D., of Brigham and Women’s Hospital, Boston, and Julie Ann Fresichlag, M.D., of Johns Hopkins Medical Institute, Baltimore, and Editor, JAMA Surgery, comment on the findings of this study in an accompanying editorial.

“The study by Vinden et al verifies that surgeons can perform elective operations without inducing undue complications, even when they have operated the night before. However, just as each patient undergoing an operation requires an individualized assessment and operative plan, each surgeon must objectively self-assess fatigue level and honestly determine whether the surgical skills necessary for daytime operations following operating the night before will be comparable to those skills and capabilities following a good night’s sleep. Patient safety and surgeon well-being deserve no less.”

(doi:10.l001/jama.2013.280374; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, NOVEMBER 5, 2013

Media Advisory: To contact corresponding author P. Michael Ho, M.D., Ph.D., call Mark Couch at 303-724-5377 or email mark.couch@ucdenver.edu. To contact editorial author Anne R. Cappola, M.D., Sc.M., call Kim Menard at 215-662-6183 or email kim.menard@uphs.upenn.edu.

Chicago — Among a group of men who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of death, heart attack, or ischemic stroke, according to a study in the November 6 issue of JAMA.

“Rates of testosterone therapy prescription have increased markedly in the United States over the past decade. Annual prescriptions for testosterone increased by more than 5-fold from 2000 to 2011, reaching 5.3 million prescriptions and a market of $1.6 billion in 2011. Professional society guidelines recommend testosterone therapy for patients with symptomatic testosterone deficiency. In addition to improving sexual function and bone mineral density and increasing free-fat mass and strength, treatment with testosterone has been shown to improve lipid profiles and insulin resistance and increase the time to ST depression [a finding on an electrocardiogram suggesting benefit] during stress testing,” according to background information in the article. However, a recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety.

Rebecca Vigen, M.D., M.S.C.S., of the University of Texas at Southwestern Medical Center, Dallas and colleagues evaluated the association between the use of testosterone therapy and all-cause mortality, myocardial infarction (MI; heart attack), and stroke among male veterans and whether this association was modified by underlying coronary artery disease (CAD). The study included 8,709 men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011. There was a high level of co-existing illnesses among this group, including prior history of heart attack, diabetes, or CAD. Of the 8,709 patients, 1,223 (14.0 percent) initiated testosterone therapy after a median (midpoint) of 531 days following angiography. The average follow-up was approximately 2 years, 3.5 months. The primary measured outcome for the study was a composite of all-cause mortality, heart attack, and ischemic stroke.

The researchers found that the proportion of patients experiencing events 3 years after coronary angiography was 19.9 percent in the no testosterone therapy group (average age, 64 years) and 25.7 percent in the testosterone therapy group (average age, 61 years), for an absolute risk difference of 5.8 percent. Even accounting for other factors that could explain the differences, use of testosterone therapy was associated with adverse outcomes and was consistent among patients with and without CAD. The increased risk of adverse outcomes associated with testosterone therapy use was not related to differences in risk factor control or rates of secondary prevention medication use because patients in both groups had similar blood pressure, low-density lipoprotein levels, and use of secondary prevention medications.

“These findings raise concerns about the potential safety of testosterone therapy,” the authors write. “Future studies including randomized controlled trials are needed to properly characterize the potential risks of testosterone therapy in men with comorbidities.”

(doi:10.l001/jama.2013.280386; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, November 5 at this link.

Editorial: Testosterone Therapy and Risk of Cardiovascular Disease in Men

“Perhaps the most important question is the generalizability of the results of this study to the broader population of men taking testosterone: men of this age group who are taking testosterone for ‘low T syndrome’ or for antiaging purposes and younger men taking it for physical enhancement,” writes Anne R. Cappola, M.D., Sc.M., of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, in an accompanying editorial.

“Are the benefits—real or perceived—for these groups of men worth any increase in risk? These populations represent a sizable group of testosterone users, and there is only anecdotal evidence that testosterone is safe for these men.”

“In light of the high volume of prescriptions and aggressive marketing by testosterone manufacturers, prescribers and patients should be wary. There is mounting evidence of a signal of cardiovascular risk, to which the study by Vigen et al contributes. This signal warrants both cautious testosterone prescribing and additional investigation.”

(doi:10.l001/jama.2013.280387; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc.

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EMBARGOED FOR EARLY RELEASE: 11:30 A.M. (CT) THURSDAY, OCTOBER 31, 2013

Media Advisory: To contact Fausto Feres, M.D., Ph.D., email fferes@lee.dante.br.

Short-term (3 months) vs. long-term (12 months) dual anti­platelet therapy did not result in poorer outcomes on certain measures (death, heart attack, stroke, and bleeding) for patients with coronary artery disease or low-risk acute coronary syndromes (such as heart attack or unstable angina) treated with drug (zotarolimus)-releasing stents, according to a study published by JAMA. The study is being published early online to coincide with its presentation at the Transcatheter Cardiovascular Therapeutics 25th annual meeting.

“The current recommendation is for at least 12 months of dual antiplatelet therapy [typically aspirin and clopidogrel] after implantation of a drug-eluting stent. However, the optimal duration of dual antiplatelet therapy with specific types of drug-eluting stents remains unknown,” according to background information in the article.

Fausto Feres, M.D., Ph.D., of Instituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil, and colleagues with the OPTIMIZE trial assessed if 3 months of dual antiplatelet therapy was noninferior to (not worse than) 12 months in patients with stable coronary artery disease or history of low-risk acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with zotarolimus-eluting stents to open narrowed coronary arteries. The study included 3,119 patients in 33 sites in Brazil between April 2010 and March 2012. Clinical follow-up was performed at 1,3,6, and 12 months.

After PCI with zotarolimus-eluting stents, patients were prescribed dual antiplatelet therapy comprising aspirin (100-200 mg daily) and clopidogrel (75 mg daily) for 3 months (n = 1,563) or 12 months (n = 1,556). The primary end point for the study was a composite of all-cause death, heart attack, stroke, or major bleeding; the expected event rate at 1 year was 9 percent. Secondary end points were a composite of all-cause death, heart attack, emergency coronary artery bypass graft surgery, or target lesion revascularization; and definite or probable stent thrombosis (blood clot).

The researchers found that about equal proportions of patients at 1 year in the short-term and long-term groups experienced the primary outcome (6.0 percent vs. 5.8 percent) and secondary outcome (8.3 percent vs. 7.4 percent). Between 91 and 360 days, no statistically significant association was observed for NACCE for the short- and long-term groups, MACE, or stent thrombosis.

The authors add that the primary finding was similar in several key sub­groups, including patients with diabetes, history of low-risk ACS, or multivessel disease.

(doi:10.l001/jama.2013. 282183; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 22, 2013

Media Advisory: To contact corresponding author Ulrike Bingel, M.D., Ph.D., email ulrike.bingel@uk-essen.de.

The hormone oxytocin may mediate processes such as empathy, trust, and social learning. These are key elements of the patient-physician relationship, which is an important mediator of placebo responses, according to background information in a Research Letter appearing in the October 23/30 issue of JAMA. Simon Kessner, of the University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and colleagues conducted a study to test whether oxytocin enhances the placebo response in an experimental placebo analgesia model.

Between January and September 2012, the researchers randomly assigned 80 healthy male volunteers to 40 IU of intranasal oxytocin or saline. The researchers and participants were blinded to study drug identity. After 45 minutes, placebo analgesia was assessed using the following standard technique. Two identical inert ointments were applied to 2 sites on each participant’s forearm. The ointments were described as an anesthetic that reduces pain (placebo) and an inert control cream (control). In the 15 minutes following application that the participant expected the anesthetic to take effect, the researchers calibrated the  intensity at which a 20-second painful heat stimulus was perceived by each individual to rate as a 60 on a scale ranging from 0 (no pain) to 100 (unbearable pain). During the subsequent test phase, a series of 10 of those calibrated stimuli was applied to each of the 2 sites in randomized order. The primary outcome was the placebo analgesic response, defined as the reduction of perceived pain intensity on the placebo site compared with the control site in the oxytocin and saline groups.

Despite identical stimulation on both sites, the difference in pain ratings at the placebo and pain sites were greater in the oxytocin group than in the saline group due to lower pain ratings at the placebo site.

“To our knowledge, our study provides the first experimental evidence that placebo responses can be pharmacologically enhanced by the application of intranasal oxytocin,” the authors write. “Further studies are needed to replicate our findings in larger clinical populations, identify the underlying mechanisms, and explore moderating variables such as sex or aspects of patient-physician communication.”

(doi:10.l001/jama.2013.277446; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 22, 2013

Media Advisory: To contact Jacob A. Udell, M.D., M.P.H., F.R.C.P.C., call Nicole Bodnar at 416-978-5811 or email Nicole.Bodnar@utoronto.ca. To contact editorial author Kathleen M. Neuzil, M.D., M.P.H., call Monica Graham at 206-302-6072 or email mgraham@path.org.

Receiving an influenza vaccination was associated with a lower risk of major adverse cardiovascular events such as heart failure or hospitalization for heart attack, with the greatest treatment effect seen among patients with recent acute coronary syndrome (ACS; such as heart attack or unstable angina), according to a meta-analysis published in the October 23/30 issue of JAMA.

“Among nontraditional cardiovascular risk factors, there remains interest in a potential association between respiratory tract infections, of which influenza and influenza-like illnesses are common causes, and subsequent cardiovascular events,” according to background information in the article. Several epidemiological studies have suggested a strong inverse relationship between influenza vaccination and the risk of fatal and nonfatal cardiovascular events.

Jacob A. Udell, M.D., M.P.H., F.R.C.P.C., of the University of Toronto, and colleagues conducted a meta-analysis of all randomized clinical trials (RCTs) of influenza vaccine that studied cardiovascular events as efficacy or safety outcomes to determine if influenza vaccination is associated with prevention of cardiovascular events. The researchers identified five published and 1 unpublished RCTs of 6,735 patients (average age, 67 years; 51 percent women; 36 percent with a cardiac history; average follow-up time, 7.9 months) that met inclusion criteria for the study. Analyses were stratified by subgroups of patients with and without a history of acute coronary syndrome (ACS) within 1 year of randomization.

In the 5 published RCTs, 95 of 3,238 patients treated with influenza vaccine (2.9 percent) developed a major adverse cardiovascular event compared with 151 of 3,231 patients (4.7 percent) treated with placebo or control within 1 year of follow-up, an absolute risk difference favoring flu vaccine of 1.74 percent. The addition of the unpublished data did not materially change the results (2.9 percent influenza vaccine vs. 4.6 percent placebo or control).

In a subgroup analysis of 3 RCTs of patients with pre-existing coronary artery disease (CAD), the risk of major adverse cardiovascular events among patients with a history of recent ACS was especially lower with vaccine (10.3 percent influenza vaccine vs. 23.1 percent placebo or control), an absolute-risk difference of 12.9 percent, compared to patients with stable CAD (6.9 percent influenza vaccine vs. 7.4 percent placebo or control). Results were similar with the addition of unpublished data.

“Within this global meta-analysis of RCTs that studied patients with high cardiovascular risk, influenza vaccination was associated with a lower risk of major adverse cardiovascular events within 1 year. Influenza vaccination was particularly associated with cardiovascular prevention in patients with recent ACS. Future research with an adequately powered multicenter trial to confirm the efficacy of this low-cost, annual, safe, easily administered, and well-tolerated therapy to reduce cardiovascular risk beyond current therapies is warranted,” the authors conclude.

(doi:10.l001/jama.2013.279206; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Dr. Udell is supported by a Canadian Institutes for Health Research and Canadian Foundation for Women’s Health postdoctoral research fellowship award. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, October 22 at this link.

Editorial: Influenza Vaccination in 2013-2014 – Achieving 100 percent Participation

In an accompanying editorial, Kathleen M. Neuzil, M.D., M.P.H., of PATH, Seattle, discusses the importance of improving influenza vaccination coverage.

“There are proven ways to increase vaccination coverage, including expanding access through nontraditional settings (e.g., pharmacy, workplace, school venues), improving the use of evidence-based practices at medical sites (e.g., standing orders, reminder or recall notification), and using immunization registries. One of the most consistent and relevant findings of operational research is that recommendation for vaccination from physicians and other health care professionals is a strong predictor of vaccine acceptance and receipt among patients. While few are in a position to develop new influenza vaccines, all health care practitioners can recommend influenza vaccine to their patients. Doing so will help achieve the goal of 100 percent vaccination for the 2013-2014 influenza season.”

(doi:10.l001/jama.2013.279207; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Neuzil reports receiving grant funding from the Bill & Melinda Gates Foundation and Centers for Disease Control and Prevention.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 22, 2013

Media Advisory: To contact Lisa R. Metsch, Ph.D., call Stephanie Berger at 212-305-4372 or email sb2247@columbia.edu. To contact editorial co-author Jason S. Haukoos, M.D., M.Sc., call Jenny Bertrand at 303-520-9591 or email Jennifer.Bertrand@dhha.org.

Brief risk-reduction counseling at the time of a rapid human immunodeficiency virus (HIV) test was not effective for reducing new sexually transmitted infections (STIs) during the subsequent 6 months among persons at risk for HIV, according to a study in the October 23/30 issue of JAMA.

In the United States, approximately 1.1 million people are estimated to be living with HIV infection. The incidence of HIV infection is considered to have remained steady over the last decade, with about 50,000 new infections occurring annually. About l in 5 people living with HIV is thought to be undiagnosed. The U.S. Preventive Services Task Force recently recommended that all persons age 15 to 65 years be screened for HIV, according to background information in the article. A major issue regarding HIV testing of such a large population is the effectiveness of HIV risk-reduction counseling at the time of testing, because counseling involves considerable time, personnel, and financial costs.

Lisa R. Metsch, Ph.D., of Columbia University’s Mailman School of Public Health, New York, and colleagues conducted a trial to assess the effectiveness of counseling in reducing STI incidence among STI clinic patients. From April to December 2010, Project AWARE randomized 5,012 patients from 9 STI clinics in the United States to receive either brief patient-centered HIV risk-reduction counseling with a rapid HIV test or the rapid HIV test with information only. Participants were assessed for multiple STIs at both the beginning of the study and 6-month follow-up. The core elements of the counseling that the patients received included a focus on the patient’s specific HIV/STI risk behavior and negotiation of realistic and achievable risk-reduction steps. The prespecified outcome was a cumulative incidence of any of the measured STIs over 6 months. All participants were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum (syphilis), herpes simplex virus 2, and HIV. Women were also tested for Trichomonas vaginalis.

The researchers found no difference in 6-month composite STI incidence by study group: STI incidence was 250 of 2,039 (12.3 percent) in the counseling group and 226 of 2,032 (11.1 percent) in the information group. This pattern was consistent at all sites. Analyses by age group, race/ethnicity, and sex (for heterosexuals) also demonstrated no effect of counseling on STI rates.

“Despite the historical emphasis on risk-reduction counseling as integral to the HIV testing process, no contemporary data exist on the effectiveness of such counseling. The results of Project AWARE help fill this gap,” the authors write.

“Overall, these study findings lend support for reconsidering the role of counseling as an essential adjunct to HIV testing. This inference is further buttressed by the additional costs associated with counseling at the time of testing: without evidence of effectiveness, counseling cannot be considered an efficient use of resources. Posttest counseling for persons testing HIV-positive remains essential, both for addressing psychological needs and for providing and ensuring follow-through with medical care and support. A more focused approach to providing information at the time of testing may allow clinics to use resources more efficiently to conduct universal testing, potentially detecting more HIV cases earlier and linking and engaging HIV-infected people in care.”

(doi:10.l001/jama.2013.280034; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Eliminating Prevention Counseling to Improve HIV Screening

“In an era of shrinking resources, clinicians and policy makers cannot ignore data that inform efficient clinical practice,” write Jason S. Haukoos, M.D., M.Sc., of the Denver Health Medical Center, and Mark W. Thrun, M.D., of Denver Public Health, in an accompanying editorial.

“Maximizing identification of individuals with undiagnosed HIV infection and reducing viral transmission will require consistent and extensive HIV testing with emphasis, for those identified with HIV infection, on linkage to care, treatment, and adherence. Although utilization of prevention counseling in the context of these post-HIV testing efforts remains to be characterized, results of the AWARE trial support the notion that prevention counseling in conjunction with HIV testing is not effective and should not be included as a routine part of practice.”

(doi:10.l001/jama.2013.280035; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Dr. Haukoos is supported in part by the National Institute of Allergy and Infectious Diseases and the Agency for Healthcare Research and Quality. Please see the article for additional information, including financial disclosures.

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EMBARGOED FOR EARLY RELEASE: 6:00 A.M. (CT) THURSDAY, OCTOBER 17, 2013

Media Advisory: To contact Jennifer F. Kawwass, M.D., call Janet Christenbury at 404-727-8599 or email Jmchris@emory.edu. To contact editorial author Evan R. Myers, M.D., M.P.H., call Rachel Harrison at 919-419-5069 or email rachel.harrison@duke.edu.

Between 2000 and 2010 in the United States the number of donor eggs used for in vitro fertilization increased, and outcomes for births from those donor eggs improved, according to a study published by JAMA. The study is being released early online to coincide with its presentation at the American Society for Reproductive Medicine and the International Federation of Fertility Societies joint annual meeting.

During the past several decades, the number of live births to women in their early 40s in the United States has increased steadily. The prevalence of oocyte (egg) donation for in vitro fertilization (IVF) has increased in the United States, but little information is available regarding maternal or infant outcomes to improve counseling and clinical decision making, according to background information in the article.

Jennifer F. Kawwass, M.D., of the Emory University School of Medicine, Atlanta, and colleagues examined trends in use of donor oocytes in the United States and assessed perinatal outcomes. The study used data from the Centers for Disease Control and Prevention’s National Assisted Reproductive Technology (ART) Surveillance System (NASS); fertility centers are mandated to report their data to the system, which includes data on more than 95 percent of all IVF cycles performed in the United States. Good perinatal outcome was defined as a single live-born infant delivered at 37 weeks or later weighing 5.5 lbs. or more.

The researchers found that at 443 clinics (93 percent of all U.S. fertility centers) the annual number of donor oocyte cycles performed in the United States increased from 10,801 in 2000 to 18,306 in 2010, as did the percentage of such cycles that involved frozen oocytes or embryos (vs. fresh) (26.7 percent to 40.3 percent) and that involved elective single-embryo transfer (vs. transfer of multiple embryos) (0.8 percent to 14.5 percent). Good perinatal outcomes increased from 18.5 percent to 24.4 percent. Average age remained stable at 28 years for donors and 41 years for recipients. Recipient age was not associated with likelihood of good perinatal outcome.

“Use of donor oocytes is an increasingly common treatment for infertile women with diminished ovarian reserve for whom the likelihood of good perinatal outcome appears to be independent of recipient age. To maximize the likelihood of a good perinatal outcome, the American Society of Reproductive Medicine recommendations suggesting transfer of a single embryo in women younger than 35 years should be considered. Additional studies evaluating the mechanisms by which race/ethnicity, infertility diagnosis, and day of embryo culture affect perinatal outcomes in both autologous [donor and recipient are the same person] and donor IVF pregnancies are warranted to develop preventive measures to increase the likelihood of obtaining a good perinatal outcome among ART users,” the authors write.

(doi:10.1001/jama.2013.280924; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Outcomes of Donor Oocyte Cycles in Assisted Reproduction

Evan R. Myers, M.D., M.P.H., of Duke University School of Medicine, Durham, N.C., comments on the findings of this study in an accompanying editorial.

“Given the promising data presented by Kawwass et al on perinatal outcomes after use of donor oocytes, the use of oocyte donors is likely to at least remain constant and may even increase. More complete data on both short- and long-term outcomes of donation are needed so donors can make truly informed choices and, once those data are available, mechanisms can be put in place to ensure that the donor recruitment and consent process at clinics is conducted according to the highest ethical standards.”

(doi:10.1001/jama.2013.280925; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 15, 2013

Media Advisory: To contact Bjorn Pasternak, M.D., email bjp@ssi.dk.

In an analysis that included more than 40,000 women exposed to the nausea medication metoclopramide in pregnancy, use of this drug was not associated with significantly increased risk of major congenital malformations overall, spontaneous abortion, and stillbirth, according to a study in the October 16 issue of JAMA.

More than 50 percent of pregnant women experience nausea and vomiting, typically early in their pregnancy. The care of most women is managed conservatively, but 10 percent to 15 percent of those with nausea and vomiting will eventually receive drug treatment. Metoclopramide is often recommended if treatment with an antihistamine or vitamin B6 has failed. Despite metoclopramide being one of the most commonly used prescription medications in pregnancy, data on the safety of its use in pregnancy are limited, according to background information in the article.

Bjorn Pasternak, M.D., Ph.D., of the Statens Serum Institut, Copenhagen, and colleagues conducted a study to investigate associations between metoclopramide use in pregnancy and serious adverse outcomes. The study included 1,222,503 pregnancies in Denmark from 1997-2011 and compared outcomes for women who used metoclopramide to those who did not.

In a group that included women exposed and unexposed (control group) to metoclopramide, there were 28,486 live-born infants exposed to metoclopramide in the first trimester of pregnancy and 113,698 unexposed infants. Of these, 721 exposed (25.3 per 1,000 births) and 3,024 unexposed infants (26.6 per 1,000 births) were diagnosed with any major malformation during the first year of life. In analyses of individual malformation categories, there were no associations between metoclopramide use in the first trimester and any of the 20 malformations, including neural tube defects, cleft lip, cleft palate and limb reduction.

The researchers also observed no increased risk of spontaneous abortion, stillbirth, preterm birth, low birth weight, and fetal growth restriction associated with metoclopramide use in pregnancy.

“These safety data may help inform decision making when treatment with metoclopramide is considered in pregnancy,” the authors conclude.

(doi:10.l001/jama.2013.278343; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by a Danish Medical Research Council grant. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Please Note: An author podcast on this study will be available post-embargo on the JAMA website.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 15, 2013

Media Advisory: To contact corresponding author James S. Goodwin, M.D., call Raul Reyes at 409-747-0794 or email rareyes@utmb.edu.

“No organization recommends prostate-specific antigen (PSA) screening in men older than 75 years. Nevertheless, testing rates remain high,” write Elizabeth Jaramillo, M.D., of the University of Texas Medical Branch, Galveston, and colleagues in a Research Letter appearing in the October 16 issue of JAMA. The authors examined whether PSA screening rates would vary substantially among primary care physicians (PCPs) and if the variance would depend on which PCP patients used.

Using complete Medicare Part A and B data for Texas, the researchers selected PCPs whose patient panels included at least 20 men 75 years or older without a prior diagnosis of prostate cancer. Primary care physicians were identified as generalist physicians who saw a man on 3 or more occasions in 2009. PSA screening rates for 2010 were estimated. The sample included 1,963 PCPs and 61,351 patients. Overall, 41.1 percent of the men received PSA screening and 28.8 percent received PSA screening ordered by their PCPs. Both rates declined with patient age.

The authors found high variability among PCPs in PSA screening, with a 10-fold difference in rates between the highest and lowest deciles (divided into ten groups) of PCPs. In addition, which PCP a man saw explained approximately 7 times more of the variance in PSA screening than did the measurable patient characteristics.

“The high variability among PCPs in ordering PSA screening for older men requires additional study to understand its causes. It has been suggested that overtesting rates be included as quality measures of PCPs. Medicare data can be used to generate such measures.”

(doi:10.l001/jama.2013.277514; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 15, 2013

Media Advisory: To contact corresponding author David J. Cohen, M.D., M.Sc., call Kerry O’Connor at 816-932-8646 or email koconnor@saint-lukes.org.

For patients with diabetes and coronary artery disease in more than one artery, treatment with coronary artery bypass graft surgery provided slightly better health status and quality of life between 6 months and 2 years than procedures using drug-eluting stents, although beyond 2 years the difference disappeared, according to a study in the October 16 issue of JAMA.

Although previous studies have demonstrated that coronary artery bypass graft (CABG) surgery is generally preferred over percutaneous coronary intervention (PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries) for patients with diabetes mellitus and coronary artery disease in more than one artery, these studies were based largely on older data from when angioplasty and stents were different. Recently, the FREEDOM trial demonstrated that for this group of patients, CABG surgery resulted in lower rates of death and heart attack but a higher risk of stroke when compared with PCI using drug-eluting stents. Whether there are differences in health status assessed from the patient’s perspective is unknown, according to background information in the article.

Mouin S. Abdallah, M.D., M.Sc., of Saint Luke’s Mid America Heart Institute, Kansas City, and colleagues conducted a substudy of the FREEDOM trial to assess functional status and quality of life. Between 2005 and 2010, 1,900 patients from 18 countries with diabetes mellitus and multivessel coronary artery disease were randomized to undergo either CABG surgery (n = 947) or PCI (n = 953) as an initial treatment strategy. Of these, a total of 1,880 patients had baseline health status assessed (935 CABG, 945 PCI) and comprised the primary analytic sample.

The researchers found that at 2-year follow-up, measures of angina frequency, physical limitations, and quality-of-life indicated greater benefit of CABG compared to PCI. Beyond 2 years, the 2 revascularization strategies provided generally similar patient-reported outcomes.

The primary results of the FREEDOM trial demonstrated that for diabetic patients with multivessel coronary artery disease, CABG led to a benefit over PCI for the composite endpoint of death, myocardial infarction, or stroke, driven by reductions in both all-cause mortality and myocardial infarction. Although both revascularization strategies led to substantial and sustained improvements in quality of life and functional status in the FREEDOM trial, angina relief was slightly better with CABG than PCI, especially among patients with the most severe angina at baseline, the authors write.

These findings suggest that CABG could be preferred as the initial revascularization strategy for such patients. “Given the increased rate of stroke, as well as the well-recognized longer recovery period with CABG surgery, however, some patients who do not wish to face these acute risks may still choose the less invasive PCI strategy. For such patients, our study provides reassurance that there are not major differences in long-term health status and quality of life between the 2 treatment strategies. Nonetheless, it is important for patients to recognize that the similar late quality-of-life outcomes with PCI and CABG in the FREEDOM trial were achieved with higher rates of antianginal medication use and the need for more frequent repeat revascularization procedures among the PCI group.”

(doi:10.l001/jama.2013.279208; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by grants from the National Heart, Lung, and Blood Institute. Cordis and Boston Scientific provided the stents; Eli Lilly provided abciximab and an unrestricted research grant; and Sanofi-Aventis and Bristol-Myers Squibb provided clopidogrel. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR EARLY RELEASE: 7 A.M. (CT) WEDNESDAY, OCTOBER 9, 2013

Andrea Morelli, M.D., of the University of Rome, Italy, and colleagues conducted a study to investigate the effect of the short-acting beta-blocker esmolol on the heart rate of patients with severe septic shock and high risk of death.

Septic shock is associated with adverse effects on cardiac function. Beta-blocker therapy controls heart rate and may improve cardiovascular performance, but concerns remain that this therapy may lead to cardiovascular decompensation (inability of the heart to maintain adequate circulation), according to background information in the article.

The randomized phase 2 study was conducted in a university hospital intensive care unit (ICU) between November 2010 and July 2012. It recruited patients in septic shock with a heart rate of 95/min or higher requiring high-dose norepinephrine to maintain an average arterial pressure of 65 mm Hg or higher. The researchers randomly assigned 77 patients to receive a continuous infusion of esmolol to maintain heart rate between 80 beats per minute (BPM) and 94 BPM for the duration of their ICU stay and 77 patients to standard treatment. The primary outcome was a reduction in heart rate below the predefined threshold of 95 BPM and maintain a heart rate between 80 and 94 BPM over a 96-hour period.

The researchers found that the target range for heart rate was achieved in all patients in the esmolol group, which was significantly lower throughout the intervention period than what was achieved in the control group. In addition, the esmolol group had a 28-day mortality rate of 49.4 percent vs. 80.5 percent in the control group. Overall survival was higher in the esmolol group.

There was no clinically relevant differences between groups in other investigated cardiopulmonary variables nor in rescue therapy requirements.

“Further investigation of the effects of esmolol on clinical outcomes is warranted,” the authors write.

(doi:10.l001/jama.2013.278477; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Andrea Morelli, M.D., email Andrea.Morelli@uniroma1.it.

Please Note: The presentation of this study at the meeting will be available after the embargo at this link: http://www.esicm.org/news-article/lives2013hottopics.

Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR EARLY RELEASE: 7 A.M. (CT) WEDNESDAY, OCTOBER 9, 2013

Laurent Papazian, M.D., Ph.D., of Hôpital Nord, Marseille, France, and colleagues conducted a study to determine whether statin therapy decreased day-28 mortality among intensive care unit patients with ventilator-associated pneumonia.

Observational studies have reported that statins improve outcomes of various infections. Ventilator-associated pneumonia (VAP) is the most common infection in the intensive care unit (ICU) and is diagnosed in approximately 8 to 28 percent of ICU patients receiving mechanical ventilation. Ventilator-associated pneumonia is associated with increased mortality rates and high health care costs. New treatments are needed to improve the outcomes of VAP, according to background information in the article.

The trial, performed in 26 intensive care units in France from January 2010 to March 2013, randomized 300 patients to receive simvastatin (60 mg) or placebo, started on the same day as antibiotic therapy and given until ICU discharge, death, or day 28, whichever occurred first.

The study was stopped for futility at the first scheduled interim analysis after enrollment of the 300 patients. The researchers found that day-28 mortality was not lower in the simvastatin group (21.2 percent) than in the placebo group (15.2 percent). There were no differences in day-14, ICU, or hospital mortality rates, or in duration of mechanical ventilation.

“These findings do not support the use of statins [for] improving VAP outcomes,” the authors conclude.

(doi:10.l001/jama.2013.280031; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Laurent Papazian, M.D., Ph.D.,, email Laurent.Papazian@ap-hm.fr.

Please Note: The presentation of this study at the meeting will be available after the embargo at this link: http://www.esicm.org/news-article/lives2013hottopics.

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EMBARGOED FOR EARLY RELEASE: 7 A.M. (CT) WEDNESDAY, OCTOBER 9, 2013

Djillali Annane, M.D., Ph.D., of Raymond Poincare Hospital, Garches, France, and colleagues conducted a study to compare the effects of 2 types of intravenous fluids on survival for critically ill patients in an intensive care unit.

Thousands of patients in intensive care units (ICUs) throughout the world are treated every day with intravenous fluids, mainly to restore effective blood volume and perfusion of organs. Fluid therapy includes a broad variety of products that are categorized as crystalloids and colloids: crystalloids are salts; colloids are salts and gelatin, starch or protein. Compared with crystalloids, colloid solutions expand blood volume and last longer. However, colloids may increase illness and death in critically ill patients and many physicians considered crystalloids the best fluid therapy in this population, according to background information in the article.

The trial included 2,857 ICU patients who required fluid resuscitation for sepsis or trauma, or hypovolemic (decreased blood volume) shock for patients without sepsis or trauma at 57 intensive care units in France, Belgium, North Africa, and Canada. Recruitment into the trial started in February 2003 and ended in August 2012 with follow-up until November 2012. Patients were randomly assigned to crystalloids (n = 1,443) or colloids (n = 1,414) for all fluid intervention (except fluid maintenance) throughout their ICU stay. The primary outcome was death within 28 days.

The study reports no difference in outcomes between groups; there were 359 deaths (25.4 percent) among patients treated with colloids vs. 390 deaths (27.0 percent) among patients treated with crystalloids. At 90 days, there were 434 deaths (30.7 percent) among patients treated with colloids vs. 493 deaths (34.2 percent) among patients treated with crystalloids.

“In conclusion, among ICU patients with hypovolemia, the use of colloids compared with crystalloids did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy,” the authors write.

(doi:10.l001/jama.2013.280502; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Djillali Annane, M.D., Ph.D.,, email Djillali.Annane@rpc.aphp.fr.

Please Note: The presentation of this study at the meeting will be available after the embargo at this link: http://www.esicm.org/news-article/lives2013hottopics.

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EMBARGOED FOR EARLY RELEASE: 7 A.M. (CT) WEDNESDAY, OCTOBER 9, 2013

Zudin A. Puthucheary, M.R.C.P., of University College London, England, and colleagues conducted a study to characterize and evaluate the time course and pathophysiology of acute muscle loss in critical illness.

“Survivors of critical illness experience significant skeletal muscle weakness and physical disability, which can persist for at least 5 years. Muscle wasting contributes substantially to weakness acquired in the intensive care unit, but its time course and underlying pathophysiological mechanisms remain poorly characterized and not well understood,” according to background information in the article.

The study included 63 critically ill patients who were prospectively recruited within 24 hours of intensive care unit (ICU) admission from August 2009 to April 2011 at a university teaching and a community hospital in England. Muscle loss was determined through serial ultrasound measurement of the rectus femoris (a muscle in the quadriceps) cross-sectional area (CSA) on days 1,3,7, and 10.

The researchers found reductions in the rectus femoris CSA observed at day 10 (-17.7 percent). Decrease in the rectus femoris CSA was greater in patients who experienced multiorgan failure compared with single organ failure: -15.7 vs. -3.0 percent by day 7; -8.7 percent vs. -1.8 percent by day 3.

In addition, muscle protein synthesis was depressed to levels equivalent to the healthy fasted state on day 1. It increased to rates similar to the healthy fed state by day 7; but the net balance remained negative (i.e., destructive metabolism). “Importantly, these overall effects occurred despite the administration of enteral nutrition. Unexpectedly, higher protein delivery in the first week was associated with greater muscle wasting,” the authors write.

“Early interventions to enhance anabolism [a constructive phase of muscle building metabolism] may be required in addition to those aimed at reducing catabolism if muscle wasting is to be limited or prevented.”

(doi:10.l001/jama.2013.278481; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Zudin A. Puthucheary, M.R.C.P., email zudin.puthucheary.09@ucl.ac.uk.

Please Note: The presentation of this study at the meeting will be available after the embargo at this link: http://www.esicm.org/news-article/lives2013hottopics.

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EMBARGOED FOR EARLY RELEASE: 10:15 A.M. (CT) TUESDAY, OCTOBER 8, 2013

Bruno Mourvillier, M.D., of the Université Paris Diderot, Sorbonne Paris Cité, Paris, and colleagues conducted a study to examine whether treatment with hypothermia would improve the functional outcome of comatose patients with bacterial meningitis compared with standard care.

Among adults with bacterial meningitis, the death rate and frequency of neurologic complications are high, indicating the need for new therapeutic approaches. Clinical trials of patients with trauma who were treated with hypothermia have shown a decrease of intracranial pressure, suggesting a potential benefit of this technique in bacterial meningitis, according to background information in the article.

The randomized trial conducted in 49 intensive care units in France between February 2009 and November 2011 assessed 130 patients for eligibility and randomized 98 comatose adults with community acquired bacterial meningitis to the hypothermia group, where patients received a loading dose of 39°F cold saline and were cooled to 90°F to 93°F for 48 hours, or standard care.

The trial was stopped early because of concerns over excess mortality in the hypothermia group (25 of 49 patients [51 percent]) compared with the control group (15 of 49 patients [31 percent]). At 3 months, 86 percent in the hypothermia group compared with 74 percent in the control group had an unfavorable outcome (as gauged via the Glasgow Outcome Scale [a functional assessment inventory]).

“In conclusion, our trial does not support the use of hypothermia in adults with severe meningitis. Moderate hypothermia did not improve outcome in patients with severe bacterial meningitis and may even be harmful. Our results may have important implications for future trials on hypothermia in patients presenting with septic shock or stroke. Careful evaluation of safety issues in these future and ongoing trials are needed,” the authors write.

(doi:10.l001/jama.2013.280506; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Bruno Mourvillier, M.D., email bruno.mourvillier@bch.aphp.fr.

Please Note: The presentation of this study at the meeting will be available after the embargo at this link: http://www.esicm.org/news-article/lives2013presidentsession.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 8, 2013

Media Advisory: To contact Justin E. Bekelman, M.D., call Holly Auer at 215-349-5659 or email holly.auer@uphs.upenn.edu.

Justin E. Bekelman, M.D., of the University of Pennsylvania Perelman School of Medicine, Philadelphia, and colleagues conducted a study to examine whether single-fraction radiation treatment, shown to be as effective as multiple-fraction treatment with less potential for harm, has been incorporated into routine clinical practice for Medicare beneficiaries with prostate cancer and at what cost savings. Single-fraction radiotherapy is where a large dose of radiation is given in one session; with multiple-fraction radiotherapy, radiation is delivered in smaller doses over a longer period of time.

“Palliative radiotherapy, comprising l or more fractions (i.e., treatments) of daily radiation, is the mainstay of treatment for painful bone metastases. In 2005, a U.S.-based randomized trial demonstrated no difference in pain relief between single- and multiple-fraction radiotherapy for uncomplicated bone metastases, confirming results from international trials,” according to background information in the article appearing in the October 9 issue of JAMA.

As reported in the Research Letter, the authors selected patients age 65 years or older with prostate cancer and bone metastases and subsequent courses of radiotherapy from January 2006 through December 2009 from the Surveillance, Epidemiology and End Results (SEER)-Medicare database. For each patient, the researchers identified the initial outpatient course of radiotherapy following the first diagnosis of bone metastasis (index course) and determined the dates and number of radiotherapy fractions based on Medicare claims for radiation delivery (Medicare reimburses each radiotherapy fraction individually).

Of 3,050 patients included in the study, 3.3 percent had single-fraction radiotherapy and 50.3 percent received more than 10 fractions.  Average 45-day radiotherapy-related expenditures were a relative 62 percent lower for patients treated with single relative to multiple fractions ($1,873 for single vs. $4,967 for multiple fractions).

“Despite evidence demonstrating comparable pain relief for single-fraction treatment, only 3.3 percent of Medicare beneficiaries with bone metastases from prostate cancer received single-fraction treatment. Patients who received single-fraction radiotherapy had poorer prognoses, perhaps reflecting the perception that single-fraction treatment should be reserved for patients with limited life expectancy or poor performance status. However, single-fraction treatment has substantial benefits for patient-centric palliative care, including greater quality of life and convenience, reduced travel time, and lower treatment costs,” the authors conclude.

(doi:10.l001/jama.2013.277081; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by grants from the National Cancer Institute and American Cancer Society, and with funding from the Leonard Davis Institute for Health Economics. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Bekelman reported receiving honoraria from the American Society for Clinical Oncology; and travel expenses from the Radiation Oncology Institute. Dr. Epstein reported receiving institutional grant support from the Institute for Health Technology Studies. No other disclosures were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 8, 2013

Media Advisory: To contact Helmut Oettle, M.D., Ph.D., email Helmut.Oettle@charite.de.

Among patients with pancreatic cancer who had surgery for removal of the cancer, treatment with the drug gemcitabine for 6 months resulted in increased overall survival as well as disease-free survival, compared with observation alone, according to a study in the October 9 issue of JAMA.

“Pancreatic cancer is a disease with a poor prognosis, mainly because of the inability to detect the tumor at an early stage, its high potential for early dissemination, and its relatively poor sensitivity to chemotherapy or radiation therapy,” according to background information in the article. Even after complete removal of the tumor, the vast majority of patients relapse within 2 years, leading to a 5-year survival rate of less than 25 percent. No consensus has been reached on a standard treatment approach for additional therapy. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival after surgery has not previously been demonstrated.

Helmut Oettle, M.D., Ph.D., of the Charite-Universitatsmedizin Berlin, Germany, and colleagues conducted follow-up of a randomized trial that previously reported improvement in disease-free survival with adjuvant (in addition to surgery) gemcitabine therapy to determine if this treatment improved overall survival. Patients with macroscopically (observation made by the unaided eye) completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria; follow-up ended in September 2012. Patients were randomly assigned to either adjuvant gemcitabine treatment for 6 months or to observation alone.

A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0 percent) had relapsed. The median (midpoint) follow-up time was 136 months (11.3 years). The median disease-free survival was 13.4 months in the treatment group compared with 6.7 months in the observation group.

By the end of the follow-up period, 316 patients (89.3 percent) had died and 38 patients were still alive, 23 in the treatment group and 15 in the observation group. The researchers found a statistically significant difference in overall survival between the study groups, with a median of 22.8 months in the gemcitabine group compared with 20.2 months in the observation group. There was also a statistically significant absolute 10.3 percent improvement in the 5-year overall survival rate (20.7 percent vs. 10.4 percent) and a 4.5 percent improvement in the 10-year survival rate (12.2 percent vs. 7.7 percent), compared with observation alone.

“[These] data show that among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation resulted in increased overall survival as well as disease-free survival. These findings support the use of gemcitabine in this setting,” the authors conclude.

(doi:10.l001/jama.2013.279201; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This trial was supported in part by a grant from Lilly Germany. The study was further supported by the German Cancer Society and promoted by a research grant from the Charite-Universitatsmedizin Berlin. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (CT) MONDAY, OCTOBER 7, 2013

Media Advisory: To contact Mary T. Hawn, M.D., M.P.H., call Tyler Greer at 205-934-2041 or email tgreer@uab.edu. To contact editorial co-author Emmanouil S. Brilakis, M.D., Ph.D., call Lisa Warshaw at 214-648-3404 or email Lisa.Warshaw@utsouthwestern.edu.

Emergency surgery and advanced cardiac disease are risk factors for major adverse cardiac events after noncardiac surgery in patients with recent coronary stent implantation, according to a study published by JAMA. The study is being released early online to coincide with its presentation at the American College of Surgeons 2013 Annual Clinical Congress.

“Approximately 600,000 percutaneous coronary stent procedures are performed annually in the United States. Twelve to 23 percent of these patients undergo noncardiac surgery within 2 years of coronary stent placement,” according to background information in the article. Noncardiac surgery after recent coronary stent placement is associated with increased risk of adverse cardiac events. Delaying necessary noncardiac surgery can pose a clinical dilemma for a large number of patients. “Guidelines recommend delaying noncardiac surgery in patients after coronary stent procedures for 1 year after drug-eluting stents (DES) and for 6 weeks after bare metal stents (BMS). The evidence underlying these recommendations is limited and conflicting.”

Mary T. Hawn, M.D., M.P.H., of the University of Alabama at Birmingham, and colleagues conducted a study to determine risk factors for adverse cardiac events in patients undergoing noncardiac surgery within 24 months of coronary stent implantation. The study included 41,989 Veterans Affairs (VA) and non-VA operations performed within 2 years of a coronary stent implantation between 2000 and 2010. The researchers examined the association between timing of surgery and stent type and major adverse cardiac events (MACE). The primary outcome for the study was a composite 30-day MACE rate of all-cause mortality, heart attack, and cardiac revascularization.

Within 24 months of 124,844 coronary stent implantations (47.6 percent DES, 52.4 percent BMS), 28,029 patients (22.5 percent) underwent noncardiac operations resulting in 1,980 MACE (4.7 percent). The time from stent placement to surgery was associated with MACE for surgery in the first 6 months after the stent procedure, but not for surgery more than 6 months after the stent procedure. The 3 factors most strongly associated with MACE were nonelective surgical admission, having a heart attack in the 6 months preceding surgery, and a revised cardiac risk index score (comprising independent variables that predict an increased risk for cardiac complications) greater than 2.

MACE rate was 5.1 percent for BMS and 4.3 percent for DES. Stent type was not associated with MACE for surgeries more than 6 months after stent placement.

A case-control analysis of 284 matched pairs of patients found no association between cessation of antiplatelet therapy and MACE.

The authors note that there are several considerations that need to be given to these findings, including that the study sample comprised primarily older male patients, thus limiting the generalizability to women or younger men; the clinical factors that influenced stent selection were largely unavailable so they could not be accounted for in the models, and, accordingly, the results could be confounded by those factors; and many patients underwent more than 1 percutaneous coronary intervention (procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries) procedure during the dates of the study, which could result in misclassification bias for time from stent placement to surgery.

(doi:10.l001/jama.2013.278787; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study is supported by a VA Health Services Research & Development grant. In addition, Drs. Maddox and Richman are supported by VA Career Development Awards. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Itani reported having received research support from Merck and Cubist. No other disclosures were reported.

Editorial: Patient With Coronary Stents Needs Surgery – What to Do?

“How should the findings by Hawn et al and other recent studies influence the approach for patients who need surgery after stents?” asks Emmanouil S. Brilakis, M.D., Ph.D., and Subhash Banerjee, M.D., of the VA North Texas Health Care System, Dallas, in an accompanying editorial.

“The approach for patients with BMS should not change; these patients usually can undergo surgery within 6 weeks after coronary stent implantation with very low risk of stent thrombosis. For patients with DES, surgery performed at least 6 months after DES implantation appears to carry low risk for stent thrombosis, especially with contemporary, second-generation DES, which have more biocompatible, durable polymer coatings. Hence, nonurgent operations should be postponed until 6 months after stent implantation.”

(doi:10.l001/jama.2013.279123; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc.

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (CT) MONDAY, OCTOBER 7, 2013

Media Advisory: To contact corresponding author Kelly K. Hunt, M.D., call Laura Sussman at 713-745-2457 or email lsussman@mdanderson.org. To contact editorial co-author Monica Morrow, M.D., call Courtney A. DeNicola at 646-227-3633 or email Denicolc@mskcc.org.

Judy C. Boughey, M.D., Kelly K. Hunt, M.D., and colleagues for the Alliance for Clinical Trials in Oncology conducted a study to determine the false-negative rate of sentinel lymph node surgery in patients with node-positive breast cancer receiving chemotherapy before surgery. A false-negative is occurrence of negative test results in subjects known to have a disease for which an individual is being tested.  The study, published by JAMA, is being released early online to coincide with its presentation at the American College of Surgeons 2013 Annual Clinical Congress.

Axillary (the armpit region) lymph node status is an important prognostic factor in breast cancer and is used to guide local, regional, and systemic treatment decisions. Accurate determination of axillary involvement after chemotherapy is important; however, removing all axillary nodes to assess for residual nodal disease exposes many patients to the potential side effects of surgery and, potentially, only a subset will benefit. To avoid the complications associated with axillary lymph node dissection (ALND), it is preferable to identify nodal disease with the less invasive sentinel lymph node (SLN) surgical procedure, which results in fewer side effects, according to background information in the article.

The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial enrolled women from 136 institutions from July 2009 to June 2011 who had various stages of breast cancer and received neoadjuvant (before surgery) chemotherapy. Following chemotherapy, patients underwent both SLN surgery and ALND. The primary end point for the study was the false-negative rate of SLN surgery after chemotherapy in women who presented with cN1 disease (disease in movable axillary lymph nodes). The researchers evaluated the likelihood that the false-negative rate in patients with 2 or more SLNs examined was greater than 10 percent, the rate expected for women undergoing SLN surgery who present with clinical node-negative (cNO) disease.

Seven hundred fifty-six women were enrolled in the study. Of 663 evaluable patients with cN1 disease, 649 underwent chemotherapy followed by both SLN surgery and ALND. The researchers found that the false-negative rate was 12.6 percent with SLN surgery and exceeded the prespecified threshold of 10 percent. “Given this [10 percent] threshold, changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND in this patient population.”

(doi:10.l001/jama.2013.278932; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This work was supported by a grant from the National Cancer Institute awarded to the American College of Surgeons Oncology Group. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Sentinel Node Biopsy After Neoadjuvant Chemotherapy

“Decisions about using systemic therapy after neoadjuvant therapy are not dependent upon identifying residual cancer in lymph nodes when all the planned chemotherapy is given preoperatively to maximize the cancer response,” write Monica Morrow, M.D., and Chau T. Dang, M.D., of Memorial Sloan-Kettering Cancer Center, New York, in an accompanying editorial.

“However, accurate detection of residual lymph node cancer may be important in prospective trials of novel agents in which post–neoadjuvant treatment decisions, including possible research protocol participation, may hinge on the detection of residual disease. When considering how much information can be extrapolated from an initial SLN biopsy, it is important to recognize that patients with residual cancer following neoadjuvant therapy have some level of resistance to systemic therapy. These patients might require more aggressive local therapy such as complete ALND or radiation therapy to the axilla. Because there is no information regarding long-term local cancer control or survival for patients initially presenting with clinically node-positive disease who receive neoadjuvant therapy but have a 20 percent to 30 percent rate of residual cancer in the axilla following SLN biopsy, we do not believe that SLN biopsy, regardless of the number of SLNs removed, can be considered standard management for these patients.”

(doi:10.l001/jama.2013.7844; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Dang reports receiving grant funding from Genentech. No other disclosures were reported.

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (CT) MONDAY, OCTOBER 7, 2013

Media Advisory: To contact Karl Y. Bilimoria, M.D., M.S., call Megan McCann at 312-926-5900 or email memccann@nmh.org. To contact editorial author Edward H. Livingston, M.D., call Jim Michalski at 312-464-5785 or email jim.michalski@jamanetwork.org.

A new study published by JAMA questions using the rate of postoperative blood clots as a hospital quality measure. The study is being released early online to coincide with the American College of Surgeons 2013 Annual Clinical Congress.

The study examined whether surveillance bias (i.e., the greater the intensity of a search for a condition the greater likelihood it will be found) influences the reported rate of venous thromboembolism (VTE; blood clot). Venous thromboembolism, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common postoperative complication that remains a leading potentially preventable cause of postoperative illness and death. The Agency for Healthcare Research and Quality developed a risk-adjusted postoperative VTE rate measure, Patient Safety Indicator 12 (PSI-12), that has been incorporated into numerous quality improvement programs and public reporting initiatives.

“However, measuring VTE rates may be flawed because of surveillance bias, in which variation in outcomes reflects variation in screening and detection, or ‘the more you look, the more you find’ phenomenon. This can occur in a number of ways: hospitals may use screening protocols, in which asymptomatic patients routinely undergo VTE imaging studies on a certain postoperative day, or clinicians have a lower threshold to order a VTE imaging study for patients with minimal or equivocal signs or symptoms (e.g., any leg swelling prompts a venous duplex [an imaging procedure]). Hospitals that are more vigilant and perform more imaging studies for VTE may identify more VTE events, thus resulting in paradoxically worse performance on the VTE outcome measure,” according to background information in the article.

To examine the effect of surveillance bias on the validity of VTE as a quality measure, Karl Y. Bilimoria, M.D., M.S., of Northwestern University and Northwestern Memorial Hospital, Chicago, and colleagues conducted a study that merged 2010 Hospital Compare and American Hospital Association data from 2,838 hospitals. Next, 2009-2010 Medicare claims data for 954,926 surgical patient discharges from 2,786 hospitals that were undergoing 1 of 11 major operations were used to calculate VTE imaging and VTE event rates.

Instead of finding the expected relationship between adherence to VTE prevention and lower VTE rates, the researchers found that VTE prevention rates were positively correlated with VTE event rates. “A paradoxical relationship was also found between a measure of hospital structural characteristics reflecting quality [hospital characteristics that examine health care quality and which reflect a hospital’s resources and focus on programs intended to provide higher-quality care] and VTE event rates: hospitals with higher structural quality scores had better VTE [prevention] adherence rates, but they had unexpectedly higher risk-adjusted VTE rates. Most important, hospital VTE rates were associated with the intensity of detecting VTE with imaging studies.”

Hospitals in the lowest imaging rate quartile diagnosed 5.0 VTEs per 1,000 discharges, whereas the highest imaging rate quartile hospitals found 13.5 VTEs per 1,000 discharges.

“Our study calls into question the merit of the PSI-12 VTE outcome measure as a quality measure and its use in public reporting and performance-based payments. Hospitals reported to have the highest risk-adjusted VTE rates may in fact be providing vigilant care by ordering imaging studies to ensure that VTE events are not missed. Patients selecting hospitals according to publicly available metrics may be misled by currently reported VTE performance. The measure could be counterproductive if a hospital performs poorly on the VTE outcome metric, expends efforts to improve VTE prophylaxis resulting in increased awareness and vigilance in looking for VTE, and then finds more VTEs and becomes an even worse performer on the VTE measure,” the authors write.

(doi:10.l001/jama.2013.280048; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by AHRQ and a Center Development Award from Northwestern University and Northwestern Memorial Hospital to Dr. Bilimoria. Dr. Ju is supported by a grant from the National Institutes of Health. Dr. Haut is supported by a career development award from AHRQ. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 10 a.m. CT Monday, October 7 at this link.

Editorial: Postoperative Venous Thromboembolic Disease – Prevention, Public Reporting, and Patient Protection

“The study by Bilimoria et al demonstrates that VTE rates appearing on the Hospital Compare website reflect how aggressively clinicians look for VTE but probably are not directly related to quality of care,” writes Edward H. Livingston, M.D., Deputy Editor, JAMA, Chicago, in an accompanying editorial.

“In fact, because some physicians more aggressively look for complications, they find more and appear to have worse outcomes on the Hospital Compare website. Less obvious in the data from Bilimoria et al is that the very high compliance rate with VTE prophylaxis might result from many patients receiving treatments from which they are not likely to benefit. This is because current process measures were based on older guidelines that overestimated the benefits of VTE prophylaxis.”

“Public reporting of VTE rates should be reconsidered or curtailed because few hospitals have sufficient numbers of patients to show statistically significant effects of prophylactic measures on VTE rates. Improving the quality of care and safety for surgical patients will require more than simply public reporting of various process and outcome measures. The surgical and medical communities must make concerted efforts to follow the best available evidence and to conduct rigorous clinical trials to find the best ways to protect patients against the ‘unpredictable, treacherous and dramatically tragic’ occurrence of postoperative VTE.”

(doi:10.l001/jama.2013.280049; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR EARLY RELEASE: 6:15 P.M. (CT) FRIDAY, OCTOBER 4, 2013

Media Advisory: To contact Anthony D. Harris, M.D., M.P.H., call Karen Lancaster at 410-328-8919 or email klancaster@umm.edu. To contact editorial author Preeti N. Malani, M.D., M.S.J., call Shantell Kirkendoll at 734-764-2220 or email smkirk@med.umich.edu.

The wearing of gloves and gowns by health care workers for all intensive care unit (ICU) patient contact did not reduce the rate of acquisition of a combination of the bacteria methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), although there was a lower risk of MRSA acquisition alone, according to a study published online by JAMA. The study is being released early to coincide with its presentation at IDWeek 2013.

Antibiotic-resistance is associated with considerable illness, death, and costs. MRSA and VRE are primary causes of health care-associated infections. “The estimated cost of antibiotic-resistance in the United States is more than $4 billion per year. Health care-associated infections are the most common complication of hospital care, affecting an estimated 1 in every 20 inpatients. Numerous studies have shown that health care workers acquire bacteria on their hands and their clothing by touching patients,” according to background information in the article.

The Centers for Disease Control and Prevention recommend use of contact precautions (wearing gloves and gowns) when caring for patients colonized or infected with antibiotic-resistant bacteria. However, colonization with MRSA, VRE, or other antibiotic-resistant bacteria often is not detected and contact precautions, therefore, are not applied. It has not been known whether wearing gloves and gowns for all patient contact, not just for patients with known colonization, decreases acquisition of antibiotic-resistant bacteria in the ICU.

Anthony D. Harris, M.D., M.P.H., of the University of Maryland School of Medicine, Baltimore, and colleagues assessed whether wearing gloves and gowns for all patient contact in the ICU compared with the use of contact precautions for patients with known antibiotic-resistant bacteria reduces acquisition rates of MRSA and VRE. The randomized trial was conducted in 20 medical and surgical ICUs in 20 U.S. hospitals from January 2012 to October 2012. In the intervention ICUs, all health care workers were required to wear gloves and gowns for all patient contact and when entering any patient room. The primary outcome was acquisition of MRSA or VRE based on surveillance cultures (92,241 swabs) collected on admission and ICU discharge from 26,180 patients.

The researchers found that there was a decrease in both the intervention and control ICUs in the composite rate of MRSA or VRE acquisition over the study periods, but the difference in change was not statistically significant. There was a borderline statistically significant reduction in MRSA that was greater in the intervention group.

The intervention did not reduce VRE acquisition, but it did reduce MRSA acquisition, the authors write. “Better hand hygiene compliance on room exit occurred in the intervention ICUs. The intervention led to fewer health care worker-patient visits and did not increase the frequency of adverse events.”

(doi:10.l001/jama.2013.277815; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by grants from the Agency for Healthcare Research and Quality and from the National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Preventing Infections in the ICU – One Size Does Not Fit All

“Although the results of Harris et al failed to demonstrate an overall benefit of universal use of gloves and gowns to reduce acquisition of MRSA or VRE, this approach may be worth considering in some high-risk settings such as surgical ICUs wherein MRSA transmission is high among patients with newly implanted medical devices. If implemented, gloving and gowning should be just part of an overall strategy that includes efforts to optimize hand hygiene and prudent use of antimicrobials,” writes Preeti N. Malani, M.D., M.S.J., of the University of Michigan Health System, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, in an accompanying editorial.

“Although it is appealing to believe there is a simple approach to what should and should not be done to prevent infection in the ICU, best practices are more nuanced and unfortunately, one size does not fit all. The final approach must be adapted to fit the epidemiology of specific ICUs and should also consider the type of resources available. The study by Harris et al serves as a poignant reminder that many questions remain for what constitutes best practice in the care of critically ill patients. Ongoing investment in these sorts of resource intensive trials is essential for continued progress.”

(doi:10.l001/jama.2013.277816; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 1, 2013

Media Advisory: To contact Mads Wissenberg, M.D., email mads.wissenberg.joergensen@regionh.dk.

In Denmark between 2001 and 2010 there was an increase in bystander cardiopulmonary resuscitation (CPR) that was associated with an increase in survival following out-of-hospital cardiac arrest, according to a study in the October 2 issue of JAMA.

Out-of-hospital cardiac arrest affects approximately 300,000 individuals in North America annually. “Despite efforts to improve prognosis, survival remains low, with aggregated survival-to-discharge rates less than 8 percent.  In many cases, time from recognition of cardiac arrest to the arrival of emergency medical services (EMS) is long, leaving bystanders in a critical position to potentially influence patient prognosis through intervention before EMS arrival. However, only a minority of cardiac arrests receive bystander CPR,” according to background information in the article.

A low frequency of bystander CPR (<20 percent) and low 30-day survival (<6 percent) were identified nearly 10 years ago in Denmark, which led to several national initiatives to strengthen bystander resuscitation attempts and advanced care. Despite these nationwide efforts, it has been unknown whether there have been changes in resuscitation attempts by bystanders and improvements in survival.

To examine this question, Mads Wissenberg, M.D., of Copenhagen University Hospital Gentofte, Hellerup, Denmark, and colleagues analyzed trends in pre-hospital factors directly related to cardiac arrest as well as trends in survival during the past 10 years. The study included 19,468 patients with out-of-hospital cardiac arrest for whom resuscitation was attempted. The median (midpoint) age of patients was 72 years; 67 percent were men.

Throughout the study period, there was an increase in the proportion of patients receiving bystander CPR (21.1 percent to 44.9 percent). The increase in proportion of people defibrillated with an automatic defibrillator by a bystander was small (1.1 percent to 2.2 percent). “The large temporal increase in rates of bystander CPR observed in our study is most likely attributable to the overall increasing level of attention to resuscitation by bystanders in Denmark, including an increase in both mandatory and voluntary first aid training, with an estimate of more than 15 percent of the Danish population having taken CPR courses between 2008 and 2010.”

During the study period, there was an increase in the proportion of patients alive on arrival at the hospital (7.9 percent to 21.8 percent), as well as an increase in 30-day (3.5 percent to 10.8 percent) and 1-year (2.9 percent to 10.2 percent) survival. Bystander CPR was positively associated with 30-day survival.

“Our nationwide study had 4 major findings: rates of bystander CPR increased substantially; survival rates at 30 days and l year more than tripled; the number of survivors per 100,000 persons more than doubled; and rates of defibrillation by bystanders remained low,” the authors write.

“Because of the co-occurrence of other initiatives to improve outcome after cardiac arrest, a causal relationship between bystander CPR and survival remains uncertain.”

(doi:10.l001/jama.2013.278483; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Please Note: An author podcast on this study will be available post-embargo on the JAMA website.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 1, 2013

Investing in Evidence-Based Care for the Severely Mentally Ill

In a Viewpoint, Mark Olfson, M.D., M.P.H., of the New York State Psychiatric Institute, New York, and colleagues discuss the potential implications of giving 4 million previously uninsured people with severe mental disorders health insurance when the Affordable Care Act (ACA) is fully implemented in 2019.

“Expansion in health insurance coverage through the ACA [will] confer new mental health benefits for patients [and will] impose new demands on the provision of mental health services. To meet these challenges, health and mental health policy makers will need to focus on bringing greater coherence, service integration, and evidence-based care to a poorly functioning system of mental health care. Ex­panding access to evidence-based treatments and increasing their use within general medical and specialty mental health settings offers a tremendous opportunity to improve the lives of patients with severe mental disorders. The good news is that the ACA has several provisions that can support proven, evidence-based care strategies and that improvements can be achieved in the accessibility, effectiveness, and quality of care for people with serious mental illnesses, even in the face of a significant growth in demand. There are significant challenges but also significant opportunities. The clinical community cannot fail to seize them.”

(doi:10.l001/jama.2013.278065; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Mark Olfson, M.D., M.P.H., call Dacia Morris at 212-543-5421 or email morrisd@pi.cpmc.columbia.edu.

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 Pricing for Orphan Drugs – Will the Market Bear What Society Cannot?

Brian P. O’Sullivan, M.D., of the University of Massachusetts Medical School, Worcester, and colleagues examine the issue of drug pricing for rare diseases and personalized medicine based on individual and disease-specific genetic information, citing costs that can range from more than $100,000 per year to more than $300,000 per year.

“There are many partners in the development of a drug, including individuals who risk their own health as research participants, physicians who collaborate in clinical trials on behalf of their patients, and the scientific community that develops the basic mechanistic understanding of a disease. Patients, physicians, and other stakeholders should be involved in the pricing process. A model of reduced profitability, particularly for lifelong therapies, is ethically responsible and institutionally plausible but will require pharmaceutical companies to develop new models and educate investors about the long-term advantage of regaining the trust of the public. In exchange for greater transparency with respect to price structuring, companies will promote improved health, consumer confidence, and long-term profitability.”

(doi:10.l001/jama.2013.278129; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Brian P. O’Sullivan, M.D., call Mark Shelton at 508-856-2000 or email UMMSCommunications@umassmed.edu.

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 How the Pioneer ACO Model Needs to Change – Lessons From Its Best-Performing ACO

On July 16, 2013, the Center for Medicare & Medicaid Innovation released results from the first performance year of its Pioneer Accountable Care Organization (ACO) Model. The Pioneer program is the first ACO pilot administered by the government and the first to report results, which indicated that each of the 32 Medicare Pioneer ACOs improved quality and patient satisfaction, and the overall Pioneer program generated a total savings of $87.6 million.

“This important experiment may offer lessons for how to avoid Medicare’s predicted fiscal crisis. Even short of that, however, the findings demonstrate that, for the experiment to ultimately succeed, value-based payment and patient incentives to reward clinicians and health care organizations that offer more real value to patients must spread rapidly to other payers. Otherwise, the very delivery systems that are improving cost and quality may drop out of these important experiments,” write John Toussaint, M.D., of Thedacare Center for Healthcare Value, Appleton, Wisc., and colleagues.

“To expect health system leaders to take the necessary risks, strong federal-state and public-private partnerships will be needed to coordinate all payers in each region and, thereby, ensure that high-value care is rewarded consistently. CMS can play a key leadership role by more actively catalyzing multipayer ACOs now, but CMS cannot force private insurers to participate in the crucial payment reforms. It will take leadership from the U.S. health insurance industry, in partnership with CMS and health systems, to achieve true reform. Today there is a unique opportunity to correct the excessive growth in health care spending. The nation should not squander that chance.”

(doi:10.l001/jama.2013.279149; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact John Toussaint, M.D., call Jane Fazer at 920-659-7466 or email jfazer@createvalue.org.

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

For More Information: contact The JAMA Network^® Media Relations Department at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 1, 2013

Media Advisory: To contact Marsha A. Raebel, Pharm.D., call Amy Whited at 303-344-7518 or email Amy.L.Whited@kp.org. To contact editorial author Daniel P. Alford, M.D., M.P.H., call Gina DiGravio at 617-638-8480 or email gina.digravio@bmc.org.

In a group of patients who took chronic opioids for noncancer pain and who underwent bariatric surgery, there was greater chronic use of opioids after surgery compared with before, findings that suggest the need for proactive management of chronic pain in these patients after surgery, according to a study in the October 2 issue of JAMA.

“Bariatric surgery is used to treat obesity, as well as its comorbid conditions such as cardiovascular and metabolic diseases and chronic pain. Bariatric surgery-related weight loss is associated with improvements in osteoarthritis-associated knee pain and function and decreased back pain in observational studies,” according to background information in the article. “Because some pain syndromes are related to obesity, it is reasonable to assume that weight loss may be associated with better pain control.” It is not known if opioid use for chronic pain in obese individuals undergoing bariatric surgery is reduced.

Marsha A. Raebel, Pharm.D., of Kaiser Permanente Colorado, Denver, and colleagues conducted a study to examine opioid use following bariatric surgery in patients using opioids chronically for pain control prior to their surgery. The study included 11,719 individuals 21 years of age and older who had bariatric surgery between 2005 and 2009, and who were assessed 1 year before and after surgery, with latest follow-up by December 31, 2010.

In the year before bariatric surgery, 56 percent of patients had no opioid use, 36 percent had some opioid use, and 8 percent had chronic opioid use. Among pre-surgery chronic users, 77 percent continued chronic opioid use after surgery. Relative to the year before surgery, the amount of opioid use by patients who were chronic opioid users before surgery increased by 13 percent the first year after surgery and by 18 percent across 3 post-surgery years.

For the group with chronic opiate use prior to surgery, change in morphine equivalents before vs. after surgery did not differ between individuals who lost more than 50 percent of their excess body mass index vs. those who lost 50 percent or less.

Neither preoperative depression nor chronic pain diagnoses influenced changes in preoperative to postoperative chronic opioid use.

“We anticipated [that] weight loss after bariatric surgery would result in reduced pain and opioid use among patients with chronic pain. However, patients with and without preoperative chronic pain, depression diagnoses, or both had similar increases in postoperative chronic opioid use after surgery as those without chronic pain or depression. One possible explanation is that some patients likely had pain unresponsive to weight loss but potentially responsive to opioids,” the authors write.

“These findings suggest the need for better pain management in these patients following surgery.”

(doi:10.l001/jama.2013.278344; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This project was supported by a grant from the Agency for Healthcare Research and Quality. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Weighing In on Opioids for Chronic Pain – The Barriers to Change

In an accompanying editorial, Daniel P. Alford, M.D., M.P.H., of Boston Medical Center, discusses the importance of clinicians reducing or eliminating opioid use among patients when warranted.

“The safe and appropriate prescribing of opioids for chronic pain has become an important national priority. Although core competencies for pain management are being developed, knowing when and how to continue, change, or discontinue opioid therapy must be included in all clinician education efforts. Although Raebel et al are correct in reporting that better pain management strategies are needed, they also may have uncovered an equally important problem—the need to know if, when, and how to safely and effectively taper or discontinue opioid therapy for patients with chronic pain.”

(doi:10.l001/jama.2013.278587; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 1, 2013

Media Advisory: To contact JoAnn E. Manson, M.D., Dr.P.H., call Tom Langford at 617-534-1605 or email tlangford@partners.org. To contact Elizabeth G. Nabel, M.D., call Lori J. Schroth at 617-534-1604 or email ljschroth@partners.org.

Extended follow-up of the two Women’s Health Initiative hormone therapy trials does not support use of hormones for chronic disease prevention, although the treatment may be appropriate for menopausal symptom management in some women, according to a study in the October 2 issue of JAMA.

The hormone therapy trials of the Women’s Health Initiative (WHI) were stopped after investigators found that the health risks outweighed the benefits. Menopausal hormone therapy continues in clinical use, but questions remain regarding its risks and benefits over the long-term for chronic disease prevention, according to background information in the article.

JoAnn E. Manson, M.D., Dr.P.H., of Brigham and Women’s Hospital, Boston, and colleagues provide a comprehensive, integrated overview of findings from the two WHI hormone therapy trials with extended post-intervention follow-up and stratification by age and other important variables. The study included 27,347 postmenopausal women, ages 50 through 79 years, who were enrolled at 40 U.S. centers in 1993. Women with an intact uterus received conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) (n = 8,506) or placebo (n = 8,102). Women with prior hysterectomy received CEE alone (n = 5,310) or placebo (n = 5,429). The intervention lasted a median [midpoint] of 5.6 years in the CEE plus MPA trial, and 7.2 years in the CEE alone trial, with 6-8 additional years of follow-up until September 30, 2010.

The researchers found that overall, the risks of CEE+MPA during intervention outweighed the benefits. Risks were increased for coronary heart disease, breast cancer, stroke, pulmonary embolism, dementia (in women 65 years of age and older), gallbladder disease, and urinary incontinence. Benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during follow-up.

For CEE in women with prior hysterectomy, the benefits and risks during the intervention phase were more balanced, with increased risks of stroke and venous thrombosis, reduced risk of hip and total fractures, and a nonsignificant reduction in breast cancer. Post-intervention with CEE, a significant decrease in breast cancer emerged and most other outcomes were neutral. For CEE alone, younger women (age 50-59 years) had more favorable results for all-cause death and heart attack.

Neither regimen affected all-cause mortality.

“In summary, current WHI findings based on results from the intervention, postintervention, and cumulative posttrial stopping phases do not support the use of either estrogen-progestin or estrogen alone for chronic disease prevention,” the authors write.

“Even though hormone therapy may be a reasonable option for management of moderate to severe menopausal symptoms among generally healthy women during early menopause, the risks associated with hormone therapy, in conjunction with the multiple testing limitations attending subgroup analyses, preclude a recommendation in support of CEE use for disease prevention even among younger women. Current findings also suggest caution when considering hormone therapy treatment in older age groups, even in the presence of persistent vasomotor symptoms, given the high risk of coronary heart disease and other outcomes associated with hormone therapy use in this setting.”

(doi:10.l001/jama.2013.278040; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The Women’s Health Initiative is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services. Wyeth-Ayerst donated the study drugs. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, October 1 at this link.

Editorial: The Women’s Health Initiative – A Victory for Women and Their Health

“Twenty-two years following its inception, the WHI is a model for publicly funded rigorous, thorough, and objective clinical trials that have broadly affected human health. More than 160,000 women participated (many with great pride), more than 900 peer-reviewed reports from the WHI Publications and Presentations Committee have been published, the WHI data set is publically available, and scores of trainees have been mentored in fields from human biology to public health by participating in its analysis. The WHI has overturned medical dogma regarding the use of menopausal hormone therapy,” writes Elizabeth G. Nabel, M.D., of Brigham and Women’s Hospital, Boston, in an accompanying editorial.

“The WHI underscores the decisive importance of taxpayer-funded research conducted by the National Institutes of Health (NIH). Further reductions in the NIH budget virtually ensure that vitally important studies like the WHI will not be conducted, and hence, U.S. society will be poorly served. The fact that the public sector undertook this historic project (and that the researchers whose work is now reported have taken it to its next stage) has moved medical science forward by the most effective means of doing so—shattering prior dogma. For that, women and all patients whose health depends on sound science are grateful.”

(doi:10.l001/jama.2013.278042; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 24, 2013

Media Advisory: To contact Jeffrey J. Perry, M.D., M.Sc., call Jennifer Ganton at 613-798-5555, ext. 73325, or email jganton@ohri.ca. To contact editorial co-author David E. Newman-Toker, M.D., Ph.D., call Stephanie Desmon at 410-955-8665 or email sdesmon1@jhmi.edu.

Researchers have developed a simple clinical decision rule that may help doctors identify patients with headache in the emergency department who have subarachnoid hemorrhage (bleeding in a certain area of the brain), according to a study in the September 25 issue of JAMA.

“Headache accounts for approximately 2 percent of all emergency department visits, and subarachnoid hemorrhage is one of the most serious diagnoses, accounting for only 1 percent to 3 percent of these headaches. Although the decision to evaluate patients with new neurologic deficits is relatively straightforward, it is much more difficult to determine which alert, neurologically intact patients who present with headache alone require investigations—yet such patients account for half of all subarachnoid hemorrhages at initial presentation,” according to background information in the article.

A clinical decision rule is a tool that uses 3 or more variables from the history, examination, or simple tests to predict a diagnosis for a patient. These rules help clinicians make diagnostic or treatment decisions. The investigators had previously developed three clinical decision rules for use in patients with headache to determine which patients require investigation (imaging, lumbar puncture) for subarachnoid hemorrhage.

Jeffrey J. Perry, M.D., M.Sc., of the Ottawa Hospital Research Institute, Ottawa, Canada, and colleagues further studied the 3 rules in a group of neurologically intact patients with acute headache at 10 Canadian emergency departments from April 2006 to July 2010 to determine which might be most useful and accurate.

Among 2,131 adult patients with a headache peaking within 1 hour and no neurologic deficits, 132 (6.2 percent) had subarachnoid hemorrhage. The researchers found that information about age, neck pain or stiffness, witnessed loss of consciousness, onset during exertion, “thunderclap headache” (defined as instantly peaking pain) and limited neck flexion on examination (defined as inability to touch chin to chest or raise the head 3 inches off the bed if supine [lying face upward]), was 100 percent sensitive (detected all cases), but only 15.3 percent specific (designated many patients without SAH as possibly having it). The authors named the rule the Ottawa SAH (subarachnoid hemorrhage) Rule.

The authors write that the rule may provide evidence for physicians to use in deciding which patients require imaging to decrease the relatively high rate of missed subarachnoid hemorrhages.

“These findings only apply to patients with these specific clinical characteristics and require additional evaluation in implementation studies before the rule is applied in routine emergency clinical care.”

(doi:10.l001/jama.2013.278018; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: High-Stakes Diagnostic Decision Rules for Serious Disorders

David E. Newman-Toker, M.D., Ph.D., of the Johns Hopkins University School of Medicine, Baltimore, and Jonathan A. Edlow, M.D., of Harvard Medical School, Boston, write in an accompanying editorial that “future studies should seek to validate the Ottawa SAH Rule using larger samples.”

“Realistically, though, this may require use of administrative data and imputation of missing results. The rule should also be studied for the effect on patient outcomes as part of a clinical care pathway for headache diagnosis, ideally with direct comparison to an alternate care pathway based on the computed tomography-lumbar puncture rule. While awaiting further scientific advances, clinicians may find the refined Ottawa SAH Rule helpful to guide diagnostic decisions, but they should limit its use to patients with acute headache who are similar to those among whom the rule has been evaluated.”

(doi:10.l001/jama.2013.278019; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 24, 2013

Prevalence of Poorer Kidney Function Increases Among Adults 80 Years of Age and Older

Recent studies have shown that older adults with chronic kidney disease (CKD; defined as an estimated glomerular filtration rate [GFR; a measure of kidney function] of less than 60 mL/min/1.73 m²) have a high prevalence of concurrent complications and increased risk for adverse outcomes including mortality, cardiovascular disease, and kidney failure. A prior study demonstrated an increase in CKD prevalence between 1988-1994 and 1999-2004 for the general U.S. population. However, trends in CKD prevalence have not been reported for the oldest old [defined as 80 years of age or older],” write C. Barrett Bowling, M.D., M.S.P.H., formerly of the Veterans Affairs Medical Center, Atlanta, and colleagues.

As reported in a Research Letter, the authors used data from national surveys (the National Health and Nutrition Examination Surveys (NHANES) 1988-1994 and 1999-2010), to study participants age 80 years or older who completed a medical evaluation in the NHANES mobile examination center (n = 3,558).

The researchers found that the prevalence of an estimated GFR of less than 60 mL/min/1.73 m² was 40.5 percent in 1988-1994, 49.9 percent in 1999-2004, and 51.2 percent in 2005-2010. The prevalence of a more severe reduction in estimated GFR (less than 45 mL/min/1.73 m²) was 14.3 percent in 1988-1994, 18.6 percent in 1999-2004, and 21.7 percent in 2005-2010.

The findings point to a rise in prevalence in CKD among people 80 years and older and suggests that “efforts to address CKD among the oldest old may be necessary,” the authors conclude.

(doi:10.l001/jama.2013.252441; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact C. Barrett Bowling, M.D., M.S.P.H., call Jennifer Johnson McEwen at 404-727-5696 or email jrjohn9@emory.edu.

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 Viewpoints Appearing in This Issue of JAMA

 The Evolving Role and Value of Libraries and Librarians in Health Care

“As clinicians try to incorporate research into practice through comparative effectiveness research and decision support, they increasingly depend on technology to bring evidence to the bedside to improve quality and patient outcomes. Integrating current information into the processes of shared decision making and continuous learning supports the application of evidence in clinical decision making. Health sciences libraries and librarians have an increasingly important role in providing that information to clinicians as well as to patients and their families,” write Julia F. Sollenberger, M.L.S., and Robert G. Holloway Jr., M.D., M.P.H., of the University of Rochester, New York.

“With ongoing changes in health care as a result of information technology, health sciences libraries and librarians can play an important role in bringing high-quality, evidence-based medical information to the bedside, helping to make patient care both efficient and effective. Health care libraries and librarians are adapting to the changing information needs of physicians, other health care professions, researchers, and patients. With rigorous evaluation, enhanced librarian training, and continuous attention to advances in technology and needs of the users, health care librarians can provide value to patient care.”

(doi:10.l001/jama.2013.277050; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Julia F. Sollenberger, M.L.S., call Julie Philipp at 585-275-1309 or email julie_philipp@urmc.rochester.edu.

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Patient-Reported Outcome Alerts – Ethical and Logistical Considerations in Clinical Trials

In this Viewpoint, Derek Kyte, M.Sc.. of the University of Birmingham, England, and colleagues examine potential approaches to managing patient-reported outcomes (PRO) alerts (where a patient’s self-reported data causes trial personnel to become concerned for their wellbeing or safety).

“There are strong ethical and scientific reasons to reach consensus about how PRO alerts should be dealt with by researchers. Ad hoc interventions may leave participants at risk of harm, place strain on individual researchers, risk cointervention bias, and compromise the integrity of the study. The optimal and most appropriate management strategy is unclear at this stage—the correct response may depend on the nature of the trial and its risk profile. Even if inter-trial consistency is not appropriate, consistency should exist at least across sites within trials. Researchers must, therefore, recognize that PRO alerts are a possibility that should be accommodated at the design stage of the study. Finally, arrangements set out in the protocol need to be reinforced by institutional review boards, with clear information for both participants and researchers.”

(doi:10.l001/jama.2013.277222; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Melanie Calvert, Ph.D., email m.calvert@bham.ac.uk.

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

For More Information: contact The JAMA Network^® Media Relations Department at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 24, 2013

Media Advisory: To contact corresponding author Timothy W. Jones, M.B.B.S., F.R.A.C.P., M.D., email Tim.Jones@health.wa.gov.au. To contact editorial author Pratik Choudhary, M.B.B.S., M.R.C.P., M.D., email pratik.choudhary@kcl.ac.uk.

Use of an insulin pump with a sensor that suspends insulin delivery when blood glucose falls below a set threshold reduced the rate of severe and moderate hypoglycemia among patients with type 1 diabetes and impaired awareness of hypoglycemia, according to a study in the September 25 issue of JAMA.

Hypoglycemia is a critical obstacle to the care of patients with type 1 diabetes. Sensor-augmented pump therapy with an automated insulin suspension or low glucose suspension function is a technology has the potential to reduce the duration and frequency of significant hypoglycemia, according to background information in the article.

Trang T. Ly, M.B.B.S., D.C.H., F.R.A.C.P., of the Princess Margaret Hospital for Children, Perth, Australia, and colleagues randomized 95 patients with type 1 diabetes, average age 19 and recruited from December 2009 to January 2012 in Australia to standard insulin pump therapy (n = 49) or low-glucose triggered automated insulin suspension (n = 46) for 6 months. The researchers selected patients with impaired awareness of hypoglycemia because they are at significantly higher risk of experiencing hypoglycemic events. Approximately one-third of patients with type 1 diabetes have evidence of impaired hypoglycemia awareness.

The researchers found that sensor-augmented pump therapy with low-glucose triggered automated insulin suspension reduced the combined rate of severe and moderate hypoglycemia in patients with type l diabetes. After 6 months of treatment and controlling for the baseline hypoglycemia rate, the number of severe and moderate hypoglycemia events in the low-glucose suspension group decreased from 175 to 35, whereas the number of events decreased from 28 to 16 in the pump-only group. Analysis of the data indicated that the adjusted incidence rate of hypoglycemia was lower for the low-glucose suspension group than for the pump-only group.

“These findings suggest that automated insulin suspension can reduce the incidence of hypoglycemic events in those most at risk, that is, those with impaired awareness of hypoglycemia,” the authors write.

(doi:10.l001/jama.2013.277818; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was partly funded by the Juvenile Diabetes Research Foundation. Insulin pumps and glucose sensors were provided by Medtronic via an unrestricted grant. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Insulin Pump Therapy With Automated Insulin Suspension

Pratik Choudhary, M.B.B.S., M.R.C.P., M.D., of King’s College London, writes in an accompanying editorial that the data from this and other studies demonstrates “the ability of sensor-augmented insulin pumps with threshold suspension function to provide a significant reduction in severe hypoglycemia.”

“These data can now be used to evaluate the health economic benefits of this therapy and also can be used by clinicians, payers, and regulatory authorities to help make this therapy and technology more widely available to patients who struggle daily with hypoglycemia.”

(doi:10.l001/jama.2013.278576; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported receiving speaker fees and travel support from Medtronic Ltd. and having participated in clinical studies funded by Medtronic.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 24, 2013

Media Advisory: To contact Sarah D. Berry, M.D., M.P.H., call Jennifer Davis at 617-363-8282 or email jdavis@hsl.harvard.edu.

A second bone mineral density (BMD) screening four years after a baseline measurement provided little additional value when assessing risk for hip or other major osteoporotic fracture among older men and women untreated for osteoporosis, and resulted in little change in risk classification used in clinical management, findings that question the common clinical practice of repeating a BMD test every 2 years, according to a study in the September 25 issue of JAMA.

Bone mineral density testing is important in the management of osteoporosis. Guidelines for initiating pharmacologic treatment for osteoporosis are based on BMD in conjunction with risk classification scores. “Despite the utility of BMD, the value of repeating a BMD screening test is unclear,” according to background information in the article. Currently, Medicare reimburses for BMD screening every 2 years regardless of baseline BMD and without a restriction on the number of repeat tests. Twenty-two percent of screened Medicare beneficiaries receive a repeat BMD test within 3 years, on average 2.2 years apart. “Given the priority of reducing health care costs while improving quality of care, it is important to determine whether repeat BMD screening is useful.”

Sarah D. Berry, M.D., M.P.H., of the Institute for Aging Research, Hebrew SeniorLife, Boston, and colleagues conducted a study to determine whether changes in BMD after 4 years provide additional information on fracture risk beyond baseline BMD. The population-based cohort study involved 310 men and 492 women from the Framingham Osteoporosis Study with 2 measures of femoral neck BMD taken four years apart between 1987-1999. The primary measured outcome was risk of hip or other major osteoporotic fracture through 2009 or 12 years following the second BMD measure. Average age was 75 years.

After a median (midpoint) follow-up of 9.6 years, the average BMD change was -0.6 percent per year. During follow-up, 113 participants (14.1 percent) experienced 1 or more major osteoporotic fractures (88 hip, 24 spine, 5 shoulder, and 33 forearm fractures). The net change in the percentage of participants with a hip fracture correctly reclassified with a second BMD measure was 3.9 percent; the net change in the percentage of participants without hip fracture correctly reclassified by a second BMD measure was -2.2 percent. The researchers found that the net change in the percentage of participants with a major osteoporotic fracture correctly reclassified with a second BMD measure was 9.7 percent; the net change in percentage of participants without major osteoporotic fracture correctly reclassified by a second BMD measure was -4.6 percent.

The authors conclude that for older patients not undergoing treatment for osteoporosis, “… BMD change provided little additional information beyond baseline BMD for the clinical management of osteoporosis.” The second BMD measure reclassified a small proportion of individuals, and it is unclear whether this reclassification justifies the current U.S. practice of performing serial BMD tests at 2.2-year intervals. “Further study is needed to determine an appropriate rescreening interval and to identify individuals who might benefit from more frequent rescreening intervals.”

(doi:10.l001/jama.2013.277817; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, September 24 at this link.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 24, 2013

Media Advisory: To contact Stephen P. Messier, Ph.D., call Will Ferguson at 336-758-5390 or email ferguswg@wfu.edu.

Among overweight and obese adults with knee osteoarthritis, combining intensive diet and exercise led to less knee pain and better function after 18 months than diet-alone and exercise-alone, according to a study in the September 25 issue of JAMA.

“Osteoarthritis (OA) is the leading cause of chronic disability among older adults. Knee OA is the most frequent cause of mobility dependency and diminished quality of life, and obesity is a major risk factor for knee OA. Current treatments for knee OA are inadequate; of patients treated pharmacologically, only about half experience a 30 percent pain reduction, usually without improved function,” according to background information in the article.

Stephen P. Messier, Ph.D., of Wake Forest University, Winston-Salem, N.C., and colleagues conducted a study to determine whether a 10 percent or greater reduction in body weight induced by diet, with or without exercise, would reduce joint loading and inflammation and improve clinical outcomes more than exercise alone. The randomized trial was conducted between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. The study included 454 overweight and obese older community-dwelling adults (age 55 years or older with a body mass index of 27-41) with pain and radiographic knee OA. The interventions consisted of intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise.

Of the participants, 399 (88 percent) completed the study (returned for 18-month follow-up). Retention did not differ between groups. Among the findings of the study:

• Average weight loss was greater in the diet and exercise group and the diet group compared with the exercise group;
• When compared with the exercise group, the diet and exercise group had less knee pain, better function, faster walking speed, and better physical health-related quality of life;

• Participants in the diet and exercise and diet groups had greater reductions in Interleukin 6 (a measure of inflammation) levels than those in the exercise group;

Those in the diet group had greater reductions in knee compressive force than those in the exercise group.

“Osteoarthritis and other obesity-related diseases place an enormous physical and financial burden on the U.S. health care system. The estimated 97 million overweight and obese Americans are at substantially higher risk for many life-threatening and disabling diseases, including OA. The findings from [this trial] suggest that intensive weight loss may have both anti-inflammatory and biomechanical benefits; when combining weight loss with exercise, patients can safely achieve a mean long-term weight loss of more than 10 percent, with an associated improvement in symptoms greater than with either intervention alone,” the authors write.

(doi:10.l001/jama.2013.277669; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 17, 2013

Media Advisory: To contact Renee Y. Hsia, M.D., call Elizabeth Fernandez at 415-514-1592 or email Elizabeth.Fernandez@UCSF.edu.

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“Emergency department (ED) use has been affected by insurance patterns over time and will likely be further affected by expansions of coverage from health care reform.” Uninsured patients are often thought of as high and frequently inappropriate ED users, but insured patients, particularly those with Medicaid coverage, may have difficulties accessing primary care and may rely on EDs more frequently than uninsured patients, write Renee Y. Hsia, M.D., M.Sc., of the University of California, San Francisco, and colleagues.

In a Research Letter appearing in the September 18 issue of JAMA, the authors investigated recent trends in the association between insurance coverage and ED use. The study was a retrospective analysis of California ED visits by adults 19 to 64 years of age from 2005-2010 that used the nonpublic versions of data from the California Office of Statewide Health Planning and Development’s Emergency Discharge Data and Patient Discharge Data. To study variations by insurance coverage, ED visits were grouped into 4 categories based on expected source of payment: Medicaid, private insurance, self-pay or uninsured, and other. The authors also looked at ED visits for ambulatory care sensitive conditions (ACSCs)

The researchers found that between 2005 and 2010, the number of visits to California EDs by adults overall increased by 13.2 percent from 5.4 to 6.1 million per year. The largest increase in visits occurred in 2009. The share of total visits increased among adults with Medicaid coverage and uninsured adults, whereas the share decreased among adults with private insurance. Visit rates to the ED among adult Medicaid beneficiaries were higher than uninsured and privately insured patients.

“Increasing ED use by Medicaid beneficiaries could reflect decreasing access to primary care, which is supported by our findings of high and increasing rates of ED use for ambulatory care sensitive conditions by Medicaid patients. The increase in ED visits was highest in 2009, likely due to the H1N1 pandemic and the influence of the economic downturn on coverage transitions and access to care,” the authors write.

(doi:10.l001/ jama.2013.228331; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

For More Information: contact The JAMA Network^® Media Relations Department at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 17, 2013

Media Advisory: To contact Richard Saitz, M.D., M.P.H., call Gina DiGravio at 617-638-8480 or email gina.digravio@bmc.org. To contact editorial author Patrick G. O’Connor, M.D., M.P.H., call Helen Dodson at 203-436-3984 or email helen.dodson@yale.edu.

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Persons with alcohol and other drug dependence who received chronic care management including relapse prevention counseling and medical, addiction and psychiatric treatment were no more abstinent than those who received usual primary care, according to a study in the September 18 issue of JAMA.

Chronic care management (CCM) is a way of delivering care that has been shown to be effective for chronic medical and mental health conditions. “Chronic care management is multidisciplinary patient-centered proactive care, a way to organize services that provides coordination and expertise, and has been effective for depression, medical illnesses, and tobacco dependence (a substance use disorder),” the authors write. Trials of integrated medical and addiction care suggest that CCM may be effective for treating addiction, particularly since care elements long known to be effective for addiction overlap with CCM approaches.

Richard Saitz, M.D., M.P.H., of Boston Medical Center, and colleagues conducted a study to examine whether CCM for alcohol and other drug dependence improves substance use outcomes compared with usual primary care. Participants (n = 563) were recruited between September 2006 to September 2008 from a freestanding residential detoxification unit, and from referrals to an urban teaching hospital and from advertisements; 95 percent completed 12-month follow-up. Participants were randomized to receive CCM (n=282) or no CCM (n=281).

The chronic care management group received longitudinal care coordinated with a primary care clinician; motivational enhancement therapy; relapse prevention counseling; and on-site medical, addiction, and psychiatric treatment, social work assistance, and referrals (to specialty addiction treatment mutual help). The primary care group received a timely appointment and a list of addiction treatment resources including a telephone number to arrange counseling.

The researchers found no difference in abstinence from stimulants, opioids, and heavy drinking between the CCM intervention and control group (44 percent vs. 42 percent, respectively, at 12 months). In a subgroup of patients with alcohol dependence, there were fewer alcohol problems among those who received the intervention.

The authors did not detect differences in secondary outcomes of addiction severity, health-related quality of life, or drug problems.

The authors write that current health care reforms in the United States include a focus on CCM in patient-centered medical homes to reduce chronic disease burden and to reduce costs (both of which are among the highest for those with addiction), in part because numerous studies have found such benefits for medical and mental health conditions. “Even though CCM is effective for a number of chronic conditions, it may be premature to assume that CCM will be the solution to improve the quality of care for and reduce costs of patients with addiction,” the authors write. Further research is warranted to determine whether more intensive or longer-duration CCM, or CCM designed differently, might do so.”

(doi:10.l001/jama.2013.277609; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was funded by a grant from the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Cheng reports having served on data monitoring committees for Johnson & Johnson and Janssen. No other disclosures were reported.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, September 17 at this link.

Editorial: Managing Substance Dependence as a Chronic Disease – Is the Glass Half Full or Half Empty?

“How should clinicians, clinical leaders, researchers, and policy makers interpret the results of this negative study?” asks Patrick G. O’Connor, M.D., M.P.H., of the Yale University School of Medicine, New Haven, Conn., in an accompanying editorial.

“… The findings may suggest that the glass is half full rather than half empty. This study places the evaluation of CCM for the treatment of substance use disorders firmly on the agenda for future research in this area. The CCM concept is sound, at least for some chronic illnesses, and highly relevant to today’s evolving health care system. More research on CCM of addiction is clearly warranted to identify specific CCM approaches that may be useful for specific substance-using populations. Clinicians and health care organizations should move forward cautiously in this area pending convincing evidence that specific CCM models are effective for the treatment of substance use disorders in selected patient populations. Comprehensive, integrated management of addiction can only benefit patients—it remains to be seen how best to deliver substance abuse treatment effectively in an evidence-based manner.”

(doi:10.l001/jama.2013.277610; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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