EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 20, 2013

Study Shows Gypsum Wallboard Does Not Keep Out Carbon Monoxide, Questioning CO Detector Exemptions For Certain Types of Residences

“Carbon monoxide (CO) poisoning is a significant U.S. health problem, responsible for approximately 500 accidental deaths annually, and a risk of 18 percent to 35 percent for cognitive brain injury 1 year after poisoning. Most morbidity and mortality from CO poisoning is believed to be preventable through public education and CO alarm use. States have been enacting legislation mandating residential CO alarm installation. However, as of December 2012, 10 of the 25 states with statutes mandating CO alarms exempted homes without fuel-burning appliances or attached garages, believing that without an internal CO source, risk is eliminated. This may not be true if CO diffuses directly through wall-board material,” write Neil B. Hampson, M.D., of Virginia Mason Medical Center, Seattle, and colleagues.

As reported in a Research Letter, a Plexiglas chamber divided by various configurations of gypsum wallboard was used to determine whether CO diffuses across drywall. Wallboard of various thickness levels were tested. Carbon monoxide test gas was infused into the chamber and then CO concentrations were measured once per minute in each chamber for 24 hours. The authors sought to determine how rapidly a concentration of CO toxic to humans would be reached in the noninfused chamber and whether diffusion would then continue.

The researchers found that carbon monoxide diffused across single-layer gypsum wallboard of 2 thicknesses, double-layer wallboard, and painted double-layer wallboard. “Gypsum’s permeability to CO is due to its porosity. … The ability of CO to diffuse across gypsum wallboard may explain at least some instances of CO poisoning in contiguous residences. Exempting residences without internal CO sources from the legislation mandating CO alarms may put people in multifamily dwellings at risk for unintentional CO poisoning.”

(JAMA. 2013;310[7]:745-746. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Neil B. Hampson, M.D., call Gale Robinette at 206-341-1509 or email gale.robinette@vmmc.org.

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 Viewpoints Appearing in This Issue of JAMA

 A Call for an End to the Diet Debates

“As the obesity epidemic persists, the time has come to end the pursuit of the ‘ideal’ diet for weight loss and disease prevention. The dietary debate in the scientific community and reported in the media about the optimal macronutrient-focused weight loss diet sheds little light on the treatment of obesity and may mislead the public regarding proper weight management. Numerous randomized trials comparing diets differing in macronutrient compositions (e.g. low-carbohydrate, low-fat, Mediterranean) have demonstrated differences in weight loss and metabolic risk factors that are small and inconsistent,” write Sherry L. Pagoto, Ph.D., of the University of Massachusetts Medical School, Worcester, and Bradley M. Appelhans, Ph.D., of Rush University Medical Center, Chicago.

“Because behavioral adherence is much more important than diet composition, the best approach is to counsel patients to choose a dietary plan they find easiest to adhere to in the long term. Patients should develop an appropriate physical activity program and learn behavioral modification to promote long-term adherence. Although research specifically focused on improving adherence is ongoing, the number of studies being conducted is small compared with head-to-head macronutrient-focused diet comparison studies. Advancing obesity treatment requires emphasis on the biological, behavioral, and environmental factors influencing adherence to lifestyle changes and developing reimbursement strategies to support lifestyle interventions.”

(JAMA. 2013;310[7]:687-688. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Sherry L. Pagoto, Ph.D., call Lisa Larson at 508-856-2689 or email LisaM.Larson@umassmed.edu.

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Early Detection and Intervention in Schizophrenia – A New Therapeutic Model

Jeffrey A. Lieberman, M.D., of the New York State Psychiatric Institute, New York, and colleagues write that “a new conceptualization of schizophrenia has led to a new care model developed for patients with first-episode schizophrenia that fosters recovery and prevents disability.”

“The elements of this care model for proactive treatment of early psychosis include (1) reducing the duration of active symptoms through rapid diagnosis and treatment of patients with first-episode psychosis (ensuring adherence to the pharmacologic regimen is critical); (2) sustaining treatment and preventing psychotic relapse following the acute treatment response in the context of maintenance medication or supported discontinuation; (3) integrating pharmacologic management with psychosocial therapies and recovery-oriented approaches that involve other mental health professionals in the context of a disease-management approach to the illness; and (4) offering social and vocational services, substance abuse treatment, family education and support, and assistance with coping with past trauma and the trauma of psychosis, as well as suicide prevention and safety planning.”

(JAMA. 2013;310[7]:689-690. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Jeffrey A. Lieberman, M.D., call Rachel Yarmolinsky at 212-543-5353 or email Yarmoli@nyspi.columbia.edu.

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 Perspectives on Complementary and Alternative Medicine Research

In this Viewpoint, Josephine P. Briggs, M.D., and Jack Killen, M.D., of the National Center for Complementary and Alternative Medicine, National Institutes of Health (NIH), Bethesda, Md., describe the 2013 NIH perspective on investment in research on complementary and alternative medicine interventions and call for a more nuanced conversation about them.

“First and foremost, the conversation should reflect current realities, including the evolution of research priorities and the shifts in funding to projects that address them rather than areas that have less scientific promise or less amenability to scientific investigation. Second, although discussions about complementary and alternative medicine often imply a clear demarcation distinguishing a monolithic alternative domain from conventional medicine, this distinction breaks down in the realities of the pluralistic U.S. health care system. The boundaries also shift—in both directions as evidence changes. Third, the conversation should recognize the state of current evidence indicating that some of these practices are useful and can appropriately be integrated into care, some should not, some are dangerous and merit regulatory attention, and many are somewhere in between.”

(JAMA. 2013;310[7]:691-692. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Josephine P. Briggs, M.D., call Katy Danielson at 301-496-7790 or email nccampress@mail.nih.gov.

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, AUGUST 20, 2013

Media Advisory: To contact Bjarke Feenstra, Ph.D., email fee@ssi.dk.

CHICAGO – Researchers have identified a new genome-wide significant locus (the place a gene occupies on a chromosome) for infantile hypertrophic pyloric stenosis (IHPS), a serious gastrointestinal condition associated with gastrointestinal obstruction, according to a study in the August 21 issue of JAMA. Characteristics of this locus also suggest the possibility of an inverse relationship between levels of circulating cholesterol in neonates and IHPS risk.

“Infantile hypertrophic pyloric stenosis is the leading cause of gastrointestinal obstruction in the first months of life, with an incidence of l to 3 per 1,000 live births in Western countries. It affects 4 to 5 times as many boys as girls and typically presents 2 to 8 weeks after birth with projectile vomiting, weight loss, and dehydration. Although IHPS is a clinically well-defined entity, the etiology [cause] of the condition is complex and remains unclear,” according to background information in the article. A genetic predisposition is well established; IHPS aggregates strongly in families and has an estimated heritability of more than 80 percent; but knowledge about specific genetic risk variants is limited.

Bjarke Feenstra, Ph.D., of the Statens Serum Institut, Copenhagen, Denmark, and colleagues conducted a study to search the genome for genetic associations with IHPS and to validate findings in 3 independent sample sets. During stage 1, the researchers used reference data from the 1,000 Genomes Project for imputation into a genome-wide data set of 1,001 Danish surgery-confirmed samples (cases diagnosed 1987-2008) and 2,371 disease-free controls. In stage 2, the 5 most significantly associated loci were tested in independent case-control sample sets from Denmark (cases diagnosed 1983-2010), Sweden (cases diagnosed 1958-2011), and the United States (cases diagnosed 1998-2005), with a total of 1,663 cases and 2,315 controls.

The researchers found a new genome-wide significant locus for IHPS at chromosome 11q23.3 in a region harboring the apolipoprotein (APOA1/C3/A4/A5) gene cluster. APOA1 encodes apolipoprotein A-I, which is the major protein component of high-density lipoprotein (HDL) cholesterol in plasma. “The functional characteristics of the 11q23.3 locus suggest the hypothesis that low levels of circulating lipids in newborns are associated with increased risk of IHPS. We addressed this hypothesis by measuring plasma levels of total, low-density lipoprotein, and HDL cholesterol as well as triglycerides in prospectively collected umbilical cord blood from a set of 46 IHPS cases and 189 controls of Danish ancestry, most of which were also in the discovery sample,” the authors write. They found lower cholesterol levels at birth in infants who went on to develop IHPS compared with matched controls who did not develop the disease.

“Further investigation is required to illuminate the functional significance of the association identified here.”

(JAMA. 2013;310(7):714-721; 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, AUGUST 20, 2013

Media Advisory: To contact Orlando M. Gutierrez, M.D., M.M.Sc., call Tyler Greer at 205-934-2041 or email tgreer@uab.edu. To contact editorial co-author Wolfgang C. Winkelmayer, M.D., Sc.D., call Tracie White at 650-723-7628 or email traciew@stanford.edu.

CHICAGO – In a large national study, higher levels of the urinary albumin-to-creatinine ratio was associated with greater risk of incident but not recurrent coronary heart disease in black individuals when compared with white individuals, according to a study in the August 21 issue of JAMA.

“Increased urinary albumin excretion is an important marker of kidney injury and a strong risk factor for cardiovascular disease. Black individuals have higher levels of urinary albumin excretion than white individuals, which may contribute to racial disparities in cardiovascular outcomes,” according to background information in the study. Previous research indicated that the association of urinary albumin-to-creatinine ratio (ACR) with incident stroke differed by race, such that higher urinary ACR was independently associated with a greater risk of incident stroke in black individuals but not in white individuals. Whether similar associations extend to coronary heart disease (CHD) is unclear.

Orlando M. Gutierrez, M.D., M.M.Sc., of the University of Alabama at Birmingham, and colleagues conducted a study to determine whether the association of urinary albumin excretion with CHD events differs by race. The study included black and white U.S. adults, 45 years and older, who were enrolled within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007 with follow-up through December 2009. The researchers examined race-stratified associations of urinary ACR in 2 groups: (1) incident CHD among 23,273 participants free of CHD at baseline; and (2) first recurrent CHD event among 4,934 participants with CHD at baseline.

Over a median (midpoint) 4.5 years of follow-up, a total of 616 incident CHD events (259 among black participants and 357 among white participants) were observed. Of these, 421 were nonfatal heart attacks and 195 were CHD-related deaths. Analysis of the data indicated that age- and sex-adjusted incidence rates increased in the higher categories of urinary ACR in both black and white participants. The adjusted incidence rates in the 2 highest categories of ACR were approximately 1.5-fold greater in black participants when compared with white participants.

“In models adjusted for traditional cardiovascular risk factors and medications, higher baseline urinary ACR was associated with greater risk of incident CHD among black participants but not white participants,” the authors write. “Among those with CHD at baseline, fully adjusted associations of baseline urinary ACR with first recurrent CHD event were similar between black participants vs. white participants.”

“These findings confirm the results of prior studies showing that urinary ACR is an important biomarker for CHD risk in the general population, even among individuals with ACR values that are less than the current threshold for defining microalbuminuria.  Additionally, to our knowledge, this is the first study to demonstrate that the higher risk of incident CHD associated with excess ACR differs by race.”

“Future studies should examine whether addition of ACR can improve the diagnosis and management of CHD in black individuals,” the researchers conclude.

(JAMA. 2013;310(7):706-713; 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: Kidney Disease and Cardiovascular Risk – Whether Black or White Race Matters

Daniel E. Weiner, M.D., M.S., of Tufts Medical Center, Boston, and Wolfgang C. Winkelmayer, M.D., Sc.D., of the Stanford University School of Medicine, Palo Alto, Calif., (and Associate Editor, JAMA), write in an accompanying editorial the “the study by Gutierrez and colleagues reinforces that even mild elevations in urine ACR are associated with increased CVD risk, even though this level of albuminuria will have no meaningful systemic effects.”

“Differentiating between low normal and high normal urinary ACR may further aid in cardiovascular risk stratification, particularly in black individuals, and motivate prevention and heightened monitoring of these individuals.”

(JAMA. 2013;310(7):697-698; 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, AUGUST 20, 2013

Media Advisory: To contact Matthew J. Parkes, B.Sc., email matthew.parkes@manchester.ac.uk

CHICAGO – Although a pooling of data from 12 studies showed a statistically significant association between use of lateral wedge insoles and lower pain in medial knee osteoarthritis, among trials comparing wedge insoles with neutral insoles, there was no significant or clinically important association between use of wedge insoles and reduction in knee pain, according to a study in the August 21 issue of JAMA.

“Osteoarthritis of the knee is a common painful chronic disease whose prevalence is increasing and for which there are few efficacious treatment options. The increase in rates of knee replacement for osteoarthritis has made the identification of effective nonsurgical treatments a high priority. Medial osteoarthritis is one of the most common subtypes of knee osteoarthritis. One type of treatment for medial knee osteoarthritis involves reducing medial (inner) loading to ease the physical stress applied to that compartment of the joint. The wedge is placed under the sole of the foot and angulated so that it is thicker over the lateral than the medial edge, transferring loading during weight bearing from the medial to the lateral knee compartment,” according to background information in the study.  However, studies examining knee pain following treatment have shown inconsistent findings.

Matthew J. Parkes, B.Sc., of the University of Manchester, England, and colleagues conducted a meta-analysis to assess the efficacy of lateral wedge treatments (shoes and insoles designed to reduce medial knee compartment loading) in reducing knee pain in patients with medial knee osteoarthritis. The authors conducted a search of the medical literature to identify randomized trials that compared shoe-based treatments (lateral heel wedge insoles or shoes with variable stiffness soles) aimed at reducing medial knee load, with a neutral or no wedge control condition. The wedge needed to be of 5° to 15° of angulation, which is a level shown in previous studies to reduce external knee adduction moment (torque). Studies must have included patient-reported pain as an outcome. Twelve trials met inclusion criteria with a total of 885 participants of whom 502 received lateral wedge treatment.

The researchers found, when considering all 12 trials, the overall effect estimate was a standard mean difference in pain between interventions that showed a moderately significant effect of a lateral wedge on pain reduction. However, the findings were highly heterogeneous across studies. Larger trials with a lower risk of bias suggested a null association.

When trials were grouped according to the control group treatment, the authors found that compared with neutral inserts, lateral wedges had no association with knee pain and heterogeneity was much lower across trial findings.

“These results suggest that compared with control interventions, lateral wedges are not efficacious for the treatment of knee pain in persons with medial knee osteoarthritis.”

(JAMA. 2013;310(7):722-730; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This review was funded by a special strategic award grant from Arthritis Research UK. Drs. LaValley and Felson are supported by a grant from the U.S. National Institutes of 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, AUGUST 20, 2013

Media Advisory: To contact Marc G. Jaffe, M.D., call Ann Marie Wallace at 510-390-3355 or email ann.m.wallace@kp.org; or call Joe Fragola at 415-902-3737 or email joe.c.fragola@kp.org. To contact editorial co-author Abhinav Goyal, M.D., M.H.S., call Jennifer Johnson McEwen at 404-727-5696 or email jrjohn9@emory.edu.

CHICAGO – Implementation of a large-scale hypertension program that included evidence-based guidelines and development and sharing of performance metrics was associated with a near-doubling of hypertension control between 2001 and 2009, compared to only modest improvements in state and national control rates, according to a study in the August 21 issue of JAMA.

“Hypertension affects 65 million adults in the United States (29 percent) and is a major contributor to cardiovascular disease. Although effective therapies have been available for more than 50 years, fewer than half of Americans with hypertension had controlled blood pressure in 2001-2002. Many quality improvement strategies for control of hypertension exist, but to date, no successful, large-scale program sustained over a long period has been described,” according to background information in the article.

Marc G. Jaffe, M.D., of the Kaiser Permanente South San Francisco Medical Center, South San Francisco, Calif., and colleagues conducted a study to examine the results of a hypertension program in Northern California and to compare rates of hypertension control in that program with statewide and national estimates. The Kaiser Permanente Northern California (KPNC) hypertension program included a multifaceted approach to blood pressure control. Key elements of the program include establishment of a comprehensive hypertension registry, development and sharing of performance metrics, evidence-based guidelines, medical assistant visits for blood pressure measurement, and single-pill combination pharmacotherapy. Patients identified as having hypertension within an integrated health care delivery system in Northern California from 2001-2009 were included.

The comparison group comprised insured patients in California between 2006-2009 who were included in the Healthcare Effectiveness Data and Information Set (HEDIS) commercial measurement by California health insurance plans participating in the National Committee for Quality Assurance (NCQA) quality measure reporting process. A secondary comparison group was included to obtain the reported national average NCQA HEDIS commercial rates of hypertension control between 2001-2009 from health plans that participated in the NCQA HEDIS quality measure reporting process.

Between 2001 and 2009, the KPNC hypertension registry increased from 349,937 to 652,763. Among hypertension registry members, the average age was 63 years. More than half of registry members were women, and the proportion was similar across study years.

The researchers found that the NCQA HEDIS commercial hypertension control rate within KPNC increased after implementation of the hypertension program from 43.6 percent in 2001 to 80.4 percent in 2009. “In contrast, the national mean NCQA HEDIS control rate increased from 55.4 percent to 64.1 percent between 2001 and 2009. California-wide control rates were available since 2006 and were similar but slightly higher than the national average (63.4 percent vs. 69.4 percent from 2006 to 2009),” the authors write.

Following the study period, the NCQA HEDIS hypertension control rate within KPNC continued to improve, from 83.7 percent in 2010 to 87.1 percent in 2011.

The authors also found that the rate of lisinopril-hydrochlorothiazide single-pill combination (SPC) prescriptions in KPNC increased from 13 to 23,144 prescriptions per month from 2001 to 2009. During this period, the percentage of angiotensin-converting enzyme (ACE) inhibitor prescriptions dispensed as an SPC (in combination with a thiazide diuretic) increased from less than 1 percent to 27.2 percent

“In summary, implementation of a large-scale hypertension program was associated with improvements in hypertension control rates between 2001 and 2009,” the researchers conclude.

(JAMA. 2013;310(7):699-705; 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, August 20 at this link.

Editorial: Health System-Wide Quality Programs to Improve Blood Pressure Control

In an accompanying editorial, Abhinav Goyal, M.D., M.H.S., and William A. Bornstein, M.D., Ph.D., of the Emory School of Medicine, Atlanta, comment on the findings of this study.

“The transition to value-based models in all sectors of U.S. health care and the looming growth of accountable care organizations and shared savings models provides a framework wherein health care organizations have the flexibility to implement care models optimized to deliver the best outcomes at the lowest cost, without being constrained to face-to-face physician encounters to drive reimbursement. In this context, studies such as the one by Jaffe et al on the science of health system-level quality improvement are particularly powerful and hopefully will prompt hypertension guidelines and perhaps other guidelines to include recommendations about system-level approaches to managing risk factors.”

(JAMA. 2013;310(7):695-696; 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. Bornstein reported serving on an advisory panel for CIGNA. Dr. Goyal reported no disclosures.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 13, 2013

Study Examines Incidence of Sports-Related Sudden Death in France

“Although screening programs prior to participation in sports have been used for many years for young competitive athletes, it has been suggested that screening programs might also be worthwhile in the general population. Description of the incidence of sports-related sudden death by specific sports as well as by sex and age may help inform the debate,” write Eloi Marijon, M.D., of the Université Paris Descartes, Sorbonne Paris Cité, Paris, and colleagues.

As reported in a Research Letter, the study was performed in France between 2005 and 2010, and overall, 60 of 96 administrative districts participated voluntarily, and included a population of approximately 35 million inhabitants. Sports-related sudden death was reported by local emergency medical services and defined as death occurring during or within 1 hour of cessation of sports activity, whether the resuscitation was successful or not. Calculation of incidence of sports-related sudden death only included cases during moderate and vigorous exertion, and was assessed by sex, age range, as well as by the 3 most frequent sports among women in France (cycling, jogging, and swimming).

There were 775 sports-related sudden death cases during moderate to vigorous exertion over 5 years. Of these cases, 42 (5 percent) were women. “The average age of sudden death in women was 44 years vs. 46 years in men. The overall average incidence rate in women was estimated to be 0.51 per million female sports participants vs. 10.1 in men. The incidence rate of sports-related sudden death significantly increased with age among men, but not among women. The overall incidence of sudden death differed by sport for men but not women,” the authors write.

“Compared with men, we found a lower incidence of sports-related sudden death in women and differences by age and sport. … Strategies for community screening prior to participation in recreational sports activities should consider both the types of sports to be undertaken and the sex of participants. The incidence of sports-related sudden death is probably underestimated in this study.”

(JAMA. 2013;310[6]:642-643. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Eloi Marijon, M.D., email eloi_marijon@yahoo.fr.

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Viewpoints Appearing in This Issue of JAMA

The Evolution of the Master Diagnostician

In this Viewpoint, Gurpreet Dhaliwal, M.D., of the University of California, San Francisco, and Allan S. Detsky, M.D., Ph.D., of the University of Toronto, examine the “characterizations of the master diagnostician of the past, present, and future and considers the ways in which medical care has, is, and will be structured to help physicians develop and optimize this fundamental skill.”

“Although the clinical environment has changed tremendously in the past 50 years, the way the mind reasons and learns has not. The challenge has always been to structure training and work environments that care for patients but to also tend to the lifelong learning of the clinicians. In different eras, physicians have gotten the different parts of that puzzle right. Medical educators, administrators, and policy makers should take the best of the past and present to structure future training and practice that makes the master diagnostician the norm rather than the exception.”

(JAMA. 2013;310[6]:579-580. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Allan S. Detsky, M.D., Ph.D., call Suniya Kukaswadia at 416-978-7752 or email suniya.kukaswadia@utoronto.ca.

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 Social Media and Physicians’ Online Identity Crisis

“Physicians are increasingly counted among Facebook’s 1 billion users and Twitter’s 500 million members. Beyond these social media platforms, other innovative social media tools are being used in medical practice, including for online consultation, in the conduct of clinical research, and in medical school curricula,” write Matthew DeCamp, M.D., Ph.D., of Johns Hopkins University, Baltimore, and colleagues.

Institutions, medical boards, and physician organizations worldwide have promulgated recommendations for physician use of social media. A common theme among these recommendations is that physicians should manage patient-physician boundaries online by separating their professional and personal identities. “In this Viewpoint, we contend that this is operationally impossible, lacking in agreement among active physician social media users, inconsistent with the concept of professional identity, and potentially harmful to physicians and patients. A simpler approach that avoids these pitfalls asks physicians not whether potential social media content is personal or professional but whether it is appropriate for a public space.”

(JAMA. 2013;310[6]:581-582. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Matthew DeCamp, M.D., Ph.D., call Leah Ramsay at 202-642-9640 or email Lramsay@jhu.edu.

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, AUGUST 13, 2013

Media Advisory: To contact Rakesh M. Suri, M.D., D.Phil., call Traci Klein at 507-284-5005 or email Klein.traci@mayo.edu. To contact editorial author Catherine M. Otto, M.D., call Leila Gray at 206-685-0381 or email leilag@uw.edu.

CHICAGO – In a study that included patients with mitral valve regurgitation due to a condition known as flail mitral valve leaflets, performance of early surgical correction compared with initial medical management was associated with greater long-term survival and lower risk of heart failure, according to a study in the August 14 issue of JAMA.

“Degenerative mitral regurgitation [backflow of blood from the left ventricle to the left atrium due to mitral valve insufficiency] is common and can be surgically repaired in the vast majority of patients, improving symptoms and restoring normal life expectancy. Despite the safety and efficacy of contemporary surgical correction, an ongoing international debate persists regarding the need for early intervention in patients without American College of Cardiology (ACC)/American Heart Association (AHA) guideline class I triggers (no or minimal symptoms and absence of left ventricular dysfunction). This is in part propagated by discordant views of the prognostic consequences of uncorrected severe mitral regurgitation; considered as benign by those supporting medical watchful waiting (nonsurgical observation until a distinct event is encountered) vs. conveying excess mortality and morbidity (including heart failure and atrial fibrillation) by those advocating early surgical intervention,” according to background information in the article.

To understand the comparative effectiveness of early surgery vs. initial medical management strategies, Rakesh M. Suri, M.D., D.Phil., of the Mayo Clinic College of Medicine, Rochester, Minn., and colleagues conducted a study to ascertain the comparative effectiveness of initial medical management (nonsurgical observation) vs. early mitral valve surgery following the diagnosis of mitral regurgitation due to flail leaflets (an abnormality of the mitral valve in which a portion of the valve has lost its normal support). For the study, the researchers used data from the Mitral Regurgitation International Database (MIDA) registry, which includes 2,097 patients with flail mitral valve regurgitation (1980-2004) receiving routine cardiac care from 6 tertiary centers (France, Italy, Belgium, and the United States). Of 1,021 patients with mitral regurgitation without ACC and AHA guideline class I triggers, 575 patients were initially medically managed and 446 underwent mitral valve surgery within 3 months following detection.

Within 3 months following diagnosis, 8 patients died, 5 (1.1 percent) after early surgery vs. 3 (0.5 percent) during initial medical management; 9 patients developed heart failure, 4 (0.9 percent) after early surgery vs. 5 (0.9 percent) during initial medical management; and 30 patients developed new-onset atrial fibrillation, 6.2 percent after early surgery vs. 1.2 percent during initial medical management.

Ninety-eight percent of patients were followed up from diagnosis until death or at least 5 years. A total of 319 deaths were observed during an average follow-up time of 10.3 years. “Survival among the entire unmatched cohort for early surgery was 95 percent at 5 years, 86 percent at 10 years, 63 percent at 20 years vs. 84 percent at 5 years, 69 percent at 10 years, and 41 percent at 20 years for initial medical management, favoring early surgery,” the authors write. Early surgical correction of mitral valve regurgitation was associated with a 5-year reduction in mortality of 53 percent.

With class II triggers (atrial fibrillation or pulmonary hypertension), survival was again better with early surgery, both overall and in the matched cohort at 10 years.

During follow-up, 167 patients incurred at least 1 incident episode of heart failure representing a rate of 16 percent at 10 years and 27 percent at 20 years. In the overall cohort, heart failure was less frequent after early surgery (7 percent for early surgery vs. 23 percent for initial medical management at 10 years and 10 percent for early surgery vs. 35 percent for initial medical management at 20 years), with a heart failure risk reduction of approximately 60 percent.

Reduction in late-onset atrial fibrillation was not observed.

“These findings emanate from institutions that together provide a very high rate of mitral valve repair (>90 percent) with low operative mortality, emphasizing that such results might also be achieved in routine practice at many advanced repair centers,” the authors write. “The advantages associated with early surgical correction of mitral valve regurgitation were confirmed in both unmatched and matched populations, using multiple statistical methods.”

(JAMA. 2013;310(6):609-616; 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: Surgery for Mitral Regurgitation – Sooner or Later?

In an accompanying editorial, Catherine M. Otto, M.D., of the University of Washington School of Medicine, Seattle, comments on how the findings of this study may influence patient care.

“The study group is atypical compared with most patients with chronic severe mitral regurgitation seen in clinical practice who are referred for surgical intervention at symptom onset or when serial imaging shows early left ventricular (LV) dysfunction. In patients with severe mitral regurgitation due to mitral valve prolapse, early surgery is reasonable if surgical risk is low and the likelihood of successful valve repair is high, which is often the case for patients with a flail leaflet; the new data support this recommendation.”

“However, if surgical risk is high or if the likelihood of valve repair is low, it remains uncertain whether early surgical intervention is appropriate in the asymptomatic patient with severe mitral regurgitation due to a flail leaflet when LV size and systolic function are normal. Although the majority of these patients will develop clear indications for valve surgery within 2 years, it may be reasonable to postpone the risks of having an intervention and having a prosthetic valve as long as possible.”

(JAMA. 2013;310(6):587-588; 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, AUGUST 13, 2013

Media Advisory: To contact Pamela N. Peterson, M.D., M.S.P.H., call Jenny Bertrand at 303-520-9591 or email Jennifer.bertrand@dhha.org.

CHICAGO – In a large population of Medicare beneficiaries with heart failure who underwent implantation of a cardiac resynchronization therapy defibrillator, patients who had the cardiac characteristics of left bundle-branch block and longer QRS duration had the lowest risks of death and all-cause, cardiovascular, and heart failure readmission, according to a study in the August 14 issue of JAMA.

“Clinical trials have shown that cardiac resynchronization therapy (CRT) improves symptoms and reduces mortality and readmission among selected patients with heart failure and left ventricular systolic dysfunction. Following broad implementation of CRT, it was recognized that one-third to one-half of patients receiving the therapy for heart failure do not improve. Identification of patients likely to benefit from CRT is particularly important, because CRT defibrillator (CRT-D) implantation is expensive, invasive, and associated with important procedural risks. A primary question regarding optimal patient selection for CRT is whether patients with longer QRS duration or left bundle-branch block (LBBB) morphology derive greater benefit than others,” according to background information in the article. QRS duration is a measurement of the electrical conducting time of the heart on an electrocardiogram. Left bundle-branch block is a cardiac conduction abnormality.

Pamela N. Peterson, M.D., M.S.P.H., of Denver Health Medical Center, Denver, and colleagues conducted a study to determine the long-term outcomes of patients undergoing CRT-D implantation and associations between combinations of QRS duration and presence of LBBB and outcomes, including all-cause mortality; all-cause, cardiovascular, and heart failure readmission; and complications. The study included Medicare beneficiaries in the National Cardiovascular Data Registry’s ICD Registry between 2006 and 2009 who underwent CRT-D implantation. Patients were stratified according to whether they were admitted for CRT-D implantation or for another reason, then categorized as having either LBBB or no LBBB and QRS duration of either 150 ms or greater or 120 to 149 ms. Patients underwent follow-up for up to 3 years, through December 2011.

Mortality rates in the primary overall study cohort were 0.8 percent at 30 days, 9.2 percent at 1 year, and 25.9 percent at 3 years. Rates of all-cause readmission were 10.2 percent at 30 days and 43.3 percent at 1 year. The researchers found that after adjustment for demographic and clinical factors, compared with patients with LBBB and QRS duration of 150 ms or greater, the other 3 groups had significantly higher risks of mortality and all-cause, cardiovascular, and heart failure readmission. The adjusted risk of 3-year mortality was lowest among patients with LBBB and QRS duration of 150 ms or greater (20.9 percent), compared with LBBB and QRS duration of 120 to 149 ms (26.5 percent), no LBBB and QRS duration of 150 ms or greater (30.7 percent), and no LBBB and QRS duration of 120 to 149 ms (32.3 percent). The adjusted risk of l-year all-cause readmission were also lowest among patients with LBBB and QRS duration of 150 ms or greater (38.6 percent), compared with LBBB and QRS duration of 120 to 149 ms (44.8 percent), no LBBB and QRS duration of 150 ms or greater (45.7 percent), and no LBBB and QRS duration of 120 to 149 ms (49.6 percent).

There were no observed associations with complications.

“Although prior data regarding the effects of CRT as a function of QRS duration are largely limited to meta-analyses of clinical trials, this study provides an important perspective on the role of QRS duration in outcomes after CRT implantation in clinical practice,” the authors write.

“These findings support the use of QRS morphology and duration to help identify patients who will have the greatest benefit from CRT-D implantation.”

(JAMA. 2013;310(6):617-626; 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, AUGUST 6, 2013

Number of Scientific Publications on Firearms Shows Modest Increase in Recent Years

“In January 1996, Congress passed an appropriations bill amendment prohibiting the U.S. Centers for Disease Control and Prevention (CDC) from using ‘funds made available for injury prevention … to advocate or promote gun control.’ This provision was triggered by evidence linking gun ownership to health harms, created uncertainty among CDC officials and researchers about what could be studied, and led to significant declines in funding,” write Joseph A. Ladapo, M.D., Ph.D., of the New York University School of Medicine, New York, and colleagues.

As reported in a Research Letter, the authors evaluated the change in the number of publications on firearms in youth compared with research on other leading causes of death before and after the Congressional action, focusing on children and adolescents because they disproportionately experience gun violence and injury. The 10 leading causes of death among children and adolescents ages 1 to 17 years were identified using CDC data on mortality between 1991 and 2010. Each cause was then matched to a Medical Subject Heading, and PubMed was searched from 1991-2010 using causes of death and child or adolescent to determine the annual number of publications.

“We only found modest increases in the number of scientific publications on firearms between 1991 and 2010, in contrast to other leading causes of death in youth. The change in number of publications on firearms was lower than anticipated compared with publications not on firearms. There was not a discrete point identified at which the pattern of publications changed. Therefore, whether the Congressional action or other events were responsible is unclear,” the authors write.

“The effect on publications after President Obama’s January 2013 memorandum directing the CDC to conduct or support research on the causes of gun violence and approaches to prevent it should be evaluated.”

(JAMA. 2013;310[5]:532-534. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Joseph A. Ladapo, M.D., Ph.D., call Lorinda Klein at 212-404-3533 or email Lorindaann.klein@nyumc.org.

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 Viewpoints Appearing in This Issue of JAMA

 Traumatic Brain Injury – An International Knowledge-Based Approach

“Traumatic brain injury [TBI] research and clinical care are decades behind other diseases, such as cancer and cardiovascular disease, and there is an important need to close existing knowledge gaps. Political will and resources are needed to create meaningful change for the global disease that is traumatic brain injury,” write Geoffrey T. Manley, M.D., Ph.D., of the University of California, San Francisco, and Andrew I. R. Maas, M.D., Ph.D., of the University of Antwerp, Belgium.

“The complexity of TBI is such that no single investigator, institution, funding organization, or private company can make progress on its own. Traumatic brain injury needs a broad-based, sustainable, multidisciplinary approach aimed at elucidating mechanisms of TBI biology, identifying risk factors, and developing treatments. First steps should include the design of longitudinal studies to follow the natural history of TBI, which should help prioritize promising avenues for research.”

(JAMA. 2013;310[5]:473-474. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Geoffrey T. Manley, M.D., Ph.D., call Juliana Bunim at 415-502-6397 or email juliana.bunim@ucsf.edu.

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 Implications of Combat Casualty Care for Mass Casualty Events

“Violence from explosives and firearms results in mass casualty events in which the injured have multiple penetrating and soft tissue injuries. Events such as those in Boston, Massachusetts; Newtown, Connecticut; and Aurora, Colorado, as well as those in other locations, such as Europe and the Middle East, demonstrate that civilian trauma may at times resemble that seen in a combat setting,” write Eric A. Elster, M.D., of the Uniformed Services University of the Health Sciences, Bethesda, Md., and colleagues. “The military has learned that implementation of evidence-based, clinical practice guidelines can reduce potentially preventable death. Certain aspects of these lessons also apply to multiple casualty scenarios in civilian settings.”

“As the United States and other nations continue to prepare for casualty scenarios from explosives or mass shooting events involving civilians, lessons from wartime trauma care and resuscitation may be helpful in planning responses. The trauma practices that have resulted from more than a decade of combat casualty care and research are transferable to the civilian world. Continuing to translate these lessons from war should provide a foundation to help reduce mortality and morbidity among civilians injured in future mass casualty events.”

(JAMA. 2013;310[5]:475-476. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Eric A. Elster, M.D., call Gwendolyn Smalls at 301-295-3981 or email gwendolyn.smalls@usuhs.edu.

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Management of Acute Stress, PTSD, and Bereavement – WHO Recommendations

“In 2010, the World Health Organization (WHO) launched the Mental Health Gap Action Program (mhGAP) Intervention Guide for nonspecialized health settings (i.e., for general health staff in first- and second-level health facilities, including primary care and district hospital settings) to address the wide treatment gap for mental disorders in low- and middle-income countries,” write Wietse A. Tol, Ph.D., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues.

In this Viewpoint, the authors describe the new guidelines that expand the mhGAP Intervention Guide to include assessment and management of conditions specifically related to exposure to stress, such as acute traumatic stress, PTSD, and bereavement.

“… practitioners are offered these evidence-based guidelines to strengthen care for people exposed to extreme stress.” These new WHO guidelines are being released to coincide with publication of the JAMA Viewpoint. After the embargo time, see http://www.who.int/mental_health/resources/emergencies.

(JAMA. 2013;310[5]:477-478. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Mark van Ommeren, Ph.D., email vanommerenm@who.int.

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An Evidence-Based Response to Intimate Partner Violence – WHO Guidelines

In June 2013, the World Health Organization (WHO) published Responding to Intimate Partner Violence and Sexual Violence Against Women, providing evidence-based recommendations to guide clinicians. “This guidance is important because a clinician may be the first professional contact for persons exposed to intimate partner violence (IPV),” write Gene Feder, M.B., B.S., M.D., F.R.C.G.P., of the University of Bristol, United Kingdom, and colleagues. The guidelines are based on systematic reviews of a range of topics, including identification and approaches to providing care for women and their children after disclosure of IPV and sexual violence. In this Viewpoint, the authors summarize and discuss the IPV recommendations.

“Violence against women is a complex psychosocial and international problem. Clinicians should be part of a larger, multisystem, and coordinated solution that takes into account individual-, community-, and system-level responses, as well as a lifespan approach to violence risk assessment and prevention for those who experience IPV as well as for perpetrators. Research evidence should inform clinical actions, regardless of the disease, condition, or exposure. Although the quality of available supporting evidence is low to moderate, the new WHO guidelines provide evidence-based recommendations to assist clinicians to respond in a caring, respectful, and safe manner to women exposed to violence and may contribute to a better health care response to IPV internationally.”

(JAMA. 2013;310[5]:479-480. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Gene Feder, M.B., B.S., M.D., F.R.C.G.P., email gene.feder@bristol.ac.uk.

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, AUGUST 6, 2013

Media Advisory: To contact Carol S. North, M.D., M.P.E., call Russell Rian at 214-648-3404 or email russell.rian@utsouthwestern.edu.

CHICAGO – A review of articles on disaster and emergency mental health response interventions and services indicates that in postdisaster settings, a systematic framework of case identification, triage, and mental health interventions should be integrated into emergency medicine and trauma care responses, according to a study in the August 7 issue of JAMA, a theme issue on violence/human rights.

“Mental and physical consequences of major disasters have garnered increasing attention to the need for an effective community response. It is estimated that much of the U.S. population will be exposed to a … natural disaster during their lives; adding technological events such as airplane crashes and intentional human acts such as terrorism to this estimate would yield even higher numbers. Mental health effects of disaster exposures are relevant to informing care for survivors of all forms of trauma, because 9 of 10 people are likely to experience trauma in their lifetimes,” according to background information in the article. “A systematic approach to the delivery of timely and appropriate disaster mental health services may facilitate their integration into the emergency medical response.”

Carol S. North, M.D., M.P.E., of the VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, and Betty Pfefferbaum, M.D., J.D., of the University of Oklahoma Health Sciences Center, Oklahoma City, reviewed and summarized evidence to provide a practical framework for delivering mental health interventions to individuals appropriate to their needs in the wake of a disaster. A search of the peer-reviewed English-language literature on disaster mental health response yielded 222 articles that met criteria for inclusion in the review.

The authors write that “unlike physical injuries, adverse mental health outcomes of disasters may not be apparent, and therefore a systematic approach to case identification and triage to appropriate interventions is required. Symptomatic individuals in postdisaster settings may experience new-onset disaster-related psychiatric disorders, exacerbations of preexisting psychopathology and/or psychological distress. Descriptive disaster mental health studies have found that many (11 percent-38 percent) distressed individuals presenting for evaluation at shelters and family assistance centers have stress-related and adjustment disorders; bereavement, major depression, and substance use disorders were also observed, and up to 40 percent of distressed individuals had preexisting disorders.”

The researchers also found that individuals with more intense reactions to disaster stress were more likely to accept referral to mental health services than those with less intense reactions.

Standard treatments for psychiatric disorders related to trauma in general and to disasters specifically are pharmacotherapy and psychotherapy. Usual clinical practice for management of trauma-related disorders and symptoms is generally appropriate.

“Evidence-based treatments are available for patients with active psychiatric disorders, but psychosocial interventions such as psychological first aid, psychological debriefing, crisis counseling, and psychoeducation for individuals with distress have not been sufficiently evaluated to establish their benefit or harm in disaster settings,” the authors write.

“The 3 components of case identification, triage, and intervention are consistent with established approaches to emergency and medical response to mass casualty incidents and may therefore facilitate integration of mental health services into the medical disaster response.”

“Compelling issues that must be addressed in improving disaster mental health response capacities focus on matching interventions and services to specified mental health outcomes (e.g., psychiatric illness vs. disaster-related distress) for exposed and unexposed groups, encouraging the use and integration of appropriate assessment and referral, and evaluating the effectiveness of the interventions and services offered.”

(JAMA. 2013;310(5):507-518; 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, AUGUST 6, 2013

Media Advisory: To contact Edna B. Foa, Ph.D., call Steve Graff at 215-349-5653 or email Stephen.Graff@uphs.upenn.edu. To contact editorial author Katherine Mills, Ph.D., email k.mills@unsw.edu.au.

CHICAGO – In a trial that included patients with alcohol dependence and posttraumatic stress disorder (PTSD), treatment with the drug naltrexone resulted in a decrease in the percentage of days drinking while use of the PTSD treatment, prolonged exposure therapy, was not associated with increased drinking or alcohol craving, according to a study in the August 7 issue of JAMA, a theme issue on violence/human rights.

“Alcohol dependence and PTSD are highly comorbid [co-existing], yet little is known about how best to treat this large, highly dysfunctional, and distressed population. Even though studies of treatments for alcohol dependence do not exclude patients with PTSD, symptoms of PTSD are not targeted with these treatments,” according to background information in the article. “In addition, there is a concern that prolonged exposure therapy for PTSD may exacerbate alcohol use.”

Edna B. Foa, Ph.D., of the University of Pennsylvania, Philadelphia, and colleagues compared the efficacy of naltrexone, which is an evidence-based treatment for alcohol dependence, and prolonged exposure therapy, which is an evidence-based treatment for PTSD, separately and in combination, along with supportive counseling. Prolonged exposure therapy is hypothesized to reduce drinking via amelioration (improvement) of PTSD symptoms that can lead to self-medication with alcohol. The randomized trial included 165 participants with PTSD and alcohol dependence. Participant enrollment began in February 2001 and ended in June 2009. Data collection was completed in August 2010. Participants were randomly assigned to (1) prolonged exposure therapy plus naltrexone, (2) prolonged exposure therapy plus pill placebo, (3) supportive counseling plus naltrexone, or (4) supportive counseling plus pill placebo. Prolonged exposure therapy was composed of 12 weekly 90-minute sessions followed by 6 biweekly sessions. All participants received supportive counseling. Independent evaluations occurred prior to treatment (week 0), at posttreatment (week 24), and at 6 months after treatment discontinuation (week 52).

The researchers found reductions in percentage of days drinking (PDD) in all groups during treatment. At posttreatment, patients receiving naltrexone had lower PDD (average, 5.4 percent) than patients receiving placebo (average, 13.3 percent). All groups also showed reductions in alcohol craving during treatment. “A significant main effect of naltrexone emerged at posttreatment such that the 2 naltrexone groups had less alcohol craving than the 2 placebo groups.”

All 4 groups showed reductions in PTSD symptoms during the treatment period, but the main effect of prolonged exposure therapy at posttreatment was not significant.

“Six months after the end of treatment, participants in all 4 groups had increases in percentage of days drinking. However, those in the prolonged exposure therapy plus naltrexone group had the smallest increases,” the authors write.

“Importantly, our findings indicated that prolonged exposure therapy was not associated with increased drinking or alcohol craving, a concern that has been voiced by some investigators. In fact, reduction in PTSD severity and drinking was evident for all 4 treatment groups. This finding contradicts the common view that trauma-focused therapy is contraindicated for individuals with alcohol dependence and PTSD, because it may exacerbate PTSD symptoms and thereby lead to increased alcohol use.”

“… our trial demonstrates that (l) patients with comorbid alcohol dependence and PTSD benefit from naltrexone treatment; (2) prolonged exposure therapy is not associated with exacerbation of alcohol dependence; and (3) combined treatment with naltrexone and prolonged exposure therapy may decrease the rate of relapse of alcohol dependence for up to 6 months after treatment discontinuation,” the researchers conclude.

(JAMA. 2013;310(5):488-495; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (primary investigator: Edna B. Foa, Ph.D.).  Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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

Editorial: Treatment of Comorbid Substance Dependence and Posttraumatic Stress Disorder

Katherine Mills, Ph.D., of the University of New South Wales, Sydney, Australia, comments on the findings of this study in an accompanying editorial.

Mills notes, “Consistent with the theory that patients with PTSD use substances to self-medicate their symptoms, patients frequently report that their PTSD symptoms are exacerbated [made worse] in the absence of substance use … As a consequence, patients in this population group have not received the care they need.”

“… the study by Foa and colleagues is a timely contribution to the literature regarding the treatment of comorbid alcohol dependence and PTSD. The study provides evidence regarding the treatment of this commonly occurring comorbidity and provides hope that the gap in treatment provision for this population may begin to narrow.”

(JAMA. 2013;310(5):482-483; 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, AUGUST 6, 2013

Media Advisory: To contact Cynthia A. LeardMann, M.P.H., call Karl Van Orden at 619-553-9289 or email Karl.VanOrden@med.navy.mil. To contact editorial author Charles C. Engel, M.D., M.P.H., call Gwendolyn Smalls at 301-295-3981 or email gwendolyn.smalls@usuhs.edu.

CHICAGO – In an examination of risk factors associated with suicide in current and former military personnel observed 2001 and 2008, male sex and mental disorders were independently associated with suicide risk but not military-specific variables, findings that do not support an association between deployment or combat with suicide, according to a study in the August 7 issue of JAMA, a theme issue on violence/human rights.

“Despite universal access to healthcare services, mandatory suicide prevention training, and other preventive efforts, suicide has become one of the leading causes of death in the U.S. military in recent years,” according to background information in the article. “Beginning in 2005, the incidence of suicide deaths in the U.S. military began to sharply increase. Unique stressors, such as combat deployments, have been assumed to underlie the increasing incidence. Previous military suicide studies, however, have relied on case series and cross-sectional investigations and have not linked data during service with postservice periods.”

Cynthia A. LeardMann, M.P.H., of the Naval Health Research Center, San Diego, and colleagues conducted a study to identify and quantify factors associated with suicide risk in a large population of military personnel. Accrual and assessment of participants was conducted in 2001, 2004 and 2007. Questionnaire data were linked with the National Death Index and the Department of Defense Medical Mortality Registry through December 31, 2008. Participants were current and former U.S. military personnel from all service branches, including active and Reserve/National Guard, who were included in the Millennium Cohort Study (N = 151,560), a U.S. military study.

Between 2001 and 2008, there were 83 suicides among the participants in the study. In models adjusted for age and sex, factors significantly associated with increased risk of suicide included male sex, depression, manic-depressive disorder, heavy or binge drinking, and alcohol-related problems. The authors found that none of the deployment-related factors (combat experience, cumulative days deployed, or number of deployments) were associated with increased suicide risk in any of the models.

The researchers speculate that the increased rate of suicide in the military “may largely be a product of an increased prevalence of mental disorders in this population, possibly resulting from indirect cumulative occupational stresses across both deployed and home-station environments over years of war.”

“In this sample of current and former U.S. military personnel, mental health concerns but not military-specific variables were found to be independently associated with suicide risk. The findings from this study do not support an association between deployment or combat with suicide, rather they are consistent with previous research indicating that mental health problems increase suicide risk. Therefore, knowing the psychiatric history, screening for mental and substance use disorders, and early recognition of associated suicidal behaviors combined with high-quality treatment are likely to provide the best potential for mitigating suicide risk.”

(JAMA. 2013;310(5):496-506; 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, August 6 at this link.

Editorial: Suicide, Mental Disorders, and the U.S. Military – Time to Focus on Mental Health Service Delivery

“These findings offer some potentially reassuring ways forward: the major modifiable mental health antecedents of military suicide—mood disorders and alcohol misuse—are mental disorders for which effective treatments exist,” writes Charles C. Engel, M.D., M.P.H., of the Uniformed Services University of the Health Sciences, Bethesda, Md., in an accompanying editorial.

“Furthermore, evidence-based service delivery models, particularly those involving primary care, are well known, supported by randomized trial evidence of lasting improvements in suicidal ideation among patients with depression, and designed to overcome population stigma and barriers to care.”

“However, lasting military success in the identification and treatment of the mental illness antecedents of suicide will require overcoming current overreliance on outdated combat and operational stress models of suicide prevention. Such success will also require addressing long-standing military ambivalence toward the medical model of mental illness—an ambivalence affecting service members, military clinicians, and senior leaders alike.”

(JAMA. 2013;310(5):484-485; 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, JULY 23, 2013

Increasing Incidence of Type 1 Diabetes Among Children in Finland Appears to Have Leveled Off

“The incidence of type l diabetes (T1D), one of the most prevalent chronic diseases in children, has increased worldwide,” write Valma Harjutsalo, Ph.D., of the Diabetes Prevention Unit, Helsinki, Finland, and colleagues, who conducted a study to examine the incidence rates of T1D between 2006 and 2011 in Finnish children younger than 15 years as well as the 32-year trend (1980-2011).

As reported in a Research Letter, all children with newly diagnosed T1D were ascertained using several nationwide registers. Age-standardized and age-specific annual incidence rates for age groups 0-4, 5-9, and 10-14 years were calculated. A total of 14,069 children (7,695 boys and 6,374 girls) were diagnosed with T1D between 1980 and 2011, of whom 3,332 were new cases between 2006 and 2011. The peak incidence was observed in 2006. Analysis indicated 2 significant changes in the longer-term trend. After a modest increase until 1988, the incidence increased annually by 3.6 percent until 2005, followed by a plateau until the end of 2011.

“The encouraging observation in this study is that the incidence of T1D in Finnish children younger than 15 years has ceased to increase after a period of accelerated increase. This may be due to changes in the environment, such as vitamin D intake. The amount of vitamin D recommended for supplementation in infants had been reduced to one-tenth since the 1950s, during which time the incidence of T1D increased 5-fold. The fortification of dairy products with vitamin D after 2003 may have contributed to the leveling off of T1D incidence,” the authors write.

(JAMA. 2013;310[4]:427-428. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Valma Harjutsalo, Ph.D., email valma.harjutsalo@helsinki.fi.

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 Viewpoints Appearing in This Issue of JAMA

Note: The following two Viewpoints address this question – Should incidental findings discovered with whole-genome sequencing or testing be sought and reported to ordering clinicians and to patients (or their surrogates)?

Reporting Genomic Sequencing Results to Ordering Clinicians – Incidental, but Not Exceptional

Robert C. Green, M.D., M.P.H., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues write that “to date, the traditions of genetic testing and reporting have exceptionalized all genetic risk information as potentially dangerous to the well-being of patients. This tradition, in the era of genome sequencing, must be reconsidered.”

“Medical genomics has arrived, and sequencing a patient’s genome for any purpose provides an opportunity to discover unexpected but medically important information. Incidental findings in genomics should not be handled differently from other incidental findings in medicine. Rather than exceptionalize the return of incidental genomic findings, clinicians and patients should embrace them as adjuvant information of potential utility and as a welcome component of modern medical practice.”

(JAMA. 2013;310[4]:365-366. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Robert C. Green, M.D., M.P.H., call Tom Langford at 617-771-4510 or email tlangford@partners.org.

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Mandatory Extended Searches in All Genome Sequencing – ‘Incidental Findings,’ Patient Autonomy, and Shared Decision Making

Lainie Friedman Ross, M.D., Ph.D., of the University of Chicago, and colleagues write that “implementing mandatory testing for conditions beyond the scope of the original request is in conflict with key ethical principles of patient autonomy and shared decision making.”

“This is not a debate about whether truly incidental findings discovered in the course of a clinical evaluation of the genome should be discussed with patients, but whether a sample collected for the diagnostic purpose of evaluating a particular clinical question must be evaluated for a list of additional health risks even if against the wishes of the patient, the clinician, or both. Our response is a resounding no because this approach violates good clinical practice and the ethical foundations of medicine.”

(JAMA. 2013;310[4]:367-368. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Lainie Friedman Ross, M.D., Ph.D., call Michael McHugh at 773-702-3641 or email michael.mchugh@uchospitals.edu.

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Return of Secondary Genomic Findings vs. Patient Autonomy – Implications for Medical Care

In April 2013, the American College of Medical Genetics (ACMG) recommended that clinical laboratories conducting whole genome sequencing and whole exome sequencing for specific clinical indications should also analyze and report any mutations identified from a list of 57 genes considered medically actionable, regardless of whether patients wish to receive the results. “These recommendations have sparked a heated debate with profound implications for countless physicians and their patients,” write Robert Klitzman, M.D., of Columbia University, New York, and colleagues.

“Given the controversy, it is critical to consider what should be done next. Several steps appear vital. First, this debate has been occurring without sufficient data. The pathogenicity of rare variants and the prevalence and general population penetrance of true mutations in these 57 genes should be determined. Patients’ preferences for and responses to this information are currently unknown, but they are actively being sought by researchers and will probably be elucidated in the next 2 to 3 years. Input from all stakeholders should be sought, including patients, patient advocacy groups, and professional organizations such as the American Society of Clinical Oncology.”

“The ACMG policy has sparked a valuable discussion, but careful consideration and debate, continued data collection, and curation and refinement of the classification of genetic variants are all necessary to arrive at the best policy for this important medical tool. Rather than rushing to implement a policy, it seems more prudent to continue discussion, research, and analysis and ensure that all the ramifications of the policy are considered before laboratories adopt the ACMG recommendations. While proponents may argue that policy is urgently needed, such short-term benefits are outweighed by the long-range advantages of developing as optimal a policy as possible.”

(JAMA. 2013;310[4]:369-370. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Robert Klitzman, M.D., call Dacia Morris at 212-543-5421 or email Morrisd@nyspi.columbia.edu.

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 Re-envisioning Specialty Care and Payment Under Global Payment Systems

“The coming tide of payment reform as well as continued, if not escalating, cost pressures as the Affordable Care Act is implemented and an additional 30 million individuals obtain some form of health insurance present great opportunities for innovations in how health care services are organized and delivered,” write Bruce E. Landon, M.D., M.B.A., of Harvard Medical School, and David H. Roberts, M.D., of Beth Israel Deaconess Medical Center, Boston.

“For the first time in U.S. history, more patients and physicians will operate in a system in which there are defined boundaries for costs. There may be substantial shifts in how resources are spent, whether shifting from specialists to primary care physicians or from inpatient to outpatient settings. These changes will have dramatic effects on specialist practice, with implications both for how specialists practice as well as for the forms and levels of their compensation. Although changes in specialist roles and responsibilities will better align specialists with the goals of integrated care systems, with likely benefit to the health care system overall, these changes are also likely to result in substantial changes in specialist pay and number.”

(JAMA. 2013;310[4]:371-372. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Bruce E. Landon, M.D., M.B.A., call David Cameron at 617-432-0441 or email david_cameron@hms.harvard.edu.

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, JULY 23, 2013

Media Advisory: To contact Pietro Manuel Ferraro, M.D., email manuel.ferraro@channing.harvard.edu.
 

CHICAGO – An analysis of data from three studies that involved a total of more than 240,000 participants found that a self-reported history of kidney stones was associated with a statistically significant increased risk of coronary heart disease among women but no significant association was evident for men, according to a study in the July 24/31 issue of JAMA.

“Nephrolithiasis [kidney stones] is a common condition, with the prevalence varying by age and sex. A recent estimate from the National Health and Nutrition Examination Survey, a representative sample of the U.S. population, reported the prevalence of a history of kidney stones of 10.6 percent in men and 7.1 percent in women. The overall prevalence has increased from 3.8 percent (1976-1980) to 8.8 percent (2007-2010),” according to background information in the article. Kidney stone disease may be associated with an increased risk of coronary heart disease (CHD). “Previous studies of the association between kidney stones and CHD have often not controlled for important risk factors, and the results have been inconsistent.”

Pietro Manuel Ferraro, M.D., of Columbus-Gemelli Hospital, Rome, and colleagues analyzed the relation between kidney stones and risk of incident CHD for individuals with a history of kidney stones. The analysis included 45,748 men and 196,357 women in the United States without a history of CHD at baseline who were participants in the Health Professionals Follow-up Study (HPFS) (45,748 men 40-75 years of age; follow-up from 1986 to 2010), Nurses’ Health Study I (NHS I) (90,235 women 30-55 years of age; follow-up from 1992 to 2010), and Nurses’ Health Study II (NHS II) (106,122 women 25-42 years of age; follow-up from 1991 to 2009). The diagnoses of kidney stones and CHD were updated biennially during follow-up. Coronary heart disease was defined as fatal or nonfatal myocardial infarction (MI; heart attack) or coronary revascularization.

Of a total of 242,105 participants, 19,678 reported a history of kidney stones. After up to 24 years of follow-up in men and 18 years in women, 16,838 incident cases of CHD occurred. “Multivariable-adjusted analysis of individual outcomes confirmed an association in NHS I and NHS II participants between history of kidney stones and myocardial infarction and revascularization. After pooling the NHS I and NHS II cohorts, women with a history of kidney stones had an increased risk of CHD, fatal and nonfatal myocardial infarction, and revascularization,” the authors write.

After multivariable adjustment, there was no significant association between history of kidney stones and CHD in the men’s cohort.

“Our finding of no significant association between history of kidney stones and risk of CHD in men but an increased risk in women is difficult to explain, even though we could not determine whether this was due to sex or some other difference between the male and female cohorts. However, differences by sex are not infrequent in studies analyzing the association between nephrolithiasis and either CHD or risk factors for CHD,” the researchers write.

“Further research is needed to determine whether the association is sex-specific and to establish the pathophysiological basis of this association.”

(JAMA. 2013;310(4):408-415; 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, JULY 23, 2013

Media Advisory: To contact Jon C. Tilburt, M.D., M.P.H., call Shelly Plutowski at 507-284-5005 or email newsbureau@mayo.edu. To contact editorial co-author Ezekiel J. Emanuel, M.D., Ph.D., call Katie Delach at 215-349-5964 or email Katie.Delach@uphs.upenn.edu.

CHICAGO – In a survey of about 2,500 U. S. physicians on their perceived role in addressing health care costs, they reported having some responsibility to address health care costs in their practice and expressed general agreement with quality initiatives that may also reduce cost, but expressed less enthusiasm for cost containment involving changes in payment models, according to a study in the July 24/31 issue of JAMA.

“The increasing cost of U.S. health care strains the economy. Because physicians’ decisions play a key role in overall health care spending and quality, several recent initiatives have called on physicians to reduce waste and exercise wise stewardship of resources. Given their roles, physicians’ perspectives on policies and strategies related to cost containment and their perceived responsibilities as stewards of health care resources in general are increasingly germane to recent pending and proposed policy reforms,” according to background information in the article.

Jon C. Tilburt, M.D., M.P.H., of the Mayo Clinic, Rochester, Minn., and colleagues conducted a survey of physicians about their views on several potential proposed policies and strategies to contain health care spending, assessed physicians’ perceived roles and responsibilities in addressing health care costs, and ascertained physician characteristics associated with those views. The survey was mailed in 2012 to 3,897 U.S. physicians randomly selected from the American Medical Association Masterfile. A total of 2,556 physicians responded (response rate = 65 percent). The survey included respondents rating their level of enthusiasm (not, somewhat, or very enthusiastic) toward 17 specific means of reducing health care costs, including but not limited to strategies proposed in the Patient Protection and Affordable Care Act; and agreement with an 11-measure cost-consciousness scale.

The researchers found that most respondents believed that trial lawyers (60 percent), health insurance companies (59 percent), hospitals and health systems (56 percent), pharmaceutical and device manufacturers (56 percent), and patients (52 percent) have a “major responsibility” for reducing health care costs, whereas only 36 percent reported that practicing physicians have “major responsibility.” Most physicians were “very enthusiastic” for “promoting continuity of care” (75 percent), “expanding access to quality and safety data” (51 percent), and “limiting access to expensive treatments with little net benefit” (51 percent) as a means of reducing health care costs.

Few respondents expressed enthusiasm for “eliminating fee-for-service payment models” (7 percent). “Most physicians reported being ‘aware of the costs of the tests/treatments [they] recommend’ (76 percent), agreed they should adhere to clinical guidelines that discourage the use of marginally beneficial care (79 percent), and agreed that they ‘should be solely devoted to individual patients’ best interests, even if that is expensive’ (78 percent) and that ‘doctors need to take a more prominent role in limiting use of unnecessary tests’ (89 percent),” the authors write.

Most physicians (85 percent) disagreed that they “should sometimes deny beneficial but costly services to certain patients because resources should go to other patients that need them more.” In models testing associations with enthusiasm for key cost-containment strategies, having a salary plus bonus or salary-only compensation type was independently associated with enthusiasm for “eliminating fee for service.” Also, group or government practice setting and having a salary plus bonus compensation type were positively associated with cost-consciousness.

“U.S. physicians’ opinions about their role in containing health care costs are complex. In this survey, we found that they express considerable enthusiasm for several proposed cost-containment strategies that aim to enhance or promote high-quality care such as improved continuity of care. However, there is considerably less enthusiasm for more substantial financing reforms, including bundled payments, penalties for readmissions, and eliminating fee-for-service reimbursement; Medicare pay cuts are unpopular across the board. They were also more likely to identify other groups, rather than physicians, such as insurers, lawyers, hospitals, and health systems, as having a major responsibility to reduce cost. These data document professional sentiments about addressing health care costs and speak directly to the acceptability of several key policy strategies for curbing those costs,” the authors write.

“Moving toward cost-conscious care in the current environment in which physicians practice starts with strategies for which there is widespread physician support might create momentum for such efforts, including improving quality and efficiency of care and bringing transparent cost information and evidence from comparative effectiveness research into electronic health records with decision support technology. More aggressive (and potentially necessary) financing changes may need to be phased in, with careful monitoring to ensure that they do not infringe on the integrity of individual clinical relationships.”

(JAMA. 2013;310(4):380-388; 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, July 23 at this link.

Editorial: Will Physicians Lead on Controlling Health Care Costs?

Ezekiel J. Emanuel, M.D., Ph.D., and Andrew Steinmetz, B.A., of the University of Pennsylvania, Philadelphia, write in an accompanying editorial that the findings of this survey “are somewhat discouraging.”

“The findings suggest that physicians do not yet have that ‘all-hands-on-deck’ mentality this historical moment demands. Indeed, the survey of 2,556 physicians suggests that in the face of this new and uncertain moment in the reform of the health care system, physicians are lapsing into the well-known, cautious instinctual approaches humans adopt whenever confronted by uncertainty: blame others and persevere with ‘business as usual.’”

“The next decade requires ‘all hands on deck’ to create meaningful, lasting change in health care. The study by Tilburt et al indicates that the medical profession is not there yet — that many physicians would prefer to sit on the sidelines while other actors in the health care system do the real work of reform. This could marginalize and demote physicians. Physicians must commit themselves to act like the captain of the health care ship and take responsibility for leading the United States to a better health care system that provides higher-quality care at lower costs.”

(JAMA. 2013;310(4):374-375; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Emanuel reported receiving payment for speaking engagements unrelated to this work.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 23, 2013

Media Advisory: To contact corresponding author Matthew J. Kuehnert, M.D., call Melissa Dankel at 404-639-4718 or email mdankel@cdc.gov. To contact editorial author Daniel R. Kaul, M.D., call Shantell Kirkendoll at 734-764-2220 or email smkirk@umich.edu.

CHICAGO – An investigation into the source of a fatal case of raccoon rabies virus exposure indicates the individual received the virus via a kidney transplant 18 months earlier, findings suggesting that rabies transmitted by this route may have a long incubation period, and that although solid organ transplant transmission of infectious encephalitis is rare, further education to increase awareness is needed, according to a study in the July 24/31 issue of JAMA.

The rabies virus causes a fatal encephalitis (inflammation of the brain) and can be transmitted through tissue or organ transplantation. “Unique rabies virus variants, distinguishable by molecular typing methods, are associated with specific animal reservoirs. Globally, an estimated 55,000 persons die of rabies every year, with most transmission attributable to dog bites. Approximately 2 human rabies deaths are reported in the United States every year and during 2000 through 2010, all but 2 domestically acquired cases were associated with bats. Despite raccoons being the most frequently reported rabid animal in the United States, only l human rabies case associated with the raccoon rabies virus variant has been reported,” according to background information in the article. In February 2013, a kidney recipient with no reported exposures to potentially rabid animals died from rabies 18 months after transplantation.

Neil M. Vora, M.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues conducted a study to determine whether organ transplantation was the source of rabies virus exposure in the kidney recipient, and to evaluate for and prevent rabies in other transplant recipients (n = 3; right kidney, heart, and liver) from the same donor. Organ donor and all transplant recipient medical records were reviewed. Laboratory tests to detect rabies virus-specific binding antibodies, rabies virus neutralizing antibodies, and rabies virus antigens were conducted on available specimens, including serum, cerebrospinal fluid, and tissues from the donor and the recipients.

The researchers found that in retrospect, the kidney donor’s symptoms prior to death were consistent with rabies (the presumed diagnosis at the time of death was ciguatera poisoning [a foodborne illness]). Subsequent interviews with family members revealed that the donor had significant wildlife exposure, and had sustained at least 2 raccoon bites, for which he did not seek medical care. Rabies virus antigen was detected in archived autopsy brain tissue collected from the donor. The rabies viruses infecting the donor and the deceased kidney recipient were consistent with the raccoon rabies virus variant and were more than 99.9 percent identical across the entire N gene, thus confirming organ transplantation as the route of transmission.

The 3 other organ recipients did not have signs or symptoms consistent with rabies or encephalitis. They have remained asymptomatic, with rabies virus neutralizing antibodies detected in their serum after completion of postexposure prophylaxis.

“This transmission event provides an opportunity for enhancing rabies awareness and recognition and highlights the need for a modified approach to organ donor screening and recipient monitoring for infectious encephalitis. This investigation also underscores the importance of collaboration between clinicians, epidemiologists, and laboratory scientists,” the authors write.

(JAMA. 2013;310(4):398-407; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This investigation was supported by the Centers for Disease Control and Prevention, Maryland Department of Health and Mental Hygiene, North Carolina Division of Public Health, and Florida Department of Health and funded as part of routine infectious disease outbreak investigation activities. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of interest and none were reported.

Editorial: Donor-Derived Infections With Central Nervous System Pathogens After Solid Organ Transplantation

In an accompanying editorial, Daniel R. Kaul, M.D., of the University of Michigan Medical School, Ann Arbor, writes that during the past decade, numerous instances have been reported of donor-derived infection among recipients of solid organ transplants with pathogens associated with central nervous system (CNS) infections, including the West Nile virus and rabies virus.

“Educational efforts to improve recognition of donors with CNS infection and the risks associated with using these donors should be directed not just at the transplant community but at the larger community of physicians involved in the care of potential donors—particularly critical care specialists, neurologists, and infectious disease physicians. These clinicians may not be aware of the potential for donor-derived infection, but accepting transplant centers must rely on the clinical impression of those caring for the potential donor. Although the risk of donor-derived disease is inherent in the process of organ transplantation and cannot be eliminated, raising awareness of the risk of using donors with undiagnosed CNS infection is the best way to reduce the occurrence of these transmissions.”

(JAMA. 2013;310(4):378-379; 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, JULY 23, 2013

Media Advisory: To contact Jeffrey H. Silber, M.D., Ph.D., call Dana Mortensen at 267-426-6092 or email mortensen@email.chop.edu. To contact editorial co-author Jeanne S. Mandelblatt, M.D., M.P.H., call Karen Mallet at 215-514-9751 or email km463@georgetown.edu.

CHICAGO – In an analysis of 5-year survival rates among black and white women diagnosed with breast cancer between 1991 and 2005, black women continued to have a lower rate of survival, with most of the difference related to factors including poorer health of black patients at diagnosis and more advanced disease, rather than treatment differences, according to a study in the July 24/31 issue of JAMA.

“For 20 years health care investigators in the United States have been keenly aware of racial disparities in survival among women with breast cancer. Numerous reports have not only identified and documented worse outcomes in black patients with breast cancer but have suggested potential reasons for the disparities based on differences in screening, presentation, comorbid conditions on presentation, tumor biology, stage, treatment, and socioeconomic status,” according to background information in the article.

Jeffrey H. Silber, M.D., Ph.D., of the Children’s Hospital of Philadelphia, and colleagues examined the extent of the racial differences in breast cancer survival in the Medicare population and the reasons the disparity exists. The study compared 7,375 black women 65 years and older diagnosed between 1991 to 2005 and 3 sets of 7,375 matched white control patients selected from 99,898 white potential control patients, using data from 16 U.S. Surveillance, Epidemiology and End Results (SEER) sites in the SEER-Medicare database. All patients received follow-up through December 2009 and the black case patients were matched to 3 white control populations on demographics (age, year of diagnosis, and SEER site), presentation (demographics variables plus patient comorbid conditions and tumor characteristics such as stage, size, grade, and estrogen receptor status), and treatment (presentation variables plus details of surgery, radiation therapy, and chemotherapy).

The researchers found that the absolute difference in 5-year survival (blacks, 55.9 percent; whites, 68.8 percent) was 12.9 percent in the demographics match. This difference remained unchanged between 1991 and 2005. After matching on presentation characteristics, the absolute difference in 5-year survival was 4.4 percent and was 3.6 percent lower for blacks than for whites matched also on treatment.

Regarding differences in treatment by race, overall, 12.6 percent of black patients did not have evidence of receiving any treatment for their breast cancer, compared with 5.9 percent of whites. Average time from diagnosis to treatment was longer among blacks than among demographics-matched whites, 29.2 days vs 22.5 days. Blacks were also more likely to have long delays in treatment: 5.8 percent of blacks did not initiate treatment within the first 3 months from diagnosis, compared to 2.5 percent of white patients. Blacks also received breast-conserving surgery without any other treatment more often than presentation-matched whites (8.2 percent vs 7.3 percent). “Nevertheless, differences in survival associated with treatment differences accounted for only 0.81 percent of the 12.9 percent survival difference,” the authors write.

There were large differences in the way black and white patients presented. “For the demographics match, blacks had significantly less evidence of at least l primary care visit than matched whites (80.5 percent vs 88.5 percent, respectively); significantly lower rates of breast cancer screening (23.5 percent vs 35.7 percent); and significantly lower rates of colon cancer and cholesterol screening,” the authors write.

“Our results suggest that it may be difficult to eliminate the racial disparity in survival from diagnosis unless differences in presentation can be reduced. There is also a disparity in treatment, with blacks receiving treatment inferior to that received by whites with similar presentation, but this explains only a small part of the observed difference in survival. The disparity in treatment might matter more if the disparity in presentation were reduced, because blacks would then be diagnosed with less advanced disease, for which treatment is more effective.”

The researchers add that black patients are diagnosed not only with more advanced breast cancers but also with more unrelated comorbid conditions. “Some of the effectiveness of cancer treatment for blacks may be blunted by other health problems. If the differences in comorbid conditions at diagnosis were reduced, it is possible that the differences in cancer treatment would matter more for the differences in survival.”
(JAMA. 2013;310(4):389-397; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This research was funded through a grant from the Agency for Healthcare Research and Quality, Department of Health and Human Services, and by the U.S. National Science Foundation. This study used the linked SEER-Medicare database. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: Black-White Differences in Breast Cancer Outcomes Among Older Medicare Beneficiaries – Does Systemic Treatment Matter?

Jeanne S. Mandelblatt, M.D., M.P.H., of the Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C., and colleagues comment on the findings of this study in an accompanying editorial.

“The rigorous study by Silber et al provides additional clues to the black-white differences in breast cancer outcomes. Ultimately, for any cancer control strategy to succeed, improved care quality appears to be a necessary, but not sufficient, condition to eliminate race-based mortality differences in the United States.”

(JAMA. 2013;310(4):376-377; 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, JULY 16, 2013

Survival Poor For Nursing Home Residents With Advanced Cognitive Impairment Who Undergo Multiple Hospitalizations For Infections or Dehydration

“Multiple hospitalizations for complications from a terminal illness may be burdensome for elderly patients and reflect poor quality care,” write Joan M. Teno, M.D., M.S., of the Warren Alpert School of Medicine of Brown University, Providence, R.I., and colleagues, who conducted a study to examine whether the occurrence of multiple hospitalizations for the complications of infections or dehydration was associated with survival.

As reported in a Research Letter, the study population was identified using data from the national Minimum Data Set repository, which includes standardized assessments regularly completed by staff on all nursing home (NH) residents in the United States between January 2000 and December 2008. The researchers identified the first baseline assessment in which a resident had a Cognitive Performance Score of 4, 5, or 6 indicating moderate to very severe cognitive impairment. Residents were followed up for l year from the baseline assessment date (through 2009), and residents were identified who had 2 or more hospitalizations for the same type of the following diagnoses: pneumonia, urinary tract infection (UTI), septicemia, or dehydration or malnutrition.

Between 2000 and 2008, 1.3 million NH residents attained a Cognitive Performance Score of 4, 5, or 6 and survived at least 30 days after that assessment. Compared with overall survival (476 days), the adjusted survival was significantly lower for all of the burdensome transitions: pneumonia, 95 days; UTI, 146 days; dehydration or malnutrition, 111 days; and septicemia, 89 days.

“Future research is needed to understand whether these transitions are based on financial incentives, poor communication, or a lack of resources needed to diagnose and treat a NH resident,” the authors write. “… the observed survival suggests that the first hospitalization with these diagnoses for NH residents with advanced cognitive impairment should result in reconsideration of the goals of care and the appropriateness of continued hospitalizations.”

(JAMA. 2013;310[3]:319-320. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Joan M. Teno, M.D., M.S., call David Orenstein at 401-863-1862 or email david_orenstein@brown.edu.

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 Viewpoints Appearing in This Issue of JAMA

 The International Registry Infrastructure for Cardiovascular Device Evaluation and Surveillance

Art Sedrakyan, M.D., Ph.D., of Weill Cornell Medical College, Cornell University, New York, and colleagues summarize “the potential for development of an International Consortium of Cardiovascular Registries, modeled on a consortium established for orthopedic devices, as an initial project in the realm of cardiovascular devices with the focus on transcatheter aortic valve replacement (TAVR).”

“… a global consortium of cardiovascular device registries has great potential to improve the public health, facilitate and strengthen regulatory processes, and advance clinical practice using innovative approaches. The exploration of the new International Consortium of Cardiovascular Registries focused on the novel technology of TAVR has multiple potential scalable positive outcomes for a larger cardiovascular initiative. The initiative may improve collaboration of the different stakeholders and enhance efficiency of registries and could facilitate the evaluation of the safety and efficacy of new devices and approaches, thereby reaching the goal of harnessing the global knowledge.”

(JAMA. 2013;310[3]:257-258. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Danica Marinac-Dabic, M.D., Ph.D., call Synim Rivers at 301-796-8729 or email Synim.Rivers@fda.hhs.gov.

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New Incentive-Based Programs – Maryland’s Health Disparities Initiatives

In this Viewpoint, E. Albert Reece, M.D., Ph.D., M.B.A., of the University of Maryland School of Medicine, Baltimore, and colleagues discuss the Maryland Health Improvement and Disparities Reduction Act of 2012, which includes incentive-based strategies to address health and health care disparities.

“The use of incentives to address disparities links progress to the change underway in the health care system. During this transition, tracking and monitoring health inequity, although essential, is insufficient. Efforts to move health care forward must not leave behind communities with longstanding disadvantages in health. Incentives can create the environment in which innovation and creativity forge new paths to progress.”

(JAMA. 2013;310[3]:259-260. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact E. Albert Reece, M.D., Ph.D., M.B.A., call Karen Robinson at 410-706-7590 or email KRobinson@som.umaryland.edu.

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, JULY 16, 2013

Media Advisory: To contact Spyros D. Mentzelopoulos, M.D., email sdmentzelopoulos@yahoo.com.

CHICAGO – Among patients who experienced in-hospital cardiac arrest requiring vasopressors (drugs that increase blood pressure), use of a combination therapy during cardiopulmonary resuscitation resulted in improved survival to hospital discharge with favorable neurological status, according to a study in the July 17 issue of JAMA.

“Neurological outcome after cardiac arrest has been the main end point of several randomized clinical trials (RCTs).  Neurologically favorable survival differs from overall survival. Among cardiac arrest survivors, the prevalence of severe cerebral disability or vegetative state ranges from 25 percent to 50 percent. In a previous single-center RCT, combined vasopressin-epinephrine during cardiopulmonary resuscitation (CPR) and corticosteroid supplementation during and after CPR vs. epinephrine [adrenaline] alone during CPR and no steroids resulted in improved overall survival to hospital discharge,” according to background information in the article. “However, this preliminary study could not reliably assess vasopressin-steroids-epinephrine (VSE) efficacy with respect to neurologically favorable survival to hospital discharge.”

Spyros D. Mentzelopoulos, M.D., Ph.D., of the University of Athens Medical School, Athens, Greece, and colleagues conducted a study to determine whether combined vasopressin-epinephrine during CPR and corticosteroid supplementation during and after CPR improved survival to hospital discharge with a favorable neurological score on the Cerebral Performance Category (CPC). The randomized, placebo-controlled trial was performed from September 2008 to October 2010 in 3 tertiary care centers in Greece and included 268 patients with cardiac arrest requiring epinephrine according to resuscitation guidelines.

Patients received either vasopressin plus epinephrine (VSE group, n = 130) or saline placebo plus epinephrine (control group, n = 138) for the first 5 CPR cycles after randomization, followed by additional epinephrine if needed. During the first CPR cycle after randomization, patients in the VSE group received methyl prednisolone and patients in the control group received saline placebo. Shock after resuscitation was treated with stress-dose hydrocortisone (VSE group, n = 76) or saline placebo (control group, n = 73). The primary outcomes for the study were return of spontaneous circulation (ROSC) for 20 minutes or longer and survival to hospital discharge with a CPC score of 1 or 2.

Patients in the VSE group had a higher probability for ROSC for 20 minutes or longer compared with patients in the control group (109/130 [83.9 percent] vs. 91/138 [65.9 percent]). Compared with patients in the control group, patients in the VSE group had a lower risk of poor outcome during follow-up and were more likely to be alive at hospital discharge with favorable neurological recovery (18/130 [13.9 percent] vs. 7/138 [5.1 percent]).

Among survivors for 4 hours or longer, VSE patients with postresuscitation shock (n = 76) vs. corresponding controls (n = 73) had a lower risk of poor outcome during follow-up and were more likely to be alive at hospital discharge with favorable neurological recovery (16/76 [21.1 percent] vs. 6/73 [8.2 percent]).

Post-arrest illness and complications throughout hospital stay and death causes were similar among survivors for 4 hours or longer.

“In this study of patients with cardiac arrest requiring vasopressors, the combination of vasopressin and epinephrine, along with methylprednisolone during CPR and hydrocortisone in postresuscitation shock, resulted in improved survival to hospital discharge with favorable neurological status, compared with epinephrine and saline placebo. These results are consistent with increased efficacy of the VSE combination vs. epinephrine alone during CPR for in-hospital, vasopressor-requiring cardiac arrest,” the authors write.

(JAMA. 2013;310(3):270-279; 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, JULY 16, 2013

Media Advisory: To contact corresponding author Samy Suissa, Ph.D., call Tod Hoffman at 514-340-8222, ext. 8661 or email thoffman@jgh.mcgill.ca.

CHICAGO – In a study that included more than 10,000 men with nonmetastatic prostate cancer, use of androgen deprivation therapy (ADT) was associated with a significantly increased risk of acute kidney injury, with variations observed with certain types of ADTs, according to a study in the July 17 issue of JAMA.

“Androgen deprivation therapy is the mainstay treatment for patients with advanced prostate cancer. While this therapy has been traditionally reserved for patients with advanced disease, ADT is increasingly being used in patients with less severe forms of the cancer, such as in patients with biochemical relapse who have no evidence of metastatic disease. Although ADT has been shown to have beneficial effects on prostate cancer progression, serious adverse events can occur during treatment,” according to background information in the article. “… the testosterone suppression associated with this therapy may lead to a hypogonadal condition that can have detrimental effects on renal function, thus raising the hypothesis that ADT-induced hypogonadism could potentially lead to acute kidney injury (AKI).” The mortality rate is high for patients with AKI (around 50 percent).

Francesco Lapi, Pharm.D., Ph.D., of Jewish General Hospital, Montreal, Canada, and colleagues conducted a study to determine whether the use of ADT was associated with an increased risk of AKI in patients newly diagnosed with prostate cancer. The researchers used medical information extracted from the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database. The study included men newly diagnosed with nonmetastatic prostate cancer between January 1997 and December 2008 who were followed up until December 2009. Cases were patients with incident AKI during follow-up who were randomly matched with up to 20 controls on age, calendar year of prostate cancer diagnosis, and duration of follow-up. Analysis was conducted to estimate the odds ratios of AKI associated with the use of ADT. ADT was categorized into 1 of 6 mutually exclusive groups: gonadotropin-releasing hormone agonists, oral antiandrogens, combined androgen blockade, bilateral orchiectomy, estrogens, and combination of the above.

A total of 10,250 patients met the study inclusion criteria. During follow-up, 232 cases with a first-ever AKI admission were identified. All cases were matched with at least l control. The researchers found that compared with never use, current use of ADT was significantly associated with a 2.5 times increased odds of AKI. “This association was mainly driven by a combined androgen blockade consisting of gonadotropin-releasing hormone agonists with oral antiandrogens, estrogens, other combination therapies, and gonadotropin-releasing hormone agonists.”

“To our knowledge, this is the first population-based study to investigate the association between the use of ADT and the risk of AKI in men with prostate cancer. In this study, the use of ADT was associated with an increased risk of AKI, with variations observed with certain types of ADTs. This association remained continuously elevated, with the highest odds ratio observed in the first year of treatment. Overall, these results remained consistent after conducting several sensitivity analyses,” the authors write.

“These findings require replication in other carefully designed studies as well as further investigation of their clinical importance.”

(JAMA. 2013;310(3):289-296; 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, JULY 16, 2013

Media Advisory: To contact corresponding author Robert W. Haley, M.D., call Russell Rian at 214-648-3404 or email russell.rian@utsouthwestern.edu. To contact Lyle R. Petersen, M.D., M.P.H., call Candice Hoffmann at 404-639-7689 or email hqx5@cdc.gov. To contact editorial author Stephen M. Ostroff, M.D., email sostroff@verizon.net.

CHICAGO – An analysis of West Nile virus epidemics in Dallas County in 2012 and previous years finds that the epidemics begin early, after unusually warm winters; are often in similar geographical locations; and are predicted by the mosquito vector index (an estimate of the average number of West Nile virus-infected mosquitoes collected per trap-night), information that may help prevent future outbreaks of West Nile virus-associated illness, according to a study in the July 17 issue of JAMA.

“After declining over the prior 5 years, mosquito-borne West Nile virus infection resurged in 2012 throughout the United States, most substantially in Dallas County, Texas. Dallas has been a known focus of mosquito-borne encephalitis since 1966, when a large epidemic of St. Louis encephalitis (SLE) occurred there, necessitating aerial spraying of insecticide for control,” according to background information in the article. “With the introduction of West Nile virus into New York City in 1999 and its subsequent spread across the country, West Nile virus appears to have displaced SLE virus. Dallas recognized its initial cases of West Nile virus encephalitis in 2002 and its first sizeable outbreak in 2006, followed by 5 years of low West Nile virus activity. In the 2012 nationwide West Nile virus resurgence, Dallas County experienced the most West Nile virus infections of any U.S. urban area, requiring intensified ground and aerial spraying of insecticides.”

Wendy M. Chung, M.D., S.M., of Dallas County Health and Human Services, Dallas, and colleagues conducted a study to examine the features associated with the West Nile virus epidemics and to identify surveillance and control measures for minimizing future outbreaks. The researchers analyzed surveillance data from Dallas County (population, 2.4 million), which included the numbers of residents diagnosed with West Nile virus infection between May 30, 2012 and December 3, 2012; mosquito trap results; weather data; and syndromic (pertaining to symptoms and syndromes) surveillance from area emergency departments.

From May 30 through December 3, 2012, patients (n = 1,162) with any West Nile virus-positive test result were reported to the health department; 615 met laboratory case criteria, and 398 cases of West Nile virus illness with 19 deaths were confirmed by clinical review in residents of Dallas County. The outbreak included 173 patients with West Nile neuroinvasive disease (WNND) and 225 with West Nile fever, and 17 West Nile virus-positive blood donors. Regarding patients with WNND, 96 percent were hospitalized; 35 percent required intensive care; 18 percent required assisted ventilation; and the case-fatality rate was 10 percent. The overall WNND incidence rate in Dallas County was 7.30 per 100,000 residents in 20l2, compared with 2.91 in 2006.

The first West Nile virus-positive mosquito pool of 2012 was detected in late May, earlier than in typical seasons. Symptoms of the first 19 cases of WNND in 2012 began in June, a month earlier than in most prior seasons; thereafter, the number of new cases escalated rapidly. Sequential increases in the weekly vector index early in the 2012 season significantly predicted the number of patients with onset of symptoms of WNND in the subsequent l to 2 weeks.

The 2012 epidemic year was distinguished from the preceding 10 years by the mildest winter, as indicated by absence of hard winter freezes, the most degree-days above daily normal temperature during the winter and spring and other features. During the 11 years since West Nile virus was first identified in Dallas, the researchers found that the annual prevalence of WNND was inversely associated with the number of days with low temperatures below 28°F in December through February.

“Although initially widely distributed, WNND cases soon clustered in neighborhoods with high housing density in the north central area of the county, reflecting higher vector indices and following geospatial patterns of West Nile virus in prior years,” the authors write.

Aerial insecticide spraying was not associated with increases in emergency department visits for respiratory symptoms or skin rash.

“This report identifies several distinguishing features of a large urban West Nile virus outbreak that may assist future prevention and control efforts for vector-borne infections,” the authors write. “Consideration of weather patterns and historical geographical hot spots and acting on the vector index may help prevent West Nile virus-associated illness.”

(JAMA. 2013;310(3):297-307; 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, July 16 at this link.

Review Article Describes Epidemiology, Characteristics and Prevention of West Nile Virus

Lyle R. Petersen, M.D., M.P.H., of the Centers for Disease Control and Prevention, U.S. Public Health Service, Department of Health and Human Services, Fort Collins, Colo., and colleagues conducted a review of the medical literature and national surveillance data to examine the ecology, virology, epidemiology, clinical characteristics, diagnosis, prevention, and control of West Nile virus.

“West Nile virus has become endemic in all 48 contiguous United States as well as all Canadian provinces since its discovery in North America in New York City in 1999. It has produced the 3 largest arbovirai neuroinvasive disease (encephalitis, meningitis, or acute flaccid paralysis) outbreaks ever recorded in the United States, with nearly 3,000 cases of neuroinvasive disease recorded each year in 2002, 2003, and 2012,”according to background information in the article.

The authors found that since 1999, there have been 16,196 human neuroinvasive disease cases and 1,549 deaths reported; more than 780,000 illnesses have likely occurred. Incidence is highest in the Midwest from mid-July to early September. “West Nile fever develops in approximately 25 percent of those infected, varies greatly in clinical severity, and symptoms may be prolonged. Neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis) develops in less than 1 percent but carries a fatality rate of approximately 10 percent. Encephalitis has a highly variable clinical course but often is associated with considerable long-term morbidity. Approximately two-thirds of those with paralysis remain with significant weakness in affected limbs.”

The authors add that diagnosis usually rests on detection of IgM antibody in serum or cerebrospinal fluid. No licensed human vaccine exists. “Prevention uses an integrated pest management approach, which focuses on surveillance, elimination of mosquito breeding sites, and larval and adult mosquito management using pesticides to keep mosquito populations low. During outbreaks or impending outbreaks, emphasis shifts to aggressive adult mosquito control to reduce the abundance of infected, biting mosquitoes. Pesticide exposure and adverse human health events following adult mosquito control operations for West Nile virus appear negligible.”

“The resurgence of West Nile virus in 2012 after several years of decreasing incidence in the United States suggests that West Nile virus will continue to produce unpredictable local and regional outbreaks,” the researchers write. “… sustainable community-based surveillance and vector management programs are critical, particularly in metropolitan areas with a history of West Nile virus and large human populations at risk.”

(JAMA. 2013;310[3]:308-315. 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: West Nile Virus – Too Important to Forget

“Periodic flares of West Nile virus, as occurred in 2012, certainly will recur,” writes Stephen M. Ostroff, M.D., formerly of the Centers for Disease Control and Prevention, Atlanta, and the Pennsylvania Department of Health, Harrisburg, in an accompanying editorial.

“Where future outbreaks of the virus will occur and how intense they will be is difficult to predict, especially in light of declining surveillance efforts and vector monitoring programs. Unusually warm winters, as occurred in Dallas during 2011-2012, are becoming more common and will favor additional West Nile virus events like the one described by Chung et al. Changing weather patterns raise the possibility of expanded zones of risk and longer transmission seasons. The tragic consequences of the Dallas West Nile virus epidemic must not be forgotten, for they serve as a cogent reminder of the need to sustain vector monitoring and prevention programs in all communities.”

(JAMA. 2013;310(3):267-268; 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, JULY 16, 2013

Media Advisory: To contact Jared P. Reis, Ph.D., call the NHLBI Communications Office at 301-496-4236 or email nhlbi_news@nhlbi.nih.gov.

CHICAGO – In a study of adults recruited and followed up over the past 3 decades in the United States, longer duration of overall and abdominal obesity beginning in young adulthood was associated with higher rates of coronary artery calcification, a subclinical predictor of coronary heart disease, according to a study in the July 17 issue of JAMA.

“Subclinical atherosclerosis, identified by the presence of coronary artery calcification (CAC), progresses over time, and predicts the development of coronary heart disease events,” according to background information in the article. The degree of overall and abdominal obesity, as reflected by an increased body mass index (BMI) and waist circumference, respectively, are important risk factors for the presence and progression of CAC. “Understanding the influence of the duration of obesity or the presence or progression of atherosclerosis is critical, given the obesity epidemic. With a doubling of obesity rates for adults and a tripling of rates for adolescents during the last 3 decades, younger individuals are experiencing a greater cumulative exposure to excess adiposity during their lifetime. However, few studies have determined the consequences of long-term obesity,” the authors write.

Jared P. Reis, Ph.D., of the National Heart, Lung, and Blood Institute, Bethesda, Md., and colleagues conducted a study to investigate whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of CAC. The study included 3,275 white and black adults 18 to 30 years of age at the beginning of the study period in 1985-1986 who did not initially have overall obesity (BMI ≥30) or abdominal obesity (men; waist circumference [WC] >40.2 inches; women: >34.6 inches) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after the beginning of the study.

Of the 3,275 eligible participants, 45.7 percent were black and 50.6 percent were women. During followup, 40.4 percent and 41.0 percent developed overall and abdominal obesity, respectively; the average duration of obesity was 13.3 years and 12.2 years for those who developed overall and abdominal obesity, respectively.

Overall, CAC was present in 27.5 percent (n = 902) of participants. The researchers found that the presence and extent of CAC were associated with duration of overall and abdominal obesity. “Approximately 38.2 percent and 39.3 percent of participants with more than 20 years of overall and abdominal obesity, respectively, had CAC compared with 24.9 percent and 24.7 percent of those who never developed overall or abdominal obesity,” the researchers write. “Extensive CAC was present in 6.5 percent and 9.0 percent of those with more than 20 years of overall and abdominal obesity, respectively, compared with 5.7 percent and 5.3 percent of those who never developed overall or abdominal obesity, respectively.”

The rates of CAC were higher with a longer duration of overall obesity and abdominal obesity. Approximately 25.2 percent and 27.7 percent of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC compared with 20.2 percent and 19.5 percent of those with 0 years.

“In conclusion, in this study a longer duration of overall and abdominal obesity beginning in young adulthood was associated with CAC and its 10-year progression through middle age independent of the degree of adiposity,” the authors write. “These findings suggest that the longer duration of exposure to excess adiposity as a result of the obesity epidemic and an earlier age at onset will have important implications on the future burden of coronary atherosclerosis and potentially on the rates of clinical cardiovascular disease in the United States.”

(JAMA. 2013;310(3):280-288; 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 EARLY RELEASE: 9 A.M. (CT) WEDNESDAY, JULY 10, 2013

Media Advisory: To contact Christopher J. L. Murray, M.D., D.Phil., call William Heisel at 206-897-2886 or email wheisel@uw.edu. To contact editorial author Harvey V. Fineberg, M.D., Ph.D., call Jennifer Walsh at 202-334-2183 or email JWalsh@nas.edu.

CHICAGO – In a major study that includes data on the status of population health from 34 countries from 1990-2010, overall population health improved in the U.S. during this period, including an increase in life expectancy; however, illness and chronic disability now account for nearly half of the health burden and improvements in the U.S. have not kept pace with advances in population health in other wealthy nations, according to a study published online by JAMA. The study is being published online in connection with an event at the White House and the National Press Club regarding the state and trends of health in the U.S. Dr. Murray and JAMA Editor-in-Chief Howard Bauchner, M.D., will be among the speakers at the National Press Club.

“The United States spends the most per capita on health care across all countries, lacks universal health coverage, and lags behind other high-income countries for life expectancy and many other health outcome measures. High costs with mediocre population health outcomes at the national level are compounded by marked disparities across communities, socioeconomic groups, and race and ethnicity groups,” according to background information in the article. “With increasing focus on population health outcomes that can be achieved through better public health, multisectoral action, and medical care, it is critical to determine which diseases, injuries, and risk factors are related to the greatest losses of health and how these risk factors and health outcomes are changing over time.”

Christopher J.L. Murray, M.D., D.Phil., of the Institute for Health Metrics and Evaluation, University of Washington, Seattle, and the U.S. Burden of Disease Collaborators, conducted a study to identify the leading diseases, injuries, and risk factors associated with the burden of disease in the United States; how these health burdens have changed over the last 2 decades; and compared these outcomes with those of 34 Organisation for Economic Co-operation and Development (OECD) countries. The researchers used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1,160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study.

Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages.

The researchers found that U.S. life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, healthy life expectancy increased from 65.8 years to 68.1 years. In 2010, diseases and injuries with the largest number of years of life lost due to premature death were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury (which includes bicycle, motorcycle, motor vehicle, and pedestrian injury). Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls.

In 2010, diseases with the largest number of years lived with disability were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. “As the U.S. population has aged, years lived with disability have comprised a larger share of disability-adjusted life-years than have YLLs. The leading risk factors related to disability-adjusted life-years were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use,” the authors write. With an increase in life expectancy and the number of years lived with disability for the average American, “individuals in the United States are living longer but are not necessarily in good health.”

Morbidity and chronic disability now account for nearly half of the health burden in the United States. “Mental and behavioral disorders, musculoskeletal disorders, vision and hearing loss, anemias, and neurological disorders all contribute to the increases in chronic disability. Research and development has been much more successful at finding solutions for cardiovascular diseases and some cancers and their associated risk factors than for these leading causes of disability,” the researchers note. “The progressive and likely irreversible shift in the disease burden profile to these causes also has implications for the type of resources needed in the U.S. health system.”

In the last two decades, improvements in population health in the United States did not keep pace with advances in population health in other wealthy nations. “Among 34 OECD countries between 1990 and 2010, the U.S. rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28^th, for the age-standardized years lived with disability rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for healthy life expectancy from 14th to 26th.”

“Regular assessments of the local burden of disease and matching information on health expenditures for the same disease and injury categories could allow for a more direct assessment of how changes in health spending have affected or, indeed, not affected changes in the burden of disease and may provide insights into where the U.S. health care system could most effectively invest its resources to obtain maximum benefits for the nation’s population health. In many cases, the best investments for improving population health would likely be public health programs and multisectoral action to address risks such as physical inactivity, diet, ambient particulate pollution, and alcohol and tobacco consumption,” the authors conclude.

(JAMA.doi:10.1001/jama.2013.13805; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study is supported in part by the Intramural Program of the National Institutes of Health, the National Institute of Environmental Health Sciences, and in part by the Bill and Melinda Gates Foundation. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: The State of Health in the United States

“Despite a level of health expenditures that would have seemed unthinkable a generation ago, the health of the U.S. population has improved only gradually and has fallen behind the pace of progress in many other wealthy nations,” writes Harvey V. Fineberg, M.D., Ph.D., of the Institute of Medicine, Washington, D.C., in an accompanying editorial.

“Setting the United States on a healthier course will surely require leadership at all levels of government and across the public and private sectors and actively engaging the health professions and the public. Analyses such as the U.S. Burden of Disease can help identify priorities for research and action and monitor the state of progress over time. If all constituents do their parts, the apt subtitle for the next generation’s analysis of U.S. health will be not ‘doing better and feeling worse (still)’ but ‘getting better faster than ever.’”

(JAMA.doi:10.1001/jama.2013.13809; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICJME Form for Disclosure of Potential Conflicts of Interest. Dr. Fineberg is president of the Institute of Medicine and serves on the board of the Institute for Health Metrics and Evaluation at the University of Washington.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 9, 2013

Dual Antiplatelet Therapy Following Coronary Stent Implantation is Associated With Improved Outcomes

Emmanouil S. Brilakis, M.D., Ph.D., of the VA North Texas Health Care System and University of Texas Southwestern Medical Center at Dallas, and colleagues conducted a review of medical literature regarding optimal medical therapy after percutaneous coronary intervention (PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries). The researchers identified 91 studies for inclusion in the review.

“Percutaneous coronary intervention is commonly performed for coronary revascularization in patients with stable angina or acute coronary syndromes (ACS), with approximately 600,000 procedures performed in the United States during 2009,” according to background information in the article. Stents are currently used in more than 90 percent of patients undergoing PCI because they significantly improve procedural success and subsequent clinical outcomes. The main complications after stent implantation are in-stent restenosis (renarrowing) and stent thrombosis (formation of a blood clot). “The goal of medical treatment after coronary stenting is to prevent stent thrombosis, slow the progression of coronary artery disease, and prevent major adverse cardiac events.”

The researchers found that dual antiplatelet therapy with aspirin and a P2Y₁₂ inhibitor (e.g., ticlopidine, clopidogrel, prasugref, ticagrelor) is associated with significant improvement in the outcomes of patients undergoing coronary stenting and remains the main medical therapy for optimizing stent-related outcomes after PCI and stent placement. Aspirin should be continued indefinitely and low dose (75-100 mg daily) is preferred over higher doses. A P2Y₁₂ inhibitor should be administered for 12 months after PCI unless the patient is at high risk for bleeding.

“Several ongoing studies will allow further optimization of the medical management of patients who receive coronary stents.”

(JAMA. 2013;310[2]:189-198. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Emmanouil S. Brilakis, M.D., Ph.D., call Erikka Neroes at 214-857-1158 or email Erikka.Neroes@va.gov.

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 Improvement Needed of Prescription Drug Postmarketing Studies

“Because rare but potentially serious adverse events of prescription drugs are often discovered only after market approval, observational postmarketing studies constitute an important part of the U.S. drug safety system,” write Kevin Fain, J.D., M.P.H., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues. “In 2007, Congress passed the Food and Drug Administration Amendments Act (FDAAA), which authorized the FDA to require postmarketing studies for a prescription drug’s approval and mandate adherence to study deadlines. We examined how fulfillment of these postmarketing studies has changed over time.”

As reported in a Research Letter, the authors extracted data on the status of all postmarketing studies for both biological license and new drug applications from the FDA annual reports published in the Federal Register and reviewed the status of all studies reported by the FDA from 2007 to 2011.

“Because of heightened public scrutiny of the status of postmarketing studies, we expected uninitiated studies to decrease and fulfilled studies to increase since 2007. Indeed, our analysis found the number of studies not yet started declined during this 5-year period, and the number of studies fulfilling obligations nearly doubled. These trends help address concerns expressed by the Institute of Medicine that many postmarketing studies before the FDAAA were not implemented or fulfilled. Despite these improvements, though, more than 40 percent of studies had not yet been started in 2011. In addition, the number of studies with delays doubled to approximately 1 in 8 as of 2011, and the proportion of all studies that have been fulfilled remains low,” the authors write.

“… despite some gains in studies initiated and fulfilled, our analysis reinforces continued concerns about the status of prescription drug postmarketing studies in the United States.”

(JAMA. 2013;310[2]:202-203. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author G. Caleb Alexander, M.D., M.S., call Tim Parsons at 410-955-7619 or email tmparson@jhsph.edu.

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Viewpoints Appearing in This Issue of JAMA

Patient-Centered Performance Management – Enhancing Value for Patients and Health Care Systems

Eve A. Kerr, M.D., M.P.H., and Rodney A. Hayward, M.D., of the VA Ann Arbor Healthcare System and University of Michigan, Ann Arbor, Mich., discuss the benefits of a patient-centered performance management system, which “would help clinicians and patients make individualized decisions about optimal care for common clinical situations, explicitly incorporate patient preferences, and reinforce such decisions through patient-centered performance measures.”

“Such a system would harness the power of comparative effectiveness research and shared decision-making to consider the full spectrum of medical interventions’ net benefits by comprehensively rewarding high-benefit care; facilitating and documenting shared decision making for services of modest or uncertain benefit; and discouraging inappropriate or harmful care.”

“There are certainly challenges to achieving a patient-centered performance management system. However, the benefits of this approach over current guideline and performance measurement approaches are great. The policy-making, health care delivery, research, and quality-improvement communities should dedicate themselves to making patient-centered performance management a reality in the foreseeable future.”

(JAMA. 2013;310[2]:137-138. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Eve A. Kerr, M.D., M.P.H., call Beata Mostafavi at 734-647-1156 or email bmostafa@umich.edu.

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 Standards for Patient-Reported Outcome-Based Performance Measures

In this Viewpoint, Ethan Basch, M.D., M.Sc., of the University of North Carolina, Chapel Hill, and colleagues examine recent initiatives by several major U.S. organizations involved with the development, endorsement, and implementation of performance measures that have converged on approaches for collecting, analyzing, and reporting outcomes that patients notice and care about (i.e., patient-centered).

“Research funding and engagement of stakeholders across the quality enterprise—including payers, health systems, professional societies, researchers, and patient groups—are essential for fostering priority setting, rigorous measure development, and integration of patient-reported outcomes-based performance measures into accountability programs. Such efforts will help bring patients’ perspectives to the center of care delivery and the center of performance measurement, where they belong.”

(JAMA. 2013;310[2]:139-140. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Ethan Basch, M.D., M.Sc., call William Davis at 910-232-6264 or email william.davis@med.unc.edu.

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Generic Clopidogrel – Time to Substitute?

Jacob Doll, M.D., of Duke University Medical Center, Durham, N.C., and colleagues  discuss the issues involved with deciding whether generic substitution of Plavix (clopidogrel) is appropriate, with exclusivity of this antiplatelet agent having expired in May 2012.

“On balance, a transition to generic clopidogrel is reasonable and probably inevitable. Because no robust system currently exists for tracking and circulating outcomes with generic clopidogrel, clinicians should be vigilant for adverse events and aggressive in reporting. Moving forward, clinical realities may demand that drug manufacturers and the FDA consider different standards of bioequivalency for drugs such as clopidogrel and more transparency in data reporting.”

(JAMA. 2013;310[2]:145-146. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Jacob Doll, M.D., call Sarah Avery at 919-660-1306 or email sarah.avery@duke.edu.

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, JULY 9, 2013

Media Advisory: To contact Dennis T. Ko, M.D., M.Sc., call Deborah Creatura at 416-480-4780 or email deborah.creatura@ices.on.ca.

CHICAGO – The increased use of cardiac catheterization in New York relative to Ontario appears related to selecting more patients at low risk of obstructive coronary artery disease, with the subsequent diagnostic yield (i.e., the proportion of tested patients in whom disease was diagnosed) of this procedure in New York significantly lower than in Ontario, according to a study in the July 10 issue of JAMA.

“The continuing increase in health care expenditures is threatening the sustainability of the health care system and the economy of many developed countries. Debates among the public, physicians, funders, and policymakers have concentrated on how to provide better quality of care at a lower cost. In the United States, a study found that only 1 in 3 patients who received elective cardiac catheterization had obstructive coronary artery disease (CAD), which raises concerns about the necessity of cardiac procedures for many patients with stable CAD. According to these findings, one might reasonably conclude that a more selective use of cardiac catheterization should be implemented to reduce its associated cost and to improve its diagnostic efficiency,” according to background information in the article.

“Previous cross-country comparison studies between the United States and Canada have highlighted large differences in the utilization of cardiac procedures because of different methods of incentivizing health care. Our group has previously shown that clinicians in New York State (New York) perform twice as many cardiac catheterizations per capita as are performed in Ontario, which could be explained by a difference in the burden of CAD or by a difference in the patient selection process for procedures. Given the increasing focus on how best to use scarce health care resources, it is important to understand the reasons underlying the different utilization patterns and their associated implications,” the authors write.

Dennis T. Ko, M.D., M.Sc., of the Institute for Clinical Evaluative Sciences, Toronto, Canada, and colleagues conducted a study to evaluate the extent of obstructive CAD and to compare the probability of detecting obstructive CAD among patients undergoing cardiac catheterization in New York and Ontario. The study included patients without a history of cardiac disease who underwent elective cardiac catheterization between October 2008 and September 2011. A total of 18,114 patients from New York and 54,933 from Ontario were included.

The observed rate of obstructive CAD was significantly lower in New York at 30.4 percent than in Ontario at 44.8 percent. In New York, 2.5 percent of patients who underwent cardiac catheterization were found to have left main stenosis, 5.2 percent had 3-vessel CAD, and 7.0 percent had left main or 3-vessel disease. In Ontario, patients were significantly more likely to have severe CAD; 5 percent had left main stenosis, 9.8 percent had 3-vessel coronary artery stenosis, and 13.0 percent had left main or 3-vessel disease.

Analysis of the data indicated that patients who received cardiac catheterization in New York had a significantly lower predicted probability of obstructive CAD than those in Ontario. “Overall, only 19.3 percent of patients in New York were predicted to have a greater than 50 percent probability of having obstructive CAD compared with 41.0 percent in Ontario. At the lowest-risk category, when the predicted probability of obstructive CAD was less than 15 percent, the proportion of patients in this category was 15.1 percent in New York and 6.9 percent in Ontario. At the highest-risk spectrum, when the predicted probability of obstructive CAD was greater than 75 percent, the proportion of patients was 1.4 percent in New York vs 7.9 percent in Ontario.”

The researchers also found that at 30 days, crude mortality for patients undergoing cardiac catheterization was slightly higher in New York at 0.65 percent (90 of 13,824) vs 0.38 percent (153 of 40,794) in Ontario. “However, this difference was driven primarily by higher mortality for patients without obstructive CAD in New York at 0.62 percent vs 0.27 percent in Ontario.”

“Several groups have proposed using obstructive CAD rate as a potential quality indicator to enhance efficiency and improve quality. Our study lends support to these proposals as we demonstrated the ability to increase diagnostic yield of cardiac catheterization through improved patient selection.”

(JAMA. 2013;310(2):163-169; 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, JULY 9, 2013

Media Advisory: To contact Maarten C. Bosland, D.V.Sc., Ph.D., call Sherri McGinnis Gonzalez at 312-996-8277 or email smcginn@uic.edu.

CHICAGO – Among men who had undergone radical prostatectomy, daily consumption of a beverage powder supplement containing soy protein isolate for 2 years did not reduce or delay development of biochemical recurrence of prostate cancer compared to men who received placebo, according to a study in the July 10 issue of JAMA.

“Prostate cancer is the most frequently diagnosed malignancy and the second most frequent cause of male cancer death in the United States and other Western countries but is far less frequent in Asian countries. Prostate cancer risk has been inversely associated with intake of soy and soy foods in observational studies, which may explain this geographic variation because soy consumption is low in the United States and high in Asian countries,” according to background information in the article.

“Although it has been repeatedly proposed that soy may prevent prostate cancer development, this hypothesis has not been tested in randomized studies with cancer as the end point. A substantive fraction (48 percent – 55 percent) of men diagnosed as having prostate cancer use dietary supplements including soy products, although the exact proportion is not known. However, no evidence exists that soy supplementation has any prostate cancer-related benefits for these men. Soy contains several constituents, including isoflavones, which possess anticancer activities in laboratory studies.”

Maarten C. Bosland, D.V.Sc., Ph.D., of the University of Illinois at Chicago, and colleagues examined whether daily consumption of a soy protein-based supplement would reduce the rate of recurrence or delayed recurrence of prostate cancer in men at high risk of recurrence after radical prostatectomy. The randomized trial was conducted from July 1997 to May 2010 at 7 U.S. centers and included 177 men. Supplement intervention was started within 4 months after surgery and continued daily for up to 2 years, with prostate-specific antigen (PSA) measurements made at 2-month intervals in the first year and every 3 months thereafter. Participants were randomized to receive a daily serving of a beverage powder containing 20 g of protein in the form of either soy protein isolate (n=87) or as placebo, calcium caseinate (n=90).

The trial was stopped early for lack of treatment effects at a planned interim analysis with 81 evaluable participants in the intervention group and 78 in the placebo group. Overall, 28.3 percent of participants developed biochemical recurrence (defined as development of a PSA level of ≥0.07 ng/mL) within 2 years of entering the trial. Twenty two (27.2 percent) of the participants in the intervention group developed confirmed biochemical recurrence, whereas 23 (29.5 percent) of the participants receiving placebo developed recurrence. “Among participants who developed recurrence, the median [midpoint] time to recurrence was somewhat shorter in the intervention group (31.5 weeks) than in the placebo group (44 weeks), but this difference was not statistically significant,” the authors write.

Adherence was greater than 90 percent. There were no differences in adverse events between the 2 groups.

“The findings of this study provide another example that associations in observational epidemiologic studies between purported preventive agents and clinical outcomes need confirmation in randomized clinical trials. Not only were these findings at variance with the epidemiologic evidence on soy consumption and prostate cancer risk, they were also not consistent with results from experiments with animal models of prostate carcinogenesis, which also suggest reduced risk,” the researchers write.

“One possible explanation for these discrepant results is that in both epidemiologic studies and animal experiments, soy exposure typically occurred for most or all of the life span of the study participants or animals; there are no reports of such studies in which soy exposure started later in life. Thus, it is conceivable that soy is protective against prostate cancer when consumption begins early in life but not later or when prostate cancer is already present. If this is the case, chemoprevention of prostate cancer with soy is unlikely to be effective if started later in life, given the high prevalence of undetected prostate cancer in middle-aged men.”

(JAMA. 2013;310(2):170-178; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This work was supported in part by grants from the National Institute of Health, with minor support from the Prevent Cancer Foundation and the United Soybean Board. Solae LLC provided the intervention materials.  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, JULY 9, 2013

Media Advisory: To contact Daniel D. Matlock, M.D., M.P.H., call Mark Couch at 303-724-5377 or email Mark.Couch@ucdenver.edu. To contact editorial author Harlan M. Krumholz, M.D., S.M., call Karen Peart at 203-432-1326 or email karen.peart@yale.edu.

CHICAGO – In a study that included nearly 6 million Medicare Advantage and Medicare fee-for-service beneficiaries from 12 states, rates of angiography and percutaneous coronary interventions were significantly lower among Medicare Advantage beneficiaries and geographic variation in procedure rates was substantial for both payment types, according to a study in the July 10 issue of JAMA.

“Treatment of cardiovascular disease is one of the largest drivers of health care cost in the United States, accounting for $273 billion annually. Cardiovascular procedures are major contributors to this high cost,” according to background information in the article. “Little is known about how different financial incentives between Medicare Advantage and Medicare fee-for-service (FFS) reimbursement structures influence use of cardiovascular procedures.”

“Under the Medicare FFS reimbursement structure, physicians are paid more for doing more procedures. In contrast, integrated delivery systems that provide care for Medicare Advantage beneficiaries receive a capitated payment, and physicians working in these settings are not paid more for doing more procedures,” the authors write.

Daniel D. Matlock, M.D., M.P.H., of the University of Colorado School of Medicine, Aurora, and colleagues conducted a study to compare the overall rates and local area rates of coronary angiography, percutaneous coronary intervention (PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries), and coronary artery bypass graft (CABG) surgery between Medicare Advantage and Medicare FFS beneficiaries living in the same communities. The study, which included 878,339 Medicare Advantage patients and 5,013,650 Medicare FFS patients older than 65 years of age, compared rates of these procedures between 2003-2007 across 32 hospital referral regions (HHRs) in 12 states.

The researchers found that compared with Medicare FFS patients, Medicare Advantage patients had lower age-, sex-, race-, and income-adjusted procedure rates for angiography and PCI but similar rates for CABG surgery. There were no differences between Medicare Advantage and Medicare FFS patients in the rates of urgent angiography. When examining procedure rates across HRRs, there was wide geographic variation among Medicare Advantage patients and Medicare FFS patients.

Across regions, the authors found no statistically significant correlation between Medicare Advantage and Medicare FFS beneficiary utilization for angiography and modest correlations for PCI and CABG surgery. Among Medicare Advantage beneficiaries, adjustment for additional cardiac risk factors had little influence on procedure rates.

“The finding that Medicare Advantage patients have lower rates of angiography and PCI underscores the need for additional research to determine the extent to which this is attributable to differences in population characteristics, more efficient utilization of procedures among Medicare Advantage patients (i.e., overutilization in Medicare FFS), or harmfully restrictive management of utilization among Medicare Advantage patients (i.e., underutilization in Medicare Advantage). One explanation for the differences in rates seen in this report could be that Medicare Advantage beneficiaries are healthier and require fewer cardiovascular procedures than Medicare FFS beneficiaries,” the authors write.

“Geographic variation in health services in the Medicare FFS population has fueled the perception of an inefficient, ineffective U.S. health care system. Until the causes of geographic variation are understood, shedding light on the sources of variability remains an important research and quality improvement endeavor. Indeed, comparing ‘the effectiveness of accountable care systems and usual care on costs, processes of care, and outcomes for geographically defined populations of patients’ is one of the Institute of Medicine’s 100 priorities for comparative effectiveness research. Capitation in various forms is anticipated to be an effective means of reducing future health care cost growth, particularly cost growth resulting from unnecessary care. Although in this study capitation was associated with lower procedure rates for angiography and PCI, the substantial geographic variation that remained despite the reimbursement structure suggests that capitation alone may not lead to reductions in the wide variations seen in use of cardiovascular procedures.”

(JAMA. 2013;310(2):155-162; 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, July 9 at this link.

Editorial: Variations in Health Care, Patient Preferences, and High-Quality Decision Making

“Scientists have documented variation in health care and have identified nonpatient factors that influence practice,” writes Harlan M. Krumholz, M.D., S.M., of the Yale University School of Medicine, New Haven, Conn., in an accompanying editorial.

“However, too little attention, for too long, has been directed toward ensuring the quality of preference-sensitive patient decisions. Moreover, if high-quality decisions, under the wide range of circumstances in medicine, are a worthy goal, investment is necessary to advance the science of clinical decision making, including increasing the understanding of the vulnerabilities of current approaches and developing ways to improve performance and ensure that the patient’s interests are best served. Ultimately, the goal is not to eliminate variation but to guarantee that its presence throughout health care systems derives from the needs and preferences of patients.”

(JAMA. 2013;310(2):151-152; 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, JULY 9, 2013

Media Advisory: To contact corresponding author Ian H. de Boer, M.D., M.S., call Leila Gray at 206-685-0381 or email leilag@uw.edu. To contact corresponding author Keith C. Norris, M.D., call Rachel Champeau at 310-794-0777 or email Rchampeau@mednet.ucla.edu.

CHICAGO – In a multiethnic group of adults, low serum 25-hydroxyvitamin D concentration was associated with increased risk of coronary heart disease events among white or Chinese participants but not among black or Hispanic participants, results that suggest that the risks and benefits of vitamin D supplementation should be evaluated carefully across race and ethnicity, according to a study in the July 10 issue of JAMA.

“Low circulating concentrations of 25-hydroxyvitamin D (25[OH]D) have been consistently associated with increased risk of clinical and subclinical coronary heart disease (CHD). Whether this relationship is causal and modifiable with vitamin D supplementation has not yet been determined in well-powered clinical trials, which are ongoing,” according to background information in the article. “Most studies of 25(OH)D and risk of CHD have examined populations that are composed largely or entirely of white participants. Results from these studies are frequently extrapolated to multiracial populations. This may not be appropriate because vitamin D metabolism and circulating 25 (OH)D concentrations vary substantially by race/ethnicity.”

Cassianne Robinson-Cohen, Ph.D., of the University of Washington, Seattle, and colleagues examined the association of serum 25(OH)D concentration with incident CHD events in a large, community-based, multiethnic population of adults. The analysis included 6,436 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), recruited from July 2000 through September 2002, who were free of known cardiovascular disease at the beginning of the study. Serum 25(OH)D concentrations were measured at baseline and associations of 25(OH)D with adjudicated CHD events were assessed through May 2012. Adjudicated CHD event was defined as myocardial infarction (heart attack), angina, cardiac arrest, or CHD death.

At the beginning of the study, the average age was 62 years and 53 percent of participants were women. Average serum 25(OH)D concentrations varied substantially by race/ethnicity. During a median (midpoint) follow-up of 8.5 years, 361 participants had a CHD event.

The researchers found significant heterogeneity in the association of 25(OH)D with CHD risk by race/ethnicity. Lower serum 25(OH)D concentration was associated with significantly higher risks of CHD among white participants (26 percent higher risk) per 10 ng/mL decrement in 25(OH)D concentration and Chinese participants (67 percent higher risk). “However, there was no evidence of association among black participants or Hispanic participants.”

“Differences in associations across race/ethnicity groups were consistent for both a broad and restricted definition of CHD and persisted after adjustment for known CHD risk factors,” the authors write.

“Well-powered clinical trials are needed to determine whether vitamin D supplements have causal and clinically relevant effects on the risk of CHD. Currently, at least 5 such trials are under way. One of these trials, the Vitamin D and Omega-3 Trial (VITAL), is targeting enrollment of a large multiracial study population, although power may be insufficient to determine whether effects vary by race even in this trial. Our study suggests that the risks and benefits of vitamin D supplementation should be evaluated carefully across race and ethnicity, and that the results of ongoing vitamin D clinical trials should be applied cautiously to individuals who are not white.”

(JAMA. 2013;310(2):179-188; 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. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Race/Ethnicity, Serum 25-Hydroxyvitamin D, and Heart Disease

In an accompanying editorial, Keith C. Norris, M.D., of the University of California, Los Angeles, and Sandra F. Williams, D.M.D., M.D., of the Cleveland Clinic, Weston, Fla., write that “… this large, well-designed, multiethnic study adds important insights to the complex relationships among race/ethnicity, 25(OH)D concentrations, and CHD risk.”

“The heterogeneity of the findings underscores the importance of exploring racial differences in clinical research and of not immediately generalizing results from ethnically homogeneous populations to other groups that may differ by race/ethnicity, sex, or age. Although the pooled data demonstrated a significant association between 25(OH)D and CHD, the subgroup analyses revealed marked differences underscoring the importance of examining such cohorts by race/ethnicity and thereby potentially discovering sociocultural or biological mediators that may affect cardiovascular health.”

(JAMA. 2013;310(2):153-154; 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. Norris reports receiving grant support from the National Institutes of Health; and payment for lectures and consulting from Abbott, Amgen, Davita, and Takeda. Dr. Williams reported no disclosures.

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