EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 10, 2013

Media Advisory: To contact corresponding author Leo Dunkel, M.D., Ph.D., email l.dunkel@qmul.ac.uk.

“Monitoring of linear growth is a well-established part of pediatric health care in the developed world. Although monitoring aims to support early diagnosis and timely treatment of disorders affecting growth, such disorders are often diagnosed late,” write Ulla Sankilampi, M.D., Ph.D., of Kuopio University Hospital, Kuopio, Finland, and colleagues.

As reported in a Research Letter, the authors compared the effectiveness of a novel computerized and automated growth monitoring (AGM) strategy integrated into an electronic health record (EHR) system in the primary care setting to standard growth monitoring (SGM) in 2008-2009. The preceding 3 years (2005-2008) were used as a comparator. Automated growth monitoring included analysis of growth data and referral of abnormal data for review, in addition to SGM.

During the control years, an annual average of 33,029 children were screened. An average of 4 children were diagnosed with a new growth disorder. During the AGM intervention year, the number of new diagnoses was 28 among the 32,404 screened children. The rate of growth disorders diagnoses was 0.1 per 1,000 screened children in the control years vs. 0.9 per 1,000 in the AGM year.

“In this population-based cohort study, we showed that screening of growth disorders using algorithms integrated into an EHR system was associated with a higher rate of detection and referral to specialist care,” the authors write. “Whether the results are generalizable to other countries remains to be determined.”

(doi:10.l001/jama.2013.218793; 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.

EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 10, 2013

Media Advisory: To contact Philippe Mathurin, M.D., email Philippe.Mathurin@chru-lille.fr. To contact editorial co-author Jonathan M. Fenkel, M.D., call Katharine Krauss at 215-955-5507 or email katharine.krauss@jefferson.edu.

Four weeks of treatment with a combination of the drug pentoxifylline and the corticosteroid prednisolone did not improve 6-month survival compared with prednisolone alone in 270 patients with severe alcoholic hepatitis, according to a study in the September 11 issue of JAMA.

Treatment of severe forms of alcoholic hepatitis is extremely challenging because of the poor outcome. European and U.S. guidelines recommend the use of prednisolone or pentoxifylline in patients with severe alcoholic hepatitis. Nevertheless, a substantial proportion of patients die after 6 months regardless of first-line therapy, according to background information in the article.

Philippe Mathurin, M.D., of the Hopital Huriez, Lille, France and colleagues compared the efficacy of a combination of prednisolone and pentoxifylline with prednisolone alone in patients with severe alcoholic hepatitis in 1 Belgian and 23 French hospitals. Duration of follow-up was 6 months. They randomly assigned 270 patients (18 to 70 years of age, who were heavy drinkers with severe biopsy-proven alcoholic hepatitis) to receive 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day (n=133) for 28 days, or 40 mg of prednisolone and matching placebo (n=137) for 28 days, between December 2007 and March 2010

Eighty-two deaths occurred in the 2 groups during the 6-month follow-up, due to complications from liver failure in 67 cases (81.7 percent) and other causes including gastrointestinal bleeding in 15 cases (18.3 percent). The researchers found no difference in 6-month survival between the 2 groups (69.9 percent in the pentoxifylline-prednisolone group [40 deaths] vs. 69.2 percent [in the placebo-prednisolone group [42 deaths]). Response to treatment and the probability of being a responder were also no different between groups.

The cumulative incidence of hepatorenal syndrome (rapid deterioration in kidney function) at 6 months was also not different in the pentoxifylline-prednisolone and the placebo-prednisolone groups.

Because of the lack of difference in survival and other outcomes, “our study does not support the use of a combination of pentoxifylline and prednisolone for severe alcoholic hepatitis,” the authors write, concluding that “future studies with an appropriate design are needed to provide robust data for developing new strategies to improve the outcome of patients with this life-threatening disease.”

(doi:10.l001/jama.2013.276300; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This work was supported by a Hospital-Based Clinical Research Program, a grant from the French Minister of Health. Pentoxifylline and its matching placebo were both supplied by Sanofi-Aventis Pharmaceuticals. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: Treatment of Severe Alcoholic Hepatitis With Corticosteroids and Pentoxifylline

In an accompanying editorial, Dina L. Halegoua-De Marzio, M.D., and Jonathan M. Fenkel, M.D., of Thomas Jefferson University Hospital, Philadelphia, comment on the findings of this study.

“… corticosteroids and pentoxifylline are currently the only and most successful medical treatments available for severe alcoholic hepatitis despite providing only modest improvements in mortality. The results reported by Mathurin and colleagues demonstrate that the sum (corticosteroids and pentoxifylline) is no greater than the individual parts for preventing mortality in well-characterized patients with severe alcoholic hepatitis. Pentoxifylline may remain a useful option for patients who have contraindications to receiving corticosteroids; however, this group was not studied by Mathurin and colleagues. The study also emphasizes the importance of developing new treatments for severe alcoholic hepatitis. These future studies also should include well-conducted evaluations of liver transplantation for carefully selected patients with severe alcoholic hepatitis not responding to medical management.”

(doi:10.l001/jama.2013.276301; 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 and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 10, 2013

Media Advisory: To contact Mary Reed, Dr.P.H., call Janet Byron at 510-891-3115 or email Janet.L.Byron@kp.org.

Among patients with diabetes, use of an outpatient electronic health record (EHR) in an integrated healthcare delivery system was associated with modest reductions in emergency department visits and hospitalizations, but was not associated with a change in office visit rates, according to a study in the September 11 issue of JAMA.

The Health Information Technology for Economic and Clinical Health (HITECH) Act authorizes up to $27 billion during 10 years to promote meaningful use of EHRs, with penalties for lack of EHR use beginning in 2015. With these substantial incentives, it is not surprising that EHR adoption in the United States appears to be increasing. Electronic health records increase access to timely and complete patient information at the point of care, with potential to improve the quality and efficiency of care delivered, including improved care coordination, according to background information in the article. “With medical care for patients with chronic diseases representing 75 percent of U.S. health care costs and hospitalizations representing one-third of all U.S. health care expenditures, better management of chronic medi­cal conditions such as diabetes represents one clinical area in which improved care theoretically could reduce spending. There is, however, limited and mixed evidence on the effect of EHRs on health outcomes or clinical events.”

Staggered EHR implementation across outpatient clinics in an integrated delivery system, Kaiser Permanente Northern California, between 2005 and 2008 created an opportunity for studying changes associated with EHR use. Mary Reed, Dr.P.H., of Kaiser Permanente Northern California, Oakland, and colleagues examined the association between EHR implementation and emergency department (ED) visits, hospitalizations, and office visits among patients with diabetes between 2004 and 2009, seen at 45 facilities in 17 medical centers. The study included all 169,711 patients in the health  plan’s clinical diabetes registry at the beginning of the study period.

The researchers found that after use of the EHR, there were fewer ED visits (a relative 5.5 percent decline from the average predicted baseline rate); hospitalizations decreased overall (a relative 5.2 percent decline from the predicted baseline average rate); and fewer nonelective hospitalizations (a relative 6.1 percent difference from the predicted baseline average rate). Hospitalizations specifically for ambulatory care-sensitive conditions also declined with EHR use (a 10.50 percent difference).

There was no statistically significant difference in office visit rates with the implementation of an EHR.

“Further studies are needed to quantify the association of EHR use with changes in costs,” the authors conclude.

(doi:10.l001/jama.2013.276733; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Research reported herein was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health and the Agency for Healthcare Research and Quality.  All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 10, 2013

Media Advisory: To contact Naomi S. Bardach, M.D., M.A.S., call Leland Kim at 415-502-NEWS or email Leland.Kim@ucsf.edu. To contact editorial co-author Rowena J. Dolor, M.D., M.H.S., call Sarah Avery at 919-660-1306 or email sarah.avery@duke.edu.

A pay-for-performance program in electronic-health-records-(EHR)-enabled small practices led to modest improvements in cardiovascular care processes and outcomes, according to a study in the September 11 issue of JAMA.

“Most evaluations of pay-for-performance (P4P) incentives have focused on large-group practices,” according to background information in the article. Small practices, where the majority of patients still receive care nationally, historically have provided lower-quality care—especially solo practices—and may have greater obstacles to improving care because they lack the scale and organizational structure to do so. It is possible that EHR-enabled solo and small-group practices will be able to respond to P4P incentives and improve quality, but this has not been demonstrated.

Naomi S. Bardach, M.D., M.A.S., of the University of California, San Francisco, and colleagues performed a randomized trial to assess the effect of P4P incentives on quality in EHR-enabled small practices in the context of an established quality improvement initiative. The study randomized small (fewer than 10 clinicians) primary care clinics in New York City from April 2009 through March 2010 to financial incentives and quarterly performance reports or performance reports alone. A city program provided all participating clinics with the same EHR software with decision support and patient registry and quality reporting capabilities. The program also provided on-site quality improvement specialists offering technical assistance. Incentivized clinics were paid for each patient whose care met the performance criteria, but they received higher payments for patients with co-existing illnesses, who had Medicaid insurance, or who were uninsured (maximum payments: $200/patient; $100,000/clinic). Quality reports were given quarterly to both the intervention and control groups.

The primary outcome measures were a comparison of between-group differences in performance improvement, from the beginning to the end of the study, between control and intervention clinics for aspirin or antithrombotic prescription, blood pressure control, cholesterol control, and smoking cessation interventions.

The researchers found that performance improved in both groups during the study, with positive changes from baseline for all measures. The adjusted change in performance was higher in the intervention than in the control group for aspirin or antithrombotic prescription for patients with diabetes or ischemic vascular disease [12.0 percent vs. 6.1 percent]; and for blood pressure control in patients with hypertension but without diabetes or ischemic vascular disease [9.7 percent vs. 4.3 percent]; and smoking cessation interventions (12.4 percent vs. 7.7 percent).

For uninsured or Medicaid (non-HMO) patients, changes in measured performance were higher in the intervention clinics than the control clinics (range of adjusted absolute differences, 7.9 percent to 12.9 percent), for all measures but cholesterol control, but the differences were not statistically significant.

“In this cluster-randomized study of P4P incentives, we found that EHR-enabled small practices were able to respond to incentives to improve cardiovascular care processes and intermediate outcomes,” the authors write. “This provides evidence that, in the context of increasing uptake of EHRs with robust clinical management tools, small practices may be able to improve their quality performance in response to an incentive.”

(doi:10.l001/jama.2013.277353; 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 and none were reported. Please see the article for additional information, including other authors, author contributions and affiliations, funding and support, etc.

Editorial: Financial Incentives in Primary Care Practice – The Struggle to Achieve Population Health Goals

In an accompanying editorial, Rowena J. Dolor, M.D., M.H.S., and Kevin A. Schulman, M.D., of the Duke University School of Medicine, Durham, N.C., comment on the two randomized trials in this issue of JAMA (Bardach et al; Petersen et al) that report the comparative effectiveness of financial incentives in primary care settings.

“Even though the findings of these 2 studies are encouraging in advancing understanding of the P4P strategy, the reports also raise questions about the solitary focus on clinician performance in achieving these population health goals. Both studies suggest that even with elegant incentives applied at the practice level, gaps in clinical performance still remain. These results suggest that although there is some room for improvement of individual performance, these gaps represent systematic shortcomings rather than an issue with performance at the individual clinician level.”

“In a population health model, a variety of strategies is used to achieve success. Some of these strategies would be clinician focused, some technology focused, some community focused, and some patient focused. The appropriate allocation of resources to each of these strategies would be based on economic analysis—how to gain the greatest increase in population health from optimizing interactions across all of these efforts. This type of framework transforms the question from the effectiveness of primary care practice to the effectiveness of primary care service embedded in a community.”

(doi:10.l001/jama.2013.277575; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 10, 2013

Media Advisory: To contact Laura A. Petersen, M.D., M.P.H., call Graciela Gutierrez at 713-798-4710 or email ggutierr@bcm.edu.

In an examination of the effect of financial incentives on hypertension care at 12 outpatient clinics, physician-level (individual) financial incentives, but not practice-level or combined incentives, resulted in greater blood pressure control or appropriate response to uncontrolled blood pressure, according to a study in the September 11 issue of JAMA. None of the incentives resulted in greater use of guideline-recommended medications compared with controls.

“As part of the Affordable Care Act, the U.S. government has introduced pay for performance to all hospitals paid by Medicare nationwide. The New York City Health and Hospitals Corporation recently announced a performance pay plan for physicians. These and other value-based purchasing systems are intended to align incentives to promote high-quality health care. Evaluations of the effectiveness of pay-for-performance programs directed at hospitals have shown contradictory results,” according to background information in the article.

Laura A. Petersen, M.D., M.P.H., of the Veterans Affairs Medical Center and Baylor College of Medicine, Houston, and colleagues conducted a randomized controlled trial to test the effect of explicit financial incentives to individual physicians and practice teams for the delivery of guideline-recommended care for hypertension in the primary care setting. The trial at 12 Veterans Affairs outpatient clinics with 5 performance periods enrolled 83 primary care physicians and 42 nonphysician personnel (e.g., nurses, pharmacists). The interventions were physician-level (individual) incentives, practice-level incentives, both, or none. Intervention participants received up to 5 payments every 4 months; all participants could access feedback reports. The primary measured outcomes were the number of patients (among a random sample) achieving guideline-recommended blood pressure thresholds or receiving an appropriate response to uncontrolled blood pressure, the number of patients prescribed guideline-recommended medications, and the number who developed hypotension (abnormally low blood pressure).

Among physicians who participated in all 5 performance periods, the average total payment for physicians over the course of the study was $4,270 in the combined physician and practice-level group, $2,672 in the individual physician-level group, and $1,648 in the practice-level group.  Change in blood pressure control or appropriate response to uncontrolled blood pressure compared with the control group was greater only in the individual incentives group. The difference in change in proportion of patients achieving blood pressure control or receiving an appropriate response between the individual incentive and no incentive group was 8.36 percent.

Although the use of guideline-recommended medication increased over the course of the study in the intervention groups, there was no change compared with controls.

The researchers did find that far more intervention than control group participants viewed their feedback reports on the website (67 percent vs. 25 percent), suggesting that participants were aware of the relationship between performance and rewards.

“Although concerns about overtreatment have been cited in criticisms of pay-for-performance programs, we did not find a higher incidence of hypotension in the panels of physicians randomized to the incentive groups,” they write.

Even small reductions in blood pressure translate into significant reductions in morbidity and mortality, and in system-wide costs, the authors write. “This trial addresses the needs of policy makers and payers for information about a clinically relevant payment intervention in routine practice. Payment-system interventions are attractive because of their potential scale and reach. However, payment-system interventions are only one piece of the solution to improve management of chronic diseases such as hypertension. More resource-intensive, tailored, patient-level self-management strategies may be needed to truly affect patient outcomes.”

(doi:10.l001/jama.2013.276303; 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 and none were reported. Please see the article for additional information, including other authors, author contributions and affiliations, funding and support, etc.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, September 10 at this link.

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EMBARGOED FOR EARLY RELEASE: 4:45 A.M. (CT) TUESDAY, SEPTEMBER 3, 2013

Media Advisory: To contact Stephen J. Nicholls, M.B.B.S., Ph.D., email stephen.nicholls@sahmri.com. To contact editorial co-author Jean-Claude Tardif, M.D., call Marie-Josee Nantel at 514-376-3330, ext. 2641; or email Marie-Josee.Nantel@icm-mhi.org.

CHICAGO – Among patients with prehypertension and coronary artery disease, use of the renin (an enzyme secreted by the kidneys) inhibitor aliskiren, compared with placebo, did not result in improvement or slowing in the progression of coronary atherosclerosis, according to a study published by JAMA. The study is being released early online to coincide with its presentation at the European Society of Cardiology Congress 2013.

“Guidelines recommend blood pressure reduction in patients with hypertension with a treatment goal of 140 mm Hg for systolic and 90 mm Hg diastolic blood pressure for most individuals. The benefit of additional blood pressure lowering agents in patients who have reached treatment goals has not been established. However, few trials have examined the benefits and risks of further intensifying blood pressure treatment in patients with established coronary artery disease (CAD), who are in the prehypertension range. Preclinical data demonstrate that renin-angiotensin-aldosterone system (RAAS) activation plays an important role in atherosclerosis and that RAAS inhibition may have a direct beneficial effect on the artery wall,” according to background information in the article. “Blood pressure reduction and RAAS inhibition are targets for treatment of atherosclerosis. The effect of renin inhibition on coronary disease progression has not been investigated.”

Stephen J. Nicholls, M.B.B.S., Ph.D., of the South Australian Health and Medical Research Institute, Adelaide, Australia, and colleagues conducted a study to determine if renin inhibition with aliskiren would slow progression of coronary atherosclerosis in patients whose blood pressure was considered optimally controlled to current treatment targets. The randomized, multicenter trial compared aliskiren with placebo in 613 participants with coronary artery disease, systolic blood pressure between 125 and 139 mm Hg (prehypertension range), and 2 additional cardiovascular risk factors. The trial was conducted at 103 academic and community hospitals in Europe, Australia, and North and South America (enrollment from March 2009 to February 2011; end of follow-up was January 2013).

Participants underwent coronary intravascular ultrasound (IVUS) imaging and were randomized to receive 300 mg of aliskiren (n = 305) or placebo (n = 308) daily for 104 weeks. Disease progression was measured by repeat IVUS examination after at least 72 weeks of treatment, with evaluable imaging data available at follow-up in 74.7 percent of patients (225 in the aliskiren group and 233 in the placebo group). The primary efficacy parameter was the change in percent atheroma (a fatty deposit) volume (PAV) from baseline to study completion.

The researchers found that there was no difference between the treatment groups with respect to measures of atheroma burden at baseline. The primary efficacy measure, PAV, decreased by 0.33 percent in the aliskiren group and increased by 0.11 percent in the placebo group (between-group difference, -0.43 percent). There were no significant differences in the proportion of participants who demonstrated regression of PAV (56.9 percent vs. 48.9 percent) and total atheroma volume (64.4 percent vs. 57.5 percent) in the aliskiren and placebo groups, respectively.

A greater number of discontinuations of participation due to adverse events were observed in the aliskiren group compared with the placebo group (8.2 percent vs. 4.5 percent, respectively).

“These findings do not support the use of aliskiren for regression or prevention of progression of coronary atherosclerosis,” the authors conclude.

(doi:10.l001/jama.2013.277169; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The study was funded by Novartis Pharmaceuticals. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Renin-Angiotensin System Inhibition and Secondary Cardiovascular Prevention

In a related editorial, Jean-Claude Tardif, M.D., and Jean Gregoire, M.D., of the Montreal Heart Institute, Montreal, Canada, comment on the findings of this study, and also discuss two other trials in which aliskiren was not effective in improving clinical outcomes in patients with cardiovascular disease.

“Where does this leave inhibition of the renin-angiotensin system for secondary cardiovascular prevention? Angiotensin-converting enzyme inhibitors or, if not tolerated, angiotensin receptor blockers provide clinical benefits and should continue being prescribed to improve outcomes in patients with coronary artery disease. Until additional evidence is available, the role of renin inhibition in this context should be limited. Because aliskiren does reduce blood pressure, perhaps this agent could be reserved for use in patients with coronary disease and hypertension who cannot tolerate ACE inhibitors and angiotensin receptor blockers.”

(doi:10.l001/jama.2013.277170; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Hepatitis B Immunization Program in Taiwan Associated With Reduction in Chronic Liver Disease Deaths

“Hepatitis B virus (HBV) infection causes infant fulminant hepatitis (IFH), and chronic HBV infection may progress to chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Taiwan launched a nationwide HBV immunization program for newborns in July 1984, which has successfully lowered the prevalence of chronic HBV carriers, incidence of HCC, and mortality of IFH in vaccinated birth cohorts. The mortality of CLD before and after HBV immunization has never been examined,” write Chun-Ju Chiang, Ph.D., of National Taiwan University, Taipei, and colleagues.

As reported in a Research Letter, the authors assessed the 30-year outcomes of the immunization program. From July 1984 to June 1986, the immunization program covered only newborns with high-risk mothers who were seropositive for HBV surface antigen. Coverage was extended to all newborns in July 1986, preschool children in July 1987, and primary school children in 1988-1990. Recombinant HBV vaccines replaced plasma-derived vaccines in 1992. The immunization coverage rates for birth cohorts from 1984 to 2010 was 88.8 percent to 96.9 percent. The mortality of IFH, CLD, and HCC and the incidence of HCC were compared among birth cohorts born before and after the launch of the program.

The researchers found that from 1977-1980 to 2001-2004, the age- and sex-adjusted rate ratios for individuals 5 to 29 years of age decreased by more than 90 percent for CLD and HCC mortality and by more than 80 percent for HCC incidence, which were higher than the previously reported reduction (70 percent) in HCC incidence for youth 6 to 19 years of age.

The mortality of IFH in vaccinated birth cohorts decreased by more than 90 percent from 1977-1980 to 2009-2011, which was greater than the previously reported reduction (approximately 70 percent) from 1975-1984 to 1985-1998. “This long-term, high-coverage immunization program was associated with lower IFH mortality through increasing individual and herd immunity of vaccinated cohorts.”

(doi:10.l001/jama.2013.276701; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Chien-Jen Chen, Sc.D., email chencj@gate.sinica.edu.tw.

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Viewpoints Appearing in This Issue of JAMA

Poverty, Health, and Societies of the Future

“Today, as never before, the opportunity exists to unite global health and the fight against poverty through action that is focused on clear goals. The 2 aspirations of a right to health and of ending extreme poverty can be pursued as 1 through universal health coverage,” write Jim Yong Kim, M.D., Ph.D., of the World Bank Group, Washington, D.C., and Margaret Chan, M.D., of the World Health Organization, Geneva, Switzerland.

“There are many barriers to ending extreme poverty, boosting shared prosperity, and achieving universal health coverage. Clinicians must continue to lead the way in delivering high-quality services to patients and demanding that all patients, regardless of class or nationality, deserve a chance at a healthy life. Achieving improved health for all will require building health equity and economic transformation as a single structure, a citadel to shelter the lives of future generations.”

(doi:10.l001/jama.2013.276910; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Jim Yong Kim, M.D., Ph.D., call Carolyn Reynolds at 202-473-0049 or email CReynolds@worldbank.org.

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What the United States Has to Gain From Global Health Research

In this Viewpoint, Roger I. Glass, M.D., Ph.D., of the Fogarty International Center, National Institutes of Health, Bethesda, Md., discusses the importance and benefits of the U.S. investing in global health research.

“… the United States has already benefitted from research in global health. Major discoveries have occurred through collaborations with other countries, competitiveness has been expanded by enlisting new partners to research, and the nation’s humanitarian spirit has been demonstrated by addressing some of the most compelling medical problems today and by assisting economic development. Now, as life expectancy in low- and middle-income countries approaches that in the United States, there is even greater urgency to cooperate and collaborate to confront these shared health problems. Whether that threat is an outbreak of severe acute respiratory syndrome or a new strain of influenza; the persistent problems of cancer, stroke, and heart disease; or the increasing epidemics of obesity and addictive disorders, the response will have to come from the collaboration of creative minds from around the world focused on how to most rapidly arrive at new and more effective solutions for prevention and treatment. Without an emphasis on global health, the United States risks falling behind in its leadership in biomedical research and its competitive position in commercialization of discoveries.”

(doi:10.l001/jama.2013.276558; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Roger I. Glass, M.D., Ph.D., call Ann Puderbaugh at 301-402-8614 or email ann.puderbaugh@nih.gov.

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 Conflict and Polio – Winning the Polio Wars

“The global polio eradication initiative is at a critical crossroads. Some 25 years ago, the World Health Organization (WHO), supported by Rotary International, launched a global goal of eradicating polio from the world by 2000. Although the eradication target may not have been achieved, there has been remarkable progress. From more than 350,000 cases of poliomyelitis globally spread over 125 countries with endemic disease in 1990, a mere 223 cases were reported in 2012, with the disease largely restricted to a few regions of Nigeria, Pakistan, and Afghanistan,” writes Zulfiqar A. Bhutta, M.B., B.S., F.R.C.P., F.R.C.P.C.H., Ph.D., of the Sick Kids Center for Global Child Health, Toronto, and The Aga Khan University, Karachi, Pakistan.

“Eradicating polio in the residual population pockets of Asia and Africa is impossible without a concerted effort to reach every child and family in conflict zones. As long as the polio program continues as a largely insulated program with limited relevance and linkage to critical public health needs, engaging impoverished and suspicious populations will remain a challenge. Such promotion of demand in communities and reduction of vaccine hesitancy are critical steps in eradicating polio in areas of conflict. There are few examples in modern history of controlling, let alone eradicating, an infectious disease in the midst of a raging conflict, and there is no reason to believe that polio will be any different. Finding peace and a political settlement in the region is an important prerequisite for global polio eradication and addressing the health and developmental needs of innocent children caught in the middle.”

(doi:10.l001/jama.2013.276583; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Zulfiqar A. Bhutta, M.B., B.S., F.R.C.P., F.R.C.P.C.H., Ph.D., call Caitlin McNamee-Lamb at 416-813-7654, ext. 201436, or email caitlin.mcnamee-lamb@sickkids.ca.

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 Industry-Sponsored Clinical Trials in Emerging Markets – Time to Review the Terms of Engagement

A decade ago, clinical trial sponsors routinely excluded low- and middle-income countries such as India and China from participation. “Today, more than 3,000 trials are under way in China, a large proportion of which are sponsored by global pharmaceutical companies,” write Stephen MacMahon, D.Sc., F.Med.Sci., of the George Institute for Global Health, Sydney, Australia, and colleagues. In China the number of pharmaceutical company-sponsored trials doubled between 2005 and 2010. “… the rapid expansion of clinical trial activity in emerging markets has raised concerns, including questions about the quality of data generated and the relevance of the products being tested to local health care priorities.”

“The last few decades have seen enormous health benefits and corporate profits flow from the results of clinical trials across a range of conditions. However, the model by which such trials are conducted must evolve if such benefits are to continue. There is a real risk that the next few decades will not generate the same returns unless there is adaptation to the new circumstances in which trials are conducted and recognition of the rights and expectations of communities in which trial participants live. The rapidly increasing value of emerging markets to global pharmaceutical companies will hopefully provide the incentive for change. Otherwise, it will be up to emerging markets to insist on it.”

(doi:10.l001/jama.2013.276913; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Stephen MacMahon, D.Sc., F.Med.Sci., email smacmahon@georgeinstitute.org.

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

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

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

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EMBARGOED FOR EARLY RELEASE: 4:30 A.M. (CT) SUNDAY, SEPTEMBER 1, 2013

Media Advisory: To contact Philippe Gabriel Steg, M.D., email gabriel.steg@bch.aphp.fr.

CHICAGO – Use of the novel anticoagulant otamixaban did not reduce ischemic events compared with unfractionated heparin plus eptifibatide but increased bleeding among patients with non–ST-segment elevation acute coronary syndromes undergoing a percutaneous coronary intervention (PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries), according to a study published by JAMA. The study is being released early online to coincide with its presentation at the European Society of Cardiology Congress 2013

“Major progress has been made in the management of non–ST-segment elevation [a certain pattern on an electrocardiogram] acute coronary syndromes (NSTE-ACS) because of the availability of potent combinations of oral antiplatelet agents, injectable anticoagulants, and increasing use of an invasive strategy. Nevertheless, the risk of adverse outcomes remains substantial, and there is no consensus on a single optimal injectable anticoagulant that can be used across the continuum of care from the emergency setting through revascularization (when applicable),” according to background information in the article. The synthetic intravenous drug otamixaban inhibits thrombin [an enzyme that acts on fibrinogen in blood causing it to clot] generation in a dose-dependent manner. A phase 2 trial showed a reduction in the combined outcome of death or myocardial infarction (heart attack) in patients treated with otamixaban compared with unfractionated heparin (UFH) plus eptifibatide (an antiplatelet drug) and showed similar bleeding rates with otamixaban at midrange doses.

Philippe Gabriel Steg, M.D., of the Université Paris-Diderot, Sorbonne-Paris Cité, Paris, and investigators with the TAO trial compared the clinical efficacy and safety of otamixaban with that of unfractionated heparin plus eptifibatide in 13,229 patients with NSTE-ACS and a planned early invasive strategy. The trial was conducted at 568 active sites in 55 countries between April 2010 and February 2013. Eligible participants were randomized to otamixaban or unfractionated heparin plus, at the time of PCI, eptifibatide.

The primary outcome of death or new myocardial infarction through day 7 occurred in 5.5 percent of the patients treated with otamixaban vs. 5.7 percent of the patients treated with UFH plus eptifibatide. Otamixaban did not significantly reduce the risk of any of the components of the primary outcomes, either death or heart attack, or of any of the secondary efficacy outcomes, including procedural thrombotic complications. Analysis of the primary outcome by 30 days confirmed the absence of a reduction with otamixaban.

In the lower-dose otamixaban group, discontinued by the data monitoring committee for futility based on the interim analysis, the rate of the primary outcome at day 7 was 6.3 percent.

Patients in the otamixaban group had about double the rate of the primary safety outcome of Thrombosis in Myocardial Infarction major or minor bleeding at day 7 compared with patients in the combination of UFH-plus-eptifibatide group (3.1 percent vs. 1.5 percent). Otamixaban consistently increased all types of bleeding events, regardless of the severity or bleeding classification scheme used. Study anticoagulant was discontinued because of bleeding in 242 patients (4.7 percent) in the otamixaban group and in 95 patients (1.7 percent) in the UFH-plus-eptifibatide group.

“Otamixaban did not reduce ischemic events compared with UFH plus eptifibatide but increased bleeding among patients with NSTE-ACS and a planned invasive strategy. These findings do not support the use of otamixaban for patients with NSTE-ACS undergoing planned early percutaneous coronary intervention,” the authors conclude.

(doi:10.l001/jama.2013.277165; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This trial was funded by Sanofi. 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, SEPTEMBER 3, 2013

Media Advisory: To contact Stanley Zlotkin, M.D., Ph.D., call Caitlin McNamee-Lamb at 416-813-7654, ext. 201436 or email caitlin.mcnamee-lamb@sickkids.ca. To contact editorial author co-author Andrew M. Prentice, Ph.D., email andrew.prentice@lshtm.ac.uk.

CHICAGO – Children in a malaria-endemic community in Ghana who received a micronutrient powder with iron did not have an increased incidence of malaria, according to a study in the September 4 issue of JAMA. Previous research has suggested that iron supplementation for children with iron deficiency in malaria-endemic areas may increase the risk of malaria

“In sub-Saharan Africa, malaria is a leading cause of childhood morbidity and mortality, and iron deficiency is among the most prevalent preventable nutritional deficiencies. The provision of iron to children with iron deficiency anemia can enhance motor and cognitive development and reduce the prevalence of severe anemia. However, studies have suggested that iron deficiency anemia may offer protection against malaria infection and that the provision of iron may increase malaria morbidity and mortality,” according to background information in the article. “In 2006, the World Health Organization and the United Nations Children’s Fund released a joint statement that recommended limiting use of iron supplements (tablets or liquids) among children in malaria-endemic areas because of concern about increased malaria risk. As a result, anemia control programs were either not initiated or stopped in these areas.”

Stanley Zlotkin, M.D., Ph.D., of the Hospital for Sick Children, Toronto, and colleagues conducted a study to determine the effect of providing micronutrient powder (MNP) with or without iron on the incidence of malaria among children living in a high malaria-burden area. The randomized trial, which included children 6 to 35 months of age (n = 1,958 living in 1,552 clusters), was conducted over 6 months in 2010 in a rural community setting in central Ghana, West Africa. A cluster was defined as a compound including 1 or more households. Children were excluded if iron supplement use occurred within the past 6 months, they had severe anemia, or severe wasting. Children were randomized by cluster to receive a MNP with or without iron for 5 months followed by 1-month of further monitoring. Insecticide-treated bed nets were provided at enrollment, as well as malaria treatment when indicated.

Throughout the intervention period, adherence to the use of MNP and insecticide-treated bed nets were similar between the iron group and the no iron group. The researchers found that the overall incidence of malaria was lower in the iron group compared with the no iron group, but after adjustment for baseline values for iron deficiency and moderate anemia, these differences were no longer statistically significant. “Similar associations were found during the 5-month intervention period only for both malaria and malaria with parasite counts greater than 5000/µL (severe malaria). A secondary analysis demonstrated that malaria risk was reduced among the subgroup of those in the iron group who had iron deficiency and anemia at baseline.”

Overall, hospital admission rates did not differ significantly between groups. However, during the 5-month intervention period, there were more children admitted to the hospital in the iron group vs. the no iron group (156 vs. 128, respectively).

“The findings from the current study not only address a gap in the literature, but also have potentially important policy implications for countries like Ghana that have not implemented iron supplementation or fortification as part of anemia control programs in part due to the joint recommendation from the WHO and UNICEF. For ethical reasons, we ensured that all participants were not denied existing malaria prevention (insecticide-treated bed nets) or malaria treatment. As such, our results most likely can be applied to other malaria-endemic settings in which similar malaria control measures are in place. Overall, given our findings and the new WHO guidelines recommending iron fortification for the prevention and treatment of anemia among children younger than 2 years (in whom the prevalence of anemia is ≥20 percent), there should be renewed interest and consideration for implementing iron fortification in Ghana as part of the national nutrition policy.”

(doi:10.l001/jama.2013.277129; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Office of Dietary Supplements provided funding for this study. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Iron Fortification and Malaria Risk in Children

In an accompanying editorial, Andrew M. Prentice, Ph.D., of the London School of Hygiene and Tropical Medicine, and colleagues write that the increase seen in this study in hospital admissions among the iron supplementation group, which by definition constitutes a potentially serious adverse event, adds to the concerns about the safety of iron administration in highly malaria-endemic environments.

“Participants in an expert panel convened by the World Health Organization in 2007 speculated that iron given with foods, either by centralized or point-of-use fortification, would be safe. However, the Ghanaian trial reported by Zlotkin et al in this issue of JAMA now becomes the fourth trial to question this suggestion, and leaves global health policy makers with an unresolved dilemma. Until a means of safely administering iron in infectious environments has been developed, there remains an imperative to reduce the infectious burden as a prerequisite to moving poor populations from their current state of widespread iron deficiency and anemia.”

(doi:10.l001/jama.2013.6771; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Media Advisory: To contact Judith Spijkerman, M.D., email j.spijkerman@umcutrecht.nl. To contact editorial author Katherine L. O’Brien, M.D., M.P.H., call Tim Parsons at 410-955-7619 or email tmparson@jhsph.edu.

CHICAGO – The use of 4 different 13-valent pneumococcal conjugate vaccine immunization schedules in healthy term infants resulted in no statistically significant differences in antibody levels between the infants after the booster dose at 12 months of age for almost all serotypes, according to a study in the September 4 issue of JAMA.

“The World Health Organization (WHO) estimated that more than 800,000 children younger than 5 years died from pneumococcal disease in 2000, making it the leading vaccine-preventable cause of death. Since the licensure in 2000 of the first 7-valent pneumococcal polysaccharide conjugate vaccine (PCV) for infants, many countries have added PCV to their existing national immunization programs. As a result, PCV immunization schedules differ between countries with respect to number of doses, age at vaccinations, and intervals between doses,” according to background information in the article. “The optimal vaccine schedule for infants should provide maximal, sustained direct and indirect protection against invasive pneumococcal disease while using a minimal number of doses. The latter is particularly relevant in the context of overcrowded national immunization programs, public resistance to vaccines, and cost-effectiveness estimates.”

Judith Spijkerman, M.D., of the University Medical Centre, Utrecht, the Netherlands, and colleagues compared immunogenicity of 4 different schedules using the 13-valent PCV (PCV13) to assess the optimal primary regimen with respect to antibody induction. The randomized clinical trial of healthy term infants in a general community in the Netherlands was conducted between June 2010 and January 2011, with 99 percent follow-up until age 12 months. Infants (n = 400) were randomly assigned (1:1:1:1) to receive PCV13 either at ages 2,4, and 6 months (2-4-6); at ages 3 and 5 months (3-5); at ages 2,3, and 4 months (2-3-4); or at ages 2 and 4 months (2-4), with a booster dose at age 11.5 months.

The researchers found that one month after the booster dose, there were no differences in IgG (Immunoglobulin G) geometric mean concentrations (GMCs) between the schedules for 70 of 78 comparisons. “The 2-4-6 schedule was superior to the 2-3-4 schedule for serotypes 18C and 23F and superior to the 2-4 schedule for serotypes 6B, 18C, and 23F. For serotype 1, the 3-5 schedule was superior to the 2-4-6, 2-3-4, and 2-4 schedules.”

Secondary outcomes (GMCs measured 1 month after the primary series, at 8 months of age, and before the booster) demonstrated differences 1 month after the primary series. “The 2-4-6 schedule was superior compared with the 3-5, 2-3-4, and 2-4 schedules for 3,9, and 11 serotypes, respectively. Differences between schedules persisted until the booster dose,” the authors write.

“To our knowledge, this is the first randomized controlled trial investigating immunogenicity of PCV13 in 4 different primary immunization schedules currently used in most high income countries. The primary outcome of this study, GMCs l month after the booster dose, showed that there were no statistically significant differences between the 4 schedules in IgG levels for most serotypes. However, differences between schedules were noted in secondary analyses. … Our findings demonstrate that optimal timing of the primary series, i.e., older age at vaccinations combined with longer intervals between vaccinations, is important to maintain optimal antibody levels during the period between the primary series and the booster dose.”

“The choice of PCV schedule will require a balance between the need for early protection and maintaining protection between the primary series and the booster, in particular before herd effects offer clinical protection against vaccine serotype disease to as yet unvaccinated or incompletely vaccinated infants. When herd immunity is established, clinical relevance of the observed differences in immune responses may become of minor importance,” the researchers conclude.

(doi:10.l001/jama.2013.228052; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was performed by order and for the account of the Dutch Ministry of Health by additional immunization program research funding. Pfizer kindly provided 1,400 PCV13 vaccines. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Optimizing the Use of Pneumococcal Conjugate Vaccine Globally

“A good deal remains to be learned about how best to use PCVs to protect the most vulnerable and the greatest number of community members,” writes Katherine L. O’Brien, M.D., M.P.H., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, in an accompanying editorial.

“Immunogenicity is just one aspect of biological effect, perhaps more important for some serotypes than others. Focus should remain squarely on ensuring that every child is immunized with at least 3 doses of PCV, beginning early in life and administered in a timely fashion. The study by Spijkerman and colleagues reassures that PCV products now in use provide a robust immune response across a range of dosing schedules and focuses attention on specific serotypes of concern. It is good news that PCVs are adaptable to various dosing schedules and therefore to demands of vaccine programs across countries. Emphasis on immunogenicity differences should not be separated from the larger context of protection at the individual level, pneumococcal disease epidemiology, vaccine program performance, and ultimately clear measures of disease outcome.”

(doi:10.l001/jama.2013. 228062; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of interest. Dr. O’Brien reported having received research grant support from GlaxoSmithKline and Pfizer and having served on external expert advisory groups related to pneumococcal vaccine for Merck, GlaxoSmithKline, and Aventis-Pasteur.

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

Media Advisory: To contact corresponding authors Guang Ning, M.D., Ph.D., email gning@sibs.ac.cn; Wenhua Zhao, Ph.D., email whzhao@ilsichina.org; or Weiqing Wang M.D., Ph.D., email wqingw@hotmail.com. To contact editorial author Juliana C. N. Chan, M.D., F.R.C.P., email jchan@cuhk.edu.hk.

CHICAGO – A study based on a nationally representative sample of adults in China in 2010 indicates that nearly 12 percent of Chinese adults had diabetes and the prevalence of prediabetes was about 50 percent, according to a study in the September 4 issue of JAMA.

“Noncommunicable chronic diseases have become the leading causes of mortality and disease burden worldwide. It was estimated that 34.5 million deaths globally were due to noncommunicable diseases in 2010, which reflected a significant increase from 1990. Mortality from diabetes doubled during this period and increased to 1.3 million deaths worldwide in 2010. In addition, diabetes is a major risk factor for ischemic heart disease and stroke, which collectively killed an estimated 12.9 million people globally in 2010,” according to background information in the article.

“The prevalence of diabetes has increased significantly in recent decades and is now reaching epidemic proportions in China. The prevalence of diabetes was less than 1 percent in the Chinese population in 1980. In subsequent national surveys conducted in 1994 and 2000-2001, the prevalence of diabetes was 2.5 percent and 5.5 percent, respectively. The most recent national survey in 2007 reported that the prevalence of diabetes was 9.7 percent, representing an estimated 92.4 million adults in China with diabetes.”

Yu Xu, Ph.D., of the Shanghai Jiao-Tong University School of Medicine, Shanghai, China, and colleagues with the 2010 China Noncommunicable Disease Surveillance Group, conducted a study to investigate the prevalence of diabetes and glycemic control in the Chinese adult population. Using a multistage, probability sampling design, the researchers conducted a cross-sectional survey in a nationally representative sample of 98,658 Chinese adults in 2010. Plasma glucose and hemoglobin A_1c levels were measured after at least a 10-hour overnight fast among all study participants, and a 2-hour oral glucose tolerance test was conducted among participants without a self-reported history of diagnosed diabetes. Diabetes and prediabetes were defined according to the 2010 American Diabetes Association criteria; whereas, a hemoglobin A_1c level of <7.0 percent was considered adequate glycemic control.

The researchers found that the overall prevalence of diabetes was estimated to be 11.6 percent in the Chinese adult population; 12.1 percent in men, and 11.0 percent in women, with an estimated prevalence of 8.1 percent for newly detected diabetes. “The prevalence of diabetes was higher in urban than in rural residents in both men and women. Furthermore, diabetes prevalence increased with age in both men and women, and men younger than 50 years had a higher prevalence, whereas women older than 60 years had a higher prevalence. In addition, the prevalence of diabetes increased with economic development, as well as in overweight and obese persons.”

The estimated prevalence of prediabetes was 50.1 percent in Chinese adults: 52.1 percent in men and 48.1 percent in women. Rural residents had slightly higher prevalence of prediabetes than did urban residents, especially in men. Additionally, prediabetes was more prevalent in economically underdeveloped regions, as well as in overweight and obese persons.

The authors also found that the proportion of patients with diabetes who were aware of their condition was 30.1 percent among the Chinese general population. Only 25.8 percent of overall patients with diabetes were treated for this condition, and only 39.7 percent of those treated had adequate glycemic control.

“These data suggest that diabetes may have reached an alert level in the Chinese general population, with the potential for a major epidemic of diabetes-related complications, including cardiovascular disease, stroke, and chronic kidney disease in China in the near future without an effective national intervention,” the researchers write. “These findings indicate the importance of diabetes as a public health problem in China.”

(doi:10.l001/jama.2013.168118; 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: Diabetes and Noncommunicable Disease – Prevent the Preventables

“Diabetes is a societal and a health care challenge due to complex interplays among genetic, perinatal, lifestyle, and environmental factors, to name but a few. Rapid modernization has resulted in an obesogenic environment characterized by food abundance, physical inactivity, and psychosocial stress,” writes Juliana C. N. Chan, M.D., F.R.C.P., of the Chinese University of Hong Kong Prince of Wales Hospital International Diabetes Federation Centre of Education, Shatin, Hong Kong, in an accompanying editorial.

“The lack of awareness, information, and feedback has caused many individuals unknowingly to engage in risk-conferring behaviors. Even when the individual becomes aware of his or her risk conditions, the health care systems in many developing areas are not designed to manage and support a person’s multiple health needs for 30 to 40 years or more. These needs include motivation, cognitive-psychological-behavioral support, laboratory assessments, technologies, medications, and hospitalizations.”

“In the final analysis, the WHO defines health as a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity. To this end, government leaderships, partnerships, and community empowerment will be needed to create a health-promoting environment, encourage self-management, and strengthen the health care system to make health a reality.”

(doi:10.l001/jama.2013.168099; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Media Advisory: To contact Clara K. Chow, Ph.D., email cchow@georgeinstitute.org.au or call Veronica McGuire at 905-525-9140, ext. 22169; or email vmcguir@mcmaster.ca.

CHICAGO – In a study that included more than 140,000 participants from17 countries of varying income levels, researchers found a large gap between both detection and control of hypertension across all countries studied, with just over half of participants with hypertension aware of their diagnosis, and about one-third of those being treated for hypertension successfully controlling their blood pressure, according to a study in the September 4 issue of JAMA.

“High blood pressure is the leading cause of cardiovascular disease (CVD) and deaths globally. It is associated with at least 7.6 million deaths per year worldwide (13.5 percent of all deaths), making it the leading risk factor for CVD. The majority of CVD occurs in low-, low-middle-, and upper-middle-income countries. The importance of blood pressure as a modifiable risk factor for CVD is well-recognized and many effective and inexpensive blood pressure-lowering treatments are available. Therefore, hypertension control and prevention of subsequent morbidity and mortality clearly should be achievable,” according to background information in the article. “Information on hypertension prevalence, awareness, treatment, and control in multiple countries and different types of communities is necessary to provide a baseline for monitoring and also to inform the development of new strategies for improving hypertension control.”

Clara K. Chow, Ph.D., of The George Institute for Global Health, Sydney, Australia, and Hamilton Health Sciences and McMaster University, Hamilton, Canada, and colleagues assessed the prevalence, awareness, treatment, and control of hypertension in participants in the Prospective Urban Rural Epidemiology (PURE) study. The study included 153,996 adults (complete data for this analysis on 142,042) 35 to 70 years of age, recruited between January 2003 and December 2009. Participants were from 628 communities in 3 high-income countries (HIC), 10 upper-middle-income and low-middle-income countries (UMIC and LMIC), and 4 low-income countries (LIC). Hypertension was defined as individuals with self-reported treated hypertension or with an average of 2 blood pressure measurements of at least 140/90 mm Hg using an automated digital device. Awareness was based on self-reports, treatment was based on the regular use of blood pressure-lowering medications, and control was defined as individuals with blood pressure lower than 140/90 mm Hg.

Among the participants, 57,840 (40.8 percent) had hypertension and 26,877 (46.5 percent) were aware of the diagnosis. Of those who were aware of the diagnosis, the majority (23,510 [87.5 percent]) were receiving pharmacological treatments, but only a minority of those receiving treatment had controlled blood pressure (7,634 [32.5 percent]).

The authors found a large gap between both detection and control of hypertension across all countries studied. “It shows that while initial therapy was started in the large majority of individuals who are detected to have hypertension, control in participants receiving treatment was very poor. The use of combination therapies, generally required to achieve blood pressure control, was low. Awareness, treatment, and control were lower in LICs compared with other countries and in rural settings of LMICs and LICs compared with urban ones. Despite men having higher rates of hypertension, women consistently had higher awareness, treatment, and control of their hypertension, consistent with a large body of research on sex and health-seeking behavior. Also, participants with more education had greater awareness, treatment, and control, particularly in LICs.”

“The widespread lack of hypertension awareness (a measure of hypertension case identification) and poor control (a measure of inadequate treatment) in all countries studied, despite the identification and control of blood pressure being prioritized by many national and global organizations and despite the availability of inexpensive and effective medications, is concerning,” the researchers write. “These findings suggest that substantial improvement in hypertension diagnosis and treatment is needed.”

(doi:10.l001/jama.2013.184182; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Media Advisory: To contact Simon Thom, M.B., B.S., M.D., email s.thom@imperial.ac.uk. To contact editorial author J. Michael Gaziano, M.D., M.P.H., call Tom Langford at 617-534-1605 or email tlangford@partners.org.

CHICAGO – In a randomized trial that included about 2,000 patients with or at high risk of cardiovascular disease (CVD), use of a fixed-dose combination medication for blood pressure, cholesterol, and platelet control compared to usual care resulted in significantly improved medication adherence after 15 months and small improvements in systolic blood pressure and low-density lipoprotein cholesterol, according to a study in the September 4 issue of JAMA.

“The long-term use of cardiovascular disease preventive therapy is low among people with established disease. This shortfall is greatest in low- and middle-income countries, but even in high-income countries treatment coverage in the community is only about 50 percent in those with coronary disease and 35 percent in those with stroke. People who are at similar risk but have not reached the clinical threshold of experiencing a CVD event are even less likely to be adequately treated. Fixed-dose combination (FDC) therapy may reduce these treatment gaps by reducing cost, complexity, therapeutic inertia, and low adherence,” according to background information in the article.  “Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment.”

Simon Thom, M.B., B.S., M.D., of the International Centre for Circulatory Health, Imperial College London, and colleagues conducted a study to assess whether FDC delivery of aspirin, statin, and 2 blood pressure-lowering agents vs. usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors, systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C). The randomized trial included 2,004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe. The trial follow-up concluded in July 2012. Participants were randomly assigned (1:1) to an FDC-based strategy (n=1,002) containing either (1) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol or (2) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide or to usual care (n=1,002).

At baseline, average BP was 137/78 mm Hg, LDL-C was 91.5 mg/dL, and 1,233 (61.5 percent) of 2,004 participants reported use of antiplatelet, statin, and 2 or more BP-lowering medications. The median (midpoint) duration of follow-up was 15 months for both groups. At the end of the study, 829 (86.3 percent) of 961 participants in the FDC group were continuing with indicated medications compared with 621 (64.7 percent) of 960 in the usual care group. In absolute terms, this amounted to a 21.6 percent difference in treatment rates. Overall, SBP (-2.6 mm Hg) and LDL-C (-4.2 mg/dL) levels were modest but significantly lower in the FDC group compared with the usual care group at the end of the study.

“Although there was consistency of effects across predefined subgroups, evidence existed of larger benefits in patients with lower adherence at baseline. In this subgroup of 727 participants (36 percent), adherence at the end of study was 77 percent vs. 23 percent, SBP was reduced by 4.9 mm Hg, and LDL-C was reduced by 6.7 mg/dL. There were no significant differences in serious adverse events or cardiovascular events between the groups,” the authors write.

“To the best of our knowledge, this was the first randomized trial to assess the long-term use of an FDC containing antiplatelet, statin, and BP-lowering drugs compared with usual care in patients with CVD. The results show that access to FDCs in patients with CVD or similarly high risk improved adherence, BP, and cholesterol levels. The reductions in BP and cholesterol level were small overall in this comparatively well-treated population but were larger in the subgroup not receiving all recommended treatments at baseline.”

(doi:10.l001/jama.2013.277064; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The project was funded by the European Commission Seventh Framework Programme. Dr. Reddy’s Laboratories (Hyderabad, India) provided the FDCs and supported the trial start-up meetings in London and India. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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

Editorial: Progress With the Polypill?

In an accompanying editorial, J. Michael Gaziano, M.D., M.P.H., of the VA Boston Healthcare System, Brigham and Women’s Hospital and Harvard Medical School, Boston, (and Associate Editor, JAMA), comments on the findings of this study.

“Although the potential remains for use of various CVD polypills in certain settings, the precise advantage of this strategy remains largely unproven. Until additional rigorous data are available that demonstrate that the polypill improves clinical CVD outcomes, it may be more important to carefully assess the multiple medications many patients currently are prescribed, often by several physicians. Another way to reduce the number of pills patients are taking is to eliminate those medications for which the benefits are marginal.”

(doi:10.l001/jama.2013.277064; 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 27, 2013

Reduction Seen in Rates of Gastroenteritis Hospitalizations in Older Children and Adults Since Implementation of Infant Rotavirus Vaccination

“Implementation of infant rotavirus vaccination in 2006 has substantially reduced the burden of severe gastroenteritis among U.S. children younger than 5 years,” write Paul A. Gastanaduy, M.D., M.P.H., of the Centers for Disease Control and Prevention, Atlanta, and colleagues. “Whether indirect protection (due to reduced transmission of rotavirus) extends to adults remains unclear.”

As reported in a Research Letter, the authors assessed patterns of gastroenteritis hospitalizations among children 5 years of age or older and among adults before and after implementation of infant rotavirus immunization. Rotavirus-coded and cause-unspecified gastroenteritis discharges from January 2000 through December 2010 were retrieved from a nationally representative database of hospital inpatient stays, the Nationwide Inpatient Sample.  Estimates were determined of annual and monthly incidence rate ratios (RR) of the postvaccine years (2008, 2009, and 2010) separately and combined vs. the prevaccine years (2000-2006); 2007 was a transition year with limited coverage and was excluded.

The researchers found that compared with prevaccine years, during 2008-2010, statistically significant reductions were observed in rotavirus-coded discharges in the age groups 0-4 years; 5-14 years; and 15-24 years. Similarly, significant reductions were observed in cause-unspecified discharges in the age groups 0-4 years; 5-14 years; 15-24 years; and 25-44 years. “Compared with prevaccine years, significant reductions in rotavirus-coded discharges occurred up to age 25 years in 2008, age 15 years in 2009, and across all age groups in 2010, with similar patterns for cause-unspecified discharges. Cause-unspecified reductions across all age groups and postvaccine years were focused in the late winter and early spring; in 2010, significant reductions were observed in March or April for all age groups.”

“The pattern of observed reductions in gastroenteritis discharges among unvaccinated older children and adults is consistent with indirect protection resulting from infant rotavirus vaccination,” the authors write. “These results point to the primacy of children in the transmission of rotavirus and illustrate how indirect benefits may amplify the effect of the U.S. rotavirus vaccination program.”

(doi: 10.1001/jama.2013.170800; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Paul A. Gastanaduy, M.D., M.P.H., call Jeanette St. Pierre at 404-639-3648  or email zcr5@cdc.gov.

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Viewpoint Appearing in This Issue of JAMA

Revealing the Incidentalome When Targeting the Tumor Genome

“… the process of decoding the genome of a patient’s tumor may incidentally reveal information about inherited predispositions to cancer and other diseases (the ‘incidentalome’). There is a need to establish approaches to decision making with respect to the return of these incidental results,” write Yvonne Bombard, Ph.D., of the Memorial Sloan-Kettering Cancer Center, New York, and colleagues.

“Optimal interpretation of the cancer genome requires a comparison with the inherited genome, but it is possible to avoid explicit listing of inherited variants. This strategy is justifiable in retrospective genomic research, but is less supportable in the prospective setting. For prospective research and clinical translation, the path forward depends on approaches that better define actionable variants and the development of the evidence base and clinical infrastructure to support preference-based disclosure of incidental findings. This will require the creation and evaluation of decision tools and the clinical capacity to provide genomic counseling for which no standards of care exist. Understanding how patients and clinicians interpret, manage, and use the genomic information they receive is essential to measure health service outcomes, risk-benefit trade-offs, and overall cost-effectiveness.”

(JAMA. 2013;310(8):795-796; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Kenneth Offit, M.D., M.P.H., call Courtney Nowak at 646-227-3633 or email denicolc@mskcc.org.

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 27, 2013

Media Advisory: To contact corresponding author Taylor S. Riall, M.D., Ph.D., call Raul Reyes at 409-747-0794 or email rareyes@utmb.edu. To contact editorial co-author Karl Y. Bilimoria, M.D., M.S., call Marla Paul at 312-503-8928 or email marla-paul@northwestern.edu.

CHICAGO – In an analysis of a procedure used to help prevent common duct injury during gallbladder removal surgery, use of intraoperative cholangiography (radiologic examination of the ducts during gallbladder surgery) was not associated with a reduced risk of common duct injury, according to a study in the August 28 issue of JAMA.

“Biliary anatomy misidentification during cholecystectomy [gallbladder removal] can result in injury to the common hepatic duct or common bile duct. Common duct injuries cause significant short- and long-term morbidity including major operations, multiple hospitalizations, and biliary strictures. Elimination of common duct injury is desirable, but it has remained stubbornly present with rates ranging from 0.3 percent to 0.5 percent,” according to background information in the article. “When routinely used, intra­operative cholangiography is thought to prevent common duct injury. However, controversy exists regarding the effectiveness of routine use in the prevention of common duct injury.”

Kristin M. Sheffield, Ph.D., and Taylor S. Riall, M.D., Ph.D., of the University of Texas Medical Branch, Galveston, and colleagues investigated the association between intraoperative cholangiography use during cholecystectomy and common duct injury, using instrumental variable analysis, an effective way to overcome unmeasured confounding (i.e., factors influencing outcomes not found in the database). The researchers identified Medicare beneficiaries from Texas Medicare claims data who underwent inpatient or outpatient cholecystectomy for conditions including biliary colic or biliary dyskinesia, acute cholecystitis, or chronic cholecystitis. Percentage of intraoperative cholangiography use at the hospital and by surgeon were the instrumental variables. Patients with claims for common duct repair operations within 1 year of cholecystectomy were considered as having major common duct injury.

A total of 92,932 Medicare beneficiaries 66 years or older underwent cholecystectomy at 307 hospitals in Texas from 2001 through 2009. There were 37,533 cholecystectomies with intraoperative cholangiography (40.4 percent) and 55,399 without (59.6 percent). Common duct injury occurred in 280 patients (0.30 percent). There were 201 common duct injuries (0.36 percent) in patients undergoing cholecystectomy without intraoperative cholangiography and 79 injuries (0.21 percent) for those having an intraoperative cholangiography.

“In a logistic regression model controlling for patient, surgeon, and hospital characteristics, the odds of common duct injury for cholecystectomies performed without intraoperative cholangiography were increased compared with those performed with it. When confounding was controlled with instrumental variable analysis, the association between cholecystectomy performed without intraoperative cholangiography and duct injury was no longer significant,” the authors write.

“Significant controversy exists regarding the role of intraoperative cholangiography in the prevention of common duct injury during cholecystectomy. Previous population-based studies using data from Medicare claims, hospital discharge records, and national inpatient registries report nearly 2-fold higher rates of injury in cholecystectomies performed without intraoperative cholangiography. In the present study using Texas Medicare claims data, the association between intraoperative cholangiography and common duct injury was highly sensitive to the analytic method used.”

“Failure to account for potentially confounding variables not routinely captured in administrative databases has a major effect on the interpretation of the findings. Intraoperative cholangiography was not associated with significant reduction in common duct injury using instrumental variable analysis. Instrumental variable analysis balances unmeasured confounding variables to better align risk factors in comparator groups. With better control for unmeasured confounding variables, intraoperative cholangiography was no longer associated with common duct injury. Based on these results, routine intraoperative cholangiography should not be advocated as means for preventing common duct injury,” the researchers conclude.

(JAMA. 2013;310(8):812-820; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study is supported by grants from the National Institutes of Health. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Kuo reports a pending grant with the Agency for Healthcare Research and Quality. No other disclosures were reported.

Editorial: Laparoscopic Cholecystectomy, Intraoperative Cholangiograms, and Common Duct Injuries

In an accompanying editorial, Karl Y. Bilimoria, M.D., M.S., of the Feinberg School of Medicine, Northwestern University, Chicago, and colleagues comment on the findings of this study.

“While the report by Sheffield et al does not definitively close the door on routine intraoperative cholangiography use, the authors have again directed attention to an important clinical debate by using a new approach to revisit the outcomes of intraoperative cholangiography using observational data. While the true effect of intraoperative cholangiography on the safety of laparoscopic cholecystectomy remains controversial, this study will undoubtedly reinvigorate the discussion.”

(JAMA. 2013;310(8):801-802; 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 27, 2013

Media Advisory: To contact J. Michael McWilliams, M.D., Ph.D., call David Cameron at 617-432-0441 or email david_cameron@hms.harvard.edu.

CHICAGO – Payment incentives implemented with a commercial accountable care organization (ACO) initiative in Massachusetts –Blue Cross Blue Shield’s Alternative Quality Contract (AQC) – were associated with lower spending for Medicare enrollees served by the provider groups participating in the AQC, findings that suggest that evaluations of ACO programs may need to consider the implications for other patient populations to assess their full clinical and economic benefits, according to a study in the August 28 issue of JAMA.

“In response to mounting pressures to deliver more cost-effective care, provider organizations have exhibited increasing willingness to assume financial risk for the quality and costs of the care they provide. More than 250 provider groups have contracted with Medicare as ACOs, and many similar payment arrangements have been reached with commercial insurers by these and other groups,” according to background information in the article. “In a multipayer system, new payment incentives implemented by one insurer for an ACO may also affect spending and quality of care for another insurer’s enrollees served by the ACO. Such spillover effects reflect the extent of organizational efforts to reform care delivery and can contribute to the net impact of ACOs.”

J. Michael McWilliams, M.D., Ph.D., of Harvard Medical School, Boston, and colleagues conducted a study to examine whether the Blue Cross Blue Shield (BCBS) of Massachusetts’ Alternative Quality Contract (AQC), an early commercial ACO initiative associated with reduced spending and improved quality for BCBS enrollees, was also associated with changes in spending and quality for Medicare beneficiaries, who were not covered by the AQC. The study included comparisons from 2007-2010 of elderly fee-for-service Medicare beneficiaries in Massachusetts served by 11 provider organizations entering the AQC in 2009 or 2010 (intervention group) vs. beneficiaries served by other providers (control group). The researchers estimated changes in spending and quality for the intervention group in the first and second years of exposure to the AQC relative to concurrent changes for the control group. The primary outcome was total quarterly medical spending per beneficiary. Secondary outcomes included spending by setting and type of service, 5 process measures of quality, potentially avoidable hospitalizations, and 30-day readmissions.

The researchers found that differential changes in sociodemographic and clinical characteristics were small for the intervention group relative to the control group, and none was statistically significant, suggesting that the findings were not due to changes in patient case mix. Adjusted total quarterly spending was $150 higher for the intervention group than for the control group, and spending trends were similar before AQC incentives were implemented for participating organizations. “In year 2 of the intervention group’s exposure to the AQC, the spending difference between the intervention and control groups was reduced to $51, constituting a significant differential change of -$99 or a 3.4 percent savings relative to an expected quarterly mean of $2,895. Savings in year 1 were not statistically significant.”

Savings in year 2 were explained largely by differential changes in outpatient care (-$73) and included significant differential changes in spending on office visits, emergency department visits, minor procedures, imaging, and laboratory tests. Estimated savings in year 2 spending on outpatient care for the intervention group were greater among beneficiaries with 5 or more conditions (-$125) than among those with fewer conditions (-$61).

“Annual rates of low-density lipoprotein cholesterol testing differentially improved for beneficiaries with diabetes in the intervention group by 3.1 percentage points and for those with cardiovascular disease by 2.5 percentage points, but performance on other quality measures did not differentially change,” the authors write.

“Our findings have several implications for payment and delivery system reforms. In general, cost-reducing spillover effects of ACO contracts with one insurer on care for other insurers’ enrollees should signal a willingness among provider organizations generating the spillovers to enter similar contracts with additional insurers; they could be rewarded for the savings and quality improvements achieved for the other insurers’ enrollees. Broad organizational responses to early ACO initiatives, like those suggested by our findings, might support a rapid transition among ACOs to global payment arrangements with multiple payers. Conversely, cost-reducing spillovers present a free-riding problem to commercial insurers engaged in ACO contracts, since competing insurers with similar provider networks could offer lower premiums without incurring the costs of managing an ACO. Additional efforts to foster multipayer participation in global payment sys­tems, such as recent state initiatives and provisions in Pioneer Medicare ACO contracts, may be important.”

“… our study suggests that organizations in Massachusetts willing to assume greater financial risk were capable of achieving modest reductions in spending for Medicare beneficiaries without compromising quality of care. Although effects of commercial and Medicare ACO initiatives similar to the AQC may differ in other markets, these findings suggest potential for these payment models to foster systemic change in care delivery. Evaluations of ACO programs may need to consider spillover effects on other patient populations to assess their full clinical and economic benefits,” the researchers conclude.

(JAMA. 2013;310(8):829-836; 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 27, 2013

Media Advisory: To contact corresponding author Lu Qi, M.D., Ph.D., call Todd Datz at 617-432-8413 or email tdatz@hsph.harvard.edu; to contact corresponding author Alessandro Doria, M.D., Ph.D., M.P.H., call Jeff Bright at 617-309-1957 or email Jeffrey.bright@joslin.harvard.edu.

CHICAGO – Researchers have identified a previously unknown genetic locus (the place a gene occupies on a chromosome) significantly associated with increased coronary heart disease risk among patients with type 2 diabetes, but the association was not found in individuals without diabetes, according to a study in the August 28 issue of JAMA. The variant is functionally related to glutamic acid metabolism, suggesting a mechanistic link.

“The prevalence of type 2 diabetes has been steadily increasing in the United States and other countries, with the total number of affected people reaching more than 370 million globally. Long-term cardiovascular complications, and especially coronary heart disease (CHD), are the principal causes of morbidity and mortality among diabetic patients,” according to background information in the article. “Diabetes is associated with an elevated risk of CHD. Previous studies have suggested that the genetic factors predisposing to excess cardiovascular risk may be different in diabetic and nondiabetic individuals.”

Lu Qi, M.D., Ph.D., of the Harvard School of Public Health, Boston, and colleagues conducted a study to identify genetic determinants of CHD that are specific to patients with diabetes. The researchers studied 5 independent sets of CHD cases and CHD-negative controls from the Nurses’ Health Study (enrolled in 1976 and followed up through 2008), Health Professionals Follow-up Study (enrolled in 1986 and followed up through 2008), Joslin Heart Study (enrolled in 2001-2008), Gargano Heart Study (enrolled in 2001-2008), and Catanzaro Study (enrolled in 2004-2010). Included were a total of 1,517 CHD cases and 2,671 CHD-negative controls, all with type 2 diabetes. Results in patients with diabetes were compared with those in 737 nondiabetic CHD cases and 1,637 nondiabetic CHD-negative controls from the Nurses’ Health Study and Health Professionals Follow-up Study cohorts.

Of the 2,543,016 genetic variants that were tested for association with CHD in stage 1 of the 3-stage genome-wide analysis, 26 met the criterion for promotion to stage 2, and 3 of these further met the criterion for promotion to stage 3. Of the 3 variants that were promoted to stage 3, a variant on chromosome 1q25 (rs10911021) was consistently associated with CHD risk among diabetic participants. No association between this variant and CHD was detected among nondiabetic participants.

“The locus is in the region of the GLUL gene on chromosome 1q25 and may affect CHD risk by reducing the expression of this gene and affecting glutamate and glutamine metabolism in endothelial cells. This genetic variant appeared to be specifically associated with CHD in the diabetic population and showed a significant gene-by-diabetes synergism on CHD risk,” the authors write. “… further studies are needed to fully understand the biological mechanisms linking it to CHD in diabetes.”

(JAMA. 2013;310(8):821-828; 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 27, 2013

Media Advisory: To contact corresponding author Shyamasundaran Kottilil, M.D., Ph.D., call Anne Oplinger at 301-402-1663 or email AOplinger@niaid.nih.gov.

CHICAGO – Treatment of chronic hepatitis C virus (HCV) genotype 1 infection with the interferon-free regimen of sofosbuvir and ribavirin resulted in a high sustained virologic response rate in a patient population with unfavorable treatment characteristics, according to a study in the August 28 issue of JAMA.

“Chronic infection with hepatitis C virus is a major cause of chronic liver disease, end-stage liver disease, hepatocellular cancer and remains the leading indication for liver transplants in western countries. The HCV epidemic in the United States is centered in large urban areas among populations with a high prevalence of unfavorable traditional predictors of treatment response,” according to background information in the article. “Recent studies show that interferon-free, directly acting antiviral agent-only regimens can successfully achieve sustained virologic response (SVR); however, populations traditionally associated with poorer treatment outcomes have been underrepresented.”

Anuoluwapo Osinusi, M.D., M.P.H., of the National Institutes of Health, Bethesda, Md., and colleagues evaluated the efficacy of sofosbuvir administered in combination with weight-based or low-dose once daily ribavirin in a treatment-naive population with unfavorable characteristics of treatment success. The randomized, 2-part, phase 2 study included 60 patients with HCV genotype 1 enrolled from October 2011-April 2012. In the study’s first part, 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks. In the second part, 50 participants with all stages of liver fibrosis were randomized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks. The primary outcome was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion (sustained virologic response of 24 weeks [SVR₂₄]). Eighty-three percent of the participants were black; 66 percent, men; and 23 percent had advanced liver disease.

Twenty-four participants (96 percent) in each group achieved viral suppression by week 4. “A total of 7 participants (28 percent) in the weight-based group and 10 (40 percent) in the low-dose group relapsed after treatment completion leading to SVR₂₄ rates of 68 percent in the weight-based group and 48 percent in the low-dose group,” the authors write.

The combination regimen was safe and well tolerated with no death or discontinuation of treatment due to adverse events. The most frequent adverse events were headache, anemia, fatigue, and nausea, the severity of which ranged from mild to moderate.

The researchers also found that the baseline factors of male sex, advanced liver disease, and high baseline HCV RNA levels were associated with relapse.

“This study demonstrates the efficacy of an interferon-free regimen in a traditionally difficult-to-treat population while exploring the reasons for treatment relapse. In this study, treatment of chronic HCV infection with a single directly acting antiviral agent (sofosbuvir) and weight-based ribavirin resulted in a high SVR rate in a population with unfavorable traditional predictors of treatment response compared with reported rates with currently used interferon-based therapy in similar populations.”

(JAMA. 2013;310(8):804-811; 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

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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