EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, APRIL 26, 2016

Media Advisory: To contact Celine Vetter, Ph.D., call Elaine St. Peter at 617-525-6375 or email estpeter@partners.org.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.4454

Among female registered nurses, working a rotating night shift for 5 years or more was associated with a small increase in the risk of coronary heart disease, according to a study appearing in the April 26 issue of JAMA.

The disruption of social and biological rhythms that occur during shift work have been hypothesized to increase chronic disease risk, and evidence supports an association between shift work and coronary heart disease (CHD), metabolic disorders, and cancer. Prospective studies linking shift work to CHD have been inconsistent and limited by short follow-up. Celine Vetter, Ph.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues examined the incidence of CHD in 189,158 initially healthy women followed up over 24 years in the Nurses’ Health Studies (NHS [1988-2012]: n = 73,623 and NHS2 [1989-2013]: n = 115,535). The researchers determined the lifetime history of rotating night shift work (3 night shifts or more per month in addition to day and evening shifts) of the nurses at baseline (updated every 2 to 4 years in the NHS2).

During follow-up, 7,303 incident CHD cases (i.e., nonfatal heart attack, CHD death, angiogram-confirmed angina pectoris, coronary artery bypass graft surgery, stents, and angioplasty) occurred in the NHS and 3,519 in the NHS2. Analysis indicated that increasing years of rotating night shift work was associated with a statistically significant but small absolute increase in CHD risk. In the NHS, the association between duration of shift work and CHD was stronger in the first half of follow-up than in the second half, suggesting waning risk after cessation of shift work. Longer time since quitting shift work was associated with decreased CHD risk among shift workers in the NHS2.

“Further research is needed to explore whether the association is related to specific work hours and individual characteristics,” the authors write.

(doi:10.1001/jama.2016.4454; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, APRIL 26, 2016

Media Advisory: To contact J. Christian Virchow, M.D., email jc.h.virchow@sunrise.ch or j.c.virchow@med.uni-rostock.de. To contact editorial author Robert A. Wood, M.D., call Lauren Nelson at 410-955-8725 or email laurennelson@jhmi.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.3964

The addition of a house dust mite (HDM) sublingual allergen immunotherapy (SLIT) tablet to maintenance medications improved time to first moderate or severe asthma exacerbation during a period of inhaled corticosteroid (ICS) reduction among adults with HDM allergy-related asthma not well controlled by ICS, according to a study appearing in the April 26 issue of JAMA.

Bronchial asthma is a serious global health problem with increasing prevalence in many countries. House dust mite sensitization is present in up to 50 percent of patients with asthma, and exposure to HDM allergen has been related to asthma severity. The HDM SLIT tablet is a potential novel treatment option for HDM allergy-related asthma. In this study by J. Christian Virchow, M.D., of the University of Rostock, Germany, and coauthors, 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products, and with HDM allergy-related rhinitis, were randomly assigned to once-daily treatment with placebo (n = 277) or HDM SLIT tablet (different dosage groups, n = 275 or n = 282) in addition to ICS and the short-acting beta2-agonist salbutamol. Efficacy was assessed during the last 6 months of the trial when ICS was reduced by 50 percent for 3 months and then completely withdrawn for 3 months. The study was conducted in 109 European trial sites.

Among the 834 patients, 693 completed the study. The researchers found that either dosage of the HDM SLIT tablet significantly reduced the risk of a moderate or severe asthma exacerbation compared with placebo. Compared with placebo, there was also an increase in allergen-specific immunoglobulin G4 (lgG4; an antibody). However, there was no significant difference for change in the asthma control questionnaire or asthma quality-of-life questionnaire for either dose. There were no reports of severe systemic allergic reactions.

“To our knowledge, this is the first controlled trial to show that adult patients with HDM allergy-related asthma who were not well controlled taking ICS can achieve an improvement in asthma control as measured by time to first asthma exacerbation with a sublingual tablet formulation of HDM allergen immunotherapy,” the authors write.

They add that further studies are needed to assess long-term efficacy and safety.

(doi:10.1001/jama.2016.3964; this study is available pre-embargo at the For The Media website.)

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

Editorial: New Horizons in Allergen Immunotherapy

“Rigorous studies of immunotherapy of all forms are clearly needed. The study by Virchow et al is a valuable contribution to the literature, especially given its focus on an important patient population with highly relevant end points,” writes Robert A. Wood, M.D., of the Johns Hopkins University School of Medicine, Baltimore, in an accompanying editorial.

“The work should not end here, as there is still a great deal of room for refinement in the practice of immunotherapy. As research continues and these therapies enter clinical practice, the goal should be to optimize each patient’s immunotherapy regimen and disease control, taking personal preferences into account, and ideally to develop additional patient profiling using specific biomarkers to further personalize the use of these treatment options.”

(doi:10.1001/jama.2016.4078; this editorial is available pre-embargo at the For The Media website.)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, APRIL 26, 2016

Media Advisory: To contact Elizabeth A. Rafferty, M.D., call Kathy Weiner at 978-266-2676 or email lmradkat@verizon.net.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1708.

In a study appearing in the April 26 issue of JAMA, Elizabeth A. Rafferty, M.D., formerly of Massachusetts General Hospital, Boston, and colleagues evaluated the screening performance of digital mammography combined with tomosynthesis (a type of imaging) compared with digital mammography alone for women with varying levels of breast density.

Breast density is associated with reduced mammographic sensitivity and specificity, and increased tumor size and worsened prognosis are associated with increased breast density. Currently, 24 states have laws mandating that women be notified of the implications of breast density, thereby encouraging discussions between patients and physicians regarding the need for supplemental screening. However, which, if any, additional testing should be recommended for women with dense breasts is not known.

This study included data from screening performance metrics from 13 U.S. institutions, which were reported for 12 months using digital mammography alone and from the date of introduction of tomosynthesis. Subgroups included the 4 breast density categories used for clinical reporting. Overall and invasive cancer detection rates and recall rate with and without tomosynthesis were analyzed in patients with both nondense and dense breasts.

Of 452,320 examinations, 278,906 were digital mammography alone and 173,414 digital mammography plus tomosynthesis; 2,157 cancers were diagnosed. The researchers found that the addition of tomosynthesis to digital mammography for screening was associated with an increase in cancer detection rate and a reduction in recall rate for women with both dense and nondense breast tissue. “These combined gains were largest for women with heterogeneously dense breasts, potentially addressing limitations in cancer detection seen with digital mammography alone in this group, but were not significant in women with extremely dense breasts.”

The authors note that for women classified as having dense breast tissue, most have heterogeneously dense breasts, mandating caution in drawing conclusions regarding the performance of tomosynthesis for the small proportion of women with extremely dense breasts.

(doi:10.1001/jama.2016.1708; this study is available pre-embargo at the For The Media website.)

Editor’s Note: Dr. Rafferty is now with L&M Radiology, West Acton, Mass. This study was funded by a research grant from Hologic. 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: 11 A.M. (ET) TUESDAY, APRIL 26, 2016

Media Advisory: To contact Nancy R. Kressin, Ph.D., email Gina DiGravio-Wilczewski at ginad@bu.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1712

In a study appearing in the April 26 issue of JAMA, Nancy R. Kressin, Ph.D., of the Veterans Affairs Boston Healthcare System, Boston University School of Medicine, and colleagues examined the content, readability, and understandability of dense breast notifications sent to women following screening mammography.

Along with their screening mammogram results, women in nearly half of U.S. states also receive notifications of breast density, a result of legislation intended to assist in making personalized decisions about further action. Dense breasts can mask cancer on mammography (masking bias), and are an independent cancer risk factor, but evidence does not yet indicate whether or what supplemental screening is appropriate. Rather, risk stratification is proposed to determine who may benefit from supplemental screening (e.g., magnetic resonance imaging for women at high risk). The text of dense breast notifications (DBNs) may affect women’s ability to understand their message.

Twenty-four states require DBNs as of January l, 2016; the researchers analyzed the characteristics of all but Delaware. They found wide variation in the states’ DBN content. All DBNs mention masking bias, 74 percent mention the association with increased cancer risk, and 65 percent mention supplemental screening as an option, advising women to consult their physician. Of 15 DBNs requiring mention of supplemental screening, 6 (40 percent) inform women that they might benefit from such screening; 4 mention specific modalities.

Most of the states have readability at the high school level or above (exceeding the recommended readability level [grades 7-8]; about 20 percent of the population reads below a grade 5 level). Only 3 states’ DBN readability level was at the grade 8 level or below; some of the highest readability levels occurred in states with the lowest literacy levels. All DBNs scored poorly on understandability.

“Such problems may create uncertainty for women attempting to make personalized decisions about supplemental screening and may exacerbate disparities in breast cancer screening related to low health literacy,” the authors write.

“Efforts should focus on enhancing the understandability of DBNs so that all women are clearly and accurately informed about their density status, its effect on their breast cancer risk, and the harms and benefits of supplemental screening.”

(doi:10.1001/jama.2016.1712; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, APRIL 19, 2016

Media Advisory: To contact Antoni Ribas, M.D., Ph.D., email Reggie Kumar at ReggieKumar@mednet.ucla.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.4059

In a study appearing in the April 19 issue of JAMA, Antoni Ribas, M.D., Ph.D., of the University of California-Los Angeles, and colleagues examined tumor response and overall survival following administration of the antibody pembrolizumab among patients with advanced melanoma.

Pembrolizumab, an antibody against programmed cell death protein 1 (PD-1), is an approved treatment for unresectable or metastatic melanoma. The PD-1 pathway limits immune responses to melanoma and can be blocked with pembrolizumab. In this phase 1 clinical trial, 655 patients with advanced or metastatic melanoma received pembrolizumab intravenously of varying doses and duration. Median duration of follow-up was 21 months. The study was performed in medical centers in Australia, Canada, France, and the United States.

The researchers found that pembrolizumab treatment was associated with an objective response rate (best overall response of complete response or partial response) of 33 percent, 12-month progression-free survival rate of 35 percent, a 23-month median overall survival, and a grade 3 or 4 adverse event rate of 14 percent, regardless of previous treatment with the antibody ipilimumab or pembrolizumab dose or schedule. In treatment-naive patients, the overall response rate was 45 percent, the 12-month progression free survival rate was 52 percent, and the median overall survival was 31 months with a 12-month survival rate of 73 percent and a 24-month survival rate of 60 percent.

Four percent of patients discontinued treatment because of a treatment-related adverse event. Treatment-related serious adverse events were reported in 9 percent of patients. There were no drug-related deaths.

(doi:10.1001/jama.2016.4059; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, APRIL 19, 2016

Media Advisory: To contact Matthew D. Snape, F.R.C.P.C.H., M.D., email matthew.snape@paediatrics.ox.ac.uk.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.4218

In a study appearing in the April 19 issue of JAMA, Matthew D. Snape, F.R.C.P.C.H., M.D., of the University of Oxford, United Kingdom, and colleagues conducted a phase 1 trial to evaluate the tolerability and immunogenicity of two candidate Ebola vaccines, an adenovirus type 26 vector vaccine (Ad26.ZEBOV), and a modified Ankara vector vaccine (MVA-BN-Filo).

The recent outbreak of Ebola virus disease in West Africa has caused in excess of 28,600 cases and 11,300 deaths since the first cases were identified in December 2013 in Guinea. The international response has included the accelerated clinical development of several candidate Ebola vaccines. In nonhuman primates, an Ad26-vectored vaccine was able to generate up to 75 percent protection from Ebola challenge.

For this study, participants (healthy volunteers, 18-50 years old) were randomly assigned to 4 groups, within which they were simultaneously randomized 5:1 to receive study vaccines or placebo. Those receiving active vaccines were primed with Ad26.ZEBOV or MVA-BN-Filo and boosted with the alternative vaccine 28 or 56 days later. A fifth, open-label group received Ad26.ZEBOV boosted by MVA-BN-Filo 14 days later. The trial was conducted in Oxford, U.K.

Among 87 study participants, 72 were randomly assigned to 4 groups of 18, and 15 were included in the open-label group. Four participants did not receive a booster dose; 67 of 75 study vaccine recipients were followed up at 8 months. An immune response was observed after primary immunization with Ad26.ZEBOV; boosting by MVA-BN-Filo resulted in sustained elevation of specific immunity. Immunization with Ad26.ZEBOV or MVA-BN-Filo did not result in any vaccine-related serious adverse events.

“Our data showed that, in contrast to MVA-BN-Filo, Ad26.ZEBOV priming generated an initial immune response, and there is evidence for protection from this vaccine given alone in nonhuman primate models. Therefore, this priming dose would be expected to generate at least partial protection against Ebola; for this reason, Ad26.ZEBOV prime schedules with MVA-BN-Filo boost are currently being further evaluated in phase 1, 2, and 3 studies,” the authors write.

(doi:10.1001/jama.2016.4128; this study is available pre-embargo at the For The Media website.)

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: 12:01 A.M. (ET) MONDAY, APRIL 11, 2016

Media Advisory: To contact Raj Chetty, Ph.D., call Rebecca Toseland at 617-495-0464 or email toseland@stanford.edu

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.4226

In the United States between 2001 and 2014, higher income was associated with greater life expectancy, and differences in life expectancy across income groups increased; however, the association between longevity and income varied substantially across areas, according to a study published online by JAMA.

Raj Chetty, Ph.D., of Stanford University, Stanford, Calif., and colleagues analyzed newly available data on income and mortality for the U.S. population to estimate race- and ethnicity-adjusted life expectancy at 40 years of age by household income percentile, sex, and geographic area, and evaluated factors associated with differences in life expectancy. Income data for the U.S. population between 40 to 76 years of age were obtained from 1.4 billion de-identified tax records between 1999 and 2014. Mortality data were obtained from Social Security Administration death records.

The average age at which individuals were analyzed was 53 years; the median household earnings among working individuals was $61,175 per year. There were 4,114,380 deaths among men (mortality rate, 596 per 100,000) and 2,694,808 deaths among women (mortality rate, 375 per 100,000).

The analysis yielded 4 primary results:

— Higher income was associated with greater longevity throughout the income distribution. The gap in life expectancy between the richest 1 percent and poorest 1 percent of individuals was 14.6 years for men and 10.1 years for women.

— Inequality in life expectancy increased over time. Between 2001 and 2014, life expectancy increased by 2.3 years for men and 2.9 years for women in the top 5 percent of the income distribution, but increased by only 0.3 years for men and 0.04 years for women in the bottom 5 percent.

— Life expectancy varied substantially across local areas. For individuals in the bottom income quartile, life expectancy differed by approximately 4.5 years between areas with the highest and lowest longevity. Changes in life expectancy between 2001 and 2014 ranged from gains of more than 4 years to losses of more than 2 years across areas.

— Geographic differences in life expectancy for individuals in the lowest income quartile were significantly correlated with health behaviors such as smoking, but were not significantly correlated with access to medical care, physical environmental factors, income inequality, or labor market conditions. Life expectancy for low-income individuals was positively correlated with the local area fraction of immigrants, fraction of college graduates, and local government expenditures per capita.

The authors write that reducing gaps in longevity may require local policy responses, and that “the strong association between geographic variation in life expectancy and health behaviors suggests that policy interventions should focus on changing health behaviors among low-income individuals. Tax policies and other local public policies may play a role in inducing such changes.”

“The findings also have implications for social insurance programs. The differences in life expectancy by income imply that the Social Security program is less redistributive than implied by its progressive benefit structure. Men and women in the top 1 percent of the income distribution can expect to claim Social Security and Medicare for 11.8 and 8.3 more years than men and women in the bottom 1 percent of the income distribution. Some have proposed indexing the age of eligibility for Medicare and full Social Security benefits to increases in life expectancy. The differences in the increases in life expectancy across income groups and areas suggests that such a policy would have to be conditioned on income and location to maintain current levels of redistribution.”

(doi:10.1001/jama.2016.4226; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, APRIL 12, 2016

Media Advisory: To contact Kiros Berhane, Ph.D., call Zen Vuong at 213-740-5277 or email zvuong@usc.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.3444

Decreases in ambient air pollution levels over the past 20 years in Southern California were associated with significant reductions in bronchitic symptoms in children with and without asthma, according to a study appearing in the April 12 issue of JAMA.

Childhood bronchitic symptoms are significant public and clinical health problems that produce a substantial burden of disease. Ambient air pollutants are important determinants of bronchitis occurrence. Since 1992, significant improvements in air quality have been observed across Southern California due to a broad range of air pollution reduction policies and strategies. Kiros Berhane, Ph.D., of the University of Southern California, Los Angeles, and colleagues examined whether improvements in ambient air quality in Southern California were associated with reductions in bronchitic symptoms in children. The study involved children (age range, 5-18 years) from 3 groups, and was conducted during the 1993-2001, 1996-2004, and 2003-2012 years in 8 Southern California communities.

A model was used to estimate the association of changes in pollution levels with bronchitic symptoms. The primary measured outcome among children was annual age-specific prevalence of bronchitic symptoms during the previous 12 months based on the parent’s or child’s report of a daily cough for 3 months in a row, congestion or phlegm other than when accompanied by a cold, or bronchitis.

The 3 cohorts included a total of 4,602 children (average age at baseline, 8 years; 49 percent girls; 45 percent Hispanic white) who had data from 2 or more annual questionnaires. Among these children, 19 percent had asthma at age 10 years. The authors found that decreases in ambient concentrations of nitrogen dioxide, ozone, and particulate matter with an aerodynamic diameter less than 10 µm (PM₁₀) and less than 2.5 µm (PM_2.5) were associated with significant decreases in bronchitic symptoms in children with and without asthma. The reductions were proportionally larger in children with asthma and remained similar when examined at 10, 13, and 15 years of age during the follow-up period. Among patients with asthma, the reductions in bronchitic symptoms tended to be larger in boys and among children from households with dogs.

“While the study design does not establish causality, the findings support potential benefit of air pollution reduction on asthma control,” the authors write.

(doi:10.1001/jama.2016.3444; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, APRIL 12, 2016

Media Advisory: To contact Alexandre B. Cavalcanti, M.D., Ph.D., email abiasi@hcor.com.br.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.3463

Implementation of a multifaceted quality improvement intervention with daily checklists, goal setting, and clinician prompting did not reduce in-hospital mortality compared with routine care among critically ill patients treated in intensive care units (ICUs) in Brazil, according to a study appearing in the April 12 issue of JAMA.

Checklists have been proposed as tools to ensure that essential components of care are not omitted. In ICUs, the use of checklists is associated with increased adherence to guidelines, reduced rates of central line-associated bloodstream infection, and earlier extubation.  Using checklists combined with daily goals assessment and clinician prompting may improve communication, adherence to care processes, and clinical outcomes. However, evidence from randomized trials supporting the use of checklists in critical care is lacking.

Alexandre B. Cavalcanti, M.D., Ph.D., of the HCor-Hospital do Coracao, Sao Paulo, Brazil and colleagues conducted a study that had two phases. Phase 1 was an observational study to assess baseline data on work climate, care processes, and clinical outcomes in 118 Brazilian ICUs. In phase 2, the same ICUs were randomized to a quality improvement intervention, including a daily checklist and goal setting during multidisciplinary rounds with follow-up clinician prompting for 11 care processes, or to routine care. The first 60 admissions of longer than 48 hours per ICU were enrolled in each phase.

A total of 6,877 patients (average age, 60 years) were enrolled in the baseline (observational) phase and 6,761 (average age, 60 years) in the randomized phase, with 3,327 patients enrolled in ICUs (n = 59) assigned to the intervention group and 3,434 patients in ICUs (n = 59) assigned to routine care. The researchers found that there was no significant difference in in-hospital mortality between the intervention group and the usual care group, with 1,096 deaths (33 percent) and 1,196 deaths (35 percent), respectively.

Potential improvements were observed in 4 of 7 care processes and 2 safety climate domains, although except for 1 outcome, urinary catheter use, these findings were not significant after adjustment for multiple comparisons.

The authors write that potential explanations for the lack of effect on mortality found in this study include that the intervention needs time to work and the observation period was too short, or that the items on the checklist have very modest or negligible effects on mortality.

(doi:10.1001/jama.2016.3463; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, APRIL 12, 2016

Media Advisory: To contact Aaron S. Kesselheim, M.D., J.D., M.P.H., call Johanna Younghans at 617-525-6373 or email Jyounghans@partners.org.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2015.16984

Physicians’ Knowledge About FDA Approval Standards for ‘Breakthrough Therapy’

In a study appearing in the April 12 issue of JAMA, Aaron S. Kesselheim, M.D., J.D., M.P.H., of Brigham and Women’s Hospital, Boston, and colleagues surveyed internists and specialists to examine their knowledge about Food and Drug Administration (FDA) approval standards and perceptions of the “breakthrough therapy” designation.

Since 2012, the FDA can designate a drug as a “breakthrough therapy” if preliminary clinical evidence—such as an improvement in a pharmacodynamic biomarker—suggests an advantage over existing options. The term is routinely used in press releases and prescribing resources. Although the term breakthrough leads consumers to overly optimistic beliefs about drug effectiveness, it is not known how physicians understand this term, or more generally, what FDA approval means.

Of 1,148 physicians contacted, 692 physicians (60 percent) responded. Participants were asked 3 questions about FDA approval and 5 about breakthrough therapies. Respondents showed limited knowledge of FDA approval: 73 percent incorrectly believed FDA approval meant comparable effectiveness to other approved drugs; 70 percent incorrectly believed approval required both a statistically significant and clinically important effect. Among the 3 breakthrough knowledge questions, 52 percent incorrectly believed that strong evidence (randomized trials) is needed to earn the breakthrough designation.

“The misconceptions identified may lead physicians to overprescribe newly approved drugs—particularly breakthrough therapies— and inadequately communicate how well these drugs work to the patients who will use them,” the authors write.

(doi:10.1001/jama.2015.16984; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, APRIL 5, 2016

Media Advisory: To contact the U.S. Preventive Services Task Force, email the Media Coordinator at Newsroom@USPSTF.net or call 202-572-2044.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.2638

The U.S. Preventive Services Task Force (USPSTF) does not recommend screening for chronic obstructive pulmonary disease (COPD) in persons who do not have symptoms suggestive of COPD. The report appears in the April 5 issue of JAMA.

This is a D recommendation, indicating that there is moderate or high certainty that screening has no net benefit or that the harms outweigh the benefits.

About 14 percent of U.S. adults age 40 to 79 years have COPD, and it is the third leading cause of death in the U.S. Persons with severe COPD are often unable to participate in normal physical activity due to deterioration of lung function. To update its 2008 recommendation, the USPSTF reviewed the evidence on whether screening for COPD in asymptomatic adults (those who do not recognize or report respiratory symptoms) improves health outcomes. The USPSTF reviewed the diagnostic accuracy of screening tools (including prescreening questionnaires and spirometry [a test of the air capacity of the lungs]); whether screening for COPD improves the delivery and uptake of targeted preventive services, such as smoking cessation or relevant immunizations; and the possible harms of screening for and treatment of mild to moderate COPD.

The USPSTF is an independent, volunteer panel of experts that makes recommendations about the effectiveness of specific preventive care services such as screenings, counseling services, and preventive medications.

Detection

Chronic obstructive pulmonary disease is defined as airflow limitation that is not fully reversible. It is a disease associated with an abnormal inflammatory response of the lung to harmful particles or gases. Diagnosis is based on postbronchodilator (a type of medication given to open up the lung’s air passages) spirometry, which detects fixed airway obstruction. Persons with COPD often, but not always, have symptoms such as dyspnea (difficulty breathing or shortness of breath), chronic cough, and chronic sputum production. Patients often have a history of exposure to risk factors such as cigarette smoke or heating fuels or occupational exposure to dusts or chemicals. Although postbronchodilator spirometry is required to make a definitive diagnosis, prescreening questionnaires can elicit current symptoms and previous exposures to harmful particles or gases.

Benefits of Detection and Early Treatment

The USPSTF found inadequate evidence that screening for COPD in asymptomatic persons using questionnaires or spirometry improves health outcomes.

Harms of Detection and Early Treatment

The USPSTF found inadequate evidence on the harms of screening. However, given the lack of benefit of early detection and treatment, the opportunity cost associated with screening asymptomatic persons may be large. The amount of time and effort required to screen for COPD in asymptomatic persons (using screening spirometry with or without prescreening questionnaires) is not trivial.

Findings

Similar to 2008, the USPSTF did not find evidence that screening for COPD in asymptomatic persons improves health-related quality of life, morbidity, or mortality. The USPSTF determined that early detection of COPD, before the development of symptoms, does not alter the course of the disease or improve patient outcomes. The USPSTF concludes with moderate certainty that screening for COPD in asymptomatic persons has no net benefit.

(doi:10.1001/jama.2016.2638; the full report is available pre-embargo to the media at the For the Media website)

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

Note: More information about the U.S. Preventive Services Task Force, its process, and its recommendations can be found on the newsroom page of its website.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, APRIL 5, 2016

Media Advisory: To contact Wendy C. King, Ph.D., call Allison Hydzik at 412-647-9975 or email hydzikam@upmc.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.3010

Among a group of patients with severe obesity who underwent bariatric surgery, a large percentage experienced improvement in pain, physical function, and walking capacity over 3 years, according to a study appearing in the April 5 issue of JAMA.

Severe obesity is associated with significant joint pain and impaired physical function (ability to bend, lift, carry, push, and walk). Excess weight can lead to joint damage and pain, resulting in activity restriction and walking limitations. Bariatric surgery is effective at achieving and maintaining weight loss, although the variability and durability of improvements in pain and physical function following Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB) are not well described.

Wendy C. King, Ph.D., of the University of Pittsburgh, and colleagues examined changes in pain and physical function in the first 3 years following bariatric surgery, and factors associated with improvement, among adults with severe obesity. Research assessments were conducted prior to surgery and annually thereafter. The study was conducted at 10 hospitals.

Of 2,458 participants, 2,221 completed baseline and follow-up assessments; 79 percent were women; median age was 47 years; median body mass index (BMI) was 46; 70 percent underwent RYGB; 25 percent underwent LAGB. Among the primary findings through 3 years of follow-up: approximately 50 percent to 70 percent of adults experienced clinically significant improvements in perceived bodily pain and physical function and in objectively measured walking capacity; and approximately three-fourths of participants with severe knee and hip pain or disability at baseline experienced improvements in osteoarthritis symptoms.

The percentage of patients with improvement in pain and physical function decreased between year 1 and year 3 following surgery.

Younger age, male sex, higher income, lower BMI, and fewer depressive symptoms presurgery; no diabetes and no venous edema (swelling of the legs) with ulcerations postsurgery (either no history or remission); and presurgery-to-postsurgery reductions in weight and depressive symptoms were associated with presurgery-to-postsurgery improvements in multiple outcomes at years 1, 2, and 3.

The study’s “large geographically diverse sample, inclusion of multiple validated measures of pain and physical function, longitudinal design, and follow-up through 3 years make it one of the most informative studies of pain and function following RYGB and LAGB to date,” the authors write.

(doi:10.1001/jama.2016.3010; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, APRIL 5, 2016

Media Advisory: To contact Philip Clarke, Ph.D., email philip.clarke@unimelb.edu.au.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.0126

In a study appearing in the April 5 issue of JAMA, Philip Clarke, Ph.D., of the University of Melbourne, Australia, and colleagues analyzed individual and prescription-level data from the Medical Expenditure Panel Survey to describe and compare trends in expenditure and price of anti-hyperglycemic medications in the United States from 2002 through 2013.

The sample consisted of 27,878 people treated for diabetes. During the study period, the prevalence of treated diabetes increased from 5.2 percent in 2002-2004 to 7.7 percent in 2011-2013. For those with recorded insulin use, the quantity per year increased from 171 mL in 2002-2004 to 206 mL in 2011-2013; over the same period, estimated spending for insulin per patient increased from $231 in 2002 to $736 in 2013. In 2013, estimated expenditure per patient amounted to $508 for analog insulin and $228 for human insulin.

The total expenditure on insulin in 2013 was significantly greater than the combined expenditure on all other anti-hyperglycemic medications of $503. The average price per milliliter of insulin increased by 197 percent from $4.34 per milliliter in 2002 to $12.92 per milliliter in 2013, whereas the average price of dipeptidyl peptidase-4 (DPP-4) inhibitors increased by 34 percent from $6.67 per tablet in 2006 to $8.92 in 2013. The average price of metformin decreased by 93 percent from $1.24 per tablet in 2002 to $0.31 per tablet in 2013.

“Significant changes in mean price of insulin, relative to comparator therapies, suggest a need to reassess the effectiveness and cost-effectiveness of alternative anti-hyperglycemic therapies,” the authors write.

(doi:10.1001/jama.2016.0126; this study is available pre-embargo at the For The Media website.)

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

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EMBARGOED FOR RELEASE: 9 A.M. (ET) SUNDAY, APRIL 3, 2016

Media Advisory: To contact Steven E. Nissen, M.D., call Andrea Pacetti at 216-316-3040 or email pacetta@ccf.org.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.3608

Steven E. Nissen, M.D., of the Cleveland Clinic, and colleagues identified patients with muscle-related adverse effects from statins and compared lipid-lowering efficacy for two nonstatin therapies, ezetimibe and evolocumab. The study was published online by JAMA, and is being released to coincide with its presentation at the American College of Cardiology’s 65th Annual Scientific Session & Expo.

A significant proportion of patients with clinical indications for statin treatment report inability to tolerate evidence-based doses, most commonly because of muscle-related adverse effects, reported by 5 percent to 20 percent of patients. These patients typically report muscle pain or weakness when treatment is initiated or dosage increased and relief when the drug is discontinued or the dosage reduced. Patients with muscle-related intolerance often refuse to take statins despite elevated low-density lipoprotein cholesterol (LDL-C) levels and a high risk of major cardiovascular events. Current management may include very low or intermittent administration of statins or use of ezetimibe, but these strategies seldom achieve reductions recommended by current guidelines.

For this study, the researchers conducted a two-stage randomized clinical trial that included 511 adult patients with uncontrolled LDL-C levels and a history of intolerance to 2 or more statins. Phase A involved a 24-week crossover procedure in which patients were randomly assigned to atorvastatin (20 mg) or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, patients were randomly assigned to evolocumab (420 mg monthly, by injection) or oral ezetimibe (10 mg daily) for 24 weeks.

In phase A, the researchers observed a 43 percent rate of discontinuation for intolerable muscle symptoms with atorvastatin but not placebo. However, 27 percent of patients reported similar symptoms with placebo but not atorvastatin, demonstrating that reported muscle symptoms are not always related to statin use. “Since statin-associated muscle symptoms are dose-related, the rate observed in [this trial] for atorvastatin (20 mg) may underestimate the problem, particularly for patients needing high-intensity statin therapy, such as those enrolled in the trial.”

During the second phase of the study, the authors found that evolocumab produced significantly larger reductions in levels of LDL-C and other lipoproteins compared to ezetimibe. Both coprimary end points (the average percent change in LDL-C level from baseline to the average of weeks 22 and 24 levels and from baseline to week 24 levels) showed a 17 percent reduction with ezetimibe and a more than 50 percent reduction with evolocumab. Despite very high baseline values, the LDL-C goal of less than 70 mg/dL was achieved in nearly 30 percent of evolocumab-treated patients and 1.4 percent of ezetimibe-treated patients.

Muscle symptoms were reported in 29 percent of ezetimibe-treated patients and 21 percent of evolocumab-treated patients. Active study drug was stopped for muscle symptoms in 7 percent of ezetimibe-treated patients and 0.7 percent of evolocumab-treated patients.

“These findings demonstrate that both drugs are unlikely to provoke muscle symptoms and can be administered successfully in such patients, although with significant differences in lipid-lowering efficacy. Since a minority of patients achieved optimal LDL-C levels despite treatment with evolocumab, it may be worth exploring the addition of ezetimibe to evolocumab for those patients requiring further LDL-C reduction. It should be noted that neither ezetimibe nor evolocumab is approved for reduction of major adverse cardiovascular events,” the authors write.

“Further studies are needed to assess long-term efficacy and safety.”

(doi:10.1001/jama.2016.3608; this study is available pre-embargo at the For The Media website.)

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

EMBARGOED FOR RELEASE: 9 A.M. (ET) MONDAY, APRIL 4, 2016

Media Advisory: To contact Michelle L. O’Donoghue, M.D., M.P.H., call Johanna Younghans at 617-525-6373 or email Jyounghans@partners.org.

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Michelle L. O’Donoghue, M.D., M.P.H., of Brigham and Women’s Hospital, Boston, and colleagues evaluated the efficacy and safety of the anti-inflammatory drug losmapimod on cardiovascular outcomes in patients hospitalized after a heart attack. The study was published online by JAMA, and is being released to coincide with its presentation at the American College of Cardiology’s 65th Annual Scientific Session & Expo.

Inflammation stimulated by the enzyme p38 mitogen-activated protein kinase (MAPK) is implicated in atherogenesis (the process of forming atheromas, plaques in the inner lining of arteries) and plaque destabilization. Pilot data in a phase 2 trial in patients with non-ST elevation myocardial infarction (NSTEMI; a certain pattern on an electrocardiogram following a heart attack) indicated that the p38 MAPK inhibitor losmapimod lessens inflammation and may improve outcomes. In this phase 3 trial, Dr. O’Donoghue and colleagues randomly assigned patients who had been hospitalized with an acute MI and had at least 1 additional predictor of cardiovascular risk to either twice-daily losmapimod (n = 1,738) or matching placebo (n = 1,765) on a background of guideline-recommended therapy. Patients were treated for 12 weeks and followed up for an additional 12 weeks. The study was conducted at 322 sites in 34 countries. Part A of the trial consisted of a group (n = 3,503) to provide an initial assessment of safety and exploratory efficacy before considering progression to part B (approximately 22,000 patients).

Among the 3,503 patients in part A, the primary end point (a composite of cardiovascular death, MI, or severe recurrent ischemia requiring urgent coronary revascularization with the principal analysis specified at week 12) occurred by 12 weeks in 123 patients treated with placebo (7 percent) and 139 patients treated with losmapimod (8.1 percent). The on-treatment rates of serious adverse events were 16 percent with losmapimod and 14.2 percent with placebo.

The authors write that the results of this exploratory efficacy study did not justify proceeding to a larger efficacy trial in the existing patient population.

“In this trial, losmapimod did not reduce the risk of recurrent major adverse cardiovascular events through 12 weeks of treatment in patients hospitalized with acute MI. Furthermore, there was no evidence that losmapimod reduced the incidence of any secondary outcomes including all-cause mortality. Therefore, our findings do not support a strategy of p38 MAPK inhibition with losmapimod in patients hospitalized with MI.”

“Because inflammation is believed to play a key role in atherogenesis, there remains intense interest to identify an anti-inflammatory therapeutic that will reduce the risk of cardiovascular events. However, because inflammation acts along multiple redundant and interconnected pathways, the identification of an appropriate target may be difficult, and it is challenging to predict clinical efficacy prior to phase 3 testing.”

(doi:10.1001/jama.2016.3609; this study is available pre-embargo at the For The Media website.)

Editor’s Note: This trial was funded by GlaxoSmithKline. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 10 A.M. (ET) TUESDAY, MARCH 29, 2016

Media Advisory: To contact Robert W. Yeh, M.D., M.Sc., email Jennifer Kritz at jkritz@bidmc.harvard.edu

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JAMA

In a study published online by JAMA, Robert W. Yeh, M.D., M.Sc., of Beth Israel Deaconess Medical Center, Boston, and colleagues conducted a study to identify factors that would predict whether the expected benefit of reduced ischemia would outweigh the expected increase in bleeding associated with continued dual antiplatelet therapy (aspirin plus thienopyridine) more than one year after coronary stent placement.

Dual antiplatelet therapy after percutaneous coronary intervention (PCI; commonly known as coronary angioplasty, a non-surgical procedure used to open narrow or blocked coronary arteries) reduces ischemia (inadequate blood supply to an area due to blockage of blood vessels leading to that area) but increases risk of bleeding. It remains unclear which patients are at high risk for late ischemic events and may thus benefit most from longer-term dual antiplatelet therapy vs those who are at high risk for late bleeding events and may be harmed.

Among 11,648 randomized DAPT (Dual Antiplatelet Therapy) Study patients from 11 countries, a prediction rule was derived stratifying patients into groups to distinguish ischemic and bleeding risk 12 to 30 months after PCI. The clinical prediction score was validated among 8,136 patients from 36 countries randomized in the PROTECT (Patient Related Outcomes With Endeavor vs Cypher Stenting) trial.

After adding or subtracting points for patients for factors such as heart attack at presentation, prior heart attack or PCI; diabetes; smoking; and older age, the researchers developed a clinical prediction score that showed modest accuracy assessing ischemic and bleeding risks.

“Use of this prediction score should be cautious until further validation is performed, and optimal clinical and procedural care to reduce overall bleeding and ischemic risks should be practiced independent of score,” the authors write.

(doi:10.1001/jama.2016.3775; this study is available pre-embargo at the For The Media website.)

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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For more information, contact JAMA Network Media Relations at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 22, 2016

Media Advisory: To contact Daniel C. Cherkin, Ph.D., call Rebecca Hughes at 206-287-2055 or email hughes.r@ghc.org. To contact editorial co-author Madhav Goyal, M.D., M.P.H., call Marin Hedin at 410-502-9429 or email mhedin2@jhmi.edu.

To place an electronic embedded link to this study and editorial in your story These links will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.2323; https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.2437

Among adults with chronic low back pain, both mindfulness-based stress reduction and cognitive behavioral therapy resulted in greater improvement in back pain and functional limitations when compared with usual care, according to a study appearing in the March 22/29 issue of JAMA.

Low back pain is a leading cause of disability in the United States. There is need for treatments with demonstrated effectiveness that are low risk and have potential for widespread availability. Mindfulness-based stress reduction (MBSR) focuses on increasing awareness and acceptance of moment-to-moment experiences including physical discomfort and difficult emotions. Only 1 large randomized clinical trial has evaluated MBSR for chronic low back pain, and that trial was limited to older adults.

Daniel C. Cherkin, Ph.D., of Group Health Research Institute, Seattle, and colleagues randomly assigned 342 adults age 20 to 70 years with chronic low back pain to receive MBSR (n = 116), cognitive behavioral therapy (CBT; n = 113), or usual care (n = 113). CBT (training to change pain-related thoughts and behaviors) and MBSR (training in mindfulness meditation and yoga) were delivered in 8 weekly 2-hour groups. Usual care included whatever other treatment, if any, the participants received. The average age of the participants was 49 years; the average duration of back pain was 7.3 years.

The researchers found that at 26 weeks, the percentage of participants with clinically meaningful improvement on a measure of functional limitations was higher for those who received MBSR (61 percent) and CBT (58 percent) than for usual care (44 percent). The percentage of participants with clinically meaningful improvement in pain bothersomeness at 26 weeks was 44 percent in the MBSR group and 45 percent in the CBT group, vs 27 percent in the usual care group. Findings for MBSR persisted with little change at 52 weeks for both primary outcomes.

“The effects were moderate in size, which has been typical of evidence-based treatments recommended for chronic low back pain. These benefits are remarkable given that only 51 percent of those randomized to receive MBSR and 57 percent of those randomized to receive CBT attended at least 6 of the 8 sessions,” the authors write.

“These findings suggest that MBSR may be an effective treatment option for patients with chronic low back pain.”

(doi:10.1001/jama.2016.2323; this study is available pre-embargo at the For The Media website.)

Editor’s Note: Research reported in this article was supported by the National Center for Complementary and Integrative Health of the National Institutes of Health. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: Is It Time to Make Mind-Body Approaches Available for Chronic Low Back Pain?

“Although understanding the specificity of treatment effects, mechanisms of action, and role of mediators are important issues for researchers, they are merely academic for many clinicians and their patients. For patients with chronic painful conditions, options are needed to help them live with less pain and disability now,” write Madhav Goyal, M.D., M.P.H., and Jennifer A. Haythornthwaite, Ph.D., of Johns Hopkins University School of Medicine, Baltimore.

“The challenge is how to ensure that these mind-body interventions are available, given the existing evidence demonstrating they may work for some patients with chronic low back pain. Most physicians encounter numerous obstacles finding appropriate referrals for mind-body therapies that their patients can access and afford. High-quality studies such as the clinical trial by Cherkin et al create a compelling argument for ensuring that an evidence-based health care system should provide access to affordable mind-body therapies.”

(doi:10.1001/jama.2016.2437; this editorial is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, MARCH 22, 2016

Media Advisory: To contact Jeffrey S. Gerber, M.D., Ph.D., email Natalie Virgilio at VIRGILION@email.chop.edu.

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Exposure to antibiotics within the first 6 months of life compared with no exposure among nearly 40,000 children was not associated with a significant difference in weight gain through age 7, according to a study appearing in the March 22/29 issue of JAMA.

Antibiotics are the most commonly prescribed medications for children, with the long-term health effects relatively unknown. Early-life antibiotic exposure has been associated with increased adiposity (body fat) in animal models. Studies of the association between infant antibiotics and childhood weight gain have reported inconsistent results. Jeffrey S. Gerber, M.D., Ph.D., of The Children’s Hospital of Philadelphia, and colleagues conducted a study that included 38,522 children and 92 twins (46 matched pairs) with differences in antibiotic exposure and assessed the association between early-life exposure and childhood weight gain. The children were of diverse racial and socioeconomic backgrounds from Pennsylvania, New Jersey, and Delaware.

Of the children in the study, 5,287 (14 percent) were exposed to antibiotics during the first 6 months of life (at an average age of 4.3 months). Antibiotic exposure was not significantly associated with rate of weight change (0.7 percent; equivalent to approximately 1.8 ounce). Among 92 twins, the 46 twins who were exposed to antibiotics during the first 6 months of life received them at an average age of 4.5 months, and exposure was not significantly associated with a weight difference (-3.2 ounces).

“These findings do not support a clinically meaningful association of early-life antibiotic use with childhood weight gain,” the authors write. “There are many reasons to limit antibiotic exposure in young, healthy children, but weight gain is likely not one of them.”

(doi:10.1001/jama.2016.2395; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, MARCH 22, 2016

Media Advisory: To contact Deborah W. Neklason, Ph.D., or N. Jewel Samadder, M.D., M.S., call Linda Aagard at 801-587-7639 or email Linda.Aagard@hci.utah.edu.

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In a study appearing in the March 22/29 issue of JAMA, Deborah W. Neklason, Ph.D., N. Jewel Samadder, M.D., M.S., of the Huntsman Cancer Institute, University of Utah, Salt Lake City, and colleagues randomly assigned 92 patients with familial adenomatous polyposis to the drugs sulindac twice daily and erlotinib daily (n = 46) or placebo (n = 46) for 6 months.

Familial adenomatous polyposis (FAP) is an inherited disorder, and patients with FAP are at markedly increased risk for duodenal (part of the small intestine) polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful.

The researchers found that sulindac in combination with erlotinib effectively reduced the total duodenal polyp burden and polyp number in participants with FAP compared with placebo. This effect was significant after 6 months of therapy.

Grade 1 and 2 adverse events were more common in the sulindac-erlotinib group, with an acne-like rash observed in 87 percent of participants receiving treatment and 20 percent of participants receiving placebo. “Adverse events may limit the use of these medications at the doses used in this study,” the authors write.

“Further research is necessary to evaluate these preliminary findings in a larger study population with longer follow-up to determine whether the observed effects will result in improved clinical outcomes.”

(doi:10.1001/jama.2016.2522; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, MARCH 22, 2016

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

To place an electronic embedded link to this study in your story This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.2374

In a study appearing in the March 22/29 issue of JAMA, Ann Marie Navar, M.D., Ph.D., of Duke University Medical Center, Durham, N.C., and colleagues examined how shared clinical trial data are being used. Concerns over bias in clinical trial reporting have stimulated calls for more open data sharing. In response, multiple pharmaceutical companies have created mechanisms for investigators to access patient-level clinical trials data.

The researchers evaluated how many clinical trials were publicly available to investigators through 3 open access platforms, and found that a total of 3,255 clinical trials were available in the platforms. The median number of trials requested by each proposal was 2. Only 505 unique trials (15.5 percent of available trials) had ever been requested. “Reasons for underutilization of clinical trials data may include lack of knowledge about these resources, possibly due to lack of publication of results from proposals, or lack of funding to support analyses.”

“Early use of platforms designed to provide access to individual patient data, developed to increase transparency of clinical trial data, has been limited. Availability of shared clinical trial data should be promoted and use of individual patient data for validation studies encouraged.”

(doi:10.1001/jama.2016.2374; this study is available pre-embargo at the For The Media website.)

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

Note: An accompanying editorial, “Data Sharing – An Ethical and Scientific Imperative,” by Howard Bauchner, M.D., Editor in Chief, JAMA, Chicago, and colleagues is available pre-embargo at the For The Media website.

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EMBARGOED FOR RELEASE: 1:30 P.M. (ET) TUESDAY, MARCH 15, 2016

Media Advisory: To contact corresponding author Deborah Dowell, M.D., M.P.H., call 404-639-3286 or email media@cdc.gov.

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The Centers for Disease Control and Prevention (CDC) has issued recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain, recommendations that are intended to improve communication about the benefits and risks, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy, according to a report published online by JAMA.

The number of people experiencing chronic pain is substantial, with U.S. prevalence estimated at 11.2 percent of the adult population. Opioids are commonly prescribed for pain, with approximately 3 percent to 4 percent of the adult U.S. population prescribed long-term opioid therapy. Opioid pain medication use presents serious risks. From 1999 to 2014, more than 165,000 persons died from overdose related to opioid pain medication in the U.S. In 2013 alone, an estimated 1.9 million persons abused or were dependent on prescription opioid pain medication. Primary care clinicians find managing chronic pain challenging. Evidence on long-term efficacy of opioids for chronic pain is limited.

For the development of these recommendations and guideline, which are for chronic pain outside of active cancer treatment, palliative care, and end-of-life care, the CDC updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology.

There are 12 recommendations for 3 areas: determining when to initiate or continue opioids for chronic pain; opioid selection, dosage, duration, follow-up, and discontinuation; and assessing risk and addressing harms of opioid use. Among the recommendations:

— Of primary importance, nonopioid therapy is preferred for treatment of chronic pain.

— Opioids should only be used when benefits for pain and function are expected to outweigh risks.

— Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks.

— When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible.

— Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages.

— For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone.

The authors write that to inform future guideline development, more research is needed to fill critical evidence gaps. “Yet given that chronic pain is a significant public health problem, the risks associated with long-term opioid therapy, the availability of effective alternative treatment options for pain, and the potential for improvement in the quality of health care with the implementation of recommended practices, a guideline for prescribing is warranted with currently available evidence.”

They add that the “CDC is committed to evaluating the guideline to identify effects on clinician and patient outcomes, both intended and unintended, and will revisit the guideline to determine if evidence gaps have been sufficiently addressed to warrant an update of the guideline and revise the recommendations in future updates when warranted.”

(doi:10.1001/jama.2016.1464; The full report is available pre-embargo at the For The Media website.)

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: 1:30 P.M. (ET) TUESDAY, MARCH 15, 2016

Media Advisory: To contact Brian T. Bateman, M.D., M.Sc., call Elaine St. Peter at 617-525-6375 or email estpeter@partners.org.

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In a study published online by JAMA, Brian T. Bateman, M.D., M.Sc., of Brigham and Women’s Hospital, Boston, and colleagues examined nationwide patterns of opioid prescribing following surgical tooth extraction.

Opioid abuse has reached epidemic proportions in the United States, and often begins with a prescription for a pain medication. Dentists are among the leading prescribers of opioid analgesics, and surgical tooth extraction is one of the most frequently performed dental procedures. Surveys suggest that dental practitioners commonly prescribe opioids following this procedure, despite evidence that a combination of nonsteroidal medications and acetaminophen may provide more effective treatment for postextraction pain.

The researchers collected data from a national database of health claims drawn from Medicaid transactions for the years 2000-2010. All patients who underwent surgical dental extraction were included. The frequency of opioid prescriptions filled within 7 days of extraction was determined, as was the nature and amount of opioids dispensed.

The analysis included 2,757,273 patients. Within 7 days of extraction, 42 percent of patients filled a prescription for an opioid medication. The most commonly dispensed opioid was hydrocodone (78 percent of all prescriptions), followed by oxycodone (15 percent), propoxyphene (3.5 percent), and codeine (1.6 percent). Patients age 14 to 17 years had the highest proportion who filled opioid prescriptions (61 percent), followed by patients age 18 to 24 years.

There was great variability in the amount of opioids dispensed for a given procedure, with an approximately 3-fold difference between the 10th and 90th percentile in the oral morphine equivalents prescribed. “Although a limited supply of opioids may be required for some patients following tooth extraction, these data suggest that disproportionally large amounts of opioids are frequently prescribed given the expected intensity and duration of postextraction pain, particularly as nonopioid analgesics may be more effective in this setting,” the authors write.

“This common dental procedure may represent an important area of excessive opioid prescribing in the United States. As the nation implements programs to reduce excessive prescribing of opioid medications, it will be important to include dental care in these approaches.”

(doi:10.1001/jama.2015.19058. The study is available pre-embargo at the For The Media website.)

Editor’s Note: Research reported in this publication was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health. 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: 1:30 P.M. (ET) TUESDAY, MARCH 15, 2016

Media Advisory: To contact Hannah Wunsch, M.D., M.Sc., call Sybil Millar at 416-480-4040 or email sybil.millar@sunnybrook.ca.

To place an electronic embedded link to this article in your story This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.0130

In a study published online by JAMA, Hannah Wunsch, M.D., M.Sc., of Sunnybrook Health Sciences Centre, Toronto, and colleagues assessed trends in the amount of hydrocodone/acetaminophen and oxycodone/acetaminophen prescribed from 2004-2012, two opioids commonly used for postoperative pain management.

The study included health care encounters of approximately 14 million primarily commercially insured patients, with information on pharmacy and medical claims with data on services and procedures. The sample included opioid-naive adults (n = 155,297) who underwent 1 or more of 4 low-risk surgical procedures in 2004, 2008, or 2012: carpal tunnel release, laparoscopic cholecystectomy (gallbladder removal), inguinal hernia repair, or knee arthroscopy. The researchers assessed the proportion of patients who filled any opioid prescription (and specifically hydrocodone/acetaminophen or oxycodone/acetaminophen) in the 7 days after hospital discharge (inpatients) or on the procedure date (outpatients).

Within 7 days, 80 percent filled a prescription for any opioid, and 86 percent of these prescriptions were for hydrocodone/acetaminophen or oxycodone/acetaminophen. The proportions of patients filling prescriptions for any opioid and for hydrocodone/acetaminophen and oxycodone/acetaminophen increased over time for all surgeries. The average morphine equivalent dose increased over time for all procedures examined, with an increase of 18 percent for patients undergoing knee arthroscopy, driven by a change in the average daily dose.

“Because the cohort was restricted to opioid-naive individuals, these changes are unlikely to represent an appropriate response by prescribing physicians to increasing rates of opioid tolerance over time within the population. Possible explanations include an increased focus on pain treatment or an increasing reliance on opioids for postoperative pain relief vs alternative therapies,” the authors write.

“Further research should assess the contribution of postoperative opioid prescribing practices to the epidemic of prescription opioid-related abuse.”

(doi:10.1001/jama.2016.0130. The study is available pre-embargo at the For The Media website.)

Editor’s Note: This work is supported in part by a New Investigator Award from the Canadian Institutes of Health Research and a Merit Award from the Department of Anesthesia at the University of Toronto. 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: 4 A.M. (ET) TUESDAY, MARCH 15, 2016

Media Advisory: To contact Michael C. Reade, D.Phil., F.C.I.C.M., email m.reade@uq.edu.au.

To place an electronic embedded link to this study in your story This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.2707

Michael C. Reade, D.Phil., F.C.I.C.M., of the University of Queensland, Brisbane, Australia, and colleagues evaluated the effectiveness of the drug dexmedetomidine when added to standard care in intensive care unit (ICU) patients with agitated delirium receiving mechanical ventilation. The study, published by JAMA, is being released to coincide with its presentation at the International Symposium on Intensive Care and Emergency Medicine.

The incidence of delirium in critically ill patients is high. Delirium is associated with increased mortality and decreased long-term cognitive function. Agitated delirium is particularly problematic in patients receiving mechanical ventilation because it increases the risk of self-extubation and removal of other essential medical devices. Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation.

In this study, 74 ICU patients in whom extubation was considered inappropriate because of the severity of agitation and delirium, were randomly assigned to be administered dexmedetomidine or placebo to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. The study was conducted at 15 ICUs in Australia and New Zealand.

The final analysis included 39 patients in the dexmedetomidine group and 32 patients in the placebo group. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 145 hours vs 128 hours, respectively). Among secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 22 hours vs 44 hours with placebo) and accelerated resolution of delirium (median, 23 hours vs 40 hours). Analysis indicated that dexmedetomidine was significantly associated with earlier extubation.

“The findings support the use of dexmedetomidine in patients such as these,” the authors write.

(doi:10.1001/jama.2016.2707; this study is available pre-embargo at the For The Media website.)

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: 4 A.M. (ET) TUESDAY, MARCH 15, 2016

Media Advisory: To contact Lonneke A. van Vught, M.D., email l.a.vanvught@amc.uva.nl.

To place an electronic embedded link to this study in your story This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.2691

Lonneke A. van Vught, M.D., of the University of Amsterdam, the Netherlands and colleagues conducted a study that included admissions in two intensive care units (ICUs) in the Netherlands stratified according to admission diagnosis (sepsis or non-infectious). The study, published by JAMA, is being released to coincide with its presentation at the International Symposium on Intensive Care and Emergency Medicine.

Sepsis is the leading cause of illness and death in hospitalized patients. It has been suggested that the immune suppression accompanying sepsis contributes to late sepsis mortality in the ICU caused by an increased occurrence of secondary infections. This study included 1,719 sepsis admissions; a comparative group included 1,921 admissions in whom infection was not present in the first 48 hours.

ICU-acquired infections occurred in 13.5 percent of sepsis admissions and 15 percent of non-sepsis ICU admissions. Patients with sepsis who developed an ICU-acquired infection had higher disease severity scores on admission than patients with sepsis who did not develop an ICU-acquired infection. The estimated difference between mortality in all patients with a sepsis admission diagnosis and mortality in those without ICU-acquired infection was 2 percent by day 60.

The authors write that a few findings from this study deserve attention. “First, the incidence of ICU-acquired infections after the first week of ICU stay was comparable in both admission groups. Second, a higher proportion of patients with a sepsis admission diagnosis acquired more than one infection in the ICU compared with patients with a non-infectious admission diagnosis. Third, patients with sepsis on admission developed more ICU-acquired infections with opportunistic pathogens like enterococci, Pseudomonas aeruginosa and viruses, hinting at possible immune suppression. Fourth, the population attributable mortality fraction of ICU-acquired infection does not seem to be higher in patients with a sepsis admission diagnosis than in patients admitted with a non-infectious condition.”

(doi:10.1001/jama.2016.2691; this study is available pre-embargo at the For The Media website.)

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: 4 A.M. (ET) TUESDAY, MARCH 15, 2016

Media Advisory: To contact Samir Jaber, M.D., Ph.D., email s-jaber@chu-montpellier.fr.

To place an electronic embedded link to this study in your story This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.2706

Samir Jaber, M.D., Ph.D., of Saint Eloi University Hospital and Montpellier School of Medicine, Montpellier, France and colleagues examined whether noninvasive ventilation vs standard oxygen therapy improves outcomes among patients developing hypoxemic (low levels of oxygen in the blood) acute respiratory failure after abdominal surgery. The study, published by JAMA, is being released to coincide with its presentation at the International Symposium on Intensive Care and Emergency Medicine.

Postoperative acute respiratory failure is a major contributor to the overall risk of surgery, leading to an increase in illness and death. Postoperative acute respiratory failure often requires tracheal reintubation and invasive mechanical ventilation. It has not been established whether noninvasive ventilation (NIV) reduces the need for invasive mechanical ventilation in patients who develop hypoxemic acute respiratory failure after abdominal surgery.

In this trial conducted at 20 French intensive care units, 293 patients who had undergone abdominal surgery and developed hypoxemic respiratory failure were randomly assigned to receive standard oxygen therapy (n = 145) or NIV delivered via facial mask (n = 148). The researchers found that reintubation occurred in 33 percent of patients in the NIV group and 46 percent of patients in the standard oxygen therapy group by 7 days after randomization. Noninvasive ventilation was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (25.4 vs 23.2 days), while fewer patients developed health care-associated infections (31 percent vs 49 percent), especially ICU acquired pneumonia. At 90 days, 15 percent of patients in the NIV group had died, compared to 22 percent in the standard oxygen therapy group.

“Among patients with hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of tracheal reintubation within 7 days. These findings support use of NIV in this setting,” the authors write.

(doi:10.1001/jama.2016.2706; this study is available pre-embargo at the For The Media website.)

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: 4 A.M. (ET) TUESDAY, MARCH 15, 2016

Media Advisory: To contact Gonzalo Hernandez, M.D., Ph.D., email ghernandezm@telefonica.net.

To place an electronic embedded link to this study in your story This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.2711

Gonzalo Hernandez, M.D., Ph.D., of Hospital Virgen de la Salud, Madrid, Spain and colleagues randomly assigned 527 mechanically ventilated patients at low risk for reintubation to undergo either high-flow or conventional oxygen therapy for 24 hours after extubation. The study, published by JAMA, is being released to coincide with its presentation at the International Symposium on Intensive Care and Emergency Medicine.

Studies of mechanically ventilated critically ill patients that combine populations that are at high and low risk for reintubation suggest that high-flow nasal cannula oxygen therapy after extubation improves oxygenation compared with conventional oxygen therapy. However, conclusive data about reintubation are lacking. A nasal cannula is a device for delivering oxygen by way of two small tubes that are inserted into the nostrils.

In this study 264 patients received high-flow therapy and 263 conventional oxygen therapy. Reintubation within 72 hours was less common in the high-flow group (13 patients [5 percent]) vs 32 (12 percent) in the conventional group. Postextubation respiratory failure was less common in the high-flow group (8 percent vs 14 percent in the conventional group). Time to reintubation was not significantly different between groups.

“The main finding of this study was that high-flow oxygen significantly reduced the reintubation rate in critically ill patients at low risk for extubation failure,” the authors write.

(doi:10.1001/jama.2016.2711; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, MARCH 15, 2016

Media Advisory: To contact Saad B. Omer, M.B.B.S., M.P.H., Ph.D., email Melva Robertson at melva.robertson@emory.edu. To contact editorial author Matthew M. Davis, M.D., M.A.P.P., email Beata Mostafavi at bmostafa@med.umich.edu.

To place an electronic embedded link to this study and editorial in your story These links will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1353; https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1529

An analysis of numerous studies and reports finds that unvaccinated or undervaccinated individuals comprised substantial proportions of cases in measles and some pertussis outbreaks, and vaccine refusal was associated with an elevated risk for measles and pertussis, including among fully vaccinated individuals, according to a study appearing in the March 15 issue of JAMA.

Recent outbreaks of vaccine-preventable diseases in the United States have prompted clinicians, public health officials and the public to pay greater attention to the growing phenomenon of vaccine refusal and hesitancy. Improved understanding of the association between vaccine refusal and the epidemiology of these diseases is needed. Saad B. Omer, M.B.B.S., M.P.H., Ph.D., of Emory University, Atlanta, and colleagues examined the association between vaccine delay, refusal, or exemption and the epidemiology of measles and pertussis, two vaccine-preventable diseases with recent U.S. outbreaks. The authors searched the medical literature for reports of U.S. measles outbreaks that have occurred since measles was declared eliminated in the United States (after January 1, 2000), endemic and epidemic pertussis since the lowest point in U.S. pertussis incidence (after January 1, 1977), and for studies that assessed disease risk in the context of vaccine delay or exemption.

The researchers identified 18 published measles studies, which described 1,416 measles cases (individual age range, 2 weeks-84 years; 178 cases younger than 12 months) and more than half (57 percent) had no history of measles vaccination. Of the 970 measles cases with detailed vaccination data, 574 cases were unvaccinated despite being vaccine eligible and 71 percent of these had nonmedical exemptions (e.g., for religious or philosophical reasons, as opposed to medical contraindications; 42 percent of total).

Among 32 reports of pertussis outbreaks, which included 10,609 individuals for whom vaccination status was reported (age range, 10 days-87 years), the 5 largest statewide epidemics had substantial proportions (range, 24 percent-45 percent) of unvaccinated or undervaccinated individuals. However, several pertussis outbreaks also occurred in highly vaccinated populations, indicating waning immunity. Nine reports (describing 12 outbreaks) provided detailed vaccination data on unimmunized cases; among 8 of these outbreaks, from 59 percent through 93 percent of unvaccinated individuals were intentionally unvaccinated.

“This review has broad implications for vaccine practice and policy. For instance, fundamental to the strength and legitimacy of justifications to override parental decisions to refuse a vaccine for their child is a clear demonstration that the risks and harms to the child of remaining unimmunized are substantial. Similarly, central to any justification to restrict individual freedom by mandating vaccines to prevent harm to others is an understanding of the nature and magnitude of these risks and harms. However, the risks of vaccine refusal remain imperfectly defined, and the association between vaccine refusal and vaccine-preventable diseases may be both population- and disease-specific,” the authors write.

(doi:10.1001/jama.2016.1353; this study is available pre-embargo at the For The Media website.)

Editor’s Note: This work is supported by an award from the Emory Vaccinology Training Program of the National Institute of Allergy and Infectious Diseases. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Toward High-Reliability Vaccination Efforts in the United States

“Without a centralized infrastructure focused on the goal of maximizing community immunity, high-reliability vaccine coverage remains challenging in the United States,” writes Matthew M. Davis, M.D., M.A.P.P., of the University of Michigan, Ann Arbor, in an accompanying editorial.

“Nonetheless, if vaccines are developed for emerging diseases that threaten the U.S. population—such as Zika, Ebola, or human immunodeficiency virus—the public will likely expect the currently complex and heterogeneous vaccination system in the United States to function as a seamless organization. The U.S. population wants vaccination to be safe, effective and available in a timely manner, and for immunization to be durable. Current challenges with measles and pertussis outbreaks provide an opportunity to develop and evaluate approaches to achieve unprecedented levels of vaccination coverage, limit waning immunity, and minimize vaccine-preventable disease for children and adults alike.”

(doi:10.1001/jama.2016.1529; this editorial is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, MARCH 15, 2016

Media Advisory: To contact Timo Laitio, M.D., Ph.D., email timo.laitio@elisanet.fi.

To place an electronic embedded link to this study in your story This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1933

Among comatose survivors of out-of-hospital cardiac arrest, treatment with inhaled xenon gas combined with hypothermia, compared with hypothermia alone, resulted in less white matter damage; however, there was no significant difference in neurological outcomes or death at 6 months, according to a study appearing in the March 15 issue of JAMA.

Survivors of out-of-hospital cardiac arrest have a poor prognosis with high rates of death and the likelihood of having severe neurological problems. Animal studies have established the neuroprotective properties of the inhaled noble gas xenon. Neuroprotection associated with xenon has been especially evident when combined with hypothermia (91.4°F to 95°F). Thus far, these neuroprotective properties have not been reported in human studies.

Timo Laitio, M.D., Ph.D., of the University of Turku, Finland, and colleagues randomly assigned 110 comatose patients who had experienced out-of-hospital cardiac arrest to receive either inhaled xenon combined with hypothermia (91.4°F) for 24 hours (n = 55) or hypothermia treatment alone (n = 55; control group). The trial was conducted at two intensive care units in Finland.

There were magnetic resonance imaging data from 97 patients a median of 53 hours after cardiac arrest. The researchers found that patients in the xenon group had less white matter damage compared to the control group. At six months, 75 patients (68 percent) were alive. There were no significant differences between the groups on measures of neurological and cognitive outcomes, or death at six months.

“These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest,” the authors write.

(doi:10.1001/jama.2016.1933; this study is available pre-embargo at the For The Media website.)

Editor’s Note: The study was funded by the Academy of Finland and via clinical research funding from the Hospital District of Southwest Finland. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 15, 2016

Media Advisory: To contact Rachel M. Freathy, Ph.D., email r.freathy@ex.ac.uk; to contact Debbie A. Lawlor, Ph.D., email d.a.lawlor@bristol.ac.uk.

To place an electronic embedded link to this study in your story This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1975

In a study that included more than 30,000 women, genetically elevated maternal body mass index (BMI) and blood glucose levels were potentially causally associated with higher offspring birth weight, while genetically elevated maternal systolic blood pressure was potentially causally related to lower birth weight, according to a study appearing in the March 15 issue of JAMA.

Neonates born to overweight or obese women are more likely to be large for gestational age. The precise mechanisms underlying this association are poorly understood. It is important to understand which maternal traits are causally associated with birth weight because this may facilitate targeted development of interventions to be tested and enable evidence-based recommendations for pregnant women.

Rachel M. Freathy, Ph.D., of the University of Exeter, and Debbie A. Lawlor, Ph.D., of the University of Bristol, U.K., and colleagues tested for genetic evidence of causal associations of maternal BMI and related traits with birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term offspring born between 1929 and 2013 were included.

The researchers found that a genetically higher maternal BMI of 4 points was associated with a 1.9 ounces higher offspring birth weight. In addition, a genetically higher circulating maternal fasting glucose of 7.2 mg/dL was associated with a 4 ounces higher birth weight, whereas genetically higher maternal systolic blood pressure (SBP) of 10 mm Hg was associated with a 7.3 ounces lower birth weight.

“These results provide evidence that genetically elevated maternal glucose and SBP may have directionally opposite causal associations with birth weight. The estimated associations between these maternal traits and birth weight (either increased or reduced) are substantial and of clinical importance. They support efforts to maintain healthy gestational glucose and blood pressure levels to ensure healthy fetal growth,” the authors write.

“If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.”

(doi:10.1001/jama.2016.1975; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, MARCH 15, 2016

Media Advisory: To contact Kathryn Rough, Sc.M., call Elaine St. Peter at 617-525-6375 or email estpeter@partners.org.

To place an electronic embedded link to this study in your story This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2015.18417

In a study appearing in the March 15 issue of JAMA, Kathryn Rough, Sc.M., of Brigham and Women’s Hospital, Boston, and colleagues examined the association between implementation of the Centers for Medicare & Medicaid Services (CMS) suppression policy of substance abuse-related claims and rates of diagnoses for non­substance abuse conditions in Medicaid data.

In a change from longstanding practice, the CMS recently began suppressing substance abuse-related claims in the Medicare and Medicaid Research Identifiable Files to comply with a 1987 federal regulation barring third party payers from releasing information from federally funded substance abuse treatment programs without patient consent. CMS removes any claim containing a diagnostic or procedure code related to substance abuse, meaning that the entire encounter captured by the claim is deleted (including all diagnosis and procedure codes). Therefore, important diagnoses linked to substance abuse might also be suppressed.

This study included Medicaid data for 2000-2006 prior to implementation of the suppression policy (i.e., containing substance abuse codes) and data for 2007-2010 after the policy was enacted, allowing comparison of data without vs with claim suppression. The researchers calculated annual inpatient and   outpatient rates of diagnoses for 6 conditions that commonly co-occur with substance abuse (hepatitis C, human immunodeficiency virus, cirrhosis, tobacco use, depression, and anxiety) and 4 conditions unrelated to substance abuse (type II diabetes, stroke, hypertension, and kidney disease).

The authors found that conditions unrelated to substance abuse appeared generally unassociated with the CMS suppression practices. However, implementation of the policy coincided with sudden and substantial decreases in the rates of inpatient diagnoses for conditions commonly co-occurring with substance abuse, and anxiety showed significant reductions in outpatient diagnosis rates.

“Underestimation of diagnoses has the potential to bias health services research studies and epidemiological analyses for which affected conditions are outcomes or confounders. In studies of health care utilization, the number of missing claims may vary in a nonrandom fashion between groups defined by demographics, disease, or locality. Comparisons between groups may lead to spurious conclusions—a hospital that regularly admits substance abusers will have artificially low rates of readmission, giving a false appearance of better performance.”

(doi:10.1001/jama.2015.18417; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, MARCH 8, 2016

Media Advisory: To contact Steven E. Nissen, M.D., email Tora Vinci at VINCIV@ccf.org or Andrea Pacetti at PACETTA@ccf.org. To contact editorial co-author Joshua M. Sharfstein, M.D., email Stephanie Desmon at sdesmon1@jhu.edu.

To place an electronic embedded link to this study and editorial in your story These links will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1558 https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1461

The cardiovascular safety of the obesity treatment naltrexone-bupropion remains uncertain because of the unanticipated early termination of a trial to determine its safety, according to a study appearing in the March 8 issue of JAMA.

Drug treatments for obesity have yielded mixed results, with pharmacological agents achieving modest weight loss but without demonstrating a reduction in cardiovascular events. Two therapies, fenfluramine and sibutramine, were removed from the market after evidence of cardiovascular harm emerged. Accordingly, the medical community and regulatory authorities have expressed concern about the cardiovascular safety of new drugs to treat obesity. The combination of the drugs naltrexone and bupropion reduced weight during phase 3 clinical trials, but the U.S. Food and Drug Administration (FDA) deferred approval based on safety concerns related to small increases in blood pressure and heart rate in these trials.

Steven E. Nissen, M.D., of the Cleveland Clinic Center for Cardiovascular Research, Cleveland, and colleagues randomly assigned 8,910 overweight or obese patients at increased cardiovascular risk to receive placebo (n=4,454) or naltrexone and bupropion (n=4,456). An Internet-based weight management program was provided to all participants. The study was conducted at 266 U.S. centers. The researchers examined whether the combination of naltrexone and bupropion increases major adverse cardiovascular events (MACE, defined as cardiovascular death, nonfatal stroke, or nonfatal heart attack) compared with placebo.

For the 25 percent interim analysis (after approximately 87 events), MACE occurred in 59 placebo-treated patients (1.3 percent) and 35 naltrexone-bupropion–treated patients (0.8 percent). After 50 percent of planned events, outcomes were less favorable for naltrexone-bupropion patients, with MACE occurring in 102 patients (2.3 percent) in the placebo group and 90 patients (2.0 percent) in the naltrexone-bupropion group. After public release of confidential interim data (after 25 percent of planned events) by the sponsor, the academic leadership of the study recommended termination of the trial and the sponsor agreed.

The authors write that given the unplanned early termination of the trial, which directly resulted from the inappropriate release of the highly favorable 25 percent interim data, these findings do not establish the prespecified margin of noninferiority (not worse than). “Accordingly, the cardiovascular safety of this treatment remains uncertain and will require evaluation in a new adequately powered outcome trial.”

“The events leading to the termination of the study serve as a valuable reminder of the importance of maintaining confidentiality during ongoing trials. Premature release of interim data can result in inappropriate prejudgment about the benefits or risks of the studied therapy and make completion of the trial highly problematic. An FDA guidance for industry explicitly states that interim data from an ongoing clinical trial should remain confidential and warns that ‘such knowledge can bias the outcome of the study by inappropriately influencing its continuing conduct or the plan of analyses.’”

(doi:10.1001/jama.2016.1558; this study is available pre-embargo at the For The Media website.)

Editor’s Note: The study was sponsored by Orexigen Therapeutics Inc., La Jolla, Calif., and Takeda Pharmaceuticals International, Deerfield, Il. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Evaluation of the Cardiovascular Risk of Naltrexone-Bupropion

“In the shadow of [this trial, LIGHT], the FDA should review its policy of permitting approval based on interim analyses of ongoing safety studies. At a minimum, when a company violates its commitment to confidentiality and the FDA requires a new trial, the agency should delay approval at least until a viable replacement study is being conducted,” write Joshua M. Sharfstein, M.D., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and Bruce M. Psaty, M.D., Ph.D., of the University of Washington, Seattle, in an accompanying editorial.

“The FDA should pursue additional safeguards to prevent breakdowns in sponsor-investigator relationships and avoid the dissolution of future trials. For example, the agency should consider having data monitoring committees report interim results directly to the FDA, not to the sponsor.”

“The LIGHT study should serve as an important message to sponsors of clinical trials. … Repeated breaches of confidentiality may leave the FDA no alternative other than to require that full safety studies be conducted prior to product approval. The demise of the LIGHT trial is a reminder that basing approval on interim safety data is a carefully drawn compromise, not an entitlement.”

(doi:10.1001/jama.2016.1461; this editorial is available pre-embargo at the For The Media website.)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 8, 2016

Media Advisory: To contact Changhai Ding, M.D., Ph.D., email changhai.ding@utas.edu.au.

To place an electronic embedded link to this study in your story This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1961

Vitamin D supplementation for individuals with knee osteoarthritis and low 25-hydroxyvitamin D levels did not reduce knee pain or slow cartilage loss, according to a study appearing in the March 8 issue of JAMA.

Symptomatic knee osteoarthritis occurs among 10 percent of men and 13 percent of women age 60 years or older. Currently there are no disease-modifying therapies for osteoarthritis. Vitamin D can reduce bone turnover and cartilage degradation, thus potentially preventing the development and progression of knee osteoarthritis. Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current evidence from clinical trials is contradictory.

Changhai Ding, M.D., Ph.D., of the University of Tasmania, Hobart, Tasmania, Australia, and colleagues randomly assigned 413 patients with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D to receive monthly treatment with oral vitamin D₃ (50,000 IU; n = 209) or an identical placebo (n = 204) for 2 years. The study was conducted in Tasmania and Melbourne, Australia.

Of 413 enrolled participants (average age, 63 years; 50 percent women), 340 (82 percent) completed the study. The researchers found that vitamin D supplementation, compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or a measure of knee pain over 2 years. There were also no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions. Vitamin D levels did increase more in the vitamin D group than in the placebo group over 2 years.

“These data suggest a lack of evidence to support vitamin D supplementation for slowing disease progression or structural change in knee osteoarthritis,” the authors write.

(doi:10.1001/jama.2016.1961; this study is available pre-embargo at the For The Media website.)

Editor’s Note: This study was supported by a grant from the Australian National Health and Medical Research Council. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 8, 2016

Media Advisory: To contact Roger Zemek, M.D., call Adrienne Vienneau at 613-737-7600, ext. 4144 or email avienneau@cheo.on.ca. To contact editorial co-author Lynn Babcock, M.D., M.S., call Jim Feuer at 513-636-4656 or email jim.feuer@cchmc.org.

To place an electronic embedded link to this study and editorial in your story These links will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1203 https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1276

A clinical risk score developed among children presenting to an emergency department with a concussion was significantly better than physician judgment in predicting future persistent postconcussion symptoms, according to a study appearing in the March 8 issue of JAMA.

Rates of concussion have doubled during the last decade, with an estimated 750,000 pediatric acute concussion visits to emergency departments (EDs) occurring annually in the United States. Although many children experience symptom resolution within 2 weeks, approximately 33 percent experience ongoing symptoms, and those that persist beyond 28 days are referred to as persistent postconcussion symptoms (PPCS), which can have serious adverse effects, resulting in school absenteeism, impaired academic performance, depressed mood and lower quality of life. Validated and pragmatic tools to identify children at high risk of developing PPCS do not exist.

Roger Zemek, M.D., of Children’s Hospital of Eastern Ontario, University of Ottawa, Canada and colleagues conducted a study to derive and validate a clinical risk score to stratify PPCS risk occurring after acute concussion in youth using readily available clinical features. The study included children and adolescents (age 5-<18 years) who presented within 48 hours of an acute head injury to a pediatric emergency department, with follow-up 28 days after the injury. The primary outcome for the study was PPCS risk score at 28 days, which was defined as 3 or more new or worsening symptoms using the patient-reported Postconcussion Symptom Inventory compared with recalled state of being prior to the injury. The PPCS risk score incorporates 9 clinical variables containing information from demographics, history, initial symptoms, cognitive complaints, and physical examination.

In total, 3,063 patients (median age, 12 years; 39 percent girls) were enrolled (n = 2,006 in the derivation cohort; n = 1,057 in the validation cohort) and 2,584 of whom completed follow-up at 28 days after the injury. Persistent postconcussion symptoms were present in 801 patients (31 percent). The 12-point PPCS risk score model for the derivation cohort included the variables of female sex, age of 13 years or older, physician-diagnosed migraine history, prior concussion with symptoms lasting longer than 1 week, headache, sensitivity to noise, fatigue, answering questions slowly, and 4 or more errors on the Balance Error Scoring System tandem stance.

“Although the clinical utility of the PPCS risk score will need to be assessed in an externally validated implementation study prior to adoption into routine practice, the risk stratification score has the potential to individualize concussion care through optimal symptom management and appropriate follow-up. Therefore, future research needs to determine if the moderate test characteristics of the PPCS risk score allow for clinicians to confidently provide reassurance, alter management plans, or both. Future clinical benefits might include identifying high-risk individuals for further screening, prioritization for specialized concussion evaluations, and initiation of emerging treatments to prevent PPCS,” the authors write.

(doi:10.1001/jama.2016.1203; this study is available pre-embargo at the For The Media website.)

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

Editorial: Identifying Children and Adolescents at Risk for Persistent Postconcussion Symptoms

Lynn Babcock, M.D., M.S., and Brad G. Kurowski, M.D., M.S., of Cincinnati Children’s Hospital Medical Center, write in an accompanying editorial that the clinical risk score developed by Zemek et al, if validated in other settings, may facilitate selection of patients who may be at highest risk of impairments as the optimal target population for much-needed interventional trials.

“Considering the variation in individual symptom profiles and trajectories, personalized patient-oriented approaches to ongoing assessments and delivery of post-injury interventions are needed to facilitate recovery in these vulnerable children and adolescents.”

(doi:10.1001/jama.2016.1276; this editorial is available pre-embargo at the For The Media website.)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 8, 2016

Media Advisory: To contact Ida Behrens, M.D., email idbe@ssi.dk.

To place an electronic embedded link to this study in your story This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1869

Women with a history of hypertensive disorders of pregnancy have a small but statistically significant increased risk of cardiomyopathy more than 5 months after delivery, according to a study appearing in the March 8 issue of JAMA.

Hypertensive disorders of pregnancy (HDP), which include preeclampsia and gestational hypertension, occur in up to 10 percent of pregnancies worldwide. In severe cases, preeclampsia can lead to multiple organ failure, seizures (eclampsia), and fetal and maternal death. Women with preeclampsia have a greatly increased risk of cardiomyopathy in the peripartum period (the last month of pregnancy until 5 months after delivery). Peripartum cardiomyopathy is often characterized by severely reduced myocardial contractility and symptoms of heart failure. Whether hypertensive disorders of pregnancy are also associated with cardiomyopathy later in life has not been known.

Ida Behrens, M.D., of Statens Serum Institut, Copenhagen, Denmark, and colleagues conducted a study that included 1,075,763 women with at least 1 pregnancy ending in live birth or stillbirth in Denmark, 1978-2012. These women had 2,067,633 eligible pregnancies during the study period, 76,108 of which were complicated by a hypertensive disorder of pregnancy (severe or moderate preeclampsia or gestational hypertension). During follow-up, 1,577 women (average age, 48.5 years at cardiomyopathy diagnosis) developed cardiomyopathy.

Compared with women without hypertensive disorders of pregnancy, women with a history of these disorders had significantly increased rates of cardiomyopathy, regardless of HDP severity, and these increases persisted more than 5 years after the latest pregnancy. This increase in risk appeared to be independent of ischemic heart disease, the risk of which is increased among women with a history of preeclampsia, and approximately 50 percent of the risk was not associated with postgestational hypertension. In this cohort, 11 percent of all cardiomyopathy events occurred in women with a history of hypertensive disorders of pregnancy.

The authors note that cardiomyopathy events are rare, even among women in this study with a history of HDP. “Accordingly, even though there was an association between HDP and increased risk of cardiomyopathy, the absolute risk was small.”

“Further research is necessary to understand whether there is a causal mechanism behind this association.”

(doi:10.1001/jama.2016.1869; this study is available pre-embargo at the For The Media website.)

Editor’s Note: This study was funded by the Danish Heart Association and the Danish Council for Independent Research. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 8, 2016

Media Advisory: To contact Sarah R. Blenner, J.D., M.P.H., email Susan O’Brien (sobrien@kentlaw.iit.edu) or Jacqueline Seaberg (jseaberg@kentlaw.iit.edu).

To place an electronic embedded link to this study in your story This link will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2015.19426

In a study appearing in the March 8 issue of JAMA, Sarah R. Blenner, J.D., M.P.H., of the Illinois Institute of Technology Chicago-Kent College of Law, Chicago, and colleagues examined the privacy policies of Android diabetes apps and the sharing of health information.

One-fifth of smartphone owners had health apps in 2012. Health apps can transmit sensitive medical data, including disease status and medication compliance. Privacy risks and the relationship between privacy disclosures and practices of health apps are understudied. For this study, the researchers identified all Android diabetes apps by searching Google Play using the term diabetes, and collected and analyzed privacy policies and permissions. The authors installed a random subset of apps to determine whether data were transmitted to third parties, defined as any website not directly under the developer’s control, such as data aggregators or advertising networks.

Most of the 211 diabetes apps (81 percent) in the study did not have privacy policies. Only 4 policies said they would ask users for permission to share data. In the transmission analysis that included 65 apps, sensitive health information from diabetes apps (e.g., insulin and blood glucose levels) was routinely collected and shared with third parties, with 86 percent of apps placing tracking cookies and 76 percent without privacy policies. Of the 19 apps with privacy policies that shared data with third parties, 11 apps disclosed this fact, whereas 8 apps did not.

“This study demonstrated that diabetes apps shared information with third parties, posing privacy risks because there are no federal legal protections against the sale or disclosure of data from medical apps to third parties. The sharing of sensitive health information by apps is generally not prohibited by the Health Insurance Portability and Accountability Act,” the authors write.

“Patients might mistakenly believe that health information entered into an app is private (particularly if the app has a privacy policy), but that generally is not the case. Medical professionals should consider privacy implications prior to encouraging patients to use health apps.”

(doi:10.1001/jama.2015.19426; this study is available pre-embargo at the For The Media website.)

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: 11 A.M. (ET) TUESDAY, MARCH 1, 2016

Media Advisory: To contact the U.S. Preventive Services Task Force, email the Media Coordinator at Newsroom@USPSTF.net or call 202-572-2044.

To place an electronic embedded link to this study in your story This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.0763

The U.S. Preventive Services Task Force (USPSTF) has concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity (clearness of vision) in adults age 65 years or older. The report appears in the March 1 issue of JAMA.

This is an I statement, indicating that evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. An I statement is not a recommendation against screening but a call for more research.

Impairment of visual acuity is a serious public health problem in older adults. In 2011, about 12 percent of U.S. adults age 65 to 74 years and 15 percent of those 75 years or older reported having problems seeing, even with glasses or contact lenses. The USPSTF reviewed the evidence on screening for visual acuity impairment associated with uncorrected refractive error, cataracts, and age-related macular degeneration (AMD) among adults 65 years or older in the primary care setting who have not reported problems with their vision; the benefits and harms of screening; the accuracy of screening; and the benefits and harms of treatment of early vision impairment due to uncorrected refractive error, cataracts, and AMD. The USPSTF is an independent, volunteer panel of experts that makes recommendations about the effectiveness of specific preventive care services such as screenings, counseling services, and preventive medications.

Detection

The USPSTF found convincing evidence that screening with a visual acuity test can identify persons with a refractive error, and that screening questions are not as accurate as visual acuity testing for assessing visual acuity. The USPSTF found adequate evidence that visual acuity testing alone does not accurately identify early AMD or cataracts.

Benefits of Detection and Early Treatment

The USPSTF found inadequate overall evidence on the benefits of screening, early detection, and treatment to provide a coherent assessment of the overall benefits. Several studies evaluated the direct benefit of screening and reported no reductions in vision disorders or vision-related function in screened populations; however, these studies had limitations, including differing control interventions, high loss to follow-up, and low uptake of treatment. The USPSTF found adequate evidence that early treatment of refractive error, cataracts, and AMD improves or prevents loss of visual acuity.

Harms of Detection and Early Treatment

The USPSTF found inadequate evidence on the harms of screening, and adequate evidence that early treatment of refractive error, cataracts, and AMD may lead to harms that are small to none.

Risk Assessment

Older age is an important risk factor for most types of visual impairment. Additional risk factors for cataracts are smoking, alcohol use, ultraviolet light exposure, diabetes, corticosteroid use, and black race. Risk factors for AMD include smoking, family history, and white race.

Treatment and Interventions

Treatments include corrective lenses for refractive error; surgical removal of cataracts; laser photocoagulation, verteporfin, and intravitreal injections of vascular endothelial growth factor inhibitors for exudative (or wet) AMD; and antioxidant vitamins and minerals for dry AMD.

USPSTF Assessment

The USPSTF concludes that the evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in older adults. The evidence is lacking to provide a coherent assessment, and the balance of benefits and harms cannot be determined.

(doi:10.1001/jama.2016.0763; Available pre-embargo to the media at http:/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.

Note: More information about the U.S. Preventive Services Task Force, its process, and its recommendations can be found on the newsroom page of its website.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 1, 2016

Media Advisory: To contact Ravi M. Patel, M.D., M.Sc., email Melva Robertson at melva.robertson@emory.edu.

To place an electronic embedded link to this study in your story This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.1204

Ravi M. Patel, M.D., M.Sc., of the Emory University School of Medicine & Children’s Healthcare of Atlanta, and colleagues examined whether red blood cell transfusion and severe anemia were associated with the rate of necrotizing enterocolitis (an acute, life-threatening, inflammatory disease occurring in the intestines of premature infants) among very low-birth-weight (VLBW) infants. The study appears in the March 1 issue of JAMA.

Necrotizing enterocolitis (NEC) is a leading cause of mortality among preterm infants with case-fatality rates of 20 percent to 30 percent. The origin and development of NEC remains unclear with conflicting data regarding the role of 2 risk factors, red blood cell (RBC) transfusion and anemia. Improving understanding of the role of RBC transfusion and anemia is important because more than half of VLBW (3.3 lbs. or less) infants receive 1 or more transfusions during hospitalization. This study included VLBW infants enrolled at 3 neonatal intensive care units in Atlanta within 5 days of birth. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death (whichever came first).

Of 600 VLBW infants enrolled, 598 were evaluated. Forty-four (7.4 percent) infants developed NEC. Thirty-two (5.4 percent) infants died (all cause). Fifty-three percent of infants (319) received a total of 1,430 RBC transfusion exposures. Analyses indicated that RBC transfusion was not significantly related to the development of NEC, although the rate of NEC was significantly increased among VLBW infants with severe anemia compared with those who did not have severe anemia.

“Because severe anemia, but not RBC transfusion, was a risk factor for NEC in this study, preventing severe anemia may be more clinically important than minimizing RBC transfusion exposure as a strategy to decrease the risk of NEC. However, the effect of such a strategy on other important neonatal outcomes is unclear, and further study is needed. Ongoing clinical trials comparing liberal vs conservative transfusion practices may provide additional experimental data regarding the risks of both severe anemia and RBC transfusion to NEC,” the authors write.

(doi:10.1001/jama.2016.1204; the study is available pre-embargo at the For The Media website.)

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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