EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 30, 2014
Media Advisory: To contact co-author Kim L. Bennell, Ph.D., email k.bennell@unimelb.edu.au.

Study Finds Acupuncture Does Not Improve Chronic Knee Pain

Among patients older than 50 years with moderate to severe chronic knee pain, neither laser nor needle acupuncture provided greater benefit on pain or function compared to sham laser acupuncture, according to a study in the October 1 issue of JAMA.

Chronic knee pain affects many people older than 50 years and is the most common pain concern among older people consulting family physicians. Nonpharmacological approaches are central to managing chronic knee pain, and patients with joint pain frequently use complementary and alternative medicine. Acupuncture is the most popular of alternative medical systems, with use increasing over time. Although traditionally administered with needles, laser acupuncture (low-intensity laser therapy to acupuncture points) is a noninvasive alternative with evidence of benefit in some pain conditions. There is debate about the benefit of acupuncture for knee pain, according to background information in the article.

Rana S. Hinman, Ph.D., of the University of Melbourne, Australia, and colleagues randomly assigned 282 patients (50 years or older) with chronic knee pain to no acupuncture (control group, n = 71) or needle (n = 70), laser (n = 71), or sham laser (n = 70) acupuncture. Treatments were delivered for 12 weeks. Participants and acupuncturists were blinded to laser and sham (inactive) laser acupuncture.

There were no significant differences in primary outcomes (measures of knee pain and physical function) between active and sham acupuncture at 12 weeks or 1 year. Both needle and laser acupuncture resulted in modest improvements in pain compared with control at 12 weeks that were not maintained at 1 year. Needle acupuncture improved physical function at 12 weeks compared with control but was not different from sham acupuncture and was not maintained at 1 year.

Most secondary outcomes (other pain and function measures, quality of life, global change, and 1-year follow-up) showed no difference. Needle acupuncture improved pain on walking at 12 weeks but was not maintained at 1 year.

The authors note that incidental factors such as treatment setting, patient expectations and attitudes (such as optimism), acupuncturist’s confidence in treatment, and patient and acupuncturist interaction may influence outcomes. “In our study, benefits of acupuncture were exclusively attributed to incidental effects, given the lack of significant differences between active acupuncture and sham treatment. Continuous subjective measures, such as pain and self-reported physical function, as used in our study, are particularly subject to placebo responses.”

“In patients older than 50 years with moderate or severe chronic knee pain, neither laser nor needle acupuncture conferred benefit over sham for pain or function. Our findings do not support acupuncture for these patients.”
(doi:10.1001/jama.2014.12660; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 6 A.M. (CT) MONDAY, SEPTEMBER 22, 2014
Media Advisory: To contact Jonathan A. Patz, M.D., M.P.H., call Kelly Tyrrell at 608-262-9772 or email ktyrrell2@wisc.edu. To contact editorial co-author Howard Bauchner, M.D., email the JAMA Network Media Relations department at mediarelations@jamanetwork.org.

To place an electronic embedded link to this study and editorial in your story This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.13186. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.13094.

Study Examines Potential Adverse Health Effects of Climate Change

An examination of the evidence over the past 20 years indicates that climate change can be associated with adverse effects on various health conditions, including heat-related and respiratory disorders, and a projected increase in days with extreme heat could exacerbate various health issues, according to an article published in JAMA. The study is being released early to coincide with the UN Climate Summit 2014. The authors note that substantial health and economic benefits could be associated with reductions in fossil fuel combustion.

Although uncertainty remains regarding the extent of climate change, this uncertainty is diminishing. Consensus is substantial that human behavior contributes to climate change, caused by activities such as fossil fuel combustion and tropical deforestation. Health is inextricably linked to climate change. It is important for clinicians to understand this relationship in order to discuss associated health risks with their patients and to inform public policy, according to background information in the article.

Jonathan A. Patz, M.D., M.P.H., of the Global Health Institute, University of Wisconsin, Madison, and colleagues conducted a study to provide new U.S.-based temperature projections and to review recent studies on health risks related to climate change and the benefits of efforts to mitigate greenhouse gas emissions. The authors searched the medical literature for articles related to climate change and health, and identified 56 articles that met criteria for inclusion in the analysis. In addition, data were averaged over 13 climate models, and the researchers compared maximum daily 8-hour average ozone with air temperature data taken from the National Oceanic and Atmospheric Administration National Climate Data Center.

Analysis of the data indicated that by 2050, many U.S. cities may experience more frequent extreme heat days. For example, New York and Milwaukee may have 3 times their current average number of days hotter than 90°F, which may exacerbate heat-related disorders, including heat stress and economic consequences of reduced work capacity. In addition, adverse health aspects related to climate change may include:

• Respiratory disorders, including those made worse by fine particular pollutants, such as asthma, and allergic diseases;
• Infectious diseases, including vector-borne diseases (such as transmitted by mosquitos) and water-borne diseases, such as childhood gastrointestinal diseases;
• Food insecurity, including reduced crop yields and an increase in plant diseases;
• Mental health disorders, such as posttraumatic stress disorder and depression, that are associated with natural disasters.

The authors write that substantial health and economic benefits could be associated with reductions in fossil fuel combustion. “Accounting for co-benefits may document that reducing greenhouse emission yields net economic benefits, that labor productivity increases, and that health system costs are reduced. Co-benefits can provide policymakers with additional incentives, beyond those of curtailing climate change, to reduce the emissions of both carbon dioxide and short-lived climate pollutants.”

They add that health professionals have an important role in understanding and communicating potential health concerns related to climate change, as well as the benefits from burning less fossil fuels.

“Because climate change may have important implications for the health of the world’s population, high-quality research must be conducted, and responsible, informed debate needs to continue. However, given that evidence over the past 20 years suggests that climate change can be associated with adverse health outcomes, strategies to reduce climate change and avert the related adverse effects are necessary.”
(doi:10.1001/jama.2014.13186; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Climate Change – A Continuing Threat to the Health of the World’s Population

“Should physicians be concerned about climate change and its associated effects on health or is it outside the remit of medicine much like poverty and war,” write Howard Bauchner, M.D., Editor-in-Chief, JAMA, and Phil B. Fontanarosa, M.D., M.B.A., Executive Editor, JAMA, Chicago, in an accompanying editorial.

“As physicians have come to recognize that many aspects of daily living affect health, such as working conditions, pollution, education, mental health, and psychosocial aspects of disease, medicine has broadened its research, clinical and policy agendas. Many physicians are now involved in addressing these problems. But is climate change similar to poverty and war, best left to other scientists and politicians, or is it of such fundamental importance — like clean water, clean air and adequate sanitation— that physicians should strive to further clarify the effects of climate change on health, educate themselves and the public, and mount a campaign to ensure that climate change does not lead to an epidemic of eroding health?”

“The great gains in well-being in the 20th century occurred because of the concerted effort to improve the health of entire populations. Today, in the early part of the 21st century, it is critical to recognize that climate change poses the same threat to health as the lack of sanitation, clean water, and pollution did in the early 20th century. Understanding and characterizing this threat and educating the medical community, public, and policy makers are crucial if the health of the world’s population is to continue to improve during the latter half of the 21st century.”
(doi:10.1001/jama.2014.13094; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 23, 2014
Media Advisory: To contact corresponding author Eric L. Grogan, M.D., M.P.H., call Craig Boerner at 615-322-4747 or email craig.boerner@vanderbilt.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.2014.11488

Lung Cancer Diagnosis Test May Be Less Effective in Areas Where Infectious Lung Disease is More Common

An analysis of 70 studies finds that use of the diagnostic imaging procedure of fludeoxyglucose F18 (FDG)-positron emission tomography (PET) combined with computed tomography (CT) may not reliably distinguish benign disease from lung cancer in populations with endemic (high prevalence) infectious lung disease compared with nonendemic regions, according to a study in the September 24 issue of JAMA.

Depending on the risk for cancer, diagnostic guidelines suggest or recommend FDG combined with PET as a noninvasive test to assess the risk of cancer or benign disease, according to background information in the article.

Stephen A. Deppen, Ph.D., of the Tennessee Valley Healthcare System and Vanderbilt University Medical Center, Nashville, and colleagues conducted a meta-analysis to examine the accuracy of FDG-PET to diagnose lung lesions in regions with locally endemic infectious lung diseases. The researchers identified 70 studies that met criteria for inclusion in the analysis. Studies reported on a total of 8,511 nodules; 5,105 (60 percent) were malignant.

Pooled sensitivity of FDG-PET for diagnosing lung cancer was 89 percent and pooled specificity was 75 percent. There was a 16 percentage points difference in specificity in regions with endemic infectious lung disease (61 percent) compared with nonendemic regions (77 percent). Lower specificity was observed when the analysis was limited to rigorously conducted and well-controlled studies.

“FDG-PET for the diagnosis of lung cancer in patients who reside in a region with significant endemic infectious lung disease should be recognized as having lower specificity than previously reported. Knowledge of this reduction in specificity should limit the use of FDG-PET to diagnose lung cancer unless substantial institutional expertise in FDG-PET interpretation has been proven. Should low-dose CT screening for lung cancer become the diagnostic standard, knowledge of FDG-PET/CT performance is even more critical because the vast majority of indeterminate lung nodules detected through screening are benign,” the authors write.
(doi:10.1001/jama.2014.11488; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 23, 2014
Media Advisory: To contact Miriam Kuppermann, Ph.D., M.P.H., call Elizabeth Fernandez at 415-514-1592 or email Elizabeth.Fernandez@UCSF.edu. To contact editorial co-author Siobhan M. Dolan, M.D., M.P.H., call Deirdre Branley at 718-430-2923 or email dbranley@einstein.yu.edu.

To place an electronic embedded link to this study and editorial in your story This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.11479. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.12205

Use of Decision-Support Guide for Prenatal Genetic Testing and Removing Costs For Testing Results in Less Prenatal Test Use

An intervention for pregnant women that included a computerized, interactive decision-support guide regarding prenatal genetic testing, and no cost for testing, resulted in less prenatal test use and more informed choices, according to a study in the September 24 issue of JAMA.

Since the introduction of amniocentesis, prenatal genetic testing guidelines have focused on identifying women at increased risk of giving birth to an infant with Down syndrome or other chromosomal abnormalities, for whom invasive diagnostic testing should be recommended. Prenatal genetic testing guidelines recommend providing patients with detailed information to allow informed, preference-based screening and diagnostic testing decisions. The effect of implementing these guidelines is not well understood, according to background information in the article.

Miriam Kuppermann, Ph.D., M.P.H., of the University of California, San Francisco, and colleagues randomly assigned 710 pregnant women to receive either a computerized, interactive decision-support guide and access to prenatal testing with no out-of-pocket expense (n = 357) or usual care as per current guidelines (n = 353). The trial was conducted from 2010-2013 at prenatal clinics and practices from throughout the San Francisco Bay area.

The researchers found that significantly fewer women who were assigned to the intervention group underwent invasive diagnostic testing compared with women randomized to the control group (5.9 percent vs 12.3 percent). The overall prenatal testing strategy used by the 2 groups also differed: women randomized to the intervention group were more likely to have no testing (25.6 percent vs 20.4 percent) or screening alone (68.5 percent vs 67.3 percent).

Also, women assigned to the intervention group had significantly higher genetic testing knowledge scores, were more likely to correctly report both the miscarriage risk of amniocentesis and their likelihood of carrying a fetus with the congenital disorder trisomy 21.

“This study’s finding that women who were randomized to the intervention group were less likely to undergo testing than those who received usual care adds support to the contention that women may not be receiving adequate counseling about their options. This underscores the need for clinicians to be clear that prenatal testing is not appropriate for everyone, and to present forgoing testing as a reasonable choice,” the authors write.

“If validated in additional populations, this approach may result in more informed and preference-based prenatal testing decision making and fewer women undergoing testing.”
(doi:10.1001/jama.2014.11479; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was funded by grants from the National Institutes of Health and the March of Dimes Foundation. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, September 23 at this link.

Editorial: Personalized Genomic Medicine and Prenatal Genetic Testing

In an accompanying editorial, Siobhan M. Dolan, M.D., M.P.H., of the Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, writes that the finding from this study that women with better understanding of the information about various prenatal testing options were less likely to undertake invasive prenatal testing is important, and it contradicts the notion that more information is always desired.

“It is possible that the nature of prenatal testing is different than other health care decisions, but the public may be increasingly aware that the numerous medical advances of the last decade have also created greater complexity in decision making. This finding also suggests that prenatal genetic testing decisions require a complex calculus that considers the timing of the testing, the certainty of the results, and the risks related to undergoing invasive genetic testing during pregnancy.”
(doi:10.1001/jama.2014.12205; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 23, 2014
Media Advisory: To contact Linda S. Geiss, M.A., call Karen Hunter at 404-639-3286 or email ksh7@cdc.gov.

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.2014.11494

Rate of Diabetes in U.S. May Be Leveling Off
Although Increase in Prevalence Continues for Certain Subgroups

Following a doubling of the incidence and prevalence of diabetes in the U.S. from 1990-2008, new data suggest a plateauing of the rate between 2008 and 2012 for adults, however the incidence continued to increase in Hispanic and non-Hispanic black adults, according to a study in the September 24 issue of JAMA.

Although there has been an increase in the prevalence and incidence of diabetes in the United States in recent decades, no studies have systematically examined long-term, national trends of this disease, according to background information in the article.

Linda S. Geiss, M.A., of the Centers for Disease Control and Prevention, Atlanta, and colleagues analyzed 1980-2012 data for 664,969 adults ages 20 to 79 years from the National Health Interview Survey and determined the annual percentage change in rates of the prevalence and incidence of diagnosed diabetes (type 1 and type 2 combined).

During 1980-2012, the trends in age-adjusted prevalence of diagnosed diabetes in the overall population were similar to those for age-adjusted incidence. The prevalence per 100 persons was 3.5 in 1990, 7.9 in 2008, and 8.3 in 2012. The incidence per 1,000 persons was 3.2 in 1990, 8.8 in 2008, and 7.1 in 2012. Both prevalence and incidence increased sharply during 1990-2008 (for prevalence, 4.5 percent, for incidence, 4.7 percent) before leveling off with no significant change during 2008-2012 (for prevalence, 0.6 percent, for incidence, -5-4 percent).

The researchers speculate that reasons for the potential slowing of the increase in diabetes may include a slowing in the rate of obesity, a major risk factor for type 2 diabetes.

Incidence and prevalence of diabetes ceased growing or leveled off in many population subgroups. However, incidence continued to increase in Hispanic and non-Hispanic black adults and prevalence continued to grow among those with a high school education or less. “This threatens to exacerbate racial/ethnic and socioeconomic disparities in diabetes prevalence and incidence. Furthermore, in light of the well-known excess risk of amputation, blindness, end-stage renal disease, disability, mortality, and health care costs associated with diabetes, the doubling of diabetes incidence and prevalence ensures that diabetes will remain a major public health problem that demands effective prevention and management programs,” the authors write.
(doi:10.1001/jama.2014.11494; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 16, 2014
Media Advisory: To contact corresponding author Marc Carrier, M.D., M.Sc., email Paddy Moore at padmoore@ohri.ca or Kina Leclair at kleclair@uOttawa.ca.

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.2014.10538.

Study Compares Effectiveness of Treatments for Blood Clots

In an analysis of the results of nearly 50 randomized trials that examined treatments of venous thromboembolisms (blood clot in a vein), there were no significant differences in clinical and safety outcomes associated with most treatment strategies when compared with the low-molecular-weight heparin-vitamin K antagonist combination, according to a study in the September 17 issue of JAMA.

Venous thromboembolism, manifested as deep vein thrombosis or pulmonary embolism (blood clot in a lung), is a common medical condition and is the third leading cause of cardiovascular death. Clinicians have many potential treatment options regarding management of this condition, although little guidance exists about which treatment is most effective yet safe, according to background information in the study.

Lana A. Castellucci, M.D., of the Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada, and colleagues conducted a network meta-analysis to summarize and compare the efficacy and safety outcomes for the treatment of venous thromboembolism associated with 8 anticoagulation options (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone). The researchers conducted a search of the medical literature and identified 45 randomized trials (44,989 patients) for inclusion in the analyses.

The UFH-vitamin K antagonist combination was associated with a higher percentage of patients experiencing recurrent venous thromboembolism during 3 months of treatment (1.84 percent) than patients taking the LMWH-vitamin K antagonist combination (1.30 percent). Rivaroxaban and apixaban were associated with the lowest bleeding risk compared with the LMWH-vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49 percent for rivaroxaban, 0.28 percent for apixaban, and 0.89 percent for the LMWH-vitamin K antagonist combination.

All other treatment regimens were associated with bleeding risks that did not differ significantly from the LMWH-vitamin K antagonist combination.

“To our knowledge, this network meta-analysis is the largest review, including nearly 45,000 patients, assessing the clinical outcomes and safety associated with different anticoagulation strategies for the treatment of acute venous thromboembolism. We provide estimates on symptomatic recurrent venous thromboembolism and major bleeding outcomes (both patient-important outcomes), which are clinically relevant and are what clinical practice guideline recommendations are based on,” the authors write.

“All management options, with the exception of the UFH-vitamin K antagonist combination, were associated with similar clinical outcomes compared with a management strategy using the LMWH­ vitamin K antagonist combination. Treatment using the UFH-vitamin K antagonist combination was associated with a higher risk of recurrent venous thromboembolism during the follow-up period.”
(doi:10.1001/jama.2014.10538; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 16, 2014
Media Advisory: To contact Lex W. Doyle, M.D., M.Sc., email lwd@unimelb.edu.au.

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.2014.11189

Magnesium Sulfate During Pregnancy Does Not Show Long-Term Benefit on Various Outcomes for Very Preterm Infants

Magnesium sulfate given intravenously to pregnant women at risk of very preterm birth was not associated with benefit on neurological, behavioral, growth, or functional outcomes in their children at school age, according to a study in the September 17 issue of JAMA.

Rates of adverse long-term neurodevelopmental outcomes for infants born at less than 28 weeks’ gestation remain high relative to full-term infants. Among the multiple uses for magnesium sulfate in obstetrics is as a neuroprotectant for preterm fetuses. Antenatal (before birth) magnesium sulfate given to pregnant women at imminent risk of very preterm delivery reduces the risk of cerebral palsy in early childhood, although its effects into school age have not been reported from randomized trials, according to background information in the article.

Lex W. Doyle, M.D., M.Sc., of the University of Melbourne, Australia, and colleagues randomly assigned magnesium sulfate or placebo to pregnant women (n = 535 magnesium; n = 527 placebo) for whom imminent birth was planned or expected before 30 weeks’ gestation. The trial was conducted in 16 centers in Australia and New Zealand.

There were 1,255 fetuses known to be alive at randomization. Of 867 survivors available for follow-up, outcomes at school age (6 to 11 years) were determined for 669 (77 percent). The researchers found that receipt of antenatal magnesium sulfate was not associated with any long-term benefits or harms compared with placebo on measures of neurological, cognitive, behavioral, growth, and functional outcomes. There was a nonsignificant reduction in the risk of death in the magnesium sulfate group.

The authors note that the absence of benefit does not negate the proven value of magnesium sulfate in reducing cerebral palsy, based on the collective evidence from all of the randomized clinical trials.

They add that the lack of long-term benefit requires confirmation in additional studies.
(doi:10.1001/jama.2014.11189; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was funded by a project grant from the National Health and Medical Research Council Australia and the Victorian Government’s Operational Infrastructure Support Program. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 16, 2014
Media Advisory: To contact Andrea S. Gershon, M.D., M.Sc., call Deborah Creatura at 416-480-4780 or email deborah.creatura@ices.on.ca. To contact editorial author Peter M. A. Calverley, M.B.Ch.B., D.Sc., email pmacal@liverpool.ac.uk.

To place an electronic embedded link to this study and editorial in your story This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.11432. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.11322.

Combination Therapy for COPD Associated With Better Outcomes

Among older adults with chronic obstructive pulmonary disease (COPD), particularly those with asthma, newly prescribed long-acting beta-agonists (LABAs) and inhaled corticosteroid combination therapy, compared with newly prescribed LABAs alone, was associated with a lower risk of death or COPD hospitalization, according to a study in the September 17 issue of JAMA.

Chronic obstructive pulmonary disease is the third leading cause of death worldwide. Medications are a mainstay of COPD management, and knowing which are most effective in real-world practice is essential. Combination therapy consisting of LABAs and inhaled corticosteroids (ICSs) has been shown to decrease exacerbations and possibly decrease the risk of death compared with placebo. However, there are still gaps in what is known about its effectiveness compared with LABAs alone, according to background information in the article.

Andrea S. Gershon, M.D., M.Sc., of the Sunnybrook Health Sciences Centre and Institute for Clinical Evaluative Sciences, Toronto, and colleagues examined the outcomes of LABA-ICS combination therapy compared with LABAs alone in older COPD patients with other illnesses, including asthma. The study, which included data from 2003 to 2011 in Ontario, included individuals ages 66 years or older who met a validated case definition of COPD; there were 8,712 new users of LABA-inhaled corticosteroid combination therapy and 3,160 new users of LABAs alone who were followed up for a median of 2.7 years and 2.5 years, respectively.

The primary outcome (the composite of death and COPD hospitalizations) was observed among 2,129 new users of LABAs (1,179 deaths [37.3 percent]); 950 COPD hospitalizations [30.1 percent]) and 5,594 new users of LABAs and ICSs (3,174 deaths [36.4 percent]; 2,420 COPD hospitalizations [27.8 percent]). There was a modest but significantly lower risk of the composite outcome among new users of LABAs and ICSs compared with new users of LABAs alone.

The greatest difference was among COPD patients with a codiagnosis of asthma (difference in composite at 5 years, -6.5 percent) and those who were not receiving inhaled long-acting anticholinergic medication (a different class of COPD medication that works by inhibiting the transmission of certain nerve impulses to help reverse airway resistance; difference in composite at 5 years, -8.4 percent).

“Our finding of an association between LABAs and ICSs and outcomes helps clarify the management of patients with COPD and asthma, as many studies of COPD medications have excluded people with asthma and vice versa,” the authors write. “In addition, practice guidelines for COPD recommend that LABAs be considered first-line treatment while asthma guidelines warn against use of LABAs without ICSs. Our findings also offer insight into the optimal treatment of COPD patients without asthma—those who would not be considered especially corticosteroid responsive.”

The researchers add that these findings should be confirmed in randomized clinical trials.
(doi:10.1001/jama.2014.11432; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Treating COPD in the Real World

Peter M. A. Calverley, M.B.Ch.B., D.Sc., of the University of Liverpool, England, comments on the findings of this study in an accompanying editorial.

“Perhaps the most noteworthy feature of the new data reported by Gershon et al is the difference in the characteristics of the patients who use these treatments from those in whom therapy was validated in randomized clinical trials (RCTs). The outcomes of treatment in these ‘real-world’ patients were somewhat better than might have been expected from RCTs, but the patients were also much more diverse and often sicker. The study by Gershon et al shows that findings from appropriately conducted database analyses complement data from RCTs and should be considered when determining treatment algorithms.”
(doi:10.1001/jama.2014.11322; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 16, 2014
Media Advisory: To contact Earl S. Ford, M.D., M.P.H., call 404-639-3286 or email Brittany Behm at jiz9@cdc.gov.

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.2014.8362.

Waistlines of U.S. Adults Continue to Increase

The prevalence of abdominal obesity and average waist circumference increased among U.S. adults from 1999 to 2012, according to a study in the September 17 issue of JAMA.

Waist circumference is a simple measure of total and intra-abdominal body fat. Although the prevalence of abdominal obesity has increased in the United States through 2008, its trend in recent years has not been known, according to background information in the article.

Earl S. Ford, M.D., M.P.H., of the U.S. Centers for Disease Control and Prevention, Atlanta, and colleagues used data from seven 2-year cycles of the National Health and Nutrition Examination Survey (NHANES) starting with 1999-2000 and concluding with 2011-2012 to determine trends in average waist circumference and prevalence of abdominal obesity among adults in the United States. Abdominal obesity was defined as a waist circumference greater than 40.2 inches (102 cm) in men and greater than 34.6 inches (88 cm) in women.

Data from 32,816 men and nonpregnant women ages 20 years or older were analyzed. The overall age-adjusted average waist circumference increased progressively and significantly, from 37.6 inches in 1999-2000 to 38.8 inches in 2011-2012. Significant increases occurred in men (0.8 inch), women (1.5 inch), non-Hispanic whites (1.2 inch), non­Hispanic blacks (1.6 inch), and Mexican Americans (1.8 inch).

The overall age-adjusted prevalence of abdominal obesity increased significantly from 46.4 percent in 1999-2000 to 54.2 percent in 2011-2012. Significant increases were present in men (37.1 percent to 43.5 percent), women (55.4 percent to 64.7 percent), non-Hispanic whites (45.8 percent to 53.8 percent), non-Hispanic blacks (52.4 percent to 60.9 percent), and Mexican Americans (48.1 percent to 57.4 percent).

The authors write that previous analyses of data from NHANES show that the prevalence of obesity calculated from body mass index (BMI) did not change significantly from 2003-2004 to 2011-2012. “In contrast, our analyses using data from the same surveys indicate that the prevalence of abdominal obesity is still increasing. The reasons for increases in waist circumference in excess of what would be expected from changes in BMI remain speculative, but several factors, including sleep deprivation, endocrine disruptors, and certain medications, have been proposed as potential explanations.”

“Our results support the routine measurement of waist circumference in clinical care consistent with current recommendations as a key step in initiating the prevention, control, and management of obesity among patients.”
(doi:10.1001/jama.2014.8362; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 9, 2014
Media Advisory: To contact corresponding author John P. A. Ioannidis, M.D., D.Sc., email Krista Conger at kristac@stanford.edu. To contact editorial co-author Eric D. Peterson, M.D., M.P.H., call Sarah Avery at 919-660-1306 or email sarah.avery@duke.edu.

To place an electronic embedded link to this study and editorial in your story This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.9646.
This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.9647.

Reanalyses of Data From RCTs Can Lead to Different Conclusions

Although only a small number of reanalyses of data from randomized clinical trials (RCTs) have been published, an examination of those that have been conducted finds that about one-third led to changes in findings that implied conclusions different from those of the original article regarding the types and number of patients who should be treated, according to a study in the September 10 issue of JAMA.

Some authors have argued that a standard of RCT data sharing and reanalysis should be more widely adopted and could have major consequences for individual and public health, and that paying consumers (the public) should have access to complete information about drugs and devices. Arguments against accessibility to raw data and reanalyses include potential risk to trial patient confidentiality; inappropriate use of data sets, resulting in spurious findings; release of commercially sensitive information; and “rogue” reanalysis by nonexperts or by analysts who have conflicts of interest, according to background information in the article.

Shanil Ebrahim, Ph.D., of Stanford University, Stanford, Calif., and colleagues conducted an electronic search of MEDLINE to identify all published studies (through March 9, 2014) that completed a reanalysis of individual patient data from previously published RCTs addressing the same hypothesis as the original RCT. The primary outcomes examined were changes in direction and magnitude of treatment effect, statistical significance, and interpretation about the types or numbers of patients who should be treated.

The researchers identified 37 reanalyses of patient-level data from previously published RCTs (reported in 36 articles). Most of the reanalyses were completed by authors involved in the original trial; five were performed by entirely independent authors. Reanalyses differed most commonly in statistical or analytical approaches (n = 18) and in definitions or measurements of the outcome of interest (n = 12). Four reanalyses changed the direction and two changed the magnitude of treatment effect; four led to changes in statistical significance of findings.

Approximately a third (35 percent) of the reanalyses led to interpretations different from that of the original article, 3 (8 percent) showing that different patients should be treated; 1 (3 percent) that fewer patients should be treated; and 9 (24 percent) that more patients should be treated.

“It is difficult to assess whether these changes in trial conclusions led eventually to major changes in clinical practice and, if so, how large these changes were. Clinical practice choices depend only partly on trial evidence, and sometimes multiple additional trials exist that inform the same question. Nevertheless, when contradicting messages exist, it is unclear which of the 2 discrepant articles will have more influence: the original is usually published in more influential journals, but the subsequent reanalysis may be viewed as a more correct appraisal of the data,” the authors write.
(doi:10.1001/jama.2014.9646; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Open Access to Clinical Trials Data

Harlan M. Krumholz, M.D., S.M., of the Yale University School of Medicine, New Haven, Conn., and Eric D. Peterson, M.D., M.P.H., of the Duke University Medical Center, Durham, N.C., and Associate Editor, JAMA, comment on this study in an accompanying editorial.

“Replication is a vital part of the scientific method. Fields outside of medicine have already embraced sharing experimental data, as have the basic biological sciences within medicine. The culture of clinical research in medicine will need to evolve for open science to succeed. The recognition that one trial can potentially lead to different findings and conclusions depending on many discretionary decisions that are made about the data and reanalyses almost mandates that those choices are transparent and described in detail—and that others have the chance to replicate them. Rather than the rare exception, open science and replication should become the standard for all trials and especially those that have high potential to influence practice.”
(doi:10.1001/jama.2014.9647; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 9, 2014
Media Advisory: To contact corresponding author Barbara A. Hutten, Ph.D., M.Sc., email b.a.hutten@amc.uva.nl.

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.2014.8892.

Long-Term Follow-up Shows Benefit of Statin Therapy for Children With Inherited Cholesterol Disorder

Ten-year follow-up of children who have been taking statin therapy for an inherited cholesterol disorder showed benefit on a measure of atherosclerosis, although levels of low-density lipoprotein suggested that stronger or earlier initiation of statin therapy may be warranted, according to a study in the September 10 issue of JAMA.

Familial hypercholesterolemia (FH) is a prevalent (1:500 individuals) inherited disorder that strongly predisposes to premature atherosclerosis and subsequent cardiovascular disease. In children with FH, atherosclerosis progression is observed before puberty. Consequently, guidelines for FH treatment advocate initiation of statins in children as young as 8 years. However, long­term efficacy and safety data for statin therapy initiated during childhood do not exist, according to background information in the article.

D. Meeike Kusters, M.D., of the Academic Medical Center, Amsterdam, the Netherlands and colleagues followed up a group of children with FH receiving statin therapy until adulthood. The study included 214 children heterozygous (possessing two different forms of a particular gene, one inherited from each parent) for FH, living in the Netherlands, ages 8 to 18 years, who were randomly assigned between 1997 and 1999 into a 2-year, placebo-controlled trial of pravastatin. After the trial, all children received pravastatin and were followed up until March 2011 along with 95 unaffected siblings. After 10 years, all participants underwent a physical examination, fasted blood sample, assessment of family and medical history, including the occurrence of adverse events, and measurement of carotid intima-media thickness (IMT; thickness of a wall of an artery), a validated marker of atherosclerosis.

Ten-year follow-up was achieved in 194 (91 percent) patients with FH and 83 (87 percent) siblings, all ages 18 to 30 years. The researchers found that statin treatment initiated during childhood in patients with FH was associated with normalization of carotid IMT progression. Moreover, earlier statin initiation was associated with thinner carotid IMT at follow-up. No serious adverse events were reported during follow-up.

The low-density lipoprotein levels of patients with FH at follow-up did not meet current treatment standards and carotid IMT was thicker than in unaffected siblings.

“More robust lipid-lowering therapy or earlier initiation of statins may be required to completely restore arterial wall morphology and avert cardiovascular events later in life in this high-risk population,” the authors write.
(doi:10.1001/jama.2014.8892; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 9, 2014
Media Advisory: To contact Barbara P. Yawn, M.D., M.Sc., M.S.P.H., call 507-287-2758 or email byawn@olmmed.org. To contact editorial author Michael R. DeBaun, M.D., M.P.H., call Craig Boerner at 615-322-4747 or email craig.boerner@vanderbilt.edu.

To place an electronic embedded link to this study and editorial in your story This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.10517. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.11103.

New Guideline Created for Managing Sickle Cell Disease

An expert panel has created a new evidence-based guideline for managing sickle cell disease (SCD), with a strong recommendation for the use of the drug hydroxyurea and transfusion therapy for many individuals with SCD, although high-quality evidence is limited, with few randomized clinical trials conducted for this disease, according to an article in the September 10 issue of JAMA.

Sickle cell disease is a life-threatening genetic disorder affecting nearly 100,000 individuals in the United States; most of those affected are of African ancestry or self-identify as black. This disease is associated with many acute and chronic complications requiring immediate medical attention. Care for persons with SCD often lacks continuity. Primary care and emergency care health professionals need up-to-date clinical guidance regarding care of persons with this disease, according to background information in the article.

In 2009, the National Heart, Lung, and Blood Institute convened an expert panel that developed the Evidence-Based Management of Sickle Cell Disease: Expert Panel Report 2014. Barbara P. Yawn, M.D., M.Sc., M.S.P.H., of the Olmsted Medical Center, Rochester, Minn., and colleagues produced a summary of this report and conducted a search of the medical literature to examine the strength of the quality of evidence for the recommendations.

Among the Strong Recommendations

• For prevention: daily oral prophylactic penicillin up to the age of 5 years, annual transcranial Doppler examinations from the ages of 2 to 16 years in those with sickle cell anemia, and long-term transfusion therapy to prevent stroke in those children with abnormal transcranial Doppler velocity (elevated speed of blood flow in the cerebral arteries).

• To address acute complications: rapid initiation of opioids for treatment of severe pain associated with a vasoocclusive crisis (blockage of blood flow due to the abnormal “sickled” red blood cells getting stuck in the blood vessels) and use of incentive spirometry (a method of encouraging deep breathing with the use of an instrument to provide feedback) in patients hospitalized for a vasoocclusive crisis.

• For chronic complications: use of analgesics and physical therapy for treatment of avascular necrosis (a condition in which poor blood supply to an area of bone leads to bone death) and use of angiotensin-converting enzyme inhibitor therapy for microalbuminuria (a subtle increase in the urinary excretion of the protein albumin that cannot be detected by a conventional urinalysis) in adults with SCD.

• For children and adults with proliferative sickle cell retinopathy: referral to expert specialists for consideration of laser photocoagulation and for echocardiography to evaluate signs of pulmonary hypertension.

• Hydroxyurea therapy is strongly recommended for adults with 3 or more severe vasoocclusive crises during any 12-month period, with SCD pain or chronic anemia interfering with daily activities, or with severe or recurrent episodes of acute chest syndrome (an SCD syndrome associated with one or more symptoms that may include fever, cough, sputum production or difficulty breathing.

A recommendation of moderate strength suggests offering treatment with hydroxyurea without regard to the presence of symptoms for infants, children, and adolescents.

The authors note that some of the strong recommendations appearing in this guideline are supported by low- or very low-quality evidence, and that evidence is lacking in many areas important to care for individuals with SCD.

“The process of developing guidelines for the management of children, adolescents, and adults with SCD has been challenging because high-quality evidence is limited in virtually every area related to SCD management. The systematic review of the literature identified a very small number of randomized clinical trials in individuals with SCD, demonstrating the extensive knowledge gaps in SCD and care of affected individuals. The expert panel realizes that this summary report and the guidelines leave many uncertainties for health professionals caring for individuals with SCD and highlight the importance of collaboration between primary care health professionals and SCD experts. However, we hope that this summary report and the SCD guideline begins to facilitate improved and more accessible care for all affected individuals, and that the discrepancies in the existing data will trigger new research programs and processes to facilitate future guidelines,” the authors conclude.
(doi:10.1001/jama.2014.10517; Available pre-embargo to the media at https://media.jamanetwork.com)

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

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, September 9 at this link.

Editorial: The Challenge of Creating an Evidence-Based Guideline for Sickle Cell Disease

Michael R. DeBaun, M.D., M.P.H., of the Vanderbilt University School of Medicine, Nashville, Tenn., comments on this guideline in an accompanying editorial.

“Yawn and colleagues have undertaken a monumental effort to produce a practical, evidence-based guideline for SCD. Many aspects of this guideline will help both individuals with the disease and clinicians. As would be expected, when the guideline is based on recommendations from randomized clinical trials, such as penicillin prophylaxis, transcranial Doppler screening, blood transfusion therapy prior to surgery, or hydroxyurea therapy for severe disease, these strong recommendations will be embraced by the SCD community. However, when recommendations are based on consensus panel expertise, practice variation will justifiably continue.”
(doi:10.1001/jama.2014.11103; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 2, 2014
Media Advisory: To contact corresponding author Charles J. Billington, M.D., call Matt DePoint at 612-625-4110 or email mdepoint@umn.edu. To contact editorial co-author David E. Arterburn, M.D., M.P.H., call Rebecca Hughes at 206-287-2055 or email hughes.r@ghc.org.

To place an electronic embedded link to this study and editorial in your story This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.10540. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.10940.

Researchers Examine Effectiveness of Blocking Nerve to Help With Weight Loss

Among patients with morbid obesity, blocking the vagus nerve, which plays a role with appetite and metabolism, did not meet pre-specified efficacy objectives compared to a control group, although the intervention did result in greater weight loss, according to a study in the September 3 issue of JAMA.

Bariatric surgery can produce significant weight loss and improvement in health but is associated with several potential adverse effects. There is interest in the development of a device that could be as effective or nearly as effective as bariatric surgery but has fewer risks and is less invasive. One such possibility is blockade of the vagus nerve using electrodes implanted through minimally invasive laparoscopic surgery, according to background information in the article.

Sayeed Ikramuddin, M.D., of the University of Minnesota, Minneapolis, and colleagues randomly assigned 239 participants who had a body mass index of 40 to 45 or 35 to 40 and 1 or more obesity-related condition to receive an implanted active vagal nerve block device (n = 162) or an implanted sham (inactive) device (n = 77). All participants received weight management education. The study was conducted at 10 sites in the United States and Australia between May and December 2011.

At 12 months in the intent-to-treat population, the average percentages of excess weight loss was 24.4 percent (9.2 percent of their initial body weight loss) in the vagal nerve block group and 15.9 percent (6.0 percent initial body weight loss) in the sham group, with an average difference of 8.5 percentage points, which did not meet the primary efficacy objective of achieving superiority with a 10 percentage-point margin. Weight loss was statistically greater in the vagal nerve block group.

At 12 months, 52 percent of participants in the vagal nerve block group achieved at least 20 percent; and 38 percent, at least 25 percent of excess weight loss, which did not meet the primary efficacy objective performance goals of at least 55 percent of participants achieving a 20 percent excess weight loss and 45 percent achieving a 25 percent excess weight loss.

The device, procedure, or therapy-related serious adverse event rate in the vagal nerve block group was 3.7 percent, significantly lower than the 15 percent primary safety objective goal. The adverse events more frequent in the vagal nerve block group were heartburn, indigestion and abdominal pain attributed to therapy; all were reported as mild or moderate in severity.

“Additional studies are needed to compare effectiveness of vagal nerve block with other obesity treatments and to assess long­term durability of weight loss and safety,” the authors conclude.
(doi:10.1001/jama.2014.10540; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: The Current State of the Evidence for Bariatric Surgery

David E. Arterburn, M.D., M.P.H., of the Group Health Research Institute, Seattle, and David P. Fisher, M.D., of the Permanente Medical Group, Richmond, Calif., write in an accompanying editorial that several conclusions can be drawn from this study.

“First, vagal nerve blockade plus moderately intensive lifestyle counseling does not appear to be much more effective than an intensive lifestyle program. Second, based on comparisons with other studies, procedures for adjustable gastric banding, which reported a 50 percent excess weight loss; Roux-en-Y gastric bypass, a 68 percent excess weight loss; and vertical sleeve gastrectomy, a 65 percent excess weight loss, are clearly more effective for initial weight loss than vagal nerve blockade. Third, the rate of serious adverse events with vagal nerve blockade (8.6 percent) is clinically important. Fourth, the long-term rates of weight regain and reoperation with vagal nerve blockade are currently unknown. Fifth, the report by Ikramuddin et al does not include a discussion of how vagal nerve blockade compares with other obesity treatments in terms of costs. Although vagal nerve blockade therapy is an innovative approach, it does not appear to be a sustained, effective treatment for severe obesity.”
(doi:10.1001/jama.2014.10940; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 2, 2014
Media Advisory: To contact Bradley N. Reames, M.D., M.S., call Nicole Fawcett at 734-764-2220 or email nfawcett@umich.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.2014.7651.

Study Finds Change in Type of Procedure Most Commonly Used for Bariatric Surgery

In an analysis of the type of bariatric surgery procedures used in Michigan in recent years, sleeve gastrectomy (SG) surpassed Roux-en-Y gastric bypass (RYGB) in 2012 as the most common procedure performed for patients seeking this type of surgery, and SG became the predominant bariatric surgery procedure for patients with type 2 diabetes, according to a study in the September 3 issue of JAMA.

Bariatric surgery is the most effective therapy available for significant and sustainable weight loss in patients with morbid obesity, and its use has increased during the last decade. Changes in procedure use over time reflect emerging evidence regarding the comparative safety and effectiveness of available procedures. An understanding of current trends in bariatric procedure use can inform primary care physicians counseling patients with morbid obesity who are considering surgical intervention, according to background information in the article.

Bradley N. Reames, M.D., M.S., of the University of Michigan, Ann Arbor, and colleagues analyzed data on 43,732 adults who underwent primary inpatient and outpatient bariatric surgery within the 39-hospital Michigan Bariatric Surgery Collaborative between June 2006 and December 2013.

The researchers found that relative use of SG increased from 6.0 percent of all procedures in 2008 to 67.3 percent of all procedures in 2013, an increase of 61 percent. During the same period, use of RYGB decreased from 58.0 percent to 27.4 percent, and use of laparoscopic adjustable gastric banding decreased from 34.5 percent to 4.6 percent.

Even though SG was the most common procedure across all subgroups in 2012 and 2013, SG rates were relatively lower in patients 65 years or older, in patients with gastroesophageal reflux disease, and in patients with type 2 diabetes.

“Although long-term outcomes of SG are still unclear, these changes may reflect the favorable perioperative safety profile and emerging evidence of successful weight loss at 2 to 3 years after SG. These findings are important to inform primary care physicians of the predominant bariatric procedure currently used, regardless of pre-existing comorbidity, and may assist in the preoperative counseling of patients considering surgical therapy for morbid obesity,” the authors write.
(doi:10.1001/jama.2014.7651; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Dr. Reames is supported by a grant from the National Cancer Institute. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 2, 2014
Media Advisory: To contact corresponding author Scarlett L. Gomez, Ph.D., call Jana Cuiper at 510-608-5160 or email Jana.Cuiper@cpic.org. To contact editorial author Lisa A. Newman, M.D., M.P.H., call Nicole Fawcett at 734-764-2220 or email nfawcett@umich.edu.

To place an electronic embedded link to this study and editorial in your story This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.10707. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.11308.

Increase Seen in Use of Double Mastectomy, Although Procedure Not Associated With Reducing Risk of Death

Among women diagnosed with early-stage breast cancer in California, the percentage undergoing a double mastectomy increased substantially between 1998 and 2011, although this procedure was not associated with a lower risk of death than breast-conserving surgery plus radiation, according to a study in the September 3 issue of JAMA. The authors did find that surgery for the removal of one breast was associated with a higher risk of death than the other options examined in the study.

Randomized trials have demonstrated similar survival for patients with early-stage breast cancer treated with breast-conserving surgery and radiation or with mastectomy. However, previous data show increasing use of mastectomy, and particularly bilateral mastectomy (removal of both breasts) among U.S. patients with breast cancer. Evidence for a survival benefit with this procedure appears limited to rare patient subgroups. “Because bilateral mastectomy is an elective procedure for unilateral breast cancer [in one breast] and may have detrimental effects in terms of complications and associated costs as well as body image and sexual function, a better understanding of its use and outcomes is crucial to improving cancer care,” according to background information in the article.

Allison W. Kurian, M.D., M.Sc., of the Stanford University School of Medicine, Stanford, Calif., and colleagues used data from the California Cancer Registry from 1998 through 2011 to compare the use of and rate of death after bilateral mastectomy, breast-conserving therapy with radiation, and unilateral mastectomy (removal of one breast).

The analyses included 189,734 patients. The researchers found that the rate of bilateral mastectomy increased from 2.0 percent in 1998 to 12.3 percent in 2011, an annual increase of 14.3 percent. The increase in bilateral mastectomy rate was greatest among women younger than 40 years: the rate increased from 3.6 percent in 1998 to 33.0 percent in 2011, increasing by 17.6 percent annually. Use of unilateral mastectomy declined in all age groups

Bilateral mastectomy was more often used by non-Hispanic white women, those with private insurance, and those who received care at a National Cancer Institute-designated cancer center; in contrast, unilateral mastectomy was more often used by racial/ethnic minorities and those with public/Medicaid insurance.

Compared with breast-conserving surgery with radiation, bilateral mastectomy was not associated with a mortality difference, whereas unilateral mastectomy was associated with higher mortality.

“In a time of increasing concern about overtreatment, the risk-benefit ratio of bilateral mastectomy warrants careful consideration and raises the larger question of how physicians and society should respond to a patient’s preference for a morbid, costly intervention of dubious effectiveness,” the authors write.

“These results may inform decision-making about the surgical treatment of breast cancer.”

(doi:10.1001/jama.2014.10707; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Contralateral Prophylactic Mastectomy
Is It a Reasonable Option?

In an accompanying editorial, Lisa A. Newman, M.D., M.P.H., of the University of Michigan, Ann Arbor, discusses the issues involved with the use of contralateral prophylactic mastectomy (risk-reducing mastectomy for the unaffected breast).

“The need for patients to be accurately informed regarding safe and oncologically acceptable treatment options is indisputable. The dense fog of complex emotions that accompanies a new cancer diagnosis can impair the ability to process this information. Patients should be encouraged to allow the intensity of these immediate reactions to subside before committing to mastectomy prematurely. Physicians should not permit excessive treatment delays to compromise outcomes, but the initial few weeks surrounding the diagnosis are more effectively utilized by time invested in patient education and procedures that contribute to comprehensive treatment planning as opposed to hastily coordinating impulsive, irreversible surgical plans.”
(doi:10.1001/jama.2014.11308; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 2, 2014
Media Advisory: To contact Bradley C. Johnston, Ph.D., email Veronica McGuire at vmcguir@mcmaster.ca. To contact editorial author Linda Van Horn, Ph.D., R.D., call Marla Paul at 312-503-8928 or email marla-paul@northwestern.edu.

To place an electronic embedded link to this study and editorial in your story This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.10397. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.10837.

Comparison of Named Diet Programs Finds Little Difference in Weight Loss Outcomes

In an analysis of data from nearly 50 trials including about 7,300 individuals, significant weight loss was observed with any low-carbohydrate or low-fat diet, with weight loss differences between diet programs small, findings that support the practice of recommending any diet that a patient will adhere to in order to lose weight, according to a study in the September 3 issue of JAMA.

Named or branded (trade-marked) weight loss programs provide structured dietary and lifestyle recommendations via popular books and in-person or online behavioral support and represent a multibillion dollar industry. Debate regarding the relative merit of the diets is accompanied by advertising claiming which macronutrient composition is superior, such as a low-carbohydrate or low-fat diet. Establishing which of the major named diets is most effective is important because overweight patients often want to know which diet results in the most effective weight loss, according to background information in the article.

Bradley C. Johnston, Ph.D., of the Hospital for Sick Children Research Institute, Toronto, and McMaster University, Hamilton, Ontario, and colleagues conducted a meta-analysis to assess the relative effectiveness of different popular diets in improving weight loss. The researchers conducted a search of the medical literature to identify studies in which overweight or obese adults (body mass index 25 or greater) were randomized to a popular self-administered named diet and reported weight or body mass index data at 3-month follow-up or longer.

The meta-analysis included 59 articles that reported 48 randomized clinical trials (7,286 individuals; median age, 46 years; median weight, 207.5 lbs.). In the diet-class analysis adjusted for exercise and behavioral support, all treatments were superior to no diet at 6-month follow-up. Compared with no diet, low-carbohydrate diets had a median difference in weight loss of 19.2 lbs. and low-fat diets had similar estimated effects (17.6 lbs.).

At 12-month follow-up, the estimated average weight losses of all diet classes compared with no diet were approximately 2.2 to 4.4 lbs. less than after 6-month follow-up. The diet classes of low fat (16 lbs.) and low carbohydrate (16 lbs.) continued to have the largest estimated treatment effects.

Weight loss differences between individual diets were minimal. For example, the Atkins diet resulted in a 3.8 lbs. greater weight loss than the Zone diet at 6-month follow-up. “Although statistical differences existed among several of the diets, the differences were small and unlikely to be important to those seeking weight loss,” the authors write.

“Our findings should be reassuring to clinicians and the public that there is no need for a one-size-fits­all approach to dieting because many different diets appear to offer considerable weight loss benefits. This is important because many patients have difficulties adhering to strict diets that may be particularly associated with cravings or be culturally challenging (such as low-carbohydrate diets). Our findings suggest that patients may choose, among those associated with the largest weight loss, the diet that gives them the least challenges with adherence. Although our study did not examine switching between diets, such a strategy may offer patients greater choices as they attempt to adhere to diet and lifestyle changes.”
(doi:10.1001/jama.2014.10397; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: A Diet by Any Other Name Is Still About Energy

Linda Van Horn, Ph.D., R.D., of the Northwestern University Feinberg School of Medicine, Chicago, comments on the findings of this study in an accompanying editorial.

“Overall, the findings from the study by Johnston et al, along with other recent data, underscore the importance of effective diet and lifestyle interventions that promote behavioral changes to support adherence to a calorie-restricted, nutrient-dense diet that ultimately accomplishes weight loss. Choosing the best diet suited to an individual’s food preferences may help foster adherence, but beyond weight loss, diet quality including micronutrient composition may further benefit longevity.”
(doi:10.1001/jama.2014.10837; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 2 A.M. (CT) SUNDAY, AUGUST 31, 2014
Media Advisory: To contact Michelle L. O’Donoghue, M.D., M.P.H., call Jessica Maki at 617-525-6373 or email jmaki3@partners.org.

Inhibiting Inflammatory Enzyme After Heart Attack Does Not Reduce Risk of Subsequent Event

In patients who experienced an acute coronary syndrome (ACS) event (such as heart attack or unstable angina), use of the drug darapladib to inhibit the enzyme lipoprotein-associated phospholipase A2 (believed to play a role in the development of atherosclerosis) did not reduce the risk of recurrent major coronary events, according to a study published by JAMA. The study is being released early online to coincide with its presentation at the European Society of Cardiology Congress.

A number of epidemiologic studies have shown that higher circulating levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity or mass are associated with an increased risk of coronary events. Darapladib is a Lp-PLA2 inhibitor that reduces Lp-PLA2 activity in plasma and in atherosclerotic plaques, according to background information in the article.

Michelle L. O’Donoghue, M.D., M.P.H., of Brigham and Women’s Hospital, Boston, and colleagues randomly assigned 13,026 participants within 30 days of hospitalization with an ACS to either once-daily darapladib or placebo along with guideline-recommended therapy. The study was conducted at 868 sites in 36 countries.

Patients were followed up for a median of 2.5 years. At the end of follow-up, the primary end point of the study, major coronary events (composite of coronary heart disease death, heart attack, or urgent coronary revascularization for myocardial ischemia) had occurred in 903 of 6,504 participants in the darapladib group and 910 of 6,522 participants in the placebo group (16.3 percent vs 15.6 percent at 3 years). Cardiovascular death, heart attack, or stroke occurred in 824 darapladib-assigned participants and 838 placebo¬treated patients (15.0 percent vs 15.0 percent at 3 years). There were no significant differences between treatment groups in the incidence and number of events for the individual components of the primary end point.

The rate of all-cause mortality at 3 years was similar between the groups (darapladib, 7.3 percent; placebo, 7.1 percent).

The incidence of any serious adverse event was similar between treatment groups.

The authors conclude that their findings “do not support a strategy of targeted Lp-PLA2 inhibition with darapladib in patients stabilized after an ACS event who are similar to those enrolled into this trial.”
(doi:10.1001/jama.2014.11061; Available pre-embargo to the media at https://media.jamanetwork.com)

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 EARLY RELEASE: 6 A.M. (CT) SATURDAY, AUGUST 30, 2014
Media Advisory: To contact Massimo Imazio, M.D., email massimo_imazio@yahoo.it.

Medication Shows Mixed Results in Reducing Complications From Cardiac Surgery

Administration of colchicine, a plant-based medication commonly used to treat gout, before and after cardiac surgery showed mixed results in reducing potential complications from this type of surgery, but it did increase the risk of gastrointestinal adverse effects, according to a study published by JAMA. The study is being released early online to coincide with its presentation at the European Society of Cardiology Congress.

Common complications after cardiac surgery include postpericardiotomy syndrome (the occurrence of the symptoms of pericarditis, including chest pain), postoperative atrial fibrillation (AF), and postoperative pericardial/pleural effusions (excess fluid around the heart and lungs), affecting more than one-third of patients. These complications may lead to prolonged hospital stay, readmissions, and need for invasive interventions. Postoperative use of colchicine helped prevent these complications in a single trial, according to background information in the article.

Massimo Imazio, M.D., of Maria Vittoria Hospital, Torino, Italy, and colleagues randomly assigned 360 cardiac surgery patients from 11 centers in Italy to receive placebo (n=180) or colchicine (n=l80) starting between 48 and 72 hours before surgery and continued for 1 month after surgery.

The primary measured outcome for the study, postpericardiotomy syndrome within 3 months, occurred in 35 patients (19.4 percent) assigned to colchicine and in 53 (29.4 percent) assigned to placebo. There were no significant differences between the colchicine and placebo groups for postoperative AF (colchicine, 33.9 percent; placebo, 41.7 percent) or postoperative pericardial/pleural effusion (colchicine, 57.2 percent; placebo, 58.9 percent).

Adverse event rates occurred in 21 patients (11.7 percent) in the placebo group and 36 (20.0 percent) in the colchicine group, primarily because of an increased incidence of gastrointestinal intolerance (6.7 percent in the placebo group; 14.4 percent in the colchicine group). Discontinuation rates were similar in both groups.

“In this multicenter trial, perioperative administration of colchicine significantly reduced the incidence of postpericardiotomy syndrome after cardiac surgery but did not reduce the risk of postoperative AF and postoperative pericardial/pleural effusions by intention-to-treat analysis,” the authors write. “About 20 percent of all patients enrolled in the trial discontinued study drug; this relatively high rate may have affected the overall efficacy of the drug, especially for postoperative AF prevention.”

“The high rate of adverse effects is a reason for concern and suggests that colchicine should be considered only in well­selected patients.”
(doi:10.1001/jama.2014.11026; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 26, 2014
Media Advisory: To contact Jacob A. Udell, M.D., M.P.H., call Heidi Singer at 416-978-5811 or email Heidi.Singer@utoronto.ca.

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.2014.6217.

Study Questions Generalizability of Findings of Cardiovascular Trials for Heart Attack Patients

An analysis of a cardiovascular registry finds that of clinical trials that included heart attack patients, participation among eligible patients was infrequent and has been declining, and trial participants had a lower risk profile and a more favorable prognosis compared with the broader population of patients who have had a heart attack, according to a study in the August 27 issue of JAMA.

Jacob A. Udell, M.D., M.P.H., of the University of Toronto, and colleagues evaluated whether participants in cardiovascular trials are representative of contemporary patients with myocardial infarction (MI; heart attack). The researchers used data from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines, an ongoing, voluntary, quality improvement registry of patients with MI treated at participating centers across the United States.

Among 141,135 registry participants at 466 centers, 4,008 (2.8 percent) were trial participants; among the 137,127 nonparticipants, 93,274 were eligible (68.0 percent) and 43,853 were ineligible (32.0 percent). Overall, 255 sites (54.7 percent) enrolled at least 1 patient; and trial participation (as a proportion of eligible patients) declined each year during the study period (2008: 5.2 percent; 2009: 4.4 percent; 2010: 3.8 percent; and 2011: 3.4 percent). Trial participants were younger, with less previous cardiovascular disease, lower predicted risk of mortality, shorter hospital stays, and more frequent treatment with evidence­based therapy than nonparticipants.

Common reasons for trial ineligibility included uncontrolled hypertension, elevated INR (abnormal clotting), severe anemia, and cardiogenic shock. In-hospital mortality was lowest for trial participants, intermediate among eligible nonparticipants, and highest among ineligible patients.

“Efforts to improve trial participation are needed to enhance generalizability of results,” the authors write.
(doi:10.1001/jama.2014.6217; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 26, 2014
Media Advisory: To contact corresponding author Petra Susan Huppi, M.D., email petra.huppi@hcuge.ch.

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.2014.9645.

EPO May Help Reduce Risk of Brain Abnormalities in Preterm Infants

High-dose erythropoietin (EPO; a hormone) administered within 42 hours of birth to preterm infants was associated with a reduced risk of brain injury, as indicated by magnetic resonance imaging, according to a study in the August 27 issue of JAMA.

Survival of premature infants has improved over the past decades, but at the expense of an increase in the number of infants affected by long-term developmental disabilities. Premature infants are at risk of developing encephalopathy of prematurity, which includes structural changes of brain white and gray matter and is associated with long-term neurodevelopmental delay. Erythropoietin has shown beneficial effects on neurodevelopmental outcomes in observational and retrospective studies, according to background information in the article.

Russia Ha-Vinh Leuchter, M.D., of the University Hospital of Geneva, Switzerland, and colleagues conducted a study in which 495 infants (born from 26 weeks to 31 weeks and 6 days of gestation) were randomly assigned to receive recombinant human erythropoietin (n=256) or placebo (n=239) intravenously before 3 hours, at 12 to18 hours, and at 36 to 42 hours after birth. In a nonrandomized subset of 165 of the 495 infants (n=77 erythropoietin; n=88 placebo), brain abnormalities were evaluated on magnetic resonance imaging (MRI) acquired at term-equivalent age.

The researchers found that at term-equivalent age, compared with untreated controls, fewer infants treated with recombinant human erythropoietin had abnormal scores for white matter injury (22 percent vs 36 percent); white matter signal intensity (3 percent vs 11 percent); periventricular white matter loss (18 percent vs 33 percent); and gray matter injury (7 percent vs 19 percent).

“These findings require assessment in a randomized trial designed primarily to assess this outcome, as well as investigation of the association with neurodevelopmental outcomes,” the authors conclude.
(doi:10.1001/jama.2014.9645; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 26, 2014
Media Advisory: To contact Laura P. Richardson, M.D., M.P.H., email Rose Ibarra at rose.ibarra@seattlechildrens.org. To contact editorial co-author Mark A. Riddle, M.D., email Ekaterina Pesheva at epeshev1@jhmi.edu.

To place an electronic embedded link to this study and editorial in your story This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.9259. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.9258.

Collaborative Care Intervention Improves Depression Among Teens

Among adolescents with depression seen in primary care, a collaborative care intervention that included patient and parent engagement and education resulted in greater improvement in depressive symptoms at 12 months than usual care, according to a study in the August 27 issue of JAMA.

Depressed youth are at greater risk of suicide, substance abuse, early pregnancy, low educational attainment, recurrent depression and poor long-term health. Fourteen percent of adolescents between the ages of 13-18 years have major depression yet few receive evidence-based treatments for their depression. The failure to accurately diagnose and treat adolescents and an inadequate supply of child mental health specialists have led to increasing focus on improving the quality of depression treatment in pediatric primary care, according to background information in the article.

Laura P. Richardson, M.D., M.P.H., of Seattle Children’s Research Institute and the University of Washington School of Medicine, Seattle, and colleagues randomly assigned 101 adolescents (ages 13-17 years) at Group Health Cooperative who had screened positive for depression to a 12-month collaborative care intervention or usual care. The intervention included an education and engagement session, during which perspectives on symptoms were elicited, depression education was provided, and active treatment participation of adolescents and parents was encouraged. During the session, a depression care manager helped the youth and parent choose and initiate treatment with antidepressant medication, brief cognitive behavioral therapy, or both. The intervention youth then received ongoing follow-up with care provided in the primary care clinic. In the usual care group, youth received depression screening results and could access mental health services through Group Health.

Intervention youth (n = 50), compared with those who received usual care (n = 51), had greater decreases in depressive symptoms by 12 months. Sixty-eight percent of intervention youth had a 50 percent or greater reduction in depressive symptoms compared to 39 percent among control youth. The overall rate of depression remission at 12 months was 50.4 percent for intervention youth and 20.7 percent for control youth.

These findings suggest that mental health services for adolescents with depression can be effectively integrated into primary care, the authors conclude.
(doi:10.1001/jama.2014.9259; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: A Practical and Effective Primary Care Intervention for Treating Adolescent Depression

Gloria M. Reeves, M.D., of the University of Maryland School of Medicine, Baltimore, and Mark A. Riddle, M.D., of the Johns Hopkins University School of Medicine, Baltimore, comment on this study in an accompanying editorial.

“Pediatric primary care clinicians have substantial potential to improve identification and treatment of adolescent depression. This study suggests that collaborative care treatment of adolescent depression can be structured to promote care that is evidence­based, personalized, and effective. Further research on this type of model has tremendous potential to benefit both families and clinicians.”
(doi:10.1001/jama.2014.9258; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Riddle receives salary support from the Center for Mental Health Services in Pediatric Primary Care. No other disclosures were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 26, 2014
Media Advisory: To contact Richard J. McManus, F.R.C.G.P., email richard.mcmanus@phc.ox.ac.uk. To contact editorial co-author Peter M. Nilsson, M.D., Ph.D., email Peter.Nilsson@med.lu.se.

To place an electronic embedded link to this study and editorial in your story This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.10057. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.10058.

Hypertension Self-Management Program Helps Reduce Blood Pressure For High-Risk Patients

Among patients with hypertension at high risk of cardiovascular disease, a program that consisted of patients measuring their blood pressure and adjusting their antihypertensive medication accordingly resulted in lower systolic blood pressure at 12 months compared to patients who received usual care, according to a study in the August 27 issue of JAMA.

Data from national and international surveys suggest that despite improvements over the last decade, significant proportions of patients have poor control of their elevated blood pressure. Self-monitoring of blood pressure with self-titration (adjusting) of antihypertensives results in lower blood pressure in patients with hypertension, but there are no data about patients in high-risk groups, according to background information in the article.

Richard J. McManus, F.R.C.G.P., of the University of Oxford, and colleagues randomly assigned 552 patients with hypertension and a history of stroke, coronary heart disease, diabetes, or chronic kidney disease to self-monitoring of blood pressure combined with an individualized self-titration algorithm or a control group (patients received usual care consisting of seeing their health care clinician for routine blood pressure measurement and adjustment of medication if necessary).

After 12 months, the average systolic blood pressure decreased in both groups, but was lower in the intervention group (128.2/73.8 mm Hg vs 137.8/76.3 mm Hg). Imputation for missing values showed a marginally lower average difference in systolic blood pressure of 8.8 mm Hg. The reduction in diastolic blood pressure was also greater in the self-monitoring group. The results were comparable in all subgroups, without excessive adverse events.

“This trial has shown for the first time, to our knowledge, that a group of high-risk individuals, with hypertension and significant cardiovascular comorbidity, are able to self-monitor and self-titrate antihypertensive treatment following a pre­specified algorithm developed with their family physician and that in doing so, they achieved a clinically significant reduction in systolic and diastolic blood pressure without an increase in adverse events,” the authors write. “This is a population with the most to gain in terms of reducing future cardiovascular events from optimized blood pressure control.”
(doi:10.1001/jama.2014.10057; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Self-titration of Antihypertensive Therapy in High-Risk Patients
Bring It Home

“Although the trial by McManus et al does not settle all questions regarding self-titration based on self-measurement, it is an important step toward adaptation of treatment for patients who want to actively take part in their own risk-factor control,” write Peter M. Nilsson, M.D., Ph.D., of Skane University Hospital, Malmo, Sweden, and Fredrik H. Nystrom, M.D., Ph.D., of Linkoping University, Linkoping, Sweden, in an accompanying editorial.

“Future trials studying the effects of self-titration on cardiovascular events are needed. With the gain in knowledge from [this trial], it may be possible to make the recruitment of patients less restricted, to incorporate education about self-measurement as a standard procedure and focus on which scheme for titration to use, or to study the timing of the home blood pressure recordings. In many countries antihypertensive drugs are now available as inexpensive generic drugs. The time has come to fully use these noncostly medications and to design optimal individualized care of patients.”

“Based on these findings, a ‘bring it home’ blood pressure-lowering strategy appears suitable for patients with hypertension and comorbidities.”
(doi:10.1001/jama.2014.10058; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 19, 2014
Media Advisory: To contact Shani Delaney, M.D., email Susan Gregg at sghanson@uw.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.2014.9237.

Prevalence of Herpes Simplex Virus Type 2 Decreases Among Pregnant Women in the Pacific Northwest

In a study that included approximately 15,000 pregnant women, seroprevalence of herpes simplex virus (HSV) type 2 decreased substantially between 1989 and 2010 while there was no overall decrease for HSV type 1, but a slight increase among black women, according to a study in the August 20 issue of JAMA.

Shani Delaney, M.D., and Anna Wald, M.D., M.P.H., of the University of Washington, Seattle, and colleagues examined trends in the seroprevalence of HSV-1 and HSV-2 among pregnant women who delivered newborns at the University of Washington Medical Center between January 1989 and May 2010. The researchers identified 15,738 women with 18,993 pregnancies who had prenatal HSV serological results.

HSV-1 seroprevalence decreased from 69.1 percent during the first decade (1989-1999) to 65.5 percent during 2000-2010, whereas HSV-2 seroprevalence decreased from 30.1 percent to 16.3 percent. After adjusting for various factors, the researchers found no significant annual trend in HSV-1 seroprevalence; however, rates of HSV-2 seroprevalence decreased significantly by 4.8 percent/year. Seroprevalence of HSV-1 increased slightly among black women (0.9 percent/year). Seroprevalence of HSV-2 decreased significantly over time among women of all races; however, rates per year decreased substantially less for black women relative to white women.

The authors note that the decline in HSV-2 seroprevalence does not necessarily avert the potential for neonatal herpes, a rare but serious complication. “Women who are seronegative entering pregnancy and acquire HSV during late pregnancy are at higher risk for transmission of HSV to their infants than seropositive women.”
(doi:10.1001/jama.2014.9237; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 19, 2014
Media Advisory: To contact corresponding author Jennifer M. Puck, M.D., email Juliana Bunim at juliana.bunim@ucsf.edu. To contact editorial author Neil A. Holtzman, M.D., M.P.H., call Ekaterina Pesheva at 410-502-9433 or email epeshev1@jhmi.edu.

To place an electronic embedded link to this study and editorial in your story This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.9132. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.9133.

Study Examines Incidence, Survival Rate of Severe Immunodeficiency Disorder in Newborns

Newborn screening performed in numerous states indicates that the incidence of the potentially life-threatening disorder, severe combined immunodeficiency, is higher than previously believed, at 1 in 58,000 births, although there is a high rate of survival, according to a study in the August 20 issue of JAMA.

The purpose of newborn screening is early detection of inborn conditions for which prompt treatments can reduce the risk of death or irreversible damage. The first heritable immune disorders to which newborn screening has been applied are those that together comprise severe combined immunodeficiency (SCID), a disorder that can result in life-threatening infections, making early detection and treatment critical. Population-based screening is the only means to detect SCID prior to the onset of infections in most cases. The incidence of SCID has been estimated to be 1 in 100,000 births. SCID was added to the national recommended uniform panel for newborn screened disorders in 2010, and currently 23 states, the District of Columbia, and the Navajo Nation screen approximately two-thirds of all infants born in the United States for SCID, according to background information in the article.

Antonia Kwan, Ph.D., M.R.C.P.C.H., of the University of California, San Francisco, and colleagues conducted the first combined analysis of more than 3 million infants screened for SCID in 10 states and the Navajo Nation. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included.

There were 52 SCID cases identified during the study period, an overall incidence of 1 in 58,000 births. The incidence was not significantly different in any state program but was higher in the Navajo Nation (1/3,500), attributed to a genetic mutation found in this population. Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87 percent, 92 percent for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia (abnormally low level of certain white blood cells) included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines.

“These findings support the view that SCID has previously been underdiagnosed in infants with fatal infections,” the authors write.

“Now that infants with SCID are being detected at a very young age in diverse medical settings, it is imperative to tailor protocols for their treatment, including choice and pharmacokinetic monitoring of drugs administered to facilitate hematopoietic cell engraftment.”
(doi:10.1001/jama.2014.9132; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Newborn Screening for Severe Combined Immunodeficiency
Progress and Challenges

“Infants born with SCID in the 27 states that do not screen for SCID have a greater chance of not being detected promptly, or at all, and are at increased risk of dying, compared with those born in the 23 states that do screen for SCID,” writes Neil A. Holtzman, M.D., M.P.H., of the Johns Hopkins Medical Institutions, Baltimore, in an accompanying editorial.

“Although many states require their own pilot programs before a new screening test is added to their battery of tests, no state could amass as much data in a reasonable time frame as have Kwan et al. Before screening becomes universal in the United States, agreement is needed on what constitutes a positive T-cell receptor excision circle [a biomarker used to help identify SCID] screening test, on ensuring referrals to physicians competent to make a diagnosis, and on providing definitive therapy to every infant detected with SCID in every state.”
(doi:10.1001/jama.2014. 9133; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 19, 2014
Media Advisory: To contact Suzanne Schuh, M.D., F.R.C.P.C., call Matet Nebres at 416-813-6380 or email matet.nebres@sickkids.ca. To contact editorial co-author Robert Vinci, M.D., email Jenny Eriksen Leary at Jenny.Eriksen@bmc.org.

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Findings Suggest Over-Reliance on Pulse Oximetry for Determining Whether Children With Respiratory Infection Should Be Hospitalized

Among infants presenting to a pediatric emergency department with mild to moderate bronchiolitis, those with an artificially elevated oxygen saturation reading were less likely to be hospitalized or receive hospital care for more than 6 hours than those with unaltered readings, suggesting that these readings should not be the only factor in the decision to admit or discharge, according to a study in the August 20 issue of JAMA.

Bronchiolitis, a viral lower respiratory tract infection, is the leading cause of infant hospitalizations in the United States, with annual costs in excess of $1 billion. Between 1980 and 2000, the rate of hospitalizations for bronchiolitis more than doubled. Pulse oximetry, which involves an instrument usually attached on the finger or ear lobe, is a noninvasive method of measuring oxygen saturation, and its routine use has been associated with changes in the management of bronchiolitis. There is no evidence that certain cutoff measurements predict progression from relatively mild to severe bronchiolitis, according to background information in the article. “If well-appearing children with mild to moderate bronchiolitis can be sent home, fewer hospitalizations and lower health care costs could result.”

Suzanne Schuh, M.D., F.R.C.P.C., of The Hospital for Sick Children, Toronto, and colleagues conducted a randomized clinical trial to determine if increasing the displayed oximetry reading three percentage points above the true values would decrease the probability of hospitalization within 72 hours or hospital care for greater than 6 hours. The study included 213 otherwise healthy infants 4 weeks to 12 months of age with mild to moderate bronchiolitis in a tertiary-care pediatric emergency department in Toronto.

The researchers found that 41 percent (44/108) of children in the true oximetry group were hospitalized within 72 hours, compared with 25 percent (26/105) in the altered oximetry group. There were 23 of 108 (21.3 percent) subsequent unscheduled medical visits for bronchiolitis in the true oximetry group and 15 of 105 (14.3 percent) in the altered oximetry group.

“Artificially increasing the oximetry display in emergency department patients with mild to moderate bronchiolitis by a physiologically small amount significantly reduced hospitalizations within 72 hours or active hospital care for more than 6 hours compared with infants with unaltered oximetry readings. This conclusion also held true after adjustment for other variables significantly associated with this outcome. Because the groups had similar severity and the adjustment for the experimental saturation resulted in lack of primary treatment effect, the difference in displayed saturations was likely the primary reason for the observed reduction in hospitalizations,” the authors write.

The researchers add that these findings suggest “that oxygen saturation should not be the only factor in the decision to admit, and its use may need to be re-evaluated.”
(doi:10.1001/jama.2014.8637; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Bronchiolitis, Deception in Research, and Clinical Decision Making

In an accompanying editorial, Robert Vinci, M.D., of the Boston University School of Medicine, and Howard Bauchner, M.D., Editor in Chief, JAMA, comment on the findings of this study.

“… it is now clear that the oxygen saturation reading can influence decision making in ways that many clinicians have thought likely—overreliance on physiologic information of uncertain importance derived from a medical device. While physicians seek to improve the science of clinical decision making, the art of medicine and clinical assessment should not be trumped by overreliance on a single physiologic parameter. The care of patients with bronchiolitis will continue to improve as experienced physicians emphasize and continue to use a complete clinical evaluation and assessment as the most important element in the care of these infants and children.”
(doi:10.1001/jama.2014.8638; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 19, 2014
Media Advisory: To contact Nancy A. Rigotti, M.D., call Terri Ogan at 617-726-0954 or email togan@partners.org.

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.2014.9237.

Intervention Helps Smokers Quit Following Hospital Stay

Among hospitalized adult smokers who wanted to quit, a postdischarge intervention that included automated telephone calls and free medication resulted in higher sustained smoking cessation rates at six months than standard postdischarge advice to use smoking cessation medication and counseling, according to a study in the August 20 issue of JAMA.

Cigarette smoking is the leading preventable cause of death in the United States. For the nearly 4 million smokers hospitalized each year, a hospital stay offers a good opportunity to quit smoking because all hospitals are now smoke-free, requiring patients to abstain temporarily from tobacco use. The major challenge for hospitals in providing evidence­based care is identifying how to sustain tobacco treatment after discharge, according to background information in the article.

Nancy A. Rigotti, M.D., of Massachusetts General Hospital, Boston, and colleagues randomly assigned 397 hospitalized daily smokers (average age, 53 years) who wanted to quit smoking after discharge to sustained or standard tobacco treatment care. Sustained care participants (n = 198) received automated interactive voice response telephone calls and their choice of free smoking cessation medication (any type approved by the U.S. Food and Drug Administration) for up to 90 days. The automated telephone calls promoted cessation, provided medication management, and triaged smokers for additional counseling. Standard care participants (n = 199) received recommendations for postdischarge pharmacotherapy and counseling.

The researchers found that more participants in the sustained care group than in the standard care group achieved the primary outcome of biochemically confirmed past 7-day tobacco abstinence (using saliva samples to measure a nicotine metabolite) at 6-month follow-up (26 percent vs 15 percent, respectively). Sustained care also resulted in higher self-reported continuous abstinence rates for 6 months after discharge (27 percent vs 16 percent for standard care).

“[This] trial demonstrated the effectiveness of a program to promote long-term tobacco cessation among hospitalized cigarette smokers who received an inpatient tobacco dependence intervention and expressed an interest in cessation treatment after discharge. The intervention aimed to sustain the tobacco cessation treatment that had begun in the hospital. It succeeded in improving the use of both counseling and pharmacotherapy by smokers after discharge, and it increased by 71 percent the proportion of patients with biochemically confirmed tobacco abstinence 6 months after discharge, which is a standard measure of long-term smoking cessation. The intervention appeared to be effective across abroad range of smokers and provided high-value care at a relatively low cost,” the authors write.

“These findings, if replicated, suggest a translatable, low-cost approach to achieving sustained smoking cessation after a hospital stay.”
(doi:10.1001/jama.2014.9237; Available pre-embargo to the media at https://media.jamanetwork.com)

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

For related articles on this subject, please see our tobacco control theme issue from earlier this year, available at this link.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 12, 2014
Media Advisory: To contact Agnes Dechartres, M.D., Ph.D., email agnes.dechartres@htd.aphp.fr. To contact editorial co-author Robert M. Golub, M.D., call Jim Michalski at 312-464-5785 or email jim.michalski@jamanetwork.org.

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.2014.8166. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.8167.

Approach Used to Conduct Meta-Analyses May Affect Outcomes

Depending on the analysis strategy used, estimating treatment outcomes in meta­analyses may differ and may result in major alterations in the conclusions derived from the analysis, according to a study in the August 13 issue of JAMA.

Meta-analyses of randomized clinical trials (RCTs) are generally considered to provide among the best evidence of efficacy of medical interventions. They should be conducted as part of a systematic review, a scientifically rigorous approach that identifies, selects, and appraises all relevant studies. Which trials to combine in a meta­analysis remains a persistent dilemma. Meta-analysis of all trials may produce a precise but biased estimate, according to background information in the article.

Agnes Dechartres, M.D., Ph.D., of the Centre de Recherche Epidemiologie et Statistique, INSERM U1153, Paris, and colleagues compared treatment outcomes estimated by meta-analysis of all trials and several alternative strategies for analysis: single most precise trial (i.e., trial with the narrowest confidence interval), meta-analysis restricted to the 25 percent largest trials, limit meta-analysis (a meta-analysis model adjusted for small-study effect), and meta-analysis restricted to trials at low overall risk of bias. The researchers included 163 meta-analyses published between 2008 and 2010 in high-impact-factor journals and between 2011 and 2013 in the Cochrane Database of Systematic Reviews: 92 (705 RCTs) with subjective outcomes and 71 (535 RCTs) with objective outcomes.

The researchers found that treatment outcome estimates differed depending on the analytic strategy used, with treatment outcomes frequently being larger with meta-analysis of all trials than with the single most precise trial, meta-analysis of the largest trials, and limit meta­analysis. The difference in treatment outcomes between these strategies was substantial in 47 of 92 (51 percent) meta-analyses of subjective outcomes and in 28 of 71 (39 percent) meta-analyses of objective outcomes. The authors did not find any difference in treatment outcomes by overall risk of bias.

“In this study, we compared meta-analysis of all trials with several ‘best­evidence’ alternative strategies and found that estimated treatment outcomes differed depending on the strategy used. We cannot say which strategy is the best because … we cannot know with 100 percent certainty the truth in any research question. Nevertheless, our results raise important questions about meta-analyses and outline the need to re­think certain principles,” the researchers write.

“We recommend that authors of meta-analyses systematically assess the robustness of their results by performing sensitivity analyses. We suggest the comparison of the meta-analysis result to the result for the single most precise trial or meta­analysis of the largest trials and careful interpretation of the meta-analysis result if they disagree.”
(doi:10.1001/jama.2014.8166; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Meta-analysis as Evidence – Building a Better Pyramid

Jesse A. Berlin, Sc.D., of Johnson & Johnson, Titusville, N.J., and Robert M. Golub, M.D., Deputy Editor, JAMA, write in an accompanying editorial that “findings such as those in the study by Dechartres et al reinforce concerns that journals and readers have about meta­analysis as a study design. Those findings deserve consideration not only in the planning of the studies but in the journal peer review and evaluation. They also reinforce the need for circumspection in study interpretation.”

“Meta-analysis has the potential to be the best source of evidence to inform decision making. The underlying methods have become much more sophisticated in the last few decades, but achieving this potential will require continued advances in the underlying science, parallel to the advances that have occurred with other biomedical research design and statistics. Until that occurs, an informed reader must approach these studies, as with all other literature, as imperfect information that requires critical appraisal and assessment of applicability of the findings to individual patients. This is not easy, and it requires skill and intelligence. Whatever clinical evidence looks like, and wherever it is placed on a pyramid, there are no shortcuts to truth.”
(doi:10.1001/jama.2014.8167; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 12, 2014
Media Advisory: To contact corresponding author K. E. Juhani Airaksinen, M.D., Ph.D., email juhani.airaksinen@tyks.fi.

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.2014.3824.

Delay in Correcting Irregular Cardiac Rhythm From Atrial Fibrillation Associated With Increased Risk of Complications

A delay of 12 hours or longer to correct an abnormal cardiac rhythm from atrial fibrillation was associated with a greater risk of thromboembolic complications such as stroke, according to a study in the August 13 issue of JAMA.

In 1995, practice guidelines recommended a limit of 48 hours after the onset of atrial fibrillation (AF) for cardioversion (the conversion of a cardiac rhythm from abnormal to normal) without anticoagulation. Whether the risk of thromboembolic complications is increased when cardioversion without anticoagulation is performed in less than 48 hours is unknown, according to background information in the article.

Ilpo Nuotio, M.D., Ph.D., of Turku University Hospital, Turku, Finland and colleagues conducted a study that included patients with a successful cardioversion in the emergency department within the first 48 hours of AF. The primary outcome, a thromboembolic event, was defined as a clinical stroke or systemic embolism (blood clot) within 30 days after cardioversion. Procedures were divided into groups according to the time to cardioversion: less than 12 hours (group 1), 12 hours to less than 24 hours (group 2), and 24 hours to less than 48 hours (group 3).

Of 2,481 patients with acute AF, 5,116 successful cardioversions were performed without anticoagulation. Thirty­eight thromboembolic events occurred in 38 patients (0.7 percent); 31were strokes. The incidence of thromboembolic complications increased from 0.3 percent in group 1 to 1.1 percent in group 3. In analysis, time to cardioversion longer than 12 hours was an independent predictor for thromboembolic complications.
(doi:10.1001/jama.2014.3824; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 12, 2014
Media Advisory: To contact corresponding author Hooman Kamel, M.D., call Ashley Paskalis at 646-317-7378 or email asp2011@med.cornell.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.2014.9143.

Experiencing Atrial Fibrillation While Hospitalized For Surgery Associated With Increased Long-Term Risk of Stroke

In a study that included 1.7 million patients undergoing inpatient surgery, experiencing atrial fibrillation while hospitalized was associated with an increased long-term risk of ischemic stroke, especially following noncardiac surgery, according to a study in the August 13 issue of JAMA.

Atrial fibrillation (AF) and flutter affect more than 33 million people worldwide. The presence of chronic AF confers a 3-fold increased risk of stroke. Perioperative (around the time of surgery) atrial fibrillation may be viewed as a transient response to physiological stress, and the long-term risk of stroke after perioperative atrial fibrillation is unclear, according to background information in the article.

Gino Gialdini, M.D., of Weill Cornell Medical College, New York, and colleagues conducted a study to determine the long-term risk of ischemic stroke after perioperative AF of patients undergoing surgery, using administrative claims data from California acute care hospitals between 2007 and 2011. For this study, perioperative was defined as AF newly diagnosed during the hospitalization for surgery.

The study included 1,729,360 eligible patients with an average follow-up time of 2.1 years. Among these patients, perioperative AF was documented in 24,711 cases (1.43 percent). After discharge from the index hospitalization for surgery, 13,952 patients (0.81 percent) went on to experience an ischemic stroke. At 1 year after hospitalization for noncardiac surgery, cumulative rates of stroke were 1.47 percent in those with perioperative AF and 0.36 percent in those without AF. At 1 year after cardiac surgery, cumulative rates of stroke were 0.99 percent in those with perioperative AF and 0.83 percent in those without AF.

Analyses indicated that perioperative AF after noncardiac surgery was associated with twice the risk of stroke and a 30 percent greater risk after cardiac surgery.

“Our results may have significant implications for the care of perioperative patients. The associations we found suggest that while many cases of perioperative AF after cardiac surgery may be an isolated response to the stress of surgery, perioperative AF after noncardiac surgery may be similar to other etiologies of AF in regard to future thromboembolic risk. Our results suggest the need for future studies involving long-term ambulatory cardiac monitoring to better delineate the risk associated with transient vs persistent perioperative AF, as well as randomized clinical trials to determine optimal strategies for antithrombotic therapy in patients with perioperative AF and a significant burden of other risk factors for stroke,” the authors write.
(doi:10.1001/jama.2014.9143; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 12, 2014
Media Advisory: To contact Øyvind Holme, M.D., email oyvind.holme@sshf.no. To contact editorial author Allan S. Brett, M.D., email Matt Splett at matt.splett@uscmed.sc.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.2014.8266. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.8613.

Flexible Sigmoidoscopy Screening Reduces Colorectal Cancer Incidence, Rate of Death

Among about 100,000 study participants, screening with flexible sigmoidoscopy resulted in a reduced incidence and rate of death of colorectal cancer, compared to no screening, according to a study in the August 13 issue of JAMA.

Colorectal cancer is the third most commonly occurring cancer worldwide. Most colorectal cancer cases develop from adenomas (benign tumors). Removal of adenomas by colonoscopy or flexible sigmoidoscopy (a thin flexible lighted tube used for inspection of the inside of the rectum and lower part of the colon) has been endorsed as a primary prevention tool for colorectal cancer, according to background information in the article.

Øyvind Holme, M.D., of the Sorlandet Hospital Kristiansand, Kristiansand, Norway and colleagues randomly assigned study participants in Norway to receive once-only flexible sigmoidoscopy (n=10, 283); a combination of once-only flexible sigmoidoscopy and fecal occult blood testing (FOBT; n=10,289), or no intervention (control group; n=78,220). Screening was performed in 1999-2000 (55-64-year age group) and in 2001 (50-54-year age group), with follow-up ending December 2011. Participants with positive screening test results were offered colonoscopy.

After a median of 11 years, 71 participants died of colorectal cancer in the screening groups vs 330 in the control group. Colorectal cancer was diagnosed in 253 participants in the screening groups vs 1,086 in the control group. Analysis of the data indicated that compared to no screening, flexible sigmoidoscopy screening reduced colorectal cancer incidence by 20 percent (absolute difference, 28.4 cases/100,000 person years) and colorectal cancer mortality by 27 percent (absolute difference, 11.7 deaths/100,000 person years). There was no significant difference in these outcomes between the flexible sigmoidoscopy only vs the flexible sigmoidoscopy and FOBT screening groups.

Younger participants 50 to 54 years of age seemed to benefit at least as much from the screening interventions as older participants ages 55 to 64 years.
(doi:10.1001/jama.2014.8266; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Flexible Sigmoidoscopy for Colorectal Cancer Screening
More Evidence, Persistent Ironies

In an accompanying editorial, Allan S. Brett, M.D., of the University of South Carolina School of Medicine, Columbia, S.C., writes that while there may be debate over the use of flexible sigmoidoscopy or colonoscopy for colorectal cancer screening, another screening technique, stool DNA testing, might render this debate moot in the not-too­distant future.

“A large, recently published study examined the performance of a multitarget stool test that identifies several DNA abnormalities associated with colorectal cancer or precancerous adenomas. With colonoscopy as the reference standard, the sensitivity of the stool DNA test was 92 percent for detecting cancer and 42 percent for detecting advanced precancerous lesions; specificity was 90 percent. Notably, the stool DNA test was much more sensitive than a separate fecal immunochemical test for hemoglobin performed for each participant. Repeated at some defined interval, stool DNA testing has potential to reduce colorectal cancer mortality substantially while sharply reducing the number of routine colonoscopies. For now, however, the muddled landscape of colorectal cancer screening in the United States continues, and the place of flexible sigmoidoscopy among screening tools remains unsettled.”
(doi:10.1001/jama.2014.8613; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 5, 2014
Media Advisory: To contact corresponding author Wen-Hung Chung, M.D., Ph.D., email chung1@cgmh.org.tw; to contact Shuen-Iu Hung, Ph.D., email sihung@ym.edu.tw.

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.2014.7859.

Study Identifies Genetic Variants Associated with Severe Skin Reactions to Commonly Used Antiepileptic Drug

Researchers have identified genetic variants that are associated with severe adverse skin reactions to the antiepileptic drug phenytoin, according to a study in the August 6 issue of JAMA.

Phenytoin is a widely prescribed antiepileptic drug and remains the most frequently used first-line antiepileptic drug in hospitalized patients. Although effective for treating neurological diseases, phenytoin can cause cutaneous (skin) adverse reactions ranging from mild to severe. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions has not been known, according to background information in the article.

Wen-Hung Chung, M.D., Ph.D., of Chang Gung Memorial Hospital, Keelung, Taiwan, and colleagues investigated the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. The case-control study was conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema (a less severe type of rash), 130 phenytoin-tolerant control participants, and 3,655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS) was conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan.

Analysis of the data indicated that variants of the gene CYP2C, including CYP2C9*3, were associated with phenytoin-related severe cutaneous adverse reactions. The statistically significant association between CYP2C9*3, known to reduce drug clearance (the elimination of a drug from the body), and phenytoin-related severe cutaneous adverse reactions was replicated by the samples from Taiwan, Japan, and Malaysia, with a meta-analysis showing an 11 times higher odds of experiencing this reaction with this variant. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a clinical link of the associated variants to the disease.

Delayed clearance was also noted in patients with severe cutaneous adverse reactions without CYP2C9*3, suggesting that nongenetic factors such as renal insufficiency, hepatic dysfunction, and concurrent use of substances that compete or inhibit the enzymes may also affect phenytoin metabolism and contribute to severe cutaneous adverse reactions.

“This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions. These findings may have potential to improve the safety profile of phenytoin in clinical practice and offer the possibility of prospective testing for preventing phenytoin-related severe cutaneous adverse reactions. More research is required to replicate the genetic association in different populations and to determine the test characteristics and clinical utility,” the authors conclude.
(doi:10.1001/jama.2014.7859; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 5, 2014
Media Advisory: To contact corresponding author Maurizio Gasparini, M.D., email maurizio.gasparini@humanitas.it.

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.2014.4783.

Using Long-Detection Interval for ICDs Associated With Reduction in Hospitalizations, Costs

Use of implantable cardioverter-defibrillators (ICDs) programmed with long-detection intervals for ventricular arrhythmias was associated with an increase in the time to first hospitalization and reductions in hospitalization rate, length of stay and costs, compared with standard interval programming, according to a study in the August 6 issue of JAMA.

An ICD programming strategy that allows delayed detection of arrhythmias has been shown to reduce unnecessary and inappropriate therapies. Alessandro Proclemer, M.D., of the Azienda Ospedaliera Universitaria S. Maria della Misericordia, Udine, Italy, and colleagues assessed the association of programming a long-detection interval on hospitalizations, length of stay (LOS) in the hospital and costs. The researchers analyzed data from the ADVANCE III study, a trial conducted at 94 international centers between 2008 and 2010 in which 1,902 patients receiving their first ICD were randomized to a long-detection interval group (n = 948; the number of intervals to detect arrhythmias was programmed at 30 of 40) or a standard interval group (n = 954; 18 of 24 intervals).

During 12 months of follow-up, 546 patients reported 865 overall hospitalizations (473 hospitalizations in 302 patients in the standard interval group and 392 hospitalizations in 244 patients in the long-detection interval group). The long-detection interval group was associated with a longer time to the first overall hospitalization and cardiovascular hospitalization compared with the standard interval group, and reductions in overall hospitalization rate and LOS, without difference in the rate of death.

Similar results were found for cardiovascular hospitalization rates and LOS. The long-detection interval group was also associated with an average reduction of $299 per patient-year for overall hospitalizations and $329 per patient-year for cardiovascular hospitalizations, compared with the standard interval group.

“These favorable results for resource use complement the demonstrated clinical effectiveness of the long-detection interval strategy and come without additional costs for the hospitals or patients,” the authors write.
(doi:10.1001/jama.2014.4783; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The ADVANCE III study was supported by Medtronic Inc. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 5, 2014
Media Advisory: To contact Arthur R. H. van Zanten, M.D., Ph.D., email zantena@zgv.nl. To contact editorial author Todd W. Rice, M.D., M.Sc., email Craig Boerner at craig.boerner@Vanderbilt.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.2014.7698. This will be the link for the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.7699.

Enriching Feeding Tube Nutrition With Immune-Modulating Nutrients Does Not Reduce Risk of Infection Among ICU Patients

Among mechanically ventilated intensive care unit (ICU) patients, receipt of high-protein nutrition via a feeding tube enriched with immune-modulating nutrients (such as glutamine, omega-3 fatty acids, and antioxidants) vs standard high-protein nutrition did not result in a significant difference in the incidence of new complications and may be harmful, as suggested by an increased risk of death at 6 months, according to a study in the August 6 issue of JAMA.

Several meta-analyses have reported that use of immune-modulating nutrients in enteral (via feeding tube) nutrition is associated with reductions in illness from infections and improved recovery from critical illness compared with standard enteral nutrition. However, there is a lack of consensus in guidelines regarding enteral administration of immune-modulating nutrients, according to background information in the article.

Arthur R. H. van Zanten, M.D., Ph.D., of the Gelderse Vallei Hospital, Ede, the Netherlands, and colleagues randomly assigned 301 adult ICU patients who were expected to be ventilated and to require enteral nutrition for more than 72 hours to either immune-modulating nutrients (IMHP) (n = 152) or high-protein enteral nutrition (HP) (n = 149). The patients were from 14 ICUs in the Netherlands, Germany, France, and Belgium. Patients were followed for up to six months.

The researchers found that there were no significant differences in the incidence of new infections between groups. Overall, 53 percent of those in the IMHP group vs 52 percent in the HP group had new infections. No significant differences were observed in outcomes such as mechanical ventilation duration, ICU and hospital lengths of stay, and a measure of organ failure. The 6-month mortality rate was higher in the medical subgroup: 54 percent in the IMHP group vs 35 percent in the HP group.

“These findings do not support the use of high-protein enteral nutrition enriched with immune-modulating nutrients in these patients,” the authors conclude.
(doi:10.1001/jama.2014.7698; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, the Netherlands was the study sponsor. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Immunonutrition in Critical Illness – Limited Benefit, Potential Harm

Todd W. Rice, M.D., M.Sc., of the Vanderbilt University School of Medicine, Nashville, Tenn., writes in an accompanying editorial that many questions surrounding immunonutrition remain unanswered.

“Are there specific critically ill populations that may benefit from some immunomodulation or supplementation of individual immunomodulating agents, such as glutamine supplementation in burns or vitamin D replacement in severe sepsis? Does administration of multiple potential immunologic modulating agents together alter the individual effects of each agent? Combined administration in a single formula or supplement in all of these trials prevents implicating any single component (i.e., omega-3 fatty acids, glutamine, or antioxidants). In addition, enteral and parenteral [intravenous] administration may result in differential effects. Although these uses of immunomodulating nutrition still need to be explored, the similarity of the results and the suggestion of harm from recently published, large, randomized trials of immunonutrition should strongly discourage intensivists from its routine prescription for critically ill patients in clinical practice outside the scope of well-designed randomized clinical trials.”
(doi:10.1001/jama.2014.7699; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 5, 2014
Media Advisory: To contact Peter Roy-Byrne, M.D., call 206-386-3103. To contact Richard Saitz, M.D., email Lisa Chedekel at chedekel@bu.edu. To contact editorial co-author Ralph Hingson, Sc.D., M.P.H., call the NIAAA Press Office at 301-443-3860 or email NIAAAPressOffice@mail.nih.gov.

To place an electronic embedded link to these studies in your story This link for the first study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.7860. This will be the link for the 2nd study: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.7862. This will be the link for the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.7863.

Studies Find Brief Interventions Ineffective for Reducing Unhealthy, Problem Drug Use

Two studies in the August 6 issue of JAMA examine the effectiveness of using brief interventions in primary care settings to reduce drug use.

In one study, Peter Roy-Byrne, M.D., formerly of the University of Washington, Seattle, and colleagues write that few data exist on the effectiveness of brief (1-2 sessions) interventions for reducing problem drug use, a common issue in disadvantaged populations seeking care in safety-net medical settings (hospitals and community health clinics serving low-income patients with limited or no insurance). Based on the established efficacy of brief interventions for hazardous alcohol use among patients seen in medical settings, national dissemination programs of screening, brief intervention, and referral to treatment for “alcohol and drugs” have been implemented on a widespread scale, according to background information in the article.

The researchers randomly assigned 868 patients from 7 safety-net primary care clinics in Washington State who had reported problem drug use in the past 90 days to a single brief intervention (n = 435) or enhanced care as usual, which included a handout and list of substance abuse resources (n = 433). The single brief intervention included a handout and list of substance abuse resources along with giving participants feedback about their drug use screening results, exploring the pros and cons of drug use, increasing participant confidence in being able to change, and discussing options for change. In addition, attempts were made for a 10-minute follow-up session by telephone within 2 weeks of the initial intervention. The patients were assessed for drug use at the beginning of the study, and at 3, 6, 9, and 12 months.

Average days used of the most common problem drug at baseline were 14.40 (brief intervention) and 13.25 (enhanced care as usual); at 3 months postintervention, averages were 11.87 (brief intervention) and 9.84 (enhanced care as usual) and not significantly different. During the 12 months following intervention, no significant treatment differences were found between the two groups for drug use or for secondary outcomes, which included admission to substance abuse treatment, emergency department and inpatient hospital admissions, arrests, death and behavior that increases risk of human immunodeficiency virus transmission.

The authors write that these “finding suggests a need for caution in promoting widespread adoption of this intervention for drug use in primary care.”

“… further research to identify subgroups responsive to this intervention, as well as the role of more intensive interventions, appears to be warranted. For example, targeting intervention efforts toward individuals with severe drug abuse, many of whom use stimulants and opiates and may be at higher risk of overdose and other harmful consequences, might increase the uptake of specialty treatment and reduce emergency department utilization.”
(doi:10.1001/jama.2014.7860; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was funded by a grant from the National Institute on Drug Abuse. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

In another study, Richard Saitz, M.D., of the Boston University School of Public Health, and colleagues tested the effectiveness of two brief counseling interventions for unhealthy drug use (any illicit drug use or prescription drug misuse) among primary care patients identified by screening.

The United States has invested substantially in screening and brief intervention for illicit drug use and prescription drug misuse, based in part on evidence of efficacy for unhealthy alcohol use. However, it is not a recommended universal preventive service in primary care because of lack of evidence of efficacy, according to background information in the article.

The researchers randomly assigned 528 adult primary care patients with unhealthy drug use to one of three groups: to receive a brief negotiated interview (BNI), which was a 10- to 15-minute structured interview conducted by health educators; an adaptation of motivational interviewing (MOTIV), which was a 30- to 45-minute intervention based on motivational interviewing with a 20- to 30-minute booster conducted by masters-level counselors; or no brief intervention. All study participants received a written list of substance use disorder treatment and mutual help resources. At the beginning of the study, 63 percent of participants reported their main drug was marijuana, 19 percent cocaine, and 17 percent opioids.

For the primary outcome (number of days of use in the past 30 days of the self-identified main drug), there were no significant differences between the BNI, MOTIV or control groups (adjusted average days using the main drug at 6 months, 11, 12 and 12 days, respectively). In addition, there were no significant between-group differences overall or in stratified analyses at 6 weeks or 6 months in drug use consequences, injection drug use, unsafe sex, health care utilization (hospitalizations and emergency department visits, overall or for addiction or mental health reasons), or mutual help group attendance.

The authors write that despite the potential for benefit with a brief intervention, drug use differs from unhealthy alcohol use in that it is often illegal and socially unacceptable, and is diverse—from occasional marijuana use, which was illegal during this study, to numerous daily heroin injections. “Prescription drug misuse is particularly complex, with diagnostic confusion between misuse for symptoms (e.g., pain, anxiety), euphoria-seeking, and drug diversion. Brief counseling may simply be inadequate to address these complexities, even as an initial strategy.”

“These results do not support widespread implementation of illicit drug use and prescription drug misuse screening and brief intervention.”
(doi:10.1001/jama.2014.7862; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Editorial: Screening and Brief Intervention and Referral to Treatment for Drug Use in Primary Care – Back to the Drawing Board

In an accompanying editorial, Ralph Hingson, Sc.D., M.P.H., of the National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md., and Wilson M. Compton, M.D., M.P.E., of the National Institute on Drug Abuse, Rockville, Md., comment on the findings of these studies.

“Although these studies offer no direct evidence of effectiveness for universal drug screening, brief intervention, and referral to treatment in primary care settings, exploring drug use with patients should remain a priority in primary care. The goal for clinical research is to develop and test new interventions with potential for benefiting patients. Drug screening and brief intervention research that focuses on adolescents and young adults is especially needed because rates of marijuana use among young people and the potency of marijuana have increased at the same time that recognition among youth of the health risks of marijuana use have declined.”

“If brief interventions are insufficient, then easily accessible treatment services with long-term follow-up may be needed, as will development of efficient primary care referral approaches to address risky substance use and related physical and mental comorbidities.”
(doi:10.1001/jama.2014.7863; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 10 A.M. (CT) TUESDAY, JULY 22, 2014
Media Advisory: To contact Jason D. Wright, M.D., email Lucky Tran at cumcnews@columbia.edu.

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Among women undergoing a minimally invasive hysterectomy using electric power morcellation, uterine cancers were present in 27 per 10,000 women at the time of the procedure, according to a study published by JAMA. There has been concern that this procedure, in which the uterus is fragmented into smaller pieces, may result in the spread of undetected malignancies.

Despite the commercial availability of electric power morcellators for 2 decades, accurate estimates of the prevalence of malignancy at the time of electric power morcellation (in this study referred to as morcellation) have been lacking, according to background information in the article.

Jason D. Wright, M.D., of the Columbia University College of Physicians and Surgeons, New York, and colleagues used a large insurance database to investigate the prevalence of underlying cancer in women who underwent uterine morcellation. The database includes more than 500 hospitals capturing 15 percent of hospitalizations.

The researchers identified 232,882 women who underwent minimally invasive hysterectomy from 2006-2012; morcellation was performed in 36,470 (15.7 percent). Among those who underwent morcellation, 99 cases of uterine cancer were identified at the time of the procedure, a prevalence of 27/10,000. Other malignancies and precancerous abnormalities were also detected. Among women who underwent morcellation, advanced age was associated with underlying cancer and endometrial hyperplasia (a condition characterized by overgrowth of the lining of the uterus).

“Although morcellators have been in use since 1993, few studies have described the prevalence of unexpected pathology at the time of hysterectomy. Prevalence information is the first step in determining the risk of spreading cancer with morcellation,” the authors write. “Patients considering morcellation should be adequately counseled about the prevalence of cancerous and precancerous conditions prior to undergoing the procedure.”
(doi:10.1001/jama.2014.9005; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 10 P.M. (CT) SUNDAY, JULY 20, 2014
Media Advisory: To contact Harsha Thirumurthy, Ph.D., call David Pesci at 919-962-2600 or email dpesci@email.unc.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.2014.9087

Among uncircumcised men in Kenya, compensation in the form of food vouchers worth approximately U.S. $9 or $15, compared with lesser or no compensation, resulted in a modest increase in the prevalence of circumcision after 2 months, according to a study published by JAMA. The study is being released to coincide with its presentation at the International AIDS Conference.

Following randomized trials that demonstrated that medical male circumcision reduces men’s risk of HIV acquisition by 50 percent to 60 percent, UNAIDS and the World Health Organization recommended the scale-up of voluntary medical male circumcision (VMMC) in 14 countries in eastern and southern Africa. Despite considerable scale-up efforts, most countries are far short of target goals. Novel strategies are needed to increase VMMC uptake. Potential barriers include concerns about lost wages during and after the procedure, according to background information in the article.

Harsha Thirumurthy, Ph.D., of the University of North Carolina at Chapel Hill, and colleagues studied 1,504 uncircumcised men (25 to 49 years of age) in Nyanza region, Kenya, who were randomly assigned to 1 of 3 intervention groups or a control group. Participants in the intervention groups received varying amounts of compensation conditional on VMMC uptake at 1 of 9 study clinics within 2 months of enrollment. Compensation took the form of food vouchers worth approximately U.S. $2.50, $8.75, or $15, which reflected a portion of transportation costs and lost wages associated with getting circumcised. The control group received no compensation.

The researchers found VMMC uptake within 2 months was higher in the $8.75 group (6.6 percent [25 of 381]) and the $15 group (9.0 percent [34 of 377]) than in the $2.50 group (1.9 percent [7 of 374]) and the control group (1.6 percent [6 of 370]). Further analysis indicated that compared with participants in the control group, those in the $15 and $8.75 groups were significantly more likely to get circumcised; those enrolled in the $2.50 group were not. The difference in VMMC uptake between the $8.75 and $15 groups was not significant.

“There was also a significant increase in VMMC uptake among married and older participants, groups that have been harder to reach previously. The interventions also significantly increased the likelihood of circumcision uptake among participants at higher risk of acquiring HIV. This latter result is especially promising from an HIV prevention standpoint,” the authors write.

“The overall increase in VMMC uptake within 2 months, as a result of providing compensation, was modest, with an increase of at most 7.4 percent in the U.S. $15.00 group. This increased uptake was in a population with an estimated circumcision prevalence of 35.6 percent. Evaluation of scaled-up implementation of the intervention is needed to determine whether it will help achieve higher circumcision coverage over longer periods of time.”
(doi:10.1001/jama.2014.9087; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (CT) SATURDAY, JULY 19, 2014
Media Advisory: To contact corresponding author Steven K. Grinspoon, M.D., call Cassandra Aviles at 617-724-6433 or email cmaviles@partners.org.

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In a preliminary study, HIV-infected patients with excess abdominal fat who received the growth hormone-releasing hormone analog tesamorelin for 6 months experienced modest reductions in liver fat, according to a study in the July 23/30 issue of JAMA, a theme issue on HIV/AIDS. Patients infected with HIV demonstrate a high prevalence of nonalcoholic fatty liver disease, estimated at 30 percent to 40 percent. The issue is being released early to coincide with the International AIDS Conference.

In human immunodeficiency virus (HIV) infection, abdominal fat accumulation is associated with ectopic (out of place) fat accumulation in the liver. Nonalcoholic fatty liver disease (NAFLD) may progress to end-stage liver disease and liver cancer. To date, there are no approved pharmacologic strategies to reduce liver fat. Tesamorelin specifically targets abdominal fat reduction but its effects on liver fat are unknown, according to background information in the article.

Takara L. Stanley, M.D., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues randomly assigned 50 antiretroviral-treated HIV-infected men and women with abdominal fat accumulation to receive tesamorelin (n=28), or placebo (n=22), subcutaneously daily for 6 months.

The researchers found a modest but statistically significant decrease in liver fat with tesamorelin. Hepatic lipid to water percentage (a measure of liver fat), decreased in the tesamorelin group (median, -2.0 percent) compared with placebo (median, 0.9 percent). In addition, there was a significant reduction in abdominal fat: the average change was -9.9 percent with tesamorelin vs 6.6 percent with placebo.

“The decrease in liver fat in this study suggests that strategies to reduce visceral adiposity merit further investigation in HIV-infected patients with NAFLD, a condition for which there are no approved treatments. Importantly, NAFLD is associated with visceral adiposity and other metabolic abnormalities in HIV,” the authors write.

“Further studies are needed to determine the clinical importance and long-term consequences of these findings.”
(doi:10.1001/jama.2014.8334; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (CT) SATURDAY, JULY 19, 2014
Media Advisory: To contact corresponding author Jared M. Baeten, M.D., Ph.D., call Bobbi Nodell at 206-543-7129 or email bnodell@uw.edu. To contact editorial co-author David A. Cooper, M.D., D.Sc., email dcooper@kirby.unsw.edu.au.

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.2014.8735

Among heterosexual African couples in which the male was HIV positive and the female was not, receipt of antiretroviral pre-exposure preventive (PrEP) therapy did not result in significant differences in pregnancy incidence, birth outcomes, and infant growth compared to females who received placebo, according to a study in the July 23/30 issue of JAMA, a theme issue on HIV/AIDS. The authors note that these findings do not provide a definitive conclusion regarding the safety of PrEP therapy prior to pregnancy. The issue is being released early to coincide with the International AIDS Conference.

Antiretroviral pre-exposure prophylaxis as daily oral tenofovir disoproxil fumarate (TDF) and co-formulated emtricitabine/tenofovir disoproxil fumarate (FTC+TDF) has been demonstrated to be efficacious for the prevention of human immunodeficiency virus (HIV) acquisition in diverse populations. PrEP could be an important component of safer conception strategies for women at risk for HIV infection, including those in HIV-serodiscordant couples (i.e., in which only one member is HIV infected), but the effect on pregnancy outcomes is not well defined, according to background information in the article.

Nelly R. Mugo, M.B.Ch.B., M.P.H., of the Kenya Medical Research Institute, Nairobi, Kenya, and University of Washington, Seattle, and colleagues conducted further follow-up of the Partners PrEP Study, a randomized, placebo-controlled trial of PrEP for HIV prevention among HIV-serodiscordant couples conducted between July 2008 and June 2013. For this analysis, which included 1,785 couples in Kenya and Uganda, the researchers assessed pregnancy incidence and outcomes among women using PrEP during the periconception period. Females had been randomized to daily oral TDF (n = 598), combination FTC+TDF (n = 566), or placebo (n = 621) through July 2011, when PrEP demonstrated efficacy for HIV prevention. Thereafter, participants continued receiving active PrEP without placebo.

A total of 431 pregnancies occurred. The researchers found that pregnancy incidence did not differ significantly by study group, and that there was no statistically significant association between women receiving PrEP and those receiving placebo and the occurrence of pregnancy losses, which was 42.5 percent for women receiving FTC+TDF, 32.3 percent for those receiving placebo, and 27.7 percent for those receiving TDF alone. After July 2011 (when the placebo group was discontinued), the frequency of pregnancy loss was 37.5 percent for FTC+TDF and 36.7 percent for TDF alone.

Occurrence of preterm birth, congenital anomalies, kidney function and growth throughout the first year of life did not differ significantly for infants born to women who received PrEP vs placebo.

The authors write that for some outcomes, including pregnancy loss, preterm birth, congenital anomalies, and infant mortality, confidence intervals were wide (suggesting uncertainty in the result and the need for more data), including both a null effect and potential harm, and thus definitive statements about safety of PrEP in the periconception period cannot be made.

“These results should be discussed with HIV-uninfected women receiving PrEP who are considering becoming pregnant.”
(doi:10.1001/jama.2014.8735; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Integrating HIV Prevention Into Practice

Bradley M. Mathers, M.B.Ch.B., M.D., and David A. Cooper, M.D., D.Sc., of the University of New South Wales, Sydney, Australia, comment on the findings of this study in an accompanying editorial.

“… it appears (from the magnitude and asymmetry of the confidence intervals) that there may be a signal suggesting potential harm as pregnancy loss based on the emtricitabine/tenofovir vs placebo comparison (absolute difference ending in pregnancy loss of 10.2 percent) and on the post hoc emtricitabine/tenofovir vs tenofovir alone comparison (absolute difference ending in pregnancy loss of 9.2 percent).”

“These intriguing findings reported by Mugo et al provide important information from one of the largest studies of exposure to these nucleoside analogues in HIV-negative persons and therefore must be considered carefully. Tenofovir and emtricitabine are both category B drugs, but this signal suggesting a possible association with pregnancy loss has not to date appeared in studies of HIV-infected persons, suggesting that this observation deserves evaluation in future studies. Moreover, the nucleosides were stopped according to the trial protocol no later than 6 weeks into the pregnancy, albeit this period is highly sensitive to subsequent adverse pregnancy outcomes, but exposure to these drugs may be longer in the real-world setting.”
(doi:10.1001/jama.2014.8606; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (CT) SATURDAY, JULY 19, 2014
Media Advisory: To contact Peter MacPherson, Ph.D., email petermacp@gmail.com.

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Among adults in the African country of Malawi offered HIV self-testing, optional home initiation of care compared with standard HIV care resulted in a significant increase in the proportion of adults initiating antiretroviral therapy, according to a study in the July 23/30 issue of JAMA, a theme issue on HIV/AIDS. The issue is being released early to coincide with the International AIDS Conference.

In 2012, an estimated 35 million individuals were infected with the human immunodeficiency virus (HIV) worldwide. Antiretroviral therapy (ART) substantially reduces the risk of HIV transmission as well as greatly reducing illness and death, raising hopes that high uptake of annual HIV testing and early initiation of ART could improve HIV prevention as well as care. Achieving high coverage of HIV testing in sub-Saharan African countries is a major challenge, with low rates of HIV testing, according to background information in the article.

Self-testing for HIV infection (defined as individuals performing and interpreting their HIV test in private) is a novel approach that has seen high acceptance in Malawi and the United States, and is a process that could overcome barriers to conventional facility-based and community-based HIV testing, which lack privacy and convenience. However, no studies in high HIV prevalence settings have investigated linkage into HIV care after HIV self-testing, the authors write.

Peter MacPherson, Ph.D., of the Liverpool School of Tropical Medicine, Liverpool, U.K., and colleagues randomly assigned 16,660 adult residents of Blantyre, Malawi, who received access to home HIV self-testing, to facility-based care or optional home initiation of HIV care, for those reporting positive HIV self-test results.

During 6 months of availability, 58 percent of the adult residents took an HIV self-test kit. Participants in the home group (6.0 percent) were significantly more likely to report a positive HIV self-test result than facility group participants (3.3 percent). A significantly greater proportion of adults in the home group initiated ART (181/8,194; 2.2 percent) compared with the facility group (63/8,466; 0.7 percent).

“The main finding of this cluster randomized trial was that population-level ART initiations were significantly increased by availability of home initiation of care,” the authors write.

“At a time when universal test and treat approaches to controlling the HIV epidemic are being considered, home initiation of HIV care shows high promise as a simple strategy to improve uptake of ART when HIV self-testing is carried out at home.”
(doi:10.1001/jama.2014.6493; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (CT) SATURDAY, JULY 19, 2014
Media Advisory: To contact Mark S. Sulkowski, M.D., call Lauren Nelson at 410-955-8725 or email lnelso35@jhmi.edu. To contact editorial co-author Michael S. Saag, M.D., email Nicole Wyatt at nwyatt@uab.edu.

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HIV-infected patients also infected with hepatitis C virus (HCV) who received a combination of the medications sofosbuvir plus ribavirin had high rates of sustained HCV virologic response 12 weeks after cessation of therapy, according to a study in the July 23/30 issue of JAMA, a theme issue on HIV/AIDS. The issue is being released early to coincide with the International AIDS Conference.

Up to 7 million persons worldwide are infected with both human immunodeficiency virus (HIV) and hepatitis C virus. Treatment of this coinfection has been limited due to the need to use interferon (an antiviral protein used to treat HCV) and drug interactions with antiretroviral therapies (ARTs), according to background information in the article.

Mark S. Sulkowski, M.D., of Johns Hopkins University, Baltimore, and colleagues evaluated the rates of sustained virologic response (SVR) (what is clinically considered “cure”) and adverse events in 223 patients infected with HIV and HCV (genotypes 1, 2, or 3) who were treated with an interferon-free combination of the drugs sofosbuvir and ribavirin for 12 or 24 weeks. The trial was conducted at 34 treatment centers in the United States and Puerto Rico from August 2012 to November 2013.

Among participants with no prior treatment for HCV, 76 percent with genotype 1, 88 percent with genotype 2, and 67 percent with genotype 3 achieved SVR12 (serum HCV <25 copies/mL 12 weeks after cessation of HCV therapy). Among patients who had previously received treatment, 92 percent with genotype 2 and 94 percent with genotype 3 achieved SVR12. Seven patients (3 percent) discontinued HCV treatment due to adverse events, of which the most common were fatigue, insomnia, headache, and nausea. No adverse effect on HIV disease or its treatment was observed. “In this open-label, nonrandomized, uncontrolled study, HIV-infected patients with HCV genotypes 1, 2, or 3 coinfection who received an oral combination of sofosbuvir plus ribavirin for 12 or 24 weeks had high rates of sustained HCV virologic response 12 weeks after cessation of therapy,” the authors write. “Further studies of this regimen in more diverse populations of coinfected patients are needed.” (doi:10.1001/jama.2014.7734; Available pre-embargo to the media at https://media.jamanetwork.com) Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 10 a.m. CT Saturday, July 19 at this link. [ama_toc_item id="24027"] Editorial: Quantum Leaps, Microeconomics, and the Treatment of Patients With Hepatitis C and HIV Coinfection Michael S. Saag, M.D., of the University of Alabama School of Medicine, Birmingham, writes in an accompanying editorial that although this study (PHOTON-l) represents a quantum leap forward in the treatment of patients coinfected with HIV and HCV, the current cost of the regimen makes wide-spread use unaffordable. “When combined with ribavirin, the average wholesale price of a 12- week course of treatment is $94,500 and $189,000 for a 24-week course, as used in the PHOTON-l study. Industry analysts indicate that the pricing of the drug is not based on the cost of ingredients or the duration of therapy, but rather the ‘cost per cure.’ With more than 185 million HCV seropositive people worldwide with HCV infection and with 4.4 million HCV seropositive persons in the United States, the world simply cannot afford to pay on a ‘cost per cure’ basis, especially when the majority of persons with chronic infection, an estimated 75 percent, do not progress to cirrhosis or end-stage liver disease over 20 to 30 years.” “Hopefully, competition among the new products coming to market in the next 18 months will result in substantially lower pricing for the drugs. Indeed, the release of the new products will be, perhaps for the first time, a genuine test of whether there is a free market, microeconomic system in the pharmaceutical industry.” (doi:10.1001/jama.2014.7734; Available pre-embargo to the media at https://media.jamanetwork.com) Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc. # # #

EMBARGOED FOR EARLY RELEASE: 10 A.M. (CT) SATURDAY, JULY 19, 2014
Media Advisory: To contact Anna Satcher Johnson, M.P.H., call the CDC’s news media line at 404-639-8895 or email NCHHSTPMediaTeam@cdc.gov.

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The annual HIV diagnosis rate in the U.S. decreased more than 30 percent from 2002-2011, with declines observed in several key populations, although increases were found among certain age groups of men who have sex with men, especially young men, according to a study in the July 23/30 issue of JAMA, a theme issue on HIV/AIDS. The issue is being released early to coincide with the International AIDS Conference.

“There has been increasing emphasis on care and treatment for persons with human immunodeficiency virus (HIV) in the United States during the past decade, including the use of antiretroviral therapy for increasing survival and decreasing transmission. Accurate HIV diagnosis data recently became available for all states, allowing for the first time an examination of long-term national trends. These data can be used to monitor awareness of serostatus among persons living with HIV, primary prevention efforts, and testing initiatives,” according to background information in the article.

Anna Satcher Johnson, M.P.H., of the Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention (CDC), Atlanta, and colleagues examined trends in HIV diagnoses from 2002-2011 among persons ages 13 years or older in the United States, using data from the National HIV Surveillance System of the CDC. All data were collected through routine HIV surveillance mandated by laws or regulations in the 50 states and the District of Columbia.

During 2002-2011, 493,372 persons were diagnosed with HIV in the United States. The annual diagnosis rate decreased by 33.2 percent, from 24.1 per 100,000 population in 2002 to 16.1 in 2011. Statistically significant decreases in diagnosis rates over time were found in nearly every demographic population with the largest changes observed in women, persons 35-44 years of age, and persons of multiple races. Changes were not evident for Asians or Native Hawaiians/other Pacific Islanders. The annual number of HIV diagnoses decreased in persons with infection attributed to injection drug use or to heterosexual contact.

From 2002-2011, diagnoses attributed to male-to-male sexual contact remained stable overall, increasing among males 13-24, 45-54, and 55 years or older, and decreasing among males 35-44 years of age. The largest change (132.5 percent increase) was observed among males 13-24 years of age.

The authors note that because of delays in diagnosis, trends in diagnoses and variations among groups may reflect earlier changes in HIV infection rates. They add that this study is limited in that trends in diagnoses can be influenced by changes in testing patterns. “The HIV testing services were expanded during the analysis period and early outcomes of testing initiatives often indicate increases in diagnoses until some level of testing saturation occurs. Our study found overall decreases in annual diagnosis rates despite the implementation of testing initiatives during the period of analysis.”

“Among men who have sex with men, unprotected risk behaviors in the presence of high prevalence and unsuppressed viral load may continue to drive HIV transmission. Disparities in rates of HIV among young men who have sex with men present prevention challenges and warrant expanded efforts.”
(doi:10.1001/jama.2014.8534; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The CDC provides funds to all states and the District of Columbia to conduct the HIV surveillance data used in this study. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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