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

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

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

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

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

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

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

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

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 Improvement Needed of Prescription Drug Postmarketing Studies

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

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

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

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

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

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

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Viewpoints Appearing in This Issue of JAMA

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

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

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

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

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

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

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 Standards for Patient-Reported Outcome-Based Performance Measures

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

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

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

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

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Generic Clopidogrel – Time to Substitute?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

(JAMA. 2013;310(2):163-169; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

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

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

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

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

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

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

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

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

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

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

Editor’s Note: This work was supported in part by grants from the National Institute of Health, with minor support from the Prevent Cancer Foundation and the United Soybean Board. Solae LLC provided the intervention materials.  Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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

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

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

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

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

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

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

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

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

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

(JAMA. 2013;310(2):155-162; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

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

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

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

(JAMA. 2013;310(2):151-152; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

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

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

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

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

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

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

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

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

(JAMA. 2013;310(2):179-188; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

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

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

(JAMA. 2013;310(2):153-154; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Norris reports receiving grant support from the National Institutes of Health; and payment for lectures and consulting from Abbott, Amgen, Davita, and Takeda. Dr. Williams reported no disclosures.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 2, 2013

The Paradox of Disease Prevention – Celebrated in Principle, Resisted in Practice

In a Special Communication, Harvey V. Fineberg, M.D., Ph.D., of the Institute of Medicine, Washington, D.C., examines a number of the reasons that disease prevention in clinical medicine and public health is often resisted, and suggests and discusses the following strategies for overcoming these obstacles:

(1) Pay for preventive services. (2) Make prevention financially rewarding for individuals and families. (3) Involve employers to promote health in the workplace and provide incentives to employees to maintain healthy practices. (4) Reengineer products and systems to make prevention simpler, lower in cost, and less dependent on individual action. (5) Use policy to reinforce choices that favor prevention. (6) Use multiple media channels to educate, elicit health-promoting behavior, and strengthen healthy habits.

“The health care community cannot expect an overnight transformation; preventive messages must be repeated across many forms of media and entertainment to become solidified over time as cultural norms. Success will require a sustained effort from individuals and families in their daily lives; from physicians, nurses, pharmacists, and other health professionals; from cultural, entertainment and sports celebrities; from employers and insurers; from political, civic, and business leaders; from public agencies at all levels; and from philanthropies. In the end, prevention is truly worth the investment to make a difficult sell just a little easier and to put everyone on the road to a healthier future,” Dr. Fineberg concludes.

(JAMA. 2013;310[1]:85-90. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Harvey V. Fineberg, M.D., Ph.D., call Jennifer Walsh at 202-334-2138 or email jwalsh@nas.edu.

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

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 Smoking Cessation, Weight Gain, and Subsequent CHD Risk Among Postmenopausal Women With and Without Diabetes

“Cigarette smoking is an important cause of cardiovascular disease, and smoking cessation reduces the risk. However, weight gain after smoking cessation may increase the risk of diabetes and weaken the benefit of quitting,” write Juhua Luo, Ph.D., of the Indiana University School of Public Health, Bloomington, Ind., and colleagues.

As reported in a Research Letter, the authors used data from the Women’s Health Initiative (WHI) to assess the association between smoking cessation, weight gain, and subsequent coronary heart disease (CHD) risk among postmenopausal women with and without diabetes. In the WHI, 161,808 postmenopausal women 50 through 79 years of age were recruited from 40 sites between 1993 and 1998 and followed up every 6 to 12 months. Women without known cancer or cardiovascular disease at baseline or CHD at year 3 were followed up until CHD diagnosis, date of death, loss to follow-up, or September 30, 2010, whichever occurred first.

Of 104,391 women followed up, 3,381 developed CHD, during an average of 8.8 years. The researchers found that smoking cessation was associated with a lower risk of CHD among postmenopausal women with and without diabetes. Weight gain following smoking cessation weakened this association, especially for women with diabetes who gained 11 lbs. or more, although power was limited in this subgroup due to the small number of cases.

(JAMA. 2013;310[1]:94-95. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Juhua Luo, Ph.D., call Mary Hardin at 317-274-5456 or email mhardin@iu.edu.

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JAMA Gets a New Look!

First Major Print Redesign in Many Years

CHICAGO — Readers of the print issues of JAMA will notice something new this week – new design features inside the journal and a revised cover. “Although the redesign will be most evident in print, it will also improve the readability of our content on our digital platforms,” writes Howard Bauchner, M.D., JAMA Editor-in-Chief, and Ronna Henry, M.D., a JAMA Deputy Editor, in an editorial in the July 3 issue.

“The goals of the redesign were to create an inviting, visually lively publication with clear navigation for readers and to ensure harmony across The JAMA Network.” The redesign project includes all 10 medical journals in The JAMA Network which are now organized in a similar manner. “The order of articles, article types, and names of content sections are identical across the network. Readers will find similarly formatted articles regardless of which journal they read.”

“While this redesign is a major milestone, we are not done yet. We will continue to seek out the best content and to use new print, web, and digital developments to enhance the communication of our content,” the editors write. “Over the past 2 years we have reached out to prospective authors around the world, developed new article types, launched a new platform, renamed the Archives journals, introduced an app that allows users access to the entire content of The JAMA Network, and redesigned our entire content.”

(JAMA. 2013; 310(1):39; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Howard Bauchner, M.D., contact JAMA Media Relations at 312-464-JAMA (5262) or email: mediarelations@jamanetwork.org.

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 Viewpoint in This Issue of JAMA

The Convenience Revolution for Treatment of Low-Acuity Conditions

In this Viewpoint, Ateev Mehrotra, M.D., of RAND Health and the University of Pittsburgh School of Medicine, provides an overview of the factors driving the proliferation of convenient care treatment options for low-acuity conditions such as bronchitis and urinary tract infections and the issues that need consideration with their increasing popularity.

“The future influence of convenient care options largely depends on 2 issues. The first involves whether they expand beyond the scope of low-acuity care. In the business model of ‘disruptive innovations,’ new market entries first focus on the less expensive and less attractive aspects of the market (for example, low-acuity conditions), then gradually expand their scope. Signs of this expansion are appearing. Retail clinics have expanded into chronic illness care, some worksite clinics and urgent care centers offer full primary care, and e-visits can offer specialty consultations.”

“The second issue is whether convenient care options offer an attractive alternative to existing primary care clinicians. Many health systems have begun to offer their own retail clinics, urgent care centers, or e-visits. Whether these new efforts are sufficient remains to be seen, but primary care practitioners risk a slow but steady decline in their scope of care if they do not offer a viable alternative to these new convenient care options.”

(JAMA. 2013;310[1]:35-36. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Ateev Mehrotra, M.D., call Andréa Stanford at 412-647-6190 or email stanfordac@upmc.edu.

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

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 2, 2013

Media Advisory: To contact Mary M. McDermott, M.D., call Erin White at 847-491-4888 or email ewhite@northwestern.edu.

CHICAGO – In a trial that included nearly 200 participants with peripheral artery disease (PAD), a home-based exercise intervention with a group-mediated cognitive behavioral intervention component improved walking performance and physical activity in patients with PAD, according to a study in the July 3 issue of JAMA.

“Few medical therapies improve the functional impairment associated with lower extremity peripheral artery disease. Supervised treadmill exercise increases maximal treadmill walking distance by 50 percent to 200 percent in individuals with PAD. However, supervised exercise is typically not covered by medical insurance and requires regular transportation to the exercise center. Thus, few patients with PAD participate in supervised treadmill exercise therapy,” according to background information in the article.

“Home-based walking exercise is a promising alternative to supervised exercise. However, several clinical trials of home-based exercise in people with PAD have been small and inconclusive. Recent, larger randomized trials have yielded mixed results. Current clinical practice guidelines state that there is insufficient evidence to recommend home-based walking exercise for people with PAD. Most physicians do not recommend home-based walking exercise to patients with PAD,” the authors write.

Mary M. McDermott, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, and colleagues conducted a study to determine whether a home-based walking exercise program that uses a group-mediated cognitive behavioral intervention, incorporating both group support and self-regulatory skills, can improve functional performance compared with a health education control group in patients with PAD with and without intermittent claudication (pain in the calf that typically is felt while walking and usually subsides with rest). The randomized clinical trial, conducted between July 2008 and December 2012, included 194 patients with PAD (72 percent without classic symptoms of intermittent claudication). The primary measured outcome was 6-month change in 6-minute walk performance.

The researchers found that at 6-month follow-up, participants in the intervention group improved their 6-minute walking distance compared with the control group by 1,173 to 1,312 feet vs. 1,159 to 1,123 feet for those in the control group, an average difference of 176 feet. Also, participants in the intervention group, compared with the control group, significantly improved their maximal treadmill walking time (7.91 to 9.44 minutes vs. 7.56 to 8.09 minutes); improved their pain-free walking time; increased their physical activity; improved their Walking Impairment Questionnaire (WIQ) distance score and WIQ speed score.

Participants randomized to the intervention group were about 3 times more likely to achieve a small meaningful improvement (66 feet) in the 6-minute walk and approximately 6 times more likely to achieve a large meaningful improvement (164 feet).

“Based on these findings, clinical practice guidelines should advise clinicians to recommend home-based walking programs with a weekly group-mediated cognitive behavioral intervention component for patients with PAD who do not have access to supervised exercise,” the authors write. “These findings have implications for the large number of patients with PAD who are unable or unwilling to participate in supervised exercise programs.”

(JAMA. 2013;310(1):57-65; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 2, 2013

Media Advisory: To contact Sven Sandin, M.Sc., email Sven.Sandin@ki.se. To contact editorial author Marcelle I. Cedars, M.D., call Karin Rush-Monroe at 415-502-NEWS or email Karin.Rush-Monroe@ucsf.edu.

CHICAGO – In a study that included more than 2.5 million children born in Sweden, compared with spontaneous conception, any in vitro fertilization (IVF) treatment was not associated with autistic disorder but was associated with a small but statistically significantly increased risk of mental retardation, according to a study in the July 3 issue of JAMA. The authors note that the prevalence of these disorders was low, and the increase in absolute risk associated with IVF was small.

“Between 1978 and 2012, approximately 5 million infants worldwide were born from in vitro fertilization,” according to background information in the article. “No study has investigated the association between different IVF procedures and neurodevelopment, and few studies have investigated whether IVF treatments are associated with neurodevelopment after the first year of life. Few studies have looked at autistic disorder and mental retardation, 2 of the most severe chronic developmental disorders, affecting 1 percent to 3 percent of all children in developed countries.”

Sven Sandin, M.Sc., of King’s College London, and colleagues examined the association between use of any IVF and different IVF procedures and the risk of autistic disorder and mental retardation in the offspring. Using Swedish national health registers, offspring born between 1982 and 2007 were followed up for a clinical diagnosis of autistic disorder or mental retardation until December 2009. The exposure of interest was IVF, categorized according to whether intracytoplasmic sperm injection (ICSI) for male infertility was used and whether embryos were fresh or frozen.

A total of 2,541,125 children were alive at 1.5 years of age and had complete data on all the covariates; 30,959 (1.2 percent) were born following an IVF procedure. Autistic disorder was diagnosed in 103 of 6,959 children (1.5 percent) and mental retardation in 180 of 15,830 children (1.1 percent) who were born after an IVF procedure. Cases had an average follow-up time of 10 years, median (midpoint) 14 years.

Analysis of the data indicated that compared with spontaneous conception, any IVF treatment was not associated with autistic disorder but was associated with a small but statistically significantly increased risk of mental retardation, although when restricted to singletons (single births), the risk for mental retardation was no longer statistically significant. “However, the results demonstrated an association between autistic disorder and mental retardation and specific IVF procedures with ICSI related to paternal origin of infertility compared with IVF without ICSI,” the authors write.

“The prevalence of these disorders was low, and the increase in absolute risk associated with IVF was small. These associations should be assessed in other populations.”

“To the best of our knowledge, this is the largest study examining the relationship between specific IVF procedures and autistic disorder and mental retardation, examining the full range of IVF procedures,” the researchers write. “Our results should be applicable to most countries where IVF and ICSI are used. There are no major differences in equipment or laboratory work across countries but there may be some differences in choice of procedure. For instance, in several countries (like the United States), ICSI is often used when the sperm sample is normal because of a presumed (but unproven) higher efficiency. Blastocyst [a structure in early embryonic development that contains a cluster of cells] transfer is infrequently used in Sweden but is more common in the United States.”

(JAMA. 2013;310(1):75-84; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was funded by Autism Speaks and the Swedish Research Council. Dr. Illiadou was supported by a grant from EU-FP7 HEALTH. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: In Vitro Fertilization and Risk of Autistic Disorder and Mental Retardation

Marcelle I. Cedars, M.D., of the University of California-San Francisco, comments on the findings of this study in an accompanying editorial.

“The study by Sandin et al has sufficient numbers of IVF procedures and outcomes and detailed information to address questions regarding specific aspects of IVF that may pose special risk. Even though the data are reassuring regarding the absence of risk of autistic disorder and the small absolute risk of mental retardation with IVF, continued study of the implications of ovarian stimulation, embryo culture, and multiple embryo transfer is required. The number of children born as a result of IVF will continue to increase and much remains to be learned about the long-term implications. Understanding and eliminating even a small risk of neurodevelopmental impairment are important goals.”

(JAMA. 2013;310(1):42-43; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 2, 2013

Media Advisory: To contact corresponding author Kenneth McDonald, M.D., email kenneth.mcdonald@ucd.ie or call 353-86-825-5428. To contact editorial author Adrian F. Hernandez, M.D., M.H.S., call Sarah Avery at 919-660-1306 or email sarah.avery@duke.edu.

CHICAGO – Among patients at risk of heart failure, collaborative care based on screening for certain levels of brain-type natriuretic peptide reduced the combined rates of left ventricular systolic dysfunction, diastolic dysfunction, and heart failure as well as emergency cardiovascular hospitalizations, according to a study in the July 3 issue of JAMA.

“The increasing prevalence of heart failure [HF] remains a major public health concern underlining the need for an effective prevention strategy. Present-day approaches, focusing mainly on risk factor intervention, have brought about some reduction in new-onset HF. However recent major reports in the United States and the European Union underline difficulties in achieving adequate risk factor control and show that present strategies will not be as effective as desired,” according to background information in the article.

Refining risk prediction may be aided by the use of brain-type natriuretic peptide (BNP; a peptide secreted by the ventricles of the heart), which has been shown in large general populations to identify those at highest risk of cardiovascular events and, more specifically, of newly diagnosed HF. Studies have shown advantages of using this peptide in this regard over conventional risk indicators. This may reflect the fact that BNF is a response to established cardiovascular damage whereas other conventional risk indicators reflect the potential for cardiovascular insult (injury), the authors write.

Mark Ledwidge, Ph.D., of St. Vincent’s Healthcare Group/St. Michael’s Hospital, Dublin, and colleagues conducted a study to determine the efficacy of a screening program using BNP and collaborative care in an at-risk population in reducing newly diagnosed heart failure and prevalence of significant left ventricular (LV) systolic and/or diastolic dysfunction. The randomized trial included 1,374 participants with cardiovascular risk factors (average age, 65 years) recruited from 39 primary care practices in Ireland between January 2005 and December 2009 and followed up until December 2011 (average follow-up, 4.2 years). Patients were randomly assigned to receive usual primary care (control condition; n=677) or screening with BNP testing (n=697). Intervention-group participants with BNP levels of 50 pg/mL or higher underwent echocardiography and collaborative care between their primary care physician and specialist cardiovascular service, including optimal risk factor management with the most appropriate therapy coaching by a specialist nurse who emphasized individual risk status and the importance of adherence to medication and healthy lifestyle behaviors.

A total of 263 patients (41.6 percent) in the intervention group had at least 1 BNP reading of 50 pg/mL or higher. The researchers found that the primary end point of left ventricular dysfunction and HF was met in 59 (8.7 percent) of 677 control-group patients and 37 (5.3 percent) of 697 intervention-group patients. Asymptomatic left ventricular dysfunction was found in 6.6 percent of control-group patients and 4.3 percent of intervention-group patients. Heart failure occurred in 2.1 percent of control-group patients and 1.0 percent of intervention-group patients.

Seventy-one patients (10.5 percent) were admitted for major adverse cardiovascular events in the control group and 51 (7.3 percent) were admitted in the intervention group. The incidence rates of emergency hospitalization for major cardiovascular events were higher in the control group vs. the intervention group. In the group with BNP levels of 50 pg/mL or higher, the incidence rates of emergency hospitalization for major adverse cardiovascular events were also higher in the control group vs. the intervention group.

“[This study] confirms BNP as a risk identifier for HF and cardiovascular events and provides unique data on the potential benefit of using levels of this peptide as a guide for care. The positive clinical effect of this intervention was associated with improved risk factor control, increased use of agents that modulate the renin-angiotensin-aldosterone system targeted at those with elevated BNP levels, and increased use of some cardiovascular diagnostics. These data suggest that a targeted strategy for HF prevention using BNP and collaborative care in a community population may be effective and that benefits extend beyond prevention of HF to an overall reduction in emergency cardiovascular admissions,” the authors write. “The need for an effective prevention approach to HF is underlined by epidemiological trends, with HF prevalence expected to increase by 30 percent in the United States by 2030.”

(JAMA. 2013;310(1):66-74; 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: Preventing Heart Failure

In an accompanying editorial, Adrian F. Hernandez, M.D., M.H.S., of the Duke University School of Medicine, Durham, N.C., writes that this study “raises several important issues for prevention of heart failure.”

“First, the clinical measurement of BNP levels has largely focused on the diagnosis of heart failure in patients who present with dyspnea [difficult or labored breathing] rather than screening for heart failure. Although substantial evidence exists to support the prognostic value of BNP levels across a spectrum of cardiovascular disease and in population-based studies, there is less evidence to support measurement as a routine screening tool for asymptomatic left ventricular dysfunction. Second, it is often challenging to identify patients at risk of heart failure given that screening tests are highly dependent on the prevalence of the disorder being targeted. Therefore, developing a test strategy to identify patients at risk of heart failure is difficult because of the heterogeneity of the population and the variable duration until clinical heart failure or systolic dysfunction develops.”

“In addition, the costs of screening tests can become enormous depending on the volume of testing and the population being screened. Nevertheless, targeting patients at higher risk of heart failure may overcome these issues and, depending on prevalence, may prove to be cost-effective.”

(JAMA. 2013;310(1):44-45; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 2, 2013

Media Advisory: To contact Karen L. Margolis, M.D., M.P.H., call Annelise Searle at 952-883-5308 or email Annelise.m.searle@healthpartners.com. To contact editorial co-author David J. Magid, M.D., M.P.H., call Amy Whited at 303-344-7518 or email amy.l.whited@kp.org.

CHICAGO – An intervention that consisted of home blood pressure (BP) telemonitoring with pharmacist management resulted in improvements in BP control and decreases in BP during 12 months, compared with usual care, and improvement in BP that was maintained for 6 months following the intervention, according to a study in the July 3 issue of JAMA.

“High blood pressure is the most common chronic condition for which patients visit primary care physicians, affecting about 30 percent of U.S. adults, with estimated annual costs exceeding $50 billion. Decades of research have shown that treatment of hypertension prevents cardiovascular events; and many well-tolerated, effective, and inexpensive drugs are readily available. Although BP control has improved during the past 2 decades, it is controlled to recommended levels in only about half of U.S. adults with hypertension,” according to background information in the article. “Several recent studies suggest that a combined intervention of telemedicine with nurse- or pharmacist-led care may be effective for improving hypertension management, but none included postintervention follow-up. Also, previous studies excluded patients with comorbidities [other illnesses] and more severe hypertension.”

Karen L. Margolis, M.D., M.P.H., of the HealthPartners Institute for Education and Research, Minneapolis, and colleagues conducted a study to determine the effect and durability of home BP telemonitoring with pharmacist case management in patients representative of the range of comorbidity and hypertension severity in typical primary care practices. The randomized clinical trial included 450 adults with uncontrolled BP recruited from 14,692 patients with electronic medical records across 16 primary care clinics in an integrated health system in Minneapolis-St. Paul, with 12 months of intervention and 6 months of postintervention follow-up.

Eight clinics were randomized to provide usual care to patients (n = 222) and 8 clinics were randomized to provide a telemonitoring intervention (n = 228). Intervention patients received home BP telemonitors and transmitted BP data to pharmacists who adjusted antihypertensive therapy accordingly. The primary measured outcome was control of systolic BP to less than 140 mm Hg and diastolic BP to less than 90 mm Hg (<130/80 mm Hg in patients with diabetes or chronic kidney disease) at 6 and 12 months. Secondary outcomes were change in BP, patient satisfaction, and BP control at 18 months (6 months after intervention stopped).

Among the 380 patients attending both the 6- and 12-month visits, the proportions of patients with controlled BP at both visits were 57.2 percent in the telemonitoring intervention group and 30.0 percent in the usual care group. At 18 months, BP was controlled in 71.8 percent of the telemonitoring intervention group and 57.1 percent of the usual care group. Among the 362 patients attending all clinic visits at 6, 12, and 18 months, the proportions of patients with controlled BP at all visits were 50.9 percent in the telemonitoring intervention group and 21.3 percent in the usual care group.

“Self-efficacy questions indicated telemonitoring intervention patients were substantially more confident than usual care patients that they could communicate with their health care team, integrate home BP monitoring in their weekly routine, follow their medication regimen, and keep their BP under control. Telemonitoring intervention patients self-reported adding less salt to food than usual care patients at all time points, but other lifestyle factors did not differ,” the authors write.

“If these results are found to be cost-effective and durable during an even longer period, it should spur wider testing and dissemination of similar alternative models of care for managing hypertension and other chronic conditions.”

(JAMA. 2013;310(1):46-56; Available pre-embargo to the media at https://media.jamanetwork.com)

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

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, July 2 at this link.

Editorial: Home Blood Pressure Monitoring

In an accompanying editorial, David J. Magid, M.D., M.P.H., of the Kaiser Permanente Colorado Institute for Health Research, Denver, and Beverly B. Green, M.D., M.P.H., of the Group Health Research Institute, Seattle, write that “for home BP monitoring to become part of routine practice, changes to the current system of reimbursement and performance measurement will be needed.”

“First, to minimize patient barriers to participation, health insurers must follow the lead of the Veterans Health Administration and provide benefit coverage for BP monitors. Second, clinicians and health care organizations must be reimbursed for services related to home BP monitoring, which are currently not covered by Medicare and many other payers; otherwise, clinicians in fee-for-service systems are unlikely to voluntarily give up reimbursements for hypertension-related office visits. Third, home BP measurements must be included in quality assurance assessments of hypertension care. Currently, the National Committee for Quality Assurance performance measure for BP control considers only BP measurements made in the clinic, even though home BP measurements correlate as well or better with 24-hour ambulatory BP measurements and are more predictive of cardiovascular outcomes than clinic measures.”

(JAMA. 2013;310(1):40-41; 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, JUNE 25, 2013

Media Advisory: To contact Gabriela Ilie, Ph.D., call Leslie Shepherd at 416-864-6094 or email shepherdl@smh.ca.

“Traumatic brain injury (TBI) among adolescents has been identified as an important health priority. However, studies of TBI among adolescents in large representative samples are lacking. This information is important to the planning and evaluation of injury prevention efforts, particularly because even minor TBI may have important adverse consequences,” write Gabriela Ilie, Ph.D., of St. Michael’s Hospital, Toronto, Canada, and colleagues, who examined the prevalence of TBI, mechanisms of injury, and adverse correlates in a large representative sample of adolescents living in Ontario, Canada.

As reported in a Research Letter, data were derived from the Centre for Addiction and Mental Health’s 2011 Ontario student drug use and health survey, consisting of anonymous, self-administered questionnaires completed in classrooms by students grades 7-12 (age range: 11-20 years; n = 8,915). Traumatic brain injury was defined as an acquired head injury in which the student was unconscious for at least 5 minutes or hospitalized overnight.

The estimated lifetime prevalence of TBI was 20.2 percent; 5.6 percent of respondents reported at least 1 TBI in the past 12 months (4.3 percent of girls and 6.9 percent of boys) and 14.6 percent reported a TBI in their lifetime but not in the past 12 months (12.8 percent of girls and 16.2 percent of boys). Sports injuries accounted for more than half of the cases in the past 12 months (56 percent) and were more common among males (46.9 percent in girls and 63.3 percent in boys). Students who reported occasional to frequent consumption of alcohol and cannabis in the past 12 months had significantly higher odds of TBI in the past 12 months than abstainers.

“In the United States, more than half a million adolescents aged 15 years or younger require hospital-based care for head injury annually, and our data suggest a much higher number of adolescents may be experiencing these injuries,” the authors write. “The magnitude of the prevalence estimates and the associated risks identified within this representative sample support suggestions to improve understanding, prevention, and response to TBI among adolescents.”

(JAMA. 2013;309[24]:2550-2552. Available pre-embargo to the media at https://media.jamanetwork.com)

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

EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JUNE 25, 2013

Media Advisory: To contact corresponding author Andrew T. Chan, M.D., M.P.H., call Jessica Maki at 617-534-1603 or email jmaki3@partners.org; for corresponding author Shuji Ogino, M.D., Ph.D., M.S., call Anne Doerr at 617-632-5665 or email anne_doerr@dfci.harvard.edu. To contact editorial author Boris Pasche, M.D., Ph.D., call Beena Thannickal at 205-975-3967 or email beenat@uab.edu.

CHICAGO – In 2 large studies, the association between aspirin use and risk of colorectal cancer was affected by mutation of the gene BRAF, with regular aspirin use associated with a lower risk of BRAF-wild-type colorectal cancer but not with risk of BRAF-mutated cancer, findings that suggest that BRAF-mutant colon tumor cells may be less sensitive to the effect of aspirin, according to a study in the June 26 issue of JAMA.

Colorectal cancer is a leading cause of cancer-related death worldwide. Randomized controlled trials have demonstrated that aspirin use reduces the risk of colorectal cancer, according to background information in the article. Experimental evidence has suggested that BRAF-mutant colonic cells might be less sensitive to the antitumor effects of aspirin than BRAF-wild-type (the typical form of a gene as it occurs in nature) neoplastic cells.

Reiko Nishihara, Ph.D., of the Dana-Farber Cancer Institute, Boston, and colleagues examined the association of aspirin use with the risk of colorectal cancer according to BRAF mutation status. The researchers collected biennial questionnaire data on aspirin use and followed up participants in the Nurses’ Health Study (from 1980) and the Health Professionals Follow-up Study (from 1986) until July 2006 for cancer incidence and until January 2012 for cancer mortality.

Among 127,865 individuals, 1,226 incident rectal and colon cancers were identified with available molecular data. The researchers found that regular aspirin use was associated with a significantly lower risk (27 percent) of BRAF-wild-type cancer. Regular aspirin use was not associated with a lower risk of BRAF-mutated cancer. “The association of aspirin use with colorectal cancer risk differed significantly according to BRAF mutation status.”

The authors also observed a lower risk of BRAF-wild-type cancer with increasing aspirin tablets per week; however, there was not a significant trend in risk reduction for BRAF-mutated cancer. “The association of aspirin tablets per week with cancer risk differed significantly by BRAF mutation status. Compared with individuals who reported no aspirin use, a significantly lower risk of BRAF-wild-type cancer was observed among individuals who used 6 to 14 tablets of aspirin per week and among those who used more than 14 tablets of aspirin per week.”

In addition, longer duration of aspirin use was associated with significant risk reduction for BRAF-wild-type cancer, whereas duration of aspirin use was not significantly associated with BRAF-mutated cancer risk.

“There was no statistically significant interaction between post-diagnosis aspirin use and BRAF mutation status in colorectal cancer-specific or overall survival analysis. This suggests that the potential protective effect of aspirin may differ by BRAF status in the early phase of tumor evolution before clinical detection but not during later phases of tumor progression,” the authors write.

“The identification of specific cancer-subtypes that are prevented by aspirin is important for several reasons. First, it enhances our understanding of the molecular pathogenesis of colorectal neoplasia and the mechanisms through which aspirin may exert its antineoplastic effects. Second, development of clinical, genetic, or molecular predictors of specific subtypes of colorectal cancer might lead to the development of more tailored screening or chemo-preventive strategies. Nevertheless, given the modest absolute risk difference, further investigations are necessary to evaluate clinical implications of our findings. Lastly, our data provide additional support for a causal association between aspirin use and risk reduction for a specific subtype of colorectal cancers. Accumulating evidence supports preventive effect of aspirin against colorectal cancer.”

(JAMA. 2013;309(24):2563-2571; 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: Differential Effects of Aspirin Before and After Diagnosis of Colorectal Cancer

In an accompanying editorial, Boris Pasche, M.D., Ph.D., of the University of Alabama at Birmingham, (and JAMA contributing editor), comments on the findings of this study.

“Nishihara el al derived their report from the Nurses’ Health Study and the Health Professionals Follow-up Study, which include a large number of female and male health professionals. This population is predominantly white: 98 percent of the participants in the Nurses’ Health Study and 95 percent of participants in the Health Professionals Follow-up Study are of a non-Hispanic white ethnic background. However, black individuals have the highest incidence of colorectal cancer in the United States and represent the ethnic group for whom colorectal cancer prevention may have the greatest benefit. Therefore, it will be important to determine whether the findings reported by Nishihara et al are confirmed in black individuals.”

“In summary, these results identify biomarkers of response to aspirin administered either preventively or therapeutically and are likely to help tailor the use of aspirin in the prevention and treatment of colorectal cancer.”

(JAMA. 2013;309(24):2598-2599; 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, JUNE 25, 2013

Media Advisory: To contact corresponding author Brent K. Hollenbeck, M.D., M.S., call Justin Harris at 734-764-2220 or email juaha@umich.edu.

CHICAGO – Use of advanced treatment technologies for prostate cancer, such as intensity-modulated radiotherapy and robotic prostatectomy, has increased among men with low-risk disease, high risk of noncancer mortality, or both, a population of patients who are unlikely to benefit from these treatments, according to a study in the June 26 issue of JAMA.

“Prostate cancer is a common and expensive disease in the United States. In part because of the untoward morbidity of traditional radiation and surgical therapies, advances in the treatment of localized disease have evolved over the last decade. Chief among these are the development of intensity-modulated radiotherapy (IMRT) and robotic prostatectomy,” according to background information in the article. “During a period of increasing population-based rates of prostate cancer treatment, both of these advanced treatment technologies have disseminated rapidly. However, the rapid growth of IMRT and robotic prostatectomy may have occurred among men with a low risk of dying from prostate cancer. Recognizing the protracted clinical course for most of these cancers, clinical guidelines recommend local treatment only for men with at least a 10-year life expectancy.”

“Aggressive direct-to-consumer marketing and incentives associated with fee-for-service payment may promote the use of these advanced treatment technologies,” the authors write. “The extent to which these advanced treatment technologies have disseminated among patients at low risk of dying from prostate cancer is uncertain.” They add that understanding patterns of new technology use in this population is particularly important given the growing concerns about overtreatment.

Bruce L. Jacobs, M.D., M.P.H., of the University of Michigan, Ann Arbor, and colleagues conducted a study to assess the use of advanced treatment technologies, compared with prior standards (i.e., traditional external beam radiation treatment [EBRT] and open radical prostatectomy) and observation, among men with a low risk of dying from prostate cancer. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, the researchers identified a retrospective group of men diagnosed with prostate cancer between 2004 and 2009 who underwent IMRT (n = 23,633), EBRT (n = 3,926), robotic prostatectomy (n = 5,881), open radical prostatectomy (n = 6,123), or observation (n = 16,384). Follow-up data were available through December 2010. Low-risk disease was defined as clinical stage ≤T2a, biopsy Gleason score ≤6, and prostate-specific antigen level ≤10 ng/mL. High risk of noncancer mortality was defined as the predicted probability of death within 10 years in the absence of a cancer diagnosis.

The researchers found that the use of advanced treatment technologies was common among men with low-risk disease (an increase from 32 percent in 2004 to 44 percent in 2009), those with a high risk of noncancer mortality (from 36 percent in 2004 to 57 percent in 2009), and those with both low-risk disease and a high risk of noncancer mortality (from 25 percent in 2004 to 34 percent in 2009).

Among all patients diagnosed with prostate cancer in SEER, the use of advanced treatment technologies for men unlikely to die of prostate cancer increased from 13 percent in 2004 to 24 percent in 2009, a relative increase of 85 percent. “That is, rates of IMRT and robotic prostatectomy use increased from 129.2 per 1,000 patients in 2004 to 244.2 per 1,000 patients diagnosed with prostate cancer in 2009. At the same time, the use of prior standard treatments for men least likely to benefit decreased from 11 percent in 2004 to 3 percent in 2009,” the authors write.

“The increasing use of both IMRT and robotic prostatectomy in populations unlikely to benefit from treatment was largely explained by their substitution for the treatments they aim to replace, namely EBRT and open radical prostatectomy.”

The researchers suggest that the absolute magnitude of the use of advanced treatment technologies in these populations has two important implications. “First, both treatments are considerably more expensive than the prior standards. Start-up costs for both approach $2 million.  Further, IMRT is associated with higher total episode payments, which translate into an additional $1.4 billion in spending annually. Thus, the implications of any potential overtreatment with these advanced treatment technologies are amplified in financial terms.”

“Second, and perhaps more important, the implementation of these technologies in populations unlikely to benefit from treatment occurred during a time of increasing awareness about the indolent nature of some prostate cancers and of growing dialogue about limiting treatment in these patients. Our findings suggest that even during this period of enhanced stewardship, incentives favoring the diffusion of these technologies outweighed those related to implementing a more conservative management strategy.”

“Continued efforts to differentiate indolent from aggressive disease and to improve the prediction of patient life expectancy may help reduce the use of advanced treatment technologies in this patient population,” the authors conclude.

(JAMA. 2013;309(24):2587-2595; 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, June 25 at this link.

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EMBARGOED FOR EARLY RELEASE: 10:30 A.M. (CT) MONDAY, JUNE 24, 2013

Media Advisory: To contact Karen E. Joynt, M.D., M.P.H., call Marge Dwyer at 617-432-8416 or email mhdwyer@hsph.harvard.edu. To contact editorial co-author Aaron E. Carroll, M.D., M.S., call Mary Hardin at 317-274-5456 or email mhardin@iu.edu.

CHICAGO – In an analysis that included a sample of patients in the top portion of Medicare spending, only a small percentage of their costs appeared to be related to preventable emergency department visits and hospitalizations, limiting the ability to lower costs for these patients through better outpatient care, according to a study in the June 26 issue of JAMA. The study is being released early to coincide with its presentation at the AcademyHealth annual research meeting.

“High and increasing health care costs are arguably the single biggest threat to the long-term fiscal solvency of federal and state governments in the United States. One compelling strategy for cost containment is focusing on the small proportion of patients in the Medicare programs who account for the vast majority of health care spending. We know from prior work that Medicare spending is highly concentrated: 10 percent of the Medicare population accounts for more than half of the costs to the program,” according to background information in the article.

The biggest sources of spending among high-cost beneficiaries are those related to acute care: emergency department (ED) visits and inpatient hospitalizations. “As a result, many interventions targeting high-cost patients have focused on case management and care coordination, aiming to prevent ED visits and hospitalizations for conditions thought amenable to improvement through high-quality outpatient management programs. The premise behind these and related interventions is that high-quality outpatient care should reduce unnecessary hospitalizations for high-cost patients. However, there are few data on the proportion of inpatient hospitalizations among high-cost patients that are potentially preventable,” the authors write.

Karen E. Joynt, M.D., M.P.H., of the Harvard School of Public Health, Boston, and colleagues conducted a study to quantify the preventability of high-cost Medicare patients’ acute care spending. The researchers summed standardized costs for each inpatient and outpatient service contained in standard 5 percent Medicare files from 2009 and 2010 across the year for each patient in their sample, and defined those in the top decile (one of ten groups) of spending in 2010 as high-cost patients and those in the top decile in both 2009 and 2010 as persistently high-cost patients. Standard algorithms were used to identify potentially preventable emergency department visits and acute care inpatient hospitalizations. A total of 1,114,469 Medicare fee-for-service beneficiaries 65 years of age or older were included.

The high-cost patient group, which included 10 percent of the patients in this sample, were older, more often male and more often black. This group was responsible for 32.9 percent of ED costs and 79.0 percent of inpatient costs. Within the high-cost group, 42.6 percent of ED visits were deemed to be preventable. These visits were associated with 41 percent of the ED costs within this group. The most common reasons for preventable hospitalization in high-cost patients were congestive heart failure, bacterial pneumonia, and chronic obstructive pulmonary disease.

Within the high-cost group, 9.6 percent of hospital costs were attributable to preventable hospitalization. Within the non-high-cost group, though overall spending was significantly lower, a higher proportion of inpatient costs were potentially preventable (16.8 percent).

“Comparable proportions of ED spending (43.3 percent) and inpatient spending (13.5 percent) were preventable among persistently high-cost patients. Regions with high primary care physician supply had higher preventable spending for high-cost patients,” the authors write.

“The biggest drivers of inpatient spending for high-cost patients were catastrophic events such as sepsis, stroke, and myocardial infarction, as well as cancer and expensive orthopedic procedures such as spine surgery and hip replacement. These findings suggest that strategies focused on enhanced outpatient management of chronic disease, while critically important, may not be focused on the biggest and most expensive problems plaguing Medicare’s high-cost patients.”

The researchers add that their “findings suggest that a complementary approach to saving money on acute care services for high-cost patients may be to additionally focus on reducing per-episode costs for high-cost disease entities through clinical innovation and care delivery redesign.”

(JAMA. 2013;309(24):2572-2578; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: New Evidence Supports, Challenges, and Informs the Ambitions of Health Reform

Aaron E. Carroll, M.D., M.S., of the Indiana University School of Medicine, Indianapolis, and Austin B. Frakt, Ph.D., of the VA Boston Healthcare System, Boston University Schools of Medicine and Public Health, Boston, comment on the findings of this study in an accompanying editorial.

“These findings certainly do not suggest abandoning efforts to reduce preventable emergency department use and hospitalizations. Joynt et al do not consider the social cost of this utilization. Even though avoiding some emergency department use and hospital admissions might not save much money—and certainly not enough to declare victory in controlling health spending—preventing such use when possible would be of substantial benefit to patients, both those who would otherwise use these services and those who have their care delayed because of overburdened emergency department and hospital resources. Even with no cost savings, reducing preventable use of high-intensity and capacity-constrained care would enhance efficiency. Improvements to quality are not always substantial cost savers but still may be worthwhile.”

(JAMA. 2013;309(24):2600-2601; 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 EARLY RELEASE: 8 A.M. (CT) SUNDAY, JUNE 23, 2013

Media Advisory: To contact Sandra L. Decker, Ph.D., call Jeff Lancashire at 301-458-4800 or email jhl1@cdc.gov. To contact co-author Genevieve M. Kenney, Ph.D., call 202-261-5568 or email jkenney@urban.org.

CHICAGO – Compared with adults already enrolled in Medicaid, low-income uninsured adults who may be eligible for Medicaid under the Affordable Care Act were less likely to have chronic conditions such as hypertension, diabetes, and hypercholesterolemia, although those with 1 of these conditions were less likely to be aware they had it or to have the disease controlled, according to a study in the June 26 issue of JAMA. The study is being released early to coincide with its presentation at the AcademyHealth annual research meeting.

Under the Affordable Care Act (ACA), states have the option to expand Medicaid coverage to most low-income adults, an option that could add millions of new Medicaid enrollees. “In states choosing to implement the expansion, with full federal financing from 2014 through 2016, this would expand Medicaid’s traditional focus away from low-income pregnant women and children, very-low-income parents, and the severely disabled to new population groups. These include childless adults and parents whose incomes are too high to qualify for Medicaid under current state eligibility criteria. This is likely to affect the type of Medicaid patients seen by physicians in states choosing to expand Medicaid. State decisions regarding Medicaid expansion will likely consider the anticipated costs and health benefits to their populations,” according to background information in the article. “Uncertainty exists regarding the scope of medical services required for new enrollees.”

Sandra L. Decker, Ph.D., of the Centers for Disease Control and Prevention, Hyattsville, Md., and colleagues conducted a study to document the health care needs and health risks of uninsured adults who could gain Medicaid coverage under the ACA. Data from the National Health and Nutrition Examination Survey 2007-2010 were used to analyze health conditions among a nationally representative sample of 1,042 uninsured adults 19 through 64 years of age with income no more than 138 percent of the federal poverty level, compared with 471 low-income adults currently enrolled in Medicaid. The 1,042 uninsured respondents correspond to a weighted estimate of 14.7 million uninsured adults who could be eligible for Medicaid coverage under the ACA based on 2007-2010 demographic characteristics. The primary measured outcomes were prevalence and control of diabetes, hypertension, and hypercholesterolemia based on examinations and laboratory tests; measures of self-reported health status including medical conditions; and risk factors such as obesity status.

The researchers found that compared with those enrolled in Medicaid, the uninsured adults reported better overall health; were less likely to be obese and sedentary; less likely to report a physical, mental, or emotional limitation; and much less likely (by 15.1 percentage points) to have multiple health conditions.

Although the uninsured adults were less likely than those enrolled in Medicaid to have diabetes, hypertension, or hypercholesterolemia (30.1 percent compared with 38.6 percent), if they had 1 of these conditions, the conditions were more likely to be undiagnosed or uncontrolled. An estimated 80.1 percent of the uninsured adults with 1 or more of these 3 conditions had at least 1 uncontrolled condition, compared with 63.4 percent of those enrolled in Medicaid.

The weighted counts corresponding to the prevalence estimates translate to approximately 1.4 million uninsured adults potentially eligible for Medicaid with at least 1 condition undiagnosed and 3.5 million with at least 1 condition uncontrolled, compared with approximately 0.6 million and 1.4 million, respectively, among those currently enrolled in Medicaid.

“One-third of potential new Medicaid enrollees are obese, half currently smoke, one-fourth report a functional limitation, and one-fourth report their health as fair or poor—all factors that could require attention from clinicians. If Medicaid uptake is low, the uninsured adults who do enroll in Medicaid may be disproportionately drawn from those with more health problems than average among those made newly eligible. Because many of the uninsured adults have not seen a physician in the past year and do not have a place they usually go for routine health care, they are likely to need care on first enrolling in Medicaid,” the authors write.

(JAMA. 2013;309(24):2579-2586; 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, JUNE 18, 2013

Study Finds Need for Improvement on State Health Care Price Websites

“With rising health care costs and 30 percent of privately insured adults enrolled in high-deductible health care plans, calls for greater health care price transparency are increasing. In response, health plans, consumer groups, and state governments are increasingly reporting health care prices. Despite recognition that price information must be relevant, accurate, and usable to improve the value of patients’ out-of-pocket expenditures, and the potential for this reporting to affect health care organizations and prices, there are no data on what kind of price information is being reported,” writes Jeffrey T. Kullgren, M.D., M.S., M.P.H., of the Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Mich., and colleagues.

As reported in a Research Letter, the authors conducted a study to examine the characteristics of state health care price websites and identify opportunities for improving the utility of this information. Systematic Internet searches were conducted between January and May 2012 to identify publicly available, patient-oriented websites hosted by a state specific institution (e.g., a state government agency or hospital association) that enabled patients to estimate or compare prices for health care services in that state. For each website, a number of factors were examined, including classifying the reporting organization, year reporting started, patient information used to generate price estimates, and types of services for which price estimates were provided.

Among the findings and recommendations of the researchers: “Greater relevance to patients could be realized by focusing information on services that are predictable, nonurgent, and subject to deductibles (e.g., routine outpatient care for chronic diseases) rather than services that are unpredictable, emergent, or would exceed most deductibles (e.g., hospitalizations for life-threatening conditions). Accuracy could be improved by reporting allowable charges for full episodes of care (i.e., aggregate prices for health care services that include all fees such as facility, professional, and other fees). Usability could be enhanced by presenting quality information alongside prices where applicable, as opposed to reporting just one type of data needed to assess value.”

(JAMA. 2013;309[23]:2437-2438. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Jeffrey T. Kullgren, M.D., M.S., M.P.H., call Derek Atkinson at 734-845-5043 or email derek.atkinson@va.gov.

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 Viewpoint in This Issue of JAMA

Building Trust in the Power of ‘Big Data’ Research to Serve the Public Good

According to a recent report from the Institute of Medicine’s (IOM) Clinical Effectiveness Research Innovation Collaborative (CERIC), routinely collected data “provide great potential for extracting useful knowledge to achieve the ‘triple aim’ in health care— better care for individuals, better care for all, and greater value for dollars spent,” writes Eric B. Larson, M.D., M.P.H., of the Group Health Research Institute, Seattle.

“Through advances in health information technology, the needed tools are available to prevent future harm, eliminate waste, and learn with better certainty which treatments are most effective. This can be accomplished without risking patient privacy or proprietary business interests. By overcoming cultural impediments based on outdated ideas about the collection and use of everyday health care information, it will be possible to fulfill the lOM’s vision of an integrated, comprehensive health care system using routinely collected health care data for continual learning that seamlessly serves individual patients and the public good.”

(JAMA. 2013;309[23]:2443-2444. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Eric B. Larson, M.D., M.P.H., call Rebecca Hughes at 206-287-2055 or email hughes.r@ghc.org.

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

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JUNE 18, 2013

Media Advisory: To contact corresponding author Jouke T. Annema, M.D., Ph.D., email j.t.annema@amc.nl.

CHICAGO – Among patients with suspected stage I/II pulmonary sarcoidosis who were undergoing confirmation of the condition via tissue sampling, the use of the procedure known as endosonographic nodal aspiration compared with bronchoscopic biopsy, the current diagnostic standard, resulted in greater diagnostic yield, according to a study in the June 19 issue of JAMA.

Sarcoidosis, a disease that causes granulomas (usually small masses) due to chronic inflammation in body tissues, has an estimated lifetime risk of 1 percent to 2 percent. The incidence of sarcoidosis in the United States is estimated at up to 40 cases per 100,000, and sarcoidosis-related mortality is increasing, according to background information in the article. The disease affects the lungs and intrathoracic lymph nodes in almost all patients. Bronchoscopy with transbronchial lung biopsies has moderate sensitivity in assessing granulomas. Endosonography with intrathoracic nodal aspiration (removal of tissue with a needle using ultrasound guidance) appears to be a promising diagnostic technique.

Martin B. von Bartheld, M.D., of Leiden University Medical Center, Leiden, the Netherlands, and colleagues conducted a study to evaluate the diagnostic yield of bronchoscopy vs. endosonography in the diagnosis of stage I/II sarcoidosis. The randomized trial was conducted at 14 centers in 6 countries between March 2009 and November 2011 and included 304 patients with suspected pulmonary sarcoidosis (stage I/II) in whom tissue confirmation of noncaseating (not exhibiting caseation [necrosis in the tissue]) granulomas was indicated.

Patients underwent either bronchoscopy with transbronchial and endobronchial lung biopsies or endosonography (esophageal or endobronchial ultrasonography) with aspiration of intrathoracic lymph nodes. The primary measured outcome was the diagnostic yield for detecting noncaseating granulomas in patients with a final diagnosis of sarcoid­osis.

A total of 149 patients were randomized to bronchoscopy and 155 to endosonography. The researchers found that granulomas were found significantly more often at endosonography than bronchoscopy (114/154 [74 percent;] vs. 72/149 [48 percent]). The diagnostic yield to detect granulomas for endosonography vs. bronchoscopy was 80 percent vs. 53 percent.

“For stage I sarcoidosis, the diagnostic yield of bronchoscopy was 38 percent compared with 66 percent for stage II. For endosonography, diagnostic yield for stage I was 84 percent compared with 77 percent for stage II,” the authors write.

Two serious adverse events occurred in the bronchoscopy group and 1 in the endosonography group; all patients recovered completely.

“How will the outcomes of this study affect future diagnostic strategies for patients with suspected sarcoidosis? Whether tissue confirmation of granulomas is indicated should be critically assessed in light of recent improvements in computed tomography-thorax imaging. For patients who require tissue sampling either to confirm sarcoidosis before treatment or to exclude similar presenting diseases such as tuberculosis and lymphoma, the outcomes of this study indicate that endosonographic evaluation is likely to have the highest diagnostic yield,” the researchers conclude.

(JAMA. 2013;309(23):2457-2464; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was partly funded by the Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands. Operation costs were borne by the respective study sites individually. No other funding from commercial sources was sought. 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, JUNE 18, 2013

Media Advisory: To contact Anette G. Ziegler, M.D., email anette-g.ziegler@helmholtz-muenchen.de. To contact editorial co-author Jay S. Skyler, M.D., call Lisa Worley at 305-243-5184 or email lworley2@med.miami.edu.

CHICAGO – The majority of children at risk of type 1 diabetes who developed 2 or more diabetes-related autoantibodies developed type 1 diabetes within 15 years, findings that highlight the need for research into finding interventions to stop the development of multiple islet autoantibodies, according to a study in the June 19 issue of JAMA.

“Type 1 diabetes is a chronic autoimmune disease that often manifests during childhood and adolescence. The lifelong requirement for insulin injections and the many complications that follow the diagnosis can be difficult for those affected. Type 1 diabetes usually has a preclinical phase that can be identified by the presence of autoantibodies to antigens of the pancreatic beta cells,” according to background information in the article. The rate of progression to diabetes after seroconversion to islet autoantibodies is uncertain.

Anette G. Ziegler, M.D., of Helmholtz Zentrum Munchen, Neuherberg, Germany, and colleagues conducted a study to estimate rates of progression to type 1 diabetes and associated characteristics based on islet autoantibody status. For the study, data were pooled from prospective cohort studies performed in Colorado (recruitment, 1993-2006), Finland (recruitment, 1994-2009), and Germany (recruitment, 1989-2006) examining children genetically at risk for type 1 diabetes for the development of insulin autoantibodies, glutamic acid decarboxylase 65 (GAD65) autoantibodies, insulinoma antigen 2 (IA2) autoantibodies, and diabetes. Participants were all children recruited and followed up in the 3 studies (Colorado, 1,962; Finland, 8,597; Germany, 2,818). Follow-up assessment in each study was concluded by July 2012.

The researchers found that progression to type 1 diabetes at 10-year follow-up after islet autoantibody seroconversion in 585 children with multiple islet autoantibodies was 69.7 percent, and in 474 children with a single islet autoantibody was 14.5 percent. Risk of diabetes in children who had no islet autoantibodies was 0.4 percent by the age of 15 years.

A total of 355 children (60.7 percent) with multiple islet autoantibodies progressed to diabetes at a median (midpoint) follow-up time after seroconversion of 3.5 years, and a median age of 6.1 years. Progression to diabetes after seroconversion was 43.5 percent at 5-year follow-up, 69.7 percent at the 10-year follow-up, and 84.2 percent at the 15-year follow-up.

Analysis indicated that more rapid progression to diabetes after seroconversion was associated with younger age at seroconversion (younger than age 3 years [10-year risk, 74.9 percent] vs. children 3 years or older [60.9 percent]); and female sex (10-year risk of 74.8 percent for girls vs. 65.7 percent for boys).

“These data show that the detection of multiple islet autoantibodies in children who are genetically at risk marks a preclinical stage of type 1 diabetes. … Thus, the development of multiple islet autoantibodies in children predicts type 1 diabetes,” the authors write. “Future prevention studies should focus on this high-risk population.”

(JAMA. 2013;309(23):2473-2479; 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: The Evolution of Type 1 Diabetes

Jay S. Skyler, M.D., and Jay M. Sosenko, M.D., of the University of Miami Miller School of Medicine, write in an accompanying editorial that the nearly inevitable progression of individuals from seropositivity to type 1 diabetes (T1D) in the current report by Ziegler et al “serves to raise the question of whether the definition of T1D needs updating, perhaps broadening to include a prediabetic state.”

“Current criteria for overt diabetes are based on what is used for type 2 diabetes. Yet the sequence of events in diabetes development suggests it is possible to modify the definition at least to include individuals who are seropositive with either dysglycemia or a high T1D risk score. This would allow potential intervention with immunomodulatory therapies directed at preservation of beta-cell function measured by C-peptide. Data from the Diabetes Control and Complications Trial have demonstrated that preservation of C-peptide results in reduced risk of severe hypoglycemia and of progression of retinopathy and nephropathy.”

(JAMA. 2013;309(23):2491-2492; 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, JUNE 18, 2013

Media Advisory: To contact Marloes W. Heijstek, M.D., email m.w.heijstek@umcutrecht.nl.

CHICAGO – Among children with juvenile idiopathic arthritis (JIA) who had undergone primary immunization, the use of a measles-mumps-rubella (MMR) booster compared with no booster did not result in worse JIA disease activity, according to a study in the June 19 issue of JAMA.

“Juvenile idiopathic arthritis is the most common childhood rheumatic disease, with a prevalence between 16 and 150 per 100,000. Patients with JIA may be susceptible to infections through the immunosuppressive effect of their disease or its treatment. Preventing infections in patients with JIA requires effective and safe vaccinations that induce protective immune responses, have no severe adverse effects, and do not affect JIA disease activity. The live attenuated MMR vaccine is administered to children worldwide via national immunization programs. In immunocompromised patients, concern exists about the safety of live attenuated vaccines given the theoretical risk of enhanced replication of the attenuated pathogens in these patients. The safety of MMR vaccination in particular has been questioned in patients with JIA because the rubella component has been linked to the induction of arthritis in small uncontrolled studies,” according to background information in the article.

Marloes W. Heijstek, M.D., of the University Medical Center Utrecht, Wilhelmina Children’s Hospital, Utrecht, the Netherlands, and colleagues conducted a study to assess whether MMR booster vaccination affects disease activity in patients with JIA. The randomized trial included 137 patients with JIA 4 to 9 years of age who were recruited from 5 academic hospitals in the Netherlands between May 2008 and July 2011. Patients were randomly assigned to receive MMR booster vaccination (n=68) or no vaccination (control group; n=69). Disease activity was measured by the Juvenile Arthritis Disease Activity Score (JADAS-27), ranging from 0 (no activity) to 57 (high activity).

The researchers found that the average JADAS-27 during the total follow-up period did not differ significantly between 63 revaccinated patients (JADAS-27, 2.8) and 68 controls (JADAS-27, 2.4). The average number of flares per patient did not differ significantly between the MMR booster group (0.44) and the control group (0.34), nor did the percentage of patients with 1 or more flares during follow-up.

All revaccinated patients were seroprotected against measles and rubella after vaccination. At 12 months, seroprotection rates were higher in revaccinated patients vs. controls (measles, 100 percent vs. 92 percent; mumps, 97 percent vs. 81 percent; and rubella, 100 percent vs. 94 percent, respectively), and antibody concentrations were higher compared with controls against measles, mumps, and rubella.

“The safety of MMR vaccination has been questioned because disease flares have been described after MMR vaccination. Our trial does not show an effect of vaccination on disease activity,” the authors write.

“Larger studies are needed to assess MMR effects in patients using biologic agents.”

(JAMA. 2013;309(23):2449-2456; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The Dutch Arthritis Association funded this study. 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, JUNE 18, 2013

Media Advisory: To contact Anurag N. Malani, M.D., call Laura Blodgett at 734-712-4536 or email blodgetl@trinity-health.org. To contact editorial co-author Thomas F. Patterson, M.D., call Sheila Hotchkin at 210-567-3026 or email Hotchkin@uthscsa.edu.

CHICAGO – Magnetic resonance imaging (MRI) at the site of injection of a contaminated lot of a steroid drug to treat symptoms such as back pain resulted in earlier identification of patients with probable or confirmed fungal spinal or paraspinal infection, allowing early initiation of medical and surgical treatment, according to a study in the June 19 issue of JAMA.

“Fungal contamination of methylprednisolone [a steroid] prepared by a compounding pharmacy resulted in an unprecedented multistate outbreak of meningitis in the fall of 2012,” according to background information in the article. “Initially, these injections were complicated by meningitis. Within 6 weeks of the outbreak, meningitis became less frequent and localized spinal and paraspinal infections became the principal manifestations of contaminated steroid injections. In contrast to the relatively brief period in which meningitis cases appeared, a steady stream of spinal and paraspinal infections continue to present long after the injections were administered. Because patients received these injections to treat back pain or neuropathic symptoms, the presentation of a slowly developing spinal or paraspinal infection has been obscured.”

Anurag N. Malani, M.D., of St. Joseph Mercy Hospital, Ann Arbor, Mich., and colleagues conducted a study to determine if patients who had not presented for medical care but who had received contaminated methylprednisolone developed spinal or paraspinal infection at the injection site detected using contrast-enhanced MRI screening. There were 172 patients who had received an injection of methylprednisolone from a highly contaminated lot at a pain facility but had not presented for medical care related to adverse effects after the injection. Screening MRI was performed between November 2012 and April 2013.

Of the 172 patients screened, 36 (21 percent) had an abnormality in their MRI. Thirty-five of the 36 patients with abnormal MRIs met the Centers for Disease Control and Prevention (CDC) case definition for probable (17 patients) or confirmed (18 patients) fungal spinal or paraspinal infection. All 35 patients were treated with antifungal agents; 24 required surgical intervention.

“At the time of surgery, 17 of 24 patients (71 percent), including 5 patients who denied having symptoms, had laboratory evidence of fungal infection,” the authors write.

Data were obtained from 115 patients regarding the presence of new or worsening back or neck pain, radiculopathy, or lower-extremity weakness Thirty-five of the 115 patients (30 percent) had at least 1 of these symptoms.

“Our findings support obtaining contrast-enhanced MRI of the injection site in patients with persistent back pain even when their pain disorder has not worsened,” the researchers write. “A proactive outreach to patients receiving injections from a highly contaminated lot, especially lot No. 06292012@26, is needed. Magnetic resonance imaging may detect infection earlier in some patients, leading to more efficacious medical and surgical treatment and improved outcomes,” the researchers conclude.

(JAMA. 2013;309(23):2465-2472; 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, June 18 at this link.

Editorial: Real-world Experience in the Midst of an Exserohilum Meningitis Outbreak

“… Malani et al have demonstrated the possibility of largely asymptomatic fungal infection among patients previously exposed to injection with contaminated lots of methylprednisolone,” writes George R. Thompson III, M.D., of the University of California, Davis and colleagues in an accompanying editorial.

“These findings suggest MRI of the injection site may be an effective screening procedure in some patients but should not be widely adopted, particularly for patients who received peripheral joint injections, given the much lower attack rate. For patients who received spinal injections with steroids from an unknown lot number, MRI-based screening may be appropriate. Whether patients with normal initial MRI findings receive reimaging at a later date remains a difficult question in this evolving outbreak.”

(JAMA. 2013;309(23):2493-2495; 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, JUNE 18, 2013

Media Advisory: To contact Jeffrey L. Saver, M.D., call Kim Irwin at 310-794-2262 or email kirwin@mednet.ucla.edu; or call Rachel Champeau at 310-794-2270 or email rchampeau@mednet.ucla.edu.

CHICAGO – In a study that included nearly 60,000 patients with acute ischemic stroke, thrombolytic treatment (to help dissolve a blood clot) that was started more rapidly after symptom onset was associated with reduced in-hospital mortality and intracranial hemorrhage and higher rates of independent walking ability at discharge and discharge to home, according to a study in the June 19 issue of JAMA.

“Intravenous (IV) tissue-type plasminogen activator (tPA) is a treatment of proven benefit for select patients with acute ischemic stroke as long as 4.5 hours after onset. Available evidence suggests a strong influence of time to therapy on the magnitude of treatment benefit,” according to background information in the article. Imaging studies show the volume of irreversibly injured tissue in acute cerebral ischemia expands rapidly over time. “However, modest sample sizes have limited characterization of the extent to which onset to treatment (OTT) time influences outcome; and the generalizability of findings to clinical practice is uncertain.”

Jeffrey L. Saver, M.D., of the David Geffen School of Medicine at UCLA, Los Angeles, and colleagues conducted a study to determine the association between time to treatment with intravenous thrombolysis and outcomes among patients with acute ischemic stroke. The study included data from 58,353 patients with acute ischemic stroke treated with tPA within 4.5 hours of symptom onset in 1,395 hospitals participating in the Get With The Guidelines-Stroke Program, April 2003 to March 2012. The median (midpoint) age of the patients was 72 years.

The median OTT time was 144 minutes, 9.3 percent had OTT time of 0 to 90 minutes, 77.2 percent had OTT time of 91 to 180 minutes, and 13.6 percent had OTT time of 181 to 270 minutes. Patient factors most strongly associated with shorter OTT included greater stroke severity, arrival by ambulance and arrival during regular hours. Overall, there were 5,142 (8.8 percent) in-hospital deaths, 2,873 (4.9 percent) patients had intracranial hemorrhage, 19,491 (33.4 percent) patients achieved independent ambulation (walking ability) at hospital discharge, and 22,541 (38.6 percent) patients were discharged to home.

The researchers found that for every 15-minute-faster interval of tPA therapy, mortality was less likely to occur, symptomatic intracranial hemorrhage was less likely to occur, independence in ambulation at discharge was more likely to occur, and discharge to home was more likely to occur. For patients treated in the first 90 minutes, compared with 181-270 minutes after onset, mortality was 26 percent less likely to occur, symptomatic intracranial hemorrhage was 28 percent less likely to occur, independence in ambulation at discharge was 51 percent more likely to occur, and discharge to home was 33 percent more likely to occur.

“These findings support intensive efforts to accelerate patient presentation and to streamline regional and hospital systems of acute stroke care to compress OTT times,” the authors conclude.

(JAMA. 2013;309(23):2480-2488; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JUNE 11, 2013

Hearing Loss Associated With Hospitalization, Poorer Self-Reported Health

“Hearing loss (HL) is a chronic condition that affects nearly 2 of every 3 adults aged 70 years or older in the United States. Hearing loss has broader implications for older adults, being independently associated with poorer cognitive and physical functioning. The association of HL with other health economic outcomes, such as health care use, is unstudied,” writes Dane J. Genther, M.D., of Johns Hopkins University School of Medicine, Baltimore, and colleagues, in a Research Letter. The authors investigated the association of HL with hospitalization and burden of disease in a nationally representative study of adults 70 years of age or older.

The researchers analyzed combined data from the 2005-2006 and 2009-2010 cycles of the National Health and Nutrition Examination Survey (NHANES), an ongoing epidemiological study designed to assess the health and functional status of the civilian, noninstitutionalized U.S. population. Air-conduction pure-tone audiometry was administered to all individuals aged 70 years or older, according to established NHANES protocols. Hearing was defined using World Health Organization criteria. Data on hospitalizations (during the previous 12 months) and on burden of disease (during the previous 30 days) were gathered through computer-assisted or interviewer-administered questionnaires.

The authors found that compared with individuals with normal hearing (n=529), individuals with HL (n=1,140) were more likely to have a positive history for cardiovascular risk factors, have a history of hospitalization in the past year (18.7 percent vs. 23.8 percent), and have more hospitalizations (1.27 vs. 1.52). “Fully adjusted models accounting for demographic and cardiovascular risk factors demonstrated that HL (per 25 dB) was significantly associated with any hospitalization, number of hospitalizations, more than 10 days of self-reported poor physical health, and more than 10 days of self-reported poor mental health,” the researchers write.

“Additional research is needed to investigate the basis of these observed associations and whether hearing rehabilitative therapies could help reduce hospitalizations and improve self-reported health in older adults with HL.”

(JAMA. 2013;309[22]:2322-2224. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Frank R. Lin, M.D., Ph.D., call David March at 410-955-1534 or email dmarch1@jhmi.edu.

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 Viewpoints in This Issue of JAMA

 Encouraging Patients to Ask Questions – How to Overcome ‘White-Coat Silence’

Timothy J. Judson, M.P.H., of Weill Cornell Medical College, New York, and colleagues examine the barriers that prevent patients and physicians from meaningful question-and-answer exchanges and offer suggestions for how these barriers may be overcome.

“In most industries, consumer experience is paramount. Encouraging patients to ask questions is a start but needs to be part of a more fundamental re-engineering of health care toward a patient-centered experience in which white coats provoke more open dialogue and less apprehensive silence.”

(JAMA. 2013;309[22]:2325-2326. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Matthew J. Press, M.D., M.Sc., call John Rodgers at 646-317-7304 or email jdr2001@med.cornell.edu.

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Enhancing Patient-Centered Communication and Collaboration by Using the Electronic Health Record in the Examination Room

Amina White, M.D., and Marion Danis, M.D., of the National Institutes of Health, Bethesda, Md., write that “the presence of a computer in the examination room and the pressure to document the visit in the electronic health record (EHR) are often perceived as adversely affecting the patient-physician interaction.” In this Viewpoint, the authors discuss how the EHR can “instead have a positive effect on this interaction and promote patient activation during the course of the outpatient visit.”

“Using the EHR as a relational tool is a strategy for improving individual and population-based health outcomes, for various studies have shown that interventions aimed at increasing patient activation have led to significant improvements in the management of chronic disease, mental illness, and other health-related behaviors or conditions. The health care community may find the EHR to be an untapped means of encouraging patient-physician collaboration and for enhancing patient activation during the clinic visit. Future empirical studies are needed to explore the potential benefits of this expanded use of the EHR on quantitative measures of patient activation.”

(JAMA. 2013;309[22]:2327-2328. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Amina White, M.D., email amina.white@nih.gov.

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 Editorial: Talking to Patients in the 21st Century

In an editorial, Abigail Zuger, M.D., of St. Luke’s-Roosevelt Hospital Center, New York, comments on the Viewpoints in this issue of JAMA that “address some of the changes in physicians’ speaking and writing habits that will be necessary to accommodate new models of practice.”

“So what communication skills will be required of the fully evolved 21st century physician? The physician will, of course, be fluent in standard clinical language, including ordinary medical terminology and the delicate phrases of care and compassion. The physician will be adept at translating medical jargon into comprehensible lay terms, knowing how to defuse words, such as obese or psychotic, that might cause alarm or hurt feelings. The physician will know how to explain statistical concepts both accurately and intelligibly with the patience and fortitude to answer patients’ questions about all things evidence-based, even the physician’s own competence.”

“The physician will know the highly technical vocabulary of relevant research agendas well enough to encourage patients to get involved. The physician will also keep up with popular culture, tracking popular direct-to-patient communications and incorporating them into the clinical dialogue. In addition, and most importantly, the physician will have virtuoso data entry and retrieval skills, with an ability to talk, think, listen, and type at the same time rivaling that of court reporters, simultaneous interpreters, and journalists on deadline. The physician will do all of this efficiently and effectively through dozens of clinical encounters a day, each one couched in a slightly different vernacular.”

(JAMA. 2013;309[22]:2384-2385. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Abigail Zuger, M.D., call Elizabeth Dowling at 212-523-4047 or email edowling@chpnet.org.

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

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JUNE 11, 2013

Media Advisory: To contact corresponding author Borge G. Nordestgaard, D.M.Sc., email Boerge.Nordestgaard@regionh.dk. To contact editorial co-author Sanjay Sethi, M.D., call Ellen Goldbaum at 716-645-4605 or email goldbaum@buffalo.edu.

CHICAGO – Simultaneously elevated levels of the biomarkers C-reactive protein, fibrinogen and leukocyte count in individuals with chronic obstructive pulmonary disease (COPD) were associated with increased risk of having exacerbations, even in those with milder COPD and in those without previous exacerbations, according to a study in the June 12 issue of JAMA.

“Exacerbations of respiratory symptoms in COPD are of major importance because of their profound and long-lasting adverse effects on patients. Frequent episodes accelerate loss of lung function, affect the quality of life of the patients, and are associated with poor survival,” according to background information in the article. Some patients with COPD have evidence of low-grade systemic inflammation with increased levels of certain inflammatory biomarkers during stable conditions, and previous studies have found that elevated levels of inflammatory biomarkers like C-reactive protein (CRP), fibrinogen, and leukocytes during stable COPD are associated with poor outcomes.

Mette Thomsen, M.D., of Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark, and colleagues tested the hypothesis that elevated levels of inflammatory biomarkers in individuals with stable COPD are associated with an increased risk of having exacerbations. The prospective study examined 61,650 participants with spirometry measurements from the Copenhagen City Heart Study (2001-2003) and the Copenhagen General Population Study (2003-2008). Of these, 6,574 had COPD. Baseline levels of CRP, fibrinogen and leukocyte count were measured in participants at a time when they were not experiencing symptoms of exacerbations. Exacerbations were recorded and defined as short-course treatment with oral corticosteroids alone or in combination with an antibiotic or as a hospital admission due to COPD.

During a median (midpoint) 4 years of follow-up time, 3,083 exacerbations were recorded (average, 0.5/participant). The researchers found that the risk of having frequent exacerbations was increased approximately 4-fold in the first year of follow-up and 3-fold using maximum follow-up time in individuals with 3 high inflammatory biomarkers compared with individuals who had no elevated biomarkers. “Importantly, relative risk estimates were consistent even in those with milder COPD and in those with no history of frequent exacerbations, suggesting that these biomarkers provide additional information to the latest Global Initiative for Chronic Obstructive Lung Disease [GOLD] 2011 grading.”

The highest 5-year absolute risks of having frequent exacerbations in those with 3 high biomarkers (vs. no high biomarkers) were 62 percent (vs. 24 percent) for those with GOLD grades C-D (n=558), 98 percent (vs. 64 percent) in those with a history of frequent exacerbations (n=127), and 52 percent (vs. 15 percent) for those with GOLD grades 3-4 (n=465).

“… our study provides novel information that may lead to a simpler assessment using measurements of inflammatory biomarkers in individuals with stable COPD to further stratify preventive therapies based on absolute risk of frequent exacerbations. The potential benefits of such stratification should be tested in future clinical trials that could include drugs of particular current interest, such as macrolides or statins,” the authors write.

(JAMA. 2013;309(22):2353-2361; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This work was supported by Herlev Hospital, Copenhagen University Hospital, the Danish Heart Foundation, the Copenhagen County Foundation, and the University of Copenhagen, all from Denmark.  Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Systemic Inflammation in Predicting COPD Exacerbations

“The study by Thomsen et al adds to the growing interest in systemic inflammation in COPD and its negative consequences and raises several interesting biological questions,” write M. Jeffery Mador, M.D., and Sanjay Sethi, M.D., of the University at Buffalo, State University of New York, Buffalo, in an accompanying editorial.

“What is the origin of systemic inflammation in COPD, as it persists in ex-smokers and therefore cannot be simply attributed to smoke exposure? Does systemic inflammation influence lungs’ innate defenses against microbial pathogens, or is it a reflection of impaired lung defense and consequent immune-inflammatory dysregulation in the lung?”

“There is tremendous enthusiasm and effort to improve current therapies and develop new therapies for exacerbation reduction in COPD. Appropriate development and use of these interventions will need careful phenotyping of patients with COPD, using clinical and biomarker measures. Thomsen et al have shown that biomarkers may hold promise for identifying high-risk patients and that assessing combinations of biomarkers, rather than a single measurement, may be needed to improve risk stratification.”

(JAMA. 2013;309(22):2390-2391; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This work was supported by the VA Merit Review. Both authors have completed and submitted the ICJME Form for Disclosure of Potential Conflicts of Interest. Dr. Mador reported having received grants from the National Institutes of Health and GlaxoSmithKline. No other disclosures were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JUNE 11, 2013

Media Advisory: To contact Sven Cnattingius, M.D., Ph.D., email sven.cnattingius@ki.se.

CHICAGO – In a study that included more than 1.5 million deliveries in Sweden, maternal overweight and obesity during pregnancy were associated with increased risk for preterm delivery, with the highest risks observed for extremely preterm deliveries, according to a study in the June 12 issue of JAMA.

“Maternal overweight and obesity has, due to the high prevalence and associated risks, replaced smoking as the most important preventable risk factor for adverse pregnancy outcomes in many countries. Preterm birth, defined as a delivery of a liveborn infant before 37 gestational weeks, is the leading cause of infant mortality, neonatal morbidity, and long-term disability among non-malformed infants, and these risks increase with decreasing gestational age,” according to background information in the article.

Sven Cnattingius, M.D., Ph.D., of the Karolinska Institutet, Stockholm, Sweden, and colleagues conducted a study to examine the associations between early pregnancy body mass index (BMI) and risk of preterm delivery by gestational age and by precursors of preterm delivery. The study included women with live single births in Sweden from 1992 through 2010. Maternal and pregnancy characteristics were obtained from the nationwide Swedish Medical Birth Register. The primary measured outcomes for the study were the risks of preterm deliveries (extremely, 22-27 weeks; very, 28-31 weeks; and moderately, 32-36 weeks). These outcomes were further characterized as spontaneous (related to preterm contractions or preterm premature rupture of membranes) and medically indicated preterm delivery (cesarean delivery before onset of labor or induced onset of labor).

BMI was calculated from information on height and weight at the first prenatal visit. BMI was used to characterize the women as underweight (BMI<18.5), normal (18.5-<25), overweight (25-<30), obese grade 1 (30-<35), obese grade 2 (35-<40), or obese grade 3 (≥40).

Among 1,599,551 deliveries with information on early pregnancy BMI, 3,082 were extremely preterm, 6,893 were very preterm, and 67,059 were moderately preterm. The researchers found that risks of extremely, very, and moderately preterm deliveries increased with BMI and the overweight and obesity-related risks were highest for extremely preterm delivery. Compared with normal-weight women, women with grade 2 and 3 obesity (BMI≥35) had 0.2 percent to 0.3 percent higher rates of extremely preterm delivery and 0.3 percent to 0.4 percent higher rates of very preterm delivery.

“Risk of spontaneous extremely preterm delivery increased with BMI among obese women (BMI≥30). Risks of medically indicated preterm deliveries increased with BMI among overweight and obese women,” the authors write.

“These results can be generalized to other populations with similar or higher rates of maternal obesity or preterm delivery in as much as the underlying pathways linking maternal obesity and preterm delivery are common across populations. In the United States, where preterm delivery rates are twice as high as in Sweden, the majority of women are either overweight (26.0 percent) or obese (27.4 percent) in early pregnancy, and severe obesity (BMI≥35) is much more common than in Sweden. In 2008, extremely (<28 weeks) preterm births accounted for 0.60 percent of all live single births and 25 percent of all U.S. infant deaths among singletons, and extremely preterm birth is also the leading cause of long-term disability.”

“Considering the high morbidity and mortality among extremely preterm infants, even small absolute differences in risks will have consequences for infant health and survival. Even though the obesity epidemic in the United States appears to have leveled off, there is a sizeable group of women entering pregnancy with very high BMI. Our results need to be confirmed in other populations given their potential public health relevance. Identifying the pathways through which maternal obesity influences offspring health is also needed to provide critical information to specifically target the women at highest risk of preterm delivery,” the researchers conclude.

(JAMA. 2013;309(22):2362-2370; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The study was funded by grants from Karolinska Institutet (Distinguished Professor Award to Dr. Cnattingius). 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, JUNE 11, 2013

Media Advisory: To contact Melissa M. Hudson, M.D., call Summer Freeman at 901-595-3061 or email summer.freeman@stjude.org.

CHICAGO – In an analysis that included more than 1,700 adult survivors of childhood cancer, researchers found a very high percentage of survivors with 1 or more chronic health conditions, with an estimated cumulative prevalence of any chronic health condition of 95 percent at age 45 years, according to a study in the June 12 issue of JAMA.

“Curative therapy for pediatric malignancies has produced a growing population of adults formerly treated for childhood cancer who are at risk for health problems that appear to increase with aging. The prevalence of cancer-related toxic effects that are systematically ascertained through formal clinical assessments has not been well studied. Ongoing clinical evaluation of well-characterized cohorts is important to advance knowledge about the influence of aging on cancer-related morbidity and mortality and to guide the development of health screening recommendations and health-preserving interventions,” according to background information in the article.

Melissa M. Hudson, M.D., of St. Jude Children’s Research Hospital and the University of Tennessee College of Medicine, Memphis, and colleagues conducted a study to determine, through systematic comprehensive medical assessment, the general health status of long-term survivors of childhood cancer and the prevalence of treatment complications following predisposing cancer treatment-related exposures. The presence of health outcomes was ascertained using systematic exposure-based medical assessments among 1,713 adult (median [midpoint] age, 32 years) survivors of childhood cancer (median time from diagnosis, 25 years) enrolled in the St. Jude Lifetime Cohort Study since October 1, 2007, and undergoing follow-up through October 31, 2012. The participants were diagnosed and treated between 1962 and 2001. The primary measured outcomes were the age-specific cumulative prevalence of adverse outcomes by organ system.

The researchers found that impaired pulmonary, auditory, cardiac, endocrine, and nervous system function were most prevalent (detected in 20 percent or more of participants at risk). The crude prevalence of adverse health outcomes was highest for pulmonary (abnormal pulmonary function, 65.2 percent), auditory (hearing loss, 62.1 percent) endocrine or reproductive (any endocrine condition, such as hypothalamic-pituitary axis disorders and male germ cell dysfunction, 62.0 percent), cardiac (any cardiac condition, such as heart valve disorders, 56.4 percent), and neurocognitive (neurocognitive impairment, 48.0 percent) function.

“Among survivors at risk for adverse outcomes following specific cancer treatment modalities, the estimated cumulative prevalence at age 50 years was 21.6 percent for cardiomyopathy, 83.5 percent for heart valve disorder, 81.3 percent for pulmonary dysfunction, 76.8 percent for pituitary dysfunction, 86.5 percent for hearing loss, 31.9 percent for primary ovarian failure, 31.1 percent for Leydig cell failure, and 40.9 percent for breast cancer,” the authors write.

Abnormalities involving hepatic, skeletal, renal, and hematopoietic function were less common (less than 20 percent).

“In this clinically evaluated cohort, 98.2 percent of participants had a chronic health condition,” the researchers note. “The overall cumulative prevalence of a chronic condition was estimated to be 95.5 percent by age 45 years and 93.5 percent 35 years after cancer diagnosis.” At age 45 years, the estimated cumulative prevalence was 80.5 percent for a serious/disabling or life-threatening chronic condition.

“In summary, this study provides global and age-specific estimates of clinically ascertained morbidity in multiple organ systems in a large systematically evaluated cohort of long-term survivors of childhood cancer. The percentage of survivors with 1 or more chronic health conditions prevalent in a young adult population was extraordinarily high. These data underscore the need for clinically focused monitoring, both for conditions that have significant morbidity if not detected and treated early, such as second malignancies and heart disease, and also for those that if remediated can improve quality of life, such as hearing loss and vision deficits.”

(JAMA. 2013;309(22):2371-2381; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by a Cancer Center Support grant from the National Cancer Institute and by the American Lebanese Syrian Associated Charities. 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, JUNE 11, 2013

Media Advisory: To contact Jeffrey S. Gerber, M.D., Ph.D., call Rachel Salis-Silverman at 267-426-6063 or email Salis@email.chop.edu. To contact editorial author Jonathan A. Finkelstein, M.D., M.P.H., call Meghan Weber at 617-919-3656 or email Meghan.Weber@childrens.harvard.edu.

CHICAGO – An intervention consisting of clinician education coupled with personalized audit and feedback about antibiotic prescribing improved adherence to prescribing guidelines for common pediatric bacterial acute respiratory tract infections, although the intervention did not affect antibiotic prescribing for viral infections, according to a study in the June 12 issue of JAMA.

“Antibiotics are the most common prescription drugs given to children. Although hospitalized children frequently receive antibiotics, the vast majority of antibiotic use occurs in the outpatient setting, roughly 75 percent of which is for acute respiratory tract infections (ARTIs). Unnecessary prescribing for viral ARTIs is well documented and has been declining. However, inappropriate prescribing also occurs for bacterial ARTIs, particularly when broad-spectrum antibiotics are used to treat infections for which narrow-spectrum antibiotics are indicated and recommended,” according to background information in the article. “Antimicrobial stewardship programs have been effective for inpatients, often through prescribing audit and feedback. However, most antimicrobial use occurs in outpatients with acute respiratory tract infections.

Jeffrey S. Gerber, M.D., Ph.D., of The Children’s Hospital of Philadelphia, and colleagues conducted a study to evaluate the effect of an antimicrobial stewardship intervention on antibiotic prescribing for pediatric outpatients. The randomized trial of outpatient antimicrobial stewardship compared prescribing between intervention and control practices using a common electronic health record. After excluding children with chronic medical conditions, antibiotic allergies, and prior antibiotic use, the researchers estimated prescribing rates for targeted ARTIs standardized for age, sex, race, and insurance from 20 months before the intervention to 12 months afterward (October 2008-June 2011). The study included a network of 18 pediatric primary care practices in Pennsylvania and New Jersey (162 clinicians). Overall, there were 1,291,824 office visits by 185,212 unique patients.

The intervention consisted of one 1-hour on-site clinician education session followed by 1 year of personalized, quarterly audit and feedback of prescribing for bacterial and viral ARTIs or usual practice. The researchers measured rates of broad-spectrum (off-guideline) antibiotic prescribing for bacterial ARTIs and antibiotics for viral ARTIs for 1 year after the intervention.

The authors found that among children who were prescribed antibiotics for any indication, the overall proportion of antibiotic prescriptions that were broad-spectrum decreased from 26.8 percent to 14.3 percent in the intervention group and from 28.4 percent to 22.6 percent in control practices (difference of differences [DOD], 6.7 percent) during the 12-months following initiation of education/audit and feedback.

“When stratifying by the individual bacterial ARTIs targeted by the intervention, broad-spectrum (off-guideline) antibiotic prescribing for pneumonia decreased from 15.7 percent to 4.2 percent in the intervention group and from 17.1 percent to 16.3 percent in the control group (DOD, 10.7 percent). Broad-spectrum prescribing for acute sinusitis decreased from 38.9 percent to 18.8 percent in the intervention group and from 40.0 percent to 33.9 percent in the control practices (DOD, 14.0 percent). Broad-spectrum prescribing for streptococcal pharyngitis started and remained low for both the intervention group (from 4.4 percent to 3.4 percent) and the control group (from 5.6 percent to 3.5 percent) (DOD, -1.1 percent),” they write.

In addition, the baseline rate of any antibiotic prescribing for viral infections was low and did not change significantly after the intervention in either the intervention group (from 7.9 percent to 7.7 percent) or the control group (from 6.4 percent to 4.5 percent) (DOD, -1.7 percent).

“This intervention nearly halved prescribing of broad-spectrum antibiotics to children during acute primary care encounters and decreased use of off-guideline antibiotics for children with pneumonia by 75 percent by 1 year after the intervention,” the researchers note.

“Our findings suggest that extending antimicrobial stewardship to the ambulatory setting, where such programs have generally not been implemented, may have important health benefits.”

“This targeted application of antimicrobial stewardship principles to the ambulatory setting has the potential to affect the most common indications for antibiotic use. Future studies should examine the key drivers of these effects on antibiotic prescribing and the generalizability of findings to other health systems and measure the sustainability and clinical outcomes associated with differential prescribing patterns,” the authors conclude.

(JAMA. 2013;309(22):2345-2352; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This research was supported by the Agency for Healthcare Research and Quality. 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, June 11 at this link.

Editorial: Putting Antibiotic Prescribing for Children Into Context

“Gerber et al and the participating practices and clinicians have accomplished meaningful improvement in antibiotic prescribing for ARTIs in their pediatric patients,” writes Jonathan A. Finkelstein, M.D., M.P.H., of Boston Children’s Hospital and Harvard Medical School, Boston, in an accompanying editorial.

“However, broad-spectrum antibiotic overuse continues in humans across age groups and conditions, as well as in agricultural use and other factors that drive emerging resistance. The good news is that a range of effective techniques for promoting judicious prescribing in ambulatory care have been developed and tested; it is also apparent that the influence and benefit of any of these interventions will vary greatly across settings. Tailoring strategies to contextual factors and adapting them further during implementation may well be more effective than merely rolling out the approach with the greatest average effect in the average practice.”

(JAMA. 2013;309(22):2388-2389; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Finkelstein reports previous consultancy for the Institute for Healthcare Improvement.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JUNE 4, 2013

Research Finds Retinal Vessel Leakage During High Altitude Exposure

“Exposure to high altitude can cause acute mountain sickness (AMS) and, in severe cases, cerebral or pulmonary edema. Capillary leakage has been hypothesized to play a role in the pathogenesis of AMS, although the mechanism of altitude-related illnesses remains largely unknown,” writes Gabriel Willmann, M.D., of the University of Tubingen, Germany, and colleagues. “Vessel leakage in the retinal periphery has not been investigated. Our objective was to assess retinal vessel integrity at high altitude using fluorescein angiography.”

As reported in a Researcher Letter, the study included 14 healthy, unacclimatized volunteers (7 male and 7 female participants, average age, 35 years) who were studied at baseline (1,119 feet), after ascent to 14,957 feet within 24 hours, and more than 14 days after return by fluorescein angiography. Photographs were independently graded in random order by 4 ophthalmologists for presence and location of leakage.

Retinal abnormalities were not noted at baseline in any of the participants. At high altitude, marked bilateral leakage of peripheral retinal vessels was observed in 7 of 14 participants (50 percent). All findings completely reversed after descent. “Retinal capillary leakage should be considered a part of the spectrum of high-altitude retinopathy,” the authors write.

(JAMA. 2013;309[21]:2210-2212. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Florian Gekeler, M.D., email gekeler@uni-tuebingen.de.

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 Viewpoints in This Issue of JAMA

The Morality of Using Mortality as a Financial Incentive – Unintended Consequences and Implications for Acute Hospital Care

In this Viewpoint, Joel M. Kupfer, M.D., of Methodist Medical Center and the University of Illinois College of Medicine-Peoria, examines the potential issues of using financial incentives to improve hospital mortality rates.

“Financial incentives can be powerful motivators but the results might not always be beneficial. Changes in program design and more widespread implementation might help overcome prior limitations but the potential for unintended consequences also may increase as the financial imperatives of hospitals to win incentives increases. It is important to move ahead with quality initiatives even though there are gaps in current knowledge. The challenge for policy makers will be to design a balanced system that can lower costs and improve care while preserving the ethical integrity of the medical profession, and respect patients’ rights to make choices about their health care.”

(JAMA. 2013;309[21]:2213-2214. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Joel M. Kupfer, M.D., call Dave Haney at 309-671-8404 or email dhaney@uicomp.uic.edu.

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 The Future of Quality Measurement for Improvement and Accountability

“The Affordable Care Act expands access to health insurance and includes numerous provisions focused on delivering care that is high quality, safe, and affordable. Reliable and meaningful quality measurement that focuses on important outcomes, including patient experience throughout the health care system, is an essential prerequisite for achieving this goal,” writes Patrick H. Conway, M.D., M.Sc., of the Department of Health and Human Services, Washington, D.C., and the Centers for Medicare & Medicaid Services, Baltimore, and colleagues.

In this Viewpoint, the authors “describe the characteristics of the quality measurement enterprise of the future, outline a potential roadmap for the transition, and identify a set of opportunities for public- and private-sector collaboration.”

“As measures are increasingly implemented in payment programs based on value, the public and private sectors must collectively work to ensure the implementation of patient-centered measures that matter, minimize clinician burden, focus on improvement, and develop an agile learning measurement enterprise. The measurement enterprise is critical for successful transformation of the health system to achieve better health outcomes as efficiently as possible.”

(JAMA. 2013;309[21]:2215-2216. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Patrick H. Conway, M.D., M.Sc., call the CMS press office at 202-690-6145 or email press@cms.hhs.gov.

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Synthesizing Evidence – Shifting the Focus From Individual Studies to the Body of Evidence

“The research enterprise behaves as if a single study could provide the ultimate answer to a clinical question,” write M. Hassan Murad, M.D., M.P.H., and Victor M. Montori, M.D., M.Sc., of the Mayo Clinic, Rochester, Minn. “Researchers offer over optimistic sample-size calculations and other design features to convince funders and institutional review boards that their study will provide the answer. Medical journals and the popular media highlight single studies, too often without regard to similar studies.”

Researchers with the Cochrane Centre have advocated for the results of individual studies to be placed in the context of the totality of evidence for the last 15 years, with limited success.  In this Viewpoint, the authors offer reasons to shift the collective focus from single studies to the accumulating body of evidence.

(JAMA. 2013;309[21]:2217-2218. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact M. Hassan Murad, M.D., M.P.H., call Shelly Plutowski at 507-284-5005 or email rplutowski@mayo.edu.

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

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JUNE 4, 2013

Media Advisory: To contact Melinda Maggard-Gibbons, M.D., M.S.H.S., call Warren Robak at 310-451-6913 or email robak@rand.org.

CHICAGO – A review of more than 50 studies found limited evidence supporting the use of bariatric surgical procedures for non-morbidly obese adults (body mass index [BMI] 30-35) with diabetes or impaired glucose intolerance, according to a study in the June 5 issue of JAMA. For the limited data that was available for this patient group, bariatric surgery was associated with greater improvements in short-term weight loss, intermediate blood glucose levels, blood pressure, and high cholesterol than nonsurgical interventions such as medications, diet, and behavioral changes.

“Bariatric surgery is often used to promote weight loss and manage obesity-related comorbidities [co-existing illnesses] in morbidly obese patients (body mass index [BMI; 35 or greater]). In this population, procedures such as laparoscopic adjustable gastric banding and Roux-en-Y gastric bypass have resulted in better glucose control and more weight loss at 1 or 2 years than nonsurgical therapy,” according to background information in the article. “Bariatric surgical procedures are being advocated as a treatment for diabetes in less-obese individuals (BMI, 30-35). However, this practice remains controversial. In 2006, the Centers for Medicare & Medicaid Services would not approve coverage for patients with lower BMI and diabetes, whereas the U.S. Food and Drug Administration has approved gastric banding for individuals with a BMI of 30 to 35 who have an obesity-related comorbidity.”

Melinda Maggard-Gibbons, M.D., M.S.H.S., of Rand Health, Santa Monica, Calif., and colleagues conducted a systematic review of the relative benefits and risks associated with surgical and nonsurgical therapies for treating diabetes or impaired glucose tolerance in patients with a BMI of 30 to 35. The authors conducted a search of the medical literature and identified 32 surgical studies, 11 systematic reviews on nonsurgical treatments, and 11 large non-surgical studies published after those  reviews that met criteria for the analysis.

The researchers found that bariatric surgery was associated with greater weight loss (range, 32-53 lbs.) and glycemic control during 1 to 2 years of follow-up than nonsurgical treatment in only three randomized clinical trials (RCTs; n=290). None of these trials had substantial numbers of patients meeting the study criteria: 1 trial of 150 patients with type 2 diabetes and an average BMI of 37; 1 trial of 80 patients without diabetes and BMI of 30 to 35; and 1 trial of 60 patients with diabetes and BMI of 30 to 40 [13 patients with BMI <35]).

Bariatric surgery seemed to be associated with weight loss and diabetes control in observational studies having 1 or 2 years of follow-up with indirect comparisons of evidence (approximately 600 patients) and meta-analyses of nonsurgical therapies (containing more than 300 RCTs).

Surgeon-reported adverse events were low (e.g., hospital deaths of 0.3 percent-1.0 percent), but data were from select centers and surgeons. Long-term adverse events are unknown.

“… there are limited data from clinical trials in this specific patient population, and it is unknown whether the benefits observed are durable long-term and if these findings might translate into reductions in the microvascular and macrovascular complications of diabetes. Until such data are available, the evidence is insufficient to reach conclusions about the appropriate use of bariatric surgery in this patient population, performance of these procedures in this target population should be under close scientific scrutiny, and additional studies comparing procedures are warranted,” the authors conclude.

(JAMA. 2013;309(21):2250-2261; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This project was funded under a contract from the AHRQ and U.S. Department of Health and Human Services. 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, JUNE 4, 2013

Media Advisory: To contact Sayeed Ikramuddin, M.D., call Matt DePoint at 612-625-4110 or email mdepoint@umn.edu. To contact editorial author Bruce M. Wolfe, M.D., call Mirabai Vogt at 503-494-7986 or email vogtmi@ohsu.edu.

CHICAGO – Among mild to moderately obese patients with type 2 diabetes, adding gastric bypass surgery to lifestyle and medical management was associated with a greater likelihood of improved levels of metabolic risk factors such as blood glucose, LDL-cholesterol and systolic blood pressure, according to a study in the June 5 issue of JAMA.

“The foundation of treatment for type 2 diabetes mellitus is weight loss, achieved through reduction of energy intake and increased physical activity via lifestyle modification. Results from the Look AHEAD (Action for Health in Diabetes) trial show that sustained weight loss through lifestyle modification improves diabetes control, but this is difficult to achieve and maintain over time,” according to background information in the article. “Controlling glycemia, blood pressure, and cholesterol is important for patients with diabetes. How best to achieve this goal is unknown.”

Sayeed Ikramuddin, M.D., of the University of Minnesota, Minneapolis, and colleagues conducted a study to compare Roux-en-Y gastric bypass with lifestyle and intensive medical management to achieve control of comorbid (co-existing) risk factors. The 12-month, 2-group randomized trial was conducted at 4 teaching hospitals in the United States and Taiwan and included 120 participants who had a hemoglobin A_1c (HbA_1c) level of 8.0 percent or higher, body mass index (BMI) between 30.0 and 39.9, C peptide level of more than 1.0 ng/mL, and type 2 diabetes for at least 6 months. The study began in April 2008. The interventions for the trial were lifestyle-intensive medical management intervention and Roux-en-Y gastric bypass surgery. Medications for hyperglycemia, hypertension, and dyslipidemia were prescribed according to protocol and surgical techniques that were standardized.

The composite goal for the study was the goal established by the American Diabetes Association (ADA) for the treatment of diabetes: HbA_1c less than 7.0 percent, low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood pressure less than 130 mm Hg.

All 120 patients received the Look AHEAD intensive lifestyle-medical management protocol, the protocol used in the Look AHEAD study and considered to be the most successful for treating diabetes in obese patients; 60 of the 120 patients were randomly assigned to undergo Roux-en-Y gastric bypass. The researchers found that at 12 months, 11 participants (19 percent) in the lifestyle-medical management group and 28 (49 percent) in the gastric bypass group achieved the primary composite end point. Among the composite end point components, the only significant treatment effect was for HbA_1c: 18 participants (32 percent) in the lifestyle-medical management group vs. 43 (75 percent) in the gastric bypass group achieved an HbA_lc level of less than 7 percent.

The lifestyle-medical management group lost an average of 7.9 percent of initial body weight at 1 year, whereas the average weight loss in the gastric bypass group was 26.1 percent. “On average, the gastric bypass group used 3.0 fewer medications to manage glycemia, dyslipidemia, and hypertension than did those in the lifestyle-medical management group. The gastric bypass group also had significantly better results for the secondary outcomes of glycemia, HDL cholesterol, triglycerides, and diastolic blood pressure,” the authors write.

Analyses indicated that achieving the composite end point was primarily attributable to weight loss. The gastric bypass group experienced more nutritional deficiency than the lifestyle-medical management group. Overall, there were 22 serious adverse events in the gastric bypass group and 15 in the lifestyle-medical management group.

This study overcame limitations of prior studies of bariatric surgery by using a widely accepted nonsurgical treatment protocol, used endpoints recommended as the major goal for treatment by the ADA, was performed by multiple surgeons of different hospitals and studied a single operative procedure, the Roux-en-Y gastric bypass, considered to be the best procedure for weight loss.

“The merit of gastric bypass treatment of moderately obese patients with type 2 diabetes depends on whether potential benefits make risks acceptable. Bariatric surgery can result in dramatic improvements in weight loss and diabetes control in moderately obese patients with type 2 diabetes who are not successful with lifestyle changes or medical management. The benefits of applying bariatric surgery must be weighed against the risk of serious adverse events,” the researchers conclude.

(JAMA. 2013;309(21):2240-2249; 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, June 4 at this link.

Editorial: Treating Diabetes With Surgery

In an accompanying editorial, Bruce M. Wolfe, M.D., of Oregon Health and Science University, Portland, and colleagues comment on the two articles in this issue of JAMA regarding weight loss surgery and diabetes.

“Recent large scale trials of intensive medical management for obesity and diabetes have been disappointing. Substantial resources are required to cause modest weight loss and diabetes control. Bariatric surgery does result in substantial weight loss with excellent diabetes control but is offset by initial high cost and risks for surgical complications. The optimal approach for treatment of obesity and diabetes remains unknown. The answer will only come from more well designed, randomized trials such as that performed by Ikramuddin et al that provide definitive answers.”

(JAMA. 2013;309(21):2274-2275; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, MAY 21, 2013

Advances in Regulatory Science at the Food and Drug Administration

In this Viewpoint, Bruce M. Psaty, M.D., Ph.D., of the University of Washington, Seattle, and colleagues discuss advances in recent years at the U.S. Food and Drug Administration (FDA) to improve drug evaluation.

“The mark of a highly functional regulatory agency is the timely identification of, and the timely and appropriate response to, safety issues. The FDA’s development of the benefit-risk framework, the creation of the Mini-Sentinel, and the use of Risk Evaluation and Mitigation Strategies (REMS) all deserve praise as key efforts to implement a lifecycle approach to drug evaluation. The optimal use of these new tools nonetheless represents a new challenge for the agency. Adequate funding for the FDA—and additional authorities, such as making REMS assessments enforceable—are essential for the agency to continue to make progress in balancing the need for expeditious approval processes with the need for protecting the health of the public.”

(JAMA. 2013;309[20]:2103-2104. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Bruce M. Psaty, M.D., Ph.D., call Leila Gray at 206-685-0381 or email leilag@uw.edu.

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 Medication Nonadherence – A Diagnosable and Treatable Medical Condition

“Medication nonadherence is widely recognized as a common and costly problem. Approximately 30 percent to 50 percent of U.S. adults are not adherent to long-term medications leading to an estimated $100 billion in preventable costs annually,” writes Zachary A. Marcum, Pharm.D., M.S., of the University of Pittsburgh, and colleagues. “How can adherence be improved? We propose that the first step is to view medication nonadherence as a diagnosable and treatable medical condition.”

“Based on identified barriers derived from systematic screening, patient-tailored interventions can be delivered in a safe, effective, and efficient manner, with systematic monitoring over time due to the dynamic process of medication adherence. Consistent with Patient-Centered Outcomes Research Institute goals and priorities, community and patient partners should be identified and included throughout the planning and implementation of future studies. Finally, synergism among multiple disciplines is necessary to successfully improve medication adherence for adults.”

(JAMA. 2013;309[20]:2105-2106. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Zachary A. Marcum, Pharm.D., M.S., call Cristina Mestre at 412-586-9776 or email mestreca@upmc.edu.

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Value of Unique Device Identification in the Digital Health Infrastructure

“In recent years, high-profile cases of medical device failure resulting in patient harm—such as implantable cardioverter-defibrillator leads and metal-on-metal hip implants—have received substantial attention both in the medical literature and popular press. These examples illustrate the need for a more effective system of monitoring device performance and protecting patient safety,” write Natalia A. Wilson, M.D, M.P.H., of Arizona State University, Tempe and Joseph Drozda Jr., M.D., of Mercy Health, Chesterfield, Mo.

In this Viewpoint, the authors discuss the Food and Drug Administration’s (FDA’s) establishment of a Unique Device Identification (UDI) System and the UDI’s Final Rule, expected in June 2013, which “will mandate that manufacturers assign unique identifiers to their marketed devices. In addition to enhancing postmarket surveillance, use of UDI should ensure the ability to track a device across health care settings; support safe and accurate device use; create a standard for device documentation in health information technology systems; enhance recall management; improve efficiency; and support health care cost savings.”

(JAMA. 2013;309[20]:2107-2108. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Natalia A. Wilson, M.D, M.P.H., call Debbie Freeman at 480-965-9271 or email Debbie.Freeman@asu.edu; or Julie Newberg at 480-727-3116 or email julie.newberg@asu.edu.

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

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, MAY 21, 2013

Media Advisory: To contact Duncan Young, D.M., email duncan.young@nda.ox.ac.uk. To contact editorial author Derek C. Angus, M.D., M.P.H., call Rick Pietzak at 412-864-4151 or email pietzakr@upmc.edu.

CHICAGO – For critically ill patients receiving mechanical ventilation, early tracheostomy (within the first 4 days after admission) was not associated with an improvement in the risk of death within 30 days compared to patients who received tracheostomy placement after 10 days, according to a study in the May 22/29 issue of JAMA.

“A tracheostomy is commonly performed when clinicians predict a patient will need prolonged mechanical ventilation,” according to background information in the article. The use of this procedure has increased, such that up to one-third of patients requiring prolonged mechanical ventilation now receive tracheostomy. Perceived beneficial effects of tracheostomies might be maximized if the procedure were performed early in a patient’s illness, the authors write. “There is little evidence to guide clinicians regarding the optimal timing for this procedure.”

Duncan Young, D.M., of John Radcliffe Hospital, Oxford, England, and colleagues conducted a study to examine whether early vs. late tracheostomy would be associated with lower mortality among adult patients requiring mechanical ventilation in critical care units. The randomized clinical trial was conducted between 2004 and 2011 at 70 adult general and 2 cardiothoracic critical care units in 13 university and 59 nonuniversity hospitals in the United Kingdom. The study included 909 adult patients receiving mechanical ventilation for less than 4 days and identified by the treating physician as likely to require at least 7 more days of mechanical ventilation. Patients were randomized 1:1 to early tracheostomy (within 4 days) or late tracheostomy (after 10 days if still indicated).

Of the 455 patients assigned to early tracheostomy, 91.9 percent received a tracheostomy and of 454 patients assigned to late tracheostomy, 44.9 percent received a tracheostomy. The researchers found that the primary outcome, all-cause mortality 30 days from randomization, was not statistically different in the 2 groups: 139 patients (30.8 percent) in the early group and 141 patients (31.5 percent) in the late group died. Two-year mortality was 51.0 percent in the early group and 53.7 percent in the late group.

For the 622 patients receiving tracheostomies, procedure-related complications were reported for a total of 39 patients (6.3 percent): twenty-three (5.5 percent) of 418 patients in the early group and 16 (7.8 percent) of 204 patients in the late group. The most frequent complication was bleeding sufficient to require intravenous fluids or another intervention.

For the 315 survivors of critical care in the early group and the 312 survivors in the late group, the median (midpoint) duration of critical care admission was 13.0 days in the early group and 13.1 days in the late group. Median total hospital stay in those surviving to discharge (256 both groups) was 33 days in the early group and 34 days in the late group.

“The implications, for clinical practice and for patients, from this study are found from the results in the late group. Not only were there no statistically significant difference in mortality between the 2 groups but, through waiting, an invasive procedure was avoided in a third of patients. Avoiding this significant proportion of tracheostomies, a procedure associated with a 6.3 percent acute complication rate in this study (and 38 percent-39 percent overall complication rates in the other recent multicenter studies), did not appear to be associated with any significant increase in health care resource use, as measured by critical care unit or hospital stay. It would appear that delaying a tracheostomy until at least day 10 of a patient’s critical care unit stay is the best policy,” the authors write.

“Early tracheostomy should therefore be avoided unless tools to accurately predict the duration of mechanical ventilation on individual patients can be developed and validated.”

(JAMA. 2013;309(20):2121-2129; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The UK Intensive Care Society funded the research prioritization work that led to this study. The study was funded by the UK Intensive Care Society and the Medical Research Council. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: When Should a Mechanically Ventilated Patient Undergo Tracheostomy?

In an accompanying editorial, Derek C. Angus, M.D., M.P.H., of the University of Pittsburgh School of Medicine (and Contributing Editor, JAMA), writes that the finding in this study that tracheostomy generally should be delayed until at least 10 days after initiating mechanical ventilation has potentially important implications.

“Thus, 2 large, multicenter European trials show very similar findings: a strategy to perform tracheostomy early (within the first week) offers no benefit over a wait-and-see strategy that delays tracheostomy until after 10 days of mechanical ventilation. However, the consistently poor ability of clinicians to predict in the first few days which patients would eventually require prolonged ventilation means the early strategy inadvertently leads to a large increase in the number of unnecessary tracheostomies.”

“Nevertheless, if clinicians were to uniformly adopt a wait-and-see strategy, the number of tracheostomies would decline. Given the significant difference in diagnosis related group (DRG) payments for patients who are mechanically ventilated with and without a tracheostomy, hospital reimbursement also would decline. How hospital profitability would be affected by such a significant change in practice is unclear.”

“In coming years, payment reforms that bundle hospital, physician, and postacute care for inpatient episodes may make this quandary less important. However, as long as hospitals are reimbursed using a DRG system, it would seem prudent to revise the reimbursement strategies for patients facing potentially prolonged mechanical ventilation to better align financial incentives with the best clinical evidence.”

(JAMA. 2013;309(20):2163-2164; 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, MAY 21, 2013

Media Advisory: To contact Wei Jiang, M.D., call Rachel Harrison at 919-419-5069 or email rachel.harrison@duke.edu.

CHICAGO – Among patients with stable coronary heart disease and mental stress-induced myocardial ischemia (MSIMI), 6 weeks of treatment with the antidepressant escitalopram, compared with placebo, resulted in a lower rate of MSIMI, according to a study in the May 22/29 issue of JAMA.

“A robust body of evidence has identified emotional stress as a potential triggering factor in coronary heart disease (CHD) and other cardiovascular events,” according to background information in the article. “During the last 3 decades, the association of emotional distress and myocardial ischemic activity [insufficient blood flow to the heart muscle, often resulting in chest pain] in the laboratory has been well studied. In the laboratory setting, MSIMI occurs in up to 70 percent of patients with clinically stable CHD and is associated with increased risk of death and cardiovascular events.” Few studies have examined therapeutics that effectively modify MSIMI. Recent evidence suggests that selective serotonin reuptake inhibitors (SSRIs) may reduce mental stress-induced hemodynamic response, metabolic risk factors, and platelet activity.

Wei Jiang, M.D., of the Duke University Medical Center, Durham, N.C., and colleagues conducted a study to investigate whether SSRI treatment can improve MSIMI. The randomized trial included patients with clinically stable coronary heart disease and laboratory-diagnosed MSIMI. Enrollment occurred from July 2007 through August 2011 at a tertiary medical center. Eligible participants were randomized 1:1 to receive escitalopram or placebo over 6 weeks. A total of 56 patients in each group completed end point assessments. Occurrence of MSIMI was defined via various measures during 1 or more of 3 mental stressor tasks: mental arithmetic, mirror trace, and public speaking with anger recall.

The researchers found that at the end of 6 weeks, more patients taking escitalopram (34.2 percent) had absence of MSIMI during the 3 mental stressors compared with patients taking placebo (17.5 percent). Analysis showed that the escitalopram group had a significantly higher rate (2.6 times) of no MSIMI compared with the placebo group. Also, hemodynamic responses to mental stress were all lower in the escitalopram group, with differences in systolic blood pressure and heart rate between the groups significant.

In addition, the 6-week escitalopram intervention was associated with greater improvements in certain measures of psychological functioning, including state anxiety and positive affect, during mental stress.

Exercise capacity was not significantly altered at week 6 in participants receiving escitalopram vs. those receiving placebo.

“In summary, 6-week pharmacologic enhancement of serotonergic function superimposed on the best evidence-based management of CHD appeared to significantly improve MSIMI occurrence. These results support and extend previous findings suggesting that modifying central and peripheral serotonergic function could improve CHD symptoms and may have implications for understanding the pathways by which negative emotions affect cardiovascular prognosis,” the authors conclude.

(JAMA. 2013;309(20):2139-2149; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was funded by the NHLBI, Bethesda, Md. Escitalopram and matched placebo were supplied by Forest Research Institute Inc., Germantown, Md. 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, May 21 at this link.

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EMBARGOED FOR EARLY RELEASE: 1:00 P.M. (CT) TUESDAY, MAY 21, 2013

Media Advisory: To contact corresponding author David A. Schwartz, M.D., call Mark Couch at 303-724-5377 or email Mark.Couch@ucdenver.edu.

CHICAGO – Variation in the gene MUC5B among patients with idiopathic pulmonary fibrosis was associated with improved survival, according to a study published online by JAMA. The study is being released early online to coincide with its presentation at the American Thoracic Society international conference.

“Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with a median [midpoint] survival of 3 years,” according to background information in the article. The prognosis is variable; patients may remain stable for several years, slowly lose lung function, progress in an intermittent fashion, or experience precipitous acute exacerbations. “Current prediction models of mortality in IPF, which are based on clinical and physiological parameters, have modest value in predicting which patients will progress. In addition to the potential for improving prognostic models, identifying genetic and molecular features that are associated with IPF mortality may provide insight into the underlying mechanisms of disease and inform clinical trials.”

Anna L. Peljto, Dr.P.H., of the University of Colorado Denver, and colleagues conducted a study to determine whether the variation (rs35705950) of the gene MUC5B, previously reported to be associated with the development of pulmonary fibrosis, is associated with survival among patients with IPF. The study included two independent cohorts of patients with IPF: the INSPIRE cohort, consisting of patients enrolled in the interferon-γ1b trial (n=438; December 2003 – May 2009; 81 centers in 7 European countries, the United States, and Canada), and the Chicago cohort, consisting of IPF participants recruited from the Interstitial Lung Disease Clinic at the University of Chicago (n = 148; 2007-2010). The INSPIRE cohort was used to model the association of MUC5B genotype with survival. The Chicago cohort was used for replication of findings.

The median follow-up period was 1.6 years for INSPIRE and 2.1 years for Chicago. During follow-up, there were 73 deaths among the INSPIRE cohort patients and 64 deaths among the Chicago cohort patients. Analysis indicated that the unadjusted 2-year cumulative incidence of death was lower among patients carrying 1 or more copies of the IPF risk allele (an alternative form of a gene) (T) in both the INSPIRE cohort and the Chicago cohort.

According to the authors, “The addition of the MUC5B genotype to the survival models significantly improved the predictive accuracy of the model in both the INSPIRE cohort and the Chicago cohort.”

“These findings suggest that the common polymorphism in the promoter of MUC5B (rs35705950), previously reported to be strongly associated with the development of familial interstitial pneumonia and idiopathic pulmonary fibrosis, is significantly associated with improved survival in IPF. These findings are consistent with a previous report of an association between the MUC5B variant and less severe pathological changes in familial interstitial pneumonia, as well as another report of slower decline in forced vital capacity for patients with IPF. This study is, to our knowledge, the first to demonstrate that a genetic variant is associated with survival in IPF.”

“Further research is necessary to refine the risk estimates and to determine the clinical implications of these findings,” the researchers conclude.

(doi:10.1001/jama.2013.5827; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This research was supported by the National Heart, Lung, and Blood Institute and the Dorothy P. and Richard P. Simmons Endowed Chair for Pulmonary Research (University of Pittsburgh School of Medicine). 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: 1:00 P.M. (CT) TUESDAY, MAY 21, 2013

Media Advisory: To contact Jorg D. Leuppi, M.D., Ph.D., email joerg.leuppi@ksli.ch. To contact editorial co-author Don D. Sin, M.D., call Justin Karasick at 604-806-8460 or email jkarasick@providencehealth.bc.ca.

CHICAGO – Among patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) requiring hospital admission, a 5-day glucocorticoid treatment course was non-inferior (not worse than) to a 14-day course with regard to re-exacerbation during 6 months of follow-up, according to a study published online by JAMA. The study is being released early online to coincide with its presentation at the American Thoracic Society international conference. The authors write that these findings support a shorter-course glucocorticoid treatment regimen, which would reduce glucocorticoid exposure and the risk of possible adverse effects.

“Acute exacerbations of COPD are a risk factor for disease deterioration, and patients with frequent exacerbations have an increased mortality,” according to background information in the article. “International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapy in acute exacerbations of COPD. However, the optimal dose and duration of therapy are unknown. … Given the adverse effects of glucocorticoids and the potentially large number of exacerbations occurring in patients with COPD, glucocorticoid exposure should be minimized.”

Jorg D. Leuppi, M.D., Ph.D., of the University Hospital of Basel, Switzerland, and colleagues conducted a study to examine whether a short-term (5 days) systemic glucocorticoid treatment in patients with COPD exacerbation is noninferior to conventional (14 days) treatment with respect to clinical outcome and whether it decreases the exposure to steroids. The randomized trial (REDUCE) was conducted in 5 Swiss teaching hospitals, enrolling 314 patients presenting to the emergency department with acute COPD exacerbation, past or present smokers without a history of asthma, from March 2006 through February 2011. Patients received treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled fashion. The predefined noninferiority criterion was an absolute increase in exacerbations of at most 15 percent. The primary measured outcome was time to next exacerbation within 180 days.

Of the 314 randomized patients, 289 (92 percent) of whom were admitted to the hospital, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. A total of 56 patients (35.9 percent) reached the primary end point of COPD exacerbation in the short-term treatment group compared with 57 patients (36.8 percent) in the conventional treatment group. Time to re-exacerbation did not differ between groups.

Among patients who experienced a re-exacerbation during follow-up, the median (midpoint) time to event was 43.5 days in the short-term group and 29 days in the conventional treatment group. Estimates of re-exacerbation rates were 37.2 percent in the short-term and 38.4 percent in the conventional treatment group.

“There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function. In the conventional group, mean (average) cumulative prednisone dose was significantly higher (793 mg vs. 379 mg), but treatment-associated adverse reactions, including hyperglycemia and hypertension, did not occur more frequently,” the authors write.

During hospital stay, there was no increase in the requirement for mechanical ventilation with the short-term treatment regimen.

“There was no significant difference in recovery of lung function and disease-related symptoms, but the shorter course resulted in a significantly reduced glucocorticoid exposure,” the researchers write. “These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD.”

(doi:10.1001/jama.2013.5023; 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: Steroids for Treatment of COPD Exacerbations – Less Is Clearly More

Don D. Sin, M.D., and Hye Yun Park, M.D., Ph.D., of the University of British Columbia James Hogg Research Centre and the Institute for Heart and Lung Health, St. Paul’s Hospital, Vancouver, British Columbia, Canada, write in an accompanying editorial that “the clinical implications of this study are clear.”

“Most patients with acute COPD exacerbations can be treated with a 5-day course of prednisone or equivalent (40 mg daily). Furthermore, this regimen can be applied across all GOLD (Global Initiative for Chronic Obstructive Lung Disease) categories of disease severity. This is welcome news for patients with COPD who experience multiple exacerbations annually and are exposed to repeated courses of systemic corticosteroids. These findings will enable clinicians to minimize steroid exposure and reduce the risk of steroid-related toxicity in these patients.”

(doi:10.1001/jama.2013.5644; 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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