EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, FEBRUARY 5, 2013

Study Examines Rate of Antipsychotic Use Among Nursing Home Residents

“The prescribing of antipsychotic medications persists at high levels in U.S. nursing homes (NHs) despite extensive data demonstrating marginal clinical benefits and serious adverse effects, including death. However, imprecise and outdated data have limited the understanding of the current state of antipsychotic medication prescribing in NHs,” writes Becky A. Briesacher, Ph.D., of the University of Massachusetts Medical School, Worcester, Mass., and colleagues.

As reported in a Research Letter, the authors conducted a study to assess the current level of antipsychotic use in NHs. The researchers analyzed September 2009 through August 2010 prescription dispensing data from a large, long-term care pharmacy that serves 48 states and half of all NH residents in the United States. Data elements included state location, patients’ sex, age, and enrollment dates, and national drug codes for all drugs dispensed regardless of payer (e.g., Medicare Part D, private insurance, and out of pocket). Overall and state-level annual prevalence of antipsychotic use was calculated as the percentage of NH residents receiving at least 1 antipsychotic drug.

“Of the overall sample of 1,402,039 NH residents, 308,449 (22.0 percent) received 1 or more prescriptions of antipsychotics. Prevalence of antipsychotic drug prescribing in NHs varied significantly, with the highest quintile [one of five groups] states (28.1 percent) located in the central south and the lowest quintile states (17.2 percent) located mostly in the west. Of 4,338,723 antipsychotic prescriptions in NHs, the majority (68.6 percent) were for the atypical agents quetiapine fumarate, risperidone, and olanzapine (n = 2,988,573).”

The authors note that their “finding that 22.0 percent of NH residents received antipsychotics in 2009-2010 is within the lower range of rates that were documented 25 years earlier before the passage of the Omnibus Budget Reconciliation Act of 1987, which instituted regulations on the appropriate use of antipsychotics in NHs.” They add that the extended duration of use (median duration, 30 to 77 days) raises “concerns about the care of frail elders residing in NHs.”

(JAMA. 2013;309[5]:440-442. Available pre-embargo to the media at https://media.jamanetwork.com)

Viewpoints in This Issue of JAMA

Enhanced Tracking of Tissue for Transplantation

“The U.S. Food and Drug Administration (FDA) estimates that tissue banks provide 1.5 million tissue grafts annually, often supplying hospitals in several different states or even countries with tissue from a single donor. Tissue allografts have become a vitally important global industry. Nevertheless, tracking mechanisms that exist in other medical contexts have notable deficiencies with respect to tracking tissues,” writes John S. DePaolo, B.A., and James M. Barbeau, M.D., J.D., of the Louisiana State University School of Medicine, New Orleans.

In this Viewpoint, the authors discuss the deficiencies and provide suggestions for improving tracking of tissue.

(JAMA. 2013;309[5]:443-444. Available pre-embargo to the media at https://media.jamanetwork.com)

FDA Regulation of Off-label Drug Promotion Under Attack

Aaron S. Kesselheim, M.D., J.D., M.P.H., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues examine the issue of regulating off-label drug promotion, and cite a recent Court of Appeals decision that “signals that courts’ evolving views of protecting corporations’ commercial speech may prove incompatible with regulating drug promotion.”

“Courts’ seemingly inexorable drift toward greater protection of commercial speech at the expense of rigorous science directly threatens the FDA’s standing as the nation’s arbiter of which drugs are safe and effective. The existing approach to governing drug promotion, honed by enormous clinical and regulatory experience, is scientifically and legally justifiable and has benefitted patients and practitioners for decades. It should not be abandoned now.”

(JAMA. 2013;309[5]:445-446. Available pre-embargo to the media at https://media.jamanetwork.com)

The European Working Time Directive

“A large-scale, uncontrolled experiment in medical care and education is in progress in the European community with important implications for the quality of medical care and education. Working hours for physicians in training are now limited to 48 hours per week, a fact that—to our knowledge—is little known to most U.S. physicians,” writes Lloyd Axelrod, M.D., of the Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

In this Viewpoint, the authors discuss the European Working Time Directive that led to this reform, the effect of this directive on European medical care and education, and the important implications for graduate training reform in the United States.

(JAMA. 2013;309[5]:447-448. Available pre-embargo to the media at https://media.jamanetwork.com)

Improving Population Health in U.S. Cities

Nicholas W. Stine, M.D., of the New York City Health and Hospitals Corporation, New York, and colleagues describe in a Viewpoint the challenges and opportunities to improving population health in U.S. cities.

“While the diversity and fragmentation of services within cities pose formidable organizational challenges, there are several key attributes of urban settings, if harnessed strategically, that offer opportunities for potentially effective population health strategies.”

(JAMA. 2013;309[5]:449-450. Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the articles 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, FEBRUARY 5, 2013

Media Advisory: To contact corresponding author Bill Vicenzino, Ph.D., email b.vicenzino@uq.edu.au.

CHICAGO – Among patients with chronic unilateral lateral epicondylalgia (“tennis elbow”), a single injection of corticosteroid medication was associated with poorer outcomes after one year and higher recurrence rates compared with placebo, while eight weeks of physiotherapy did not significantly improve long-term outcomes, according to a study appearing in the February 6 issue of JAMA.

“Use of corticosteroid injections to treat lateral epicondylalgia is increasingly discouraged, partly because evidence of long-term efficacy has not been found, and due to high recurrence rates,” according to background information in the article. Combining corticosteroid injection with physiotherapy to compensate for the poor long-term outcomes of corticosteroid injections has been evaluated in only 2 small studies, and the long-term effects of combining these therapies are not known.

Brooke K. Coombes, Ph.D., of the University of Queensland, St. Lucia, Australia, and colleagues conducted a study to evaluate the effectiveness of corticosteroid injection, multimodal physiotherapy, or both in 165 patients with unilateral lateral epicondylalgia of longer than 6 weeks’ duration. The patients were enrolled between July 2008 and May 2010; 1-year follow-up was completed in May 2011. Patients were randomized to either corticosteroid injection (n = 43), placebo injection (n = 41), corticosteroid injection plus physiotherapy (n = 40), or placebo injection plus physiotherapy (n = 41). The 2 primary outcomes were 1-year global rating of change scores for complete recovery or much improvement and 1-year recurrence (defined as complete recovery or much improvement at 4 or 8 weeks, but not later) analyzed on an intention-to-treat basis. Secondary outcomes included complete recovery or much improvement at 4 and 26 weeks.

The researchers found that corticosteroid injection demonstrated lower complete recovery or much improvement at 1 year compared with placebo injection (83 percent vs. 96 percent) and greater recurrence (54 percent vs. 12 percent). There were no differences between physiotherapy and no physiotherapy at 1 year for complete recovery or much improvement (91 percent vs. 88 percent) or recurrence (29 percent vs. 38 percent).

There were no significant interaction effects at 26 weeks. The corticosteroid injection demonstrated lower complete recovery or much improvement compared with the placebo injection (55 percent vs. 85 percent). Physiotherapy compared with no physiotherapy demonstrated no effects on the outcomes of complete recovery or much improvement (71 percent vs. 69 percent), and with no significant differences on measures of worst pain; resting pain; pain and disability; and quality of life.

“At 4 weeks, there was a significant interaction between corticosteroid injection and physiotherapy, whereby patients receiving the placebo injection plus physiotherapy had greater complete recovery or much improvement vs. no physiotherapy (39 percent vs. 10 percent, respectively). However, there was no difference between patients receiving the corticosteroid injection plus physiotherapy vs. corticosteroid alone (68 percent vs. 71 percent, respectively),” the authors write.

“Contrary to our hypothesis and to a generally held clinical view, we found that multimodal physiotherapy provided no beneficial long-term effect on complete recovery or much improvement, recurrence, pain, disability, or quality of life, thereby not supporting the hypothesis that the combined approach is superior. However, physiotherapy should not be dismissed altogether because in the absence of the corticosteroid, it provided short-term benefit across all outcomes, as well as the lowest recurrence rates (4.9 percent) and 100 percent complete recovery or much improvement at 1 year.”

(JAMA. 2013;309(5):461-469; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by the Australian National Health and Medical Research Council grant awarded to Drs. Bisset, Brooks, and Vicenzino. 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, FEBRUARY 5, 2013

Media Advisory: To contact Anna A. Ahimastos, Ph.D., email A.Ahimastos@alfred.org.au. To contact editorial author Mary McGrae McDermott, M.D., call Marla Paul at 312-503-8928 or email marla-paul@northwestern.edu.

CHICAGO – Among patients with peripheral artery disease and intermittent claudication (pain in the calf that comes and goes, typically felt while walking), 24 weeks of treatment with the angiotensin-converting enzyme (ACE) inhibitor ramipril was associated with improvement in pain-free and maximum walking times and the physical health aspect of quality of life, according to a study appearing in the February 6 issue of JAMA.

“Approximately 27 million individuals in Europe and North America have peripheral artery disease (PAD). Intermittent claudication occurs in approximately one-third of patients with PAD and typically presents as pain within leg muscle groups that occurs during walking but is relieved by rest. Patients with intermittent claudication have significant impairment in ambulatory function, resulting in functional disability and significant lifestyle limitation. Treatment of these patients is aimed at reducing cardiovascular risk, increasing functional performance, and improving health-related quality of life,” according to background information in the article.  Current drug treatments to improve walking distance have limited efficacy. A pilot trial with ramipril showed promising results. However, that trial was small and the findings were restricted to a subset of patients who comprise approximately one-half of all patients with claudication.

Anna A. Ahimastos, Ph.D., of the Baker IDI Heart and Diabetes Institute, Melbourne, Australia, and colleagues conducted a study to examine the association of ramipril therapy on walking distance and health-related quality of life as compared with placebo in a larger, more general PAD population. The randomized, placebo-controlled trial included 212 patients with peripheral artery disease (average age, 65.5 years), initiated in May 2008 and completed in August 2011. Patients were randomized to receive 10 mg/d of ramipril (n = 106) or matching placebo (n = 106) for 24 weeks. The primary outcome measures for the study were maximum and pain-free walking times, as recorded during a standard treadmill test. The Walking Impairment Questionnaire (WIQ) and Short-Form 36 Health Survey (SF-36) were used to assess walking ability and quality of life, respectively.

The researchers found that relative to placebo, ramipril was associated with a 75-second increase in average pain-free walking time and a 255-second increase in maximum walking time (a 77 percent and 123 percent increase in pain-free and maximum walking times, respectively). Compared to placebo, ramipril was also associated with improvements in WIQ scores (median distance, speed score and stair climbing) and the overall SF-36 median Physical Component Summary score.

“The increase in WIQ scores suggests that ramipril improves patient-perceived ability to perform normal daily activities. Ramipril therapy was also associated with moderate improvement in the physical health component of the SF-36 score. Importantly, these associations were additional to those achieved with standard clinical management by a general practitioner or vascular specialist. Further benefits may be achieved by adherence to lifestyle recommendations including smoking cessation and regular exercise, as well as more aggressive medical management of cardiovascular risk factors,” the authors write.

“To our knowledge, this is the first adequately powered randomized trial demonstrating that treatment with ramipril is associated with improved treadmill walking performance in patients with PAD.”

(JAMA. 2013;309(5):453-460; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by the National Heart Foundation of Australia, the National Health and Medical Research Council of Australia, and the Operational Infrastructure Support Program of the Victorian State Government, Australia. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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

Editorial: Medications for Improving Walking Performance in Peripheral Artery Disease – Still Miles to Go

Mary McGrae McDermott, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, (also Contributing Editor, JAMA) comments on the results of this study in an accompanying editorial.

“A recent report from the Global Disease Burden study concluded that global disease burden continues to shift away from communicable to noncommunicable diseases and from premature death to greater years lived with disability. New therapies are needed to improve mobility and reduce disability among men and women living with PAD and other chronic diseases. Further study is needed to confirm the findings reported by Ahimastos et al and to determine whether ramipril therapy and other ACE inhibitors improve walking performance in ethnically diverse populations.”

(JAMA. 2013;309(5):487-488; 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. McDermott reported serving as a consultant for Ironwood Pharmaceuticals, a company that develops drugs used to treat peripheral artery disease (PAD), and serving as the medical editor for PAD for the Foundation for Informed Medical Decision Making.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, FEBRUARY 5, 2013

Media Advisory: To contact Joan M. Teno, M.D., M.S., call David Orenstein at 401-863-1862 or email david_orenstein@brown.edu. To contact editorial co-author Mary E. Tinetti, M.D., call Karen Peart at 203-432-1326 or email karen.peart@yale.edu.

CHICAGO – In a study that included data on more than 800,000 Medicare beneficiaries who died between 2000 – 2009, a lower proportion died in an acute care hospital in recent years, although both intensive care unit (ICU) use and the rate of health care transitions increased during the last month of life, according to a study appearing in the February 6 issue of JAMA.

“Site of death has been proposed as a quality measure for end-of-life care because, despite general population surveys indicating the majority of respondents and those with serious illness want to die at home, in actuality, most die in an institutional setting. One study found poorer quality of care in the institutional setting compared with care at home, especially with hospice services. The place of care and site of death have implications for the grief and posttraumatic stress disorders experienced by family members,” according to background information in the article.

Joan M. Teno, M.D., M.S., of the Warren Alpert Medical School of Brown University, Providence, R.I., and colleagues analyzed Medicare claims data to document places of care and health care transitions for Medicare decedents in the last months of life to assess end-of-life care. The study consisted of a random 20 percent sample of fee-for-service Medicare beneficiaries, 66 years of age and older, who died in 2000 (n = 270,202), 2005 (n = 291,819), or 2009 (n = 286,282). Based on billing data, patients were classified as having a medical diagnosis of cancer, chronic obstructive pulmonary disease, or dementia in the last 180 days of life. The main outcome measures for the study were site of death, place of care, rates of health care transitions, and potentially burdensome transitions (e.g., health care transitions in the last 3 days of life).

Among the findings of the researchers, the percentage of deaths that occurred in acute care hospitals decreased from 32.6 percent in 2000 to 24.6 percent in 2009. More decedents in 2009 than in 2000 had an ICU stay in the last month of life (from 24.3 percent to 29.2 percent). Hospice use at the time of death increased from 21.6 percent in 2000 to 42.2 percent in 2009.

“Short hospice stays increased from 22.2 percent in 2000 to 28.4 percent of hospice decedents using hospice for 3 days or less. Of these late hospice referrals in 2009, 40.3 percent were preceded by hospitalizations with an ICU stay,” the authors write.

Transitions in the last 3 days of life increased from 10.3 percent to 14.2 percent in 2009. The average rate of health care transitions in the last 90 days of life increased from 2.1 per decedent in 2000 to 3.1 per decedent in 2009, with an increase in 2 types of potentially burdensome transitions: transitions in the last 3 days of life and multiple hospitalizations in the last 90 days of life.

“Our findings of an increase in the number of short hospice stays following a hospitalization, often involving an ICU stay, suggest that increasing hospice use may not lead to a reduction in resource utilization. Short hospice lengths of stay raise concerns that hospice is an ‘add-on’ to a growing pattern of more utilization of intensive services at the end of life,” the researchers write.

(JAMA. 2013;309(5):470-477; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This research was funded by a National Institute on Aging grant and in part by the Robert Wood Johnson Foundation. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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

Editorial: Changes in End-of-Life Care Over the Past Decade – More Not Better

In an accompanying editorial, Grace Jenq, M.D., and Mary E. Tinetti, M.D., of the Yale School of Medicine, New Haven, Conn., write that “site of death has been proposed as a measure of the quality of end-of-life care, perhaps based on studies showing that the majority of people, including those with serious illness, want to die at home.”

“The study by Teno et al suggests that site of death is an insufficient metric given the many transitions endured, and intensive care services received, prior to the actual event of death. A more appropriate metric might be whether patients’ goals were elicited and care predicated on meeting those goals was instituted soon enough to make a difference in end-of-life care.”

(JAMA. 2013;309(5):489-490; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 12:55 P.M. (CT) TUESDAY, JANUARY 22, 2013

Media Advisory: To contact Amal Jubran, M.D., call Maureen Dyman at 708-202-5627 or email Maureen.Dyman@va.gov.

CHICAGO – Among patients with a tracheostomy requiring prolonged mechanical ventilation and treated at a single long-term care facility, unassisted breathing using an oxygen delivery device connected to a tracheostomy collar, compared with using a method known as pressure support, resulted in earlier weaning (gradually decreasing dependence on assisted ventilation), although there was no difference between the methods in patient survival at 6 and 12 months, according to a JAMA study published online. The study is being released early to coincide with its presentation at the Society of Critical Care Medicine’s 42^nd Critical Care Congress.

“Patients requiring prolonged mechanical ventilation, defined as more than 21 days, account for more than 13 percent of ventilated patients and 37 percent of intensive care unit (ICU) costs. Because of changes in U.S. reimbursement practices, these patients are usually transferred to centers that specialize in weaning, also known as long-term acute care hospitals (LTACHs). The number of LTACHs increased from 192 to 408 between 1997 and 2006, and costs increased by 267 percent, reaching $1.3 billion in 2006,” according to background information in the article. The number of ICU patients transferred to LTACHs for weaning from prolonged ventilation is expected to increase substantially. “The most effective method of weaning such patients has not been investigated.”

Amal Jubran, M.D., of the Edward Hines Jr. Veterans Affairs Hospital, Hines, IL., and colleagues conducted a study to compare the length of time required for weaning from prolonged ventilation with pressure support vs. unassisted breathing through an oxygen-delivery device connected to a tracheostomy collar (holds the tracheostomy tube in place). Pressure support is mechanical ventilatory assistance in which the ventilator provides support for each breath using a preset amount of pressure. Between 2000 and 2010, a randomized study was conducted in tracheotomized patients transferred to a single LTACH (RML Specialty Hospital, Hinsdale, IL.) for weaning from prolonged ventilation. Of 500 patients who underwent a 5-day screening procedure, 316 did not tolerate the procedure and were randomly assigned to receive weaning with pressure support (n = 155) or a tracheostomy collar (n = 161). Survival at 6- and 12-month time points was also determined.

Of 316 patients, 4 were withdrawn and not included in analysis. Of 152 patients in the pressure-support group, 68 (44.7 percent) were weaned; 22 (14.5 percent) died. Of 160 patients in the tracheostomy collar group, 85 (53.1 percent) were weaned; 16 (10.0 percent) died. Among the entire group of randomized patients, median (midpoint) weaning time was shorter with tracheostomy collar use than with pressure support: 15 days vs. 19 days. Among patients who completed the study (n = 194), median weaning time was shorter with tracheostomy collar use than with pressure support: 13 days vs. 19 days.

The researchers also found there was no significant difference in mortality between the pressure-support group vs. the tracheostomy collar group at 6 months (55.92 percent vs. 51.25 percent) and 12 months (66.45 percent vs. 60.00 percent). Frequency of adverse events (new episode of pneumonia, arrhythmias, pneumothorax) was similar in the 2 groups.

“This study has 3 major findings. First, tracheostomy collar use resulted in earlier weaning than did pressure support in patients who required prolonged mechanical ventilation. Second, the influence of weaning method on rate of successful weaning was related to time taken to fail the screening procedure: weaning was faster with tracheostomy collar use than with pressure support in the late-failure group but not in the early-failure group. Third, mortality was equivalent in the pressure-support and tracheostomy collar groups at 6 and 12 months,” the authors write.

(doi:10.1001/jama.2013.159; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This work was supported by funding from the National Institute of Nursing Research. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Tobin declares receipt of royalties from McGraw-Hill for 2 books published on critical care medicine. The other authors report no disclosures.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JANUARY 22, 2013

Study Identifies What Type of Hospitals are More Likely to Receive Penalties For Failing to Reduce Hospital Readmissions

“The federal Hospital Readmissions Reduction Program (HRRP) took effect on October 1, 2012, the first day of fiscal year 2013. Under this program, using claims data from July 2008 through June 2011, the Centers for Medicare & Medicaid Services (CMS) determined, for each eligible U.S. hospital, whether their readmission rates were higher than would be predicted by CMS models based on their case mix. Hospitals with higher-than-predicted readmission rates will have their total Medicare reimbursement for fiscal year 2013 cut by up to 1 percent based on these calculations. The CMS recently made these payment cuts public,” writes Karen E. Joynt, M.D., M.P.H., of Brigham and Women’s Hospital, and Ashish K. Jha, M.D., M.P.H., of the Harvard School of Public Health, Boston. The authors conducted a study to examine the risk of penalties for U.S. hospitals that care for medically complex or socioeconomically vulnerable patients, namely large teaching hospitals and safety-net hospitals.

As reported in a Research Letter, the authors used the publicly available HRRP Supplemental Data File and categorized hospitals as having high penalties (top half of penalized hospitals), low penalties (bottom half), and no penalties. These data were linked to the 2011 American Hospital Association annual survey to identify hospitals that likely care for sicker patients (large hospitals with 400 or more beds and major teaching hospitals with membership in the Council of Teaching Hospitals) as well as safety-net hospitals (SNHs, those in the highest quartile of the disproportionate share hospital index, a measure used by the CMS to quantify care provided for the poor).

“We found that large hospitals, teaching hospitals, and SNHs are more likely to receive payment cuts under the HRRP. It is unclear exactly why these hospitals have higher readmission rates than their smaller, non-teaching, non-SNH counterparts, but prior research suggests that differences between hospitals are likely related to both case mix (medical complexity) and socioeconomic mix of the patient population. There is less evidence that differences in readmissions are related to measured hospital quality.”

(JAMA. 2013;309[4]:342-343. Available pre-embargo to the media at https://media.jamanetwork.com)

Viewpoints in This Issue of JAMA

Thirty-Day Readmissions – The Clock Is Ticking

In this Viewpoint, Muthiah Vaduganathan, M.D., M.P.H., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues discuss the widely accepted 30-day time frame that is often used to help define response to therapies, and the use of rehospitalization as a target end point. The authors use heart failure as an example to point out the various facets of postdischarge hospital outcomes.

“Heart failure is a chronic, undulating condition. Focusing on an arbitrary time frame and end point inadequately characterizes the situation. A more nuanced and comprehensive approach is required to effectively alter the postdischarge course of patients admitted for heart failure and other conditions. Specific quality metrics should be rigorously tested and validated in target populations to ensure those measures are feasible and effective for improving the clinical end points. Longer-term end points may help capture a larger at-risk population and reduce the early competing risks of mortality and rehospitalization. Clear criteria for admission, readmission, and discharge must be established to encourage necessary admissions for appropriate length of stay.”

(JAMA. 2013;309[4]:345-346. Available pre-embargo to the media at https://media.jamanetwork.com)

Time to Get Serious About Pay for Performance

In this Viewpoint, Ashish K. Jha, M.D., M.P.H., of the Harvard School of Public Health, Boston, addresses three issues regarding pay for performance: incentive size, incentive structure, and metric choice; and how pay for performance initiatives might be improved.

“Pay for performance—putting real money at risk to motivate hospitals to take responsibility for patient outcomes— remains an attractive notion. However, it will only succeed by making bold choices, monitoring its effects closely, and changing the approach when the evidence suggests it is not working. Experimentation with different models that put more dollars at risk for poorly performing hospitals may be one option, using these dollars to focus them on patient outcomes. While some institutions will lose in this new scheme, their patients are already losing now—too many continue to have adverse outcomes in U.S. hospitals because of poor-quality care. Pay for performance represents an enormous opportunity to right the ship, but only if policy makers are willing to be courageous, learn along the way, and remain focused on the primary mission of the health care system: to ensure that patients achieve the best outcomes possible.”

(JAMA. 2013;309[4]:347-348. Available pre-embargo to the media at https://media.jamanetwork.com)

Tension Between Quality Measurement, Public Quality Reporting, and Pay for Performance

Steven A. Farmer, M.D., Ph.D., of the Northwestern University Feinberg School of Medicine, Chicago, and colleagues examine reasons why two major initiatives that seek to improve quality of U.S. health care—public reporting of outcomes and pay for performance (P4P)—“have the potential to reduce the reliability of the administrative data on which they are often based and generate spurious estimates of performance.”

“How can outcomes be measured without abandoning P4P or public reporting? There is need for a national, standardized system for outcome reporting. This system must be separate from billing data and structured so that it is minimally affected by the incentives to alter coding created by public reporting and P4P. The system should be designed to provide time-consistent measures of actual outcomes, which billing data do not. A new outcome reporting system will not be simple or inexpensive, but there appear to be no alternatives to this approach.”

“Quality improvement efforts must engage hospitals in capturing accurate and timely quality information not because regulators seek data, but to ensure that their health care product provides optimal care and is competitive in the marketplace.”

(JAMA. 2013;309[4]:349-350. Available pre-embargo to the media at https://media.jamanetwork.com)

Recasting Readmissions by Placing the Hospital Role in Community Context

Douglas McCarthy, M.B.A., of the Institute for Healthcare Improvement, Cambridge, Mass., and colleagues “suggest that it may be more advantageous to view [hospital] readmissions within a broader systems and community context that effectively engages all stakeholders to cooperatively improve outcomes.” The authors also discuss the Hospital Readmissions Reduction Program (established by the U.S. Affordable Care Act), which requires the Centers for Medicare & Medicaid Services to reduce Medicare payments to hospitals with excess readmissions for select conditions.

“The Hospital Readmission Reduction Program has raised awareness of readmissions as an indicator of a fragmented health care delivery system. Yet financial penalties alone are not likely to drive change. As the nation moves toward comprehensive payment and delivery system reforms to promote integrated care, the focus should shift toward reducing avoidable hospital use, not just readmission, by strengthening primary and preventive care and chronic disease management for populations of patients at risk of poor health outcomes.”

(JAMA. 2013;309[4]:351-352. Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the articles 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, JANUARY 22, 2013

Media Advisory: To contact corresponding author Harlan M. Krumholz, M.D., S.M., call Karen Peart at 203-432-1326 or email karen.peart@yale.edu.

CHICAGO – Among approximately 3 million Medicare patients hospitalized for heart failure, heart attack, or pneumonia, readmissions were frequent throughout the 30 days following the hospitalization, and resulted from a wide variety of diagnoses that often differed from the cause of the index hospitalization, according to a study appearing in the January 23/30 issue of JAMA.

“Hospital readmissions are common and can be a marker of poor health care quality and efficiency. To lower readmission rates, the Centers for Medicare & Medicaid Services (CMS) began publicly reporting 30-day risk-standardized readmission rates for heart failure (HF), acute myocardial infarction [MI; heart attack], and pneumonia after these measures were endorsed by the National Quality Forum. These measures are part of a federal strategy to provide incentives to improve quality of care by reducing preventable readmissions. Critical to the development of effective programs to reduce readmission is an understanding of the diagnoses and timing associated with these events,” according to background information in the article. “Insights into the diversity and variation of readmission diagnoses can illustrate the potential benefits of general vs. disease-specific interventions in reducing the overall number of readmissions.”

Kumar Dharmarajan, M.D., M.B.A., of Columbia University Medical Center, New York, and colleagues analyzed 2007-2009 Medicare fee-for-service claims data to examine readmission diagnoses and timing among Medicare beneficiaries readmitted within 30 days after hospitalization for HF, heart attack, or pneumonia, conditions that are primarily responsible for almost 15 percent of hospitalizations in older persons, and are the focus of current public reporting efforts.

During the time period analyzed, the researchers identified 329,308 30-day readmissions after 1,330,157 hospitalizations for HF (24.8 percent readmitted), 108,992 30-day readmissions after 548,834 hospitalizations for acute MI (19.9 percent readmitted), and 214,239 30-day readmissions after 1,168,624 hospitalizations for pneumonia (18.3 percent readmitted). Following hospitalization for HF and acute MI, readmission was most often due to HF (35.2 percent and 19.3 percent of readmissions, respectively). Following hospitalizations for pneumonia, readmission was most likely for recurrent pneumonia (22.4 percent).

“Of all 30-day readmissions, we found that 61.0 percent of the HF, 67.6 percent of the acute MI, and 62.6 percent of the pneumonia cohorts occurred during days 0 through 15 following discharge. More than 30 percent of 30-day readmissions occurred during days 16 through 30 for all 3 cohorts,” the authors write.

Median (midpoint) times to readmission were 12 days for patients initially hospitalized with HF, 10 days for patients initially hospitalized with acute MI, and 12 days for patients initially hospitalized with pneumonia. Neither readmission diagnoses nor timing substantively varied by age, sex, or race.

“The diagnoses associated with 30-day readmission are diverse and are not associated with patient demographic characteristics or time after discharge for older patients initially hospitalized with HF, acute MI, or pneumonia. Although a high percentage of 30-day readmissions occurred relatively soon after hospitalization, readmissions remained frequent during days 16 through 30 after discharge regardless of patient age, sex, or race. This heightened vulnerability of recently hospitalized patients to a broad spectrum of conditions throughout the postdischarge period favors a generalized approach to preventing readmissions that is broadly applicable across potential readmission diagnoses and effective for at least the full month after hospitalization. Strategies that are specific to particular diseases or periods may only address a fraction of patients at risk for rehospitalization,” the authors write.

(JAMA. 2013;309(4):355-363; 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, January 22 at this link.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JANUARY 22, 2013

Media Advisory: To contact corresponding author Joanne Lynn, M.D., M.A., M.S., call Ken Schwartz at 571-733-5709 or email Ken.Schwartz@altarum.org. To contact editorial author Mark V. Williams, M.D., call Marla Paul at 312-503-8928 or email marla-paul@northwestern.edu.

CHICAGO – Communities in which quality improvement initiatives for care transitions were implemented for Medicare beneficiaries had declines in rates of all-cause 30 day rehospitalizations and all hospitalizations, but no significant reductions in the rates of all-cause 30-day rehospitalizations as a percentage of hospital discharges, according to a study appearing in the January 23/30 issue of JAMA.

“Many Medicare beneficiaries have serious illnesses and disabilities and receive services from multiple clinicians and health care settings, engendering risks of errors in transitions and rehospitalizations,” according to background information in the article. “The Centers for Medicare & Medicaid Services (CMS) piloted various strategies for improving care and reducing costs in 2006-2007, including one that tested having Quality Improvement Organizations (QIOs) lead improvements in care transitions. Medicare’s QIOs serve each state and territory, aiming to improve the value of services.”

Jane Brock, M.D., M.S.P.H., of the Colorado Foundation for Medical Care, Englewood, and colleagues conducted a study to evaluate whether QIO-facilitated community-wide quality improvement (QI) could improve care transitions for Medicare beneficiaries and whether this work would correlate with reduced rehospitalizations. The study included an analysis of performance differences for 14 intervention communities and 50 comparison communities from before (2006-2008) and during (2009-2010) implementation. Intervention communities had between 22,070 and 90,843 Medicare fee-for-service (FFS) beneficiaries. For the intervention, QIOs facilitated community-wide quality improvement activities to implement evidence-based improvements in care transitions by community organizing, technical assistance, and monitoring of participation, implementation, effectiveness, and adverse effects.

The researchers found that the 14 intervention communities had an average reduction of 5.70 percent in rehospitalizations per 1,000 and of 5.74 percent in hospitalizations per 1,000 for FFS Medicare beneficiaries over the 2-year intervention period, with progressive improvement throughout. “During the same period, the 50 comparison communities had smaller mean reductions in rehospitalizations (2.05 percent) and hospitalizations (3.17 percent). Process control charts confirmed signals of important changes with the onset of the intervention. However, the widely used measure of rehospitalizations as a percentage of hospital discharges did not change during the study period, with a difference of 0.06 percent in the intervention communities and a difference of -0.16 percent in the comparison communities. The diversion to other Medicare-covered services was small, and mortality and patient-reported quality either did not change or improved.”

“This CMS QIO initiative demonstrated that Medicare beneficiaries in communities in which QI initiatives were implemented to promote evidence-based care transitions, compared with Medicare patients in communities without this QI implementation, had lower all-cause 30-day rehospitalization rates per 1,000 and all-cause hospitalization rates per 1,000 but no significant reductions in the rates of all-cause 30-day rehospitalizations as a percentage of hospital discharges,” the authors write.

(JAMA. 2013;309(4):381-391; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: A Requirement to Reduce Readmissions – Take Care of the Patient, Not Just the Disease

Mark V. Williams, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, comments on the three studies in this issue of JAMA that examine acute care, rehospitalization, and care transition among adult patients.

“The findings from these 3 reports also illustrate what experienced hospitalists, emergency physicians, and perhaps other physicians clearly recognize—the increasing fragmentation of patient care and consequent inappropriate use. Lack of coordinated care transitions has affected patients in the United States for half a century, but individual patients now see an increasing number of physicians, increasing the possibility of medical error, duplication of services, reduced quality, and increased cost. This has likely been driven, at least in part, by the marked expansion in the number of subspecialists, who now outnumber primary care physicians by about 2 to l. Medicare beneficiaries and their families must navigate seeing a median [midpoint] of 2 primary care physicians and 5 specialists during a 2-year period, and about one-third change their assigned physician from one year to another. This fragmentation escalates as patients approach the end of their lives with numerous physicians involved in a patient’s care.”

(JAMA. 2013;309(4):396-398; 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, JANUARY 22, 2013

Media Advisory: To contact Jay G. Berry, M.D., M.P.H., call Meghan Weber at 617-919-3110 or email meghan.weber@childrens.harvard.edu. To contact editorial co-author Rajendu Srivastava, M.D., F.R.C.P.C., M.P.H., call Phil Sahm at 801-581-2517 or email phil.sahm@hsc.utah.edu.

CHICAGO – In a national sample of 72 children’s hospitals, 6.5 percent of hospitalized children experienced an unplanned readmission within 30 days, with significant variability in readmission rates across conditions and hospitals, according to a study appearing in the January 23/30 issue of JAMA.

“Clinicians, hospitals, health systems, patients, and purchasers of health care are using readmission rates as an indicator of the quality of care that patients receive during a hospital admission and after discharge,” according to background information in the article. “Although readmissions for adults have been the subject of substantial research, readmissions for children have received less attention. … To understand potential opportunities to improve pediatric practice and reduce readmissions, information is needed on which diseases have the highest number of readmissions and whether there are differences in readmission rates across hospitals.”

Jay G. Berry, M.D., M.P.H., of Boston Children’s Hospital, and colleagues conducted a study to examine the percentage of hospitalized children who have unplanned readmissions, which admission diagnoses have the most readmissions, and whether readmission rates vary across hospitals. The analysis included data from 568,845 admissions at 72 children’s hospitals between July 2009 and June 2010 in the National Association of Children’s Hospitals and Related Institutions Case Mix Comparative data set. The primary outcome measures for the study were 30-day unplanned readmissions following admission for any diagnosis and for the 10 admission diagnoses with the highest readmission prevalence.

The researchers found that the 30-day readmission rate was 6.5 percent (n = 36,734); among readmitted children, 39.0 percent (n = 14,325) were readmitted in the first 7 days and 61.6 percent (n = 22,628) in the first 14 days. Readmission rates were higher for children 13 to 18 years of age (7.6 percent) than for children ages 5 to 12 years (6.1 percent), 1 to 4 years (6.2 percent), and less than 1 year (6.2 percent).

“Adjusted rates were 28.6 percent greater in hospitals with high vs. low readmission rates (7.2 percent vs. 5.6 percent). For the 10 admission diagnoses with the highest readmission prevalence, the adjusted rates were 17.0 percent to 66.0 percent greater in hospitals with high vs. low readmission rates. For example, sickle cell rates were 20.1 percent vs. 12.7 percent in high vs. low hospitals, respectively,” the authors write.

The highest rates for condition-specific unadjusted 30-day readmissions were for admissions for anemia or neutropenia (22.5 percent), ventricular shunt procedures (18.1 percent), and sickle cell anemia crisis (16.9 percent). For each condition-specific admission, 27.3 percent to 86.2 percent of readmissions were for a diagnosis involving the same organ system or a related etiology as the index admission. According to the authors, “For 9 of 10 index admission diagnoses, the most common readmission diagnosis was the same as the index diagnosis. Sickle cell had the highest percentage of readmissions (79.4 percent) that were for the same diagnosis as the index admission.”

“… we found substantial readmission rate variation across children’s hospitals that remained after controlling for patient age and chronic conditions. If hospitals with the highest readmission rates in this study were able to achieve the rates of the best performing hospitals, then the overall count of readmissions would be much smaller. It is possible that the distribution of pediatric readmission rates in this study could help hospitals interpret their own performance, identify target conditions for quality improvement, and determine whether an examination of the causes of their readmissions would be useful,” the authors write.

(JAMA. 2013;309(4):372-380; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Funding was provided by the Agency for Healthcare Research and Quality. Dr. Berry was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: Pediatric Readmissions as a Hospital Quality Measure

Rajendu Srivastava, M.D., F.R.C.P.C., M.P.H., of the University of Utah Health Sciences Center, Salt Lake City, and Ron Keren, M.D., M.P.H., of the University of Pennsylvania School of Medicine, Philadelphia, comment on the findings of this study in an accompanying editorial.

“More research is needed to understand to what extent pediatric readmissions are due to poor adherence to evidence-based best practices as opposed to patient and family resources and capabilities or some combination. Given that the overall rate of pediatric readmissions is 6.5 percent, clinicians, researchers, and policy makers will need to focus their efforts on conditions and patient characteristics associated with the highest baseline rate of readmissions and the greatest variation in rates across hospitals. A reasonable place to start would be with children with medical complexity who experience frequent hospitalizations and readmissions. Research needs to better determine how many readmissions are due to poor hospital quality of care vs. other reasons for readmissions and how many are preventable.”

(JAMA. 2013;309(4):396-398; 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, JANUARY 22, 2013

Media Advisory: To contact Anita A. Vashi, M.D., M.P.H., call Karen Peart at 203-432-1326 or email karen.peart@yale.edu.

CHICAGO – In a study that included more than 4 million patients, nearly 20 percent of hospitalizations resulted in at least 1 acute care encounter within the 30 days following discharge, with emergency department visits accounting for about 40 percent of post-discharge hospital-based acute care use, according to a study appearing in the January 23/30 issue of JAMA.

“Hospital readmissions within 30 days of discharge are common, costly, and often related to the index hospitalization,” according to background information in the article. “Current efforts to improve health care focus on hospital readmission rates as a marker of quality and on the effectiveness of transitions in care during the period after acute care is received. Emergency department (ED) visits are also a marker of hospital-based acute care following discharge but little is known about ED use during this period.”

Anita A. Vashi, M.D., M.P.H., of the Yale University School of Medicine, New Haven, Conn., and colleagues conducted a study to determine the degree to which ED visits (treat-and-release encounters) and hospital readmissions contribute to overall use of acute care services within 30 days of hospital discharge. The study included patients ages 18 years or older (average age: 53 years) who were discharged between July 2008 and September 2009 from acute care hospitals in 3 large, geographically diverse states (California, Florida, and Nebraska) with data recorded in the Healthcare Cost and Utilization Project state inpatient and ED databases. The majority of patients were female (53.5 percent) and approximately half of the patients were white (48.0 percent).

The final study group included 5,032,254 index hospitalizations among 4,028,555 patients. The researchers found that of all the hospitalizations in the study, 17.9 percent resulted in at least 1 acute care encounter in the 30 days following discharge; 7.5 percent of discharges were followed by at least 1 ED encounter; and 12.3 percent by at least 1 readmission. For every 1,000 discharges, there were 97.5 ED treat-and-release visits and 147.6 hospital readmissions in the 30 days following discharge. Visits to the ED comprised 39.8 percent of the post-discharge acute care encounters. Also, approximately one-third of hospital-based acute care use occurred during the first 7 days following hospital discharge, and more than half occurred during the first 14 days postdischarge.

There was substantial variability in use rates of acute care across the 470 different index discharge conditions. The number of ED treat-and-release visits ranged from a low of 22.4 encounters/1,000 discharges for breast malignancy to a high of 282.5 encounters/1,000 discharges for uncomplicated benign prostatic hypertrophy.

“Although patients returned to the ED for a variety of reasons, for the highest volume conditions, ED treat-and-release visits were always related to the index hospitalization,” the authors write.

“In conclusion, hospital-based acute care encounters are frequent among patients recently discharged from an inpatient setting. An improved understanding of how the ED setting is best used in the management of acute care needs—particularly for patients recently discharged from the hospital—is an important component of the effort to improve care transitions. The use of hospital readmissions as a lone metric for postdischarge health care quality may be incomplete without considering the role of the ED. Just as the Patient Protection and Affordable Care Act requires the development of programs to reduce readmissions, further initiatives are necessary to understand the drivers of postdischarge ED use and the clinical and financial efficiency associated with providing such acute care in the ED.”

(JAMA. 2013;309(4):364-371; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Dr. Carr is supported by a career development award from the Agency for Healthcare Research and Quality. Dr. Ross is supported by the National Institute on Aging and by the American Federation for Aging Research through the Paul B. Beeson Career Development Award Program. 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, JANUARY 15, 2013

Mega-Trials for Blockbusters

John P. A. Ioannidis, M.D., D.Sc., of the Stanford University School of Medicine, Stanford, Calif., writes that mega-trials (very large, simple trials) should be conducted for licensed interventions with annual sales that exceed $1 billion, i.e., a blockbuster. These blockbusters “should have at least 1 trial performed with at least 10,000 patients randomized to the intervention of interest and as many randomized either to placebo (if deemed to be a reasonable choice) or to another active intervention that is the least expensive effective intervention available.”

“Blockbuster drugs are eventually used by millions of patients. Typically there is evidence from randomized trials suggesting that these drugs are effective—at least for some end points (not necessarily the most serious ones), for some follow-up (not necessarily long enough), and in some specific circumstances (not necessarily representing what happens in real life). The supporting randomized trials typically include only a few hundred participants or, in the best case, a few thousand participants, often with relatively short-term follow-up and are conducted among populations selected to avoid patients with co-morbid conditions and those who take some other drugs.”

“Eventually many blockbusters may prove to be fully worth their cost. Conversely, if some of these widely used products fail to demonstrate benefit in mega-trials, this could mean saving tens of billions of dollars per year and perhaps thousands of lives.”

(JAMA. 2013;309[3]:239-240. Available pre-embargo to the media at https://media.jamanetwork.com)

Prespecified Falsification End Points – Can They Validate True Observational Associations?

Vinay Prasad, M.D., of the National Cancer Institute, Bethesda, Md., and Anupam B. Jena, M.D., Ph.D., of Harvard Medical School and Massachusetts General Hospital, Boston, write that “as observational studies have increased in number—fueled by a boom in electronic recordkeeping and the ease with which observational analyses of large databases can be performed—so too have failures to confirm initial research findings.” The authors suggest that to help identify whether the associations identified in an observational study are true rather than spurious correlations is the use of prespecified falsification hypotheses, which is a claim, distinct from the one being tested, that researchers believe is highly unlikely to be causally related to the intervention in question. “Prespecified falsification hypotheses may provide an intuitive and useful safeguard when observational data are used to find rare harms.”

“Prespecified falsification hypotheses can improve the validity of studies finding rare harms when researchers cannot determine answers to these questions from randomized controlled trials, either because of limited sample sizes or limited follow-up. However, falsification analysis is not a perfect tool for validating the associations in observational studies, nor is it intended to be. The absence of implausible falsification hypotheses does not imply that the primary association of interest is causal, nor does their presence guarantee that real relations do not exist. However, when many false relationships are present, caution is warranted in the interpretation of study findings.”

(JAMA. 2013;309[3]:241-242. Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the articles 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, JANUARY 15, 2013

Media Advisory: To contact Jean Reignier, M.D., Ph.D., email jean.reignier@chd-vendee.fr. To contact editorial author Todd W. Rice, M.D., M.Sc., call Craig Boerner at 615-322-4747 or email craig.boerner@vanderbilt.edu.

CHICAGO – Patients undergoing mechanical ventilation and receiving nutrition via a feeding tube who did not receive monitoring of residual gastric volume (amount of liquid left in the stomach after use of feeding tube) were not at a significantly greater risk of developing ventilator-associated pneumonia, according to a study appearing in the January 16 issue of JAMA. There is concern that monitoring of residual gastric volume leads to unnecessary interruptions of use of the feeding tube and subsequent inadequate feeding.

“Early enteral nutrition [receipt of food via a feeding tube] is the standard of care in critically ill patients receiving invasive mechanical ventilation. However, numerous studies have shown that early enteral nutrition is frequently not used or associated with inadequate calorie delivery,” according to background information in the article. The main reason for non-use is gastrointestinal intolerance to enteral nutrition. “Monitoring of residual gastric volume is recommended to prevent ventilator-associated pneumonia (VAP) in patients receiving early enteral nutrition. However, studies have challenged the reliability and effectiveness of this measure.”

Jean Reignier, M.D., Ph.D., of the District Hospital Center, La Roche-sur-Yon, France and colleagues conducted a study to test the hypothesis that absence of residual gastric volume monitoring was not associated with an increased incidence of VAP compared with routine residual gastric volume monitoring. The randomized, noninferiority (outcome not worse than treatment compared to) trial was conducted from May 2010 through March 2011 in adults requiring invasive mechanical ventilation for more than 2 days and given enteral nutrition within 36 hours after intubation at 9 French intensive care units (ICUs); 452 patients were randomized and 449 included in the intention-to-treat analysis (3 withdrew initial consent).  The intervention for this study was the absence of residual gastric volume monitoring.

The researchers found that in the intention-to-treat population, VAP occurred in 38 of 227 patients (16.7 percent) in the intervention group and in 35 of 222 patients (15.8 percent) in the control group. Patients in the intervention group were 77 percent more likely to receive 100 percent of their calorie goal than patients in the control group. Absence of residual gastric volume monitoring was not inferior to residual gastric volume monitoring regarding new infections, intensive care unit and hospital stay lengths, organ failure scores, or mortality rates.

“In conclusion, the current study supports the hypothesis that a protocol of enteral nutrition management without residual gastric volume monitoring is not inferior to a similar protocol including residual gastric volume monitoring in terms of protection against VAP. Residual gastric volume monitoring leads to unnecessary interruptions of enteral nutrition delivery with subsequent inadequate feeding and should be removed from the standard care of critically ill patients receiving invasive mechanical ventilation and early enteral nutrition,” the authors write.

(JAMA. 2013;309(3):249-256; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The Centre Hospitalier Departemental de la Vendee was the study sponsor. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflict of Interest and none were reported.

Editorial: Gastric Residual Volume – End of an Era

Todd W. Rice, M.D., M.Sc., of the Vanderbilt University School of Medicine, Nashville, Tenn., comments on the findings of this study in an accompanying editorial.

“Despite emerging evidence to the contrary, many enteral feeding protocols continue to interrupt enteral feeding for relatively low gastric residual volumes (GRVs), some with thresholds as low as 150 mL or twice the enteral feeding rate the patient is receiving at the time. The finding from the study by Reignier et al should instill confidence in clinicians to change practice and not routinely check GRVs in all patients mechanically ventilated receiving enteral nutrition.”

(JAMA. 2013;309(3):283-284; 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, JANUARY 15, 2013

Media Advisory: To contact corresponding author William H. Shrank, M.D., M.S.H.S., call Brian Cook or Isabella Leung of the CMS Press Office at 202-690-6145 or email press@cms.hhs.gov. To contact editorial author Jack Hoadley, Ph.D., call Lauren Mullins at 202-687-2269 or email lm973@georgetown.edu.

CHICAGO – In a study that included nearly 1.3 million Medicare beneficiaries who were either first-time enrollees or enrollees switching plans, researchers found a positive association between enrollment and publicly reported Medicare Advantage star ratings reflecting plan quality, according to a study appearing in the January 16 issue of JAMA.

“To inform enrollment decisions and spur improvement in the Medicare Advantage marketplace, the U.S. Centers for Medicare & Medicaid Services (CMS) provides star ratings reflecting Medicare Advantage plan quality. A combined Part C and D overall rating was created in 2011 for Medicare Advantage and prescription drug (MAPD) plans,” according to background information in the article. The star ratings incorporate data from several sources. “In 2011, MAPD star ratings ranged from 2.5 to 5 stars. Only 3 MAPD contracts received 5 stars; some were unrated because they were too new or small,” the authors write. “While star ratings clearly matter to insurers, it is unclear whether they matter to beneficiaries.”

Rachel O. Reid, M.S., of the Centers for Medicare & Medicaid Services, Baltimore, and colleagues conducted a study to assess the association between publicly reported Medicare Advantage plan quality ratings and enrollment. Of the 7.6 million beneficiaries with an eligible 2011 MAPD enrollment, the study population consisted of 952,352 first-time enrollees and 322,699 enrollees switching plans. The analysis controlled for beneficiary and plan characteristics.

Among the key characteristics of included plans by star rating, the highest-rated plans more often had higher premiums, while unrated plans more often had higher out-of-pocket costs or were private fee-for-service or local PPO plans.

The researchers found that among first-time enrollees, higher star ratings were associated with increased likelihood to enroll in a given plan (9.5 percentage points per 1-star increase). The highest rating available to a beneficiary was associated with a 1.9 percentage-point increase in likelihood to enroll. Star ratings were less strongly associated with enrollment for the youngest, black, low-income, rural, and Midwestern enrollees.

Among beneficiaries switching plans, higher star ratings were associated with increased likelihood to enroll in a given plan (4.4 percentage points per 1-star increase). A star rating at least as high as a beneficiary’s prior plan’s rating was associated with a 6.3 percentage-point increase in likelihood to enroll.

“Star ratings were less strongly associated with enrollment among the youngest, low-income, and rural beneficiaries and negatively associated among Midwestern beneficiaries. Compared with other races/ethnicities, star ratings were more strongly associated with enrollment for white beneficiaries,” the authors write.

“We found a positive association between CMS’s 5-star Medicare Advantage quality ratings and enrollment. Bolstering the business case for quality in the Medicare Advantage market, these findings may provide firms with additional incentive to cultivate higher quality, CMS with justification to continue to advance public reporting, and policy makers with a rationale to pursue quality reporting in other health insurance markets,” the authors conclude.

(JAMA. 2013;309(3):267-274; 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. Shrank reported serving as a consultant to United Healthcare; and receiving grant support from CVS Caremark, Aetna, and Express Scripts. The other authors did not report any disclosures.

Please Note: For this study, there will be a digital news release available, 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, January 15 at this link.

Editorial: Performance Ratings and Plan Selection by Medicare Beneficiaries

“Despite the limitations in this study, it is valuable to see some evidence that Medicare Advantage enrollees may be using ratings as one factor in making choices,” writes Jack Hoadley, Ph.D., of Georgetown University, Washington, D.C., in an accompanying editorial.

“It is critical for the program to keep improving the available plan ratings and to make them increasingly available and relevant to the needs of consumers. Key questions for future study include what tools and what measures do consumers seek when they select plans? How do consumers use ratings as part of a plan selection strategy? How can the plan selection process be simplified and streamlined?”

(JAMA. 2013;309(3):287-288; 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, JANUARY 15, 2013

Media Advisory: To contact Kohei Hasegawa, M.D., M.P.H., call Kristen Stanton at 617-643-3907 or email kstanton3@partners.org. To contact editorial co-author Donald M. Yealy, M.D., call Rick Pietzak at 412-864-4151 or email pietzakr@upmc.edu.

CHICAGO – In patients with out-of-hospital cardiac arrest, cardiopulmonary resuscitation with advanced airway management, such as endotracheal intubation, was a significant predictor of poor neurological outcome compared with conventional bag-valve-mask ventilation, contradicting the assumption that an aggressive airway intervention is associated with improved outcomes, according to a study appearing in the January 16 issue of JAMA.

“Out-of-hospital cardiac arrest (OHCA) is a major public health problem, occurring in 375,000 to 390,000 individuals in the United States each year,” according to background information in the article. The rate of survival after OHCA has increased with advances in care; however, the rate is still low, with recent estimates reporting 8 percent to 10 percent. “Although advanced airway management, such as endotracheal intubation or insertion of supraglottic [above the vocal apparatus of the larynx] airways, has long been the criterion standard for airway management of patients with OHCA, recent studies have challenged the survival benefit of advanced airway management compared with conventional bag-valve-mask ventilation in this clinical setting. However, large-scale studies evaluating the association between advanced airway management and patient-centered outcomes such as neurological status do not exist.”

Kohei Hasegawa, M.D., M.P.H., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues conducted a study to examine whether cardiopulmonary resuscitation (CPR) with any type of out-of-hospital advanced airway management by emergency medical service (EMS) personnel, compared with CPR with conventional bag-valve-mask ventilation, would be associated with favorable neurological outcome in adult OHCA. The nationwide, population-based study involved 649,654 adult patients in Japan who had an OHCA and in whom resuscitation was attempted by emergency responders with subsequent transport to medical institutions from January 2005 through December 2010. The primary outcome for the study was favorable neurological outcome 1 month after an OHCA.

Of the eligible 649,359 patients with OHCA included in the study, 57 percent underwent bag-valve-mask ventilation and 43 percent advanced airway management, including 6 percent with endotracheal intubation and 37 percent with use of supraglottic airways. Overall, rates of return of spontaneous circulation, 1-month survival, and neurologically favorable survival were 6.5 percent, 4.7 percent, and 2.2 percent, respectively. The rates of neurologically favorable survival were 1.0 percent in the endotracheal intubation group, 1.1 percent in the supraglottic airway group, and 2.9 percent in the bag-valve-mask ventilation group, with patients in the advanced airway group having a 62 percent lower odds of a favorable neurological outcome compared with the bag-valve-mask group. The odds of neurologically favorable survival were significantly lower both for endotracheal intubation and for supraglottic airways.

“Our observations contradict the assumption that aggressive airway intervention is associated with improved outcomes and provide an opportunity to reconsider the approach to prehospital airway management in this population,” the authors write.

“Should clinicians avoid advanced airway management during CPR based on the best available observational evidence? Although one option would be to remove advanced airway management from the skill set of all out-of-hospital rescuers, that approach would disregard situations in which advanced airway management would be expected to be efficacious, especially for long-distance transfers and respiratory failure not yet with cardiac arrest. Future research will need to identify whether there are subsets of patients for whom prehospital advanced airway management is beneficial.”

(JAMA. 2013;309(3):257-266; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by a grant to Dr. Hiraide for emergency management scientific research from the Fire and Disaster Management Agency. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: Managing the Airway During Cardiac Arrest

In an accompanying editorial, Henry E. Wang, M.D., M.S., of the University of Alabama School of Medicine, Birmingham, and Donald M. Yealy, M.D., of the University of Pittsburgh, write that the “study by Hasegawa et al sends a clear message.”

“Emergency medical services professionals across the world must engage in the scientific process. A large, well-designed research effort is needed to define the benefit from endotracheal intubation, supraglottic airway insertion, or more simple actions during resuscitation after cardiac arrest. Absent this investment, the emergency medical services community risks turning a blind eye and embracing ineffective or harmful airway interventions. Patients with cardiac arrest and the out-of-hospital rescuers who care for them deserve to know what is best.”

(JAMA. 2013;309(3):285-286; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Yealy reports providing expert testimony for multiple medical malpractice firms and receiving royalties from Wolters Kluwer. No other disclosures were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JANUARY 8, 2013

How to Decide Whether a Clinical Practice Guideline Is Trustworthy

David F. Ransohoff, M.D., of the University of North Carolina School of Medicine, Chapel Hill, and colleagues discuss concerns about the process of developing clinical practice guidelines and the standards for developing practice guidelines created by the Institute of Medicine (IOM).

“Guidelines, especially those that try to set limits, will always raise controversy. Clinicians, patients, and policy makers should insist upon a constructive dialog about the evidence and its translation into recommendations. An explicit, transparent process for evaluating adherence to the IOM committee’s standards should elevate this conversation to a higher plane.”

(JAMA. 2013;309[2]:139-140. Available pre-embargo to the media at https://media.jamanetwork.com)

Changing Physical Activity Participation for the Medical Profession

Antronette K. Yancey, M.D., M.P.H., of the UCLA Fielding School of Public Health, Los Angeles, and colleagues offer suggestions on how health professionals can improve and incorporate physical activity into their lifestyle.

“Simple and quick episodes of moderate to vigorous physical activity can be incorporated into the workplace without disrupting workflow or productivity. Given the value of regular physical activity to health, the medical profession should lead the way in adopting such practices.”

(JAMA. 2013;309[2]:141-142. Available pre-embargo to the media at https://media.jamanetwork.com)

Physical Activity and Structured Exercise for Patients With Stable Ischemic Heart Disease

William E. Boden, M.D., of the Samuel Stratton VA Medical Center and Albany Medical College, Albany, New York, and colleagues examine the gap between scientific evidence and clinical practice regarding structured exercise and increased physical activity for patients with stable ischemic heart disease.

“In an era of spiraling health care expenditures, structured exercise regimens, increased physical activity, or both may be the ultimate low-cost therapy for achieving improved health outcomes. If the ‘exercise is medicine’ adage is to be applied and optimized, the prescription at present remains underfilled for too many patients with stable ischemic heart disease. Thus, the medical community should embrace this clinically effective and cost-effective strategy as a first-line therapy, thereby enabling patients to realize the health benefits from a lifestyle intervention that must become more mainstream in U.S. medical practice.”

(JAMA. 2013;309[2]:143-144. Available pre-embargo to the media at https://media.jamanetwork.com)

Appropriate Use of Non-English-Language Skills in Clinical Care

“An estimated 25 million U.S. residents have limited English proficiency (LEP) and in a 2006 national survey of 2,022 internists, 54 percent reported encountering patients with LEP at least weekly, with many seeing LEP patients every day,” writes Marsha Regenstein, Ph.D., M.C.P., of the George Washington University School of Public Health and Health Services, Washington, D.C., and colleagues. In this Viewpoint, the authors examine the issue of the use of non-English-language skills in clinical care, including clinical encounters potentially needing language interpreters.

“Clinicians should also consider ways to detect when a non-English-language encounter is becoming more likely to cause communication errors. In particular, using teach-back, a National Quality Forum-endorsed practice in which clinicians explicitly state key points of instruction and ask patients to restate them to ensure clarity, is useful in many settings. This can be an especially important means for ongoing communication quality assurance for physicians using their non-English language skills in clinical practice.”

(JAMA. 2013;309[2]:145-146. Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the articles 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, JANUARY 8, 2013

Media Advisory: To contact co-author Dick Tibboel, M.D., Ph.D., email d.tibboel@erasmusmc.nl. To contact editorial author Kanwaljeet J. S. Anand, M.B.B.S., D.Phil., F.R.C.P.C.H., call Sheila Champlin at 901-448-4957 or email schampli@uthsc.edu.

CHICAGO – Among infants undergoing major surgery, postoperative use of intermittent intravenous paracetamol (acetaminophen) for the management of pain resulted in a lower cumulative morphine dose over 48 hours, according to a study appearing in the January 9 issue of JAMA.

Opioid therapy for the treatment of pain is associated with adverse effects.  Researchers are seeking alternative analgesic regimens in neonates and infants, according to background information in the article. Paracetamol has been proposed as an alternative, with one study showing promise.

Ilse Ceelie, M.D., Ph.D., of Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands, and colleagues performed a trial with infants who had undergone major abdominal and thoracic (noncardiac) surgery to determine if intravenous paracetamol would reduce the cumulative morphine dose needed to provide adequate analgesia by at least 30 percent. The randomized study was conducted in a pediatric intensive care unit and included 71 patients (neonates or infants younger than 1 year) undergoing surgery between March 2008 and July 2010, with follow-up of 48 hours. All patients received a dose of morphine 30 minutes before the end of surgery, followed by continuous morphine or intermittent intravenous paracetamol up to 48 hours postsurgery. Infants in both study groups received morphine as rescue medication based on the guidance of the validated pain assessment instruments.

The researchers found that the cumulative morphine dose in the paracetamol group was 66 percent lower than that in the morphine group (median [midpoint], 121 μg/kg per 48 hours vs. 357 μg/kg per 48 hours). “Considering the 2 stratified age groups separately, the cumulative morphine dose in the paracetamol group was 49 percent lower than that in the morphine group for the neonates (age 0 through 10 days) (median, 111 μg/kg per 48 hours vs. 218 μg/kg per 48 hours) and 73 percent lower for the older infants (aged 11 days to 1 year) (median, 152 μg/kg per 48 hours vs. 553 μg/kg per 48 hours).”

The authors also found that neither the total morphine rescue dose, the amount or number of morphine rescue doses or the number of patients requiring rescue doses differed significantly between the paracetamol and morphine groups. Also, there were no significant differences for percentage of adverse effects or pain scores between treatment groups.

“This randomized controlled trial shows that infants who receive intravenous paracetamol as primary analgesic after major surgery require significantly less morphine than those who receive a continuous morphine infusion. Judging from the rescue morphine doses, a similar level of analgesia was obtained in either group. These results suggest that intravenous paracetamol may be an interesting alternative as primary analgesic in neonates and infants,” the authors conclude.

(JAMA. 2013;309(2):149-154; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by a grant from ZonMw Priority Medicines for Children.  All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: Pain Panacea for Opiophobia In Infants?

Kanwaljeet J. S. Anand, M.B.B.S., D.Phil., F.R.C.P.C.H., of the University of Tennessee Health Science Center and Children’s Foundation Research Center, Le Bonheur Children’s Hospital, Memphis, comments on the findings of this study in an accompanying editorial.

“Titrating morphine analgesia carefully (based on pain scores) is more labor intensive than the common practice of slightly oversedating infants who require opioid analgesia for painful conditions, such as following operations. However, this approach may avoid the respiratory depression, hypotension, and opioid tolerance observed in many centers. Busy clinical units will have to choose between the nursing resources required to follow such a labor-intensive protocol or to tolerate a relatively low incidence of oversedation and opioid-related adverse effects. Theoretically elegant approaches have little value in clinical practice if they are not practically feasible in the clinical settings for which they were designed. However, research studies such as the report by Ceelie et al are invaluable because they bring methodological rigor and continue to set new standards for future clinical practice.”

(JAMA. 2013;309(2):183-184; 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, JANUARY 8, 2013

Media Advisory: To contact Vanessa G. Allen, M.D., M.P.H., call Nicole Helsberg at 647-260-7466 or email nicole.helsberg@oahpp.ca. To contact editorial author Robert D. Kirkcaldy, M.D., M.P.H., call the NCHHSTP Media Office at 404-639-8895 or email NCHHSTPMediaTeam@cdc.gov.

CHICAGO – In an examination of the effectiveness of cefixime, the only oral cephalosporin antimicrobial recommended for treatment of Neisseria gonorrhoeae (gonorrhea) infections, researchers found a clinical treatment failure rate of nearly 7 percent for patients treated at a clinic in Toronto, according to a preliminary study published in the January 9 issue of JAMA.

“Because of Neisseria gonorrhoeae resistance to all prior first-line antimicrobial agents, cephalosporin [antibiotic] therapy with adjuvant azithromycin or doxycycline is recommended for treatment of gonorrhea,” according to background information in the article. Cefixime is the only oral cephalosporin recommended for gonorrhea treatment. “An increase in the minimum inhibitory concentration [MIC; lowest concentration of an anti-microbial agent that will prevent the growth of an organism] of N gonorrhoeae to cefixime, and to a lesser extent, an intramuscularly administered cephalosporin, ceftriaxone, has been identified in cultured isolates worldwide. The World Health Organization has sounded alarms for the threat of untreatable gonorrhea.”

Vanessa G. Allen, M.D., M.P.H., of Public Health Ontario, Toronto, Canada, and colleagues conducted a study to determine whether N gonorrhoeae strains with reduced susceptibilities to cefixime are associated with clinical failures. The study group consisted of N gonorrhoeae culture-positive individuals identified between May 2010 and April 2011 and treated at a sexual health clinic in Toronto with cefixime as recommended by Public Health Agency of Canada guidelines. The primary outcome measure for the study was cefixime treatment failure, defined as the repeat isolation of N gonorrhoeae at the test-of-cure visit identical to the pretreatment isolate by molecular typing and explicit denial of re-exposure.

There were 291 N gonorrhoeae culture-positive individuals identified. Of 133 who returned for test of cure, 13 were culture positive; 9 patients were determined to have experienced cefixime treatment failure, with an overall rate of clinical treatment failure of 6.77 percent. The rate of clinical failure associated with a cefixime MIC of 0.12 μg/mL or greater was 25 percent compared with 1.90 percent of infections with cefixime MICs less than 0.12 μg/mL.

“This study presents the first series of clinical failures of gonorrhea associated with the use of cefixime in North America, identified by the concurrent strategies of routine test-of-cure and culture-based testing for N gonorrhoeae,” the authors write.

“In light of the increases in cefixime MICs among isolates of N gonorrhoeae across North America, this study offers preliminary clinical data to support the recent CDC recommendations that cefixime is no longer optimal first-line therapy for the successful treatment of gonorrhea. As elevated MICs to ceftriaxone are also emerging, albeit at 1 to 2 MIC dilutions less than the cefixime MIC, proactive strategies for the identification of clinical failures of N gonorrhoeae to this last commercially available agent are required.”

(JAMA. 2013;309(2):163-170; 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.

Editorial: Cephalosporin-Resistant Gonorrhea in North America

In an accompanying editorial, Robert D. Kirkcaldy, M.D., M.P.H., of the Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, and colleagues write that the findings of this study, of documented cephalosporin treatment failures in North America, although expected, “its arrival is deeply troubling; clinicians now face the emergence of cephalosporin-resistant N gonorrhoeae without any well-studied, effective backup treatment options.”

“New antibiotics for treating gonococcal infections are needed. A clinical trial sponsored by the National Institute of Allergy and Infectious Diseases examining novel combinations of existing drugs just completed enrollment, and a small study of a new oral agent is ongoing. But the antibiotic pipeline is running dry: continued investment in antibiotic development is critical. Meanwhile, the gonococcus has continued to develop the capability to defeat each new antibiotic used. The threat of drug-resistant gonorrhea is increasing and has reached North America. Clinicians, drug developers, and public health professionals must act now.”

(JAMA. 2013;309(2):185-187; 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, JANUARY 8, 2013

Media Advisory: To contact Timothy McAlindon, D.M., M.P.H., call Julie Jette at 617-636-3265 or email jjette@tuftsmedicalcenter.org.

CHICAGO – In a two year randomized trial, patients with symptomatic knee osteoarthritis who received vitamin D supplementation did not have a significant difference in knee pain or cartilage volume loss compared to patients who received placebo, according to a study appearing in the January 9 issue of JAMA.

“Knee osteoarthritis (OA) is a common age-related musculoskeletal disorder that has significant functional impact and has considerable societal costs through work loss, early retirement, and arthroplasty. Despite its impact, there are no medical treatments established to influence the course of the disease,” according to background information in the article. “Some studies have suggested that vitamin D may protect against structural progression.”

Timothy McAlindon, D.M., M.P.H., of Tufts Medical Center, Boston, and colleagues conducted a clinical trial to examine whether vitamin D supplementation is associated with reductions in symptomatic and structural progression of knee OA. The 2-year randomized, placebo-controlled clinical trial included 146 participants with symptomatic knee OA (average age, 62 years; 61 percent women), who were enrolled in the study between March 2006 and June 2009. Participants were randomized to receive either placebo or oral cholecalciferol, 2,000 IU/day, with dose escalation to increase serum levels to more than 36 ng/mL. Eighty-five percent of the participants completed the study.

The primary measured outcomes for the study were knee pain severity (Western Ontario and McMaster Universities [WOMAC] pain scale, 0-20: 0, no pain; 20, extreme pain), and cartilage volume loss measured by magnetic resonance imaging. Secondary outcomes included physical function, knee function (WOMAC function scale, 0-68: 0, no difficulty; 68, extreme difficulty), cartilage thickness, bone marrow lesions, and radiographic joint space width.

Serum 25-hydroxyvitamin D levels increased by an average 16.1 ng/mL in the treatment group and by an average 2.1 ng/mL in the placebo group. Knee pain at the beginning of the study was slightly worse in the treatment group (average, 6.9) than in the placebo group (average, 5.8). Knee function at the beginning of the study was significantly worse in the treatment group (average, 22.7) than in the placebo group (average, 18.5). In the subset analyses for the WOMAC pain outcome, the effects were generally similar, and nonsignificant. The researchers found that knee pain decreased in both groups by an average -2.31 in the treatment group and -1.46 in the placebo group, with no significant differences at any time. The percentage of cartilage volume decreased by the same extent in both groups, by about 4 percent. There were no differences in any of the secondary clinical end points.

There were 31 serious adverse events in the vitamin D group and 23 in the placebo group but the number of participants who experienced an event was 16 in each group.

“… additional results from epidemiologic studies that emerged during the course of this study have been mixed demonstrating positive and negative associations. Two studies appeared to show strong associations of bone density with the development of knee OA, but some of those investigators later published concerns about the possibility of such associations arising as a result of contingent confounding. Therefore, together with the results of this clinical trial, the overall data suggest that vitamin D supplementation at a dose sufficient to elevate 25-hydroxyvitamin D levels to more than 36 ng/mL does not have major effects on clinical or structural outcomes in knee OA, at least in a U.S. sample,” the authors conclude.

(JAMA. 2013;309(2):155-162; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was funded by a grant from the National Institutes of Health, NIAMS, and the Office of Dietary Supplements, a grant from the National Center for Research Resources, and a grant from the Houston Veterans Affairs Health Services Research and Development Service. 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, JANUARY 1, 2013

How and Why U.S. Health Care Differs From That in Other OECD Countries

Victor R. Fuchs, Ph.D., of Stanford University, Stanford, Calif., compares U.S. health care to that in other countries of the Organization for Economic Co-operation and Development (OECD), and “reaches one inescapable conclusion—U.S. health care is very different from health care in other countries.” In this Viewpoint, the author examines the differences, and suggests a strategy for obtaining further health care reform.

“Comprehensive health care reform in the United States is necessary to avoid a financial disaster, but enactment of such reform will require attention to U.S. history, values, and politics.”

(JAMA. 2013;309[1]:33-34. Available pre-embargo to the media at https://media.jamanetwork.com)

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

The Era of Delivery System Reform Begins

Zirui Song, Ph.D., of the Harvard Medical School, Boston, and Thomas H. Lee, M.D., of Brigham and Women’s Hospital and Partners Healthcare, Boston, discuss delivery system reform for the modern physician organization.

“Physician organizations will need help, not just from patients, but also from payers at the bargaining table, drug companies at the checkout line, and a legal system that protects physicians when choosing against unnecessary care. But if these organizations can begin to shift the culture of medicine—if they can find ways to deliver better care at lower cost—they can begin to navigate health care through the era of delivery system reform.”

(JAMA. 2013;309[1]:35-36. Available pre-embargo to the media at https://media.jamanetwork.com)

Rebooting Cancer Tissue Handling in the Sequencing Era – Toward Routine Use of Frozen Tumor Tissue

Laura Goetz, M.D., M.P.H., of the Scripps Translational Science Institute, La Jolla, Calif., and colleagues examine the relevant issues behind the incorporation of optimal tissue sampling techniques into routine pathologic practice and make recommendations for the cancer genomic medicine of the future.

“Moving the pathology and oncology communities toward a new practice incorporating larger tissue samples and the routine use of frozen tissue represents a formidable but attainable change, one that will undoubtedly involve patients’ preferences and consent. How quickly a new practice should emerge depends on clinical studies indicating improved patient outcomes associated with detailed genetic evaluation. As genomic testing becomes part of routine care and patients become increasingly informed, medicine will have to adapt to meet the demands of the next generation of patients with cancer, now informed about sequencing options for their particular malignancy.”

(JAMA. 2013;309[1]:37-38. Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the articles 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, JANUARY 1, 2013

Media Advisory: To contact Carolien Roos, M.D., email c.roos@obgyn.umcn.nl.

CHICAGO – In women with threatened (symptoms of) preterm labor, maintenance therapy to suppress labor with the calcium-channel blocker nifedipine for 12 days did not result in a significant reduction in adverse perinatal (just before and after birth) outcomes, such as perinatal death, chronic lung disease or neonatal sepsis, when compared with placebo, according to a study in the January 2 issue of JAMA.

Preterm birth is the most common cause of neonatal illness and death worldwide. “Almost 75 percent of perinatal deaths occur in infants born before 37 weeks’ gestation. Consequently, preterm birth is associated with a large burden of disease, high costs for medical care, special education, and institutionalized care for disabled infants. In threatened preterm labor before 34 weeks, delay of delivery for 48 hours allows antenatal corticosteroid treatment to improve fetal maturity and transfer of the pregnant woman to a center with a neonatal intensive care unit,” according to background information in the article. Delay of delivery for more than 48 hours may improve perinatal outcome. “However, the effectiveness of maintenance tocolysis [medication to suppress labor], after an initial course of tocolysis and corticosteroids for 48 hours, on pregnancy and perinatal outcome has not been demonstrated.”

Carolien Roos, M.D., of Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands, and colleagues evaluated the effect of maintenance tocolysis with nifedipine on perinatal outcome. Maintenance tocolysis with nifedipine has been assessed in 3 small trials that showed contradictory results. This randomized controlled trial was conducted in 11 perinatal units including all tertiary centers in the Netherlands. From June 2008 to February 2010, women with threatened preterm labor between 26 weeks and 32 weeks (plus 2 days) gestation, who had not delivered after 48 hours of tocolysis and a completed course of corticosteroids, were enrolled. Surviving infants were followed up until 6 months after birth (ended August 2010).

A total of 406 women were randomly assigned to maintenance tocolysis with nifedipine orally (n = 201) or placebo (n = 205) for 12 days. Average gestational age at randomization was 29.2 weeks for both groups. The primary outcome measure for the study was a composite of adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage >grade 2, periventricular leukomalacia >grade 1, or necrotizing enterocolitis).

The researchers found that adverse perinatal outcome was not significantly different between the groups, with 24 (11.9 percent) cases in the nifedipine group and 28 (13.7 percent) in the placebo group (risk difference 1.8 percent). Perinatal death occurred in 5 (2.5 percent) in the nifedipine group and in 4 (2.0 percent) in the placebo group. Average gestational age at delivery was comparable for both groups: 34.1 weeks for the nifedipine group and 34.2 weeks for the placebo group.

Birth weight was not significantly different between the 2 groups. Neonatal intensive care unit admission occurred in 40.8 percent of neonates in the nifedipine group and in 39.7 percent in the placebo group. The length of neonatal intensive care unit admission was 10 days for both groups.

“Although the lower than anticipated rate of adverse perinatal outcomes in the control group indicates that a benefit of nifedipine cannot completely be excluded, its use for maintenance tocolysis does not appear beneficial at this time,” the authors write. “Future research should be directed toward therapies tailored to the specific underlying causes of preterm labor.”

(JAMA. 2013;309(1):41-47; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This trial was funded by ZonMw, the Netherlands Organization for Health Research and a grant from the Development Healthcare Efficiency Program. 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, JANUARY 1, 2013

Media Advisory: To contact Sana M. Al-Khatib, M.D., M.H.S., call Sarah Avery at 919-660-1306 or email sarah.avery@duke.edu.

CHICAGO – Comparing the largest registry of implantable cardioverter-defibrillator (ICD) implants in the United States with 2 primary prevention randomized clinical trials, researchers found that patients who met certain criteria and who received a primary prevention ICD in clinical practice had survival that was not significantly different from patients who received an ICD in the clinical trials, findings that support the continued use of primary prevention ICDs in similar patients seen in clinical practice, according to a study in the January 2 issue of JAMA.

“The implantable cardioverter-defibrillator is a highly effective therapy for preventing sudden cardiac death in patients with heart failure. However, the outcomes of this therapy in routine clinical practice are largely uncertain. Because randomized clinical trials generally enroll patients with fewer comorbidities [other illnesses] and are usually conducted in highly controlled and monitored settings, the results of the primary prevention ICD trials may not be generalizable to routine clinical practice,” according to background information in the article. The authors add that whether these findings “are generalizable to clinical practice needs to be investigated, especially given the cost and potential complications associated with this device, such as infection and lead and device failure.”

Sana M. Al-Khatib, M.D., M.H.S., of the Duke Clinical Research Institute, Durham, N.C., and colleagues conducted a study to determine whether a difference in survival exists between trial-eligible patients who receive a primary prevention ICD as documented in a large national registry and similar patients who received an ICD in the 2 largest primary prevention clinical trials, MADIT-II (n = 742) and SCD-HeFT (n = 829). The study consisted of a retrospective analysis of data for patients enrolled in the National Cardiovascular Data Registry ICD Registry between January 1, 2006, and December 31, 2007, meeting the MADIT-II criteria (2,464 propensity score-matched patients) or the SCD-HeFT criteria (3,352 propensity score-matched patients). Mortality data for the registry patients were collected through December 31, 2009. The median (midpoint) follow-up time in MADIT-II, SCD-HeFT, and the ICD Registry was 19.5, 46.1, and 35.2 months, respectively. Patients receiving ICDs in clinical practice were significantly older and had more comorbidities than patients enrolled in the clinical trials.

After analysis of the data, the authors found no significant difference in survival between MADIT-II-like patients in the ICD Registry and MADIT-II patients randomized to receive an ICD (2-year mortality rates: 13.9 percent vs. 15.6 percent). Also, the survival of MADIT-II-like patients in the ICD Registry was significantly better than the survival of MADIT-II patients randomized to receive medical therapy (2-year mortality rates: 13.9 percent vs. 22 percent).

There was also no significant survival difference between SCD-HeFT-like patients in the ICD Registry and patients randomized to receive ICD therapy in SCD-HeFT (3-year mortality rates: 17.3 percent vs. 17.4 percent). The survival of SCD-HeFT-like patients in the ICD Registry was significantly better than the survival of SCD-HeFT patients randomized to placebo (3-year mortality rates: 17.3 percent vs. 22.4 percent).

“Importantly, the generalizability of these results held even after limiting the analyses to patients 65 years and older,” the researchers write.

The authors note that prior work in other fields has demonstrated that it is often challenging to generalize the findings from randomized clinical trials to clinical practice. “Patients enrolled in randomized clinical trials of primary prevention ICD therapy were monitored carefully over the course of the trials, and physicians who implanted and followed those devices were highly experienced. This level of care may not occur in real-world, practice.”

“… it is reasonable to question whether the results of the trials can be expected in clinical practice. Through propensity score matching and adjustment for differences between registry patients and patients enrolled in the clinical trials, our matched sample became similar to patients enrolled in the clinical trials. This enabled us to address the concern that the care of patients in the highly controlled and monitored setting of clinical trials compromises the external validity of the results.”

(JAMA. 2013;309(1):55-62; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This analysis was funded 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.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JANUARY 1, 2013

Media Advisory: To contact Olof Stephansson, M.D., Ph.D., email olof.stephansson@ki.se.

CHICAGO – In a study that included nearly 30,000 women from Nordic countries who had filled a selective serotonin reuptake inhibitor (SSRI) prescription during pregnancy, researchers found no significant association between use of these medications during pregnancy and risk of stillbirth, neonatal death, or postneonatal death, after accounting for factors including maternal psychiatric disease, according to a study in the January 2 issue of JAMA.

“Depression during pregnancy is common with prevalences ranging between 7 percent and 19 percent in economically developed countries. Maternal depression is associated with poorer pregnancy outcomes, including increased risk of preterm delivery, which in turn may cause neonatal morbidity and mortality,” according to background information in the article. “Use of selective serotonin reuptake inhibitors during pregnancy has been associated with congenital anomalies, neonatal withdrawal syndrome, and persistent pulmonary hypertension of the newborn. However, the risk of stillbirth and infant mortality when accounting for previous maternal psychiatric disease remains unknown.”

Olof Stephansson, M.D., Ph.D., of the Karolinska Institutet, Stockholm, Sweden and colleagues conducted a study to examine whether SSRI exposure during pregnancy was associated with increased risks of stillbirth, neonatal death, and postneonatal death. The study included women with single births  from all Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) at different periods from 1996 through 2007. The researchers obtained information on maternal use of SSRIs from prescription registries; maternal characteristics, pregnancy, and neonatal outcomes were obtained from patient and medical birth registries. The authors estimated relative risks of stillbirth, neonatal death, and postneonatal death associated with SSRI use during pregnancy taking into account maternal characteristics and previous psychiatric hospitalization.

Among 1,633,877 singleton births in the study, there were 6,054 stillbirths; 3,609 neonatal deaths; and 1,578 postneonatal deaths. A total of 29,228 (1.79 percent) of mothers had filled a prescription for an SSRI during pregnancy. The researchers found that women exposed to an SSRI had higher rates of stillbirth (4.62 vs. 3.69 per 1000) and postneonatal death (1.38 vs. 0.96 per 1000) than those who did not. The rate of neonatal death was similar between groups (2.54 vs. 2.21 per 1000). “Yet in multivariate models, SSRI use was not associated with stillbirth, neonatal death, or postneonatal death. Estimates were further attenuated when stratified by previous hospitalization for psychiatric disease,” the authors write.

“The present study of more than 1.6 million births suggests that SSRI use during pregnancy was not associated with increased risks of stillbirth, neonatal death, or postneonatal death. The increased rates of stillbirth and postneonatal mortality among infants exposed to an SSRI during pregnancy were explained by the severity of the underlying maternal psychiatric disease and unfavorable distribution of maternal characteristics such as cigarette smoking and advanced maternal age.”

“However, decisions regarding use of SSRIs during pregnancy must take into account other perinatal outcomes and the risks associated with maternal mental illness,” the researchers conclude.

(JAMA. 2013;309(1):48-54; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was funded by the Swedish Pharmacy Company and by the authors’ affiliations. Olof Stephansson was supported by a postdoctorate scholarship from the Swedish Society of Medicine. 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, JANUARY 1, 2013

Media Advisory: To contact corresponding author Robert S. Sherwin, M.D., call Helen Dodson at 303-436-3984 or email helen.dodson@yale.edu. To contact editorial co-author Jonathan Q. Purnell, M.D., call Mirabai Vogt at 503-494-7986 or email vogtmi@ohsu.edu.

CHICAGO – In a study examining possible factors regarding the associations between fructose consumption and weight gain, brain magnetic resonance imaging of study participants indicated that ingestion of glucose but not fructose reduced cerebral blood flow and activity in brain regions that regulate appetite, and ingestion of glucose but not fructose produced increased ratings of satiety and fullness, according to a preliminary study published in the January 2 issue of JAMA.

“Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety,” according to background information in the article. “Thus, fructose possibly increases food-seeking behavior and increases food intake.” How brain regions associated with fructose- and glucose-mediated changes in animal feeding behaviors translates to humans is not completely understood.

Kathleen A. Page, M.D., of Yale University School of Medicine, New Haven, Conn., and colleagues conducted a study to examine neurophysiological factors that might underlie associations between fructose consumption and weight gain. The study included 20 healthy adult volunteers who underwent two magnetic resonance imaging sessions in conjunction with fructose or glucose drink ingestion. The primary outcome measure for the study was the relative changes in hypothalamic (a region of the brain) regional cerebral blood flow (CBF) after glucose or fructose ingestion.

The researchers found that there was a significantly greater reduction in hypothalamic CBF after glucose vs. fructose ingestion. “Glucose but not fructose ingestion reduced the activation of the hypothalamus, insula, and striatum—brain regions that regulate appetite, motivation, and reward processing; glucose ingestion also increased functional connections between the hypothalamic-striatal network and increased satiety.”

“The disparate responses to fructose were associated with reduced systemic levels of the satiety-signaling hormone insulin and were not likely attributable to an inability of fructose to cross the blood-brain barrier into the hypothalamus or to a lack of hypothalamic expression of genes necessary for fructose metabolism.”

(JAMA. 2013;309(1):63-70; 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: Fructose Ingestion and Cerebral, Metabolic, and Satiety Responses

Jonathan Q. Purnell, M.D., and Damien A. Fair, PA-C, Ph.D., of Oregon Health & Science University, Portland, write in an accompanying editorial that “these findings support the conceptual framework that when the human brain is exposed to fructose, neurobiological pathways involved in appetite regulation are modulated, thereby promoting increased food intake.”

“… the implications of the study by Page et al as well as the mounting evidence from epidemiologic, metabolic feeding, and animal studies, are that the advances in food processing and economic forces leading to increased intake of added sugar and accompanying fructose in U.S. society are indeed extending the supersizing concept to the population’s collective waistlines.”

(JAMA. 2013;309(1):85-86; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JANUARY 1, 2013

Media Advisory: To contact Katherine M. Flegal, Ph.D., call Karen Hunter at 404-639-3286 or email ksh7@cdc.gov. To contact editorial co-author Steven B. Heymsfield, M.D., email Steven.heymsfield@pbrc.edu.

CHICAGO – In an analysis of nearly 100 studies that included approximately 3 million adults, relative to normal weight, overall obesity (combining all grades) and higher levels of obesity were both associated with a significantly higher all-cause risk of death, while overweight was associated with significantly lower all-cause mortality, according to a study in the January 2 issue of JAMA.

“Estimates of the relative mortality risks associated with normal weight, overweight, and obesity may help to inform decision making in the clinical setting,” according to background information in the article.

Katherine M. Flegal, Ph.D., of the National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Md., and colleagues conducted a study to compile and summarize published analyses of body mass index (BMI) and all-cause mortality that provide hazard ratios (HRs) for standard BMI categories. For the review and meta-analysis, the researchers identified 97 studies that met inclusion criteria, which provided a combined sample size of more than 2.88 million individuals and more than 270,000 deaths. Regions of origin of participants included the United States or Canada (n = 41 studies), Europe (n = 37), Australia (n = 7), China or Taiwan (n = 4), Japan (n = 2), Brazil (n = 2), Israel (n = 2), India (n = l), and Mexico (n = l).

All-cause mortality HRs for overweight (BMI of 25-<30), obesity (BMI of ≥30), grade 1 obesity (BMI of 30-<35), and grades 2 and 3 obesity (BMI of ≥35) were calculated relative to normal weight (BMI of 18.5-<25).

The researchers found that the summary HRs indicated a 6 percent lower risk of death for overweight; a 18 percent higher risk of death for obesity (all grades); a 5 percent lower risk of death for grade 1 obesity; and a 29 percent increased risk of death for grades 2 and 3 obesity.

The authors note that the finding that grade 1 obesity was not associated with higher mortality suggests that that the excess mortality in obesity may predominantly be due to elevated mortality at higher BMI levels.

The researchers add that their findings are consistent with observations of lower mortality among overweight and moderately obese patients. “Possible explanations have included earlier presentation of heavier patients, greater likelihood of receiving optimal medical treatment, cardioprotective metabolic effects of increased body fat, and benefits of higher metabolic reserves.”

The use of predefined standard BMI groupings can facilitate between-study comparisons, the authors conclude.

(JAMA. 2013;309(1):71-82; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: There was no external funding for this work. The Centers for Disease Control and Prevention and the National Cancer Institute reviewed and approved the manuscript before submission. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Please Note: For this study, there will be multimedia content available, 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, January 1 at this link.

Editorial: Does Body Mass Index Adequately Convey a Patient’s Mortality Risk?

“Can overweight as defined by BMI actually have a protective association with mortality?” write Steven B. Heymsfield, M.D., and William T. Cefalu, M.D., of the Pennington Biomedical Research Center, Baton Rouge, La., in an accompanying editorial

“The presence of a wasting disease, heart disease, diabetes, renal dialysis, or older age are all associated with an inverse relationship between BMI and mortality rate, an observation termed the obesity paradox or reverse epidemiology. The optimal BMI linked with lowest mortality in patients with chronic disease may be within the overweight and obesity range. Even in the absence of chronic disease, small excess amounts of adipose tissue may provide needed energy reserves during acute catabolic illnesses, have beneficial mechanical effects with some types of traumatic injuries, and convey other salutary effects that need to be investigated in light of the studies by Flegal et al and others.”

“Not all patients classified as being overweight or having grade 1 obesity, particularly those with chronic diseases, can be assumed to require weight loss treatment. Establishing BMI is only the first step toward a more comprehensive risk evaluation.”

(JAMA. 2013;309(1):87-88; 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, DECEMBER 25, 2012

Obesity May Be Declining Among Preschool-Aged Children Living in Low-Income Families

“Obesity and extreme obesity in childhood, which are more prevalent among minority and low-income families, have been associated with other cardiovascular risk factors, increased health care costs, and premature death. Obesity and extreme obesity during early childhood are likely to continue into adulthood. Understanding trends in extreme obesity is important because the prevalence of cardiovascular risk factors increases with severity of childhood obesity,” writes Liping Pan, M.D., M.P.H., of the Centers for Disease Control and Prevention, Atlanta, and colleagues. National trends in extreme obesity among young children living in low-income families have not been known.

As reported in a Research Letter, the authors analyzed data from the Pediatric Nutrition Surveillance System (PedNSS), which includes almost 50 percent of children eligible for federally funded maternal and child health and nutrition programs. The analysis for this study included 26.7 million children ages 2 through 4 years from 30 states and the District of Columbia that consistently reported data to PedNSS from 1998 through 2010. One routine clinic visit with demographic information and measured height and weight was randomly selected for each child. Obesity (body mass index [BMI] 95th percentile or greater for age and sex) and extreme obesity (BMI 120 percent or greater of the 95th percentile) were defined according to the 2000 CDC growth charts.

The 2010 study population was slightly younger and had proportionally more Hispanics and fewer non-Hispanic whites and blacks compared with the 1998 population.  The researchers found that the prevalence of obesity increased from 13.05 percent in 1998 to 15.21 percent in 2003. The prevalence of extreme obesity increased from 1.75 percent in 1998 to 2.22 percent in 2003. However, the prevalence of obesity decreased slightly to 14.94 percent in 2010; and the prevalence of extreme obesity decreased to 2.07 percent in 2010.

“To our knowledge, this is the first national study to show that the prevalence of obesity and extreme obesity among young U.S. children may have begun to decline,” the authors write. “The results of this study indicate modest recent progress of obesity prevention among young children. These findings may have important health implications because of the lifelong health risks of obesity and extreme obesity in early childhood.”

(JAMA. 2012;308[24]:2563-2565. Available pre-embargo to the media at https://media.jamanetwork.com)

Viewpoints in This Week’s JAMA

Opportunities to Reduce Childhood Hunger and Obesity

David S. Ludwig, M.D., Ph.D., of Boston Children’s Hospital, and colleagues discuss the Supplemental Nutrition Assistance Program (SNAP, formerly known as the Food Stamp Program), and provide recommendations for improving nutritional quality for children in the U.S.

“SNAP is essential for hunger prevention in the United States, but its exclusive focus on food quantity contributes to malnutrition and obesity, and is misaligned with the goal of helping beneficiaries lead healthier lives. The nation’s $75 billion investment in SNAP could provide a major opportunity to reduce the burden of diet-related disease among low-income children and families if policies that promote nutritional quality are instituted.”

(JAMA. 2012;308[24]:2567-2568. Available pre-embargo to the media at https://media.jamanetwork.com)

Measure, Promote, and Reward Mobility to Prevent Falls in Older Patients

Samir K. Sinha, M.D., D.Phil., and Allan S. Detsky, M.D., Ph.D., of the University of Toronto, Ontario, Canada, examine the importance of maintaining and improving mobility among older patients to reduce the risk of a fall.

“A focus on maintaining and improving mobility should be encouraged when an older adult becomes acutely ill and particularly vulnerable to permanently losing functional capacity during a hospitalization. More importantly, encouraging routine strength and balance training in community-dwelling older adults should be a priority. This strategy not only could lower the risk of hospitalization due to falls and fractures but also, more importantly and even at advanced ages, could enhance quality and length of life.”

(JAMA. 2012;308[24]:2573-2574. Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the articles 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, DECEMBER 25, 2012

Media Advisory: To contact Bryant J. Webber, M.D., call Sharon Willis at 301-295-3578 or email sharon.willis@usuhs.edu. To contact editorial author Daniel Levy, M.D., call the NHLBI press office at 301-496-4236 or email nhlbi_news@nhlbi.nih.gov.

CHICAGO – Among deployed U.S. service members who died of combat or unintentional injuries between 2001-2011 and underwent autopsies, the prevalence of coronary atherosclerosis was 8.5 percent, with factors associated with a higher prevalence of the disease including older age, lower educational level and prior diagnoses of dyslipidemia, hypertension, and obesity, according to a study in the December 26 issue of JAMA.

“An early breakthrough in the understanding of the natural history of atherosclerotic heart disease was achieved in 1953, when Enos and colleagues at the Armed Forces Institute of Pathology reported a 77 percent prevalence of coronary atherosclerosis among U.S. soldiers killed in the Korean War. By demonstrating anatomically that atherosclerosis affected a large proportion of young individuals without clinical evidence of heart disease, their study revolutionized the understanding of the onset and progression of cardiovascular disease. A follow-up report in the Vietnam War era, along with a number of autopsy studies in the civilian population provided additional evidence that the onset of atherosclerosis may occur at an early age,” according to background information in the article. Since the publication of these studies, health policies have been implemented to reduce the risk of cardiovascular disease associated with risk factors such as hypertension, diabetes, cholesterol, and smoking.

Bryant J. Webber, M.D., of the Uniformed Services University of the Health Sciences, Bethesda, Md., and colleagues conducted a study to assess the prevalence of atherosclerosis in the U.S. armed forces. The study included all U.S. service members who died of combat or unintentional injuries in support of Operations Enduring Freedom and Iraqi Freedom/New Dawn between October 2001 and August 2011 and whose cardiovascular autopsy reports were available at the time of data collection in January 2012. Prevalence of atherosclerosis was analyzed by various demographic characteristics and medical history. Classifications of coronary atherosclerosis severity were determined prior to data analysis and designed to provide consistency with previous military studies: minimal (fatty streaking only), moderate (10 percent – 49 percent luminal [interior of the vessel] narrowing of one or more vessels), and severe (50 percent or more narrowing of one or more vessels). Of the 3,832 service members included in the analysis, the average age was 26 years.

The overall prevalence of coronary or aortic atherosclerosis was 12.1 percent. The prevalence of any coronary atherosclerosis was 8.5 percent; severe coronary atherosclerosis was present in 2.3 percent, moderate in 4.7 percent, and minimal in 1.5 percent. The researchers found that age consistently produced the strongest association with prevalent atherosclerosis. Service members with atherosclerosis (average age, 30.5) were approximately 5 years older than those without; those 40 years of age and older had about 7 times the prevalence of disease as compared with those 24 years of age and younger (45.9 percent vs. 6.6 percent)

Lower education level and higher military entrance body mass index (BMI) were significantly associated with prevalent atherosclerosis, after adjusting for age. As compared with those who completed high school or less, those who completed at least some college had lower prevalence of disease. As compared with those with a normal BMI on military entrance, those with a BMI in the overweight or obese range had a significantly higher prevalence of atherosclerosis

The authors also found that age-adjusted atherosclerosis prevalence was associated with several diagnoses. As compared with those with no major cardiovascular risk factor diagnoses, those with a diagnosis of dyslipidemia (50.0 percent vs. 11.1 percent), hypertension (43.6 percent vs. 11.1 percent), or obesity (22.3 percent vs. 11.1 percent) had a significantly higher prevalence of atherosclerosis.

The researchers note that the prevalence rates found in this study demonstrate a decline from the rates of 77 percent noted in the Korean War and 45 percent in the Vietnam War, but add that targets for further improvement remain.

“Military and civilian health care systems should continue to help patients reduce their cardiovascular risk factors, beginning in childhood and continuing throughout adult life. Despite remarkable progress in prevention and treatment, cardiovascular disease remains the leading cause of death in the United States and other developed nations, and even small improvements in the prevalence of smoking and other risk factors may reduce death rates further and prolong healthy lives.”

(JAMA. 2012;308(24):2577-2583; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by the Uniformed Services University of the Health Sciences, Armed Forces Medical Examiner System, and Armed Forces Health Surveillance Center. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Please Note: For this study, there will be multimedia content available, 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, December 25 at this link.

Editorial: Combating the Epidemic of Heart Disease

Daniel Levy, M.D., of the National Heart, Lung, and Blood Institute, Bethesda, Md., comments on the findings of this study in an accompanying editorial.

“Autopsy studies have demonstrated that coronary disease begins at a young age. Consequently, primary prevention campaigns to address obesity and related risks should begin in childhood. Declines in cardiovascular disease risk factors have almost certainly contributed to the observed reductions in prevalence of subclinical atherosclerosis, incidence of clinical atherosclerotic disease, and deaths from heart disease. Although age-adjusted heart disease death rates have declined by 72 percent since their peak during the Vietnam War years, cardiovascular disease remains the leading cause of death in the United States. The national battle against heart disease is not over; increasing rates of obesity and diabetes signal a need to engage earlier and with greater intensity in a campaign of pre-emption and prevention.

(JAMA. 2012;308(24):2624-2625; 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, DECEMBER 25, 2012

Media Advisory: To contact corresponding author Harry L. A. Janssen, M.D., Ph.D., email h.janssen@erasmusmc.nl.

CHICAGO – Among patients with chronic hepatitis C virus infection and advanced hepatic fibrosis (development of excess fibrous connective tissue), sustained virological response (SVR) to interferon-based treatment was associated with a lower risk of all-cause mortality compared with patients without SVR, according to a study in the December 26 issue of JAMA.

“Chronic hepatitis C virus (HCV) infection is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease. The incidence of HCV-related cirrhosis and its complications is expected to increase in upcoming years. Davis et al estimated that currently 25 percent of the approximately 3.5 million U.S. patients with chronic HCV infection have cirrhosis and that the proportion of patients with cirrhosis is likely to increase up to 45 percent by 2030,” according to background information in the article.

“Sustained virological response is defined as absence of viremia [the presence of a virus in the blood] 24 weeks after cessation of all antiviral medication. Although SVR has long-term durability, data on the relationship with improved survival to support its use as a surrogate end point of antiviral therapy is scarce. Demonstrating direct clinical benefits would better justify the use of intensive and costly antiviral therapy …” the authors write.

Adriaan J. van der Meer, M.D., of Erasmus MC University Medical Center, Rotterdam, the Netherlands and colleagues conducted a study to examine whether achievement of SVR vs. without SVR is associated with a prolonged overall survival in patients with chronic HCV infection and advanced hepatic fibrosis. The study, conducted at five tertiary care hospitals in Europe and Canada, included 530 patients with chronic HCV infection who started an interferon-based treatment regimen between 1990 and 2003, following histological proof of advanced hepatic fibrosis or cirrhosis. Complete follow-up ranged between January 2010 and October 2011. The patients were followed up for a median (midpoint) of 8.4 years. The baseline median age was 48 years and 369 patients (70 percent) were men.

There were 192 patients (36 percent) who achieved SVR; 13 patients with SVR and 100 without SVR died (10-year cumulative all-cause mortality rate, 8.9 percent with SVR and 26.0 percent without SVR). In further analysis, the researchers found that SVR was associated with a reduced risk of all-cause mortality and liver-related mortality or transplantation. Other baseline factors significantly associated with all-cause mortality included older age, HCV genotype 3 infection, presence of diabetes, and a history of severe alcohol use. Of the 100 deaths in patients without SVR, the cause was liver-related in 70 patients (70 percent), not liver-related in 15 percent of patients, and unknown in another 15 percent.

The 10-year cumulative incidence rate of liver-related mortality or transplantation was 1.9 percent with SVR and 27.4 percent without SVR. After 10 years, the cumulative occurrence of HCC was 5.1 percent in patients with SVR and 21.8 percent in patients without SVR. The 10-year cumulative liver failure rate was 2.1 percent in patients with SVR vs. 29.9 percent in patients without SVR.

“In our international, multicenter, long-term follow-up study, SVR was associated with prolonged overall survival. The risk of all-cause mortality was almost 4-fold lower in patients with SVR compared with patients without SVR. Our study with a long follow-up duration demonstrated a lower risk for all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis who achieved SVR. In addition, we were able to further establish and quantify the risk reduction of HCC, liver failure, and liver-related mortality or liver transplantation in patients with SVR,” the authors conclude.

(JAMA. 2012;308(24):2584-2593; 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, DECEMBER 18, 2012

Iodine Supplementation During Pregnancy and Lactation

Alex Stagnaro-Green, M.D., M.H.P.E., of the George Washington University School of Medicine and Health Sciences, Washington, D.C., and colleagues discuss the possible adverse effects of iodine deficiency and the importance of supplementation during pregnancy and while breastfeeding.

“The status quo can be maintained in which iodine supplementation is recommended, but provided in only 50 percent of prenatal vitamins. The alternative is for relevant medical organizations to work collaboratively with pharmaceutical and vitamin manufacturers to ensure that all prenatal multivitamins contain 150 μg of potassium iodine. In the interim, clinicians should recommend only those prenatal vitamins that contain iodine. The path seems clear. It is time for all prenatal vitamins to contain iodine.”

(JAMA. 2012;308[22]:2463-2464. Available pre-embargo to the media at https://media.jamanetwork.com)

Making Health Care Reform Work – Where Physician and Employer Interests Converge

Harris Allen, Ph.D., of the Harris Allen Group, Brookline, Mass., and colleagues write that physicians and businesses share a common goal—to advance better health; yet the business community maintains a low profile in health care reform under the Affordable Care Act (ACA). In this Viewpoint, the authors examine missed opportunities for strengthening employer linkages with the ACA, and what can be done for improvement.

“Employers need to reprise their role in health care reform efforts in a manner that will help advance their shared goal of better health with physicians. Building on the ACA’s legislative authority, businesses can reach out to their commercial carriers to coordinate, unify, and standardize performance payment metrics and insist that they include not only direct but also indirect health care costs. Extending the process of standardization to both types of measures holds much promise for minimizing reporting complexity and clinical care redundancy in ways that will materially enhance physician capacity to deliver care in the unfolding reform environment.”

(JAMA. 2012;308[22]:2465-2466. Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Please see the articles 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, DECEMBER 18, 2012

Media Advisory: To contact Edward W. Gregg, Ph.D., call Karen Hunter at 404-639-3286 or email ksh7@cdc.gov. To contact editorial co-author David E. Arterburn, M.D., M.P.H., call Joan DeClaire at 206-287-2653 or email declaire.j@ghc.org.

CHICAGO – Among overweight adults, participation in an intensive lifestyle intervention (that included counseling sessions and targets to reduce caloric intake and increase physical activity) was associated with a greater likelihood of partial remission of type 2 diabetes, however the absolute remission rates were modest, according to a study in the December 19 issue of JAMA.

“Diabetes traditionally has been considered a progressive, incurable condition wherein the best case scenario after diagnosis is tight metabolic and risk factor management to forestall vascular and neuropathic complications,” according to background information in the article. Some bariatric surgery studies have suggested that many diabetes cases among obese patients can be resolved. “Patients diagnosed as having type 2 diabetes frequently ask their physicians whether their condition is reversible, and some physicians may provide hopeful advice that lifestyle change can normalize glucose levels,” the authors write. “However, the rate of remission of type 2 diabetes that may be achieved using non-surgical approaches has not been reported.”

Edward W. Gregg, Ph.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues conducted a study to examine the association of an intensive lifestyle intervention with frequency of partial and complete remission of type 2 diabetes. The study consisted of an ancillary observational analysis of a 4-year randomized controlled trial (baseline visit, August 2001-April 2004; last follow-up, April 2008) comparing an intensive lifestyle intervention (ILI) with a diabetes support and education control condition (DSE). The study included 4,503 U.S. adults with body mass index of 25 or higher and type 2 diabetes.

Participants were randomly assigned to receive the ILI, which included weekly group and individual counseling in the first 6 months followed by 3 sessions per month for the second 6 months and twice-monthly contact and regular refresher group series and campaigns in years 2 to 4 (n = 2,241); or the DSE, which was an offer of 3 group sessions per year on diet, physical activity, and social support (n = 2,262). The ILI aimed to reduce total caloric intake to 1,200 to 1,800 calories a day through reductions in total and saturated fat intake and by increasing physical activity levels to a goal of 175 minutes/week. Liquid meal replacements were provided to assist dietary goals.

Participants in the ILI group lost significantly more weight than DSE participants at year 1 (-8.6 percent vs. -0.7 percent) and at year 4 (-4.7 percent vs. -0.8 percent) and had greater increases in fitness at both year 1 (20.6 percent vs. 5.3 percent) and year 4 (4.9 percent vs. -1.5 percent). The researchers found that the prevalence of complete remission (i.e., glucose normalization without medication) was more common in the ILI group than in the DSE group across all years of the study. However, the absolute prevalence was low, ranging from 1.3 percent for ILI vs. 0.1 percent for DSE in year 1; to 0.7 percent for ILI vs. 0.2 percent for DSE in year 4.

Additional analyses indicated that ILI participants were significantly more likely to experience any remission (partial or complete), with a prevalence of 11.5 percent during the first year, decreasing to 7.3 percent during year 4, compared with 2.0 percent in the DSE group at both time points. Rates of any remission were notably higher (15 percent – 21 percent) among persons with substantial weight loss or fitness change, shorter duration of extant diabetes, or a lower HbA_1c level (a measure of blood glucose) at entry and those not using insulin.

“The ILI group was significantly more likely to have continuous, sustained remission, as 9.2 percent experienced at least a 2-year remission (vs. for DSE, 1.7 percent) at some point during follow-up, 6.4 percent had at least a 3-year remission (vs. DSE, 1.3 percent), and 3.5 percent had a continuous 4-year remission (vs. DSE, 0.5 percent). The results from the complete case analyses were similar,” the authors write.

“The increasing worldwide prevalence of type 2 diabetes, along with its wide-ranging complications, has led to hopes that the disease can be reversed or prevented. These analyses of more than 4,500 overweight adults with type 2 diabetes confirm that complete remission associated with an intensive life-style intervention, when defined by glucose normalization without need for drugs, is rare. However, partial remission, defined as a transition to prediabetic or normal glucose levels without drug treatment for a specific period, is an obtainable goal for some patients with type 2 diabetes.”

(JAMA. 2012;308(23):2489-2496; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: A Look Ahead at the Future of Diabetes Prevention and Treatment

David E. Arterburn, M.D., M.P.H., of the Group Health Research Institute, Seattle, and Patrick J. O’Connor, M.D., M.A., M.P.H., of the HealthPartners Institute for Education and Research, Minneapolis, write in an accompanying editorial that “evidence-based and cost-effective diabetes prevention strategies should be more broadly applied using the full range of available technologies and incentives.”

“But that is not enough. Research, education, and policy efforts need to be focused further upstream, toward primary prevention: reducing incident obesity in children, adolescents, and adults, especially among those with a family history of obesity or diabetes. Prevention of diabetes and obesity should be a rallying cry for all clinicians who care about the health of the nation.”

(JAMA. 2012;308(23):2517-2518; 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, DECEMBER 18, 2012

Media Advisory: To contact corresponding author Gilles Montalescot, M.D., Ph.D., email gilles.montalescot@psl.aphp.fr.

CHICAGO – Among patients scheduled for a percutaneous coronary intervention (PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries), pretreatment with the antiplatelet agent clopidogrel was not associated with a lower risk of overall mortality but was associated with a significantly lower risk of major coronary events, according to a review and meta-analysis of previous studies published in the December 19 issue of JAMA.

“In addition to aspirin, clopidogrel has been shown to improve ischemic outcomes of patients with stable coronary artery disease following PCI and of patients with acute coronary syndromes (ACS; such as heart attack or unstable angina) who were either medically treated or who had undergone either revascularization by fibrinolysis or PCI,” according to background information on the article. “Clopidogrel pretreatment is recommended for patients with ACS and stable coronary artery disease who are scheduled for PCI, but whether using clopidogrel as a pretreatment for PCI is associated with positive clinical outcomes has not been established.”

Anne Bellemain-Appaix, M.D., of the Service de Cardiologie-La Fontonne Hospital, Antibes, France, and colleagues conducted a review and meta-analysis of data from randomized trials and registries involving patients with coronary artery disease (stable or with ACS) undergoing catheterization for potential revascularization to evaluate the association between clopidogrel pretreatment with mortality and major bleeding after PCI. After a search of the medical literature, the researchers identified 15 articles published between August 2001 and September 2012 that met the study inclusion criteria: 6 randomized controlled trials (RCTs), 2 observational analyses of RCTs, and 7 observational studies. Pretreatment was defined as the administration of clopidogrel before PCI or catheterization. The primary efficacy and safety end points were all-cause mortality and major bleeding. Secondary end points included major cardiac events.

Of the 37,814 patients included in the meta-analysis, 8,608 patients had participated in RCTs; 10,945 in observational analyses of RCTs; and 18,261 in observational studies. In the RCT cohort of patients, clopidogrel pretreatment was not significantly associated with a reduction of all-cause mortality (absolute risk, 1.54 percent vs. 1.97 percent). These results were consistent across the observational analyses of RCTs and the observational studies analyses. Clopidogrel pretreatment was also not associated with a significantly increased risk of major bleeding in the main analysis of RCTs (absolute risk, 3.57 percent vs. 3.08 percent).

In the main analysis, clopidogrel pretreatment was significantly associated with a reduction of major coronary events (absolute risk, 9.83 percent vs. 12.35 percent) and heart attack (absolute risk, 4.53 percent vs. 5.90 percent).

The authors note that although no significant heterogeneity existed for clinical presentation, the higher-risk ST-segment elevation myocardial infarction (STEMI; a certain pattern on an electrocardiogram following a heart attack) population appeared to gain the most benefit from pretreatment. “In contrast, patients undergoing elective PCI had no apparent benefit from clopidogrel pretreatment, questioning the need of such a systematic strategy at least in low-risk patients.”

“Although a pretreatment strategy has been recommended for years in patients undergoing PCI, this study shows the limits of the available evidence, with no significant benefit on hard outcomes. The value of pretreatment, including with new antiplatelet agents, needs to be assessed in large prospective studies.”

(JAMA. 2012;308(23):2507-2517; 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, DECEMBER 18, 2012

Media Advisory: To contact Barbara E. K. Klein, M.D., M.P.H., call Susan Lampert Smith at 608-262-7335 or email slsmith2@wisc.edu.

CHICAGO – Among nearly 5,000 study participants, regular aspirin use reported ten years prior was associated with a small but statistically significant increase in the risk of neovascular age-related macular degeneration, according to a study in the December 19 issue of JAMA.

“Aspirin use in the United States is widespread, with an estimated 19.3 percent of adults reporting regular consumption, and reported use increases with age,” according to background information in the study. “The results of cross-sectional studies of aspirin use and its relation to age-related macular degeneration (AMD) have been inconsistent. AMD is a potentially blinding condition for which prevalence and incidence are increasing with the increased survival of the population, and regular use of aspirin is common and becoming more widespread in persons in the age range at highest risk for this disease. Therefore, it is imperative to further examine this potential association.”

Barbara E. K. Klein, M.D., M.P.H., of the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues conducted a study to examine the association between aspirin use and AMD. The researchers used data from the Beaver Dam Eye Study, a longitudinal population-based study of age-related eye diseases conducted in Wisconsin. Examinations were performed every 5 years over a 20-year period (1988-1990 through 2008-2010). Study participants (n = 4,926) were 43 to 86 years of age at entry in the study. At subsequent examinations, participants were asked if they had regularly used aspirin at least twice a week for more than 3 months. The average duration of follow-up was 14.8 years.

For the study, the researchers measured the incidences of different types of AMD (early, late, and 2 subtypes of late AMD [neovascular AMD and pure geographic atrophy]).

There were 512 incident cases of early AMD and 117 incident cases of late AMD over the course of the study. The researchers found that regular use of aspirin use 10 years prior to the retinal examination was associated with late AMD (age- and sex-adjusted incidence, 1.8 percent for users vs. 1.0 percent for nonusers). When examining the relationships by late AMD subtype, neovascular AMD was significantly associated with such use (age-and sex-adjusted incidence, 1.4 percent for users vs. 0.6 percent for nonusers), but not for pure geographic atrophy. Aspirin use 5 years or 10 years prior to retinal examination was not associated with incident early AMD.

“Our findings are consistent with a small but statistically significant association between regular aspirin use and incidence of neovascular AMD. Additional replication is required to confirm our observations. If confirmed, defining the causal mechanisms may be important in developing methods to block this effect to prevent or retard the development of neovascular AMD in persons who use aspirin, especially to prevent CVD,” the authors conclude.

(JAMA. 2012;308(23):2469-2478; 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, DECEMBER 18, 2012

Media Advisory: To contact co-author Steven D. Stellman, Ph.D., M.P.H., call Jean Weinberg at 347-396-4177 or email jweinberg@health.nyc.gov; or Marcus Liem at 347-396-2919 or email mliem@health.nyc.gov.

CHICAGO – Among rescue and recovery workers exposed to the dust, debris, and fumes following the World Trade Center terrorist attack, there was an increased incidence of prostate and thyroid cancers and multiple myeloma, although it is not clear how big a factor medical screening and non-WTC risk factors contributed to these increases, according to a study in the December 19 issue of JAMA. The authors did not find a statistically significant increased incidence for all cancer sites combined, and note that the findings on the three cancers that did increase should be viewed with caution for several reasons, including that they were based on a small number of cancers, multiple comparisons, and a relatively short follow-up time.

“The terrorist attacks on the World Trade Center (WTC) on September 11, 2001, claimed more than 2,700 lives and exposed hundreds of thousands of people to dust, debris, pulverized building materials, and potentially toxic emissions, resulting in short- and medium-term health effects,” according to background information in the article. The dust, smoke, and aerosols were complex mixtures of volatile chemicals and respirable particulate matter and contained known and suspected carcinogens. “The presence of carcinogenic agents raises the possibility that exposure to the WTC environment could eventually lead to cancers.”

Jiehui Li, M.B.B.S., M.Sc., of the New York City Department of Health and Mental Hygiene, Long Island City, New York, and colleagues conducted a study to evaluate cancer incidence among WTC rescue/recovery workers and volunteers and those not involved with rescue/recovery work. The observational study included 55,778 New York State residents enrolled in the World Trade Center Health Registry in 2003-2004, including rescue/recovery workers (n = 21,850) and those not involved in rescue/recovery (n = 33,928), who were followed-up from enrollment through December 2008. Within-group comparisons using various models also assessed the relationship between intensity of World Trade Center exposure and selected cancers.

Cancer cases were identified through linkage with 11 state cancer registries. Standardized incidence ratios (SIRs) adjusted for age, race/ethnicity, and sex were computed with 2003-2008 New York State rates as the reference, focusing on cancers diagnosed in 2007-2008 as being most likely to be related to exposure during September 11 and its aftermath. The total and site-specific incidence rate differences between the study population and the New York State population in 2007-2008 also were calculated.

Through December 31, 2008, 1,187 incident cancers were reported among the 55,778 eligible enrollees. Of these 1,187 cancers, 439 (37 percent) were diagnosed among rescue/recovery workers and 748 (63 percent) were among participants not involved in rescue/recovery. The median (midpoint) age at diagnosis across all cancer sites was 57 years. For all sites combined, cancer incidence was not significantly different from that in the reference population during either the early period (enrollment through 2006) or the later period (2007-2008). The researchers found that of the 23 cancer sites investigated, 3 had significantly elevated incidence during the later period: prostate, thyroid, and multiple myeloma. Of these 3, thyroid cancer also was significantly elevated during the early period.

“No increased incidence was observed in 2007-2008 among those not involved in rescue/recovery. Using within-cohort comparisons, the intensity of World Trade Center exposure was not significantly associated with cancer of the lung, prostate, thyroid, non-Hodgkin lymphoma, or hematological cancer in either group,” the authors write.

“Given the relatively short follow-up time and lack of data on medical screening and other risk factors, the increase in prostate and thyroid cancers and multiple myeloma should be interpreted with caution. The etiological role of WTC exposures in these 3 cancers is unclear. Longer follow-up of rescue/recovery workers and participants not involved in rescue/recovery is needed with attention to selected cancer sites and to examine risk for cancers with typically long latency periods.”

(JAMA. 2012;308(23):2479-2488; 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: For this study, there will be multimedia content available, 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, December 18 at this link.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 11, 2012

Study Finds Association Between Weight of Pancreas and Potential Diabetes Biomarker

Autopsy and imaging studies suggest that among adults with type 1 diabetes (T1D), their pancreas is smaller and weighs less than the pancreas of adults without the disease. However, it is unknown when pancreatic atrophy begins in T1D. Martha Campbell-Thompson, D.V.M., Ph.D., of the University of Florida, Gainesville, and colleagues conducted a study to examine pancreas weight early in the natural history of T1D from at-risk individuals without diabetes but with disease-associated autoantibodies, obtained through the Network for Pancreatic Organ Donors with Diabetes program. All donors were identified by organ procurement organizations that coordinate organ and tissue donations for clinical transplantation or research.

As reported in a Research Letter, the final analysis included 51 donors (no diabetes, n = 23; positive for autoantibody only, n = 8; type 1 diabetes, n = 20). The authors found that the average weight of pancreata (plural form of pancreas) from those without diabetes (controls) was 81.4 g compared with 61.3 g from the group positive for a single autoantibody only and 44.9 g from the T1D group.

“In this study, the weight of pancreata in individuals without T1D, but with serum markers that potentially precede the clinical manifestations, as well as in individuals with T1D, was less than in controls. This suggests that early atrophy of the organ may be an important subclinical feature of T1D pathogenesis,” the authors write. “Future studies should include validation and analysis of the potential mechanisms underlying this observation to understand whether early pancreatic atrophy contributes to the pathogenesis of T1D.”

(JAMA. 2012;308[22]:2337-2339. Available pre-embargo to the media at https://media.jamanetwork.com)

Viewpoints in This Week’s JAMA

Lixivaptan for Hyponatremia – The Numbers Game

Ryan T. Borne, M.D., and Mori J. Krantz, M.D., of the Denver Health Hospital and Authority, examine the approval of the drug lixivaptan for the treatment of hyponatremia (abnormally low level of sodium in the blood) and the questions regarding the benefit of this class of drugs (vasopressin receptor antagonist).

“Sole reliance on laboratory surrogates can lead to widespread adoption of ineffective or harmful treatments. Regulators should create a landscape that supports evaluation of safety and efficacy across all phases of development and exhibit caution when making inferences based on predictive data from epidemiologic studies. Therapeutically modifying a given surrogate marker tightly linked in epidemiologic studies with improved outcomes cannot guarantee clinical efficacy,” they write. “… in the case of the vasopressin receptor antagonist class, it remains dubious that an increase in serum sodium levels will ultimately be demonstrated to improve outcomes in clinical trials given the myriad etiologies for hyponatremia. The manufacturers of lixivaptan sought approval for use in less severe hyponatremia and even among outpatients. The potential risks and benefits of lixivaptan and this expanded label are being carefully considered by the FDA.”

(JAMA. 2012;308[22]:2345-2346. Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 11, 2012

Media Advisory: To contact corresponding author David S. Friedman, M.D., M.P.H., Ph.D., call John Lazarou at 410-502-8902 or email jlazaro1@jhmi.edu. To contact editorial co-author David C. Musch, Ph.D., M.P.H., call Betsy Nisbet at 734-647-5586 or email bsnisbet@umich.edu.

CHICAGO – The prevalence of nonrefractive visual impairment (not due to need for glasses) in the U.S. has increased significantly in recent years, which may be partly related to a higher prevalence of diabetes, an associated risk factor, according to a study in the December 12 issue of JAMA.

“It is estimated that more than 14 million individuals in the United States aged 12 years and older are visually impaired (<20/40). Of these cases, 11 million are attributable to refractive error. In the United States, the most common causes of nonrefractive visual impairment are age-related macular degeneration, cataract, diabetic retinopathy, glaucoma, and other retinal disorders,” according to background information in the article. Previous studies have shown that visual impairment is common in persons with diabetes. “The prevalence of diagnosed diabetes has increased among adults in recent years, rising from 4.9 percent in 1990 to 6.5 percent in 1998, 7.9 percent in 2001, 10.7 percent in 2007, and 11.3 percent in 2010.”

Fang Ko, M.D., of the Johns Hopkins University School of Medicine, Baltimore, and colleagues conducted a study to assess the prevalence of nonrefractive visual impairment and factors associated with risk of visual impairment. The study included data from the National Health and Nutrition Examination Survey (NHANES), a representative sample of the U.S. population. In 1999-2002 and 2005-2008, 9,471 and 10,480 participants 20 years of age or older received questionnaires, laboratory tests, and physical examinations. Visual acuity of less than 20/40 aided by autorefractor (a device for measuring a person’s refractive error) was classified as nonrefractive visual impairment.

The researchers found that prevalence of nonrefractive visual impairment increased 21 percent, from 1.4 percent in 1999-2002 to 1.7 percent in 2005-2008; and increased 40 percent among non-Hispanic whites 20-39 years of age, from 0.5 percent to 0.7 percent. In analysis among all participants, factors associated with nonrefractive visual impairment included older age, poverty, lower education level, and diabetes diagnosed 10 or more years ago. Among these risk factors, only the latter has increased in prevalence between the 2 time periods considered. Prevalence of diabetes with 10 or more years since diagnosis increased 22 percent overall from 2.8 percent to 3.6 percent; and 133 percent among non-Hispanic whites 20-39 years of age, from 0.3 percent to 0.7 percent.

“We report a previously unrecognized increase of visual impairment among U.S. adults that cannot be attributed to refractive error,” the authors write. “If the current finding becomes a persisting trend, it could result in increasing rates of disability in the U.S. population, including greater numbers of patients with end-organ diabetic damage who would require ophthalmic care. These results have important implications for resource allocation in the debate of distribution of limited medical services and funding. Continued monitoring of visual disability and diabetes, as well as additional research addressing causes, prevention, and treatment, is warranted.”

(JAMA. 2012;308(22):2361-2368; 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: For this study, there will be multimedia content available, 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, December 11 at this link.

Editorial: Diabetes and Nonrefractive Visual Impairment – The Young Have It

David C. Musch, Ph.D., M.P.H., and Thomas W. Gardner, M.D., M.S., of the University of Michigan, Ann Arbor, write in an accompanying editorial that the results of this study “are indeed meaningful, considering the cohort of young people for whom a milieu of sociodemographic and lifestyle factors have led to increased risk of type 2 diabetes and its consequences, which include nonrefractive visual impairment.”

“… this report should send an important message to pediatricians, family practitioners, internists, and ophthalmologists who already are seeing an increase of type 2 diabetes among their younger patients, and should alert public health planners, who need to prepare for the effects on the health care system. The findings of Ko et al should also stimulate funding for new and ongoing efforts to prevent the underlying causes that lead to diabetes and its complications such as obesity-prevention programs aimed at children and adolescents.”

(JAMA. 2012;308(22):2403-2404; 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, DECEMBER 11, 2012

Media Advisory: To contact corresponding author Konrad E. Bloch, M.D., email konrad.bloch@usz.ch.

CHICAGO – For individuals with obstructive sleep apnea traveling to higher altitudes (which may exacerbate symptoms), use of a combination therapy resulted in improvement in symptoms including  reduced insomnia and better control of sleep apnea, according to a preliminary study published in the December 12 issue of JAMA.

As travel to the mountains for professional and recreational activities is increasingly popular, involving millions of persons worldwide, the estimated number of patients with obstructive sleep apnea (OSA) among mountain tourists is also high, and may involve several hundred thousand persons each year, which may expose them to hypoxemia (abnormally low levels of oxygen in the blood) and exacerbation of sleep apnea. “The treatment in this setting is not established,” according to background information in the article.

Tsogyal D. Latshang, M.D., of the University of Zurich, Switzerland, and colleagues conducted a study to evaluate whether taking of the drug acetazolamide (a respiratory stimulant used to treat acute mountain sickness and high-altitude periodic breathing) combined with auto-adjusted continuous positive airway pressure (autoCPAP, computer-controlled continuous mask pressure adjustment) would provide better oxygenation and control of sleep-related breathing disturbances than autoCPAP alone in patients with OSA spending a few days at moderate altitude. The randomized trial included 51 patients with OSA living below an altitude of 800 meters (2,625 feet) and receiving CPAP therapy who underwent studies at a university hospital at 490 meters (1,608 feet) and resorts in Swiss mountain villages at 1,630 meters (5,348 feet) and 2,590 meters (8,497 feet) in the summer of 2009. Patients were studied during 2 stays of 3 days each in the mountain villages. At altitude, patients either took acetazolamide (750 mg/d) or placebo in addition to autoCPAP.

The researchers found that at 1,630 meters and 2,590 meters, combined acetazolamide and autoCPAP treatment was associated with higher oxygen saturation and a lower apnea/hypopnea index (AHI) compared with placebo and autoCPAP. AutoCPAP and acetazolamide increased the median [midpoint] nocturnal oxygen saturation by 1.0 percent at 1,630 meters and by 2.0 percent at 2,590 meters. Also, acetazolamide and autoCPAP resulted in better control of sleep apnea at these altitudes than placebo and autoCPAP: median apnea/ hypopnea index was 5.8 events per hour (5.8/h) and 6.8/h vs. 10.7/h and 19.3/h, respectively; median reduction was 3.2/h and 9.2/h. Median night-time spent with oxygen saturation less than 90 percent at 2,590 meters was 13 percent vs. 57 percent.

“The current randomized, placebo-controlled, double-blind trial provides several novel findings that are clinically relevant for patients with OSA traveling to altitude. First, the data show that combined therapy with acetazolamide and autoCPAP provides a better oxygenation during sleep and wakefulness, prevents an exacerbation of sleep apnea at altitude, and reduces the time spent awake during nights compared with autoCPAP alone. Second, the results demonstrate that autoCPAP alone is an effective therapy for obstructive apneas/hypopneas even at altitude where central apneas/hypopneas emerge,” the authors write.

“Our study provides important information for patients with OSA planning a stay at altitude because they can continue using their CPAP in autoadjusting mode during altitude travel and enhance this treatment with acetazolamide if they want to spend less time awake at night, to achieve a higher arterial oxygen saturation and an optimal control of sleep apnea.”

(JAMA. 2012;308(22):2390-2398; 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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