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

Study Finds Need for Improvement on State Health Care Price Websites

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

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

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

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

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

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 Viewpoint in This Issue of JAMA

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Editor’s Note: This study was partly funded by the Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands. Operation costs were borne by the respective study sites individually. No other funding from commercial sources was sought. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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

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

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

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

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

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

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

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

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

(JAMA. 2013;309(23):2473-2479; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: The Evolution of Type 1 Diabetes

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

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

(JAMA. 2013;309(23):2491-2492; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

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

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

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

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

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

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

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

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

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

Editor’s Note: The Dutch Arthritis Association funded this study. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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

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

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

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

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

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

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

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

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

(JAMA. 2013;309(23):2465-2472; Available pre-embargo to the media at https://media.jamanetwork.com)

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

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, June 18 at this link.

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

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

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

(JAMA. 2013;309(23):2493-2495; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

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

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

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

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

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

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

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

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

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

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

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

Hearing Loss Associated With Hospitalization, Poorer Self-Reported Health

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

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

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

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

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

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

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 Viewpoints in This Issue of JAMA

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

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

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

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

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

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

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

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

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

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

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 Editorial: Talking to Patients in the 21st Century

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Editorial: Systemic Inflammation in Predicting COPD Exacerbations

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Editor’s Note: The study was funded by grants from Karolinska Institutet (Distinguished Professor Award to Dr. Cnattingius). Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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

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

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

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

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

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

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

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

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

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

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

Editor’s Note: This study was supported by a Cancer Center Support grant from the National Cancer Institute and by the American Lebanese Syrian Associated Charities. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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

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

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

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

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

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

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

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

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

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

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

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

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

Editor’s Note: This research was supported by the Agency for Healthcare Research and Quality. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, June 11 at this link.

Editorial: Putting Antibiotic Prescribing for Children Into Context

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

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

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

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

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

Research Finds Retinal Vessel Leakage During High Altitude Exposure

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

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

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

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

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

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 Viewpoints in This Issue of JAMA

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

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

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

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

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

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 The Future of Quality Measurement for Improvement and Accountability

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Editor’s Note: This project was funded under a contract from the AHRQ and U.S. Department of Health and Human Services. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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

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

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

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

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

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

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

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

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

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

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

(JAMA. 2013;309(21):2240-2249; Available pre-embargo to the media at https://media.jamanetwork.com)

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

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, June 4 at this link.

Editorial: Treating Diabetes With Surgery

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

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

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

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

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

Advances in Regulatory Science at the Food and Drug Administration

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

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

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

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

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 Medication Nonadherence – A Diagnosable and Treatable Medical Condition

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

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

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

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

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Value of Unique Device Identification in the Digital Health Infrastructure

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Editorial: When Should a Mechanically Ventilated Patient Undergo Tracheostomy?

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

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

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

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

(JAMA. 2013;309(20):2163-2164; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

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

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

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

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

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

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

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

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

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

Editor’s Note: This study was funded by the NHLBI, Bethesda, Md. Escitalopram and matched placebo were supplied by Forest Research Institute Inc., Germantown, Md. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, May 21 at this link.

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

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

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

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

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

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

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

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

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

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

Editor’s Note: This research was supported by the National Heart, Lung, and Blood Institute and the Dorothy P. and Richard P. Simmons Endowed Chair for Pulmonary Research (University of Pittsburgh School of Medicine). Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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

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

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

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

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

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

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

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

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

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

(doi:10.1001/jama.2013.5023; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Steroids for Treatment of COPD Exacerbations – Less Is Clearly More

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

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

(doi:10.1001/jama.2013.5644; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 1:00 P.M. (CT) MONDAY, MAY 20, 2013

Media Advisory: To contact Gordon S. Doig, Ph.D., email gdoig@med.usyd.edu.au. To contact editorial co-author Juan B. Ochoa Gautier, M.D., call Rick Pietzak at 412-864-4151 or email pietzakr@upmc.edu.

CHICAGO – The early (within 24 hours of intensive care unit [ICU] admission) provision of intravenous nutrition among critically ill patients with contraindications (a condition that makes a particular procedure potentially inadvisable) to early use of enteral nutrition (such as through a feeding tube) did not result in significant differences in 60 day mortality or shorter ICU or hospital length of stay, compared with standard care, according to a study in the May 22/29 issue of JAMA. The study is being released early online to coincide with its presentation at the American Thoracic Society international conference. The intervention did result in a significant reduction in days of invasive mechanical ventilation.

“Parenteral nutrition [PN; intravenous administration of nutritional support] has been in common use since the 1960s and is accepted as the standard of care for patients with chronic nonfunctioning gastrointestinal tracts,” according to background information in the article. In critical illness, controversy surrounds the appropriate use of parenteral nutrition. “Systematic reviews suggest adult patients in ICUs with relative contraindications to early enteral nutrition [EN; feeding through the gastrointestinal tract, such as with the use of a feeding tube] may benefit from PN provided within 24 hours of ICU admission.”

Gordon S. Doig, Ph.D., of the University of Sydney, Australia, and colleagues conducted a multicenter clinical trial to assess the effects of providing parenteral nutrition within 24 hours of ICU admission to adult critically ill patients who would not otherwise receive nutrition therapy because of short-term relative contraindications to enteral nutrition. The randomized trial was conducted between October 2006 and June 2011 in ICUs of 31 community and tertiary hospitals in Australia and New Zealand. Participants were critically ill adults who were expected to remain in the ICU longer than 2 days.

A total of 1,372 patients were randomized (686 to standard care, 686 to early PN). Of 682 patients receiving standard care, 199 patients (29.2 percent) initially began EN, 186 patients (27.3 percent) initially began PN, and 278 patients (40.8 percent) remained unfed. Time to EN or PN in patients receiving standard care was 2.8 days. Patients receiving early PN began PN an average of 44 minutes after enrollment in the trial.

The researchers found that day-60 mortality did not differ significantly between groups (22.8 percent for standard care vs. 21.5 percent for early PN). There were also no significant differences between groups in rates of new infection. Standard care patients experienced significantly greater muscle wasting and significantly greater fat loss over the duration of their ICU stay.

Early PN patients rated day-60 quality of life statistically, but not clinically meaningfully, higher. Early PN patients required fewer days of invasive ventilation, but this did not result in a statistically significant reduction in ICU or hospital length of stay.

No harm was associated with the use of early parenteral nutrition in this trial.

(JAMA. 2013;309(20):2130-2138; 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: Early Nutrition in Critically III Patients – Feed Carefully and in Moderation

“The findings reported by Doig et al add important knowledge to the ongoing debate about when, how much, and through what route critically ill patients should be fed,” write Juan B. Ochoa Gautier, M.D., of the University of Pittsburgh, and Flavia R. Machado, M.D., Ph.D., of the Federal University of Sao Paulo, Brazil, in an accompanying editorial.

“This article joins several articles that suggest either benefit or harm from supplemental parenteral nutrition or whether ‘trophic feeding’ is ‘just as good’ as meeting nutritional goals in medical patients in the ICU during the first 7 days of their hospitalization. A significant amount of additional work is required to determine how to best deliver nutrition interventions in the ICU. It is essential (and indeed ethically imperative) for investigators at the forefront of this debate to be circumspect in their conclusions and clinical recommendations, to avoid their findings being misinterpreted and creating more harm than good. For now clinicians should attempt to optimize oral/enteral nutrition, avoid forced starvation if at all possible, and judiciously use supplemental parenteral nutrition.”

(JAMA. 2013;309(20):2165-2166; 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. Ochoa reported having a license on a patent focused on arginine metabolism and cancer treatment with NewLink. No other disclosures were reported.

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EMBARGOED FOR EARLY RELEASE: 1:00 P.M. (CT) MONDAY, MAY 20, 2013

Media Advisory: To contact Linda L. Chlan, Ph.D., R.N., call Kathryn Kelley at 614-688-1062 or email kelley.81@osu.edu. To contact editorial co-author Elie Azoulay, M.D., Ph.D., email elie.azoulay@sls.aphp.fr.

CHICAGO – Among intensive care unit patients receiving acute ventilatory support for respiratory failure, use of patient-preferred music resulted in greater reduction in anxiety and sedation frequency and intensity compared with usual care, according to a study published online by JAMA. The study is being released early online to coincide with its presentation at the American Thoracic Society international conference.

“Critically ill mechanically ventilated patients receive intravenous sedative and analgesic medications to reduce anxiety and promote comfort and ventilator synchrony,” according to background information in the article. These potent medications are often administered at high doses for prolonged periods and are associated with various adverse effects. “Mechanically ventilated patients have little control over pharmacological interventions to relieve anxiety; dosing and frequency of sedative and analgesic medications are controlled by intensive care unit (ICU) clinicians. Interventions are needed that reduce anxiety, actively involve patients, and minimize the use of sedative medications.” The authors note that “listening to preferred, relaxing music has reduced anxiety in mechanically ventilated patients in limited trials. It is not known if music can reduce anxiety throughout the course of ventilatory support, or reduce exposure to sedative medications.”

Linda L. Chlan, Ph.D., R.N., of Ohio State University, Columbus, and colleagues conducted a study to evaluate if a patient-directed music (PDM) intervention could reduce anxiety and sedative exposure in ICU patients receiving mechanical ventilation. The clinical trial included 373 patients from 12 ICUs at 5 hospitals in the Minneapolis-St. Paul area receiving acute mechanical ventilatory support for respiratory failure between September 2006 and March 2011. Of the patients included in the study, 86 percent were white, 52 percent were female, and the average age was 59 years. Patients were randomized to self-initiated PDM (n=126) with preferred selections tailored by a music therapist whenever desired while receiving ventilatory support; self-initiated use of noise-canceling headphones (NCH; n = 122); or usual care (n = 125). The main outcomes examined were daily assessments of anxiety (on a 100-mm visual analog scale) and 2 aggregate measures of sedative exposure (intensity and frequency).

The PDM patients listened to music for an average of 80 minutes/day; the NCH patients wore the noise-abating units for an average of 34.0 minutes/day. Analysis showed that patients in the PDM group had an anxiety score that was 19.5 points lower than patients in the usual care group.

For an average patient on the fifth study day (the average time patients were enrolled), a usual care patient received 5 doses of any 1 of the 8 study-defined sedative medications. An equivalent PDM patient received 3 doses of sedative medications on the fifth day, a relative reduction of 38 percent. By the end of the fifth day, a PDM patient had a relative reduction of 36 percent in their sedation intensity score and 36.5 percent in their anxiety score.

PDM did not result in greater reduction in anxiety or sedation intensity compared with NCH.

“Music provides patients with a comforting and familiar stimulus and the PDM intervention empowers patients in their own anxiety management; it is an inexpensive, easily implemented nonpharmacological intervention that can reduce anxiety, reduce sedative medication exposure, and potentially associated adverse effects. The PDM patients received less frequent and less intense sedative regimens while reporting decreased anxiety levels,” the authors write.

(doi:10.1001/jama.2013.5670; 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: Music Therapy for Reducing Anxiety in Critically Ill Patients

In an accompanying editorial, Elie Azoulay, M.D., Ph.D., of the Universite Paris-Diderot, Sorbonne Paris-Cite, and colleagues comment on the findings of this study.

“Reducing anxiety and amount of sedation in mechanically ventilated patients is of the utmost importance, particularly because the result may be a decrease in the post-ICU burden, which weighs heavily on many patients, as well as numerous complications related to sedation. The trial by Chlan et al provides preliminary data that create new possibilities for improving the well-being of ICU patients. Further studies are needed to better understand how music therapy might improve the ICU experience for critically ill patients.”

(doi:10.1001/jama.2013.5657; 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. Dr. Azoulay reports serving on the board of Gilead, and receiving payment for lectures and grants from Pfizer, Merck Sharp & Dohme, and Gilead. Ms. Chaize and Dr. Kentish-Barnes report no disclosures.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, MAY 14, 2013

No Significant Change Seen in Overall Smokeless Tobacco Use Among U.S. Youths

Tobacco use remains the leading preventable cause of death and disease in the United States. Declines in smoking among youths were observed from the late 1990s. “However, limited information exists on trends in smokeless tobacco use among U.S. youths,” writes Israel T. Agaku, D.M.D., M.P.H., of the Harvard School of Public Health, Boston, and colleagues.

As reported in a Research Letter, the authors analyzed recent trends in prevalence of smokeless tobacco use among youths using the 2000-2011 National Youth Tobacco Survey, a biennial national cross-sectional survey of U.S. middle school and high school students. Samples during 2000 through 2011 ranged from 35,828 students in 324 schools in 2000 to 18,866 students in 178 schools in 2011. Current smokeless tobacco use was defined as use of snuff, chewing, or dipping tobacco for 1 or more days within the past 30 days.

The researchers found that no significant change in overall smokeless tobacco prevalence occurred between 2000 (5.3 percent) and 2011 (5.2 percent). Downward trends were observed in the age groups of 9 to 11 and 12 to 14 years. Prevalence increased in the age group of 15 to 17 years.

“The prevalence of smokeless tobacco use among U.S. youths did not change between 2000 and 2011 and remained generally low. However, subgroup differences were observed. The use of modified traditional smokeless tobacco products, such as moist snuff, coupled with lower taxes on smokeless tobacco products (vs. cigarettes) may have contributed to the stable prevalence of smokeless tobacco (vs. the declining trend for cigarettes),” they write. “… these findings emphasize the need for evidence-based interventions to reduce smokeless tobacco use among youths.”

(JAMA. 2013;309[19]:1992-1994. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Israel T. Agaku, D.M.D., M.P.H., call 770-728-3220 or email iagaku@post.harvard.edu.

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Viewpoints in This Issue of JAMA

Two counter Viewpoints address the question: Should religious-based organizations be required to provide contraceptive coverage?

Contraception Is a Fundamental Primary Care Service

The Affordable Care Act (ACA) requires health care plans after August 1, 2012, to cover preventive health services recommended by the Institute of Medicine and endorsed by the Department of Health and Human Services. “Some religious organizations and private employers, however, have demanded exemption from providing contraception, arguing that it violates their religious beliefs,” writes Dana R. Gossett, M.D., M.S.C.I., of the Northwestern University Feinberg School of Medicine, Chicago, and colleagues. “We believe that allowing such an exception is at odds with evidence-based preventive care, inconsistent with actual patterns of contraceptive use among women who are religious, and a sectarian incursion into private health care decisions that is without parallel in the U.S. health care system.”

“Women whose health coverage is provided by a religious organization would face access barriers and additional costs compared with women whose coverage is provided by secular organizations, despite similar rates of demand and use. Lowering economic barriers to the most effective forms of birth control, long-acting reversible contraception, has been demonstrated to improve utilization and decrease rates of abortion and teenage pregnancy.”

“Both men and women engage in sexual activity, but women disproportionately bear the consequences of sexual activity in their risk of pregnancy and its attendant health outcomes. The strategy for managing the health of the nation cannot systematically discriminate against any one group of citizens. It is in the interest of the medical community and society at large to prevent such discrimination.”

(JAMA. 2013;309[19]:1997-1998. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Dana R. Gossett, M.D., M.S.C.I., call Erin White at 847-491-4888 or email ewhite@northwestern.edu.

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Contraceptives and the Law – A View From a Catholic Medical Institution

“As faculty members at the Creighton University School of Medicine—one of 4 Catholic medical schools in the United States—we question whether the public health benefits of mandated contraception coverage in the United States are so substantial that individuals and institutions should be forced to take actions that violate their collective moral conscience, thereby doing unnecessary harm to the principle of religious freedom,” writes Eric A. Zimmer, S.J., Ph.D., of the Creighton University School of Medicine and Creighton Center for Health Policy Ethics, Omaha, Neb., and colleagues.

“What is now at issue is whether the U.S. government, in policies that promote dissemination of cost-free birth control as a social imperative, has properly weighed the benefits vs. the harms created by this policy. The government should always strive to respect religious freedom, including that within institutions. If this right is to be restricted for the sake of a public health need, rigorous standards should be applied to validate this need and to weigh the relative value of preventive health care interventions proposed.”

“A careful analysis is required that attempts to balance the value of regulation of reproductive activity against the legal, medical, and ethical implications of this mandate. A thorough evaluation will take time, but the immediate issue to be decided is whether there is such a pressing public health need that the U.S. government should use its ultimate power to overcome the religious objections of employers and force them to provide services inconsistent with their beliefs and value systems.”

(JAMA. 2013;309[19]:1999-2000. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Marc S. Rendell, M.D., call Jen Homann at 402-280-2864 or email JenniferHomann@creighton.edu.

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

EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, MAY 14, 2013

Media Advisory: To contact Ingrid Nygaard, M.D., call Phil Sahm at 801-581-2517 or email phil.sahm@hsc.utah.edu. To contact editorial author Cheryl B. Iglesia, M.D., call Karen Mallet at 215-514-9751 or email km463@georgetown.edu.

CHICAGO – Results after seven years of follow-up suggest that women considering abdominal sacrocolpopexy (surgery for pelvic organ prolapse [POP]) should be counseled that this procedure effectively provides relief from POP symptoms; however, the anatomic support deteriorates over time; and that adding an anti-incontinence procedure decreases, but does not eliminate the risk of stress urinary incontinence, and mesh erosion can be a problem, according to a study in the May 15 issue of JAMA.

“Pelvic organ prolapse occurs when the uterus or vaginal walls bulge into or beyond the vaginal introitus [vaginal opening]. It is a common occurrence and 7 percent to 19 percent of women receive surgical repair,” according to background information in the article. More than 225,000 surgeries are performed annually in the United States for POP. Abdominal sacrocolpopexy is the most durable operation for advanced POP and serves as the criterion standard against which other operations are compared, but little is known about safety and long-term effectiveness.

Ingrid Nygaard, M.D., of the University of Utah School of Medicine, Salt Lake City, and colleagues conducted a study to describe anatomic and symptomatic outcomes up to 7 years after abdominal sacrocolpopexy and to determine whether these are affected by anti-incontinence surgery (Burch urethropexy). The study consisted of a long-term follow-up of the randomized, 2-year Colpopexy and Urinary Reduction Efforts (CARE) trial of women with stress continence who underwent abdominal sacrocolpopexy between 2002 and 2005 for symptomatic POP and also received either concomitant Burch urethropexy or no urethropexy. Ninety-two percent (215/233) of eligible 2-year CARE trial completers were enrolled in the extended CARE study; and 181 (84 percent) and 126 (59 percent) completed 5 and 7 years of follow-up, respectively. The median (midpoint) follow-up was 7 years.

Of 215 women enrolled in the extended CARE study, 104 had undergone abdominal sacrocolpopexy plus Burch urethropexy and 111 had undergone abdominal sacrocolpopexy alone. The researchers found that that POP and urinary incontinence (UI) treatment failure rates gradually increased during the follow-up period. By year 7, the estimated probabilities of POP treatment failure for the urethropexy group and the no urethropexy group, respectively, were 0.27 and 0.22 for anatomic failure; 0.29 and 0.24 for symptomatic failure; and 0.48 and 0.34 for a composite of both.

Overall for the duration of the study, the estimated probability of stress urinary incontinence (SUI) was 0.62 for the urethropexy and 0.77 for the no urethropexy group. The expected time to treatment failure for the SUI outcome in the urethropexy group vs. the no urethropexy group was 131.3 months vs. 40.2 months, respectively.

The probability of mesh erosion at 7 years was 10.5 percent.

“Three key points emerge from these data. First, as a criterion standard for the surgical treatment of POP, abdominal sacrocolpopexy is less effective than desired. … Second, surgical prevention of SUI at the time of abdominal POP surgery involves no clinically significant trade-offs identified to date. … In addition, we found that complications related to synthetic mesh continue to occur over time,” the authors write.

“We anticipate that continued research in mesh development will lead to new materials and applications with fewer adverse events, but our data highlight the importance of careful long-term evaluation of new devices. Comparative effectiveness trials with long-term follow-up of at least 5 years are needed to compare abdominal sacrocolpopexy that we described in this report with vaginal prolapse procedures that include and do not include mesh augmentation.”

“Abdominal sacrocolpopexy effectiveness should be balanced with long term risks of mesh or suture erosion.”

(JAMA. 2013;309(19):2016-2024; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This research was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Office of Research on Women’s Health at the National Institutes of Health. 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: Pelvic Organ Prolapse Surgery – Long-term Outcomes and Implications for Shared Decision Making

“This study has important clinical implications and calls into question the designation of the abdominal sacrocolpopexy as the criterion standard procedure for prolapse repair,” writes Cheryl B. Iglesia, M.D., of the Georgetown University School of Medicine, Washington, D.C., in an accompanying editorial.

“In this era of shared decision making, the next logical question is, ‘How do physicians advise patients who are contemplating pelvic reconstructive surgery for prolapse?’ Rates of prolapse and incontinence surgery are expected to increase substantially during the next 40 years as the population ages. Patients need to discuss with their physicians the available surgical and nonsurgical options for prolapse and incontinence, medical comorbidities, and review of available data. Surgeons and patients should also discuss prophylactic concomitant or staged surgery for stress incontinence at the time of prolapse repair. Timing of prolapse repair based on quality-of-life decisions should also be discussed preoperatively.”

(JAMA. 2013;309(19):2045-2046; 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. Iglesia reported serving as a consultant to the U.S. Food and Drug Administration on a mesh panel in September 2011.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, MAY 14, 2013

Media Advisory: To contact Pamela N. Peterson, M.D., M.S.P.H., call Jenny Bertrand at 303-602-4924 or email Jennifer.bertrand@dhha.org.

CHICAGO – Even though patients receiving an implantable cardioverter-defibrillator (ICD) for primary prevention often receive a dual-chamber ICD, an analysis that included more than 32,000 patients receiving an ICD without indications for pacing finds that the use of a dual-chamber device compared with a single-chamber device was associated with a higher risk of device-related complications and similar 1-year mortality and hospitalization outcomes, according to a study in the May 15 issue of JAMA.

“The central decision regarding ICD therapy is whether to use a single- or dual-chamber device,” according to background information in the article. More complex dual-chamber devices may offer theoretical benefits beyond single-chamber devices for patients without an indication for pacing, but may also have greater risks. In a national sample, more than two-thirds of patients receiving an ICD received a dual-chamber device. “The outcomes of dual- vs. single-chamber devices are uncertain.”

Pamela N. Peterson, M.D., M.S.P.H., of the Denver Health Medical Center, and colleagues conducted a study to compare outcomes, including mortality, hospitalizations, and longer-term implant-related complications between single- and dual-chamber devices. The study included admissions in the National Cardiovascular Data Registry’s (NCDR) ICD registry from 2006-2009 that could be linked to Centers for Medicare & Medicaid Services fee-for-service Medicare claims data. Patients were included if they received an ICD for primary prevention and did not have a documented indication for pacing.

Among 32,034 patients, 12,246 (38 percent) received a single-chamber device and 19,788 (62 percent) received a dual-chamber device. After analysis of the data, the researchers found that rates of complications were lower for single-chamber devices (3.51 percent vs. 4.72 percent), but device type was not significantly associated with 1-year mortality (unadjusted rate, 9.85 percent vs. 9.77 percent), 1-year all-cause hospitalization (unadjusted rate, 43.86 percent vs. 44.83 percent), or hospitalization for heart failure (unadjusted rate, 14.73 percent vs. 15.38 percent).

The authors suggest that their study advances the understanding of the risks of dual-chamber devices. “Because implanting a dual-chamber ICD is a more complex and time-consuming procedure than implanting a single-chamber device, the possibility of device-related complications such as infection and lead displacement requiring device revision is likely to increase. Indeed, we observed a greater risk of complications among patients receiving dual-chamber devices.”

“Many patients receiving primary prevention ICDs receive dual-chamber devices. Dual-chamber devices do not appear to offer any clinical benefit over single-chamber devices with regard to death, all-cause readmission, or heart failure readmission in the year following implant. However, dual-chamber ICDs are associated with higher rates of complications. Therefore, among patients without clear pacing indications, the decision to implant a dual-chamber ICD for primary prevention should be considered carefully.”

(JAMA. 2013;309(19):2025-2034; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Dr. Peterson is supported by a grant from the Agency for Healthcare Research and Quality. This research was supported by the American College of Cardiology Foundation’s National Cardiovascular Data Registry (NCDR). 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, MAY 7, 2013

Media Advisory:  To contact Jeffrey Ecker, M.D., call Susan McGreevey at 617-724-2764 or email: smcgreevey@partners.org

CHICAGO – A Clinical Crossroads review article in the May 8 issue of JAMA discusses the potential benefits and risks for pregnant women who request cesarean delivery without an indication of need rather than proceeding with a plan for vaginal delivery.

Jeffrey Ecker, M.D., from Massachusetts General Hospital, Boston, is the author of the article that examines this issue of cesarean delivery on maternal request (CDMR).   Dr. Ecker writes the term “refers to cesarean delivery performed without maternal or fetal indication; i.e., with no expectation of improving the physical health of the mother or neonate.”    Dr. Ecker notes that available data indicate that CDMR occurs in less than three percent of all deliveries in the United States.

“Reasons for considering CDMR include fear of specific elements of labor and concern for fetal or maternal morbidities attributable to vaginal delivery,” Dr. Ecker writes.   “Compared with a plan for vaginal delivery, CDMR may be associated with lower rates of hemorrhage, maternal incontinence, and rate but serious neonatal outcomes.  However, CDMR is associated with a higher risk of neonatal respiratory morbidity.”   And Dr. Ecker writes that repeated caesarean deliveries have higher rates of operative complications and placental abnormalities.

The article concludes: “There is no immediate expectation for CDMR to reduce the health risks of mothers or infants.   Accordingly, counseling and decisions regarding CDMR should be made after considering a woman’s full reproductive plans.”

(JAMA. 2013; 309(18):1930-1936)

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, MAY 7, 2013

Study Finds Increase in Fall-Related Traumatic Brain Injuries Among Elderly Men and Women

“Traumatic brain injury (TBI) is a major cause of hospitalization, disability, and death-worldwide, and among older adults, falling is the most common cause of TBI,” writes Niina Korhonen, B.M., of the Injury and Osteoporosis Research Center, Tampere, Finland, and colleagues in a Research Letter. The authors previously reported that the number and incidence of adults 80 years of age or older admitted to the hospital due to fall-induced TBI in Finland increased from 1970 through 1999. This analysis is a follow-up of this population through 2011.

The study included data from the Finnish National Hospital Discharge Register, a nationwide, computer-based register that provides data for severe injuries among the Finnish population. The researchers found that the total number of older Finnish adults with a fall-induced TBI increased considerably from 60 women and 25 men in 1970 to 1,205 women and 612 men in 2011. The age-adjusted incidence of TBI (per 100,000 persons) also showed an increase from 168.2 women in 1970 to 653.6 in 2011 (an increase of 289 percent) and from 174.6 to 724.0, respectively, in men (an increase of 315 percent).

“Our 40-year follow-up shows that the number and age-adjusted incidence of fall-induced TBI in Finnish men and women aged 80 years or older increased considerably between 1970 and 2011. Compared with the data in our previous study, the increase has continued since 1999,” the authors write. “Further studies are needed to better understand the reasons for the increase in fall-related TBI in older persons (aged >80 years) so that effective interventions for falls and injury prevention can be initiated.”

(JAMA. 2013;309[18]:1891-1892. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Niina Korhonen, B.M., email njkorhon@student.uef.fi.

Viewpoints in This Issue of JAMA

Investments in Infrastructure for Diverse Research Resources and the Health of the Public

“Active surveillance of drugs and devices in the postmarket setting is an essential component of the lifecycle approach to drug evaluation. The U.S. Food and Drug Administration (FDA) Amendments Act of 2007 required the agency to develop ‘a postmarket risk identification and analysis system.’ In response, scientists from the FDA and investigators from collaborating institutions have been actively and productively engaged in the creation of the Sentinel Initiative, including the Mini-Sentinel pilot program, which has become an exciting and powerful research resource,” write Bruce M. Psaty, M.D., Ph.D., and Eric B. Larson, M.D., M.P.H., of the University of Washington, Seattle.

In this Viewpoint, the authors discuss the Mini-Sentinel program.

“Major benefits and the major harms are often best represented separately—an approach that allows patients and physicians to incorporate their own preferences about particular risks or benefits. In updating the postmarket risk-benefit profile, the FDA should ensure that the full range of expertise is brought to bear on the decision-making process. In some instances, the postmarket active surveillance may also result in regulatory action. For many regulatory actions, Mini-Sentinel can also provide a timely mechanism for tracking their effects on the use of the medicinal product and the health of the public.”

(JAMA. 2013;309[18]:1895-1896. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Bruce M. Psaty, M.D., Ph.D., call Clare LaFond at 206-685-1323 or email clareh@uw.edu.

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 Developing Quality Measures to Address Overuse

“Medical societies and other organizations have worked for many years to develop quality measures to assess underuse of beneficial health care services (e.g., failure to use antiplatelet therapy for patients with acute myocardial infarction). More recently, organizations have begun efforts to address unnecessary tests and treatments and the high costs of health care by developing ‘overuse’ measures,” write Jason S. Mathias, M.D., M.S., and David W. Baker, M.D., M.P.H., of the Feinberg School of Medicine, Northwestern University, Chicago. Overuse is defined as the use of a service that is unlikely to improve patient outcomes or for which potential harms exceed likely benefits.

The standards for developing and evaluating overuse measures are not clearly defined and may differ from those for underuse measures. In this Viewpoint, the authors examine two key issues that need “careful consideration in the development, implementation, and evaluation of overuse measures as compared with more typical underuse measures: level of evidence and mitigating potential unintended consequences.”

“Compared with traditional underuse measures, the rules of evidence for developing overuse measures are less well defined, and thoughtful strategies are needed to avoid unintended consequences of overuse measures. When carefully developed, implemented, and monitored, overuse measures have the potential to be part of the solution to the cost, quality, and safety problems in the U.S. health care system.”

(JAMA. 2013;309[18]:1897-1898. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact David W. Baker, M.D., M.P.H., call Marla Paul at 312-503-8928 or email marla-paul@northwestern.edu.

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, MAY 7, 2013

Media Advisory: To contact corresponding author Markus M. Lerch, M.D., F.R.C.P., email lerch@uni-greifswald.de. To contact editorial author Emad M. El-Omar, M.D., email e.el-omar@abdn.ac.uk.

CHICAGO – Two genome-wide association studies and a subsequent meta-analysis have found that certain genetic variations are associated with susceptibility to Helicobacter pylori, a bacteria that is a major cause of gastritis and stomach ulcers and is linked to stomach cancer, findings that may help explain some of the observed variation in individual risk for H pylori infection, according to a study in the May 8 issue of JAMA.

“[H pylori] is the major cause of gastritis (80 percent) and gastroduodenal ulcer disease (15 percent-20 percent) and the only bacterial pathogen believed to cause cancer,” according to background information in the article. “H pylori prevalence is as high as 90 percent in some developing countries but 10 percent of a given population is never colonized, regardless of exposure. Genetic factors are hypothesized to confer H pylori susceptibility.”

Julia Mayerle, M.D., of University Medicine Greifswald, Greifswald, Germany, and colleagues conducted a study to identify genetic loci associated with H pylori seroprevalence. Two independent genome-wide association studies (GWASs) and a subsequent meta-analysis were conducted for anti-H pylori immunoglobulin G (IgG) serology in the Study of Health in Pomerania (SHIP) (recruitment, 1997-2001 [n =3,830]) as well as the Rotterdam Study (RS-I) (recruitment, 1990-1993) and RS-II (recruitment, 2000-2001 [n=7,108]) populations. Whole-blood RNA gene expression profiles were analyzed in RS-III (recruitment, 2006-2008 [n = 762]) and SHIP-TREND (recruitment, 2008-2012 [n=991]), and fecal H pylori antigen in SHIP-TREND (n=961).

Of 10,938 participants, 6,160 (56.3  percent) were seropositive for H pylori. GWAS meta-analysis identified an association between the gene TLR1 and H pylori seroprevalence, “a finding that requires replication in non-white populations,” the authors write.

“At this time, the clinical implications of the current findings are unknown. Based on these data, genetic testing to evaluate H pylori susceptibility outside of research projects would be premature.”

“If confirmed, genetic variations in TLR1 may help explain some of the observed variation in individual risk for H pylori infection,” the researchers conclude.

(JAMA. 2013;309(18):1912-1920; 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: Helicobacter pylori Susceptibility in the GWAS Era

In an accompanying editorial, Emad M. El-Omar, M.D., of Aberdeen University, Aberdeen, United Kingdom, writes that the authors of this study are appropriate to state, “based on their data, genetic testing to evaluate H pylori susceptibility is premature.”

“This would be superfluous, because nongenetic testing for the infection can be accomplished at a fraction of the cost. There is a bigger picture: understanding genetic susceptibility to H pylori is essential for understanding how to overcome this infection. The current approach to eradication of the infection is limited and based entirely on prescribing a cocktail of antibiotics with an acid inhibitor to symptomatic individuals. However, H pylori antibiotic resistance is increasing steadily, and eventually curing even benign conditions such as peptic ulcer disease arising from H pylori will be difficult. When considering gastric cancer, another H pylori-induced global killer, the necessity for understanding the pathogenesis of the infection and the role of host genetics in susceptibility is even greater. The corollary is that better understanding of infections, including genetic epidemiology, is crucial to design measures to eradicate the downstream consequences of H pylori in large populations.”

(JAMA. 2013;309(18):1939-1940; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, MAY 7, 2013

Media Advisory: To contact Maurizio Gasparini, M.D., email maurizio.gasparini@humanitas.it. To contact editorial author Merritt H. Raitt, M.D., call Tamara Hargens-Bradley at 503-494-8231 or email hargenst@ohsu.edu.

CHICAGO – Programming an implantable cardioverter-defibrillator (ICD) with a long-detection interval compared with a standard-detection interval resulted in a reduction in anti-tachycardia pacing episodes, ICD shocks delivered, and inappropriate shocks, according to a study in the May 8 issue of JAMA.

“Therapy with ICDs is now the standard of care in primary and secondary prevention. As indications for implants have expanded, concern about possible adverse effects of ICD therapies on prognosis and quality of life has arisen. Several authors have reported that ICD therapies, both appropriate and inappropriate, are associated with an increased risk of death and worsening of heart failure. To reduce these unfavorable outcomes, several studies have focused on identifying the best device programming strategies, either by targeting the anti-tachycardia pacing [ATP; use of pacing stimulation techniques for termination of tachyarrhythmias] algorithms for interrupting fast ventricular tachyarrhythmias [abnormal heart rhythm] or by investigating the use of prolonged arrhythmia detection intervals,” according to background information in the article. “Using more intervals to detect ventricular tachyarrhythmias has been associated with reducing unnecessary ICD therapies.”

Maurizio Gasparini, M.D., of the Humanitas Clinical and Research Center, Rozzano, Italy, and colleagues conducted a study (ADVANCE III) to determine whether using 30 of 40 intervals to detect ventricular arrhythmias (VT) (long detection) during spontaneous fast VT episodes reduces ATP and shock delivery more than 18 of 24 intervals (standard detection). The randomized trial included 1,902 primary and secondary prevention patients (average age, 65 years; 84 percent men; 75 percent primary prevention ICD) with ischemic and nonischemic etiology undergoing first ICD implant at 1 of 94 international centers (March 2008-December 2010). Patients were randomized 1:1 to programming with long (n=948) or standard-detection (n=954) intervals.

Overall, 530 episodes were recorded and classified by the devices as ventricular arrhythmias. During a median (midpoint) follow-up of 12 months, the long-detection group had a 37 percent lower rate of delivered therapies (ATP and shocks) (346 vs. 557) compared to the standard-interval detection group. Estimates of the time to the first ICD therapy (ATP or shock) showed a significantly lower probability of receiving a therapy in the long-detection group.

The researchers also found that the frequency of appropriate shocks was similar between the groups, while the long-detection group was associated with a significantly lower incidence (45 percent lower rate) of inappropriate shocks. In addition, a lower hospitalization rate was observed in the long-detection group. No significant difference in mortality rates was seen between the groups.

“ADVANCE III demonstrated that the use of a long detection setting, in ICDs with the capability of delivering ATP during capacitor charge, significantly reduced the rate of ventricular therapies delivered and inappropriate shocks compared with the standard detection setting,” the authors write. “This programming strategy may be a useful approach for ICD recipients.”

(JAMA. 2013;309(18):1903-1911; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Reducing Shocks and Improving Outcomes With Implantable Defibrillators

Merritt H. Raitt, M.D., of the Portland Veterans Administration Medical Center and Oregon Health and Science University, Portland, comments on the findings of this study in an accompanying editorial.

“The findings from the ADVANCE III trial by Gasparini et al add important new information to the evidence base of ICD programming for prevention of ventricular arrhythmias. Regardless of whether these programming interventions lead to reduced mortality, the unequivocal reduction in ICD shocks and the reduction in hospitalization without an increase in adverse events such as syncope suggests that this programming approach should be considered for adoption in the care of patients with ICDs and clinical characteristics similar to those enrolled in these studies.”

(JAMA. 2013;309(18):1937-1938; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 6 P.M. (CT) SUNDAY, MAY 5, 2013

Media Advisory: To contact Emily Y. Chew, M.D., call Jean Horrigan at 301-496-5248 or email jh@nei.nih.gov.

CHICAGO – In a large, multicenter, randomized clinical trial that included persons at high risk for progression to advanced age-related macular degeneration (AMD), adding the carotenoids lutein and zeaxanthin, the omega-3 fatty acids DHA and EPA, or both to a formulation of antioxidant vitamins and minerals that has shown effectiveness in reducing risk did not further reduce risk of progression to advanced AMD, according to a study published by JAMA. The study is being released early online to coincide with its presentation at the Association for Research in Vision and Ophthalmology annual meeting.

“Age-related macular degeneration , the leading cause of blindness in the developed world, accounts for more than 50 percent of all blindness in United States,” according to background information in the article. In 2004 it was estimated that 8 million individuals had intermediate AMD and approximately 2 million had advanced AMD, with no effective proven therapies for atrophic AMD. “Without more effective ways of slowing progression, the number of persons with advanced AMD is expected to double over the next 20 years, resulting in increasing socioeconomic burden,” the authors write. “Oral supplementation with the Age-Related Eye Disease Study (AREDS) formulation (antioxidant vitamins C, E, and beta carotene and zinc) has been shown to reduce the risk of progression to advanced AMD. Observational data suggest that increased dietary intake of lutein and zeaxanthin, omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]), or both might further reduce this risk.”

Emily Y. Chew, M.D., of the National Eye Institute, National Institutes of Health, Bethesda, Md., and colleagues with the Age-Related Eye Disease Study 2 (AREDS2) Research Group examined whether adding lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation might further reduce the risk of progression to advanced AMD. A secondary goal was to evaluate the effect of eliminating beta carotene, lowering zinc doses, or both in the AREDS formulation. AREDS2, a multicenter, randomized phase 3 study was conducted in 2006-2012, enrolling 4,203 participants 50 to 85 years of age at risk for progression to advanced AMD with bilateral large drusen (tiny yellow or white deposits in the retina of the eye or on the optic nerve head) or large drusen in 1 eye and advanced AMD in the fellow eye.

Participants were randomized to receive lutein (10 mg) and zeaxanthin (2 mg), DHA (350 mg) + EPA (650 mg), lutein + zeaxanthin and DHA + EPA, or placebo. All participants were also asked to take the original AREDS formulation or accept a secondary randomization to 4 variations of the AREDS formulation, including elimination of beta carotene, lowering of zinc dose, or both.

A total of 1,608 participants had experienced at least 1 advanced AMD event by the end of the study (1,940 events in 6,891 study eyes). The researchers found that the probabilities of progression to advanced AMD by 5 years were 31 percent for placebo, 29 percent for lutein + zeaxanthin, 31 percent for DHA + EPA, and 30 percent for lutein + zeaxanthin and DHA + EPA. In the primary analyses, comparisons with placebo demonstrated no statistically significant reductions in progression to advanced AMD.

“There was no apparent effect of beta carotene elimination or lower-dose zinc on progression to advanced AMD. More lung cancers were noted in the beta carotene vs. no beta carotene group (23 [2 percent] vs. 11 [0.9 percent]), mostly in former smokers,” the authors write.

None of the nutrients affected development of moderate or worse vision loss.

The researchers add that “these null results may be attributable to the true lack of efficacy. Other factors to consider include inadequate dose, inadequate duration of treatment, or both.”

“Based on apparent risks of beta carotene and possible benefits that are only evident within exploratory subgroup analyses, lutein + zeaxanthin requires further investigation for potential inclusion in the AREDS supplements.”

(doi:10.1001/jama.2013.4997; 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 6 p.m. CT Sunday, May 5 at this link.

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EMBARGOED FOR EARLY RELEASE: 8:15 A.M. (CT) SUNDAY, MAY 5, 2013

Media Advisory: To contact Barbara Schmidt, M.D., M.Sc., call Alison Fraser at 267-426-6054 or email FraserA1@email.chop.edu. To contact editorial co-author Eduardo Bancalari, M.D., call Lisa Worley at 305-243-5184 or email LWorley2@med.miami.edu.

CHICAGO – In a randomized trial performed to help resolve the uncertainty about the optimal oxygen saturation therapy in extremely preterm infants, researchers found that targeting saturations of 85 percent to 89 percent compared with 91 percent to 95 percent had no significant effect on the rate of death or disability at 18 months, according to a study published by JAMA. The study is being released early online to coincide with its presentation at the Pediatric Academic Societies annual meeting.

“Extremely preterm infants are monitored with pulse oximeters for several weeks after birth because they may require supplemental oxygen intermittently or continuously. The goal of oxygen therapy is to deliver sufficient oxygen to the tissues while minimizing oxygen toxicity and oxidative stress. It remains uncertain what values of arterial oxygen saturations achieve this balance in immature infants, who are especially vulnerable to the harmful effects of oxygen,” according to background information in the article.

Barbara Schmidt, M.D., M.Sc., of the Children’s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, and colleagues conducted a study to compare the effects of targeting lower or higher arterial oxygen saturations in extremely preterm infants on the rate of death or disability. The randomized trial, conducted in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel, included 1,201 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days, who were enrolled within 24 hours after birth between December 2006 and August 2010. Follow-up assessments began in October 2008 and ended in August 2012.

Study participants were monitored until postmenstrual ages (the time elapsed between the first day of the mother’s last menstrual period and birth [gestational age] plus the time elapsed after birth [chronological age]) of 36 to 40 weeks with pulse oximeters that displayed saturations of either 3 percent above or below the true values. Caregivers adjusted the concentration of oxygen to achieve saturations between 88 percent and 92 percent, which produced 2 treatment groups with true target saturations of 85 percent to 89 percent (n=602) or 91 percent to 95 percent (n=599). Alarms were triggered when displayed saturations decreased to 86 percent or increased to 94 percent. The primary outcome was a composite of death, gross motor disability, cognitive or language delay, severe hearing loss, or bilateral blindness at a corrected age of 18 months. Secondary outcomes included retinopathy of prematurity and brain injury.

The researchers found that targeting lower compared with higher oxygen saturations had no significant effect on the rate of death or disability at 18 months. “Of the 578 infants with data for this outcome who were assigned to the lower target range, 298 (51.6 percent) died or survived with disability compared with 283 of the 569 infants (49.7 percent) assigned to the higher target range,” the authors write. “Of the 585 infants with known vital status at 18 months in the lower saturation target group, 97 (16.6 percent) had died compared with 88 of 577 (15.3 percent) in the higher saturation target group.”

Targeting lower compared with higher saturations reduced the average postmenstrual age at last use of oxygen therapy, but had no significant effect on any other outcomes, including the rate of severe retinopathy of prematurity.

“Clinicians who try to translate the disparate results of the recent oxygen saturation targeting trials into their practice may find it prudent to target saturations between 85 percent and 95 percent while strictly enforcing alarm limits of 85 percent at all times, and of 95 percent during times of oxygen therapy. Our findings do not support recommendations that targeting saturations in the upper 80 percent range should be avoided. Because it is very difficult to maintain infants in a tight saturation target range, such recommendations may lead to increased tolerance of saturations above 95 percent and an increased risk of severe retinopathy. Although no longer a major cause of bilateral blindness, severe retinopathy remains a marker of serious childhood disabilities,” the authors conclude.

(doi:10.1001/jama.2013.5555; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Funded exclusively by the Canadian Institutes of Health Research. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Oxygenation Targets and Outcomes in Premature Infants

In an accompanying editorial, Eduardo Bancalari, M.D., and Nelson Claure, M.Sc., Ph.D., of the University of Miami Miller School of Medicine, comment on the findings of this and other studies that have examined this issue.

“Oxygen therapy continues to present neonatal clinicians with a difficult conundrum where efforts to reduce complications associated with hyperoxemia in premature infants may affect their survival. How the results of these trials should be translated into clinical practice is still controversial. If the long-term outcomes are not affected by the different saturation targets, should the shorter-term outcomes of death, severe retinopathy of prematurity, and bronchopulmonary dysplasia be used to formulate a recommendation? After all, no other outcome is as important as survival. Until the remaining questions raised by these studies are answered by the combined meta-analysis or new evidence becomes available, minimizing extreme oxygenation levels by targeting saturations between 90 and 95 percent appears to be a reasonable approach.”

(doi:10.1001/jama.2013.5831; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 11:15 A.M. (CT) SATURDAY, MAY 4, 2013

Media Advisory: To contact corresponding author Bethany J. Foster, M.D., M.Sc., call Julie Robert at 514-934-1934 ext. 71381; or email julie.robert@muhc.mcgill.ca.

CHICAGO – In a study that included more than 20,000 patients, there was a significant decrease in the United States in mortality rates over time among children and adolescents initiating end-stage kidney disease treatment with dialysis between 1990 and 2010, according to a study in the May 8 issue of JAMA. The study is being released early online to coincide with its presentation at the Pediatric Academic Societies annual meeting.

“Individuals with end-stage kidney disease (ESKD) face a significantly shortened life expectancy. In no group of ESKD patients is the loss of potential years of life larger than in children and adolescents. Although transplant remains the treatment of choice to maximize survival, growth, and development, 75 percent of children with ESKD require treatment with dialysis prior to receiving a kidney transplant. Dialysis is therefore a life-saving therapy for children with ESKD while they await transplant. Nevertheless, all-cause mortality rates in children receiving maintenance dialysis are at least 30 times higher than the general pediatric population, with even higher relative risks in very young children,” the authors write. “There have been substantial improvements in the care of children with ESKD between 1990 and 2010. However, to our knowledge, it is not known if mortality has changed over time in the United States, particularly in recent years.”

Mark M. Mitsnefes, M.D., M.Sc., of Cincinnati Children’s Hospital Medical Center, and colleagues conducted a study to determine if all-cause, cardiovascular, and infection-related mortality rates have changed between 1990 and 2010 among patients younger than 21 years of age with ESKD initially treated with dialysis and if changes in mortality rates over time differed by age at treatment initiation. The researchers used data from the United States Renal Data System. Children with a prior kidney transplant were excluded.

The researchers identified 23,401 children and adolescents who met study criteria. Crude mortality rates during dialysis treatment were higher among children younger than 5 years at the start of dialysis compared with those who were 5 years and older. The authors found that the all-cause mortality risk decreased progressively over calendar time for both those younger than 5 years and those 5 years and older at initiation. There was also a decrease over calendar time for cardiovascular and infection-related mortality risk among children younger than 5 years at initiation and among those 5 years and older.

“Numerous factors may have contributed to the observed reductions in mortality risk over time. Improved pre-dialysis care, advances in dialysis technology, and greater experience of clinicians may each have played a role,” the authors write.

“Almost all children initiating ESKD treatment are considered eligible for transplant. However, most will require dialysis during their lifetime, either before transplant or after allograft loss. In the United States, there was a significant decrease in mortality rates over time among children and adolescents initiating ESKD treatment with dialysis between 1990 and 2010. Further research is needed to determine the specific factors responsible for this decrease.”

(JAMA. 2013;309(18):1921-1929; 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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