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

Media Advisory: To contact Helmut Oettle, M.D., Ph.D., email Helmut.Oettle@charite.de.

Among patients with pancreatic cancer who had surgery for removal of the cancer, treatment with the drug gemcitabine for 6 months resulted in increased overall survival as well as disease-free survival, compared with observation alone, according to a study in the October 9 issue of JAMA.

“Pancreatic cancer is a disease with a poor prognosis, mainly because of the inability to detect the tumor at an early stage, its high potential for early dissemination, and its relatively poor sensitivity to chemotherapy or radiation therapy,” according to background information in the article. Even after complete removal of the tumor, the vast majority of patients relapse within 2 years, leading to a 5-year survival rate of less than 25 percent. No consensus has been reached on a standard treatment approach for additional therapy. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival after surgery has not previously been demonstrated.

Helmut Oettle, M.D., Ph.D., of the Charite-Universitatsmedizin Berlin, Germany, and colleagues conducted follow-up of a randomized trial that previously reported improvement in disease-free survival with adjuvant (in addition to surgery) gemcitabine therapy to determine if this treatment improved overall survival. Patients with macroscopically (observation made by the unaided eye) completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria; follow-up ended in September 2012. Patients were randomly assigned to either adjuvant gemcitabine treatment for 6 months or to observation alone.

A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0 percent) had relapsed. The median (midpoint) follow-up time was 136 months (11.3 years). The median disease-free survival was 13.4 months in the treatment group compared with 6.7 months in the observation group.

By the end of the follow-up period, 316 patients (89.3 percent) had died and 38 patients were still alive, 23 in the treatment group and 15 in the observation group. The researchers found a statistically significant difference in overall survival between the study groups, with a median of 22.8 months in the gemcitabine group compared with 20.2 months in the observation group. There was also a statistically significant absolute 10.3 percent improvement in the 5-year overall survival rate (20.7 percent vs. 10.4 percent) and a 4.5 percent improvement in the 10-year survival rate (12.2 percent vs. 7.7 percent), compared with observation alone.

“[These] data show that among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation resulted in increased overall survival as well as disease-free survival. These findings support the use of gemcitabine in this setting,” the authors conclude.

(doi:10.l001/jama.2013.279201; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This trial was supported in part by a grant from Lilly Germany. The study was further supported by the German Cancer Society and promoted by a research grant from the Charite-Universitatsmedizin Berlin. 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: 10 A.M. (CT) MONDAY, OCTOBER 7, 2013

Media Advisory: To contact Mary T. Hawn, M.D., M.P.H., call Tyler Greer at 205-934-2041 or email tgreer@uab.edu. To contact editorial co-author Emmanouil S. Brilakis, M.D., Ph.D., call Lisa Warshaw at 214-648-3404 or email Lisa.Warshaw@utsouthwestern.edu.

Emergency surgery and advanced cardiac disease are risk factors for major adverse cardiac events after noncardiac surgery in patients with recent coronary stent implantation, according to a study published by JAMA. The study is being released early online to coincide with its presentation at the American College of Surgeons 2013 Annual Clinical Congress.

“Approximately 600,000 percutaneous coronary stent procedures are performed annually in the United States. Twelve to 23 percent of these patients undergo noncardiac surgery within 2 years of coronary stent placement,” according to background information in the article. Noncardiac surgery after recent coronary stent placement is associated with increased risk of adverse cardiac events. Delaying necessary noncardiac surgery can pose a clinical dilemma for a large number of patients. “Guidelines recommend delaying noncardiac surgery in patients after coronary stent procedures for 1 year after drug-eluting stents (DES) and for 6 weeks after bare metal stents (BMS). The evidence underlying these recommendations is limited and conflicting.”

Mary T. Hawn, M.D., M.P.H., of the University of Alabama at Birmingham, and colleagues conducted a study to determine risk factors for adverse cardiac events in patients undergoing noncardiac surgery within 24 months of coronary stent implantation. The study included 41,989 Veterans Affairs (VA) and non-VA operations performed within 2 years of a coronary stent implantation between 2000 and 2010. The researchers examined the association between timing of surgery and stent type and major adverse cardiac events (MACE). The primary outcome for the study was a composite 30-day MACE rate of all-cause mortality, heart attack, and cardiac revascularization.

Within 24 months of 124,844 coronary stent implantations (47.6 percent DES, 52.4 percent BMS), 28,029 patients (22.5 percent) underwent noncardiac operations resulting in 1,980 MACE (4.7 percent). The time from stent placement to surgery was associated with MACE for surgery in the first 6 months after the stent procedure, but not for surgery more than 6 months after the stent procedure. The 3 factors most strongly associated with MACE were nonelective surgical admission, having a heart attack in the 6 months preceding surgery, and a revised cardiac risk index score (comprising independent variables that predict an increased risk for cardiac complications) greater than 2.

MACE rate was 5.1 percent for BMS and 4.3 percent for DES. Stent type was not associated with MACE for surgeries more than 6 months after stent placement.

A case-control analysis of 284 matched pairs of patients found no association between cessation of antiplatelet therapy and MACE.

The authors note that there are several considerations that need to be given to these findings, including that the study sample comprised primarily older male patients, thus limiting the generalizability to women or younger men; the clinical factors that influenced stent selection were largely unavailable so they could not be accounted for in the models, and, accordingly, the results could be confounded by those factors; and many patients underwent more than 1 percutaneous coronary intervention (procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries) procedure during the dates of the study, which could result in misclassification bias for time from stent placement to surgery.

(doi:10.l001/jama.2013.278787; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study is supported by a VA Health Services Research & Development grant. In addition, Drs. Maddox and Richman are supported by VA Career Development Awards. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Itani reported having received research support from Merck and Cubist. No other disclosures were reported.

Editorial: Patient With Coronary Stents Needs Surgery – What to Do?

“How should the findings by Hawn et al and other recent studies influence the approach for patients who need surgery after stents?” asks Emmanouil S. Brilakis, M.D., Ph.D., and Subhash Banerjee, M.D., of the VA North Texas Health Care System, Dallas, in an accompanying editorial.

“The approach for patients with BMS should not change; these patients usually can undergo surgery within 6 weeks after coronary stent implantation with very low risk of stent thrombosis. For patients with DES, surgery performed at least 6 months after DES implantation appears to carry low risk for stent thrombosis, especially with contemporary, second-generation DES, which have more biocompatible, durable polymer coatings. Hence, nonurgent operations should be postponed until 6 months after stent implantation.”

(doi:10.l001/jama.2013.279123; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (CT) MONDAY, OCTOBER 7, 2013

Media Advisory: To contact corresponding author Kelly K. Hunt, M.D., call Laura Sussman at 713-745-2457 or email lsussman@mdanderson.org. To contact editorial co-author Monica Morrow, M.D., call Courtney A. DeNicola at 646-227-3633 or email Denicolc@mskcc.org.

Judy C. Boughey, M.D., Kelly K. Hunt, M.D., and colleagues for the Alliance for Clinical Trials in Oncology conducted a study to determine the false-negative rate of sentinel lymph node surgery in patients with node-positive breast cancer receiving chemotherapy before surgery. A false-negative is occurrence of negative test results in subjects known to have a disease for which an individual is being tested.  The study, published by JAMA, is being released early online to coincide with its presentation at the American College of Surgeons 2013 Annual Clinical Congress.

Axillary (the armpit region) lymph node status is an important prognostic factor in breast cancer and is used to guide local, regional, and systemic treatment decisions. Accurate determination of axillary involvement after chemotherapy is important; however, removing all axillary nodes to assess for residual nodal disease exposes many patients to the potential side effects of surgery and, potentially, only a subset will benefit. To avoid the complications associated with axillary lymph node dissection (ALND), it is preferable to identify nodal disease with the less invasive sentinel lymph node (SLN) surgical procedure, which results in fewer side effects, according to background information in the article.

The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial enrolled women from 136 institutions from July 2009 to June 2011 who had various stages of breast cancer and received neoadjuvant (before surgery) chemotherapy. Following chemotherapy, patients underwent both SLN surgery and ALND. The primary end point for the study was the false-negative rate of SLN surgery after chemotherapy in women who presented with cN1 disease (disease in movable axillary lymph nodes). The researchers evaluated the likelihood that the false-negative rate in patients with 2 or more SLNs examined was greater than 10 percent, the rate expected for women undergoing SLN surgery who present with clinical node-negative (cNO) disease.

Seven hundred fifty-six women were enrolled in the study. Of 663 evaluable patients with cN1 disease, 649 underwent chemotherapy followed by both SLN surgery and ALND. The researchers found that the false-negative rate was 12.6 percent with SLN surgery and exceeded the prespecified threshold of 10 percent. “Given this [10 percent] threshold, changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND in this patient population.”

(doi:10.l001/jama.2013.278932; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This work was supported by a grant from the National Cancer Institute awarded to the American College of Surgeons Oncology Group. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Sentinel Node Biopsy After Neoadjuvant Chemotherapy

“Decisions about using systemic therapy after neoadjuvant therapy are not dependent upon identifying residual cancer in lymph nodes when all the planned chemotherapy is given preoperatively to maximize the cancer response,” write Monica Morrow, M.D., and Chau T. Dang, M.D., of Memorial Sloan-Kettering Cancer Center, New York, in an accompanying editorial.

“However, accurate detection of residual lymph node cancer may be important in prospective trials of novel agents in which post–neoadjuvant treatment decisions, including possible research protocol participation, may hinge on the detection of residual disease. When considering how much information can be extrapolated from an initial SLN biopsy, it is important to recognize that patients with residual cancer following neoadjuvant therapy have some level of resistance to systemic therapy. These patients might require more aggressive local therapy such as complete ALND or radiation therapy to the axilla. Because there is no information regarding long-term local cancer control or survival for patients initially presenting with clinically node-positive disease who receive neoadjuvant therapy but have a 20 percent to 30 percent rate of residual cancer in the axilla following SLN biopsy, we do not believe that SLN biopsy, regardless of the number of SLNs removed, can be considered standard management for these patients.”

(doi:10.l001/jama.2013.7844; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Dang reports receiving grant funding from Genentech. No other disclosures were reported.

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (CT) MONDAY, OCTOBER 7, 2013

Media Advisory: To contact Karl Y. Bilimoria, M.D., M.S., call Megan McCann at 312-926-5900 or email memccann@nmh.org. To contact editorial author Edward H. Livingston, M.D., call Jim Michalski at 312-464-5785 or email jim.michalski@jamanetwork.org.

A new study published by JAMA questions using the rate of postoperative blood clots as a hospital quality measure. The study is being released early online to coincide with the American College of Surgeons 2013 Annual Clinical Congress.

The study examined whether surveillance bias (i.e., the greater the intensity of a search for a condition the greater likelihood it will be found) influences the reported rate of venous thromboembolism (VTE; blood clot). Venous thromboembolism, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common postoperative complication that remains a leading potentially preventable cause of postoperative illness and death. The Agency for Healthcare Research and Quality developed a risk-adjusted postoperative VTE rate measure, Patient Safety Indicator 12 (PSI-12), that has been incorporated into numerous quality improvement programs and public reporting initiatives.

“However, measuring VTE rates may be flawed because of surveillance bias, in which variation in outcomes reflects variation in screening and detection, or ‘the more you look, the more you find’ phenomenon. This can occur in a number of ways: hospitals may use screening protocols, in which asymptomatic patients routinely undergo VTE imaging studies on a certain postoperative day, or clinicians have a lower threshold to order a VTE imaging study for patients with minimal or equivocal signs or symptoms (e.g., any leg swelling prompts a venous duplex [an imaging procedure]). Hospitals that are more vigilant and perform more imaging studies for VTE may identify more VTE events, thus resulting in paradoxically worse performance on the VTE outcome measure,” according to background information in the article.

To examine the effect of surveillance bias on the validity of VTE as a quality measure, Karl Y. Bilimoria, M.D., M.S., of Northwestern University and Northwestern Memorial Hospital, Chicago, and colleagues conducted a study that merged 2010 Hospital Compare and American Hospital Association data from 2,838 hospitals. Next, 2009-2010 Medicare claims data for 954,926 surgical patient discharges from 2,786 hospitals that were undergoing 1 of 11 major operations were used to calculate VTE imaging and VTE event rates.

Instead of finding the expected relationship between adherence to VTE prevention and lower VTE rates, the researchers found that VTE prevention rates were positively correlated with VTE event rates. “A paradoxical relationship was also found between a measure of hospital structural characteristics reflecting quality [hospital characteristics that examine health care quality and which reflect a hospital’s resources and focus on programs intended to provide higher-quality care] and VTE event rates: hospitals with higher structural quality scores had better VTE [prevention] adherence rates, but they had unexpectedly higher risk-adjusted VTE rates. Most important, hospital VTE rates were associated with the intensity of detecting VTE with imaging studies.”

Hospitals in the lowest imaging rate quartile diagnosed 5.0 VTEs per 1,000 discharges, whereas the highest imaging rate quartile hospitals found 13.5 VTEs per 1,000 discharges.

“Our study calls into question the merit of the PSI-12 VTE outcome measure as a quality measure and its use in public reporting and performance-based payments. Hospitals reported to have the highest risk-adjusted VTE rates may in fact be providing vigilant care by ordering imaging studies to ensure that VTE events are not missed. Patients selecting hospitals according to publicly available metrics may be misled by currently reported VTE performance. The measure could be counterproductive if a hospital performs poorly on the VTE outcome metric, expends efforts to improve VTE prophylaxis resulting in increased awareness and vigilance in looking for VTE, and then finds more VTEs and becomes an even worse performer on the VTE measure,” the authors write.

(doi:10.l001/jama.2013.280048; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by AHRQ and a Center Development Award from Northwestern University and Northwestern Memorial Hospital to Dr. Bilimoria. Dr. Ju is supported by a grant from the National Institutes of Health. Dr. Haut is supported by a career development award from AHRQ. 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 10 a.m. CT Monday, October 7 at this link.

Editorial: Postoperative Venous Thromboembolic Disease – Prevention, Public Reporting, and Patient Protection

“The study by Bilimoria et al demonstrates that VTE rates appearing on the Hospital Compare website reflect how aggressively clinicians look for VTE but probably are not directly related to quality of care,” writes Edward H. Livingston, M.D., Deputy Editor, JAMA, Chicago, in an accompanying editorial.

“In fact, because some physicians more aggressively look for complications, they find more and appear to have worse outcomes on the Hospital Compare website. Less obvious in the data from Bilimoria et al is that the very high compliance rate with VTE prophylaxis might result from many patients receiving treatments from which they are not likely to benefit. This is because current process measures were based on older guidelines that overestimated the benefits of VTE prophylaxis.”

“Public reporting of VTE rates should be reconsidered or curtailed because few hospitals have sufficient numbers of patients to show statistically significant effects of prophylactic measures on VTE rates. Improving the quality of care and safety for surgical patients will require more than simply public reporting of various process and outcome measures. The surgical and medical communities must make concerted efforts to follow the best available evidence and to conduct rigorous clinical trials to find the best ways to protect patients against the ‘unpredictable, treacherous and dramatically tragic’ occurrence of postoperative VTE.”

(doi:10.l001/jama.2013.280049; 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: 6:15 P.M. (CT) FRIDAY, OCTOBER 4, 2013

Media Advisory: To contact Anthony D. Harris, M.D., M.P.H., call Karen Lancaster at 410-328-8919 or email klancaster@umm.edu. To contact editorial author Preeti N. Malani, M.D., M.S.J., call Shantell Kirkendoll at 734-764-2220 or email smkirk@med.umich.edu.

The wearing of gloves and gowns by health care workers for all intensive care unit (ICU) patient contact did not reduce the rate of acquisition of a combination of the bacteria methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), although there was a lower risk of MRSA acquisition alone, according to a study published online by JAMA. The study is being released early to coincide with its presentation at IDWeek 2013.

Antibiotic-resistance is associated with considerable illness, death, and costs. MRSA and VRE are primary causes of health care-associated infections. “The estimated cost of antibiotic-resistance in the United States is more than $4 billion per year. Health care-associated infections are the most common complication of hospital care, affecting an estimated 1 in every 20 inpatients. Numerous studies have shown that health care workers acquire bacteria on their hands and their clothing by touching patients,” according to background information in the article.

The Centers for Disease Control and Prevention recommend use of contact precautions (wearing gloves and gowns) when caring for patients colonized or infected with antibiotic-resistant bacteria. However, colonization with MRSA, VRE, or other antibiotic-resistant bacteria often is not detected and contact precautions, therefore, are not applied. It has not been known whether wearing gloves and gowns for all patient contact, not just for patients with known colonization, decreases acquisition of antibiotic-resistant bacteria in the ICU.

Anthony D. Harris, M.D., M.P.H., of the University of Maryland School of Medicine, Baltimore, and colleagues assessed whether wearing gloves and gowns for all patient contact in the ICU compared with the use of contact precautions for patients with known antibiotic-resistant bacteria reduces acquisition rates of MRSA and VRE. The randomized trial was conducted in 20 medical and surgical ICUs in 20 U.S. hospitals from January 2012 to October 2012. In the intervention ICUs, all health care workers were required to wear gloves and gowns for all patient contact and when entering any patient room. The primary outcome was acquisition of MRSA or VRE based on surveillance cultures (92,241 swabs) collected on admission and ICU discharge from 26,180 patients.

The researchers found that there was a decrease in both the intervention and control ICUs in the composite rate of MRSA or VRE acquisition over the study periods, but the difference in change was not statistically significant. There was a borderline statistically significant reduction in MRSA that was greater in the intervention group.

The intervention did not reduce VRE acquisition, but it did reduce MRSA acquisition, the authors write. “Better hand hygiene compliance on room exit occurred in the intervention ICUs. The intervention led to fewer health care worker-patient visits and did not increase the frequency of adverse events.”

(doi:10.l001/jama.2013.277815; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Preventing Infections in the ICU – One Size Does Not Fit All

“Although the results of Harris et al failed to demonstrate an overall benefit of universal use of gloves and gowns to reduce acquisition of MRSA or VRE, this approach may be worth considering in some high-risk settings such as surgical ICUs wherein MRSA transmission is high among patients with newly implanted medical devices. If implemented, gloving and gowning should be just part of an overall strategy that includes efforts to optimize hand hygiene and prudent use of antimicrobials,” writes Preeti N. Malani, M.D., M.S.J., of the University of Michigan Health System, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, in an accompanying editorial.

“Although it is appealing to believe there is a simple approach to what should and should not be done to prevent infection in the ICU, best practices are more nuanced and unfortunately, one size does not fit all. The final approach must be adapted to fit the epidemiology of specific ICUs and should also consider the type of resources available. The study by Harris et al serves as a poignant reminder that many questions remain for what constitutes best practice in the care of critically ill patients. Ongoing investment in these sorts of resource intensive trials is essential for continued progress.”

(doi:10.l001/jama.2013.277816; 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, OCTOBER 1, 2013

Media Advisory: To contact Mads Wissenberg, M.D., email mads.wissenberg.joergensen@regionh.dk.

In Denmark between 2001 and 2010 there was an increase in bystander cardiopulmonary resuscitation (CPR) that was associated with an increase in survival following out-of-hospital cardiac arrest, according to a study in the October 2 issue of JAMA.

Out-of-hospital cardiac arrest affects approximately 300,000 individuals in North America annually. “Despite efforts to improve prognosis, survival remains low, with aggregated survival-to-discharge rates less than 8 percent.  In many cases, time from recognition of cardiac arrest to the arrival of emergency medical services (EMS) is long, leaving bystanders in a critical position to potentially influence patient prognosis through intervention before EMS arrival. However, only a minority of cardiac arrests receive bystander CPR,” according to background information in the article.

A low frequency of bystander CPR (<20 percent) and low 30-day survival (<6 percent) were identified nearly 10 years ago in Denmark, which led to several national initiatives to strengthen bystander resuscitation attempts and advanced care. Despite these nationwide efforts, it has been unknown whether there have been changes in resuscitation attempts by bystanders and improvements in survival.

To examine this question, Mads Wissenberg, M.D., of Copenhagen University Hospital Gentofte, Hellerup, Denmark, and colleagues analyzed trends in pre-hospital factors directly related to cardiac arrest as well as trends in survival during the past 10 years. The study included 19,468 patients with out-of-hospital cardiac arrest for whom resuscitation was attempted. The median (midpoint) age of patients was 72 years; 67 percent were men.

Throughout the study period, there was an increase in the proportion of patients receiving bystander CPR (21.1 percent to 44.9 percent). The increase in proportion of people defibrillated with an automatic defibrillator by a bystander was small (1.1 percent to 2.2 percent). “The large temporal increase in rates of bystander CPR observed in our study is most likely attributable to the overall increasing level of attention to resuscitation by bystanders in Denmark, including an increase in both mandatory and voluntary first aid training, with an estimate of more than 15 percent of the Danish population having taken CPR courses between 2008 and 2010.”

During the study period, there was an increase in the proportion of patients alive on arrival at the hospital (7.9 percent to 21.8 percent), as well as an increase in 30-day (3.5 percent to 10.8 percent) and 1-year (2.9 percent to 10.2 percent) survival. Bystander CPR was positively associated with 30-day survival.

“Our nationwide study had 4 major findings: rates of bystander CPR increased substantially; survival rates at 30 days and l year more than tripled; the number of survivors per 100,000 persons more than doubled; and rates of defibrillation by bystanders remained low,” the authors write.

“Because of the co-occurrence of other initiatives to improve outcome after cardiac arrest, a causal relationship between bystander CPR and survival remains uncertain.”

(doi:10.l001/jama.2013.278483; 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, OCTOBER 1, 2013

Investing in Evidence-Based Care for the Severely Mentally Ill

In a Viewpoint, Mark Olfson, M.D., M.P.H., of the New York State Psychiatric Institute, New York, and colleagues discuss the potential implications of giving 4 million previously uninsured people with severe mental disorders health insurance when the Affordable Care Act (ACA) is fully implemented in 2019.

“Expansion in health insurance coverage through the ACA [will] confer new mental health benefits for patients [and will] impose new demands on the provision of mental health services. To meet these challenges, health and mental health policy makers will need to focus on bringing greater coherence, service integration, and evidence-based care to a poorly functioning system of mental health care. Ex­panding access to evidence-based treatments and increasing their use within general medical and specialty mental health settings offers a tremendous opportunity to improve the lives of patients with severe mental disorders. The good news is that the ACA has several provisions that can support proven, evidence-based care strategies and that improvements can be achieved in the accessibility, effectiveness, and quality of care for people with serious mental illnesses, even in the face of a significant growth in demand. There are significant challenges but also significant opportunities. The clinical community cannot fail to seize them.”

(doi:10.l001/jama.2013.278065; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Mark Olfson, M.D., M.P.H., call Dacia Morris at 212-543-5421 or email morrisd@pi.cpmc.columbia.edu.

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 Pricing for Orphan Drugs – Will the Market Bear What Society Cannot?

Brian P. O’Sullivan, M.D., of the University of Massachusetts Medical School, Worcester, and colleagues examine the issue of drug pricing for rare diseases and personalized medicine based on individual and disease-specific genetic information, citing costs that can range from more than $100,000 per year to more than $300,000 per year.

“There are many partners in the development of a drug, including individuals who risk their own health as research participants, physicians who collaborate in clinical trials on behalf of their patients, and the scientific community that develops the basic mechanistic understanding of a disease. Patients, physicians, and other stakeholders should be involved in the pricing process. A model of reduced profitability, particularly for lifelong therapies, is ethically responsible and institutionally plausible but will require pharmaceutical companies to develop new models and educate investors about the long-term advantage of regaining the trust of the public. In exchange for greater transparency with respect to price structuring, companies will promote improved health, consumer confidence, and long-term profitability.”

(doi:10.l001/jama.2013.278129; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Brian P. O’Sullivan, M.D., call Mark Shelton at 508-856-2000 or email UMMSCommunications@umassmed.edu.

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 How the Pioneer ACO Model Needs to Change – Lessons From Its Best-Performing ACO

On July 16, 2013, the Center for Medicare & Medicaid Innovation released results from the first performance year of its Pioneer Accountable Care Organization (ACO) Model. The Pioneer program is the first ACO pilot administered by the government and the first to report results, which indicated that each of the 32 Medicare Pioneer ACOs improved quality and patient satisfaction, and the overall Pioneer program generated a total savings of $87.6 million.

“This important experiment may offer lessons for how to avoid Medicare’s predicted fiscal crisis. Even short of that, however, the findings demonstrate that, for the experiment to ultimately succeed, value-based payment and patient incentives to reward clinicians and health care organizations that offer more real value to patients must spread rapidly to other payers. Otherwise, the very delivery systems that are improving cost and quality may drop out of these important experiments,” write John Toussaint, M.D., of Thedacare Center for Healthcare Value, Appleton, Wisc., and colleagues.

“To expect health system leaders to take the necessary risks, strong federal-state and public-private partnerships will be needed to coordinate all payers in each region and, thereby, ensure that high-value care is rewarded consistently. CMS can play a key leadership role by more actively catalyzing multipayer ACOs now, but CMS cannot force private insurers to participate in the crucial payment reforms. It will take leadership from the U.S. health insurance industry, in partnership with CMS and health systems, to achieve true reform. Today there is a unique opportunity to correct the excessive growth in health care spending. The nation should not squander that chance.”

(doi:10.l001/jama.2013.279149; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact John Toussaint, M.D., call Jane Fazer at 920-659-7466 or email jfazer@createvalue.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, OCTOBER 1, 2013

Media Advisory: To contact Marsha A. Raebel, Pharm.D., call Amy Whited at 303-344-7518 or email Amy.L.Whited@kp.org. To contact editorial author Daniel P. Alford, M.D., M.P.H., call Gina DiGravio at 617-638-8480 or email gina.digravio@bmc.org.

In a group of patients who took chronic opioids for noncancer pain and who underwent bariatric surgery, there was greater chronic use of opioids after surgery compared with before, findings that suggest the need for proactive management of chronic pain in these patients after surgery, according to a study in the October 2 issue of JAMA.

“Bariatric surgery is used to treat obesity, as well as its comorbid conditions such as cardiovascular and metabolic diseases and chronic pain. Bariatric surgery-related weight loss is associated with improvements in osteoarthritis-associated knee pain and function and decreased back pain in observational studies,” according to background information in the article. “Because some pain syndromes are related to obesity, it is reasonable to assume that weight loss may be associated with better pain control.” It is not known if opioid use for chronic pain in obese individuals undergoing bariatric surgery is reduced.

Marsha A. Raebel, Pharm.D., of Kaiser Permanente Colorado, Denver, and colleagues conducted a study to examine opioid use following bariatric surgery in patients using opioids chronically for pain control prior to their surgery. The study included 11,719 individuals 21 years of age and older who had bariatric surgery between 2005 and 2009, and who were assessed 1 year before and after surgery, with latest follow-up by December 31, 2010.

In the year before bariatric surgery, 56 percent of patients had no opioid use, 36 percent had some opioid use, and 8 percent had chronic opioid use. Among pre-surgery chronic users, 77 percent continued chronic opioid use after surgery. Relative to the year before surgery, the amount of opioid use by patients who were chronic opioid users before surgery increased by 13 percent the first year after surgery and by 18 percent across 3 post-surgery years.

For the group with chronic opiate use prior to surgery, change in morphine equivalents before vs. after surgery did not differ between individuals who lost more than 50 percent of their excess body mass index vs. those who lost 50 percent or less.

Neither preoperative depression nor chronic pain diagnoses influenced changes in preoperative to postoperative chronic opioid use.

“We anticipated [that] weight loss after bariatric surgery would result in reduced pain and opioid use among patients with chronic pain. However, patients with and without preoperative chronic pain, depression diagnoses, or both had similar increases in postoperative chronic opioid use after surgery as those without chronic pain or depression. One possible explanation is that some patients likely had pain unresponsive to weight loss but potentially responsive to opioids,” the authors write.

“These findings suggest the need for better pain management in these patients following surgery.”

(doi:10.l001/jama.2013.278344; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Weighing In on Opioids for Chronic Pain – The Barriers to Change

In an accompanying editorial, Daniel P. Alford, M.D., M.P.H., of Boston Medical Center, discusses the importance of clinicians reducing or eliminating opioid use among patients when warranted.

“The safe and appropriate prescribing of opioids for chronic pain has become an important national priority. Although core competencies for pain management are being developed, knowing when and how to continue, change, or discontinue opioid therapy must be included in all clinician education efforts. Although Raebel et al are correct in reporting that better pain management strategies are needed, they also may have uncovered an equally important problem—the need to know if, when, and how to safely and effectively taper or discontinue opioid therapy for patients with chronic pain.”

(doi:10.l001/jama.2013.278587; 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, OCTOBER 1, 2013

Media Advisory: To contact JoAnn E. Manson, M.D., Dr.P.H., call Tom Langford at 617-534-1605 or email tlangford@partners.org. To contact Elizabeth G. Nabel, M.D., call Lori J. Schroth at 617-534-1604 or email ljschroth@partners.org.

Extended follow-up of the two Women’s Health Initiative hormone therapy trials does not support use of hormones for chronic disease prevention, although the treatment may be appropriate for menopausal symptom management in some women, according to a study in the October 2 issue of JAMA.

The hormone therapy trials of the Women’s Health Initiative (WHI) were stopped after investigators found that the health risks outweighed the benefits. Menopausal hormone therapy continues in clinical use, but questions remain regarding its risks and benefits over the long-term for chronic disease prevention, according to background information in the article.

JoAnn E. Manson, M.D., Dr.P.H., of Brigham and Women’s Hospital, Boston, and colleagues provide a comprehensive, integrated overview of findings from the two WHI hormone therapy trials with extended post-intervention follow-up and stratification by age and other important variables. The study included 27,347 postmenopausal women, ages 50 through 79 years, who were enrolled at 40 U.S. centers in 1993. Women with an intact uterus received conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) (n = 8,506) or placebo (n = 8,102). Women with prior hysterectomy received CEE alone (n = 5,310) or placebo (n = 5,429). The intervention lasted a median [midpoint] of 5.6 years in the CEE plus MPA trial, and 7.2 years in the CEE alone trial, with 6-8 additional years of follow-up until September 30, 2010.

The researchers found that overall, the risks of CEE+MPA during intervention outweighed the benefits. Risks were increased for coronary heart disease, breast cancer, stroke, pulmonary embolism, dementia (in women 65 years of age and older), gallbladder disease, and urinary incontinence. Benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during follow-up.

For CEE in women with prior hysterectomy, the benefits and risks during the intervention phase were more balanced, with increased risks of stroke and venous thrombosis, reduced risk of hip and total fractures, and a nonsignificant reduction in breast cancer. Post-intervention with CEE, a significant decrease in breast cancer emerged and most other outcomes were neutral. For CEE alone, younger women (age 50-59 years) had more favorable results for all-cause death and heart attack.

Neither regimen affected all-cause mortality.

“In summary, current WHI findings based on results from the intervention, postintervention, and cumulative posttrial stopping phases do not support the use of either estrogen-progestin or estrogen alone for chronic disease prevention,” the authors write.

“Even though hormone therapy may be a reasonable option for management of moderate to severe menopausal symptoms among generally healthy women during early menopause, the risks associated with hormone therapy, in conjunction with the multiple testing limitations attending subgroup analyses, preclude a recommendation in support of CEE use for disease prevention even among younger women. Current findings also suggest caution when considering hormone therapy treatment in older age groups, even in the presence of persistent vasomotor symptoms, given the high risk of coronary heart disease and other outcomes associated with hormone therapy use in this setting.”

(doi:10.l001/jama.2013.278040; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The Women’s Health Initiative is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services. Wyeth-Ayerst donated the study drugs. 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, October 1 at this link.

Editorial: The Women’s Health Initiative – A Victory for Women and Their Health

“Twenty-two years following its inception, the WHI is a model for publicly funded rigorous, thorough, and objective clinical trials that have broadly affected human health. More than 160,000 women participated (many with great pride), more than 900 peer-reviewed reports from the WHI Publications and Presentations Committee have been published, the WHI data set is publically available, and scores of trainees have been mentored in fields from human biology to public health by participating in its analysis. The WHI has overturned medical dogma regarding the use of menopausal hormone therapy,” writes Elizabeth G. Nabel, M.D., of Brigham and Women’s Hospital, Boston, in an accompanying editorial.

“The WHI underscores the decisive importance of taxpayer-funded research conducted by the National Institutes of Health (NIH). Further reductions in the NIH budget virtually ensure that vitally important studies like the WHI will not be conducted, and hence, U.S. society will be poorly served. The fact that the public sector undertook this historic project (and that the researchers whose work is now reported have taken it to its next stage) has moved medical science forward by the most effective means of doing so—shattering prior dogma. For that, women and all patients whose health depends on sound science are grateful.”

(doi:10.l001/jama.2013.278042; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 24, 2013

Media Advisory: To contact Jeffrey J. Perry, M.D., M.Sc., call Jennifer Ganton at 613-798-5555, ext. 73325, or email jganton@ohri.ca. To contact editorial co-author David E. Newman-Toker, M.D., Ph.D., call Stephanie Desmon at 410-955-8665 or email sdesmon1@jhmi.edu.

Researchers have developed a simple clinical decision rule that may help doctors identify patients with headache in the emergency department who have subarachnoid hemorrhage (bleeding in a certain area of the brain), according to a study in the September 25 issue of JAMA.

“Headache accounts for approximately 2 percent of all emergency department visits, and subarachnoid hemorrhage is one of the most serious diagnoses, accounting for only 1 percent to 3 percent of these headaches. Although the decision to evaluate patients with new neurologic deficits is relatively straightforward, it is much more difficult to determine which alert, neurologically intact patients who present with headache alone require investigations—yet such patients account for half of all subarachnoid hemorrhages at initial presentation,” according to background information in the article.

A clinical decision rule is a tool that uses 3 or more variables from the history, examination, or simple tests to predict a diagnosis for a patient. These rules help clinicians make diagnostic or treatment decisions. The investigators had previously developed three clinical decision rules for use in patients with headache to determine which patients require investigation (imaging, lumbar puncture) for subarachnoid hemorrhage.

Jeffrey J. Perry, M.D., M.Sc., of the Ottawa Hospital Research Institute, Ottawa, Canada, and colleagues further studied the 3 rules in a group of neurologically intact patients with acute headache at 10 Canadian emergency departments from April 2006 to July 2010 to determine which might be most useful and accurate.

Among 2,131 adult patients with a headache peaking within 1 hour and no neurologic deficits, 132 (6.2 percent) had subarachnoid hemorrhage. The researchers found that information about age, neck pain or stiffness, witnessed loss of consciousness, onset during exertion, “thunderclap headache” (defined as instantly peaking pain) and limited neck flexion on examination (defined as inability to touch chin to chest or raise the head 3 inches off the bed if supine [lying face upward]), was 100 percent sensitive (detected all cases), but only 15.3 percent specific (designated many patients without SAH as possibly having it). The authors named the rule the Ottawa SAH (subarachnoid hemorrhage) Rule.

The authors write that the rule may provide evidence for physicians to use in deciding which patients require imaging to decrease the relatively high rate of missed subarachnoid hemorrhages.

“These findings only apply to patients with these specific clinical characteristics and require additional evaluation in implementation studies before the rule is applied in routine emergency clinical care.”

(doi:10.l001/jama.2013.278018; 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: High-Stakes Diagnostic Decision Rules for Serious Disorders

David E. Newman-Toker, M.D., Ph.D., of the Johns Hopkins University School of Medicine, Baltimore, and Jonathan A. Edlow, M.D., of Harvard Medical School, Boston, write in an accompanying editorial that “future studies should seek to validate the Ottawa SAH Rule using larger samples.”

“Realistically, though, this may require use of administrative data and imputation of missing results. The rule should also be studied for the effect on patient outcomes as part of a clinical care pathway for headache diagnosis, ideally with direct comparison to an alternate care pathway based on the computed tomography-lumbar puncture rule. While awaiting further scientific advances, clinicians may find the refined Ottawa SAH Rule helpful to guide diagnostic decisions, but they should limit its use to patients with acute headache who are similar to those among whom the rule has been evaluated.”

(doi:10.l001/jama.2013.278019; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 24, 2013

Prevalence of Poorer Kidney Function Increases Among Adults 80 Years of Age and Older

Recent studies have shown that older adults with chronic kidney disease (CKD; defined as an estimated glomerular filtration rate [GFR; a measure of kidney function] of less than 60 mL/min/1.73 m²) have a high prevalence of concurrent complications and increased risk for adverse outcomes including mortality, cardiovascular disease, and kidney failure. A prior study demonstrated an increase in CKD prevalence between 1988-1994 and 1999-2004 for the general U.S. population. However, trends in CKD prevalence have not been reported for the oldest old [defined as 80 years of age or older],” write C. Barrett Bowling, M.D., M.S.P.H., formerly of the Veterans Affairs Medical Center, Atlanta, and colleagues.

As reported in a Research Letter, the authors used data from national surveys (the National Health and Nutrition Examination Surveys (NHANES) 1988-1994 and 1999-2010), to study participants age 80 years or older who completed a medical evaluation in the NHANES mobile examination center (n = 3,558).

The researchers found that the prevalence of an estimated GFR of less than 60 mL/min/1.73 m² was 40.5 percent in 1988-1994, 49.9 percent in 1999-2004, and 51.2 percent in 2005-2010. The prevalence of a more severe reduction in estimated GFR (less than 45 mL/min/1.73 m²) was 14.3 percent in 1988-1994, 18.6 percent in 1999-2004, and 21.7 percent in 2005-2010.

The findings point to a rise in prevalence in CKD among people 80 years and older and suggests that “efforts to address CKD among the oldest old may be necessary,” the authors conclude.

(doi:10.l001/jama.2013.252441; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact C. Barrett Bowling, M.D., M.S.P.H., call Jennifer Johnson McEwen at 404-727-5696 or email jrjohn9@emory.edu.

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 Viewpoints Appearing in This Issue of JAMA

 The Evolving Role and Value of Libraries and Librarians in Health Care

“As clinicians try to incorporate research into practice through comparative effectiveness research and decision support, they increasingly depend on technology to bring evidence to the bedside to improve quality and patient outcomes. Integrating current information into the processes of shared decision making and continuous learning supports the application of evidence in clinical decision making. Health sciences libraries and librarians have an increasingly important role in providing that information to clinicians as well as to patients and their families,” write Julia F. Sollenberger, M.L.S., and Robert G. Holloway Jr., M.D., M.P.H., of the University of Rochester, New York.

“With ongoing changes in health care as a result of information technology, health sciences libraries and librarians can play an important role in bringing high-quality, evidence-based medical information to the bedside, helping to make patient care both efficient and effective. Health care libraries and librarians are adapting to the changing information needs of physicians, other health care professions, researchers, and patients. With rigorous evaluation, enhanced librarian training, and continuous attention to advances in technology and needs of the users, health care librarians can provide value to patient care.”

(doi:10.l001/jama.2013.277050; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Julia F. Sollenberger, M.L.S., call Julie Philipp at 585-275-1309 or email julie_philipp@urmc.rochester.edu.

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Patient-Reported Outcome Alerts – Ethical and Logistical Considerations in Clinical Trials

In this Viewpoint, Derek Kyte, M.Sc.. of the University of Birmingham, England, and colleagues examine potential approaches to managing patient-reported outcomes (PRO) alerts (where a patient’s self-reported data causes trial personnel to become concerned for their wellbeing or safety).

“There are strong ethical and scientific reasons to reach consensus about how PRO alerts should be dealt with by researchers. Ad hoc interventions may leave participants at risk of harm, place strain on individual researchers, risk cointervention bias, and compromise the integrity of the study. The optimal and most appropriate management strategy is unclear at this stage—the correct response may depend on the nature of the trial and its risk profile. Even if inter-trial consistency is not appropriate, consistency should exist at least across sites within trials. Researchers must, therefore, recognize that PRO alerts are a possibility that should be accommodated at the design stage of the study. Finally, arrangements set out in the protocol need to be reinforced by institutional review boards, with clear information for both participants and researchers.”

(doi:10.l001/jama.2013.277222; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Melanie Calvert, Ph.D., email m.calvert@bham.ac.uk.

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, SEPTEMBER 24, 2013

Media Advisory: To contact corresponding author Timothy W. Jones, M.B.B.S., F.R.A.C.P., M.D., email Tim.Jones@health.wa.gov.au. To contact editorial author Pratik Choudhary, M.B.B.S., M.R.C.P., M.D., email pratik.choudhary@kcl.ac.uk.

Use of an insulin pump with a sensor that suspends insulin delivery when blood glucose falls below a set threshold reduced the rate of severe and moderate hypoglycemia among patients with type 1 diabetes and impaired awareness of hypoglycemia, according to a study in the September 25 issue of JAMA.

Hypoglycemia is a critical obstacle to the care of patients with type 1 diabetes. Sensor-augmented pump therapy with an automated insulin suspension or low glucose suspension function is a technology has the potential to reduce the duration and frequency of significant hypoglycemia, according to background information in the article.

Trang T. Ly, M.B.B.S., D.C.H., F.R.A.C.P., of the Princess Margaret Hospital for Children, Perth, Australia, and colleagues randomized 95 patients with type 1 diabetes, average age 19 and recruited from December 2009 to January 2012 in Australia to standard insulin pump therapy (n = 49) or low-glucose triggered automated insulin suspension (n = 46) for 6 months. The researchers selected patients with impaired awareness of hypoglycemia because they are at significantly higher risk of experiencing hypoglycemic events. Approximately one-third of patients with type 1 diabetes have evidence of impaired hypoglycemia awareness.

The researchers found that sensor-augmented pump therapy with low-glucose triggered automated insulin suspension reduced the combined rate of severe and moderate hypoglycemia in patients with type l diabetes. After 6 months of treatment and controlling for the baseline hypoglycemia rate, the number of severe and moderate hypoglycemia events in the low-glucose suspension group decreased from 175 to 35, whereas the number of events decreased from 28 to 16 in the pump-only group. Analysis of the data indicated that the adjusted incidence rate of hypoglycemia was lower for the low-glucose suspension group than for the pump-only group.

“These findings suggest that automated insulin suspension can reduce the incidence of hypoglycemic events in those most at risk, that is, those with impaired awareness of hypoglycemia,” the authors write.

(doi:10.l001/jama.2013.277818; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was partly funded by the Juvenile Diabetes Research Foundation. Insulin pumps and glucose sensors were provided by Medtronic via an unrestricted grant. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Insulin Pump Therapy With Automated Insulin Suspension

Pratik Choudhary, M.B.B.S., M.R.C.P., M.D., of King’s College London, writes in an accompanying editorial that the data from this and other studies demonstrates “the ability of sensor-augmented insulin pumps with threshold suspension function to provide a significant reduction in severe hypoglycemia.”

“These data can now be used to evaluate the health economic benefits of this therapy and also can be used by clinicians, payers, and regulatory authorities to help make this therapy and technology more widely available to patients who struggle daily with hypoglycemia.”

(doi:10.l001/jama.2013.278576; 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 reported receiving speaker fees and travel support from Medtronic Ltd. and having participated in clinical studies funded by Medtronic.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 24, 2013

Media Advisory: To contact Sarah D. Berry, M.D., M.P.H., call Jennifer Davis at 617-363-8282 or email jdavis@hsl.harvard.edu.

A second bone mineral density (BMD) screening four years after a baseline measurement provided little additional value when assessing risk for hip or other major osteoporotic fracture among older men and women untreated for osteoporosis, and resulted in little change in risk classification used in clinical management, findings that question the common clinical practice of repeating a BMD test every 2 years, according to a study in the September 25 issue of JAMA.

Bone mineral density testing is important in the management of osteoporosis. Guidelines for initiating pharmacologic treatment for osteoporosis are based on BMD in conjunction with risk classification scores. “Despite the utility of BMD, the value of repeating a BMD screening test is unclear,” according to background information in the article. Currently, Medicare reimburses for BMD screening every 2 years regardless of baseline BMD and without a restriction on the number of repeat tests. Twenty-two percent of screened Medicare beneficiaries receive a repeat BMD test within 3 years, on average 2.2 years apart. “Given the priority of reducing health care costs while improving quality of care, it is important to determine whether repeat BMD screening is useful.”

Sarah D. Berry, M.D., M.P.H., of the Institute for Aging Research, Hebrew SeniorLife, Boston, and colleagues conducted a study to determine whether changes in BMD after 4 years provide additional information on fracture risk beyond baseline BMD. The population-based cohort study involved 310 men and 492 women from the Framingham Osteoporosis Study with 2 measures of femoral neck BMD taken four years apart between 1987-1999. The primary measured outcome was risk of hip or other major osteoporotic fracture through 2009 or 12 years following the second BMD measure. Average age was 75 years.

After a median (midpoint) follow-up of 9.6 years, the average BMD change was -0.6 percent per year. During follow-up, 113 participants (14.1 percent) experienced 1 or more major osteoporotic fractures (88 hip, 24 spine, 5 shoulder, and 33 forearm fractures). The net change in the percentage of participants with a hip fracture correctly reclassified with a second BMD measure was 3.9 percent; the net change in the percentage of participants without hip fracture correctly reclassified by a second BMD measure was -2.2 percent. The researchers found that the net change in the percentage of participants with a major osteoporotic fracture correctly reclassified with a second BMD measure was 9.7 percent; the net change in percentage of participants without major osteoporotic fracture correctly reclassified by a second BMD measure was -4.6 percent.

The authors conclude that for older patients not undergoing treatment for osteoporosis, “… BMD change provided little additional information beyond baseline BMD for the clinical management of osteoporosis.” The second BMD measure reclassified a small proportion of individuals, and it is unclear whether this reclassification justifies the current U.S. practice of performing serial BMD tests at 2.2-year intervals. “Further study is needed to determine an appropriate rescreening interval and to identify individuals who might benefit from more frequent rescreening intervals.”

(doi:10.l001/jama.2013.277817; Available pre-embargo to the media at https://media.jamanetwork.com)

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

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, September 24 at this link.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 24, 2013

Media Advisory: To contact Stephen P. Messier, Ph.D., call Will Ferguson at 336-758-5390 or email ferguswg@wfu.edu.

Among overweight and obese adults with knee osteoarthritis, combining intensive diet and exercise led to less knee pain and better function after 18 months than diet-alone and exercise-alone, according to a study in the September 25 issue of JAMA.

“Osteoarthritis (OA) is the leading cause of chronic disability among older adults. Knee OA is the most frequent cause of mobility dependency and diminished quality of life, and obesity is a major risk factor for knee OA. Current treatments for knee OA are inadequate; of patients treated pharmacologically, only about half experience a 30 percent pain reduction, usually without improved function,” according to background information in the article.

Stephen P. Messier, Ph.D., of Wake Forest University, Winston-Salem, N.C., and colleagues conducted a study to determine whether a 10 percent or greater reduction in body weight induced by diet, with or without exercise, would reduce joint loading and inflammation and improve clinical outcomes more than exercise alone. The randomized trial was conducted between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. The study included 454 overweight and obese older community-dwelling adults (age 55 years or older with a body mass index of 27-41) with pain and radiographic knee OA. The interventions consisted of intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise.

Of the participants, 399 (88 percent) completed the study (returned for 18-month follow-up). Retention did not differ between groups. Among the findings of the study:

• Average weight loss was greater in the diet and exercise group and the diet group compared with the exercise group;
• When compared with the exercise group, the diet and exercise group had less knee pain, better function, faster walking speed, and better physical health-related quality of life;

• Participants in the diet and exercise and diet groups had greater reductions in Interleukin 6 (a measure of inflammation) levels than those in the exercise group;

Those in the diet group had greater reductions in knee compressive force than those in the exercise group.

“Osteoarthritis and other obesity-related diseases place an enormous physical and financial burden on the U.S. health care system. The estimated 97 million overweight and obese Americans are at substantially higher risk for many life-threatening and disabling diseases, including OA. The findings from [this trial] suggest that intensive weight loss may have both anti-inflammatory and biomechanical benefits; when combining weight loss with exercise, patients can safely achieve a mean long-term weight loss of more than 10 percent, with an associated improvement in symptoms greater than with either intervention alone,” the authors write.

(doi:10.l001/jama.2013.277669; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 17, 2013

Media Advisory: To contact Renee Y. Hsia, M.D., call Elizabeth Fernandez at 415-514-1592 or email Elizabeth.Fernandez@UCSF.edu.

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“Emergency department (ED) use has been affected by insurance patterns over time and will likely be further affected by expansions of coverage from health care reform.” Uninsured patients are often thought of as high and frequently inappropriate ED users, but insured patients, particularly those with Medicaid coverage, may have difficulties accessing primary care and may rely on EDs more frequently than uninsured patients, write Renee Y. Hsia, M.D., M.Sc., of the University of California, San Francisco, and colleagues.

In a Research Letter appearing in the September 18 issue of JAMA, the authors investigated recent trends in the association between insurance coverage and ED use. The study was a retrospective analysis of California ED visits by adults 19 to 64 years of age from 2005-2010 that used the nonpublic versions of data from the California Office of Statewide Health Planning and Development’s Emergency Discharge Data and Patient Discharge Data. To study variations by insurance coverage, ED visits were grouped into 4 categories based on expected source of payment: Medicaid, private insurance, self-pay or uninsured, and other. The authors also looked at ED visits for ambulatory care sensitive conditions (ACSCs)

The researchers found that between 2005 and 2010, the number of visits to California EDs by adults overall increased by 13.2 percent from 5.4 to 6.1 million per year. The largest increase in visits occurred in 2009. The share of total visits increased among adults with Medicaid coverage and uninsured adults, whereas the share decreased among adults with private insurance. Visit rates to the ED among adult Medicaid beneficiaries were higher than uninsured and privately insured patients.

“Increasing ED use by Medicaid beneficiaries could reflect decreasing access to primary care, which is supported by our findings of high and increasing rates of ED use for ambulatory care sensitive conditions by Medicaid patients. The increase in ED visits was highest in 2009, likely due to the H1N1 pandemic and the influence of the economic downturn on coverage transitions and access to care,” the authors write.

(doi:10.l001/ jama.2013.228331; Available pre-embargo to the media at https://media.jamanetwork.com)

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

For 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, SEPTEMBER 17, 2013

Media Advisory: To contact Richard Saitz, M.D., M.P.H., call Gina DiGravio at 617-638-8480 or email gina.digravio@bmc.org. To contact editorial author Patrick G. O’Connor, M.D., M.P.H., call Helen Dodson at 203-436-3984 or email helen.dodson@yale.edu.

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Persons with alcohol and other drug dependence who received chronic care management including relapse prevention counseling and medical, addiction and psychiatric treatment were no more abstinent than those who received usual primary care, according to a study in the September 18 issue of JAMA.

Chronic care management (CCM) is a way of delivering care that has been shown to be effective for chronic medical and mental health conditions. “Chronic care management is multidisciplinary patient-centered proactive care, a way to organize services that provides coordination and expertise, and has been effective for depression, medical illnesses, and tobacco dependence (a substance use disorder),” the authors write. Trials of integrated medical and addiction care suggest that CCM may be effective for treating addiction, particularly since care elements long known to be effective for addiction overlap with CCM approaches.

Richard Saitz, M.D., M.P.H., of Boston Medical Center, and colleagues conducted a study to examine whether CCM for alcohol and other drug dependence improves substance use outcomes compared with usual primary care. Participants (n = 563) were recruited between September 2006 to September 2008 from a freestanding residential detoxification unit, and from referrals to an urban teaching hospital and from advertisements; 95 percent completed 12-month follow-up. Participants were randomized to receive CCM (n=282) or no CCM (n=281).

The chronic care management group received longitudinal care coordinated with a primary care clinician; motivational enhancement therapy; relapse prevention counseling; and on-site medical, addiction, and psychiatric treatment, social work assistance, and referrals (to specialty addiction treatment mutual help). The primary care group received a timely appointment and a list of addiction treatment resources including a telephone number to arrange counseling.

The researchers found no difference in abstinence from stimulants, opioids, and heavy drinking between the CCM intervention and control group (44 percent vs. 42 percent, respectively, at 12 months). In a subgroup of patients with alcohol dependence, there were fewer alcohol problems among those who received the intervention.

The authors did not detect differences in secondary outcomes of addiction severity, health-related quality of life, or drug problems.

The authors write that current health care reforms in the United States include a focus on CCM in patient-centered medical homes to reduce chronic disease burden and to reduce costs (both of which are among the highest for those with addiction), in part because numerous studies have found such benefits for medical and mental health conditions. “Even though CCM is effective for a number of chronic conditions, it may be premature to assume that CCM will be the solution to improve the quality of care for and reduce costs of patients with addiction,” the authors write. Further research is warranted to determine whether more intensive or longer-duration CCM, or CCM designed differently, might do so.”

(doi:10.l001/jama.2013.277609; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was funded by a grant from the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Cheng reports having served on data monitoring committees for Johnson & Johnson and Janssen. No other disclosures were reported.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, September 17 at this link.

Editorial: Managing Substance Dependence as a Chronic Disease – Is the Glass Half Full or Half Empty?

“How should clinicians, clinical leaders, researchers, and policy makers interpret the results of this negative study?” asks Patrick G. O’Connor, M.D., M.P.H., of the Yale University School of Medicine, New Haven, Conn., in an accompanying editorial.

“… The findings may suggest that the glass is half full rather than half empty. This study places the evaluation of CCM for the treatment of substance use disorders firmly on the agenda for future research in this area. The CCM concept is sound, at least for some chronic illnesses, and highly relevant to today’s evolving health care system. More research on CCM of addiction is clearly warranted to identify specific CCM approaches that may be useful for specific substance-using populations. Clinicians and health care organizations should move forward cautiously in this area pending convincing evidence that specific CCM models are effective for the treatment of substance use disorders in selected patient populations. Comprehensive, integrated management of addiction can only benefit patients—it remains to be seen how best to deliver substance abuse treatment effectively in an evidence-based manner.”

(doi:10.l001/jama.2013.277610; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 10, 2013

Media Advisory: To contact corresponding author Leo Dunkel, M.D., Ph.D., email l.dunkel@qmul.ac.uk.

“Monitoring of linear growth is a well-established part of pediatric health care in the developed world. Although monitoring aims to support early diagnosis and timely treatment of disorders affecting growth, such disorders are often diagnosed late,” write Ulla Sankilampi, M.D., Ph.D., of Kuopio University Hospital, Kuopio, Finland, and colleagues.

As reported in a Research Letter, the authors compared the effectiveness of a novel computerized and automated growth monitoring (AGM) strategy integrated into an electronic health record (EHR) system in the primary care setting to standard growth monitoring (SGM) in 2008-2009. The preceding 3 years (2005-2008) were used as a comparator. Automated growth monitoring included analysis of growth data and referral of abnormal data for review, in addition to SGM.

During the control years, an annual average of 33,029 children were screened. An average of 4 children were diagnosed with a new growth disorder. During the AGM intervention year, the number of new diagnoses was 28 among the 32,404 screened children. The rate of growth disorders diagnoses was 0.1 per 1,000 screened children in the control years vs. 0.9 per 1,000 in the AGM year.

“In this population-based cohort study, we showed that screening of growth disorders using algorithms integrated into an EHR system was associated with a higher rate of detection and referral to specialist care,” the authors write. “Whether the results are generalizable to other countries remains to be determined.”

(doi:10.l001/jama.2013.218793; Available pre-embargo to the media at https://media.jamanetwork.com)

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

EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 10, 2013

Media Advisory: To contact Philippe Mathurin, M.D., email Philippe.Mathurin@chru-lille.fr. To contact editorial co-author Jonathan M. Fenkel, M.D., call Katharine Krauss at 215-955-5507 or email katharine.krauss@jefferson.edu.

Four weeks of treatment with a combination of the drug pentoxifylline and the corticosteroid prednisolone did not improve 6-month survival compared with prednisolone alone in 270 patients with severe alcoholic hepatitis, according to a study in the September 11 issue of JAMA.

Treatment of severe forms of alcoholic hepatitis is extremely challenging because of the poor outcome. European and U.S. guidelines recommend the use of prednisolone or pentoxifylline in patients with severe alcoholic hepatitis. Nevertheless, a substantial proportion of patients die after 6 months regardless of first-line therapy, according to background information in the article.

Philippe Mathurin, M.D., of the Hopital Huriez, Lille, France and colleagues compared the efficacy of a combination of prednisolone and pentoxifylline with prednisolone alone in patients with severe alcoholic hepatitis in 1 Belgian and 23 French hospitals. Duration of follow-up was 6 months. They randomly assigned 270 patients (18 to 70 years of age, who were heavy drinkers with severe biopsy-proven alcoholic hepatitis) to receive 40 mg of prednisolone once a day and 400 mg of pentoxifylline 3 times a day (n=133) for 28 days, or 40 mg of prednisolone and matching placebo (n=137) for 28 days, between December 2007 and March 2010

Eighty-two deaths occurred in the 2 groups during the 6-month follow-up, due to complications from liver failure in 67 cases (81.7 percent) and other causes including gastrointestinal bleeding in 15 cases (18.3 percent). The researchers found no difference in 6-month survival between the 2 groups (69.9 percent in the pentoxifylline-prednisolone group [40 deaths] vs. 69.2 percent [in the placebo-prednisolone group [42 deaths]). Response to treatment and the probability of being a responder were also no different between groups.

The cumulative incidence of hepatorenal syndrome (rapid deterioration in kidney function) at 6 months was also not different in the pentoxifylline-prednisolone and the placebo-prednisolone groups.

Because of the lack of difference in survival and other outcomes, “our study does not support the use of a combination of pentoxifylline and prednisolone for severe alcoholic hepatitis,” the authors write, concluding that “future studies with an appropriate design are needed to provide robust data for developing new strategies to improve the outcome of patients with this life-threatening disease.”

(doi:10.l001/jama.2013.276300; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This work was supported by a Hospital-Based Clinical Research Program, a grant from the French Minister of Health. Pentoxifylline and its matching placebo were both supplied by Sanofi-Aventis Pharmaceuticals. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: Treatment of Severe Alcoholic Hepatitis With Corticosteroids and Pentoxifylline

In an accompanying editorial, Dina L. Halegoua-De Marzio, M.D., and Jonathan M. Fenkel, M.D., of Thomas Jefferson University Hospital, Philadelphia, comment on the findings of this study.

“… corticosteroids and pentoxifylline are currently the only and most successful medical treatments available for severe alcoholic hepatitis despite providing only modest improvements in mortality. The results reported by Mathurin and colleagues demonstrate that the sum (corticosteroids and pentoxifylline) is no greater than the individual parts for preventing mortality in well-characterized patients with severe alcoholic hepatitis. Pentoxifylline may remain a useful option for patients who have contraindications to receiving corticosteroids; however, this group was not studied by Mathurin and colleagues. The study also emphasizes the importance of developing new treatments for severe alcoholic hepatitis. These future studies also should include well-conducted evaluations of liver transplantation for carefully selected patients with severe alcoholic hepatitis not responding to medical management.”

(doi:10.l001/jama.2013.276301; 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, SEPTEMBER 10, 2013

Media Advisory: To contact Mary Reed, Dr.P.H., call Janet Byron at 510-891-3115 or email Janet.L.Byron@kp.org.

Among patients with diabetes, use of an outpatient electronic health record (EHR) in an integrated healthcare delivery system was associated with modest reductions in emergency department visits and hospitalizations, but was not associated with a change in office visit rates, according to a study in the September 11 issue of JAMA.

The Health Information Technology for Economic and Clinical Health (HITECH) Act authorizes up to $27 billion during 10 years to promote meaningful use of EHRs, with penalties for lack of EHR use beginning in 2015. With these substantial incentives, it is not surprising that EHR adoption in the United States appears to be increasing. Electronic health records increase access to timely and complete patient information at the point of care, with potential to improve the quality and efficiency of care delivered, including improved care coordination, according to background information in the article. “With medical care for patients with chronic diseases representing 75 percent of U.S. health care costs and hospitalizations representing one-third of all U.S. health care expenditures, better management of chronic medi­cal conditions such as diabetes represents one clinical area in which improved care theoretically could reduce spending. There is, however, limited and mixed evidence on the effect of EHRs on health outcomes or clinical events.”

Staggered EHR implementation across outpatient clinics in an integrated delivery system, Kaiser Permanente Northern California, between 2005 and 2008 created an opportunity for studying changes associated with EHR use. Mary Reed, Dr.P.H., of Kaiser Permanente Northern California, Oakland, and colleagues examined the association between EHR implementation and emergency department (ED) visits, hospitalizations, and office visits among patients with diabetes between 2004 and 2009, seen at 45 facilities in 17 medical centers. The study included all 169,711 patients in the health  plan’s clinical diabetes registry at the beginning of the study period.

The researchers found that after use of the EHR, there were fewer ED visits (a relative 5.5 percent decline from the average predicted baseline rate); hospitalizations decreased overall (a relative 5.2 percent decline from the predicted baseline average rate); and fewer nonelective hospitalizations (a relative 6.1 percent difference from the predicted baseline average rate). Hospitalizations specifically for ambulatory care-sensitive conditions also declined with EHR use (a 10.50 percent difference).

There was no statistically significant difference in office visit rates with the implementation of an EHR.

“Further studies are needed to quantify the association of EHR use with changes in costs,” the authors conclude.

(doi:10.l001/jama.2013.276733; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Research reported herein was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health and the Agency for Healthcare Research and Quality.  All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 10, 2013

Media Advisory: To contact Naomi S. Bardach, M.D., M.A.S., call Leland Kim at 415-502-NEWS or email Leland.Kim@ucsf.edu. To contact editorial co-author Rowena J. Dolor, M.D., M.H.S., call Sarah Avery at 919-660-1306 or email sarah.avery@duke.edu.

A pay-for-performance program in electronic-health-records-(EHR)-enabled small practices led to modest improvements in cardiovascular care processes and outcomes, according to a study in the September 11 issue of JAMA.

“Most evaluations of pay-for-performance (P4P) incentives have focused on large-group practices,” according to background information in the article. Small practices, where the majority of patients still receive care nationally, historically have provided lower-quality care—especially solo practices—and may have greater obstacles to improving care because they lack the scale and organizational structure to do so. It is possible that EHR-enabled solo and small-group practices will be able to respond to P4P incentives and improve quality, but this has not been demonstrated.

Naomi S. Bardach, M.D., M.A.S., of the University of California, San Francisco, and colleagues performed a randomized trial to assess the effect of P4P incentives on quality in EHR-enabled small practices in the context of an established quality improvement initiative. The study randomized small (fewer than 10 clinicians) primary care clinics in New York City from April 2009 through March 2010 to financial incentives and quarterly performance reports or performance reports alone. A city program provided all participating clinics with the same EHR software with decision support and patient registry and quality reporting capabilities. The program also provided on-site quality improvement specialists offering technical assistance. Incentivized clinics were paid for each patient whose care met the performance criteria, but they received higher payments for patients with co-existing illnesses, who had Medicaid insurance, or who were uninsured (maximum payments: $200/patient; $100,000/clinic). Quality reports were given quarterly to both the intervention and control groups.

The primary outcome measures were a comparison of between-group differences in performance improvement, from the beginning to the end of the study, between control and intervention clinics for aspirin or antithrombotic prescription, blood pressure control, cholesterol control, and smoking cessation interventions.

The researchers found that performance improved in both groups during the study, with positive changes from baseline for all measures. The adjusted change in performance was higher in the intervention than in the control group for aspirin or antithrombotic prescription for patients with diabetes or ischemic vascular disease [12.0 percent vs. 6.1 percent]; and for blood pressure control in patients with hypertension but without diabetes or ischemic vascular disease [9.7 percent vs. 4.3 percent]; and smoking cessation interventions (12.4 percent vs. 7.7 percent).

For uninsured or Medicaid (non-HMO) patients, changes in measured performance were higher in the intervention clinics than the control clinics (range of adjusted absolute differences, 7.9 percent to 12.9 percent), for all measures but cholesterol control, but the differences were not statistically significant.

“In this cluster-randomized study of P4P incentives, we found that EHR-enabled small practices were able to respond to incentives to improve cardiovascular care processes and intermediate outcomes,” the authors write. “This provides evidence that, in the context of increasing uptake of EHRs with robust clinical management tools, small practices may be able to improve their quality performance in response to an incentive.”

(doi:10.l001/jama.2013.277353; 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. Please see the article for additional information, including other authors, author contributions and affiliations, funding and support, etc.

Editorial: Financial Incentives in Primary Care Practice – The Struggle to Achieve Population Health Goals

In an accompanying editorial, Rowena J. Dolor, M.D., M.H.S., and Kevin A. Schulman, M.D., of the Duke University School of Medicine, Durham, N.C., comment on the two randomized trials in this issue of JAMA (Bardach et al; Petersen et al) that report the comparative effectiveness of financial incentives in primary care settings.

“Even though the findings of these 2 studies are encouraging in advancing understanding of the P4P strategy, the reports also raise questions about the solitary focus on clinician performance in achieving these population health goals. Both studies suggest that even with elegant incentives applied at the practice level, gaps in clinical performance still remain. These results suggest that although there is some room for improvement of individual performance, these gaps represent systematic shortcomings rather than an issue with performance at the individual clinician level.”

“In a population health model, a variety of strategies is used to achieve success. Some of these strategies would be clinician focused, some technology focused, some community focused, and some patient focused. The appropriate allocation of resources to each of these strategies would be based on economic analysis—how to gain the greatest increase in population health from optimizing interactions across all of these efforts. This type of framework transforms the question from the effectiveness of primary care practice to the effectiveness of primary care service embedded in a community.”

(doi:10.l001/jama.2013.277575; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, SEPTEMBER 10, 2013

Media Advisory: To contact Laura A. Petersen, M.D., M.P.H., call Graciela Gutierrez at 713-798-4710 or email ggutierr@bcm.edu.

In an examination of the effect of financial incentives on hypertension care at 12 outpatient clinics, physician-level (individual) financial incentives, but not practice-level or combined incentives, resulted in greater blood pressure control or appropriate response to uncontrolled blood pressure, according to a study in the September 11 issue of JAMA. None of the incentives resulted in greater use of guideline-recommended medications compared with controls.

“As part of the Affordable Care Act, the U.S. government has introduced pay for performance to all hospitals paid by Medicare nationwide. The New York City Health and Hospitals Corporation recently announced a performance pay plan for physicians. These and other value-based purchasing systems are intended to align incentives to promote high-quality health care. Evaluations of the effectiveness of pay-for-performance programs directed at hospitals have shown contradictory results,” according to background information in the article.

Laura A. Petersen, M.D., M.P.H., of the Veterans Affairs Medical Center and Baylor College of Medicine, Houston, and colleagues conducted a randomized controlled trial to test the effect of explicit financial incentives to individual physicians and practice teams for the delivery of guideline-recommended care for hypertension in the primary care setting. The trial at 12 Veterans Affairs outpatient clinics with 5 performance periods enrolled 83 primary care physicians and 42 nonphysician personnel (e.g., nurses, pharmacists). The interventions were physician-level (individual) incentives, practice-level incentives, both, or none. Intervention participants received up to 5 payments every 4 months; all participants could access feedback reports. The primary measured outcomes were the number of patients (among a random sample) achieving guideline-recommended blood pressure thresholds or receiving an appropriate response to uncontrolled blood pressure, the number of patients prescribed guideline-recommended medications, and the number who developed hypotension (abnormally low blood pressure).

Among physicians who participated in all 5 performance periods, the average total payment for physicians over the course of the study was $4,270 in the combined physician and practice-level group, $2,672 in the individual physician-level group, and $1,648 in the practice-level group.  Change in blood pressure control or appropriate response to uncontrolled blood pressure compared with the control group was greater only in the individual incentives group. The difference in change in proportion of patients achieving blood pressure control or receiving an appropriate response between the individual incentive and no incentive group was 8.36 percent.

Although the use of guideline-recommended medication increased over the course of the study in the intervention groups, there was no change compared with controls.

The researchers did find that far more intervention than control group participants viewed their feedback reports on the website (67 percent vs. 25 percent), suggesting that participants were aware of the relationship between performance and rewards.

“Although concerns about overtreatment have been cited in criticisms of pay-for-performance programs, we did not find a higher incidence of hypotension in the panels of physicians randomized to the incentive groups,” they write.

Even small reductions in blood pressure translate into significant reductions in morbidity and mortality, and in system-wide costs, the authors write. “This trial addresses the needs of policy makers and payers for information about a clinically relevant payment intervention in routine practice. Payment-system interventions are attractive because of their potential scale and reach. However, payment-system interventions are only one piece of the solution to improve management of chronic diseases such as hypertension. More resource-intensive, tailored, patient-level self-management strategies may be needed to truly affect patient outcomes.”

(doi:10.l001/jama.2013.276303; 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. Please see the article for additional information, including other authors, author contributions and affiliations, funding and support, etc.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, September 10 at this link.

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EMBARGOED FOR EARLY RELEASE: 4:45 A.M. (CT) TUESDAY, SEPTEMBER 3, 2013

Media Advisory: To contact Stephen J. Nicholls, M.B.B.S., Ph.D., email stephen.nicholls@sahmri.com. To contact editorial co-author Jean-Claude Tardif, M.D., call Marie-Josee Nantel at 514-376-3330, ext. 2641; or email Marie-Josee.Nantel@icm-mhi.org.

CHICAGO – Among patients with prehypertension and coronary artery disease, use of the renin (an enzyme secreted by the kidneys) inhibitor aliskiren, compared with placebo, did not result in improvement or slowing in the progression of coronary atherosclerosis, according to a study published by JAMA. The study is being released early online to coincide with its presentation at the European Society of Cardiology Congress 2013.

“Guidelines recommend blood pressure reduction in patients with hypertension with a treatment goal of 140 mm Hg for systolic and 90 mm Hg diastolic blood pressure for most individuals. The benefit of additional blood pressure lowering agents in patients who have reached treatment goals has not been established. However, few trials have examined the benefits and risks of further intensifying blood pressure treatment in patients with established coronary artery disease (CAD), who are in the prehypertension range. Preclinical data demonstrate that renin-angiotensin-aldosterone system (RAAS) activation plays an important role in atherosclerosis and that RAAS inhibition may have a direct beneficial effect on the artery wall,” according to background information in the article. “Blood pressure reduction and RAAS inhibition are targets for treatment of atherosclerosis. The effect of renin inhibition on coronary disease progression has not been investigated.”

Stephen J. Nicholls, M.B.B.S., Ph.D., of the South Australian Health and Medical Research Institute, Adelaide, Australia, and colleagues conducted a study to determine if renin inhibition with aliskiren would slow progression of coronary atherosclerosis in patients whose blood pressure was considered optimally controlled to current treatment targets. The randomized, multicenter trial compared aliskiren with placebo in 613 participants with coronary artery disease, systolic blood pressure between 125 and 139 mm Hg (prehypertension range), and 2 additional cardiovascular risk factors. The trial was conducted at 103 academic and community hospitals in Europe, Australia, and North and South America (enrollment from March 2009 to February 2011; end of follow-up was January 2013).

Participants underwent coronary intravascular ultrasound (IVUS) imaging and were randomized to receive 300 mg of aliskiren (n = 305) or placebo (n = 308) daily for 104 weeks. Disease progression was measured by repeat IVUS examination after at least 72 weeks of treatment, with evaluable imaging data available at follow-up in 74.7 percent of patients (225 in the aliskiren group and 233 in the placebo group). The primary efficacy parameter was the change in percent atheroma (a fatty deposit) volume (PAV) from baseline to study completion.

The researchers found that there was no difference between the treatment groups with respect to measures of atheroma burden at baseline. The primary efficacy measure, PAV, decreased by 0.33 percent in the aliskiren group and increased by 0.11 percent in the placebo group (between-group difference, -0.43 percent). There were no significant differences in the proportion of participants who demonstrated regression of PAV (56.9 percent vs. 48.9 percent) and total atheroma volume (64.4 percent vs. 57.5 percent) in the aliskiren and placebo groups, respectively.

A greater number of discontinuations of participation due to adverse events were observed in the aliskiren group compared with the placebo group (8.2 percent vs. 4.5 percent, respectively).

“These findings do not support the use of aliskiren for regression or prevention of progression of coronary atherosclerosis,” the authors conclude.

(doi:10.l001/jama.2013.277169; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Renin-Angiotensin System Inhibition and Secondary Cardiovascular Prevention

In a related editorial, Jean-Claude Tardif, M.D., and Jean Gregoire, M.D., of the Montreal Heart Institute, Montreal, Canada, comment on the findings of this study, and also discuss two other trials in which aliskiren was not effective in improving clinical outcomes in patients with cardiovascular disease.

“Where does this leave inhibition of the renin-angiotensin system for secondary cardiovascular prevention? Angiotensin-converting enzyme inhibitors or, if not tolerated, angiotensin receptor blockers provide clinical benefits and should continue being prescribed to improve outcomes in patients with coronary artery disease. Until additional evidence is available, the role of renin inhibition in this context should be limited. Because aliskiren does reduce blood pressure, perhaps this agent could be reserved for use in patients with coronary disease and hypertension who cannot tolerate ACE inhibitors and angiotensin receptor blockers.”

(doi:10.l001/jama.2013.277170; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Hepatitis B Immunization Program in Taiwan Associated With Reduction in Chronic Liver Disease Deaths

“Hepatitis B virus (HBV) infection causes infant fulminant hepatitis (IFH), and chronic HBV infection may progress to chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Taiwan launched a nationwide HBV immunization program for newborns in July 1984, which has successfully lowered the prevalence of chronic HBV carriers, incidence of HCC, and mortality of IFH in vaccinated birth cohorts. The mortality of CLD before and after HBV immunization has never been examined,” write Chun-Ju Chiang, Ph.D., of National Taiwan University, Taipei, and colleagues.

As reported in a Research Letter, the authors assessed the 30-year outcomes of the immunization program. From July 1984 to June 1986, the immunization program covered only newborns with high-risk mothers who were seropositive for HBV surface antigen. Coverage was extended to all newborns in July 1986, preschool children in July 1987, and primary school children in 1988-1990. Recombinant HBV vaccines replaced plasma-derived vaccines in 1992. The immunization coverage rates for birth cohorts from 1984 to 2010 was 88.8 percent to 96.9 percent. The mortality of IFH, CLD, and HCC and the incidence of HCC were compared among birth cohorts born before and after the launch of the program.

The researchers found that from 1977-1980 to 2001-2004, the age- and sex-adjusted rate ratios for individuals 5 to 29 years of age decreased by more than 90 percent for CLD and HCC mortality and by more than 80 percent for HCC incidence, which were higher than the previously reported reduction (70 percent) in HCC incidence for youth 6 to 19 years of age.

The mortality of IFH in vaccinated birth cohorts decreased by more than 90 percent from 1977-1980 to 2009-2011, which was greater than the previously reported reduction (approximately 70 percent) from 1975-1984 to 1985-1998. “This long-term, high-coverage immunization program was associated with lower IFH mortality through increasing individual and herd immunity of vaccinated cohorts.”

(doi:10.l001/jama.2013.276701; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Chien-Jen Chen, Sc.D., email chencj@gate.sinica.edu.tw.

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Viewpoints Appearing in This Issue of JAMA

Poverty, Health, and Societies of the Future

“Today, as never before, the opportunity exists to unite global health and the fight against poverty through action that is focused on clear goals. The 2 aspirations of a right to health and of ending extreme poverty can be pursued as 1 through universal health coverage,” write Jim Yong Kim, M.D., Ph.D., of the World Bank Group, Washington, D.C., and Margaret Chan, M.D., of the World Health Organization, Geneva, Switzerland.

“There are many barriers to ending extreme poverty, boosting shared prosperity, and achieving universal health coverage. Clinicians must continue to lead the way in delivering high-quality services to patients and demanding that all patients, regardless of class or nationality, deserve a chance at a healthy life. Achieving improved health for all will require building health equity and economic transformation as a single structure, a citadel to shelter the lives of future generations.”

(doi:10.l001/jama.2013.276910; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Jim Yong Kim, M.D., Ph.D., call Carolyn Reynolds at 202-473-0049 or email CReynolds@worldbank.org.

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What the United States Has to Gain From Global Health Research

In this Viewpoint, Roger I. Glass, M.D., Ph.D., of the Fogarty International Center, National Institutes of Health, Bethesda, Md., discusses the importance and benefits of the U.S. investing in global health research.

“… the United States has already benefitted from research in global health. Major discoveries have occurred through collaborations with other countries, competitiveness has been expanded by enlisting new partners to research, and the nation’s humanitarian spirit has been demonstrated by addressing some of the most compelling medical problems today and by assisting economic development. Now, as life expectancy in low- and middle-income countries approaches that in the United States, there is even greater urgency to cooperate and collaborate to confront these shared health problems. Whether that threat is an outbreak of severe acute respiratory syndrome or a new strain of influenza; the persistent problems of cancer, stroke, and heart disease; or the increasing epidemics of obesity and addictive disorders, the response will have to come from the collaboration of creative minds from around the world focused on how to most rapidly arrive at new and more effective solutions for prevention and treatment. Without an emphasis on global health, the United States risks falling behind in its leadership in biomedical research and its competitive position in commercialization of discoveries.”

(doi:10.l001/jama.2013.276558; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Roger I. Glass, M.D., Ph.D., call Ann Puderbaugh at 301-402-8614 or email ann.puderbaugh@nih.gov.

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 Conflict and Polio – Winning the Polio Wars

“The global polio eradication initiative is at a critical crossroads. Some 25 years ago, the World Health Organization (WHO), supported by Rotary International, launched a global goal of eradicating polio from the world by 2000. Although the eradication target may not have been achieved, there has been remarkable progress. From more than 350,000 cases of poliomyelitis globally spread over 125 countries with endemic disease in 1990, a mere 223 cases were reported in 2012, with the disease largely restricted to a few regions of Nigeria, Pakistan, and Afghanistan,” writes Zulfiqar A. Bhutta, M.B., B.S., F.R.C.P., F.R.C.P.C.H., Ph.D., of the Sick Kids Center for Global Child Health, Toronto, and The Aga Khan University, Karachi, Pakistan.

“Eradicating polio in the residual population pockets of Asia and Africa is impossible without a concerted effort to reach every child and family in conflict zones. As long as the polio program continues as a largely insulated program with limited relevance and linkage to critical public health needs, engaging impoverished and suspicious populations will remain a challenge. Such promotion of demand in communities and reduction of vaccine hesitancy are critical steps in eradicating polio in areas of conflict. There are few examples in modern history of controlling, let alone eradicating, an infectious disease in the midst of a raging conflict, and there is no reason to believe that polio will be any different. Finding peace and a political settlement in the region is an important prerequisite for global polio eradication and addressing the health and developmental needs of innocent children caught in the middle.”

(doi:10.l001/jama.2013.276583; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Zulfiqar A. Bhutta, M.B., B.S., F.R.C.P., F.R.C.P.C.H., Ph.D., call Caitlin McNamee-Lamb at 416-813-7654, ext. 201436, or email caitlin.mcnamee-lamb@sickkids.ca.

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 Industry-Sponsored Clinical Trials in Emerging Markets – Time to Review the Terms of Engagement

A decade ago, clinical trial sponsors routinely excluded low- and middle-income countries such as India and China from participation. “Today, more than 3,000 trials are under way in China, a large proportion of which are sponsored by global pharmaceutical companies,” write Stephen MacMahon, D.Sc., F.Med.Sci., of the George Institute for Global Health, Sydney, Australia, and colleagues. In China the number of pharmaceutical company-sponsored trials doubled between 2005 and 2010. “… the rapid expansion of clinical trial activity in emerging markets has raised concerns, including questions about the quality of data generated and the relevance of the products being tested to local health care priorities.”

“The last few decades have seen enormous health benefits and corporate profits flow from the results of clinical trials across a range of conditions. However, the model by which such trials are conducted must evolve if such benefits are to continue. There is a real risk that the next few decades will not generate the same returns unless there is adaptation to the new circumstances in which trials are conducted and recognition of the rights and expectations of communities in which trial participants live. The rapidly increasing value of emerging markets to global pharmaceutical companies will hopefully provide the incentive for change. Otherwise, it will be up to emerging markets to insist on it.”

(doi:10.l001/jama.2013.276913; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Stephen MacMahon, D.Sc., F.Med.Sci., email smacmahon@georgeinstitute.org.

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

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 EARLY RELEASE: 4:30 A.M. (CT) SUNDAY, SEPTEMBER 1, 2013

Media Advisory: To contact Philippe Gabriel Steg, M.D., email gabriel.steg@bch.aphp.fr.

CHICAGO – Use of the novel anticoagulant otamixaban did not reduce ischemic events compared with unfractionated heparin plus eptifibatide but increased bleeding among patients with non–ST-segment elevation acute coronary syndromes undergoing a percutaneous coronary intervention (PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries), according to a study published by JAMA. The study is being released early online to coincide with its presentation at the European Society of Cardiology Congress 2013

“Major progress has been made in the management of non–ST-segment elevation [a certain pattern on an electrocardiogram] acute coronary syndromes (NSTE-ACS) because of the availability of potent combinations of oral antiplatelet agents, injectable anticoagulants, and increasing use of an invasive strategy. Nevertheless, the risk of adverse outcomes remains substantial, and there is no consensus on a single optimal injectable anticoagulant that can be used across the continuum of care from the emergency setting through revascularization (when applicable),” according to background information in the article. The synthetic intravenous drug otamixaban inhibits thrombin [an enzyme that acts on fibrinogen in blood causing it to clot] generation in a dose-dependent manner. A phase 2 trial showed a reduction in the combined outcome of death or myocardial infarction (heart attack) in patients treated with otamixaban compared with unfractionated heparin (UFH) plus eptifibatide (an antiplatelet drug) and showed similar bleeding rates with otamixaban at midrange doses.

Philippe Gabriel Steg, M.D., of the Université Paris-Diderot, Sorbonne-Paris Cité, Paris, and investigators with the TAO trial compared the clinical efficacy and safety of otamixaban with that of unfractionated heparin plus eptifibatide in 13,229 patients with NSTE-ACS and a planned early invasive strategy. The trial was conducted at 568 active sites in 55 countries between April 2010 and February 2013. Eligible participants were randomized to otamixaban or unfractionated heparin plus, at the time of PCI, eptifibatide.

The primary outcome of death or new myocardial infarction through day 7 occurred in 5.5 percent of the patients treated with otamixaban vs. 5.7 percent of the patients treated with UFH plus eptifibatide. Otamixaban did not significantly reduce the risk of any of the components of the primary outcomes, either death or heart attack, or of any of the secondary efficacy outcomes, including procedural thrombotic complications. Analysis of the primary outcome by 30 days confirmed the absence of a reduction with otamixaban.

In the lower-dose otamixaban group, discontinued by the data monitoring committee for futility based on the interim analysis, the rate of the primary outcome at day 7 was 6.3 percent.

Patients in the otamixaban group had about double the rate of the primary safety outcome of Thrombosis in Myocardial Infarction major or minor bleeding at day 7 compared with patients in the combination of UFH-plus-eptifibatide group (3.1 percent vs. 1.5 percent). Otamixaban consistently increased all types of bleeding events, regardless of the severity or bleeding classification scheme used. Study anticoagulant was discontinued because of bleeding in 242 patients (4.7 percent) in the otamixaban group and in 95 patients (1.7 percent) in the UFH-plus-eptifibatide group.

“Otamixaban did not reduce ischemic events compared with UFH plus eptifibatide but increased bleeding among patients with NSTE-ACS and a planned invasive strategy. These findings do not support the use of otamixaban for patients with NSTE-ACS undergoing planned early percutaneous coronary intervention,” the authors conclude.

(doi:10.l001/jama.2013.277165; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Media Advisory: To contact Stanley Zlotkin, M.D., Ph.D., call Caitlin McNamee-Lamb at 416-813-7654, ext. 201436 or email caitlin.mcnamee-lamb@sickkids.ca. To contact editorial author co-author Andrew M. Prentice, Ph.D., email andrew.prentice@lshtm.ac.uk.

CHICAGO – Children in a malaria-endemic community in Ghana who received a micronutrient powder with iron did not have an increased incidence of malaria, according to a study in the September 4 issue of JAMA. Previous research has suggested that iron supplementation for children with iron deficiency in malaria-endemic areas may increase the risk of malaria

“In sub-Saharan Africa, malaria is a leading cause of childhood morbidity and mortality, and iron deficiency is among the most prevalent preventable nutritional deficiencies. The provision of iron to children with iron deficiency anemia can enhance motor and cognitive development and reduce the prevalence of severe anemia. However, studies have suggested that iron deficiency anemia may offer protection against malaria infection and that the provision of iron may increase malaria morbidity and mortality,” according to background information in the article. “In 2006, the World Health Organization and the United Nations Children’s Fund released a joint statement that recommended limiting use of iron supplements (tablets or liquids) among children in malaria-endemic areas because of concern about increased malaria risk. As a result, anemia control programs were either not initiated or stopped in these areas.”

Stanley Zlotkin, M.D., Ph.D., of the Hospital for Sick Children, Toronto, and colleagues conducted a study to determine the effect of providing micronutrient powder (MNP) with or without iron on the incidence of malaria among children living in a high malaria-burden area. The randomized trial, which included children 6 to 35 months of age (n = 1,958 living in 1,552 clusters), was conducted over 6 months in 2010 in a rural community setting in central Ghana, West Africa. A cluster was defined as a compound including 1 or more households. Children were excluded if iron supplement use occurred within the past 6 months, they had severe anemia, or severe wasting. Children were randomized by cluster to receive a MNP with or without iron for 5 months followed by 1-month of further monitoring. Insecticide-treated bed nets were provided at enrollment, as well as malaria treatment when indicated.

Throughout the intervention period, adherence to the use of MNP and insecticide-treated bed nets were similar between the iron group and the no iron group. The researchers found that the overall incidence of malaria was lower in the iron group compared with the no iron group, but after adjustment for baseline values for iron deficiency and moderate anemia, these differences were no longer statistically significant. “Similar associations were found during the 5-month intervention period only for both malaria and malaria with parasite counts greater than 5000/µL (severe malaria). A secondary analysis demonstrated that malaria risk was reduced among the subgroup of those in the iron group who had iron deficiency and anemia at baseline.”

Overall, hospital admission rates did not differ significantly between groups. However, during the 5-month intervention period, there were more children admitted to the hospital in the iron group vs. the no iron group (156 vs. 128, respectively).

“The findings from the current study not only address a gap in the literature, but also have potentially important policy implications for countries like Ghana that have not implemented iron supplementation or fortification as part of anemia control programs in part due to the joint recommendation from the WHO and UNICEF. For ethical reasons, we ensured that all participants were not denied existing malaria prevention (insecticide-treated bed nets) or malaria treatment. As such, our results most likely can be applied to other malaria-endemic settings in which similar malaria control measures are in place. Overall, given our findings and the new WHO guidelines recommending iron fortification for the prevention and treatment of anemia among children younger than 2 years (in whom the prevalence of anemia is ≥20 percent), there should be renewed interest and consideration for implementing iron fortification in Ghana as part of the national nutrition policy.”

(doi:10.l001/jama.2013.277129; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Office of Dietary Supplements provided funding for this study. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Iron Fortification and Malaria Risk in Children

In an accompanying editorial, Andrew M. Prentice, Ph.D., of the London School of Hygiene and Tropical Medicine, and colleagues write that the increase seen in this study in hospital admissions among the iron supplementation group, which by definition constitutes a potentially serious adverse event, adds to the concerns about the safety of iron administration in highly malaria-endemic environments.

“Participants in an expert panel convened by the World Health Organization in 2007 speculated that iron given with foods, either by centralized or point-of-use fortification, would be safe. However, the Ghanaian trial reported by Zlotkin et al in this issue of JAMA now becomes the fourth trial to question this suggestion, and leaves global health policy makers with an unresolved dilemma. Until a means of safely administering iron in infectious environments has been developed, there remains an imperative to reduce the infectious burden as a prerequisite to moving poor populations from their current state of widespread iron deficiency and anemia.”

(doi:10.l001/jama.2013.6771; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Media Advisory: To contact Judith Spijkerman, M.D., email j.spijkerman@umcutrecht.nl. To contact editorial author Katherine L. O’Brien, M.D., M.P.H., call Tim Parsons at 410-955-7619 or email tmparson@jhsph.edu.

CHICAGO – The use of 4 different 13-valent pneumococcal conjugate vaccine immunization schedules in healthy term infants resulted in no statistically significant differences in antibody levels between the infants after the booster dose at 12 months of age for almost all serotypes, according to a study in the September 4 issue of JAMA.

“The World Health Organization (WHO) estimated that more than 800,000 children younger than 5 years died from pneumococcal disease in 2000, making it the leading vaccine-preventable cause of death. Since the licensure in 2000 of the first 7-valent pneumococcal polysaccharide conjugate vaccine (PCV) for infants, many countries have added PCV to their existing national immunization programs. As a result, PCV immunization schedules differ between countries with respect to number of doses, age at vaccinations, and intervals between doses,” according to background information in the article. “The optimal vaccine schedule for infants should provide maximal, sustained direct and indirect protection against invasive pneumococcal disease while using a minimal number of doses. The latter is particularly relevant in the context of overcrowded national immunization programs, public resistance to vaccines, and cost-effectiveness estimates.”

Judith Spijkerman, M.D., of the University Medical Centre, Utrecht, the Netherlands, and colleagues compared immunogenicity of 4 different schedules using the 13-valent PCV (PCV13) to assess the optimal primary regimen with respect to antibody induction. The randomized clinical trial of healthy term infants in a general community in the Netherlands was conducted between June 2010 and January 2011, with 99 percent follow-up until age 12 months. Infants (n = 400) were randomly assigned (1:1:1:1) to receive PCV13 either at ages 2,4, and 6 months (2-4-6); at ages 3 and 5 months (3-5); at ages 2,3, and 4 months (2-3-4); or at ages 2 and 4 months (2-4), with a booster dose at age 11.5 months.

The researchers found that one month after the booster dose, there were no differences in IgG (Immunoglobulin G) geometric mean concentrations (GMCs) between the schedules for 70 of 78 comparisons. “The 2-4-6 schedule was superior to the 2-3-4 schedule for serotypes 18C and 23F and superior to the 2-4 schedule for serotypes 6B, 18C, and 23F. For serotype 1, the 3-5 schedule was superior to the 2-4-6, 2-3-4, and 2-4 schedules.”

Secondary outcomes (GMCs measured 1 month after the primary series, at 8 months of age, and before the booster) demonstrated differences 1 month after the primary series. “The 2-4-6 schedule was superior compared with the 3-5, 2-3-4, and 2-4 schedules for 3,9, and 11 serotypes, respectively. Differences between schedules persisted until the booster dose,” the authors write.

“To our knowledge, this is the first randomized controlled trial investigating immunogenicity of PCV13 in 4 different primary immunization schedules currently used in most high income countries. The primary outcome of this study, GMCs l month after the booster dose, showed that there were no statistically significant differences between the 4 schedules in IgG levels for most serotypes. However, differences between schedules were noted in secondary analyses. … Our findings demonstrate that optimal timing of the primary series, i.e., older age at vaccinations combined with longer intervals between vaccinations, is important to maintain optimal antibody levels during the period between the primary series and the booster dose.”

“The choice of PCV schedule will require a balance between the need for early protection and maintaining protection between the primary series and the booster, in particular before herd effects offer clinical protection against vaccine serotype disease to as yet unvaccinated or incompletely vaccinated infants. When herd immunity is established, clinical relevance of the observed differences in immune responses may become of minor importance,” the researchers conclude.

(doi:10.l001/jama.2013.228052; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was performed by order and for the account of the Dutch Ministry of Health by additional immunization program research funding. Pfizer kindly provided 1,400 PCV13 vaccines. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Optimizing the Use of Pneumococcal Conjugate Vaccine Globally

“A good deal remains to be learned about how best to use PCVs to protect the most vulnerable and the greatest number of community members,” writes Katherine L. O’Brien, M.D., M.P.H., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, in an accompanying editorial.

“Immunogenicity is just one aspect of biological effect, perhaps more important for some serotypes than others. Focus should remain squarely on ensuring that every child is immunized with at least 3 doses of PCV, beginning early in life and administered in a timely fashion. The study by Spijkerman and colleagues reassures that PCV products now in use provide a robust immune response across a range of dosing schedules and focuses attention on specific serotypes of concern. It is good news that PCVs are adaptable to various dosing schedules and therefore to demands of vaccine programs across countries. Emphasis on immunogenicity differences should not be separated from the larger context of protection at the individual level, pneumococcal disease epidemiology, vaccine program performance, and ultimately clear measures of disease outcome.”

(doi:10.l001/jama.2013. 228062; 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. O’Brien reported having received research grant support from GlaxoSmithKline and Pfizer and having served on external expert advisory groups related to pneumococcal vaccine for Merck, GlaxoSmithKline, and Aventis-Pasteur.

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

Media Advisory: To contact corresponding authors Guang Ning, M.D., Ph.D., email gning@sibs.ac.cn; Wenhua Zhao, Ph.D., email whzhao@ilsichina.org; or Weiqing Wang M.D., Ph.D., email wqingw@hotmail.com. To contact editorial author Juliana C. N. Chan, M.D., F.R.C.P., email jchan@cuhk.edu.hk.

CHICAGO – A study based on a nationally representative sample of adults in China in 2010 indicates that nearly 12 percent of Chinese adults had diabetes and the prevalence of prediabetes was about 50 percent, according to a study in the September 4 issue of JAMA.

“Noncommunicable chronic diseases have become the leading causes of mortality and disease burden worldwide. It was estimated that 34.5 million deaths globally were due to noncommunicable diseases in 2010, which reflected a significant increase from 1990. Mortality from diabetes doubled during this period and increased to 1.3 million deaths worldwide in 2010. In addition, diabetes is a major risk factor for ischemic heart disease and stroke, which collectively killed an estimated 12.9 million people globally in 2010,” according to background information in the article.

“The prevalence of diabetes has increased significantly in recent decades and is now reaching epidemic proportions in China. The prevalence of diabetes was less than 1 percent in the Chinese population in 1980. In subsequent national surveys conducted in 1994 and 2000-2001, the prevalence of diabetes was 2.5 percent and 5.5 percent, respectively. The most recent national survey in 2007 reported that the prevalence of diabetes was 9.7 percent, representing an estimated 92.4 million adults in China with diabetes.”

Yu Xu, Ph.D., of the Shanghai Jiao-Tong University School of Medicine, Shanghai, China, and colleagues with the 2010 China Noncommunicable Disease Surveillance Group, conducted a study to investigate the prevalence of diabetes and glycemic control in the Chinese adult population. Using a multistage, probability sampling design, the researchers conducted a cross-sectional survey in a nationally representative sample of 98,658 Chinese adults in 2010. Plasma glucose and hemoglobin A_1c levels were measured after at least a 10-hour overnight fast among all study participants, and a 2-hour oral glucose tolerance test was conducted among participants without a self-reported history of diagnosed diabetes. Diabetes and prediabetes were defined according to the 2010 American Diabetes Association criteria; whereas, a hemoglobin A_1c level of <7.0 percent was considered adequate glycemic control.

The researchers found that the overall prevalence of diabetes was estimated to be 11.6 percent in the Chinese adult population; 12.1 percent in men, and 11.0 percent in women, with an estimated prevalence of 8.1 percent for newly detected diabetes. “The prevalence of diabetes was higher in urban than in rural residents in both men and women. Furthermore, diabetes prevalence increased with age in both men and women, and men younger than 50 years had a higher prevalence, whereas women older than 60 years had a higher prevalence. In addition, the prevalence of diabetes increased with economic development, as well as in overweight and obese persons.”

The estimated prevalence of prediabetes was 50.1 percent in Chinese adults: 52.1 percent in men and 48.1 percent in women. Rural residents had slightly higher prevalence of prediabetes than did urban residents, especially in men. Additionally, prediabetes was more prevalent in economically underdeveloped regions, as well as in overweight and obese persons.

The authors also found that the proportion of patients with diabetes who were aware of their condition was 30.1 percent among the Chinese general population. Only 25.8 percent of overall patients with diabetes were treated for this condition, and only 39.7 percent of those treated had adequate glycemic control.

“These data suggest that diabetes may have reached an alert level in the Chinese general population, with the potential for a major epidemic of diabetes-related complications, including cardiovascular disease, stroke, and chronic kidney disease in China in the near future without an effective national intervention,” the researchers write. “These findings indicate the importance of diabetes as a public health problem in China.”

(doi:10.l001/jama.2013.168118; 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: Diabetes and Noncommunicable Disease – Prevent the Preventables

“Diabetes is a societal and a health care challenge due to complex interplays among genetic, perinatal, lifestyle, and environmental factors, to name but a few. Rapid modernization has resulted in an obesogenic environment characterized by food abundance, physical inactivity, and psychosocial stress,” writes Juliana C. N. Chan, M.D., F.R.C.P., of the Chinese University of Hong Kong Prince of Wales Hospital International Diabetes Federation Centre of Education, Shatin, Hong Kong, in an accompanying editorial.

“The lack of awareness, information, and feedback has caused many individuals unknowingly to engage in risk-conferring behaviors. Even when the individual becomes aware of his or her risk conditions, the health care systems in many developing areas are not designed to manage and support a person’s multiple health needs for 30 to 40 years or more. These needs include motivation, cognitive-psychological-behavioral support, laboratory assessments, technologies, medications, and hospitalizations.”

“In the final analysis, the WHO defines health as a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity. To this end, government leaderships, partnerships, and community empowerment will be needed to create a health-promoting environment, encourage self-management, and strengthen the health care system to make health a reality.”

(doi:10.l001/jama.2013.168099; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Media Advisory: To contact Clara K. Chow, Ph.D., email cchow@georgeinstitute.org.au or call Veronica McGuire at 905-525-9140, ext. 22169; or email vmcguir@mcmaster.ca.

CHICAGO – In a study that included more than 140,000 participants from17 countries of varying income levels, researchers found a large gap between both detection and control of hypertension across all countries studied, with just over half of participants with hypertension aware of their diagnosis, and about one-third of those being treated for hypertension successfully controlling their blood pressure, according to a study in the September 4 issue of JAMA.

“High blood pressure is the leading cause of cardiovascular disease (CVD) and deaths globally. It is associated with at least 7.6 million deaths per year worldwide (13.5 percent of all deaths), making it the leading risk factor for CVD. The majority of CVD occurs in low-, low-middle-, and upper-middle-income countries. The importance of blood pressure as a modifiable risk factor for CVD is well-recognized and many effective and inexpensive blood pressure-lowering treatments are available. Therefore, hypertension control and prevention of subsequent morbidity and mortality clearly should be achievable,” according to background information in the article. “Information on hypertension prevalence, awareness, treatment, and control in multiple countries and different types of communities is necessary to provide a baseline for monitoring and also to inform the development of new strategies for improving hypertension control.”

Clara K. Chow, Ph.D., of The George Institute for Global Health, Sydney, Australia, and Hamilton Health Sciences and McMaster University, Hamilton, Canada, and colleagues assessed the prevalence, awareness, treatment, and control of hypertension in participants in the Prospective Urban Rural Epidemiology (PURE) study. The study included 153,996 adults (complete data for this analysis on 142,042) 35 to 70 years of age, recruited between January 2003 and December 2009. Participants were from 628 communities in 3 high-income countries (HIC), 10 upper-middle-income and low-middle-income countries (UMIC and LMIC), and 4 low-income countries (LIC). Hypertension was defined as individuals with self-reported treated hypertension or with an average of 2 blood pressure measurements of at least 140/90 mm Hg using an automated digital device. Awareness was based on self-reports, treatment was based on the regular use of blood pressure-lowering medications, and control was defined as individuals with blood pressure lower than 140/90 mm Hg.

Among the participants, 57,840 (40.8 percent) had hypertension and 26,877 (46.5 percent) were aware of the diagnosis. Of those who were aware of the diagnosis, the majority (23,510 [87.5 percent]) were receiving pharmacological treatments, but only a minority of those receiving treatment had controlled blood pressure (7,634 [32.5 percent]).

The authors found a large gap between both detection and control of hypertension across all countries studied. “It shows that while initial therapy was started in the large majority of individuals who are detected to have hypertension, control in participants receiving treatment was very poor. The use of combination therapies, generally required to achieve blood pressure control, was low. Awareness, treatment, and control were lower in LICs compared with other countries and in rural settings of LMICs and LICs compared with urban ones. Despite men having higher rates of hypertension, women consistently had higher awareness, treatment, and control of their hypertension, consistent with a large body of research on sex and health-seeking behavior. Also, participants with more education had greater awareness, treatment, and control, particularly in LICs.”

“The widespread lack of hypertension awareness (a measure of hypertension case identification) and poor control (a measure of inadequate treatment) in all countries studied, despite the identification and control of blood pressure being prioritized by many national and global organizations and despite the availability of inexpensive and effective medications, is concerning,” the researchers write. “These findings suggest that substantial improvement in hypertension diagnosis and treatment is needed.”

(doi:10.l001/jama.2013.184182; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Media Advisory: To contact Simon Thom, M.B., B.S., M.D., email s.thom@imperial.ac.uk. To contact editorial author J. Michael Gaziano, M.D., M.P.H., call Tom Langford at 617-534-1605 or email tlangford@partners.org.

CHICAGO – In a randomized trial that included about 2,000 patients with or at high risk of cardiovascular disease (CVD), use of a fixed-dose combination medication for blood pressure, cholesterol, and platelet control compared to usual care resulted in significantly improved medication adherence after 15 months and small improvements in systolic blood pressure and low-density lipoprotein cholesterol, according to a study in the September 4 issue of JAMA.

“The long-term use of cardiovascular disease preventive therapy is low among people with established disease. This shortfall is greatest in low- and middle-income countries, but even in high-income countries treatment coverage in the community is only about 50 percent in those with coronary disease and 35 percent in those with stroke. People who are at similar risk but have not reached the clinical threshold of experiencing a CVD event are even less likely to be adequately treated. Fixed-dose combination (FDC) therapy may reduce these treatment gaps by reducing cost, complexity, therapeutic inertia, and low adherence,” according to background information in the article.  “Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment.”

Simon Thom, M.B., B.S., M.D., of the International Centre for Circulatory Health, Imperial College London, and colleagues conducted a study to assess whether FDC delivery of aspirin, statin, and 2 blood pressure-lowering agents vs. usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors, systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C). The randomized trial included 2,004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe. The trial follow-up concluded in July 2012. Participants were randomly assigned (1:1) to an FDC-based strategy (n=1,002) containing either (1) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol or (2) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide or to usual care (n=1,002).

At baseline, average BP was 137/78 mm Hg, LDL-C was 91.5 mg/dL, and 1,233 (61.5 percent) of 2,004 participants reported use of antiplatelet, statin, and 2 or more BP-lowering medications. The median (midpoint) duration of follow-up was 15 months for both groups. At the end of the study, 829 (86.3 percent) of 961 participants in the FDC group were continuing with indicated medications compared with 621 (64.7 percent) of 960 in the usual care group. In absolute terms, this amounted to a 21.6 percent difference in treatment rates. Overall, SBP (-2.6 mm Hg) and LDL-C (-4.2 mg/dL) levels were modest but significantly lower in the FDC group compared with the usual care group at the end of the study.

“Although there was consistency of effects across predefined subgroups, evidence existed of larger benefits in patients with lower adherence at baseline. In this subgroup of 727 participants (36 percent), adherence at the end of study was 77 percent vs. 23 percent, SBP was reduced by 4.9 mm Hg, and LDL-C was reduced by 6.7 mg/dL. There were no significant differences in serious adverse events or cardiovascular events between the groups,” the authors write.

“To the best of our knowledge, this was the first randomized trial to assess the long-term use of an FDC containing antiplatelet, statin, and BP-lowering drugs compared with usual care in patients with CVD. The results show that access to FDCs in patients with CVD or similarly high risk improved adherence, BP, and cholesterol levels. The reductions in BP and cholesterol level were small overall in this comparatively well-treated population but were larger in the subgroup not receiving all recommended treatments at baseline.”

(doi:10.l001/jama.2013.277064; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The project was funded by the European Commission Seventh Framework Programme. Dr. Reddy’s Laboratories (Hyderabad, India) provided the FDCs and supported the trial start-up meetings in London and India. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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

Editorial: Progress With the Polypill?

In an accompanying editorial, J. Michael Gaziano, M.D., M.P.H., of the VA Boston Healthcare System, Brigham and Women’s Hospital and Harvard Medical School, Boston, (and Associate Editor, JAMA), comments on the findings of this study.

“Although the potential remains for use of various CVD polypills in certain settings, the precise advantage of this strategy remains largely unproven. Until additional rigorous data are available that demonstrate that the polypill improves clinical CVD outcomes, it may be more important to carefully assess the multiple medications many patients currently are prescribed, often by several physicians. Another way to reduce the number of pills patients are taking is to eliminate those medications for which the benefits are marginal.”

(doi:10.l001/jama.2013.277064; 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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