EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 10, 2015

Media Advisory: To contact Joseph E. Kiss, M.D., email Jim Fitzgerald at jfitzgerald@itxm.org.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2015.119

Iron Supplementation Improves Hemoglobin Recovery Time Following Blood Donation

Among blood donors with normal hemoglobin levels, low­-dose oral iron supplementation, compared with no supplementation, reduced the time to recovery of the postdonation decrease in hemoglobin concentration in donors with low or higher levels of a marker of overall iron storage (ferritin), according to a study in the February 10 issue of JAMA.

It is estimated that 25 percent to 35 percent of blood donors become iron depleted from regular blood donation. Although blood donation is allowed every 8 weeks in the United States, recovery of hemoglobin to the currently accepted standard is frequently delayed, and some donors become anemic. Hemoglobin level and iron status are getting renewed attention as a donor safety issue based on increasing evidence that iron depletion is associated with fatigue, decreased exercise capacity and neurocognitive changes, according to background information in the article.

Joseph E. Kiss, M.D., of the Institute for Transfusion Medicine, Pittsburgh, and colleagues randomly assigned 215 eligible study participants (who had not donated whole blood or red blood cells within 4 months) to receive one tablet of ferrous gluconate (37.5 mg of elemental iron) daily or no iron for 24 weeks after donating a unit of whole blood (500 ml). The study was conducted at four regional blood centers in the United States. The primary outcomes for the study were time to recovery of 80 percent of the postdonation decrease in hemoglobin and recovery of ferritin level (an indicator of the amount of total iron stored in the body).

The researchers found that compared with participants who did not receive iron supplementation, those who did had shortened time to 80 percent hemoglobin recovery in both the low-ferritin (average 32 days vs 158 days) and higher-ferritin groups (average 31 days vs 78 days). Recovery of iron stores in all participants who received supplements took a median of 76 days; for participants not taking iron, median recovery time was longer than 168 days. Without iron supplements, 67 percent of participants did not recover iron stores by 168 days.

“Although the absolute amount of hemoglobin decrease was relatively small and of marginal clinical consequence after a single blood donation, donating blood is an iterative [repeated] process that leads to progressive iron loss and anemia in some frequent blood donors, so it is important that the hemoglobin decrease after blood donation be recovered before the next blood donation,” the authors write.

(doi:10.1001/jama.2015.119; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This work was supported by the National Heart, Lung, and Blood Institute. Dr. Mast reported having received a grant from Novo Nordisk and honoraria from Siemens. No other disclosures were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 10, 2015

Media Advisory: To contact Kazem Rahimi, D.M., M.Sc., email Maya Kay at mkay@georgeinstitute.org.au. To contact editorial author Bryan Williams, M.D., email bryan.williams@ucl.ac.uk.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.18574. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2015.89

For Patients with Type 2 Diabetes, Blood Pressure-Lowering Treatment Linked to Longer Survival, Lower Risk of CVD Events

Blood pressure-lowering treatment among patients with type 2 diabetes is associated with a lower risk of cardiovascular disease (CVD) and heart disease events and improved mortality, according to a study in the February 10 issue of JAMA.

By 2030, it is estimated that there will be at least 400 million individuals with type 2 diabetes mellitus worldwide. Type 2 diabetes is associated with a substantially increased risk of events such as heart attack and stroke. Blood pressure (BP) levels are on average higher among individuals with diabetes and increased BP is a well-established risk factor for people with diabetes. Lowering BP in individuals with diabetes is an area of current controversy, with particular debate surrounding who should be offered therapy and the BP targets to be achieved, according to background information in the article.

Kazem Rahimi, D.M., M.Sc., of the George Institute for Global Health, University of Oxford, Oxford, U.K., and colleagues conducted a review and meta-analysis of large-scale randomized controlled trials of BP-lowering treatment including patients with diabetes, published between January 1966 and October 2014. A search of the medical literature identified 40 trials judged to be of low risk of bias (100,354 participants), and were included in the analysis to examine the associations between BP-lowering treatment and vascular disease in type 2 diabetes.

The researchers found that each 10-mm Hg lower systolic BP was associated with a lower risk of mortality, cardiovascular disease events, coronary heart disease events, stroke, albuminuria (the presence of excessive protein in the urine), and retinopathy (loss of vision related to diabetes). The associations between BP-lowering treatments and outcomes were not significantly different, irrespective of drug class, except for stroke and heart failure.

Although proportional associations of BP­lowering treatment for most outcomes studied were diminished below a systolic BP level of 140 mm Hg, data indicated that further reduction below 130 mm Hg is associated with a lower risk of stroke, retinopathy, and albuminuria, potentially leading to net benefits for many individuals at high risk for those outcomes.

“Among patients with type 2 diabetes, BP lowering was associated with improved mortality and other clinical outcomes. These findings support the use of medications for BP lowering in these patients,” the authors write.

(doi:10.1001/jama.2014.18574; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Treating Hypertension in Patients With Diabetes

“These findings are timely, clear, and important and lend support to current guideline recommendations to consider offering patients with type 2 diabetes antihypertensive therapy when their systolic BP is 140 mm Hg or greater, aiming for a target systolic BP toward 130 mm Hg but not usually lower than this,” writes Bryan Williams, M.D., of University College London, in an accompanying editorial.

“However, the findings of the study by Emdin et al suggest that for some patients, these treatment thresholds and targets might be too conservative, especially for optimally reducing the risk of stroke and the development or progression of albuminuria. This conundrum highlights the problems with clinician overreliance on guidelines and guideline overdependence on an often, uncritical adoption of evidence, despite the limitations of the clinical trials. Guidelines are just that, and are necessarily conservative in providing population-based recommendations that physicians must interpret in the context of the individual patient being treated.”

(doi:10.1001/jama.2015.89; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Dr. Williams has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reports receipt of funding as a senior investigator for the National Institute for Health Research.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 3, 2015

Media Advisory: To contact John B. Holcomb, M.D., email Rob Cahill at Robert.Cahill@uth.tmc.edu.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2015.12.

Study Compares Effectiveness of Different Transfusion Strategies for Severe Trauma

Among patients with severe trauma and major bleeding, those who received a transfusion of a balanced ratio of plasma, platelets, and red blood cells (RBCs) were more likely to have their bleeding stopped and less likely to die due to loss of blood by 24 hours compared to patients who received a transfusion with a higher ratio of RBCs, according to a study in the February 3 issue of JAMA. There was no significant difference in overall death at 24 hours or at 30 days between the two transfusion strategies.

Approximately 20 percent to 40 percent of trauma deaths occurring after hospital admission involve massive hemorrhage from an injury to the trunk of the body and are potentially preventable with rapid hemorrhage control and improved resuscitation techniques. These patients often require massive transfusion. Earlier transfusion with balanced blood product ratios (1:1:1 ratios for plasma, platelets, and red blood cells), defined as “damage control resuscitation”, has been associated with improved outcomes; however, there have been no large multicenter clinical trials, according to background information in the article.

John B. Holcomb, M.D., of the University of Texas Health Science Center at Houston, and colleagues conducted a study in which 680 severely injured patients who arrived at 1 of 12 level I trauma centers and were predicted to require massive transfusion were randomly assigned to receive blood product ratios of 1:1:1 for units of plasma to platelets to red blood cells (a ratio that is the closest approximation to reconstituted whole blood), or 1:1:2, during active resuscitation in addition to all local standard-of-care interventions. Patients were assigned to one these component ratios within 8 minutes of calling the blood bank, allowing the rapid delivery and infusion of the predetermined ratios.

The researchers found no significant differences for the primary outcomes of the study: mortality at 24 hours (12.7 percent in 1:1:1group vs 17.0 percent in 1:1:2 group) or at 30 days (22.4 percent vs 26.1 percent, respectively).  Exsanguination (extensive loss of blood), which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1group (9.2 percent vs 14.6 percent in 1:1:2 group). More patients in the 1:1:1 group achieved hemostasis (the stoppage of bleeding) than in the 1:1:2 group (86 percent vs 78 percent, respectively).

Despite concerns that the 1:1:1 group would experience higher rates of multiple inflammatory-mediated complications such as acute respiratory distress syndrome, multiple organ failure, infection, blood clots, and sepsis, no differences were detected between the two treatment groups.

“Given the lower percentage of deaths from exsanguination and our failure to find differences in safety, clinicians should consider using a 1:1:1 transfusion protocol, starting with the initial units transfused while patients are actively bleeding, and then transitioning to laboratory-guided treatment once hemorrhage control is achieved. Future studies of hemorrhage control products, devices, and interventions should concentrate on the physiologically relevant period of active bleeding after injury and use acute complications and later deaths (24 hours and 30 days) as safety end points,” the authors write.

(doi:10.1001/jama.2015.12; 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: 11 A.M. (ET) TUESDAY, FEBRUARY 3, 2015

Media Advisory: To contact Hemal K. Kanzaria, M.D., M.S.H.P.M., call Enrique Rivero at 310-794-2273 or email ERivero@mednet.ucla.edu.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.17550.

Care of Patients Prior to Making a Diagnosis Rarely Assessed By Quality Measures

An examination of process measures endorsed by the National Quality Forum finds that these measures focus predominantly on management of patients with established diagnoses, and that quality measures for patient presenting symptoms often do not reflect the most common reasons patients seek care, according to a study in the February 3 issue of JAMA.

Health care reform efforts, such as accountable care organizations, focus on improving value partly through controlling use of services, including diagnostic tests. Publicly reported quality measures that evaluate care provided prior to arriving at a diagnosis could prevent financial incentives from producing harm. The National Quality Forum (NQF) currently serves as the consensus-based quality-measure-endorsement entity called for in the Affordable Care Act. Endorsed measures are often adopted by the Centers for Medicare & Medicaid Services in payment and public reporting programs, according to background information in the article.

Hemal K. Kanzaria, M.D., M.S.H.P.M., of the University of California, Los Angeles, and colleagues examined NQF-endorsed process measures that evaluate the prediagnostic (prior to making a diagnosis) care of patients presenting with signs or symptoms. There were 372 process quality measures listed on the NQF website as of June 4, 2014; from these, 385 codings were determined, by categorizing the process quality measures by a system developed by the Institute of Medicine. Approximately two-thirds (n = 267) targeted disease management and 12 percent (n = 46) targeted evaluation/diagnosis. The remaining were evenly distributed among prevention, screening, and follow-up.

Of 313 measures pertaining to evaluation/diagnosis or management, 211 (67 percent) began with an established diagnosis, whereas 14 (4.5 percent) started with a sign/symptom. The sign/symptom-based measures focused on geriatric care (e.g., memory loss, falls, urine leakage) or emergency department care (e.g., chest pain). In contrast, many common reasons for which patients seek care, including fever, cough, headache, shortness of breath, earache, rash, and throat symptoms, were not reflected by the quality measures. The performance of a lab test or medical imaging study was the action required by 59 of 313 (19 percent) endorsed quality measures; many others required actions related to medication prescribing.

“… we believe that using a comprehensive set of endorsed sign/symptom-based measures could help patients receive timely care as payment models are changed and may prevent financial incentives from resulting in underuse of necessary care. Efforts to develop valid sign/symptom-based quality measures will be challenging; however, as cost pressures increase, they may be necessary to maintain and improve the accuracy of patient diagnosis upon which all subsequent care depends,” the authors write.

(doi:10.1001/jama.2014.17550; 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: 11 A.M. (ET) TUESDAY, FEBRUARY 3, 2015

Media Advisory: To contact corresponding author Karl Y. Bilimoria, M.D., M.S., email Bret Coons at bcoons@nm.org. To contact editorial author Lucian L. Leape, M.D., email Todd Datz at tdatz@hsph.harvard.edu.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.18614. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.18666.

 
Hospital Readmissions after Surgery Associated Mostly With Complications Related to Surgical Procedure

In a study that included readmission information from nearly 350 hospitals, readmissions the first 30 days after surgery were associated with new postdischarge complications related to the surgical procedure and not a worsening of any medical conditions the patient already had while hospitalized for surgery, according to a study in the February 3 issue of JAMA.

Readmission as a quality and cost-containment metric is now a major issue for hospitals, clinicians, and policy makers. Financial penalties for readmission have been expanded beyond medical conditions to include surgical procedures. Hospitals are working to reduce readmissions; however, little is known about the reasons for readmission after surgery. Identification of these reasons could help direct future surgical quality improvement efforts and policy decisions designed to reduce surgical readmission rates, according to background information in the article.

Ryan P. Merkow, M.D., M.S., of the American College of Surgeons, Chicago, and colleagues examined the reasons, timing, and factors associated with unplanned postoperative hospital readmissions within 30 days after surgery. The study included data from patients undergoing surgery at one of 346 hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) between January and December 2012. Readmission rates and reasons were assessed for all surgical procedures and for six representative operations: bariatric procedures, colectomy or proctectomy, hysterectomy, total hip or knee arthroplasty, ventral hernia repair, and lower extremity vascular bypass.

The unplanned 30 day readmission rate for 498,875 operations was 5.7 percent. For the individual procedures, the rate of readmission ranged from 3.8 percent after hysterectomy to 14.9 percent after lower extremity vascular bypass. The most common reason for unplanned readmission was surgical site infection (SSI; 19.5 percent), ranging from 11.4 percent after bariatric surgery to 36.4 percent after lower extremity vascular bypass.

The most common reason for readmission after bariatric surgery was ileus (blockage of the intestine) or obstruction (24.5 percent), and ileus or obstruction was the second most common reason for readmission overall (10.3 percent) and for colectomy or proctectomy, ventral hernia repair, and hysterectomy. Other common causes included dehydration or nutritional deficiency, bleeding or anemia, blood clots, and surgical device issues.

When examining early (within 7 days of discharge) and late (more than 7 days after discharge) unplanned readmissions separately, the top 3 reasons for readmission were similar overall (SSI, ileus or obstruction, and bleeding) and when examining each of the 6 procedure groups individually. Only 2.3 percent of patients were readmitted for the same complication they had experienced during their index hospitalization.

“Understanding the underlying reasons for readmission, the timing, and the associated factors should help hospitals to undertake targeted quality improvement initiatives to reduce readmissions. However, surgical readmissions mostly reflect postdischarge complications, and readmission rates may be difficult to reduce until effective strategies are put forth to reduce common complications such as SSI. Efforts should focus on reducing complication rates overall than simply those that occur after discharge, and this will subsequently reduce readmission rates as well. Readmissions after surgery may not be an appropriate measure for pay-for-performance programs but rather better suited as measure for hospitals to track internally,” the authors write.

(doi:10.1001/jama.2014.18614; 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: Hospital Readmissions Following Surgery

In an accompanying editorial, Lucian L. Leape, M.D., of the Harvard School of Public Health, Boston, comments on this study.

“The findings reported by Merkow et al are noteworthy because they are derived from analysis of ACS NSQIP data, widely regarded as among the most reliable measures of quality. These results contrast with most readmission studies that rely on administrative data, which are known to have major deficiencies. In addition, the authors make several useful suggestions as to how these findings could be used to reduce readmissions—but an important question is how can the data be used to reduce the pain and suffering that complications cause for patients? … The findings reported by Merkow et al provide an unprecedented opportunity to apply these lessons to make substantial reductions in surgical complications.”

(doi:10.1001/jama.2014.18666; 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: 11 A.M. (ET) TUESDAY, FEBRUARY 3, 2015

Media Advisory: To contact Nicholas H. Osborne, M.D., M.S., email Kara Gavin at kegavin@umich.edu. To contact David A. Etzioni, M.D., M.S.H.S., email Jim McVeigh at Mcveigh.Jim@mayo.edu. To contact editorial author Donald M. Berwick, M.D., M.P.P., email Madge Kaplan at mkaplan@ihi.org.

To place an electronic embedded link to this study and editorial in your story  This link to the 1^st study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2015.25. This link to the 2^nd study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2015.90. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2015.4.

Studies Find No Association Between Participation in Surgical Quality Improvement Program and Improvement in Outcomes, Complications, Risk of Death

Participation by hospitals in the American College of Surgeons National Surgical Quality Improvement Program has not been associated with an improvement in surgical outcomes, serious complications, hospital readmissions, risk of death or lower Medicare payments, according to two studies in the February 3 issue of JAMA.

Increased scrutiny of hospital performance has led to an increase of clinical registries used to benchmark outcomes. One of the most visible national quality reporting programs is the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). The program provides hospitals with reports that include a detailed description of their risk-adjusted outcomes (e.g., mortality, specific complications, and length of stay). These reports allow hospitals to benchmark their performance relative to all other ACS NSQIP hospitals. Participating hospitals are encouraged to focus improvement efforts on areas in which they perform poorly. The extent to which participation in ACS NSQIP improves outcomes is unclear.

In one study, Nicholas H. Osborne, M.D., M.S., of the University of Michigan, Ann Arbor, and colleagues evaluated the association of participation in the ACS NSQIP with surgical outcomes and payments among Medicare patients. The researchers used national Medicare data (2003-2012) for a total of 1,226,479 patients undergoing general and vascular surgery at 263 hospitals participating in ACS NSQIP and 526 nonparticipating (control) hospitals.

The authors found that although there were slight trends toward improved outcomes in ACS NSQIP hospitals before vs after enrollment (year 1, year 2, and year 3), there were similar trends in control hospitals, with no significant improvements in outcomes after enrollment in ACS NSQIP. For example, in analyses comparing outcomes at 3 years after (vs before) enrollment, there were no significant differences in risk-adjusted 30-day mortality (4.3 percent vs 4.5 percent), serious complications (11.1 percent vs 11.0 percent), reoperations (0.49 percent vs 0.45 percent), or readmissions (13.3 percent vs 12.8 percent).

There were also no differences at 3 years after (vs before) enrollment in average total Medicare payments, or payments for the index admission or hospital readmission.

“Enrollment in a national surgical quality reporting program was not associated with improved outcomes or lower payments among Medicare patients. Feedback of outcomes alone may not be sufficient to improve surgical outcomes,” the authors write.

(doi:10.1001/jama.2015.25; Available pre-embargo to the media at https://media.jamanetwork.com)

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

In another study, David A. Etzioni, M.D., M.S.H.S., of Mayo Clinic Arizona, Phoenix, and colleagues compared rates of any complications, serious complications, and death during a hospitalization for elective general/vascular surgery at hospitals that did vs did not participate in the NSQIP.

Data from the University HealthSystem Consortium from January 2009 to July 2013 were used to identify elective hospitalizations representing a broad spectrum of elective general/vascular operations in the United States. The study group included 345,357 hospitalizations occurring in 113 different academic hospitals; 172,882 (50.1 percent) hospitalizations were in NSQIP hospitals. Hospitalized patients were predominantly female (62 percent), with an average age of 56 years. The types of procedures performed most commonly were hernia repairs (15.7 percent), bariatric (10.5 percent), mastectomy (9.7 percent), and cholecystectomy (9.0 percent).

Over the course of the study period, risk-adjusted rates of postoperative complications, serious complications, and mortality decreased for hospitalizations at both NSQIP and non­NSQIP hospitals. After accounting for patient risk, procedure type, underlying hospital performance, and temporal (transient) trends, the researchers found no significant differences over time between NSQIP and non­NSQIP hospitals in terms of likelihood of inpatient complications, serious complications, or risk of death.

The authors suggest that the “failure of this and other studies to demonstrate an association between outcomes-oriented reporting systems and improved surgical outcomes may be related to difficulties translating outcomes reports into evidence-based approaches to quality improvement.”

“This study has implications for hospitals and health care systems considering the role of programs that monitor surgical outcomes. Among hospitals providing care to patients undergoing general and vascular surgical procedures, our findings suggest that a surgical outcomes reporting system does not provide a clear mechanism for quality improvement.”

(doi:10.1001/jama.2015.90; 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: Measuring Surgical Outcomes for Improvement

“The most likely explanation for the findings of these 2 studies is that end-results information, although necessary for improvement, is not sufficient, and that the skills necessary to make effective changes in processes and cultures do not yet pervade U.S. hospitals, to say the least. Both research groups speculate about that as a reason for their results,” writes Donald M. Berwick, M.D., M.P.P., of the Institute for Healthcare Improvement, Cambridge, Mass., in an accompanying editorial.

“ACS NSQIP and its champions and proponents should take these important studies as prompts, not to decrease investment in the careful analysis and reporting of surgical results but rather to link that information more energetically to processes of learning, skill building, and change within participating hospitals. Hospitals not enrolled in ACS NSQIP should not use these studies as an excuse to avoid measuring and investigating their own surgical results systematically, one way or another. But all hospitals should take note that measurement, alone, is not enough for improvement.”

(doi:10.1001/jama.2015.4; 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: 11 A.M. (ET) TUESDAY, JANUARY 27, 2015

Media Advisory: To contact Tom Tomlinson, Ph.D., email Sarina Gleason at Sarina.Gleason@cabs.msu.edu.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16363.

Survey Indicates Willingness of General Population to Donate Tissue Samples to Biobank for Research

A survey of nearly 1,600 individuals found that the majority were willing to donate tissue samples and medical information to a biobank for research and that most were willing to donate using a blanket consent, according to a study in the January 27 issue of JAMA.

Research biobanks are increasing in number and importance, with great potential for advancing knowledge of human health, disease, and treatment. Recruitment of donors is vital to their success and relies largely on blanket consent, in which donors give one-time permission for any future research uses of their coded specimen. Previous studies suggest that donors may have moral, religious, and cultural concerns about the use to which their specimens are put, which may affect their willingness to give blanket consent. These earlier studies, however, surveyed groups that were not representative of the U.S. population, according to background information in the article.

Tom Tomlinson, Ph.D., of Michigan State University, East Lansing, and colleagues used the GfK KnowledgePanel (a probability-based online panel of adults, designed to represent the U.S. population) to field a survey examining associations between moral concerns and the willingness to donate to a biobank. Respondents read an introductory description of a fictional biobank and then used a 6-point scale—from strongly agree to strongly disagree—to indicate their willingness to donate, first using blanket consent and then “even if” their samples might be used in each of 7 potential research scenarios presenting moral concerns. The researchers then gave respondents short descriptions of the benefits and consequences of 5 methods of gaining consent and asked them to indicate which were the acceptable, best, and worst options.

The final analysis included 1,599 of 2,654 participants. Respondents were older (51 years vs 45 years for nonrespondents), were more commonly white, and had higher levels of education and household income. Using blanket consent, 68 percent were willing to donate. In all but 1 scenario, moral concerns were associated with a significant reduction in willingness to donate.

When asked about different approaches to gaining consent, 43.6 percent of respondents found the blanket consent method to be unacceptable. Specific consent, in which donors are asked to consent to each study using their specimen, was considered the worst option by 45.0 percent. These findings suggest “that an adequate approach for dealing with donors’ moral concerns may lie between these 2 extremes,” the authors write.

“As recruitment of donors becomes more widespread, such concerns [as raised in this study] may need to be addressed to moderate possible effects on donation rates.”

(doi:10.1001/jama.2014.16363; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The work was supported by a grant from the National Human Genome Research Institute. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, JANUARY 27, 2015

Media Advisory: To contact Peter A. Pinto, M.D., email the NCI Press Office at ncipressofficers@mail.nih.gov. To contact editorial co-author Ethan Basch, M.D., email Katy Jones at katy_jones@med.unc.edu.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.17942.  This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.17943.

Targeted Biopsy Technique Associated With Increased Detection of High-Risk Prostate Cancer, Decreased Detection of Low-Risk Cancer

Among men undergoing biopsy for suspected prostate cancer, targeted magnetic resonance/ultrasound fusion biopsy, compared with a standard biopsy technique, was associated with increased detection of high-risk prostate cancer and decreased detection of low-risk prostate cancer, according to a study in the January 27 issue of JAMA.

The current diagnostic procedure for men suspected of prostate cancer is a standard extended-sextant biopsy (i.e., standard biopsy). Advances in imaging have led to the development of targeted magnetic resonance (MR)/ultrasound fusion biopsy (i.e., targeted biopsy), which has been shown to detect prostate cancer. The implications of targeted biopsy alone vs standard biopsy or the 2 methods combined are not well understood, according to background information in the article.

Peter A. Pinto, M.D., and M. Minhaj Siddiqui, M.D., of the National Cancer Institute, National Institutes of Health, Bethesda, Md., and colleagues examined the outcomes of 1,003 men who underwent an imaging procedure to identify regions of prostate cancer suspicion followed by targeted biopsy and concurrent standard biopsy from 2007 through 2014 at the National Cancer Institute. Patients were referred for elevated level of prostate-specific antigen (PSA) or abnormal digital rectal examination results, often with prior negative biopsy results.

Targeted biopsy diagnosed a similar number of cancer cases (461 patients) to standard biopsy (469 patients). There was exact agreement between targeted and standard biopsy in 690 men (69 percent) undergoing biopsy. However, the 2 approaches differed in that targeted biopsy diagnosed 30 percent more high-risk cancers vs standard biopsy (173 vs 122 cases) and 17 percent fewer low-risk cancers (213 vs 258 cases).

Adding standard biopsy to targeted biopsy lead to 103 more cases of cancer (22 percent); however, of these, 83 percent were low risk while only 5 percent were high risk; 12 percent were intermediate risk. Thus, the usefulness of combining these methods was found to be limited, with the number needed to biopsy by standard biopsy in addition to targeted biopsy to diagnose 1 additional high-risk tumor was 200 men.

The predictive ability of targeted biopsy for differentiating low-risk from intermediate- and high-risk disease in 170 men with whole-gland pathology after prostatectomy (surgical removal of the prostate gland) was greater than that of standard biopsy or the 2 approaches combined.

“This study demonstrated that targeted biopsy could significantly change the distribution of risk in men newly diagnosed with prostate cancer toward diagnosis of more high­risk disease. Although these improvements in risk stratification could translate into substantial clinical benefits, it is important to recognize that this study is preliminary with regard to clinical end points such as recurrence of disease and prostate cancer-specific mortality. These findings provide a strong rationale for the conduct of randomized clinical trials to determine the effect of targeted biopsy on clinical outcomes,” the authors write.

(doi:10.1001/jama.2014.17942; 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: MR/Ultrasound Fusion-Guided Biopsy in Prostate Cancer

“Decisions to adopt new technologies such as this one that occupy a largely unregulated space ultimately rely on clinicians and payers, based on available data,” write Lawrence H. Schwartz, M.D., of the Columbia University College of Physicians and Surgeons, New York, and Ethan Basch, M.D., of the University of North Carolina, Chapel Hill, and Associate Editor, JAMA, in an accompanying editorial.

“Any test that can inform decision making and potentially spare patients harm is immediately appealing, even if the effect on clinical outcomes is unknown. Nonetheless, a new test should not be widely adopted in the absence of direct evidence showing benefits on quality of life, life expectancy, or ideally both. Therefore, the scientific community has the responsibility to ensure through clinical research that promising new technologies such as MR/ultrasound fusion imaging-guided biopsies bring value to patients.”

(doi:10.1001/jama.2014.17943; 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: 5:15 P.M. (ET) TUESDAY, JANUARY 20, 2015

Media Advisory: To contact Michael J. Noto, M.D., Ph.D., email Craig Boerner at craig.boerner@Vanderbilt.Edu. To contact editorial co-author Didier Pittet, M.D., M.S., email didier.pittet@hcuge.ch.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.18400. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.18482.

Findings Do Not Support Chlorhexidine Bathing in ICUs

Once daily bathing with disposable cloths with the topical antimicrobial agent chlorhexidine of critically ill patients did not reduce the incidence of health care-associated infections, according to a study appearing in JAMA. The study is being released to coincide with its presentation at the Society of Critical Care Medicine’s 44th Critical Care Congress.

Infections acquired during hospitalization (health care associated infections) are associated with increased hospital length of stay, rates of death, and increased costs. The skin of hospitalized patients is a reservoir for infectious pathogens. Subsequent invasion by skin flora is thought to be a mechanism contributing to health care-associated infections. Chlorhexidine is a broad-spectrum topical antimicrobial agent that, when used to bathe the skin, may decrease the bacterial burden, thereby reducing infections. Chlorhexidine bathing is incorporated into some expert guidelines, according to background information in the article.

Michael J. Noto, M.D., Ph.D., of Vanderbilt University, Nashville, Tenn., and colleagues conducted a study in which five adult intensive care units in Nashville performed once-daily bathing of all patients (n = 9,340) with disposable cloths impregnated with 2 percent chlorhexidine or nonantimicrobial cloths as a control. Bathing treatments were performed for a 10-week period followed by a 2-week washout period (a period allowed in order to eliminate the effect of the first intervention before starting a new intervention), during which patients were bathed with nonantimicrobial disposable cloths, before crossover (switching) to the alternate bathing treatment for another 10 weeks.

A total of 55 infections occurred during the chlorhexidine bathing period (4 central line-associated bloodstream infections [CLABSIs], 21 catheter-associated urinary tract infections [CAUTIs], 17 ventilator-associated pneumonia [VAP], and 13 Clostridium difficile) and 60 infections during the control bathing periods (4 CLABSI, 32 CAUTI, 8 VAP, and 16 C difficile infections). After adjusting for various factors, no significant difference between groups in the rate of the primary outcome (composite of these infections) was detected.

Other infection-related secondary outcomes, including health care-associated bloodstream infections, blood culture contamination, and clinical cultures positive for multi-drug resistant organisms were also not improved by chlorhexidine.

“The finding that chlorhexidine bathing did not reduce infections in this study suggests that such bathing may not be necessary, resulting in cost saving and avoidance of unnecessary [antimicrobial] exposure without adversely affecting clinical outcome,” the authors write.

(doi:10.1001/jama.2014.18400; 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: Daily Chlorhexidine Bathing for Critically Ill Patients

In an accompanying editorial, Didier Pittet, M.D., M.S., of the University of Geneva Hospitals, Geneva, Switzerland, and Derek C. Angus, M.D., M.P.H., of the University of Pittsburgh School of Medicine, and Associate Editor, JAMA, write that “widespread treatment of patients with antimicrobials – whether antibiotics, antivirals, antifungals, or biocides – has never been a good idea.”

“Issues around chlorhexidine use include allergy, costs, resistance, and even safety. Although chlorhexidine bathing was found previously to reduce health care-acquired infection, the largest benefit appears to be in settings where the baseline prevalence of multidrug-resistant organisms is high. In these settings, the same benefits potentially could be gained through other approaches, such as improved hand hygiene, which may be safer and less likely to affect the ecology of bacterial resistance in the ICU. The current study by Noto et al suggests that widespread adoption of daily chlorhexidine bathing is not indicated at this point, a position also articulated in the 2014 Society for Healthcare Epidemiology of America guidelines. Rather, for institutions with infection rates similar to those reported in the current study, a simpler, less expensive approach that focuses on basic hygiene practices seems best.”

(doi:10.1001/jama.2014.18482; 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: 11 A.M. (ET) TUESDAY, JANUARY 20, 2015

Media Advisory: To contact corresponding author Juliane E. Kämmer, Ph.D., email kaemmer@mpib-berlin.mpg.de.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.15770.

Working Collaboratively May Help Reduce Medical Errors

Medical students who worked in pairs were more accurate in diagnosing simulated patient cases compared to students who worked alone, according to a study in the January 20 issue of JAMA.

Diagnostic errors contribute substantially to preventable medical error. Cognitive error is among the leading causes of diagnostic errors and mostly results from faulty data synthesis, according to background information in the article.

Wolf E. Hautz, M.D., M.M.E., of the Charite Campus Mitte and Campus Virchow Klinikum, Berlin, Germany, and colleagues investigated the effect of working in pairs as opposed to alone on diagnostic performance among fourth-year medical students. Participants were randomly assigned to work individually or in pairs. Their main task was to evaluate six simulated cases of difficult breathing on a computer. Each case started with a video presentation of a prototypical patient. Thereafter, participants could select, in any order, from 30 diagnostic tests and as many as desired, but were instructed to be as fast and accurate as possible.  Results were presented as real-world clinical information (heart sounds or x-ray images).  To complete a case, participants had to select 1 of 20 diagnoses and indicate their confidence in the answer.

Of 88 students recruited, 28 worked individually and 60 in pairs. Pairs of students were more accurate than individuals in selecting a correct diagnosis (68 percent vs 50 percent) despite having comparable knowledge about the topic and selecting an equal number of diagnostic tests. Pairs needed longer time than individuals to reach a diagnosis, but the tests they selected would have taken less time in a real clinical setting. Pairs were more confident with their selected diagnoses than individuals.

“Similar to other studies, collaboration may have helped correct errors, fill knowledge gaps, and counteract reasoning flaws,” the authors write.

(doi:10.1001/jama.2014.15770; 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: 5:15 P.M. (ET) TUESDAY, JANUARY 20, 2015

Media Advisory: To contact Martha A.Q. Curley, R.N., Ph.D., email Christine Coleman at chrcol@nursing.upenn.edu. To contact editorial author Sangeeta Mehta, M.D., F.R.C.P.C., email Sally Szuster at sszuster@mtsinai.on.ca.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.18399.  This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2015.1.

Use of Sedation Protocol Does Not Reduce Time on Ventilator for Children With Respiratory Failure

Among children undergoing mechanical ventilation for acute respiratory failure, the use of a nurse-implemented, goal­directed sedation protocol compared with usual care did not reduce the duration of mechanical ventilation, according to a study appearing in JAMA. The study is being released to coincide with its presentation at the Society of Critical Care Medicine’s 44th Critical Care Congress.

Although sedation therapy benefits critically ill infants and children, it is also associated with adverse effects. Numerous studies in adult critical care support a minimal yet effective approach to sedation management. In contrast, few data inform sedation practices in pediatric critical care. Knowledge generated in adult critical care may not translate to the care of critically ill children, according to background information in the article.

Martha A.Q. Curley, R.N., Ph.D., of the University of Pennsylvania, Philadelphia, and colleagues studied 2,449 children (average age, 4.7 years) mechanically ventilated for acute respiratory failure in pediatric intensive care units (PICUs) to a sedation intervention (17 sites; n = 1,225 patients) or sedation with usual care (14 sites; n = 1,224 patients). The intervention PICUs used a protocol that included targeted sedation, arousal assessments, extubation (removal of breathing tube) readiness testing, sedation adjustment every 8 hours, and sedation weaning. Patients were followed up until 72 hours after opioids were discontinued, 28 days, or hospital discharge.  The study (RESTORE) was conducted from 2009-2013.

The duration of mechanical ventilation, the primary outcome for the study, was not different between the 2 groups (intervention: median, 6.5 days vs control: median, 6.5 days).  There were no group differences in the time to recovery from acute respiratory failure, duration of weaning from mechanical ventilation, PICU and hospital lengths of stay or 28- or 90-day in-hospital mortality. There were no significant differences in sedation-related adverse events including inadequate pain management, inadequate sedation management, extubation failure, ventilator-associated pneumonia, catheter-associated bloodstream infection, or new tracheostomy. Intervention patients experienced more postextubation stridor (an abnormal sound made when the breathing passages are narrowed; 7 percent vs 4 percent) and fewer stage 2 or worse immobility-related pressure ulcers (<1 percent vs 2 percent).

“Exploratory analyses of several secondary outcomes indicated that the sedation protocol was associated with a difference in patients’ sedation experience; patients in the intervention group were able to be safely managed in a more awake and calm state while intubated, receiving fewer days of opioid exposure and fewer sedative classes without an increase in inadequate pain or sedation management or clinically significant iatrogenic [consequence of treatment] withdrawal compared with patients receiving usual care, but they experienced more days with reported pain and agitation, suggesting a complex relationship among wakefulness, pain, and agitation,” the authors write.

The researchers add that although this study focused on the process of how sedatives are administered, future studies should compare the best sedative agent for varied lengths of critical illness. “Outcomes of interest include efficacy as well as an evaluation of the immediate risk-benefit ratio and an evaluation of the long-term effect of sedatives on neurocognitive development and posttraumatic stress.”

(doi:10.1001/jama.2014.18399; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Protocolized Sedation in Critically Ill Children

“Curley and colleagues answered the call for the conduct of a large clinical trial in children and have contributed valuable data to help advance approaches to sedation management in critically ill children,” writes Sangeeta Mehta, M.D., F.R.C.P.C., of Mount Sinai Hospital and the University of Toronto, in an accompanying editorial.

“While it is disappointing that this trial showed no advantage of a complex sedation management strategy, it is reassuring that the overall clinical outcomes related to ‘usual care’ in the 14 control PICUs were not significantly different than protocolized sedation in the intervention PICUs. It is imperative that high-quality research in this field continues, not only to learn more about the short- and long-term effects of sedation strategies but, more importantly, to improve clinical care and outcomes for these vulnerable patients.”

(doi:10.1001/jama.2015.1; 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: 11 A.M. (ET) TUESDAY, JANUARY 20, 2015

Media Advisory: To contact Sheree L. Boulet, Dr.P.H., M.P.H., call Brittany Behm at 404-639-3286 or email media@cdc.gov.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.17985.

Use of IVF Procedure for Male Infertility Has Doubled, Although Not Associated With Improved Outcomes

The use of an assisted reproduction technique known as intracytoplasmic sperm injection (ICSI) doubled between 1996 and 2012, although compared with conventional in vitro fertilization (IVF), use of ICSI was not associated with improved reproductive outcomes, according to a study in the January 20 issue of JAMA.

Intracytoplasmic sperm injection is an IVF procedure in which a single sperm is injected directly into an egg. The introduction of ICSI in 1992 revolutionized the treatment of couples with male factor infertility (infertility due to abnormal semen characteristics, abnormal sperm function, or surgical sterilization), and made paternity possible for a large proportion of men with no measurable sperm count. In contrast to conventional IVF, ICSI bypasses natural barriers to fertilization, thereby increasing the possibility of the transmission of genetic defects compared to conventional IVF. In addition, the procedure is also considerably more expensive than conventional IVF and adds to financial burdens already experienced by many couples undergoing fertility treatment, according to background information in the article.

Sheree L. Boulet, Dr.P.H., M.P.H., of the Centers for Disease Control and Prevention, Atlanta, and colleagues assessed national trends and reproductive outcomes of fresh IVF cycles (embryos transferred without being frozen) associated with the use of ICSI compared with conventional IVF. The researchers used data on fresh IVF and ICSI cycles reported to the U.S. National Assisted Reproductive Technology Surveillance System during 1996-2012.

Of the 1,395,634 fresh IVF cycles from 1996 through 2012, 908,767 (65.1 percent) used ICSI and 499,135 (35.8 percent) reported male factor infertility. Among cycles with male factor infertility, ICSI use increased from 76.3 percent to 93.3 percent; for those without male factor infertility, ICSI use increased from 15.4 percent to 66.9 percent.

During 2008-2012, male factor infertility was reported for 35.7 percent (176,911/494,907) of fresh cycles. In the absence of male factor infertility, ICSI use was associated with small but statistically significant decreases in implantation, pregnancy, live birth, multiple live birth, and low birth weight rates compared with conventional IVF.

“Although such differences may be a function of the large sample size and thus not clinically relevant, our findings suggest that use of ICSI may improve fertilization rates but not implantation or pregnancy rates in the setting of unexplained infertility, advanced maternal age, and low oocyte [a cell from which an egg develops] yield,” the authors write.

(doi:10.1001/jama.2014.17985; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health. 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: 11 A.M. (ET) TUESDAY, JANUARY 20, 2015

Media Advisory: To contact Richard K. Burt, M.D., call Bret Coons at 312-926-2955 or email bcoons@nm.org. To contact editorial author Stephen L. Hauser, M.D., call Pete Farley at 415- 502-4608 or email peter.farley@ucsf.edu.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.17986. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.18150.

Stem Cell Transplantation Shows Potential for Reducing Disability in Patients with MS

Results from a preliminary study indicate that among patients with relapsing-remitting multiple sclerosis (MS), treatment with nonmyeloablative hematopoietic stem cell transplantation (low intensity stem cell transplantation) was associated with improvement in measures of disability and quality of life, according to a study in the January 20 issue of JAMA.

Fifty percent of patients with MS are unable to continue employment by 10 years from diagnosis or are unable to walk by 25 years. Despite an annual cost of approximately $47,000 per patient to treat MS, no therapy approved by the U.S. Food and Drug Administration has been shown to significantly reverse neurological disability or improve quality of life, according to background information in the article.

Multiple sclerosis is thought to be an immune­mediated disorder of the central nervous system. Autologous (the use of one’s own cells) hematopoietic (blood) stem cell transplantation (HSCT) is a form of immune suppression but unlike standard immune-based drugs, autologous HSCT is designed to reset rather than suppress the immune system. Richard K. Burt, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, and colleagues studied the association of nonmyeloablative HSCT with neurological disability and other clinical outcomes in patients with relapsing-remitting MS (defined as acute relapses followed by partial or complete recovery and stable clinical manifestations between relapses; n = 123) or secondary-progressive MS (defined as a gradual progression of disability with or without superimposed relapses; n = 28) treated between 2003 and 2014.

Outcome analysis was available for 145 patients with an average follow-up of 2.5 years. On a measure of disability (Expanded Disability Status Scale [EDSS] score), there was significant improvement in 41 patients (50 percent of patients tested at 2 years) and in 23 patients (64 percent of patients tested at 4 years). “To our knowledge, this is the first report of significant and sustained improvement in the EDSS score following any treatment for MS,” the authors write.

Receipt of HSCT was also associated with improvement in physical function, cognitive function and quality of life. There was also a reduction on another measure of clinical disease severity, volume of brain lesions associated with MS seen on magnetic resonance imaging (MRI). Four-year relapse-free survival was 80 percent and progression-free survival was 87 percent.

Patient selection is important in determining outcome, the researchers write. “In the post hoc analysis, the EDSS score did not improve in patients with secondary-progressive MS or in those with disease duration longer than 10 years.”

The authors note the results are limited because this was an observational study without a control group. “Definitive conclusions will require a randomized trial; however, this analysis provides the rationale, appropriate patient selection, and therapeutic approach for a randomized study.”

(doi:10.1001/jama.2014.17986; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was made possible by financial support from the Danhakl family, the Cumming Foundation, the Zakat Foundation, the McNamara Purcell Foundation, and Morgan Stanley and Company. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Hematopoietic Stem Cell Transplantation for MS

Stephen L. Hauser, M.D., of the University of California, San Francisco, writes in an accompanying editorial that the study by Burt et al, taken together with other available evidence, enables several conclusions to be made with reasonable confidence.

“First, autologous HSCT does not appear to be effective against established progressive forms of MS and, absent new data, additional trials of these protocols are probably not indicated for patients with progressive MS. Second, immunosuppressive regimens that include HSCT appear to be effective against the relapsing-remitting form of MS, at least over several years of observation. However, it is by no means clear that the beneficial effects result from the infusion of stem cells rather than from the conditioning regimen. Given the availability of highly effective FDA-approved therapies against relapsing-remitting MS, it would seem reasonable to use these proven monotherapies in the clinical setting before considering complex HSCT regimens.”

“Third, the mechanism of action of autologous HSCT in MS needs to be clarified. … Fourth, it is important to remember that MS is a chronic disease, usually arising in young adults and lasting throughout the lifespan. Many important disability-related outcomes take many years or decades to develop. To understand the role of any therapy for MS, and especially an intensive regimen with uncertain long-term risk, very long follow-up periods are required to meaningfully assess if the disease has indeed been rebooted over the long-term, and also to increase confidence that these therapies have not caused undue harm.”

(doi:10.1001/jama.2014.18150; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Dr. Hauser has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported serving on scientific advisory boards for Symbiotix, Annexon, and Bionure.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, JANUARY 20, 2015

Media Advisory: To contact corresponding author Sachin Yende, M.D., M.S., email Richard Pietzak at pietzakr@upmc.edu.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.18229.

Hospitalization for Pneumonia Associated with Increased Risk of Cardiovascular Disease

Hospitalization with pneumonia in older adults was associated with an increased short-term and long-term risk of cardiovascular disease (CVD), suggesting that pneumonia may be an important risk factor for CVD, according to a study in the January 20 issue of JAMA.

Cardiovascular disease is the principal cause of illness and death worldwide. Characterizing the risk factors for CVD is important to design optimal preventive strategies. Several studies that examined the association between infection and subsequent long­term risk of CVD have had conflicting results. Characterizing the short-term and long-term risk of CVD after infection is important because it could suggest that infection is a risk factor for CVD, according to background information in the article.

Vicente F. Corrales-Medina, M.D., M.Sc., of the University of Ottawa, Ottawa Ontario, Canada, and colleagues examined whether hospitalization for pneumonia is associated with an increased short-term and long-term risk of CVD. The researchers chose pneumonia because respiratory tract infections have been consistently associated with increased risk of CVD, pneumonia is a well-characterized infectious syndrome that affects 1.2 percent of the population in the northern hemisphere each year, and it is the most common medical diagnosis responsible for hospitalizations in the United States.

The study included two community-based groups: the Cardiovascular Health Study (CHS, n = 5,888; enrollment age, 65 years or older; enrollment period, 1989-1994) and the Atherosclerosis Risk in Communities study (ARIC, n = 15,792; enrollment age, 45-64 years of age; enrollment period, 1987-1989). Participants hospitalized with pneumonia were matched to two controls. Pneumonia cases and controls were followed for occurrence of CVD over 10 years after matching.

Of 591 pneumonia cases in CHS, 206 had CVD events (heart attack, stroke, and fatal coronary heart disease) over 10 years after pneumonia hospitalization. In ARIC, of 680 pneumonia cases, 112 had CVD events over 10 years after hospitalization.  Analysis indicated that hospitalization with pneumonia was associated with a subsequent increase in the risk of CVD. The risk was highest (4-fold) in the first 30 days after pneumonia, and although it progressively declined during the first year, it remained approximately 1.5-fold higher in subsequent years. This association persisted after adjusting for demographics, the burden of cardiovascular risk factors, crude measures of frailty, and was observed across a range of infection severity.

“Moreover, in our analyses, the magnitude of risk for CVD associated with pneumonia was similar or higher compared with the risk of CVD associated with traditional risk factors, such as smoking, diabetes, and hypertension. Thus, our results suggest that pneumonia is an important risk factor for CVD,” the authors write.

(doi:10.1001/jama.2014.18229; 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: 11 A.M. (ET) TUESDAY, JANUARY 13, 2015

Media Advisory: To contact Alexander M. Friedman, M.D., email amf2104@columbia.edu.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.14774.

Use of Surgical Procedure to Facilitate Child Birth Declines

Between 2006 and 2012 in the U.S., there was a decline in rates of episiotomy, a surgical procedure for widening the outlet of the birth canal to make it easier for the mother to give birth, according to a study in the January 13 issue of JAMA.

Episiotomy is a common obstetric procedure, estimated to be performed in 25 percent of vaginal deliveries in the United States in 2004. Restrictive use of episiotomy has been recommended given the risks of the procedure and unclear benefits of routine use. Decreasing use of the procedure was documented in the 1990s; however, whether rates have continued to decrease after evidence­based recommendations has not been known, according to background information in the article.

Alexander M. Friedman, M.D., of the Columbia University College of Physicians and Surgeons, New York, and colleagues used the Perspective database to identify women who underwent a vaginal delivery from 2006-2012. The database includes more than 500 hospitals (approximately 15 percent of hospitalizations nationally, including deliveries).

This analysis included 2,261,070 women who were hospitalized for a vaginal delivery in 510 hospitals, of whom 325,193 underwent episiotomy (14.4 percent). There was a decline in the rate of episiotomy between 2006 (17.3 percent) and 2012 (11.6 percent). Several demographic characteristics were associated with receipt of episiotomy: 15.7 percent of white women vs 7.9 percent of black women; and 17.2 percent with commercial insurance vs 11.2 percent with Medicaid insurance. Hospital factors (rural location and teaching status) were associated with less use.

“These observations suggest nonmedical factors are related to use of episiotomy,” the authors write.

Adjusted hospital rates of episiotomy use demonstrated significant variation. Among the 10 percent of hospitals that used the procedure most frequently, the average adjusted hospital episiotomy rate was 34.1 percent vs 2.5 percent in the 10 percent of hospitals that used the procedure least frequently.

(doi:10.1001/jama.2014.14774; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, JANUARY 13, 2015

Media Advisory: To contact Mihaela Teodorescu, M.D., M.S., call Gian Galassi at 608-263-5561 or email ggalassi@uwhealth.org.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.17822.

Asthma Associated With Increased Risk of Obstructive Sleep Apnea

Participants in a sleep study who had asthma had an increased risk for developing obstructive sleep apnea, with this association stronger with having had asthma longer, according to a study in the January 13 issue of JAMA.

In adults, obstructive sleep apnea (OSA) is highly and increasingly prevalent, and is associated with adversely affecting health and a higher risk of death. Although a few studies have suggested an asthma-OSA association, it has been unknown whether asthma is a causal risk factor for OSA, according to background information in the article.

Mihaela Teodorescu, M.D., M.S., of the William S. Middleton Memorial Veteran’s Hospital, and the University of Wisconsin School of Medicine and Public Health, Madison, Wisc., and colleagues examined the relationship between asthma and new OSA in the Wisconsin Sleep Cohort Study, which consists of randomly selected adult employees of state agencies, 30 to 60 years of age in 1988. Since study inception, participants have attended in-laboratory overnight polysomnography and provided health-related questionnaires approximately every 4 years. Eligible participants were identified as free of OSA at study entry.

Twenty-two of 81 participants (27 percent) with asthma experienced incident OSA over their first observed 4-year follow-up intervals vs 75 of 466 participants (16 percent) without asthma. Using all available 4-year intervals (i.e., including multiple 4-year interval observations per participant), participants with asthma experienced 45 incident OSA cases during 167 4-year intervals (27 percent) and participants without asthma experienced 160 incident OSA cases during 938 4-year intervals (17 percent). Participants with preexisting asthma had a nearly 40 percent increased risk for new OSA compared with those without asthma.

Asthma duration was related to both new OSA and new OSA with habitual sleepiness (defined as answering often [5-15 times a month], and almost always [>15 times a month] to the question “Do you have feelings of excessive daytime sleepiness”).

“This study prospectively examined the relationship of asthma with OSA assessed with laboratory-based polysomnography and found that preexistent asthma was a risk factor for the development of clinically relevant OSA in adulthood over a 4-year period. Furthermore, the asthma-OSA association was significantly dose-dependent on duration of asthma,” the authors write.

“Studies investigating the mechanisms underlying this association and the value of periodic OSA evaluation in patients with asthma are warranted.”

(doi:10.1001/jama.2014.17822; 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: 11 A.M. (ET) TUESDAY, JANUARY 13, 2015

Media Advisory: To contact Hamilton Moses III, M.D., Hamilton Moses III, M.D., call Heather Dewar at 410-502-9463 or email hdewar@jhmi.edu. To contact author Victor J. Dzau, M.D., call Jennifer Walsh at 202-334-2183 or email jwalsh@nas.edu.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.15939.  This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.17660.

Rate of Investment in Medical Research has Declined in U.S., Increased Globally

From 2004 to 2012, the rate of investment in medical research in the U.S. declined, while there has been an increase in research investment globally, particularly in Asia, according to a study in the January 13 issue of JAMA.

For the last century, medical research, including public health advances, has been the primary source of and an essential contributor to improvement in the health and longevity of individuals and populations in developed countries. The United States has historically been where research has found the greatest support and has generated more than half the world’s funding for many decades. Few previous analyses have compared medical research in the United States with other developed countries, according to background information in the article.

Hamilton Moses III, M.D., of the Alerion Institute and Alerion Advisors LLC, North Garden, Va., and Johns Hopkins School of Medicine, Baltimore, and colleagues examined developments over the past two decades in the pattern of who conducts and who supports medical research, as well as resulting patents, publications, and new drug and device approvals. Publicly available data from 1994 to 2012 were compiled showing trends in U.S. and international research funding, productivity, and disease burden by source and industry type. Patents and publications (1981-2011) were evaluated using citation rates and impact factors.

Among the findings of the study:

Reduced science investment The largest increase in biomedical and health services research funding in the U.S. occurred between 1994 and 2004, when funding grew at 6 percent per year. However, from 2004 to 2012, the rate of investment growth declined to 0.8 percent annually and (in real terms) decreased in 3 of the last 5 years, reaching $117 billion (4.5 percent) of total health care expenditures. From 1994 to 2004, the medical device, biotechnology, and pharmaceutical industries had annual growth rates greater than 6 percent per year, with biotechnology demonstrating the largest increases. The share of U.S. medical research funding from industry accounted for 46 percent in 1994 and grew to 58 percent in 2012.

Industry reduced early-stage research, favoring medical devices, bioengineered drugs, and late-stage clinical trials, particularly for cancer and rare diseases. National Institutes of Health (NIH) allocations did not correlate proportionately with disease burden. Cancer and HIV/AIDS were funded well above the predicted levels based on U.S. disability alone, with cancer accounting for 16 percent of total NIH funding and 25 percent of all medicines currently in clinical trials.

Underfunding of service innovation Health services research (which examines access to care, the quality and cost of care, and the health and well-being of individuals, communities, and populations), accounted for between 0.2 percent and 0.3 percent of national health expenditures between 2003 and 2011, an approximately 20-fold difference in comparison with total medical research funding. Private insurers ranked last (0.04 percent of revenue) and health systems 19th (0.1 percent of revenue) among 22 industries in their investment in innovation. An increment of $8 billion to $15 billion yearly would occur if service firms were to reach median research and development funding.

Globalization U.S. government research funding declined from 57 percent (2004) to 50 percent (2012) of the global total, as did that of U.S. companies (50 percent to 41 percent), with the total U.S. (public plus private) share of global research funding declining from 57 percent to 44 percent. Asia, particularly China, tripled investment from $2.6 billion (2004) to $9.7 billion (2012). The U.S. share of life science patents declined from 57 percent (1981) to 51 percent (2011), as did those considered most valuable, from 73 percent (1981) to 59 percent (2011).

“The analysis underscores the need for the United States to find new sources to support medical research, if the clinical value of its past science investment and opportunities to improve care are to be fully realized. Substantial new private resources are feasible, though public funding can play a greater role. Both will require non-traditional approaches if they are to be politically and economically realistic. Given global trends, the United States will relinquish its historical innovation lead in the next decade unless such measures are undertaken,” the authors conclude.

(doi:10.1001/jama.2014.15939; 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: Restore the U.S. Lead in Biomedical Research

“To achieve a new strategic vision for research, the United States will need a roadmap that sets priorities, describes needed structural and organizational changes, and creates an environment that enables innovation,” write Victor J. Dzau, M.D., of the Institute of Medicine, Washington, D.C., and Harvey V. Fineberg, M.D., Ph.D., of the University of California, San Francisco, in an accompanying editorial.

“The needed changes include better coordination across funders and research institutions, development of new funding sources, improved grant evaluation processes, changes in education and training, rationalization of capital investments, and improved operational efficiencies. By taking the necessary political and institutional steps to ensure commitment of adequate resources over time, adopting a comprehensive research strategy, and attaining greater coordination and efficiency, the United States can retain its leadership position in biomedical research.”

(doi:10.1001/jama.2014.17660; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, JANUARY 13, 2015

Media Advisory: To contact corresponding author Steven A. Narod, M.D., F.R.C.P.C., call Julie Saccone at 416-323-6400, ext. 4054, or email julie.saccone@wchospital.ca. To contact editorial co-author Olufunmilayo I. Olopade, M.B.B.S., F.A.C.P., call John Easton at 773-795-5225 or email john.easton@uchospitals.edu.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.17322. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.17323.

Breast Cancer Diagnoses, Survival Varies by Race, Ethnicity

Among nearly 375,000 U.S. women diagnosed with invasive breast cancer, the likelihood of diagnosis at an early stage, and survival after stage I diagnosis, varied by race and ethnicity, with much of the difference accounted for by biological differences, according to a study in the January 13 issue of JAMA.

In the United States, incidence rates of breast cancer among women vary substantially by racial/ethnic group. Race/ethnicity and sociodemographic factors may influence a woman’s adherence to recommendations for clinical breast examination, breast self-examination, or screening mammogram and the likelihood of her seeking appropriate care in the event that a breast mass is noticed. A growing body of evidence suggests that biological factors may also be important in determining stage at diagnosis (i.e., the growth rate and metastatic potential of small-sized breast cancer tumors may vary between women due to inherent differences in grade and other or unknown pathological features), according to background information in the article.

Javaid Iqbal, M.D., of Women’s College Hospital, Toronto, and colleagues examined the proportion of breast cancers that were identified at an early stage (stage I) in different racial/ethnic groups in the United States and whether ethnic differences may be better explained by early detection or by intrinsic biological differences in tumor aggressiveness. The study included women diagnosed with invasive breast cancer from 2004 to 2011 who were identified in the Surveillance, Epidemiology, and End Results (SEER) 18 registries database (n = 452,215). For each of 8 racial/ethnic groups, biological aggressiveness (triple-negative cancers [negative for estrogen receptor, progesterone receptor, and ERBB2 (formerly HER2 or HER2/neu)], lymph node metastases, and distant metastases) of small-sized tumors of 2.0 cm or less was estimated. In addition, the odds were determined for being diagnosed at stage I compared with a later stage, as was the risk of death from stage I breast cancer by racial/ethnic group.

Of 373,563 women with invasive breast cancer, 268 675 (71.9 percent) were non-Hispanic white; 34,928 (9.4 percent), Hispanic white; 38,751 (10.4 percent), black; 25,211(6.7 percent), Asian; and 5,998 (1.6 percent), other ethnicities. Average follow-up time was 40.6 months. The researchers found that Japanese women were significantly more likely to be diagnosed at stage I (56.1 percent) than non-Hispanic white women (50.8 percent), while black women were less likely to be diagnosed at stage I (37.0 percent), as were women of South Asian ethnicity (Asian Indian, Pakistani) (40.4 percent).

The 7-year actuarial risk for death from stage I breast cancer was highest for black women (6.2 percent) compared with white women (3.0 percent); it was 1.7 percent for South Asian women. The probability of a woman dying due to small-sized breast cancer tumors (2.0 cm or less) was significantly higher for black women (9.0 percent) compared with non-Hispanic white women (4.6 percent).

The authors write that much of the difference in diagnosis and survival could be statistically accounted for by intrinsic biological differences such as lymph node metastasis, distant metastasis, and triple-negative behavior of tumors.

(doi:10.1001/jama.2014.17322; 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: Race, Ethnicity, and the Diagnosis of Breast Cancer

In an accompanying editorial, Bobby Daly, M.D., M.B.A., and Olufunmilayo I. Olopade, M.B.B.S., F.A.C.P., of the University of Chicago, write that there is an unprecedented opportunity to deliver high­ quality precision medicine regardless of race/ethnicity or socioeconomic status.

“Access to the use of genetic or molecular markers to guide choice of targeted therapy and reduce the costs of care can be made more equitable. For women with triple-negative disease, access to prompt diagnosis and initiation of chemotherapy can be lifesaving because these tumors metastasize early. Closing the survival gap will only occur once health care leaders initiate system changes that improve access to high-quality care along with a more comprehensive study of breast cancer biology through inclusion of a substantial number of minority patients in ‘omics’ research and in clinical trials.”

(doi:10.1001/jama.2014.17323; 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: 11 A.M. (ET) TUESDAY, JANUARY 13, 2015

Media Advisory: To contact corresponding author Roderick E. Prior, M.D., email reprior@fchn.org. To contact editorial co-author Darwin R. Labarthe, M.D., M.P.H., Ph.D., email Marla Paul at marla-paul@northwestern.edu.

Please Note: A press conference regarding this study will be held at noon ET Tuesday, January 13, at Franklin Memorial Hospital in Farmington, Maine. Speakers will include co-authors of the study and U.S. Senator Angus King. The press conference will be available via teleconference by calling 855-806-7318, participant code 102474. For additional information, email reprior@fchn.org.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16969. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16963.

Community-Wide Cardiovascular Disease Prevention Programs Associated with Reductions in Hospitalizations, Deaths, Over a 40 Year Period

In a rural Maine county, sustained, community-wide programs targeting cardiovascular risk factors and behavior changes were associated with reductions in hospitalization and death rates over a 40 year period (1970-2010) compared with the rest of the state, with substantial improvements seen for hypertension and cholesterol control and smoking cessation, according to a study in the January 13 issue of JAMA.

Reducing the burden of cardiovascular disease (CVD) has been a public health priority for more than 50 years and will continue to be in the foreseeable future. Few comprehensive cardiovascular risk reduction programs, particularly those in rural, low-income communities, have sustained community-wide interventions for more than 10 years and demonstrated improvements in known risk factors and reductions in illness and death, according to background information in the article.

N. Burgess Record, M.D., of Franklin Memorial Hospital, Farmington, Maine, and colleagues studied health outcomes associated with a comprehensive cardiovascular risk reduction program in Franklin County, Maine, a low-income rural community. In the late 1960s, local community groups in Franklin County identified CVD prevention as a priority. A new Community Action Agency (CAA), a new nonprofit medical group practice (Rural Health Associates [RHA]), and later the community’s hospital initiated and coordinated their efforts. With hospital medical staff sponsorship, RHA established the community-wide Franklin Cardiovascular Health Program (FCHP) in 1974.

The programs targeted hypertension, cholesterol, and smoking, as well as diet and physical activity. The current analysis included residents of Franklin County (population, 22,444 in 1970), and used the preceding decade as a baseline and compared Franklin County with other Maine counties and state averages.

In its first 4 years, FCHP screened about 50 percent of county adults. Individuals with hypertension showed significant movement from detection to treatment and blood pressure control; the proportion in control increased from 18.3 percent to 43.0 percent from 1975 to 1978, an absolute increase of 24.7 percent. After introducing cholesterol screening in 1986, FCHP reached 40 percent of county adults within 5 years, half of whom had elevated cholesterols. Over subsequent decades, cholesterol control had an absolute increase of 28.5 percent, from 0.4 percent to 28.9 percent, from 1986 to 2010. Similarly, after initiation of multiple community smoking cessation projects, community-wide smoking quit rates improved significantly, from 48.5 percent to 69.5 percent, and became significantly higher than that for the rest of Maine; these differences later disappeared when Maine’s overall quit rate increased.

Franklin County hospitalizations per capita were less than expected for the period 1994-2006. The lower overall hospitalization rates were associated with $5,450,362 reductions in total in- and out-of-area hospital charges for Franklin County residents per year.

After being at or above overall Maine mortality rates in the 1960s, Franklin County rates decreased below Maine rates for almost the entire period 1970-2010. Cardiovascular­specific mortality rates decreased similarly. The greatest differences coincided with periods of peak efforts to improve health care access, detect and control hypertension and hypercholesterolemia, and reduce smoking.

“The experience in Franklin County suggests that community health improvement programs may be both feasible and effective. This may be especially true in socio-economically disadvantaged communities where the needs are the greatest, as the increasing association of lower household income with higher mortality in Maine suggests,” the authors write.

“Further studies are needed to assess the generalizability of such programs to other U.S. county populations, especially rural ones, and to other parts of the world.”

(doi:10.1001/jama.2014.16969; 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: Improving Cardiovascular Health in a Rural Population

Darwin R. Labarthe, M.D., M.P.H., Ph.D., and Jeremiah Stamler, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, comment on the findings of this study in an accompanying editorial.

“This report by Record et al in this issue of JAMA should reinforce the importance of cardiovascular health promotion and disease prevention policies and practices at the community level; stimulate efforts in communities to document and publish their past experience in this area to inform related ongoing work; and foster wider application of program evaluation and implementation research, exploiting new data sources and technologies to accelerate replication and scaling-up of community-based prevention. Intervening developments—not least among them the Affordable Care Act—have made this task more clearly achievable today than in 1970, when the Franklin County program began. At a time when population health is increasingly important, the Franklin County program demonstrates that with an integrated concerted effort based on good evidence, the cardiovascular health of a community can be improved.”

“The Franklin County, Maine, program demonstrates significant accomplishments in one northern U.S. rural community that have made a difference in cardiovascular outcomes. The experience deserves consideration as a model for other communities to emulate, adapt, and implement.”

(doi:10.1001/jama.2014.16963; 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: 11 A.M. (ET) TUESDAY, JANUARY 6, 2015

Media Advisory: To contact Jennifer F. Kawwass, M.D., email Holly Korschun at hkorsch@emory.edu.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.14488.

Study Finds Low Rate of Complications with Assisted Reproductive Technology Procedures

In the United States from 2000-2011, autologous (woman uses her own egg) and donor assisted reproductive technology procedures were associated with low complication risks, according to a study in the January 6 issue of JAMA.

Use of assisted reproductive technology (ART) continues to increase in the United States and globally. In an effort to improve patient safety, stimulation protocols (medication regimens used for ovulation induction) have become less aggressive, oocyte (the egg before it is released at ovulation) retrieval has transitioned from laparoscopic to transvaginal, and overall pregnancy rates have improved. However, limited data exist regarding the incidence of maternal complications, according to background information in the article.

Jennifer F. Kawwass, M.D., of the Emory University School of Medicine, Atlanta, and colleagues examined the incidence and trends in reported patient and donor complications in fresh (non-frozen) ART cycles using the U.S. Centers for Disease Control and Prevention National ART Surveillance System (NASS), a federally mandated reporting system. Reported complications (defined as having been directly related to ART and occurring within 12 weeks of cycle initiation) include infection, hemorrhage requiring transfusion, moderate or severe ovarian hyperstimulation syndrome (OHSS; an over-response to ovarian stimulation), medication adverse event, anesthetic complication, hospitalization, patient death within 12 weeks of stimulation, and other complications.

Among 1,135,206 autologous cycles, the most commonly reported patient complications were OHSS (peak of 153.5/10,000 autologous cycles) and hospitalizations (peak of 34.8/10,000 autologous cycles); rates of other complications remained below 10/10,000 cycles. Rates declined from 2000-2011 for reported medication adverse events and hospitalizations; no other significant trends were detected among reported infections, hemorrhages, OHSS, severe OHSS, anesthetic-related complications, and deaths within 12 weeks of stimulation start or during pregnancy.

Fifty-eight total deaths were reported (18 stimulation­related and 40 maternal deaths prior to infant birth). The maternal death rate ranged from 1.6 per 100,000 ART­conceived live births in 2008 to 14.2 in 2004. Reported complications following donor ART cycles were less frequent; none showed a significant trend. No donor deaths were reported; 13 maternal deaths prior to infant birth were reported among oocyte donor recipients.

“Increased awareness of the most common complication, OHSS, may prompt additional study to characterize predictors of this and other adverse events to inform the development of effective approaches necessary to decrease complication occurrence,” the authors write.

(doi:10.1001/jama.2014.14488; 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: 11 A.M. (ET) TUESDAY, JANUARY 6, 2015

Media Advisory: To contact Nikolai Madrid Scheller, M.B., email nims@ssi.dk.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16946.

HPV Vaccination Not Associated With Increased Risk of Multiple Sclerosis

Although some reports have suggested a link between human papillomavirus (HPV) vaccination and development of multiple sclerosis or other demyelinating diseases (a group of central nervous system disorders), a follow-up of girls and women in Denmark and Sweden who received this vaccination found no increased risk for these disorders, according to a study in the January 6 issue of JAMA.

Since the licensure of the quadrivalent human papillomavirus (qHPV) vaccine in 2006 and the later licensure of the bivalent HPV (bHPV) vaccine, more than 175 million doses have been distributed worldwide. The introduction of large-scale vaccination in a new target group—girls and young women—has been accompanied by a number of safety concerns, with the potential to undermine public confidence in the new vaccines. One concern is the development of multiple sclerosis, which has been fuelled by social and news media reports of cases occurring after HPV vaccination, and an increasing number of case reports published in the medical literature describing vaccine recipients who developed multiple sclerosis as well as other demyelinating diseases. It is not known if the occurrence of these conditions after HPV vaccination merely reflects the background rates in girls and young women or represents a true increased risk, according to background information in the article.

Nikolai Madrid Scheller, M.B., of the Statens Serum Institut, Copenhagen, Denmark, and colleagues conducted a study that included Danish and Swedish girls and women ages 10 years to 44 years, followed up from 2006 to 2013. The researchers used nationwide registers to identify the study group, information on qHPV vaccination, and data on incident diagnoses of multiple sclerosis and other demyelinating diseases.

A total of 3,983,824 girls and women were eligible for inclusion in the study group. Of these, a total of 789,082 were vaccinated during the study period, with a total of 1,927,581 qHPV vaccine doses. During follow-up, 4,322 multiple sclerosis cases and 3,300 cases of other demyelinating diseases were identified, of which 73 and 90, respectively, occurred within the risk period (two years following vaccination). After analysis of the data, the researchers found no increased risk of multiple sclerosis or other demyelinating diseases associated with qHPV vaccination.

“Our study adds to the body of data that support a favorable overall safety profile of the qHPV vaccine and expands on this knowledge by providing comprehensive analyses of multiple sclerosis and other demyelinating diseases. The size of the study and the use of nationwide registry data of unselected populations from Denmark and Sweden allowed adequately powered analyses that are likely generalizable,” the authors write.

“These findings do not support concerns about a causal relationship between qHPV vaccination and demyelinating diseases.”

(doi:10.1001/jama.2014.16946; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The Swedish Foundation for Strategic Research, Novo Nordisk Foundation, and The Danish Medical Research Council funded the study. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, JANUARY 6, 2015

Media Advisory: To contact corresponding author Helen M. Colhoun, M.D., email h.colhoun@dundee.ac.uk. To contact editorial co-author Lori Laffel, M.D., M.P.H., email Jeff Bright at jeff.bright@joslin.harvard.edu.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16425. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16327.

Scottish Study Finds Substantially Shorter Life Expectancy for Patients with Type 1 Diabetes

For patients with type 1 diabetes in Scotland, at age 20 years, the average man has an estimated life expectancy loss of about 11 years; for women, it is 13 years, compared with the general Scottish population without type 1 diabetes, according to a study in the January 6 issue of JAMA.

Major advances in treatment of type 1 diabetes have occurred in the past three decades. Accurate contemporary estimates of life expectancy would be useful as a measure of the current effect of diabetes and as a benchmark for assessing changes in diabetes care through time. Although there are many reports of the standardized mortality ratios for type 1 diabetes, few studies have provided life expectancy data, according to background information in the article.

Shona J. Livingstone, M.Sc., of the University of Dundee, Dundee, Scotland, and colleagues used a large national registry of patients with type 1 diabetes living in Scotland to provide contemporary comparisons of life expectancy with the general population without type 1 diabetes. The analysis included individuals who were 20 years of age or older from 2008 through 2010 (n = 24,691) with type 1diabetes.

Life expectancy at an attained age of 20 years was an additional 46.2 years among men with type 1 diabetes and 57.3 years among men without it, an estimated loss in life expectancy with diabetes of 11.1 years. Life expectancy from age 20 years was an additional 48.l years among women with type 1 diabetes and 61.0 years among women without it, an estimated loss with diabetes of 12.9 years. In the general population without type 1 diabetes, 76 percent of men and 83 percent of women survived to age 70 years compared with 47 percent of men and 55 percent of women with type 1 diabetes.

Even among patients with type 1 diabetes and preserved kidney function, life expectancy was reduced, with an estimated loss from age 20 years of 8.3 years for men and 7.9 years for women. Overall, the largest percentage of the estimated loss in life expectancy was related to ischemic heart disease, but death from diabetic coma or the condition ketoacidosis was associated with the largest percentage of the estimated loss occurring before age 50 years.

The authors note that whether their findings are generalizable internationally cannot be directly assessed because there are no large contemporary or historical nationally representative studies from other countries. “Therefore, it would be of interest to see contemporary larger scale data from the United States and other countries too.”

(doi:10.1001/jama.2014.16425; 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: Mortality in Type 1 Diabetes in the Current Era

In an editorial commenting on the two studies in this issue of JAMA that examine diabetes and mortality, Michelle Katz, M.D., M.P.H., and Lori Laffel, M.D., M.P.H., of the Joslin Diabetes Center, Boston, write that more is needed to improve the life-expectancy in type 1 diabetes.

“The search for genetic factors and biomarkers related to risk of diabetes complications generally and risk of diabetic nephropathy specifically needs to accelerate. There continues to be inadequate access to advanced diabetes technologies, education and support from health care professionals, and, at times, even family encouragement, which all need to improve. Patients, families, and the health care community await more steps forward. There is some reassurance for the present; efforts to improve glycemic control and therapies that provide renal protection and cardiovascular risk reduction can prevent or postpone complications and preserve the futures of persons with type 1 diabetes.”

(doi:10.1001/jama.2014.16327; 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: 11 A.M. (ET) TUESDAY, JANUARY 6, 2015

Media Advisory: To contact David E. Arterburn, M.D., M.P.H., email Rebecca Hughes at hughes.r@ghc.org.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16968

Bariatric Surgery Associated With Improved Long-Term Survival

Among obese patients receiving care in the Veterans Affairs health system, those who underwent bariatric surgery, compared with obese patients who did not have this surgery, had a lower all-cause rate of death at 5 years and up to 10 years following the procedure, according to a study in the January 6 issue of JAMA.

Bariatric surgery is associated with improvement in weight, obesity-related conditions, and quality of life among severely obese adults. Accumulating evidence suggests that bariatric surgery improves survival among patients with severe obesity, but these studies have examined lower-risk, predominantly female patients. The long-term outcomes of bariatric surgery on patients with substantial co-existing illnesses are not known, according to background information in the article.

David E. Arterburn, M.D., M.P.H., of the Group Health Research Institute, Seattle, and colleagues examined long-term survival among 2,500 patients (74 percent men) who underwent bariatric surgery in Veterans Affairs (VA) bariatric centers from 2000-2011 and matched them to 7,462 control patients who did not undergo bariatric surgery. Bariatric procedures included gastric bypass (74 percent), sleeve gastrectomy (15 percent), adjustable gastric banding (10 percent), and other (1 percent). Surgical patients had an average age of 52 years and an average body mass index (BMI) of 47; control patients had an average age of 53 years and an average BMI of 46.

At the end of the 14-year study period, there were a total of 263 deaths in the surgical group and 1,277 deaths in the control group. Estimated mortality rates for surgical patients were 2.4 percent at 1 year, 6.4 percent at 5 years, and 13.8 percent at 10 years; for control patients, estimated mortality rates were 1.7 percent at 1 year, 10.4 percent at 5 years, and 23.9 percent at 10 years. Bariatric surgery was not associated with all-cause mortality in the first year of follow-up, but associated with significantly lower mortality after 1 to 5 years and 5 to 14 years.

The researchers found no significant difference in the association of bariatric surgery on mortality across groups defined by sex, diabetes diagnosis, and super obesity (BMI greater than 50); “however, future studies with larger samples and longer-term follow-up should seek to confirm these findings.”

The authors write that the results of this study “provide further evidence for the beneficial relationship between surgery and survival that has been demonstrated in younger, predominantly female populations.”

(doi:10.1001/jama.2014.16968; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This research was funded by the Health Services Research and Development, Department of Veterans Affairs and by a research career scientist award from the Department of Veterans Affairs. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, JANUARY 6, 2015

Media Advisory: To contact Trevor J. Orchard, M.D., email Allison Hydzik at hydzikam@upmc.edu.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16107

Intensive Treatment for Type 1 Diabetes Associated With Decreased Risk of Death

After an average of 27 years’ follow-up of patients with type 1 diabetes, 6.5 years of initial intensive diabetes therapy was associated with a modestly lower all-cause rate of death, compared with conventional therapy, according to a study in the January 6 issue of JAMA.

Based on the demonstrated reductions in illness, intensive diabetes therapy is now the recommended standard of care; however, it has not been established whether mortality in type 1 diabetes mellitus is affected following a period of intensive diabetes therapy. In type 2 diabetes treatment, reducing glycemia (blood sugar) closer to the nondiabetic range has not consistently reduced mortality, according to background information in the article.

Trevor J. Orchard, M.D., of the University of Pittsburgh, and colleagues examined whether mortality differed between the original intensive and conventional treatment groups in the long-term follow-up of the Diabetes Control and Complications Trial (DCCT) cohort. The DCCT (1983-1993) randomly assigned 1,441 healthy volunteers with type 1 diabetes mellitus between the ages of 13 and 39 years to intensive or conventional therapy, with the goal of studying the effects of near-normal blood sugars on long-term diabetes complications. After the DCCT ended, participants were followed up in a multisite (27 U.S. and Canadian academic clinical centers) observational study (Epidemiology of Diabetes Interventions and Complications; EDIC) until December 31, 2012.

During the initial clinical trial, participants were randomly assigned to receive intensive therapy (n = 711) aimed at achieving blood sugar control  as close to the nondiabetic range as safely possible, or conventional therapy (n = 730) with the goal of avoiding symptomatic hypoglycemia (abnormally low blood sugar) and hyperglycemia (abnormally high blood sugar).  At the end of the DCCT, after an average of 6.5 years, intensive therapy was taught and recommended to all participants and diabetes care was returned to personal physicians.

Vital status was ascertained for 1,429 (99.2 percent) participants. Of the 107 (7.4 percent) deaths, 43 (6.0 percent) were in the intensive treatment group and 64 (8.8 percent) were in the conventional treatment group. Overall mortality risk in the intensive group was lower than that in the conventional group, although the absolute risk reduction was small.

Primary causes of death were cardiovascular disease, cancer, acute diabetes complications, and accidents or suicide. Higher levels of glycated hemoglobin (a common lab test that gauges overall blood sugar control) were associated with all-cause mortality, as well as the development of albuminuria (the presence of excessive protein in the urine).

The authors write that intensive therapy is associated with increased hypoglycemic risk, which in turn has been associated with increased mortality. “The current data suggest net mortality benefit from intensive therapy … These results provide reassurance that adoption of 6.5 years of intensive therapy in type 1 diabetes does not incur increased risk of overall mortality.”

(doi:10.1001/jama.2014.16107; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 23, 2014

Media Advisory: To contact Keith P. West Jr., Dr.P.H., call Stephanie Desmon at 410-955-7619 or email Sdesmon1@jhu.edu.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16819.

Maternal Supplementation with Multiple Micronutrients, Compared With Iron-Folic Acid, Does Not Reduce Infant Mortality

In Bangladesh, daily maternal supplementation of multiple micronutrients compared to iron-folic acid before and after childbirth did not reduce all-cause infant mortality to age 6 months, but did result in significant reductions in preterm birth and low birth weight, according to a study in the December 24/31 issue of JAMA.

Multiple micronutrient deficiencies are common among pregnant women in resource-poor regions of the world, especially in southern Asia. Coexisting with poor maternal nutrition across the region are excessive burdens of low birth weight (LBW), preterm birth, small size for gestational age, stillbirth, infant mortality, and maternal mortality. Gestational micronutrient deficiencies may contribute to avertable adverse birth outcomes. Data for effects of antenatal (before birth) multiple micronutrient (MM) supplementation on longer-term infant mortality are sparse for guiding policies in southern Asia, according to background information in the article.

Keith P. West Jr., Dr.P.H., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues conducted a study in which pregnant women in Bangladesh (n = 44,567) were randomly assigned to receive supplements containing 15 micronutrients or iron-folic acid alone, taken daily from early pregnancy to 12 weeks postpartum.

Among the 22,405 pregnancies in the multiple micronutrient group and the 22,162 pregnancies in the iron-folic acid group, there were 14,374 and 14,142 live-born infants, respectively, included in the analysis. At 6 months, multiple micronutrients did not significantly reduce infant mortality; there were 764 deaths (54.0 per 1,000 live births) in the iron-folic acid group and 741 deaths (51.6 per 1,000 live births) in the multiple micronutrient group.

Multiple micronutrient supplementation resulted in a non-statistically significant reduction in stillbirths (43.1 vs 48.2 per 1,000 births) and significant reductions in preterm births (18.6 vs 21.8 per 100 live births) and low birth weight (40.2 vs 45.7 per 100 live births).

“Our study’s null finding is in agreement with a small number of trials that have provided an antenatal multiple micronutrient vs iron supplement, with or without folic acid, and found no effect on neonatal mortality,” the authors write.

“Reasons for a null effect on postnatal survival after improvement in some birth outcomes with antenatal multiple micronutrient supplement use remain unknown but may reflect a complex interplay between maternal and newborn sizes and differential responses to supplementation by causes of death.”

(doi:10.1001/jama.2014.16819; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 23, 2014

Media Advisory: To contact Chang-Fu Kuo, M.D., email zandis@gmail.com.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.14484.

Many Patients with Gout Do Not Receive Recommended Treatment

Among patients in England with gout, only a minority of those with indications to receive urate-lowering therapy were treated according to guideline recommendations, according to a study in the December 24/31 issue of JAMA.

Current guidelines recommend urate (a metabolite derived from uric acid)-lowering treatment for patients with more severe gout or accompanying conditions. However, after the first diagnosis, it remains unclear when such treatment is appropriate, according to background information in the article.

Chang-Fu Kuo, M.D., of Chang Gung Memorial Hospital, Taoyuan, Taiwan, and colleagues investigated the timing of eligibility for and prescription of urate-lowering treatment following first gout diagnosis. Patients diagnosed with incident gout in 1997-2010 were identified using the Clinical Practice Research Datalink, containing anonymized information including patient demographics, diagnoses, examination findings, laboratory results, and prescribed medications from approximately 8 percent of the U.K. population.

Of 52,164 patients with incident gout, the median time to first treatment indication (such as multiple attacks, chronic kidney disease, diuretic use) was 5 months and the cumulative probability of fulfilling any indication was 44 percent at 0 years from diagnosis, 61 percent at 1 year, 87 percent at 5 years, and 94 percent at 10 years. The cumulative probabilities for prescription at the same time points were 0 percent, 17 percent, 30 percent, and 41 percent.

The median prescription rate for urate-lowering treatment among practices was 32.5 percent. Examined patient- and practice-level factors accounted for only one-fifth of the variance in prescriptions. “The unexplained variance may be accounted for by factors not available in the database. Recognized barriers to care include suboptimal patient and physician knowledge of gout, its treatment, and clinical recommendations, and patient and physician preferences for treatment.”

“In conclusion, our study supports including urate-lowering treatment in the information about gout provided to patients around the time of first diagnosis.”

(doi:10.1001/jama.2014.14484; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 23, 2014

Media Advisory: To contact corresponding author Francesca Dominici, Ph.D., call Todd Datz at 617-432-8413 or email tdatz@hsph.harvard.edu.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.15715.

Extreme Heat in U.S. Associated With Increased Risk of Hospitalization Among Older Adults

Between 1999 and 2010, periods of extreme heat in the U.S. were associated with an increased risk of hospitalization for older adults for fluid and electrolyte disorders, kidney failure, urinary tract infections, septicemia and heat stroke, according to a study in the December 24/31 issue of JAMA. The authors note that the absolute risk increase was small and of uncertain clinical importance.

Extreme heat is the most common cause of severe weather fatalities in the United States, and these weather-related outcomes are expected to escalate as heat waves become more frequent, more intense, and longer lasting with climate change. Although extreme heat is known to adversely affect multiple physiological processes, previous studies of the health effects have examined only a few major categories of health outcomes, such as cardiovascular and respiratory diseases or well-known heat-related diseases, such as heat stroke or dehydration, according to background information in the article.

Jennifer F. Bobb, Ph.D., of the Harvard School of Public Health, Boston, and colleagues used Medicare inpatient claims data to systematically examine possible ways in which exposure to heat waves might be associated with serious illness requiring hospitalization in older adults. The study included hospital admissions of Medicare enrollees (23.7 million fee-for-service beneficiaries [65 years of age or older] per year; 85 percent of all Medicare enrollees) for the period 1999 to 2010 in 1,943 counties in the United States, along with at least five summers of near-complete (>95 percent) daily temperature data. Heat wave periods, defined as two or more consecutive days with temperatures exceeding the 99th percentile of county-specific daily temperatures, were matched to non-heat wave periods by county and week.

Of 214 disease groups that accounted for 99.9% of hospitalizations, 5 diseases (fluid and electrolyte disorders, renal [kidney] failure, urinary tract infections, heat stroke, and septicemia [body-wide illness with toxicity due to invasion of the bloodstream by bacteria usually coming from a localized site of infection]) had statistically significantly elevated risk of hospitalization during heat wave days. These risks were larger when the heat wave periods were longer and more extreme and were largest on the heat wave day but remained elevated and statistically significant for 1 to 5 subsequent days.

Absolute risk differences were 0.34 excess daily admissions per 100,000 individuals at risk for fluid and electrolyte disorders, 0.25 for renal failure, 0.24 for urinary tract infections, 0.21 for septicemia, and 0.16 for heat stroke.

The researchers write that their analysis of hospitalization rates on days after a heat wave provides 2 additional insights. “For some diseases, risk of hospitalization remained elevated for up to 5 days following a heat wave day. This suggests that prevention and treatment of heat-related illnesses is critical not only during the heat wave itself but also on subsequent days. Additionally, quantifying the extra number of hospital admissions attributable to heat waves without consideration of a delayed effect may underestimate the health care burden of heat.”

(doi:10.1001/jama.2014.15715; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 23, 2014

Media Advisory: To contact Seetha Shankaran, M.D., email Philip Van Hulle at pvanhulle@med.wayne.edu. To contact editorial co-author Neil Marlow, D.M., F.Med.Sci., email N.Marlow@ucl.ac.uk.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16058.  This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.15959.

Longer Duration, Deeper Body Cooling for Newborns with Neurological Condition Does Not Reduce Risk of Death

Among full-term newborns with moderate or severe hypoxic ischemic encephalopathy (damage to cells in the central nervous system from inadequate oxygen), receiving deeper or longer duration cooling did not reduce risk of neonatal intensive care unit death, compared to usual care, according to a study in the December 24/31 issue of JAMA.

Hypoxic ischemic encephalopathy is an important cause of childhood neurodevelopmental deficits among infants born at full-term. Hypothermia (reduced body temperature) at 33.5°C for 72 hours reduces death or disability, according to background information in the article. Longer cooling and deeper cooling has been found to be neuroprotective in animal models.

Seetha Shankaran, M.D., of Wayne State University, Detroit, and colleagues conducted a study in which full-term infants were randomly assigned to four hypothermia groups: 33.5°C for 72 hours, 32.0°C for 72 hours, 33.5°C for 120 hours, and 32.0°C for 120 hours, to examine if longer duration and deeper cooling would improve outcomes at 18 to 22 months. Infants admitted to the neonatal intensive care until within 6 hours of birth were candidates for the study when seizures or moderate or severe encephalopathy was present. The trial was closed for safety and futility issues and included 364 infants (of 726 planned).

Mortality in the neonatal intensive care unit (NICU) was 7 percent for the 33.5°C for 72 hours group, 14 percent for the 32.0°C for 72 hours group, 16 percent for the 33.5°C for 120 hours group, and 17 percent for the 32.0°C for 120 hours group.

Among neonates with moderate hypoxic ischemic encephalopathy, death in the NICU occurred in 4 percent in the 72 hours group; 8 percent in the 120 hours group; 7 percent in the 33.5°C group; and in 5 percent in the 32.0°C group. Among neonates with severe hypoxic ischemic encephalopathy, deaths in the NICU occurred in 34 percent in the 72 hours group; 42 percent in the 120 hours group; 31 percent in the 33.5°C group; and in 44 percent in the 32.0°C group.

Safety outcomes were similar between the 120 hours group vs 72 hours group and the 32.0°C group vs 33.5°C group, except major bleeding occurred among 1 percent in the 120 hours group vs 3 percent in the 72 hours group. Futility analysis determined that the probability of detecting a statistically significant benefit for longer cooling, deeper cooling, or both for NICU death was less than 2 percent.

“Among neonates of at least 36 weeks’ gestational age with moderate or severe hypoxic ischemic encephalopathy, deeper cooling or longer duration of cooling compared with hypothermia at 33.5°C for 72 hours did not reduce NICU death. These results have implications for patient care and the design of future trials,” the authors conclude.

(doi:10.1001/jama.2014.16058; 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: Depth and Duration of Cooling for Perinatal Asphyxial Encephalopathy

In an accompanying editorial, Nicola J. Robertson, M.B.Ch.B., Ph.D., and Neil Marlow, D.M., F.Med.Sci., of University College London, United Kingdom, comment on the findings of this study.

“Therapeutic hypothermia would not be a safe and effective therapy in neonatal care if not for the willingness and enthusiasm of neonatologists to take on the extra work needed to enter neonates into clinical trials. In the trial by Shankaran et al, clinical practice did not bear out preceding preclinical studies. However, the persistent high mortality and morbidity found with perinatal asphyxial encephalopathy encourages continuing efforts to improve the efficacy of treatment and minimize intercurrent and subsequent complications from this unpredictable and often devastating condition. The current focus is on adjunct therapies that can augment 72 hours of hypothermic neuroprotection at 33°C to 34°C.”

(doi:10.1001/jama.2014.15959; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 23, 2014

Media Advisory: To contact Ricardo A. Mosquera, M.D., email Deborah Mann Lake at deborah.m.lake@uth.tmc.edu. To contact editorial author James M. Perrin, M.D., call Cassandra Aviles at 617-724-6433 or email cmaviles@partners.org.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16419.  This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16514.

Comprehensive Care for High-Risk, Chronically Ill Children Reduces Serious Illnesses, Costs

High-risk children with chronic illness who received care at a clinic that provided both primary and specialty care and features to promote prompt effective care had an increase in access to care and parent satisfaction and a reduction in serious illnesses and costs, according to a study in the December 24/31 issue of JAMA.

Although the patient-centered or family-centered medical home is widely recommended, its value in improving clinical outcomes or reducing health care costs remains to be demonstrated. Medical homes are potentially the most cost-effective for high-risk patients, particularly high-risk children with chronic illness whose care is often fragmented, costly, and ineffective. “With the inadequate current payments for outpatient pediatric care and the necessity to restrain health care spending, the payments required to develop and sustain such medical homes may not be forthcoming unless they are shown to improve outcomes with minimal or no increase in costs,” the authors write.

Ricardo A. Mosquera, M.D., of the University of Texas Medical School, Houston, and colleagues randomly assigned 201 high-risk children with chronic illness to receive comprehensive care (n = 105; included treatment from primary care clinicians and specialists in the same clinic with multiple features to promote prompt effective care) or usual care (n = 96; provided locally in private offices or faculty-supervised clinics without modification). Patients were defined as high-risk with chronic illness if they had three or more emergency department visits, two or more hospitalizations, or one or more pediatric intensive care unit admissions during the previous year, and a greater than 50 percent estimated risk for hospitalization. The children were treated at a high-risk clinic at the University of Texas in Houston.

Comprehensive care (or enhanced medical home), compared to usual care, reduced the number of children with a serious illness (by 55 percent) and total hospital and clinic costs ($16,523 vs. $26,781 per child-year respectively). Rates were also reduced for emergency department visits, hospitalizations, number of days in the hospital, intensive care unit (ICU) admissions and days in the ICU.

“In this randomized clinical trial, the triple aim of improved care, improved health, and lower costs was achieved in an enhanced medical home providing comprehensive care to high- risk children with chronic illness compared with usual care,” the authors write.

“These findings from a single site of selected patients with a limited number of clinicians require study in larger, broader populations before conclusions about generalizability to other settings can be reached.”

(doi:10.1001/jama.2014.16419; 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.

TV Note – There will 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, December 23 at this link.

Editorial: Patient-Centered Medical Home for High-Risk Children With Chronic Illness

James M. Perrin, M.D., of Harvard Medical School and MassGeneral Hospital for Children, Boston, writes in an accompanying editorial that lessons from this study and the dual-eligible accountable care organizations can inform the development of medical home programs for patients with complex conditions.

“First, regular, almost daily, contact with the patient is critical. It is more difficult to reduce hospitalization rates once a patient enters the emergency department. Second, care must be comprehensive and responsive to the needs of the patient. What may seem a trivial problem to physicians may be important to patients. Third, care teams should have intimate knowledge of the patient (and their families).”

Dr. Perrin adds that although not a part of the current study, new technologies also can enhance management of complex chronic conditions. “Equipping families with mobile technologies that would allow them to enter data about their child’s health and wellness status could provide clinic staff real-time information and encourage scheduling of follow-up visits based mainly on the child’s clinical status and less on arbitrary prearranged follow-up times.”

(doi:10.1001/jama.2014.16514; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 16, 2014

Media Advisory: To contact corresponding author Tongyu Lin, M.D., Ph.D., email tongyulin@hotmail.com. To contact editorial co-author Jeremy S. Abramson, M.D., call Terri Ogan at 617-726-0954 or email togan@partners.org.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.15704. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16095.

Study Compares Effectiveness of Antiviral Drugs to Prevent Hepatitis B Virus-Related Hepatitis among Patients Receiving Chemotherapy for Lymphoma

Among patients with lymphoma undergoing a certain type of chemotherapy, receiving the antiviral drug entecavir resulted in a lower incidence of hepatitis B virus (HBV)-related hepatitis and HBV reactivation, compared with the antiviral drug lamivudine, according to a study in the December 17 issue of JAMA.

Hepatitis B virus reactivation is a well­documented chemotherapy complication, with diverse manifestations including life-threatening liver failure, as well as delays in chemotherapy or premature termination, all of which can jeopardize clinical outcomes. The reported incidence of HBV reactivation in patients seropositive for the hepatitis B surface antigen undergoing chemotherapy is 26 percent to 53 percent. This HBV reactivation risk exists for patients with lymphoma treated with chemotherapies containing the drug rituximab. An optimal approach to prevention of HBV reactivation has not been determined, according to background information in the article.

He Huang, M.D., of the Sun Yat-sen University Cancer Center, Guangzhou, China, and colleagues randomly assigned 121 patients seropositive for the hepatitis B surface antigen with untreated diffuse large B-cell lymphoma receiving chemotherapy treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) to either entecavir (n = 61) or lamivudine (n = 60). Patients received these drugs beginning 1 week before the initiation of R-CHOP treatment to 6 months after completion of chemotherapy. The study was conducted from February 2008 through December 2012 at 10 medical centers in China. This trial was a substudy of a parent study designed to compare a 3-week with a 2-week R-CHOP chemotherapy regimen for untreated diffuse large B-cell lymphoma.

The date of last patient follow-up was May 25, 2013. The researchers found that the rates were significantly lower for the entecavir group vs the lamivudine group for hepatitis (8.2 percent vs 23.3 percent), HBV-related hepatitis (0 percent vs 13.3 percent), HBV reactivation (6.6 percent vs 30 percent), delayed hepatitis B (0 percent vs 8.3 percent), and chemotherapy disruption (1.6 percent vs 18.3 percent).

Of the patients in the entecavir group, 24.6 percent experienced treatment-related adverse events, compared to 30.0 percent of patients in the lamivudine group.

The authors note that because entecavir is more expensive than lamivudine, further studies are needed to determine whether all patients seropositive for the hepatitis B surface antigen who receive rituximab-based immunosuppressive therapy should be given entecavir to prevent HBV flares and to determine which patients will benefit most from entecavir prophylaxis.

“If replicated, these findings support the use of entecavir in these patients.”

(doi:10.1001/jama.2014.15704; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by a grant from the Foundation of 5010 Clinical Trials of Sun Yat-sen University. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: Reactivation in Patients Receiving Rituximab-Based Chemotherapy for Lymphoma

Jeremy S. Abramson, M.D., and Raymond T. Chung, M.D., of Massachusetts General Hospital, Boston, comment on the findings of this study in an accompanying editorial.

“For HBV carriers as well as patients with cleared HBV infection, entecavir prophylaxis can be recommended to reduce the rate of HBV reactivation and hepatitis. For patients unable to receive antiviral prophylaxis, HBV DNA viral loads must be closely monitored during and after completion of chemotherapy. A more nuanced approach may be possible, in which patients at low risk for HBV reactivation can be identified and preferentially followed up with surveillance alone, such as those who are seropositive for both the core antibody and surface antibody. The answer to this question warrants ongoing investigation, as does the definition of the optimal duration of prophylactic antiviral therapy. The screening for and management of patients infected with HBV who receive chemotherapy should be viewed as nothing less than optimal care of patients with lymphoma.”

(doi:10.1001/jama.2014.16095; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 16, 2014

Media Advisory: To contact Frank M. Sacks, M.D., call Jessica Caragher at 617-525-6373 or email jcaragher@partners.org. To contact editorial author Robert H. Eckel, M.D., call Mark Couch at 303-724-5377 or email mark.couch@ucdenver.edu.

To place an electronic embedded link to this study and editorial in your story  This link to the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16658. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.15338.

Low-Glycemic Index Carbohydrate Diet Does Not Improve Cardiovascular Risk Factors, Insulin Resistance

In a study that included overweight and obese participants, those with diets with low glycemic index of dietary carbohydrate did not have improvements in insulin sensitivity, lipid levels, or systolic blood pressure, according to a study in the December 17 issue of JAMA.

Foods that have similar carbohydrate content can differ in the amount they raise blood glucose, a property called the glycemic index. Even though some nutrition policies advocate consumption of low-glycemic index foods and even promote food labeling with glycemic index values, the independent benefits of glycemic index, and its effect on risk factors for cardiovascular disease and diabetes, are not well understood, according to background information in the article.

Frank M. Sacks, M.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues conducted a trial in which 163 overweight adults with prehypertension or stage 1 hypertension were given 4 different complete diets that contained all of their meals, snacks, and calorie-containing beverages, each for 5 weeks; and completed at least 2 study diets. The four diets were (1) a high-glycemic index (65 percent on the glucose scale), high-carbohydrate diet (58 percent energy); (2) a low-glycemic index (40 percent), high-carbohydrate diet; (3) a high-glycemic index, low-carbohydrate diet (40 percent energy); and (4) a low-glycemic index, low-carbohydrate diet. Each diet was based on a healthful Dietary Approaches to Stop Hypertension (DASH)-type diet, which is rich in fruits, vegetables, and low-fat dairy foods, and low in saturated and total fat.

The researchers found that at high dietary carbohydrate content, the low- compared with high-glycemic index level decreased insulin sensitivity; increased low-density lipoprotein (LDL) cholesterol; and did not affect levels of high-density lipoprotein (HDL) cholesterol, triglycerides, or blood pressure. At low carbohydrate content, the low- compared with high-glycemic index level did not affect the outcomes except for decreasing triglycerides. In the primary diet contrast, the low-glycemic index, low-carbohydrate diet, compared with the high-glycemic index, high-carbohydrate diet, did not affect insulin sensitivity, systolic blood pressure, LDL cholesterol, or HDL cholesterol but did lower triglycerides.

“In the context of an overall DASH-type diet, using glycemic index to select specific foods may not improve cardiovascular risk factors or insulin resistance,” the authors conclude.

(doi:10.1001/jama.2014.16658; 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.

TV Note – This week’s JAMA Report video is on the effect of a high- vs low-glycemic index carbohydrate diet on cardiovascular risk and insulin resistance. The video, along with embedded and downloadable video, audio files, text, documents and related links will be available at 3 p.m. CT Tuesday, December 16 at this link.

Editorial: Role of Glycemic Index in the Context of an Overall Heart-Healthy Diet

Robert H. Eckel, M.D., of the University of Colorado Anschutz Medical Campus, Aurora, writes in an accompanying editorial that many of the results of this study were contrary to what had been expected.

“When glycemic index was lower in the high­carbohydrate diet, insulin sensitivity not only did not increase but decreased. With the same diet pattern, levels of LDL cholesterol and apolipoprotein B (a secondary end point) increased, with no changes in HDL cholesterol or triglyceride level or blood pressure.”

“The unexpected findings of the study by Sacks et al suggest that the concept of glycemic index is less important than previously thought, especially in the context of an overall healthy diet, as tested in this study. These findings should therefore direct attention back to the importance of maintaining an overall heart-healthy lifestyle, including diet pattern.”

(doi:10.1001/jama.2014.15338; 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: 10:00 A.M. (CT) WEDNESDAY, DECEMBER 10, 2014

Media Advisory: To contact Justin E. Bekelman, M.D., call Steve Graff at 215-349-5653 or email stephen.graff@uphs.upenn.edu.

Many Breast Cancer Surgery Patients Do Not Receive Shorter, Less Costly Radiation Treatment

Although the use of a type of radiation treatment that is shorter in duration and less costly has increased among women with early-stage breast cancer who had breast conserving surgery, most patients who meet guidelines to receive this treatment do not, according to a study appearing in JAMA. The study is being released to coincide with the San Antonio Breast Cancer Symposium.

Breast cancer accounts for the largest portion of national expenditures on cancer care, estimated to reach $158 billion in 2020. Breast conservation therapy is the most common treatment for early-stage breast cancer. Whole breast irradiation (WBI), recommended for most women after breast conserving surgery, reduces local recurrence and improves overall survival. Conventional WBI, comprising 5 to 7 weeks of daily radiation fractions (i.e., treatments), has been the mainstay of treatment in the United States. Hypofractionated WBI is a shorter duration treatment alternative to conventional WBI, comprising fewer but higher-dose fractions generally delivered over 3 weeks. Based on high quality evidence from clinical trials, expert guidelines in 2011 endorsed hypofractionated WBI for selected patients with early-stage breast cancer and permitted hypofractionated WBI for other patients, according to background information in the article.

“Hypofractionated WBI increases convenience, reduces treatment burden, and lowers health care costs while offering similar cancer control and cosmesis [cosmetic outcomes] to conventional WBI. Furthermore, patients prefer shorter radiation treatment regimens,” the authors write.

Justin E. Bekelman, M.D., of the University of Pennsylvania Perelman School of Medicine, Philadelphia, and colleagues examined the usage and costs of hypofractionated WBI between 2008 and 2013—before and after the publication of key clinical trials and updated practice guidelines. The researchers used administrative claims data from 14 commercial health care plans covering 7.4 percent of U.S. adult women in 2013, and classified patients with incident early-stage breast cancer treated with lumpectomy and WBI from 2008 and 2013 into 2 groups: (1) the hypofractionation- endorsed cohort (n = 8,924) included patients 50 years of age or older without prior chemotherapy or axillary lymph node involvement and (2) the hypofractionation-permitted cohort (n = 6,719) included patients younger than 50 years or those with prior chemotherapy or axillary lymph node involvement. For this analysis, hypofractionated WBI was 3-5 weeks of treatment; conventional WBI was 5-7 weeks.

The researchers found that hypofractionated WBI increased from 10.6 percent in 2008 to 34.5 percent in 2013 in the hypofractionation-endorsed group and from 8.1 percent in 2008 to 21.2 percent in 2013 in the hypofractionation-permitted group. Adjusted average total health care expenditures in the 1 year after diagnosis were $28,747 for hypofractionated and $31,641 for conventional WBI in the hypofractionation-endorsed group (difference, $2,894) and $64,273 for hypofractionated and $72,860 for conventional WBI in the hypofractionation-permitted group (difference, $8,587). Adjusted average total 1-year patient out-of-pocket expenses were not significantly different between hypofractionated vs conventional WBI in either group.

“In the United States, although the 2011 practice guidelines concluded that hypofractionated and conventional WBI were ‘equally effective for in-breast tumor control and comparable in long-term side effects’ for selected women, the guidelines stopped short of recommending hypofractionated WBI as a care standard to be used in place of conventional WBI. The absence of a clear recommendation may have contributed to slower uptake of hypofractionation in the United States than in other countries. In 2013, we observed more pronounced uptake of hypofractionation; evaluation of future treatment patterns will be important to document whether or not this trend reflects the beginning of more widespread adoption,” the authors write.

(doi:10.1001/jama.2014.16616; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Dr. Bekelman received support from a grant from the National Cancer Institute. WellPoint provided funds to support research at HealthCore, a wholly-owned WellPoint subsidiary. 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, DECEMBER 9, 2014

Media Advisory: To contact Stephen R. Pitts, M.D., M.P.H., email Janet Christenbury at JMCHRIS@emory.edu.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16172.

Study Finds Greater Emergency Department Resource Use by Supervised Residents vs. Attending Physicians Alone

In a sample of U.S. emergency departments, compared to attending physicians alone, supervised visits (involving both resident and attending physicians) were associated with a greater likelihood of hospital admission and use of advanced imaging and with longer emergency department stays, according to a study in the December 10 issue of JAMA, a theme issue on medical education.

A common assumption is that care at academic medical centers costs more than care at nonteaching hospitals in part because of a higher frequency of testing and other resource use in teaching settings. Cost-effective care is among the “mile­stones” now used to evaluate emergency medicine residents and accredit emergency medicine residency programs.  Although there is evidence that resident supervision may improve some patient outcomes, few studies of supervised learning have explicitly evaluated resource use as an outcome, according to background information in the article.

Stephen R. Pitts, M.D., M.P.H., of the Emory University School of Medicine, Atlanta, and colleagues compared resources used in supervised vs attending-only visits with data from the National Hospital Ambulatory Medical Care Survey (2010), a sample of U.S. emergency departments (EDs) and ED visits.

Of 29,182 ED visits to the 336 nonpediatric EDs in the sample, 3,374 visits were supervised visits. Compared with the 25,808 attending-only visits, supervised visits were significantly associated with more frequent hospital admission (21 percent vs 14 percent), advanced imaging (computed tomography, ultrasound, or magnetic resonance imaging; 28 percent vs 21 percent), and a longer median ED stay (226 vs 153 minutes), but not with blood testing (53 percent vs 45 percent).

“In our study of a nationally representative sample of ED visits, we hypothesized that supervised visits would consume more resources than nonsupervised visits, reasoning that supervised learning favors a more deliberate, reflective decision-making style than nonteaching clinical visits. We confirmed consistently higher use of several ED resources among supervised visits even after adjustment for several other possible determinants of resource use that were available in the survey,” the authors write.

(doi:10.1001/jama.2014.16172; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 9, 2014

Media Advisory: To contact Sunny Smith, M.D., call Jacqueline Carr at 619-543-6427 or email jcarr@ucsd.edu.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.16066.

Number of Medical Schools with Student-Run Free Clinics Has More Than Doubled

There has been a doubling during the last decade in the number of U.S. medical schools that have student-run free clinics, with more than half of medical students involved with these clinics, according to a study in the December 10 issue of JAMA, a theme issue on medical education.

Sunny Smith, M.D., of the University of California, San Diego, and colleagues conducted a study to assess whether there has been growth of student-run free clinics (SRFCs) in medical schools and describe the characteristics of these clinics. The first national study of SRFCs conducted in 2005 described 111 SRFCs at 49 Association of American Medical Colleges (AAMC) member institutions. The researchers developed a 39 item survey with yes/no, multiple-choice, and open-ended responses. SRFCs and their medical student leaders were identified through the Society of Student-Run Free Clinics.

The authors identified SRFCs at 106 of 141 (75.2 percent) U.S. AAMC member institutions. The survey response rate was 81.1 percent (86/106). The 86 responding institutions reported 208 SRFC sites. More than half of medical students were reported to be involved in SRFCs, including first- through fourth­ year students. Fifty-three percent of institutions reportedly offered no academic credit for participation.

The most common core services provided by the SRFCs were outpatient adult medicine, health care maintenance, chronic disease management, language interpreters and social work. The most common diseases treated were diabetes and hypertension.

In open-ended responses, students identified the greatest strengths of SRFCs as serving the underserved and student education. The biggest challenges were obtaining sufficient faculty staffing and funding.

“Despite the lack of academic credit at many institutions, most medical students are volunteering in this setting. Given the ubiquity of SRFCs in the education of future physicians, further research is needed to assess their educational and clinical outcomes,” the authors write.

“The lack of funding and sufficient faculty supervisors identified as the biggest challenges in SRFCs are actionable items because institutional support could help stabilize and improve these educational opportunities for years to come.”

(doi:10.1001/jama.2014.16066; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 9, 2014

Media Advisory: To contact Bradley M. Gray, Ph.D., call Lorie Slass at 215-399-4005 or email lslass@abim.org. To contact John Hayes, M.D., email Gary Kunich at gary.kunich@va.gov. To contact editorial author Thomas H. Lee, M.D., M.Sc., email Kristen Berry at kberry@ariamarketing.com.

To place an electronic embedded link to this study and editorial in your story  This link to the 1^st study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.12716. This link to the 2nd study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.13992. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.13566.

Studies Examine Effect on Patient Care and Costs of Requirements for Maintaining Board Certification

Two studies in the December 10 issue of JAMA, a theme issue on medical education, evaluate the effect of the requirement of maintaining board certification on hospitalizations, health care costs and quality of patient care.

One of the largest changes in physician accreditation policy was the initiation of a 10-year Maintenance of Certification (MOC) requirement in 1990 by the American Board of Internal Medicine (ABIM). This change was also adopted by 24 certifying boards of the American Board of Medical Specialties, affecting 85 percent of all U.S. physicians. Despite the importance of this change, there has been limited research examining associations between the MOC requirement and patient outcomes.

In one study, Bradley M. Gray, Ph.D., of the American Board of Internal Medicine, Philadelphia, and colleagues examined outcomes of care for Medicare beneficiaries treated in 2001 by two groups of ABIM-certified internal medicine physicians (general internists). One group (n = 956), initially certified in 1991, was required to fulfill the MOC program in 2001 (MOC-required) and treated 84,215 beneficiaries in the sample; the other group (n = 974), initially certified in 1989, was grandfathered out of the MOC requirement (MOC-grandfathered) and treated 69,830 similar beneficiaries in the sample. The primary outcome measured was ambulatory care-sensitive hospitalizations (ACSHs), which are hospitalizations triggered by conditions (such as diabetes and asthma) thought to be potentially preventable through better access to and quality of outpatient care.  Other outcomes included health care cost measures (adjusted to 2013 dollars).

Annual incidence of ACSHs (per 1,000 beneficiaries) increased from the pre-MOC period (37.9 for MOC-required beneficiaries vs 37.0 for MOC-grandfathered beneficiaries) to the post-MOC period (61.8 for MOC-required beneficiaries vs 61.4 for MOC-grandfathered beneficiaries) for both groups, as did annual per-beneficiary health care costs (pre-MOC period, $5,157 for MOC-required beneficiaries vs $5,133 for MOC-grandfathered beneficiaries; post-MOC period, $7,633 for MOC-required beneficiaries vs $7,793 for MOC-grandfathered beneficiaries). The MOC requirement was not statistically associated with group differences in the growth of the annual ACSH rate.

The researchers found that the MOC requirement was associated with a decreased growth in costs related to laboratory tests, imaging, and specialty visits.

“Imposition of the MOC requirement was not associated with a difference in the increase in ACSHs but was associated with a small reduction in the growth differences of costs for a cohort of Medicare beneficiaries,” the authors write.

The authors note that this research should be replicated for the current MOC program using more robust measures of care quality, across other patient populations as well as across internal medicine subspecialties, and for other certification boards’ MOC requirements.

(doi:10.1001/jama.2014.12716; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Financial and material support was provided by the American Board of Internal Medicine. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

In an another study in the December 10 issue of JAMA, John Hayes, M.D., of the Clement J. Zablocki VA Medical Center, Milwaukee, Wisc., and colleagues examined whether there are differences in the quality of primary care provided between internists with time-limited board certification and those with time-unlimited certification. Before 1990, board certification was time-unlimited. Since 1990, to maintain certification internists must pass an examination every 10 years.

American Board of Internal Medicine initiatives encourage internists with time-unlimited certificates to recertify. However, there are limited data evaluating differences in performance between internists with time-limited or time-unlimited board certification, according to background information in the article.

The study consisted of an analysis of data for 10 primary care performance measures (such as blood pressure control, colorectal cancer screening) from 1 year (2012-2013) at four Veterans Affairs (VA) medical centers. Participants were internists with time-limited (n = 71) or time-unlimited (n = 34) ABIM certification providing primary care to 68,213 patients.

After adjustment for various factors, the researchers found no significant differences in outcomes for patients cared for by internists with time-limited or time-unlimited certification for any of the performance measures. “To whatever extent a goal of MOC is to improve the quality of patient care, these findings raise a question of whether that goal is being achieved, at least among internists at these VA hospitals.”

“Additional research to examine the difference in patient outcomes among holders of time-unlimited and time-limited certificates in VA and nonacademic settings and the association with other ABIM goals may help clarify the potential benefit of MOC participation,” the authors conclude.

(doi:10.1001/jama.2014.13992; 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: Certifying the Good Physician – A Work in Progress

Physicians should work constructively to help MOC improve, much as physicians should work continuously to improve how they collaborate with colleagues and with patients, writes Thomas H. Lee, M.D., M.Sc., of Press Ganey, Brigham and Women’s Hospital, Harvard Medical School, Boston, in an editorial in this issue of JAMA.

“In addition, physicians must make the commitment to lifelong, meaningful learning to ensure that their knowledge and skills remain current and relevant. Patients would be disappointed by anything less. The medical profession may never fully understand the effect of MOC, but that does not mean that physicians should give up or stop trying to make it better. The MOC program is a work in progress, as are all good physicians.”

(doi:10.1001/jama.2014.13566; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 9, 2014

Media Advisory: To contact Lisa Diamond, M.D., M.P.H., call Courtney DeNicola Nowak at 212-639-3573 or email denicolc@mskcc.org.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.15444.

Gap Exists Between Languages Spoken by Medical Residency Applicants and U.S. Patients with Limited English Proficiency

An analysis of the non-English-language skills of U.S. medical residency applicants finds that although they are linguistically diverse, most of their languages do not match the languages spoken by the U.S. population with limited English proficiency, according to a study in the December 10 issue of JAMA, a theme issue on medical education.

More than 25 million U.S. residents have limited English proficiency, an 80 percent increase from 1990 to 2010. Limited English proficiency (LEP) may impede participation in the English­language-dominant health care system. Little is known about the non-English-language skills of physicians in training, according to background information in the article.

Lisa Diamond, M.D., M.P.H., of Memorial Sloan Kettering Cancer Center, New York, and colleagues conducted a study to characterize the language diversity of all U.S. residency applicants through the Electronic Residency Application Service and contrast applicant language skills with the predominant languages of the U.S. population with LEP. Applicants were asked to self-report proficiency in all languages spoken. The five response options were: native/functionally native; advanced; good; fair; and basic. The applicants’ linguistic diversity was contrasted with the U.S. LEP population. The top 25 LEP languages spoken were obtained from the U.S. Census Bureau for individuals 5 years and older between 2007 and 2011.

Most (84.4 percent) of the 52,982 applicants for 2013 reported some proficiency in at least 1 non-English language. The most common languages were Spanish (53.2 percent), Hindi (20.5 percent), French (15.6 percent), Urdu (10.1 percent), and Arabic (9.8 percent). Only 21 percent of applicants reported advanced Spanish proficiency.

Among the 25.1million U.S. LEP speakers, 16.4 million speak Spanish. For every 100,000 U.S. LEP speakers, there were 105 applicants who reported at least advanced proficiency in a non­English language. Relative to this rate, there was an over-representation of Hindi-speaking applicants, and an under-representation of Spanish, Vietnamese, Korean, and Tagalog, which are 4 of the top 5 U.S. LEP languages.

“Further research is needed on whether increasing the number of bilingual residents, educating trainees on language services, or implementing medical Spanish courses as a supplement to (not a substitute for) interpreter use would improve care for LEP patients,” the authors write.

(doi:10.1001/jama.2014.15444; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Dr. Diamond was supported by Memorial Sloan Kettering Cancer Center, Department of Psychiatry and Behavioral Sciences, Immigrant Health and Cancer Disparities Service. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 9, 2014

Media Advisory: To contact co-author Fitzhugh Mullan, M.D., call Kathy Fackelmann at 202-994-8354 or email kfackelmann@gwu.edu.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.15973.

Region of Medical Residency Training May Affect Future Spending Patterns of Physician

Among primary care physicians, the spending patterns in the regions in which their residency program was located were associated with expenditures for subsequent care they provided as practicing physicians, with those trained in lower-spending regions continuing to practice in a less costly manner, even when they moved to higher-spending regions, and vice versa, according to a study in the December 10 issue of JAMA, a theme issue on medical education.

Regional and system-level variations in Medicare spending and overall intensity of medical services delivered to patients represent the collective practice decisions of clinicians in these different systems. Some research suggests that the nature of residency training influences the nature of physician practice, which raises the question of whether exposure to different practice and spending patterns during residency influences physicians’ practice patterns and cost of care after training, according to background information in the article.

Candice Chen, M.D., M.P.H., of George Washington University, Washington, D.C., and colleagues examined the relationship between spending patterns in the region of a physician’s graduate medical education training and individual physician practice spending patterns after training. The study consisted of an analysis of 2011 Medicare claims data (Part A hospital and Part B physician) for a random, nationally representative sample of family medicine and internal medicine physicians completing residency between 1992 and 2010 with Medicare patient panels of 40 or more patients (2,851 physicians providing care to 491,948 Medicare beneficiaries). Locations of practice and residency training were matched with Dartmouth Atlas Hospital Referral Region (HRR) files. Training and practice HRRs were categorized into low-, average-, and high-spending groups, with approximately equal distribution of beneficiary numbers.

For physicians practicing in high-spending regions, those trained in high-spending regions had an average spending per Medicare beneficiary per year $1,926 higher than those trained in low-spending regions. For practice in average-spending HRRs, average spending per beneficiary was $897 higher for physicians trained in high- vs low-spending regions. For practice in low-spending HRRs, the difference across training HRR levels was not significant ($533).

Overall, there was approximately a 7 percent difference in spending between physicians trained in the highest and lowest training HRR spending groups, corresponding to an estimated $522 difference between low- and high-spending training regions.

For physicians 1 to 7 years in practice, there was a 29 percent difference in spending between those trained in low- and high-spending regions; however, after 16 to 19 years, there was no significant difference.

“These observations suggest an imprinting of care-related spending behaviors that may take place during residency. Decay of the effect over time would be consistent with a training imprint that wanes because of practice environment. These findings are notable for the initial size and continuation of the association of training with physician spending patterns for up to 15 years after training. This potential imprinting has implications for physician training and potentially for hiring, particularly because major efforts are under way to reduce health care spending,” the authors write.

(doi:10.1001/jama.2014.15973; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 9, 2014

Media Advisory: To contact Mitesh S. Patel, M.D., M.B.A., M.S., call Anna Duerr at 215-349-8369 or email anna.duerr@uphs.upenn.edu. To contact the corresponding author for the 2^nd study, Karl Y. Bilimoria, M.D., M.S., call Marla Paul at 312-503-8928 or email marla-paul@northwestern.edu. To contact editorial co-author James A. Arrighi, M.D., call David Orenstein at 401-863-1862 or email david_orenstein@brown.edu.

To place an electronic embedded link to this study and editorial in your story  This link to the 1^st study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.15273. This link to the 2nd study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.15277. This will be the link to the editorial: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.15580.

Resident Duty Hour Reforms Do Not Appear to Have Had Significant Effect on Patient Outcomes or on Resident Board Examination Scores

An examination of the effect of resident duty hour reforms in 2011 finds no significant change in mortality or readmission rates for hospitalized patients or outcomes for general surgery patients, according to two studies in the December 10 issue of JAMA, a theme issue on medical education.

In 2011, the Accreditation Council for Graduate Medical Education (ACGME) implemented new duty hour reforms for all ACGME-accredited residency programs. The revisions maintain the weekly limit of 80 hours set forth by the 2003 duty hour reforms but reduced the work hour limit from 30 consecutive hours to 16 hours for first­year residents (interns) and 24 hours for upper-year residents (with an additional 4 hours to perform transitions of care and participate in educational activities). Initial duty hour reforms in 2003 were prompted by wide­spread concern about the effects of resident fatigue. There has been concern that the 2011 duty hour reforms may adversely affect the quality of resident education, increase handoffs in care, and put both patient safety and outcomes at risk.

In one study, Mitesh S. Patel, M.D., M.B.A., M.S., of the Veterans Administration Hospital and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and colleagues evaluated the association of the 2011 ACGME duty hour reforms with mortality and readmissions among hospitalized Medicare patients during the first year after the reforms. The study analyzed Medicare patient admissions (6,384,273 admissions from 2,790,356 patients) to short-term, acute care hospitals (n = 3,104) with principal medical diagnoses of heart attack, stroke, gastrointestinal bleeding, or congestive heart failure or a classification of general, orthopedic, or vascular surgery.

After an analysis of the number of hospital admissions, deaths and readmissions in the two years before duty hour reforms compared with these figures in the first year after the reforms, the researchers found no significant positive or negative associations of duty hour reforms with 30-day mortality for any of the medical conditions or surgical categories in this study, and no significant positive or negative associations of these reforms with 30-day all-cause readmissions for combined medical conditions or combined surgical categories.

The authors write that their findings suggest that in the first year after the 2011 duty hour reforms, the goals of improving the quality and safety of patient care, as measured by decreased 30-day mortality and all-cause readmissions rates “were not being achieved. Conversely, concerns that outcomes might actually worsen because of decreased continuity of care have not been borne out.”

(doi:10.1001/jama.2014.15273; 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.

In an another study in the December 10 issue of JAMA, Ravi Rajaram, M.D., of the American College of Surgeons, Chicago, and colleagues conducted a study to determine if the 2011 ACGME duty hour reform was associated with a change in general surgery patient outcomes or in resident examination performance.

The study examined general surgery patient outcomes two years before (academic years 2009-2010) and after (academic years 2012-2013) the 2011 duty hour reform. Patients were those undergoing surgery at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program. General surgery resident performance on the annual in-training, written board, and oral board examinations was assessed for this same period.

In the main analysis, 204,641 patients were identified from 23 teaching (n = 102,525) and 31 nonteaching (n = 102,116) hospitals. In adjusted analyses, the researchers found that the duty hour reform was not associated with a significant change in death or serious illness in either post-reform year 1 or post-reform year 2 or when both post-reform years were combined. There was also no association between duty hour reform and any other postoperative adverse outcome.

Average in-training examination scores did not significantly change from 2010 to 2013 for first-year residents, for residents from other postgraduate years, or for first-time examinees taking the written or oral board examinations during this period.

The authors write that the study findings could be interpreted in at least two ways. “First, there is no evidence of worsened patient care or resident education, and given assumed improvements to resident well-being, this could indicate that current policies should continue forward as they are. Conversely, the potential harm from poor continuity of care, increased handoffs, trainees feeling unprepared to practice, and concern regarding residents developing a shift-work mentality engendered by these policies could suggest that the duty hour reform may require significant revision  or reconsideration. Although many of these concerns have not been substantiated by consistent evidence, they reflect the intense interest duty hour reform has generated from the clinical and educational community.”

“The implications of these findings should be considered when evaluating the merit of the 2011 ACGME duty hour reform and revising related policies in the future.”

(doi:10.1001/jama.2014.15277; 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: Duty Hour Requirements – Time for a New Approach?

“How should the studies in this issue of JAMA and other literature on duty hour restrictions be interpreted,” asks James A. Arrighi, M.D., of the Warren Alpert Medical School of Brown University and the Lifespan Cardiovascular Institute, Providence, R.I., and James C. Hebert, M.D., of the University of Vermont College of Medicine and Fletcher Allen Healthcare, Burlington, Vt., in an accompanying editorial.

“First, with regard to potential short-term policy decisions on duty hour requirements, is it important to decide whether a null association with safety and education metrics is a positive or negative finding? In our roles as residency review committee chairs, we think this is the wrong question to ask because there was no justification for making the rules more complex or restrictive, as occurred in 2011.”

“Second, in the absence of improvement in patient outcomes in these 2 studies, how should the 2011 duty hour revisions be judged? … Many program directors have expressed great concern about the potential negative effects of this second set of changes, including effects on resident education, preparedness for senior roles, patient safety, and continuity of care. Thus, in the absence of clear data demonstrating benefit, the concerns of the educational community should be given credence and not be dismissed as mere perceptions.”

“Third, although high-quality observational studies such as these are very helpful, randomized data are lacking. Recognizing this gap in research, the educational community has proposed 2 randomized trials on duty hour requirements in medical and surgical residents that may provide more definitive information.”

(doi:10.1001/jama.2014.15580; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, DECEMBER 2, 2014

Media Advisory: To contact corresponding author Shabbir M. H. Alibhai, M.D., M.Sc., call Jane Finlayson at 416-946-2846 or email jane.finlayson@uhn.ca.

To place an electronic embedded link to this study in your story  This link for the study will be live at the embargo time: https://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2014.14038

Prescriptions for Drugs to Strengthen Bones Remains Low Despite Recommended Use for Men Receiving Androgen Deprivation Therapy

Although some guidelines recommend use of bisphosphonates (a class of drugs used to strengthen bone) for men on androgen deprivation therapy, an analysis finds that prescriptions for these drugs remains low, even for those men at high risk of subsequent fractures, according to a study in the December 3 issue of JAMA.

Androgen deprivation therapy (ADT) is an effective, widely used therapy for men with prostate cancer. Adverse effects include bone loss and increased fracture risk. Canadian guidelines recommended bisphosphonate use in men with osteoporosis or fragility fracture as early as 2002 and in men on ADT in 2006. Bisphosphonate prescribing patterns are relatively unknown and may have changed over time because of increasing awareness of bone effects of ADT and evidence of bisphosphonate efficacy, according to background information in the article.

Using administrative databases at the Institute for Clinical Evaluative Sciences and the Ontario Cancer Registry, Husayn Gulamhusein, B.H.Sc., of the University Health Network, Toronto, and colleagues examined rates of bisphosphonate prescriptions in men initiating ADT in Ontario between 1995 and 2012. The study group included men 66 years of age or older starting ADT for prostate cancer, who had undergone surgical removal of one or both testicles or received at least 6 months of continuous medical ADT and survived at least 1 year after ADT initiation. Any bisphosphonate claim within 12 months of ADT initiation was captured through drug database claims. Bisphosphonate prescription over time was examined for three groups: all nonusers of bisphosphonates, those with prior osteoporosis, and those with prior fragility fracture.

A total of 35,487 men with prostate cancer who began ADT during the study period were identified. Bisphosphonate claims among all nonusers increased from 0.35 per 100 persons in 1995-1997 to 3.40 per 100 persons in 2010-2012. Even among those with prior osteoporosis or fragility fracture, rates remained low. Among all 3 groups, peak bisphosphonate claims occurred in 2007-2009, with a high of 11.89 per 100 persons in those with prior osteoporosis.

As the most widely used class of prescription drugs for osteoporosis, the authors write that these findings suggest “limited awareness among clinicians regarding optimal bone health management.”

The researchers speculate that the decrease in bisphosphonate prescriptions after 2009 may be partly due to recent negative media regarding the association of bisphosphonates with rare osteonecrosis (bone death) of the jaw and atypical femoral fractures. “This is appropriate for groups at low risk for fractures, but the decrease in use for high-risk patients is concerning.”

“Although the optimal rate of bisphosphonate use in men on ADT is unknown, it is reasonable that most men with prior osteoporosis or fracture should be taking a bisphosphonate or other effective bone medication.”

(doi:10.1001/jama.2014.14038; 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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