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

Media Advisory: To contact J. Randall Curtis, M.D., M.P.H., call Elizabeth Hunter at 206-616-3192 or email elh415@uw.edu. To contact editorial co-author Abraham Verghese, M.D., call Margarita Gallardo at 650-723-7897 or email mjgallardo@stanford.edu.

Chicago – Among internal medicine and nurse practitioner trainees, simulation-based communication skills training compared with usual education did not improve quality of communication about end-of-life care or quality of end-of-life care but was associated with a small increase in patients’ symptoms of depression, according to a study appearing in the December 4 issue of JAMA, a medical education theme issue.

“Observational studies have suggested that communication about end-of-life care is associated with decreased intensity of care, increased quality of life, and improved quality of dying. In addition, interventions that focus on communication about palliative and end-of-life care, using palliative care specialists, have demonstrated improved quality of life, decreased symptoms of depression, and reduced intensity of care at the end of life,” according to background information in the article. “Simulation-based training improves skill acquisition, but effects on patient-reported outcomes are unknown.”

J. Randall Curtis, M.D., M.P.H., of the University of Washington, Seattle, and colleagues conducted a trial to examine whether a communication skills-building workshop aimed at internal medicine (n = 391) and nurse practitioner (n = 81) trainees, using simulation during which trainees practiced skills associated with palliative and end-of-life care communication, had any effect on patient-, family-, and clinician-reported outcomes.  Participants were randomized to the 8-session, simulation-based, communication skills intervention (n = 232) or usual education (n = 240).

The primary outcome was patient-reported quality of communication (QOC). Secondary outcomes were patient-reported quality of end-of-life care (QEOLC) and depressive symptoms and family-reported QOC and QEOLC.

The researchers received 1,866 patient evaluations completed by 1,717 patients evaluating 345 trainees; and 936 surveys completed by 898 family respondents, evaluating 295 trainees. Analysis of the data indicated that the intervention was not associated with improvement in QOC or QEOLC. After adjustment, comparing intervention with control, there was no difference in the QOC or QEOLC score for patients or families, but it was associated with increased depression scores among patients of post-intervention trainees.

“These findings raise questions about skills transfer from simulation training to actual patient care and the adequacy of communication skills assessment,” the authors write.

(doi:10.l001/jama.2013.282081; Available pre-embargo to the media at https://media.jamanetwork.com)

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

Editorial: Improving Communication With Patients – Learning by Doing

In an accompanying editorial, Jeffrey Chi, M.D., and Abraham Verghese, M.D., of the Stanford University School of Medicine, Stanford, Calif., write that there are many possible reasons for the unexpected results of this study.

“Patients and families are not formally trained to evaluate communication skills. Additionally, the acquisition of skills was tested over the course of a 10-month period following workshop participation and not immediately following specific end-of-life discussions. It is possible that the improvement in participants’ skills was not enough to make a measurable difference to patients; conversely, it is possible that trainees did not recall training and so were not able to apply the communication skills.”

“The study by Curtis et al provides an important lesson about the nature of pedagogy [teaching or training] in medicine: new and innovative ways are needed to teach skills, and continued measurement, reassessment, and validation are needed to determine if those teaching methods have succeeded. The final arbiter is of course the patient and patient outcomes. Much work remains to be done.”

(doi:10.l001/jama.2013.281828; 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 3, 2013

Media Advisory: To contact Richard P. Deane, M.B., B.Ch., email deaneri@tcd.ie.

Chicago – Among fourth-year medical students completing an 8-week obstetrics/gynecology clinical rotation, there was a positive association between attendance at clinical and tutorial-based activities and overall examination scores, according to a study appearing in the December 4 issue of JAMA, a medical education theme issue.

“Student attendance is thought to be an important factor in the academic performance of medical students on the basis that clinical contact and teaching are necessary to develop competence. Student attendance also has wider implications for institutions providing medical education. The educational value of clinical teaching is resource-dependent and expensive. Medical schools are increasingly challenged in providing clinical teaching in the face of increasing student numbers. In this context, medical schools must appraise the educational value of attendance at their clinical teaching programs,” according to background information in the article. “Previous studies evaluating the relationship between attendance and academic performance among medical students have been limited and related to classroom-based lectures only rather than clinical activities.”

Richard P. Deane, M.B., B.Ch., and Deirdre J. Murphy, M.D., of Trinity College, University of Dublin, Ireland, evaluated the relationship between student attendance and academic performance in a medical student obstetrics/gynecology clinical rotation during a full academic year (September 2011 to June 2012) at a university teaching hospital in Dublin. Students were expected to attend 64 activities (26 clinical activities and 38 tutorial-based activities) but attendance was not mandatory. All 147 fourth-year medical students who completed an 8-week obstetrics/gynecology rotation were included.

The average attendance rate was 89 percent (n = 57/64 activities). Male students (84 percent attendance) and students who failed an end-of-year examination previously (84 percent attendance) had significantly lower rates. The researchers found that both clinical attendance and tutorial-based attendance were positively correlated with overall examination score. The associations persisted after controlling for confounding factors (factors that can influence outcomes) of student sex, age, country of origin, previous failure in an end-of-year examination, and the timing of the rotation during the academic year.

Distinction grades (grades above the expected basic standard [i.e., demonstrated additional items for the competency tested]) were present only among students with attendance rates of 80 percent or higher. The odds of a distinction grade increased with each 10 percent increase in attendance. The majority of failure grades occurred in students with attendance rates lower than 80 percent.

The researchers write that further research is needed to understand whether the relationship found in this study is causal, and whether improving attendance rates can improve academic performance.

“If a causal relationship can be identified, interventions to preemptively target potential poor attenders should be investigated to avoid the cycle of persistent failure and remedial education among a subset of students from year to year. The effect of rapidly evolving electronic learning resources on attendance patterns should also be evaluated.”

(doi:10.l001/jama.2013.282228; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Media Advisory: To contact David O. Warner, M.D., call Bryan Anderson at 507-284-5005 or email Anderson.bryan@mayo.edu.

Chicago – Among anesthesiology residents entering primary training from 1975 to 2009, 0.86 percent had a confirmed substance use disorder during training, with the incidence of this disorder increasing over the study period and the risk of relapse high, according to a study appearing in the December 4 issue of JAMA, a medical education theme issue.

Substance use disorder (SUD) is a serious public health problem, and physicians are susceptible. Anesthesiologists have ready access to potent substances such as intravenous opioids, although only indirect evidence exists that SUD is more common in anesthesiologists than in other physicians, according to background information in the article. “Formulation of policy and individual treatment plans is hampered by lack of data regarding the epidemiology and outcomes of physician SUD.”

David O. Warner, M.D., of the Mayo Clinic, Rochester, Minn., and colleagues examined the incidence and outcomes of SUD among anesthesiology residents in the United State. The analysis included physicians who began training in anesthesiology residency programs from July 1, 1975, to July 1, 2009 (n = 44,612). Follow-up for incidence was to the end of training, and for relapse was until December 31, 2010.

Of the 44,612 residents, 384 (0.86 percent) had SUD confirmed during training. During the study period, an initial high rate was followed by a period of lower rates in 1996-2002, but the highest rates occurred since 2003. The most common substance used was intravenous opioids, followed by alcohol, marijuana or cocaine, anesthetics/hypnotics, and oral opioids. Twenty-eight individuals (7.3 percent) died during the training period; all deaths were related to SUD.

The researchers estimated that approximately 43 percent of survivors experienced at least 1 relapse by 30 years after the initial episode. Rates of relapse and death did not depend on the category of substance used. Risk of relapse during the follow-up period was high, indicating persistence of risk after training. Risk of death was also high; at least 11 percent of those with evidence of SUD died of a cause directly related to SUD.

“To our knowledge, this report provides the first comprehensive description of the epidemiology and outcomes of SUD for any in-training physician specialty group, showing that the incidence of SUD has increased over the study period and that relapse rates are not improving,” the authors write.

“Despite the considerable attention paid to this issue, there is no evidence that the incidence and outcomes of SUD among these physicians are improving over time.”

(doi:10.l001/jama.2013.281954; 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 3, 2013

Media Advisory: To contact James Guevara, M.D., M.P.H., call Dana Weidig at 267-426-6092 or email weidigd@email.chop.edu.

Chicago – From 2000 to 2010, the presence of a minority faculty development program at U.S. medical schools was not associated with greater underrepresented minority faculty representation, recruitment, or promotion, according to a study appearing in the December 4 issue of JAMA, a medical education theme issue.

“Minority physicians and scientists have been inadequately represented among medical school faculty when compared with their representation in the U.S. population. Although their representation has increased over time, underrepresented minority faculty are less likely to be promoted and spend a longer period in a probationary rank. In addition, underrepresented minority faculty have been less likely to hold senior faculty and administrative positions and less likely to receive National Institutes of Health research awards,” according to background information in the article. To increase the recruitment and retention of underrepresented minority faculty, a number of medical schools in recent years have developed minority faculty development programs. “Although it is clear that efforts to enhance diversity and inclusion are increasing, it is not clear whether minority faculty development programs are effective in general at enhancing the recruitment and retention of underrepresented minority faculty.”

James Guevara, M.D., M.P.H., of the Children’s Hospital of Philadelphia, and colleagues conducted a study to determine whether minority faculty development programs targeting underrepresented minority faculty are associated with increases in underrepresented minority faculty representation, recruitment, and promotion. The study consisted of an analysis of the Association of American Medical Colleges Faculty Roster, a database of U.S. medical school faculty, and included full-time faculty at schools located in the 50 U.S. states or District of Columbia and reporting data from 2000-2010.

Underrepresented minority faculty were defined as faculty self-reported to be black, Hispanic, Native American, Alaskan Native, Native Hawaiian, or Pacific Islander faculty.

The overall number of underrepresented minority faculty increased during the study period (from 6,565 (6.8 percent) in 2000 to 9,009 (8.0 percent) in 2010) as did the percentage of newly hired faculty self-reporting underrepresented minority status (from 9.4 percent in 2000 to 12.1 percent in 2010) and newly promoted (6.3 percent to 7.9 percent). Hispanic faculty members increased from 3.6 percent in 2000 to 4.3 percent in 2010, while black faculty members increased 3.2 percent to 3.4 percent.

Of 124 eligible schools, 36 (29 percent) were identified with a minority faculty development program in 2010. Schools with minority faculty development programs had a similar increase in percentage of underrepresented minority faculty as schools without minority faculty development programs (6.5 percent in 2000 to 7.4 percent in 2010 vs. 7.0 percent to 8.3 percent). After adjustment for faculty and school characteristics, minority faculty development programs were not associated with greater representation of minority faculty, recruitment, or promotion.

In subgroup analyses, minority faculty development programs that were present for ≥ 5 years and had more components were associated with greater increases in underrepresented minority faculty representation.

The researchers add that the percentage of underrepresented minority faculty increased modestly from 2000 to 2010 at U.S. medical schools.

“Although the definition of underrepresented minority is evolving to reflect local and regional perspectives, findings from this study demonstrate that faculty who are underrepresented in medicine, relative to the general population, have seen little increase in absolute or percentage representation across all schools during this time period, while the prevalence of individuals of underrepresented minority status in the general population had increased to greater than 30 percent by 2010,” the authors write.

“This relatively small increase may have been the result of an increase in the percentage of faculty hires that involve underrepresented minority faculty and efforts to increase the pipeline of medical school faculty.”

(doi:10.l001/jama.2013.282116; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was funded by a New Connections grant from the Robert Wood Johnson Foundation. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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

Media Advisory: To contact Amy J. Starmer, M.D., M.P.H., call Meghan Weber at 617-919-3110 or email Meghan.Weber@childrens.harvard.edu. To contact editorial author Leora Horwitz, M.D., M.H.S., call Helen Dodson at 203-436-3984 or email helen.dodson@yale.edu.

Chicago – Implementation of a multifaceted program to improve patient handoffs (change in staff caring for a patient) among physicians-in-training residents at a children’s hospital was associated with a reduction in medical errors and preventable adverse events, according to a study appearing in the December 4 issue of JAMA, a medical education theme issue.

Handoff miscommunications are a leading cause of medical errors. “The Agency for Healthcare Research and Quality (AHRQ) and the Accreditation Council for Graduate Medical Education (ACGME) have identified improving handoffs as a priority in U.S. nationwide efforts to improve patient safety. The ACGME now requires residency programs to provide formal instruction in handoffs. Despite these new requirements and the increasing frequency of handoffs as a result of reductions in resident-physician work hours, many institutions do not have robust procedures for training residents or ensuring high-quality handoffs,” according to background information in the article.

Amy J. Starmer, M.D., M.P.H., of Boston Children’s Hospital and Harvard Medical School, Boston, and colleagues examined whether introduction of a multifaceted handoff program was associated with a reduction in medical errors and preventable adverse events, fewer omissions of key data in written handoffs, improved verbal handoffs, and changes in resident-physician workflow. The study included 1,255 patient admissions (642 before and 613 after the intervention) involving 84 resident physicians (42 before and 42 after the intervention) on 2 inpatient units at Boston Children’s Hospital.

The intervention consisted of a 2-hour communication training session that included interactive discussion regarding best practices for verbal and written handoffs; the introduction of a mnemonic (a memory aid) to standardize verbal handoffs; the restructuring of verbal handoffs to include integration of interns’ and senior residents’ separate handoffs into a unified team handoff; relocation of handoff to a private and quiet space; and introduction of periodic handoff oversight by a chief resident or attending physician. In addition, for one unit, a computerized handoff tool was created that was integrated into the electronic medical record.

Following implementation of the intervention, medical errors decreased from 33.8 per 100 admissions to 18.3 per 100 admissions, and preventable adverse events decreased from 3.3 per 100 admissions to 1.5 per 100 admissions. The researchers found that there were fewer omissions of key handoff elements on printed handoff documents, especially on the unit that received the computerized handoff tool. Verbal handoffs were more likely to occur in a quiet and private location after the intervention.

“Implementation of the intervention was not associated with adverse effects on resident workflow: time spent on verbal handoffs did not change, and time spent at the computer did not increase; residents spent more time in the post-intervention period in direct contact with patients,” the authors write.

“Given the increasing frequency of handoffs in hospitals following resident work-hour reductions and the high frequency with which miscommunications lead to serious medical errors, disseminating high-quality handoff improvement programs has the potential for benefit. Further work to improve and standardize handoffs across specialties and settings may lead to improvement in the safety of patients in teaching hospitals nationwide.”

(doi:10.l001/jama.2013.281961; 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: Does Improving Handoffs Reduce Medical Error Rates?

Leora Horwitz, M.D., M.H.S., of the Yale School of Medicine, New Haven, Conn., comments on this study in an accompanying editorial.

“As hospitals and residency programs seek to manage increasing complexity and fragmentation without reverting to an archaic model of round-the-clock care, the focus will be on safe handoffs and mitigating discontinuity. The study by Starmer et al presents tantalizing evidence that improving handoffs can actually reduce harm to patients. In the meantime, while awaiting results from larger multi-institutional studies, it is reasonable to ensure that at least basic elements of safe handoffs are in place.”

(doi:10.l001/jama.2013.281827; 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, NOVEMBER 26, 2013

Media Advisory: To contact David Alain Wohl, M.D., call Lisa Chensvold at 919-843-5719 or email lisa_chensvold@med.unc.edu.

Chicago – An analysis indicates that the prevalence of undiagnosed human immunodeficiency virus (HIV) infection among state prison entrants in North Carolina was low, at 0.09 percent, according to a study appearing in the November 27 issue of JAMA.

“A substantial proportion of individuals infected with the human immunodeficiency virus in the United States enter a correctional facility annually. Therefore, incarceration presents an opportunity for HIV detection. Even though many states have adopted policies of mass HIV screening of inmates, the extent to which HIV testing on prison entry detects new infections is unclear,” according to background information in the article.

David Alain Wohl, M.D., of the University of North Carolina, Chapel Hill, and colleagues examined HIV prevalence among inmates entering a state prison system and the proportion known to state public health authorities as having previously tested HIV seropositive. Individuals were evaluated who entered the North Carolina Department of Public Safety (NC DPS) between June 2008 and April 2009. Testing entering inmates for HIV in North Carolina was voluntary; however, a state statute mandated screening for syphilis. Excess blood was batch tested for HIV antibodies. Before removing links to the inmate’s HIV test result, identifiers were used to merge prison test results with the North Carolina Department of Health and Human Services (NC DHHS) HIV testing database.

During the study period, 23,373 inmates entered the NC DPS. Of these inmates, 22,134 (94.7 percent) had HIV testing performed on blood remaining after syphilis testing. Testing of excess blood revealed that 320 inmates (1.45 percent) were HIV seropositive. Of those who tested HIV seropositive, 300 (93.8 percent) were known by the NC DHHS to be infected with HIV prior to incarceration. Therefore, 20 of 22,134, or 0.09 percent of tested inmates and not known to be infected previously.

“… in contrast to the perception that undiagnosed HIV infection is prevalent among incarcerated individuals, our results indicate that few new cases of HIV enter prison,” the authors write. “Other at-risk populations with higher levels of undiagnosed HIV infection may constitute a higher priority for screening for HIV than prisoners.”

(doi:10.l001/jama.2013.280740; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This research was supported by a grant from the National Institute of Mental Health and from the University of North Carolina Center for AIDS Research. 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, NOVEMBER 26, 2013

Media Advisory: To contact Bjorn Pasternak, M.D., Ph.D., email bjp@ssi.dk. To contact editorial author Allan S. Brett, M.D., call Jeff Stensland at 803-777-3686 or email stenslan@mailbox.sc.edu.

Chicago – In contrast to findings of a recent study, researchers in Denmark did not find an association between use of a class of antibiotics known as fluoroquinolones (such as ciprofloxacin) and an increased risk of retinal detachment, according to a study appearing in the November 27 issue of JAMA.

Retinal detachment (a separation of the retina from its connection at the back of the eye) is an acute eye disorder that may lead to loss of vision despite prompt surgical intervention. A recent study found that use of fluoroquinolones was strongly associated with retinal detachment, reporting a 4.5-fold significantly increased risk for ongoing exposure. A possible mechanism was effects of the drug on connective tissue, according to background information in the article. “Given the prevalent use of fluoroquinolones, this could, if confirmed in the general population, translate to many excess cases of retinal detachment that are potentially preventable.”

Bjorn Pasternak, M.D., Ph.D., of the Statens Serum Institut, Copenhagen, Denmark, and colleagues used data from a nationwide register to investigate whether oral fluoroquinolone use was associated with increased risk of retinal detachment. The register had information about 748,792 episodes of fluoroquinolone use and 5,520,446 control episodes of nonuse, including data on participant characteristics, drugs used, and cases of retinal detachment with surgical treatment.

The fluoroquinolones used were ciprofloxacin (88.2 percent), ofloxacin (9.2 percent), fleroxacine (1.2 percent), moxifloxacin (0.8 percent), and others (0.7 percent).

Of 566 patients with retinal detachment, 72 were exposed to fluoroquinolones; 5 during current use (days 1-10), 7 during recent use (days 11-30), 14 during past use (days 31-60), and 46 during distant use (2-6 months). Among patients not exposed to fluoroquinolones, 494 cases occurred. Analysis of the data indicated that fluoroquinolone use compared with nonuse was not associated with increased risk of retinal detachment.

The authors write that given limited power, the study can only rule out more than a 3-fold relative increase in the risk of retinal detachment associated with current fluoroquinolone use. However, any differences in absolute risk are likely to have limited, if any, clinical significance: in terms of absolute risk, current use of fluoroquinolones would, in the worst-case scenario, account for no more than 11 additional cases of retinal detachment per 1,000,000 treatment episodes.

(doi:10.l001/jama.2013.280500; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by The Danish Medical Research Council. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: Oral Fluoroquinolone Use and Retinal Detachment – Reconciling Conflicting Findings in Observational Research

Allan S. Brett, M.D., of the University of South Carolina School of Medicine, Columbia, S.C., comments in an accompanying editorial on the findings in studies regarding an association between fluoroquinolone use and retinal detachment.

“For the physician caring for an inpatient with an indication for fluoroquinolone therapy, retinal detachment should not cross the physician’s mind. But the next time an outpatient with no good indication for a quinolone asks for one ‘because I got better last time I took it,’ the physician might mention a remote possibility of retinal detachment among the many reasons for declining the request.”

(doi:10.l001/jama.2013.280501; 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, NOVEMBER 26, 2013

Media Advisory: To contact Bruno Mourvillier, M.D., email bruno.mourvillier@bch.aphp.fr.

Chicago – In a study of adults with severe bacterial meningitis, therapeutic hypothermia (reduction of body temperature) did not improve outcomes, and it may even have been harmful, according to a study appearing in the November 27 issue of JAMA.

Among adults with bacterial meningitis, the case fatality rate and frequency of neurologic complications are high, especially among patients with pneumococcal meningitis. In animal models of meningitis, moderate hypothermia has shown favorable effects, according to background information in the article.

Bruno Mourvillier, M.D., of the Universite Paris Diderot, Sorbonne Paris Cite, Paris, and colleagues examined the effect of induced hypothermia on outcomes in patients with severe bacterial meningitis. The study, conducted at 49 intensive care units in France, randomized 98 comatose adults to hypothermia (n = 49), comprising a loading dose of 4°C cold saline and cooling to 32°C to 34°C for 48 hours; or standard care (n = 49). The primary outcome measure was the score at 3 months on the Glasgow Outcome Scale, an assessment of physical function following cerebral injuries.

The trial was stopped early at the request of the data and safety monitoring board because of concerns over excess mortality in the hypothermia group (25 of 49 patients [51 percent]) vs. the control group (15 of 49 patients [31 percent]). Pneumococcal meningitis was diagnosed in 77 percent of patients. At 3 months, 86 percent in the hypothermia group compared with 74 percent of controls had an unfavorable outcome.

After adjustment for factors that might explain the findings, mortality remained higher, although the increase was no longer statistically significant, in the hypothermia group. Subgroup analysis on patients with pneumococcal meningitis showed similar results. “Although there was a trend toward higher mortality and rate of unfavorable outcome in the hypothermia group, early stopping of clinical trials is known to exaggerate treatment effects, precluding firm conclusions about harm of therapeutic hypothermia in bacterial meningitis,” the authors write.

“In conclusion, our trial does not support the use of hypothermia in adults with severe meningitis. Moderate hypothermia did not improve outcome in patients with severe bacterial meningitis and may even be harmful. Our results may have important implications for future trials on hypothermia in patients presenting with septic shock or stroke. Careful evaluation of safety issues in these future and ongoing trials are needed.”

(doi:10.l001/jama.2013.280506; 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, NOVEMBER 26, 2013

Media Advisory: To contact Marzia Lazzerini, Ph.D., email lazzerini@burlo.trieste.it.

Chicago – Among children and adolescents with Crohn disease not responding to treatment, use of the drug thalidomide resulted in improved clinical remission after 8 weeks of treatment compared with placebo, according to a study appearing in the November 27 issue of JAMA.

As many as 1.2 million people in Europe and more than half a million in the United States are estimated to have Crohn disease, a chronic inflammatory disease involving the digestive system.  Its incidence is increasing globally.  “About 25 percent of people with Crohn disease develop symptoms as children, and these cases are generally more severe than adult-onset cases. Resistance or intolerance to therapy is common in children with Crohn disease, with up to approximately 18 percent of cases requiring surgery within 5 years from disease onset,” according to background information in the article. Thalidomide is a drug used to treat inflammatory diseases of the skin and mucous membranes. Observational studies on thalidomide in patients with Crohn disease have reported encouraging results.

Marzia Lazzerini, Ph.D., of the Institute for Maternal and Child Health, Trieste, Italy and colleagues evaluated the efficacy and adverse effects of thalidomide in inducing clinical remission in children and adolescents with refractory (not responding to treatment) Crohn disease. The study included 56 children and was conducted August 2008-September 2012 in 6 pediatric care centers in Italy. Children were randomized to thalidomide or placebo once daily for 8 weeks. The primary measured outcomes were a reduction in the Pediatric Crohn Disease Activity Index (PCDAI) score of ≥ 25 percent or ≥ 75 percent at weeks 4 and 8 (clinical remission). Nonresponders to placebo received thalidomide for an additional 8 weeks. All responders continued to receive thalidomide for an additional minimum 52 weeks.

The researchers found that clinical remission was achieved by more children treated with thalidomide (13/28 [46.4 percent] vs. 3/26 [11.5 percent]). Responses were not different at 4 weeks, but greater improvement was observed at 8 weeks in the thalidomide group. Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4 percent) subsequently reached remission at week 8. Overall, 31 of 49 children treated with thalidomide (63.3 percent) achieved clinical remission, and 32 of 49 (65.3 percent) achieved 75 percent response.

Average duration of clinical remission in the thalidomide group was 181 weeks vs. 6.3 weeks in the placebo group.

“These findings require replication to definitively determine the utility of this treatment,” the authors conclude.

(doi:10.l001/jama.2013.280777; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This work was supported by the Italian Medicines Agency, on funds for Independent Research. The drug producer (Pharmion until 2009; Celgene after 2009) provided the study drug. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, NOVEMBER 26, 2013

Media Advisory: To contact Marianna K. Baum, Ph.D., call Maydel Santana-Bravo at 305-348-1555 or email santanam@fiu.edu.

Chicago – Long-term (24-month) supplementation with multivitamins plus selenium for human immunodeficiency virus (HIV)-infected patients in Botswana in the early stages of disease who had not received antiretroviral therapy delayed time to HIV disease progression, was safe and reduced the risk of immune decline and illness, according to a study appearing in the November 27 issue of JAMA.

“Micronutrient deficiencies, known to influence immune function, are prevalent even before the development of symptoms of HIV disease and are associated with accelerated HIV disease progression. Micronutrient supplementation has improved markers of HIV disease progression (CD4 cell count, HIV viral load) and mortality in clinical trials; however, these studies were conducted either in the late stages of HIV disease or in pregnant women,” according to background information in the article.

Marianna K. Baum, Ph.D., of Florida International University, Miami, and colleagues examined whether specific supplemental micronutrients enhance the immune system and slow HIV disease progression during the early stages of the disease in antiretroviral therapy (ART)-naive adults. They randomized 878 HIV patients to supplementation with daily multivitamins (B vitamins and vitamins C and E), selenium alone, multivitamins with selenium, or placebo for 24 months. The vitamins (vitamins B, C and E, and the trace element selenium) are nutrients essential for maintaining a responsive immune system. Selenium may also have an important role in preventing HIV replication.

Participants receiving the combined supplement of multivitamins plus selenium had a lower risk compared to placebo of reaching a CD4 cell count 250/µL or less (a measure that is consistent with the standard of care in Botswana for initiation of ART at the time of the study). This supplement also reduced the risk of a combination of measures of disease progression (CD4 cell count ≤ 250/µL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier).

“This evidence supports the use of specific micronutrient supplementation as an effective intervention in HIV-infected adults in early stages of HIV disease, significantly reducing the risk for disease progression in asymptomatic, ART-naive, HIV-infected adults. This reduced risk may translate into delay in the time when the HIV-infected patients experience immune dysfunction and into broader access to HIV treatment in developing countries,” the authors conclude.

The researchers add that their “findings are generalizable to other HIV subtype C-infected cohorts in resource-limited settings where the provision of ART is being scaled up, rolled out, or not yet available to all in conditions similar to those in Botswana at the time of this study.”

(doi:10.l001/jama.2013.280923; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was funded by the National Institute on Drug Abuse. 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 Early Release: 10:45 a.m CT Monday, November 18, 2013

Chicago – Horng H. Chen, M.B.B.Ch., of the Mayo Clinic, Rochester, Minn., and colleagues conducted a randomized trial to determine whether, as compared with placebo, the addition of low-doses of the drugs dopamine or nesiritide to diuretic therapy would enhance urine output and preserve kidney function in patients with acute heart failure and kidney dysfunction.

“Primary treatment goal in acute heart failure is to achieve adequate [urine output] while avoiding renal dysfunction and other adverse effects. Patients with acute heart failure and moderate or severe renal dysfunction are at risk for inadequate [urine output] and worsening renal function, both of which are associated with worse outcomes,” according to background information in the article. “Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance [urine output] and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested.”

The multicenter, clinical trial included 360 hospitalized participants with acute heart failure and renal dysfunction.

The researchers found that compared with placebo, low-dose dopamine had no effect on 72-hour cumulative urine volume (a measure of decongestion) or on a measure of kidney function. Similarly, low-dose nesiritide had no effect on these measures. There was no effect of low-dose dopamine or low-dose nesiritide on other urine measure, weight change, renal function, or clinical outcomes, compared with placebo.

“These findings do not support the use of low-dose dopamine or low-dose nesiritide as a renal adjuvant therapy in patients with acute heart failure and renal dysfunction,” the authors write.

(doi:10.l001/jama.2013.282190; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Horng H. Chen, M.B.B.Ch., call Traci Klein at 507-990-1182 or email Klein.traci@mayo.edu.

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Embargoed for Early Release: 3 p.m CT Monday, November 18, 2013

Chicago – Stephen J. Nicholls, M.B.B.S., Ph.D., of the South Australian Health and Medical Research Institute and University of Adelaide, Adelaide, Australia, and colleagues determined the effects of varespladib, a drug that inhibits the enzyme secretory phospholipase A₂ on cardiovascular risk in patients with acute coronary syndrome (ACS; such as heart attack or unstable angina).

Despite contemporary therapies, patients with ACS face a substantial risk of early, recurrent adverse cardiovascular events. Increasing evidence supports a potential role of inflammation in the progression and clinical instability of coronary heart disease. Secretory phospholipase A₂ (sPLA₂) is an enzyme involved with inflammation and implicated in atherosclerosis. The results of some studies have stimulated interest in sPLA₂ inhibition as a cardioprotective strategy. The sPLA₂ inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown, according to background information in the article.

The trial was conducted at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America and included 5,145 patients randomized within 96 hours of presentation of an ACS to either 500-mg/d varespladib (n = 2,572) or placebo (n = 2,573) for 16 weeks (study termination on March 9, 2012). The participants also received atorvastatin and other established therapies. The primary efficacy measure was a composite of cardiovascular mortality, nonfatal heart attack, nonfatal stroke, and unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated.

At a prespecified interim analysis, including 212 patients with primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1 percent) treated with varespladib compared with 109 patients (5.1 percent) treated with placebo. Varespladib was associated with a greater risk of heart attack (78 [3.4 percent] vs. 47 [2.2 percent]). The composite secondary end point of cardiovascular mortality, heart attack, and stroke was observed in 107 patients (4.6 percent) in the varespladib group and 79 patients (3.8 percent) in the placebo group.

“The sPLA₂ inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS,” the authors write.

(doi:10.l001/jama.2013.282836; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Stephen J. Nicholls, M.B.B.S., Ph.D., email stephen.nicholls@sahmri.com.

Embargoed for Early Release: 9:00 a.m CT Monday, November 18, 2013

Chicago – Alan W. Heldman, M.D., of the University of Miami Miller School of Medicine, and colleagues conducted a study to examine the safety of transendocardial stem cell injection (TESI) with autologous mesenchymal stem cells and bone marrow mononuclear cells in patients with ischemic cardiomyopathy.

An effective proregenerative treatment for ischemic cardiomyopathy would address a major unmet need for many patients. An unresolved issue is whether mesenchymal stem cells have similar safety and possibly greater efficacy than bone marrow mononuclear cells, according to background information in the article.

The included 65 patients with ischemic cardiomyopathy and compared injection of mesenchymal stem cells (n=19) with placebo (n = 11) and bone marrow mononuclear cells (n = 19) with placebo (n = 10), with 1 year of follow-up. The primary measured outcome was treatment-emergent 30-day serious adverse event rate defined as a composite of death, heart attack, stroke, hospitalization for worsening heart failure, perforation (rupture), tamponade (compression of the heart due to collection of blood or fluid), or sustained ventricular arrhythmias.

No patient had treatment emergent-serious adverse event at day 30. Exploratory analyses of 1-year incidence of serious adverse events was 31.6 percent for mesenchymal stem cells, 31.6 percent for bone marrow cells, and 38.1 percent for placebo. Over 1 year, the Minnesota Living with Heart Failure score (a measure of quality of life) improved with mesenchymal stem cells and with bone marrow cells but not with placebo. The 6-minute walk distance increased with mesenchymal stem cells only.

“These results provide the basis for larger studies to provide definitive assessment of safety and to assess efficacy of this new therapeutic approach,” the authors write.

(doi:10.l001/jama.2013.282909; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Joshua M. Hare, M.D., call Lisa Worley at 305-458-9654 or email lworley2@med.miami.edu.

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Embargoed for Early Release: 9:00 a.m CT Monday, November 18, 2013

Chicago – Joseph Poole, M.D., Ph.D., of the Emory University School of Medicine, Atlanta, and colleagues studied whether therapy with granulocyte-macrophage colony stimulating factor (GM-CSF), an agent that functions as a white blood cell growth factor, would improve walking performance in patients with symptomatic peripheral artery disease (a form of vascular disease in which there is partial or total blockage of an artery, usually one leading to a leg or arm).

“Peripheral artery disease (PAD) affects more than 8 million individuals in the United States. Although exercise, smoking cessation, antiplatelet therapy, cilostazol [a medication for PAD], statins, and revascularization are used to treat PAD, men and women with PAD have significantly greater functional impairment and faster functional decline than those without PAD. Stem and progenitor cell (PC) therapy that promotes neoangiogenesis [formation of blood vessels] is an emerging treatment modality in PAD,” according to background information in the article. Progenitor cells are involved in vascular repair and regeneration.

The phase 2, placebo-controlled study included 159 patients with intermittent claudication (pain in leg muscles, aggravated by walking and caused by an insufficient supply of blood). Participants were randomized to received 4 weeks of subcutaneous (under the skin) injections of GM-CSF (leukine), 3 times a week (n = 80), or placebo (n = 79).

The researchers found that therapy with GM-CSF did not improve treadmill walking time, a measure of PAD severity at 3-month follow-up. “The improvement in a subset of secondary outcomes observed with GM-CSF suggests that GM-CSF may warrant further study in patients with claudication. In addition, further investigation is needed to investigate the variability of responsiveness to GM-CSF and its clinical significance.”

(doi:10.l001/jama.2013.282540; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Arshed A. Quyyumi, M.D., Ph.D., call Jennifer Johnson McEwen at 404-441-5929 or email jrjohn9@emory.edu.

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Embargoed for Early Release: 9:00 a.m CT Monday, November 18, 2013

Chicago – Michael H. Criqui, M.D., M.P.H., of the University of California, San Diego, and colleagues determined the independent associations of coronary artery calcium (CAC) volume and CAC density with cardiovascular disease events. An increasing body of evidence suggests that greater calcium density in plaques (measured by computed tomography) is associated with decreased CVD risk.

The study included 3,398 men and women from 4 race/ethnicity groups; non-Hispanic white, African-American, Hispanic, and Chinese. Participants were 45-84 years of age, free of known CVD at baseline, had CAC greater than 0 on their baseline CT, and were followed up through October 2010.

During a median (midpoint) of 7.6 years of follow-up, there were 175 CHD events and an additional 90 other CVD events for a total of 265 CVD events. Analysis of the data found that CAC volume was positively and independently associated with CHD and CVD risk. At any level of CAC volume, CAC density was inversely and significantly associated with CHD and CVD risk.

“The role of CAC density should be considered when evaluating current CAC scoring systems,” the authors write.

(doi:10.l001/jama.2013. 282535; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Michael H. Criqui, M.D., M.P.H., call Debra Kain at 619-543-6163 or email ddkain@ucsd.edu.

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Embargoed for Early Release: 3:00 p.m CT Sunday, November 17, 2013

Chicago – Jiang He, M.D., Ph.D., of the Tulane University School of Public Health and Tropical Medicine, New Orleans, and colleagues examined whether moderate lowering of blood pressure within the first 48 hours after the onset of an acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge.

“Stroke is the second leading cause of death and the leading cause of serious, long-term disability worldwide. Clinical trials have documented that lowering blood pressure reduces the risk of stroke in hypertensive and normotensive patients with a history of stroke or transient ischemic attack. Although the benefit of lowering blood pressure for primary and secondary prevention of stroke has been established, the effect of immediate antihypertensive treatment in patients with acute ischemic stroke and elevated blood pressure is uncertain,” according to background information in the article.

The China Antihypertensive Trial in Acute Ischemic Stroke, a randomized controlled trial, was conducted among 4,071 patients with ischemic stroke within 48 hours of symptom onset and elevated systolic blood pressure. Patients were recruited from 26 hospitals across China between August 2009 and May 2013. Patients (n = 2,038) were assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10 percent to 25 percent within the first 24 hours after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2,033).

Average systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg (-12.7 percent) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg (-7.2 percent) in the control group within 24 hours after randomization. Average systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after randomization. The primary outcome (a combination of death and major disability at 14 days or hospital discharge) did not differ between treatment groups (683 events [antihypertensive treatment] vs. 681 events [control]) at 14 days or hospital discharge. The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups.

These findings suggest that the decision to lower blood pressure with antihypertensive treatment in patients with acute ischemic stroke does not improve or worsen outcome and therefore should be based on individual clinical judgment, the authors write.

(doi:10.l001/jama.2013.282543; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Jiang He, M.D., Ph.D., call Arthur Nead at 504-247-1443 or email anead@tulane.edu. To contact co-corresponding author Yong-Hong Zhang, M.D., Ph.D., email yhzhang@suda.edu.cn.

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Embargoed for Early Release: 3:00 p.m CT Sunday, November 17, 2013

Chicago – Francis Kim, M.D., of Harborview Medical Center, Seattle, and colleagues evaluated whether early prehospital cooling (lowering body temperature) improved survival to hospital discharge and neurological outcome in cardiac arrest patients with or without ventricular fibrillation (VF).

Cardiac arrest can cause brain injury and many patients never awaken after resuscitation. Hypothermia is a promising treatment that can help brain recovery. “Hospital cooling improves outcome after cardiac arrest, but prehospital cooling immediately after return of spontaneous circulation may result in better outcomes,” according to background information in the article. “The optimal timing for induction of hypothermia is uncertain.”

For this trial, 1,359 patients (583 with VF and 776 without VF) with prehospital cardiac arrest and resuscitated by paramedics were assigned to standard care with or without prehospital cooling, accomplished by infusing up to 2 liters of 4°C normal saline as soon as possible following return of spontaneous circulation. Nearly all of the patients resuscitated from VF and admitted to the hospital received hospital cooling regardless of their randomization.

The intervention reduced core temperature by more than 1°C and patients reached the goal temperature about 1 hour sooner than in the control group. The researchers found that survival to hospital discharge was similar in the intervention and control groups among patients with VF (62.7 percent vs. 64.3 percent, respectively) and among patients without VF (19.2 percent vs. 16.3 percent, respectively). The intervention was also not associated with improved neurological status of full recovery or mild impairment at discharge for patients with or without VF.

“Although hypothermia is a promising strategy to improve resuscitation and brain recovery following cardiac arrest, the results of the current study do not support routine use of cold intravenous fluid in the prehospital setting to improve clinical outcomes,” the authors write.

(doi:10.l001/jama.2013.282173; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Francis Kim, M.D., call Leila Gray at 206-941-4506 or email leilag@uw.edu.

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Embargoed for Early Release: 1:00 p.m CT Sunday, November 17, 2013

Chicago – Sten Rubertsson, M.D., Ph.D., of Uppsala University, Sweden and colleagues assessed whether cardiopulmonary resuscitation (CPR) in which chest compressions are delivered with a mechanical device would result in superior 4-hour survival in patients with out-of-hospital cardiac arrest compared to CPR with manual chest compression.

“Many factors affect the chances of survival after cardiac arrest, including early recognition of arrest, effective CPR and defibrillation, and postresuscitation care. One important link is the delivery of high-quality chest compressions to achieve restoration of spontaneous circulation. The effectiveness of manual chest compressions depends on the endurance and skills of rescuers, and manual compressions provide only approximately 30 percent of normal cardiac output. Manual CPR is also limited by prolonged hands-off time, and its quality is particularly poor when it is administered during patient transport. Mechanical chest compression devices have therefore been developed to improve CPR,” according to background information in the article.  “A strategy using mechanical chest compressions might improve the poor outcome in out-of-hospital cardiac arrest, but such a strategy has not been tested in large clinical trials.”

This multicenter clinical trial, which included 2,589 patients with out-of-hospital cardiac arrest, was conducted between January 2008 and February 2013 in 4 Swedish, 1 British, and 1 Dutch ambulance services and their referring hospitals. Duration of follow-up was 6 months. Patients were randomized to receive chest compressions from a mechanical device combined with defibrillation during the compressions (n = 1,300) or manual CPR according to guidelines (n = 1,289). The mechanical chest compressions device had an integrated suction cup designed to deliver compressions according to resuscitation guidelines.

Four-hour survival was achieved in 307 patients (23.6 percent) with mechanical CPR and 305 (23.7 percent) with manual CPR. Among patients surviving at 6 months, 99 percent in the mechanical CPR group and 94 percent in the manual CPR group had good neurological outcomes.

“In patients with out-of-hospital cardiac arrest, mechanical chest compressions in combination with defibrillation during ongoing compressions provided no improved 4-hour survival vs. manual CPR according to guidelines. There was a good neurological outcome in the vast majority of survivors in both groups, and neurological outcomes improved over time,” the authors write.

(doi:10.l001/jama.2013.282538; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Sten Rubertsson, M.D., Ph.D., email sten.rubertsson@akademiska.se.

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Embargoed for Early Release: 11:00 a.m CT Sunday, November 17, 2013

Chicago – Jose Augusto Barreto-Filho, M.D., Ph.D., of the Federal University of Sergipe and the Clinica e Hospital Sao Lucas, Sergipe, Brazil, and colleagues assessed procedure rates and outcomes of surgical aortic valve replacement (AVR) among 82,755,924 Medicare fee-for-service beneficiaries between 1999 and 2011.

“Aortic valve disease in the United States is a major cardiovascular problem that is likely to grow as the population ages. Aortic valve replacement is the standard treatment even for very elderly patients despite its risks in this age group. With transcatheter aortic valve replacement emerging as a less invasive option, contemporary data from real-world practice are needed to provide a perspective on the outcomes that are being achieved with surgery,” according to background information in the article.

The primary measured outcomes for the study were procedure rates for surgical AVR alone and with coronary artery bypass graft (CABG) surgery, 30-day and 1-year mortality, and 30-day readmission rates.

The researchers found that rates of AVR increased between 1999 and 2011, including AVR without CABG surgery, while the rate of AVR with CABG surgery decreased during this time period.  Procedure rates increased in all age, sex, and race strata, most notably in patients 75 years or older.

Mortality decreased at 30 days (absolute decrease, 3.4 percent; adjusted annual decrease, 4.1 percent) per year and at 1 year (absolute decrease, 2.6 percent; adjusted annual decrease, 2.5 percent). Thirty-day all-cause readmission also decreased by 1.1 percent per year. In addition, AVR with CABG surgery decreased and women and black patients had lower procedure and higher mortality rates.

“These findings may provide a useful benchmark for outcomes of aortic valve replacement surgery for older patients eligible for surgery considering newer transcatheter treatments,” the authors write.

(doi:10.l001/jama.2013.282437; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Harlan M. Krumholz, M.D., S.M., call Karen N. Peart at 203-980-2222 or email karen.peart@yale.edu.

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Embargoed for Early Release: 11:00 a.m CT Sunday, November 17, 2013

Chicago – Michael J. Mack, M.D., of the Baylor Health Care System, Plano, Texas, and colleagues describe the experience in the U.S. with transcatheter aortic valve replacement (TAVR), including patient selection, procedural details, and in-hospital and 30-day outcomes following TAVR, a less invasive procedure than open heart-valve surgery for replacing the aortic valve in the heart.

In November 2011, the U.S. Food and Drug Administration (FDA) approved use of a valve that could be implanted using a catheter for TAVR for the treatment of severe, symptomatic aortic stenosis in patients with inoperable status. The label for the valve was expanded in September 2012 to include patients at high-risk but operable status. Since commercial approval, this first-to-U.S.-market TAVR device has been introduced to nearly 250 U.S. clinical sites. “Although the [initial] trials demonstrated efficacy of TAVR within a select cohort of patients and hospital centers, there are no data on dissemination and utilization patterns of this technology in routine clinical practice in the United States. Additionally, concerns persist regarding the safety and effectiveness of this novel technology as it moves beyond protocolized trial care and highly experienced centers and operators,” according to background information in the study.

For this study, the researchers gathered results from all eligible U.S. TAVR cases (n = 7,710) from 224 participating registry hospitals following the device commercialization (November 2011 – May 2013).  Successful device implantation occurred in 7,069 patients (92 percent). In-hospital mortality was 5.5 percent. Other major complications included stroke (2.0 percent), dialysis-dependent renal failure (1.9 percent), and major vascular injury (6.4 percent).

Median hospital stay was 6 days, with 4,613 patients (63 percent) discharged home. Among patients with available follow-up at 30 days (n = 3,133), mortality was 7.6 percent (noncardiovascular cause, 52 percent); stroke occurred in 2.8 percent, and new dialysis in 2.5 percent.

“This analysis represents the first public report from the U.S. national Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry and documents 2 major findings. First, postapproval commercial introduction of this new technology with an early-generation device has yielded success rates and complication patterns that are similar to those documented in carefully performed randomized trials. Second, the outcomes of procedures even with this early-generation approved device are similar to the global experience of TAVR, which now is based on second- and third-generation improved devices. These findings help address a lingering question of clinical outcomes with the first-generation TAVR device after controlled U.S. dissemination to a relatively narrow group of treatment centers,” the authors write. “Longer-term follow-up is essential to assess continued safety and efficacy as well as patient health status.”

(doi:10.l001/jama.2013.282043; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Michael J. Mack, M.D., call Susan Hall at 214-566-2589 or email Susan.Hall@baylorhealth.edu.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 11 a.m. CT Sunday, November 17 at this link.

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Embargoed for Early Release: 11:00 a.m CT Sunday, November 17, 2013

Chicago – Seth S. Martin, M.D., of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, and colleagues developed a method for estimating low-density lipoprotein cholesterol (LDL-C) levels that is more accurate than the standard measure.

Low-density lipoprotein cholesterol is the primary target for treatment in national and international clinical practice guidelines. Conventionally, LDL-C is estimated by the Friedewald equation, which estimates LDL-C as (total cholesterol) – (high-density lipoprotein cholesterol [HDL-C]) – (triglycerides/5) in mg/dL. The final term assumes a fixed ratio of triglyceride levels to very low-density lipoprotein cholesterol (TG:VLDL-C) of 5:1. “Applying a factor of 5 to every individual patient is problematic given variance in the TG:VLDL-C ratio across the range of triglyceride and non-HDL-C levels,” according to background information in the study.

The researchers used a sample of lipid profiles obtained from 2009 through 2011 from 1,350,908 children, adolescents, and adults in the United States.

From this large sample of lipid profiles, the authors created and validated a novel method to estimate LDL-C from the standard lipid profile, consisting of a 180-cell table (grid) of median TG:VLDL-C values based on triglyceride and non-HDL-C values. Rather than assuming a fixed factor of 5, it applies an adjustable factor for the TG:VLDL-C ratio based on triglyceride and non-HDL-C concentrations. “The greatest advantage occurs in classification of LDL-C concentrations lower than 70 mg/dL, especially in patients with elevated triglyceride concentrations. In addition to the novel analytic approach, a major strength of this study is its size, 3,015 times larger than the original Friedewald database.”

“These findings require external validation, as well as assessment of their clinical importance. The novel method could be easily implemented in most laboratory reporting systems at virtually no cost.”

(doi:10.l001/jama.2013.280532; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Seth S. Martin, M.D., call Ellen Beth Levitt at 410-598-4711 or email eblevitt@jhmi.edu.

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Embargoed for Early Release: 11:00 a.m CT Sunday, November 17, 2013

Chicago – Hany S. Abed, B.Pharm., M.B.B.S., of the University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia and colleagues evaluated the effect of a structured weight reduction program on atrial fibrillation symptoms.

“Atrial fibrillation has been described as the epidemic of the new millennium, with a projection that by 2050 there will be 12 million to 15 million affected individuals in the United States. In the United States, the direct economic cost of atrial fibrillation is estimated at $6 billion annually. Although population aging is regarded as an important contributor, obesity may account for a substantial proportion of the increasing prevalence,” according to background information in the article. Whether weight reduction and cardiometabolic risk factor management can reduce the burden of atrial fibrillation has not been known.

The study was conducted between June 2010 and December 2011 among overweight and obese patients with symptomatic atrial fibrillation. Patients underwent a median (midpoint) of 15 months of follow-up. Patients were randomized to weight management (intervention; n = 75) or general lifestyle advice (control; n = 75). Both groups underwent intensive management of cardiometabolic risk factors (hypertension, hyperlipidemia, glucose intolerance, sleep apnea, and alcohol and tobacco use).

The intervention group experienced greater reduction, compared with the control group, in weight (33 and 12.5 lbs., respectively,) and in atrial fibrillation, symptom severity, number of episodes, and cumulative duration in minutes.

“In this study, a structured weight management program for highly symptomatic patients with atrial fibrillation reduced symptom burden and severity and reduced antiarrhythmic use when compared with attempts to optimally manage risk factors alone,” the authors write.

(doi:10.l001/jama.2013.280521; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Prashanthan Sanders, M.B.B.S., Ph.D., email prash.sanders@adelaide.edu.au.

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EMBARGOED FOR EARLY RELEASE: 9 A.M. (CT) SATURDAY, NOVEMBER 9, 2013

Media Advisory: To contact corresponding author Amit X. Garg, M.D., Ph.D., call Julia Capaldi at 519-685-8500, ext. 75616, or email julia.capaldi@lawsonresearch.com.

Chicago – Among older adults taking a calcium-channel blocker, simultaneous use of the antibiotic clarithromycin, compared with azithromycin, was associated with a small but statistically significant greater 30-day risk of hospitalization with acute kidney injury, according to a study published by JAMA. The study is being published early online to coincide with its presentation at the American Society of Nephrology’s Kidney Week 2013.

The commonly used antibiotics clarithromycin and erythromycin are clinically important inhibitors of the enzyme CYP3A4, while azithromycin is much less so. Calcium-channel blockers are metabolized by this enzyme. Blood concentrations of these drugs may rise to harmful levels when CYP3A4 activity is inhibited.  “Currently, the U.S. Food and Drug Administration warns that ‘serious adverse reactions have been reported in patients taking clarithromycin concomitantly with CYP3A4 substrates, which includes hypotension [abnormally low blood pressure] with calcium-channel blockers [that are] metabolized by CYP3A4.’ Yet, calcium-channel blockers and clarithromycin continue to be frequently coprescribed in routine care,” according to background information in the article. When hypotension occurs, the kidney is particularly prone to injury from poor circulation. “Despite this knowledge, the risk of acute kidney injury following coprescription of clarithromycin with a calcium-channel blocker is unknown.”

Sonja Gandhi, B.Sc., of Western University, London, Canada, and colleagues conducted a study to investigate the interaction between calcium-channel blockers (amlodipine, felodipine, nifedipine, diltiazem, or verapamil) and the antibiotic clarithromycin (n = 96,226), compared with azithromycin (n = 94,083), with a focus on acute kidney injury, among older adults (average age, 76 years).

Amlodipine was the most commonly prescribed calcium-channel blocker (more than 50 percent of patients).

The researchers found that coprescribing clarithromycin with a calcium-channel blocker was associated with a higher risk of hospitalization with acute kidney injury compared with coprescribing azithromycin (0.44 percent vs. 0.22 percent); in absolute terms, coprescription with clarithromycin resulted in a 0.22 percent higher incidence of hospitalization with acute kidney injury.

When examined by type of calcium-channel blocker, the risk of hospitalization with acute kidney injury was highest among patients coprescribed clarithromycin with nifedipine (absolute risk increase, 0.63 percent). Coprescription of a calcium-channel blocker with clarithromycin was also associated with a higher risk of hospitalization with hypotension (0.12 percent vs. 0.07 percent patients taking azithromycin; absolute risk increase, 0.04 percent) and all-cause mortality (1.02 percent vs. 0.59 percent patients taking azithromycin; absolute risk increase, 0.43 percent).

“Although the absolute increases in the risks were small, these outcomes have important clinical implications. Our results suggest that potentially hundreds of hospitalizations and deaths in our region may have been associated with this largely preventable drug-drug interaction. This burden on the health care system, given the high costs of managing acute kidney injury, might have been avoided,” the authors write.

“… our study highlights the need for quality improvement initiatives that will mitigate the clinical effects of such drug interactions. Potential strategies may include temporary cessation of the calcium-channel blocker for the duration of clarithromycin therapy or selection of a non-CYP3A4 inhibiting antibiotic (such as azithromycin) when clinically appropriate.”

(doi:10.l001/jama.2013.282426; 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 EARLY RELEASE: 9:30 A.M. (ET) TUESDAY, NOVEMBER 12, 2013

Media Advisory: To contact Ezekiel J. Emanuel, M.D., Ph.D., call Katie Delach at 215-349-5964 or email Katie.Delach@uphs.upenn.edu.

Washington, D.C. – The U.S. health care system needs a new, audacious goal: limit health care expenditure growth to the growth of national economy. “That is, by the end of the decade, health care costs per person will not grow faster than the economy as a whole,” writes Ezekiel J. Emanuel, M.D., Ph.D., of The Perelman School of Medicine and the Wharton School, University of Pennsylvania, Philadelphia, in a Viewpoint appearing in the November 13 issue of JAMA, a theme issue on critical issues in U.S. health care.

Dr. Emanuel presented the article at a JAMA media briefing at the National Press Club in Washington, D.C.

Dr. Emanuel writes that the health care system is in need of what author Jim Collins, a business strategist, called a big hairy audacious goal (BHAG): by 2020, per capita health care costs will increase no more than gross domestic product (GDP)+0 percent. Collins used the term BHAG “to define a kind of goal, like going to the moon, that can make an organization—or a nation—stretch beyond what it thought was possible to achieve remarkable things.”

“The goal of reining in per capita cost growth is clear and easily measured. It is not going to happen overnight; it is going to take at least until 2020 to achieve. Success is not guaranteed. During the last 50 years, only a few years in the mid 1990s have seen per capita cost growth track closely to the growth of the economy. But by the end of the decade, getting there is possible. Most importantly, if the effort is successful, the entire health care system will have been transformed.”

Dr. Emanuel notes that states have begun to adopt this BHAG. “In 2012, Massachusetts enacted another important health reform law to improve quality and reduce costs. It had a spending target of limiting health care cost growth to growth of the state economy—the equivalent of GDP+0 percent. Maryland and Arkansas have adopted similar cost-control goals.”

“So what will it take to get to the moon in health care? It will require substantially more focus on delivering care to the 10 percent of patients with chronic illness. It will require turning care delivery upside-down. Instead of focusing on care in the hospital, more outpatient monitoring of these patients, and more interventions at home, are necessary to keep them healthy and with fewer emergency department visits and hospitalizations. To achieve this requires electronic records with real-time tracking of leading physiologic indicators. It requires team-based care coordination between office, hospital, pharmacy, and home. It requires reducing the use of inappropriate interventions. If all this happens, the other goal that everyone believes is critical—improved quality of care—will be achieved.”

Dr. Emanuel concludes that most importantly, the goal of limiting U.S. health care expenditure growth to the growth of the national economy “will organize and focus energies and skills in a way that will permanently transform health care for the better. Ultimately, President Kennedy may have said it best: ‘”We choose to go to the moon in this decade and do the other things, not because they are easy, but because they are hard, because that goal will serve to organize and measure the best of our energies and skills, because that challenge is one that we are willing to accept, one we are unwilling to postpone, and one which we intend to win.”’

(doi:10.l001/jama.2013. 281967; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported receiving payment for speaking engagements unrelated to this work.

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EMBARGOED FOR EARLY RELEASE: 9:30 A.M. (ET) TUESDAY, NOVEMBER 12, 2013

Media Advisory: To contact Joanne Lynn, M.D., M.A., M.S., call Ken Schwartz at 571-733-5709 or email Ken.schwartz@altarum.org.

Washington, D.C. – “The United States needs arrangements that allow elderly people to live with confidence, comfort, and meaningfulness at a cost that families can afford and the nation can sustain … Without significant structural changes in service delivery, an aging nation faces a future of substantial costs and needless pain and distress among those who are old,” writes Joanne Lynn, M.D., M.A., M.S., of the Center for Elder Care and Advanced Illness, Altarum Institute, Washington, D.C., in a Viewpoint appearing in the November 13 issue of JAMA, a theme issue on critical issues in U.S. health care.

Dr. Lynn presented the article at a JAMA media briefing at the National Press Club in Washington, D.C.

The current “care system” for an elderly person with self-care disability and numerous diagnoses “provides disjointed specialty services, ignores the challenges of living with disabilities, tolerates routine errors in medications and transitions, disdains individual preferences, and provides little support for paid or volunteer caregivers. This maladapted service delivery system now generates about half of the person’s lifetime costs for health care services, yet patients and families are left fearful and disoriented, with pain, discomfort, and distress.”

Dr. Lynn provides specific changes she contends are critical for improving care for this population, an approach she calls “MediCaring”. She writes that discussions about living with frailty now are virtually absent from popular media, political discussion, and professional education. “To counteract this shortcoming, reformers will need to generate discussion about the challenges of aging, disability, and death, along with the continuing opportunities to live meaningfully and comfortably. Medical  professionals, political leaders, and popular culture must generate vigorous discussion about how people live well with frailty and how best to die.”

“Each frail elderly person has unique resources, priorities, fears, medical issues, and aspirations, and each should be given an opportunity to evaluate his or her potential futures and to have an individualized plan for services. A multidisciplinary team should conduct an appropriately comprehensive assessment and work with the patient and family to generate a care plan that documents the patient’s goals and the chosen service strategies.”

“The service delivery system should encompass health care and long-term services and supports as equal partners,” Dr. Lynn writes. “A balanced system would give integrated multidisciplinary teams the tools and authority to match services with each frail person’s priority needs. … Today, a physician can order any drug for any Medicare patient at any cost—but that physician cannot order a substitute caregiver or adequate housing, except perhaps by arranging nursing home admission. The mismatch of service availability with the priorities of frail elderly people engenders high costs as well as frustration and heightened fear of decline and death for frail elders.”

Dr. Lynn also suggests that “by allowing localities to take a role in monitoring and managing their arrangements for supporting frail elders, the services could become more reliable and appropriate, and most or all of the funding for supplementing social services for people who cannot afford them could come from sharing in the savings from better health care.”

“Essential reforms include requiring development and use of comprehensive care plans; modifying medical care to ensure continuity, comprehensiveness, honesty about treatment goals, and comfort; bringing health care and long-term services and supports together into stable funding and management arrangements; and enabling some degree of local monitoring and control. Meeting the challenges of long lives requires substantial changes, quickly, in how people in the United States envision health care, community obligations, and the lives of frail older adults.”

(doi:10.l001/jama.2013.281923; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 9:30 A.M. (ET) TUESDAY, NOVEMBER 12, 2013

Media Advisory: To contact Hamilton Moses III, M.D., call Stephanie Desmon at 410-955-8665 or email sdesmon1@jhmi.edu.
Washington, D.C. – An examination of health care in the U.S. finds that despite the extraordinary economic success of many of its participants, the health care system has performed relatively poorly by some measures; and that outcomes have improved, but more slowly than in the past and more slowly than in comparable countries, according to an article in the November 13 issue of JAMA, a theme issue on critical issues in U.S. health care.

Hamilton Moses III, M.D., of the Alerion Institute, North Garden, Va., and the Johns Hopkins School of Medicine, presented the article at a JAMA media briefing at the National Press Club in Washington, D.C.

Dr. Moses and colleagues from The Boston Consulting Group and University of Rochester, using publicly available data, conducted an analysis to identify trends in health care, principally from 1980 to 2011. The areas they addressed included the economics of health care; the profile of people who receive care and organizations that provide care; and the value created in terms of objective health outcomes and perceptions of quality of care. In addition, they examined the potential factors driving change, including consolidation of insurers and health systems; health care information; and the patient as consumer.

Among the findings:

Economics and Outcomes

• In 2011, U.S. health care employed 15.7 percent (21 million people) of the workforce, with expenditures of $2.7 trillion, doubling since 1980 as a percentage of U.S. gross domestic product (GDP) to 17.9 percent.

Between 2000 and 2010, health care increased faster than any other industry (2.9 percent/year) but trailed government (3.3%/year); health’s proportion of GDP doubled between 1980 and 2011. Government funding increased from 31 percent in 1980 to 42 percent in 2011. Costs have tripled in real terms over the past 2 decades. However, the average rate of increase has declined consistently since the mid-1970s and sharply over the last decade.

• Despite the increases in resources devoted to health care, multiple health metrics, including life expectancy at birth and survival with many diseases, shows the United States trailing peer nations.

Contributors to Costs

In addition, the researchers note that findings from their analysis contradict several common assumptions:

• Price of professional services, drugs and devices, and administrative costs, not demand for services or aging of the population, produced 91 percent of cost increases since 2000.

• Personal out-of-pocket spending on insurance premiums and co-payments have declined from 23 percent to 11 percent since 1980.

• In 2011, chronic illnesses account for 84 percent of costs overall among the entire population, not only of the elderly. Chronic illness among individuals younger than 65 years accounts for 67 percent of spending.

Contributors to Change

The authors add that three factors have produced the most change:

• Consolidation, with fewer insurers and general hospitals (but more single-specialty hospitals and large physician groups) has produced financial concentration in health systems, insurers, pharmacies, and benefit managers;

• Information technology, in which investment has occurred but value is elusive;

• The patient as consumer, whereby influence is sought outside traditional channels, using social media, informal networks, new public sources of information, and self-management software.

These forces create a triangle of tension among patient aims for choice, personal attention, and unbiased guidance; physician aims for professionalism and autonomy; and public and private payer aims for aggregate economic value across large populations. “Measurements of cost and outcome (applied to groups) are supplanting individuals’ preferences. Clinicians increasingly are expected to substitute social and economic goals for the needs of a single patient.”

The researchers write that at the highest level, the U.S. health system is struggling to adapt to competing goals, desires, and expectations. “The conflict among patient desires, physician interests, and social policy is certain to increase. Those tensions will likely become a palpable force that may hinder care integration and inhibit other changes that favor improved outcome and savings. The usual approach is to address each constituency in isolation rather than optimizing efforts across them. The triangle will need to be reconciled. This is the chief challenge of the next decade.”

“A national conversation, guided by the best data and information, aimed at explicit understanding of choices, tradeoffs, and expectations, using broader definitions of health and value, is needed.”

(doi:10.l001/jama.2013.281425; Available pre-embargo to the media at https://media.jamanetwork.com)

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

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 9:30 a.m. ET Tuesday, November 12 at this link.

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (CT) MONDAY, NOVEMBER 4, 2013

Media Advisory: To contact Nicholas J. Christian, Ph.D., email Allison Hydzik (HydzikAM@upmc.edu) or Cyndy McGrath (McGrathC3@upmc.edu) or call 412-647-9975.

In an analysis that included nearly 1,000 patients, self-reported weights following bariatric surgery were close to measured weights, suggesting that self-reported weights used in studies are accurate enough to be used when measured weights are not available, according to a Research Letter published online by JAMA.

“Obtaining standardized weights in long-term studies can be difficult. Self-reported weights are more easily obtained, but less accurate than those from a calibrated scale and may be inaccurately reported,” according to background information in the article.

Nicholas J. Christian, Ph.D., of the University of Pittsburgh Graduate School of Public Health, and colleagues investigated whether self-reported weights following bariatric surgery differed from weights obtained by study personnel using a standard scale. They used data collected between April 2010 and November 2012 at annual assessments from the Longitudinal Assessment of Bariatric Surgery-2, an observational cohort study of 2,458 adults undergoing an initial Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric band (LAGB), or other bariatric procedure at 10 centers. Participants were sent mailed questionnaires each year and asked to report their: (1) weight from last medical office or weight loss program visit (self-reported medical weight) and (2) last self-weighing (self-reported personal weight).

The final analysis included 988 participants, including 164 with a self-reported medical weight, 580 with a self-reported personal weight, and 244 with both self-reported weights. Across the 2 groups who self-reported weight, women and men underreported their weight by an average 2.2 lbs. or less and the degree of underreporting was not different between women and men. Self-reported medical weights were closer to measured weights than were self-reported personal weights for both women and men.

“Small differences between self-reported and measured weights were found and may be due to differences in clothing, inaccurate personal scales, time between measurements, or intentional misrepresentation,” the authors write. “Self-reported weights after bariatric surgery may be more accurate because participants who undergo surgery to lose weight may be especially attentive to their weight.”

(doi:10.l001/jama.2013.281043; 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 EARLY RELEASE: 10:00 A.M. (CT) MONDAY, NOVEMBER 4, 2013

Media Advisory: To contact Anita P. Courcoulas, M.D., M.P.H., call Andréa Stanford at 412-647-6190 or email Stanfordac@upmc.edu.

In 3-year follow-up after bariatric surgery, substantial weight loss was observed among individuals who were severely obese, with most of the change occurring during the first year; however, there was variability in the amount of weight loss, as well as in diabetes, blood pressure, and lipid outcomes, according to a study published online by JAMA.

“Bariatric surgery results in large, sustained weight loss in severely obese [body mass index (BMI) ≥ 35] populations. Although generally accepted as the most effective means for inducing weight loss in very heavy patients, few studies exist reporting outcomes longer than 2 years after the surgery was performed,” according to background information in the article.

Anita P. Courcoulas, M.D., M.P.H., of the University of Pittsburgh Medical Center, and colleagues used Longitudinal Assessment of Bariatric Surgery (LABS) Consortium data to study change in weight and selected health parameters after common bariatric surgical procedures. The Longitudinal Assessment of Bariatric Surgery (LABS) Consortium is a multicenter observational cohort study at 10 hospitals in 6 clinical centers in the United States. Their study included adults undergoing a first-time bariatric surgical procedure as part of routine clinical care by participating surgeons between 2006 and 2009 and followed until September 2012. Participants (n = 2,458) completed research assessments using standardized and detailed data collection prior to surgery and at 6 months, 12 months, and annually after surgery. At baseline, 774 participants (33 percent) had diabetes, 1,252 (63 percent) dyslipidemia, and 1,601 (68 percent) hypertension.

Three years after Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB), the researchers assessed percent weight change from baseline and the percentage of patients with diabetes who achieved certain measures without pharmacologic therapy. Dyslipidemia or hypertension resolution at 3 years was also assessed.

At the beginning of the study, median (midpoint) BMI was 45.9, and median baseline weight was 284 lbs.; 1,738 participants underwent RYGB, 610 LAGB, and 110 other procedures. Three years after surgery, median percent weight loss was 31.5% of baseline (90 lbs.) for participants who underwent RYGB and 15.9 percent (44 lbs.) for LAGB. As a group, participants experienced most of their total weight change the first year after surgery.

The authors write that variability in weight change “indicates a potential opportunity to improve patient selection and education prior to operation as well as enhance support for continued adherence to lifestyle adjustments in the postoperative years.”

Three years after surgery, the percentages of participants experiencing at least partial diabetes remission were 67.5 percent for RYGB and 28.6 percent for LAGB. Dyslipidemia was in remission for 61.9 percent of RYGB participants and 27.1 percent of LAGB participants at 3 years. Changes in hyperlipidemia were similar. Hypertension was in remission at 3 years in 38.2 percent of RYGB and 17.4 percent of LAGB participants.

“Longer-term follow-up of this cohort will determine the durability of these improvements over time and factors associated with variability in effect.”

(doi:10.l001/jama.2013.280928; 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, NOVEMBER 5, 2013

Media Advisory: To contact corresponding author Gunnel Henriksson, M.D., Ph.D., email Gunnel.Henriksson@med.lu.se.

Autoantibodies are present many years before symptom onset in patients with primary Sjögren syndrome, an autoimmune disease, according to a Research Letter published in the November 6 issue of JAMA.

Primary Sjögren syndrome is a disease in which immune cells attack and destroy glands that produce tears and saliva. Autoantibodies are characteristic of this syndrome and may be involved in its development. Roland Jonsson, D.M.D., Ph.D., of the University of Bergen, Norway, and colleagues measured autoantibodies before symptom onset in these patients.

All patients with primary Sjögren syndrome at Malmo University Hospital in Malmo, Sweden, have been included in a registry since 1984. Controls were randomly selected from biobanks and matched by sex, age, and date of earliest sampling (within 60 days before or after) to each case.

Of 360 cases in the registry, 44 (41 women and 3 men) provided 64 presymptomatic serum samples obtained an average of 7 years before symptom onset. In 29 cases (66 percent), autoantibodies were detected before symptom onset. All 29 cases had autoantibodies in their earliest available serum sample, as early as 18 years before symptom onset.

“To our knowledge, this is the first systematic investigation of presymptomatic autoantibodies in Sjögren syndrome. Most cases produced autoantibodies many years before clinical onset of the disease; the median [midpoint] time of 4 to 6 years is an underestimate because all seropositive cases had autoantibodies in their earliest available serum sample,” the authors write.

“Autoantibody profiling may identify individuals at risk many years before disease onset. However, the significance of these presymptomatic autoantibodies for determining prognosis and treatment remains to be determined.”

(doi:10.l001/jama.2013.278448; 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, NOVEMBER 5, 2013

Media Advisory: To contact Richard L. Kravitz, M.D., M.S.P.H., call Charles Casey at 916-734-9048 or email  charles.casey@ucdmc.ucdavis.edu.

Chicago — Among depressed patients evaluated in a primary care setting, use of an interactive multimedia computer program immediately prior to a primary care visit resulted in the increased receipt of antidepressant prescription recommendation, mental health referral, or both; however, it did not result in improvement in mental health at 12-week follow-up, according to a study in the November 6 issue of JAMA.

“Despite progress, depression in primary care remains underrecognized and undertreated. Barriers to improvement include system, clinician, and patient factors. System-level interventions are effective in increasing recognition and treatment of depression, but these interventions are difficult to disseminate,” according to background information in the article.

Richard L. Kravitz, M.D., M.S.P.H., of the University of California, Davis, and colleagues examined whether targeted and tailored communication strategies could enhance patient engagement and initial care for patients with depression and the extent to which the interventions promoted prescribing or recommendation of antidepressant medication, depression-related discussion, and antidepressant requests among patients who were not depressed. The trial compared a depression engagement video (DEV), tailored interactive multimedia computer program (IMCP) and control among 925 adult patients treated by 135 primary care clinicians (603 patients with depression and 322 patients without depression) conducted from June 2010 through March 2012 at 7 primary care clinical sites in California. Patients were randomized to a DEV targeted to sex and income, an IMCP tailored to individual patient characteristics, and a sleep hygiene (recommendations for improving sleep) video (control).

Of the 925 eligible patients, 867 were included in the primary analysis (depressed, 559; nondepressed, 308). The researchers found that among depressed patients, rates of achieving the primary outcome (a composite measure of receiving an antidepressant recommendation, a mental health referral, or both during the initial visit) were 17.5 percent for DEV, 26 percent for IMCP, and 16.3 percent for control. Both the DEV and the IMCP increased patient-reported requests for information about depression. However, there were no improvements in mental health (as gauged by a questionnaire) at the 12-week follow-up in response to either intervention.

Among nondepressed patients, no evidence of harm was observed from either intervention for the outcome of clinician-reported antidepressant prescribing, but the authors could not exclude harm (defined as a higher rate of antidepressant prescriptions for nondepressed patients associated with each intervention) based on patient-reported antidepressant recommendation.

“Further research is needed to determine effects on clinical outcomes and whether the benefits outweigh possible harms,” the authors conclude.

(doi:10.l001/jama.2013.280038; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This work was supported by grants from the National Institute of Mental Health. 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, NOVEMBER 5, 2013

Media Advisory: To contact Christopher Vinden, M.D., call Julia Capaldi at 519-685-8500, ext. 75616 or email Julia.Capaldi@LawsonResearch.Com. To contact editorial co-author Michael J. Zinner, M.D., call Tom Langford at 617-525-6375 or email tlangford@partners.org.

Chicago — Surgeons who had operated the night before an elective daytime gallbladder surgery did not have a higher rate of complications, according to a study in the November 6 issue of JAMA.

“Lack of sleep is associated with impaired performance in many situations. To theoretically prevent medical errors, work-hour restrictions on surgeons in training were imposed. There are now proposals for similar work-hour restrictions on practicing surgeons. Several studies found no association between surgeon sleep deprivation as assessed by operating the night prior to an operation or when surgeons report few hours of sleep and patient outcomes. Prior studies were limited because of small sample sizes and being from single academic institutions. Consequently, there is insufficient evidence to conclude that surgeon performance is compromised by insufficient sleep the night prior to performing surgery,” according to background information in the article.

Christopher Vinden, M.D., of Western University, London, Ontario, Canada, and colleagues examined if there was any association between operating the night before performing an elective cholecystectomy (gallbladder removal) and complications. The analysis was conducted using administrative health care databases in Ontario. Participants were 2,078 patients (across 102 community hospitals) who underwent elective laparoscopic cholecystectomies performed by surgeons (n = 331) who operated the overnight before (between midnight and 7 a.m.). Each of these patients was matched with 4 other elective laparoscopic cholecystectomy recipients (n = 8,312), performed by the same surgeon when there was no evidence that surgeon having operated the overnight before.

The primary outcome was conversion of a planned laparoscopic cholecystectomy (removing the gallbladder using a camera and tiny incisions) to an open cholecystectomy (large incision of the abdomen to remove the gallbladder) during the procedure. Although not always considered a complication, conversion to open cholecystectomy may serve as an aggregate end point for many complications, and patients view conversion as an unwanted outcome. Secondary outcomes included evidence of iatrogenic injures (injuries caused by the surgery) or death.

The researchers found no association between conversion rates to open operations and whether or not surgeons operated the night before (2.2 percent with vs. 1.9 percent without overnight operation); or to the risk of iatrogenic injuries (0.7 percent vs. 0.9 percent); or death (≤ 0.2 percent vs. 0.1 percent). These proportions were not statistically different.

The authors write that policies limiting attending surgeon work hours are controversial. “Critics suggest such policies reduce continuity in care, increase communication errors, and introduce the potential for a bystander effect (in which one surgeon may expect another to bear the burden for authority and responsibility). Restructuring health care delivery to prevent surgeons operating during the day after they operated the previous night would have important cost, staffing, and resource implications.”

“These findings do not support safety concerns related to surgeons operating the night before performing elective surgery.”

(doi:10.l001/jama.2013.280372; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Editorial: Surgeons, Sleep, and Patient Safety

Michael J. Zinner, M.D., of Brigham and Women’s Hospital, Boston, and Julie Ann Fresichlag, M.D., of Johns Hopkins Medical Institute, Baltimore, and Editor, JAMA Surgery, comment on the findings of this study in an accompanying editorial.

“The study by Vinden et al verifies that surgeons can perform elective operations without inducing undue complications, even when they have operated the night before. However, just as each patient undergoing an operation requires an individualized assessment and operative plan, each surgeon must objectively self-assess fatigue level and honestly determine whether the surgical skills necessary for daytime operations following operating the night before will be comparable to those skills and capabilities following a good night’s sleep. Patient safety and surgeon well-being deserve no less.”

(doi:10.l001/jama.2013.280374; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Media Advisory: To contact corresponding author P. Michael Ho, M.D., Ph.D., call Mark Couch at 303-724-5377 or email mark.couch@ucdenver.edu. To contact editorial author Anne R. Cappola, M.D., Sc.M., call Kim Menard at 215-662-6183 or email kim.menard@uphs.upenn.edu.

Chicago — Among a group of men who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of death, heart attack, or ischemic stroke, according to a study in the November 6 issue of JAMA.

“Rates of testosterone therapy prescription have increased markedly in the United States over the past decade. Annual prescriptions for testosterone increased by more than 5-fold from 2000 to 2011, reaching 5.3 million prescriptions and a market of $1.6 billion in 2011. Professional society guidelines recommend testosterone therapy for patients with symptomatic testosterone deficiency. In addition to improving sexual function and bone mineral density and increasing free-fat mass and strength, treatment with testosterone has been shown to improve lipid profiles and insulin resistance and increase the time to ST depression [a finding on an electrocardiogram suggesting benefit] during stress testing,” according to background information in the article. However, a recent randomized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety.

Rebecca Vigen, M.D., M.S.C.S., of the University of Texas at Southwestern Medical Center, Dallas and colleagues evaluated the association between the use of testosterone therapy and all-cause mortality, myocardial infarction (MI; heart attack), and stroke among male veterans and whether this association was modified by underlying coronary artery disease (CAD). The study included 8,709 men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011. There was a high level of co-existing illnesses among this group, including prior history of heart attack, diabetes, or CAD. Of the 8,709 patients, 1,223 (14.0 percent) initiated testosterone therapy after a median (midpoint) of 531 days following angiography. The average follow-up was approximately 2 years, 3.5 months. The primary measured outcome for the study was a composite of all-cause mortality, heart attack, and ischemic stroke.

The researchers found that the proportion of patients experiencing events 3 years after coronary angiography was 19.9 percent in the no testosterone therapy group (average age, 64 years) and 25.7 percent in the testosterone therapy group (average age, 61 years), for an absolute risk difference of 5.8 percent. Even accounting for other factors that could explain the differences, use of testosterone therapy was associated with adverse outcomes and was consistent among patients with and without CAD. The increased risk of adverse outcomes associated with testosterone therapy use was not related to differences in risk factor control or rates of secondary prevention medication use because patients in both groups had similar blood pressure, low-density lipoprotein levels, and use of secondary prevention medications.

“These findings raise concerns about the potential safety of testosterone therapy,” the authors write. “Future studies including randomized controlled trials are needed to properly characterize the potential risks of testosterone therapy in men with comorbidities.”

(doi:10.l001/jama.2013.280386; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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

Editorial: Testosterone Therapy and Risk of Cardiovascular Disease in Men

“Perhaps the most important question is the generalizability of the results of this study to the broader population of men taking testosterone: men of this age group who are taking testosterone for ‘low T syndrome’ or for antiaging purposes and younger men taking it for physical enhancement,” writes Anne R. Cappola, M.D., Sc.M., of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, in an accompanying editorial.

“Are the benefits—real or perceived—for these groups of men worth any increase in risk? These populations represent a sizable group of testosterone users, and there is only anecdotal evidence that testosterone is safe for these men.”

“In light of the high volume of prescriptions and aggressive marketing by testosterone manufacturers, prescribers and patients should be wary. There is mounting evidence of a signal of cardiovascular risk, to which the study by Vigen et al contributes. This signal warrants both cautious testosterone prescribing and additional investigation.”

(doi:10.l001/jama.2013.280387; Available pre-embargo to the media at https://media.jamanetwork.com)

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

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EMBARGOED FOR EARLY RELEASE: 11:30 A.M. (CT) THURSDAY, OCTOBER 31, 2013

Media Advisory: To contact Fausto Feres, M.D., Ph.D., email fferes@lee.dante.br.

Short-term (3 months) vs. long-term (12 months) dual anti­platelet therapy did not result in poorer outcomes on certain measures (death, heart attack, stroke, and bleeding) for patients with coronary artery disease or low-risk acute coronary syndromes (such as heart attack or unstable angina) treated with drug (zotarolimus)-releasing stents, according to a study published by JAMA. The study is being published early online to coincide with its presentation at the Transcatheter Cardiovascular Therapeutics 25th annual meeting.

“The current recommendation is for at least 12 months of dual antiplatelet therapy [typically aspirin and clopidogrel] after implantation of a drug-eluting stent. However, the optimal duration of dual antiplatelet therapy with specific types of drug-eluting stents remains unknown,” according to background information in the article.

Fausto Feres, M.D., Ph.D., of Instituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil, and colleagues with the OPTIMIZE trial assessed if 3 months of dual antiplatelet therapy was noninferior to (not worse than) 12 months in patients with stable coronary artery disease or history of low-risk acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with zotarolimus-eluting stents to open narrowed coronary arteries. The study included 3,119 patients in 33 sites in Brazil between April 2010 and March 2012. Clinical follow-up was performed at 1,3,6, and 12 months.

After PCI with zotarolimus-eluting stents, patients were prescribed dual antiplatelet therapy comprising aspirin (100-200 mg daily) and clopidogrel (75 mg daily) for 3 months (n = 1,563) or 12 months (n = 1,556). The primary end point for the study was a composite of all-cause death, heart attack, stroke, or major bleeding; the expected event rate at 1 year was 9 percent. Secondary end points were a composite of all-cause death, heart attack, emergency coronary artery bypass graft surgery, or target lesion revascularization; and definite or probable stent thrombosis (blood clot).

The researchers found that about equal proportions of patients at 1 year in the short-term and long-term groups experienced the primary outcome (6.0 percent vs. 5.8 percent) and secondary outcome (8.3 percent vs. 7.4 percent). Between 91 and 360 days, no statistically significant association was observed for NACCE for the short- and long-term groups, MACE, or stent thrombosis.

The authors add that the primary finding was similar in several key sub­groups, including patients with diabetes, history of low-risk ACS, or multivessel disease.

(doi:10.l001/jama.2013. 282183; 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, OCTOBER 22, 2013

Media Advisory: To contact corresponding author Ulrike Bingel, M.D., Ph.D., email ulrike.bingel@uk-essen.de.

The hormone oxytocin may mediate processes such as empathy, trust, and social learning. These are key elements of the patient-physician relationship, which is an important mediator of placebo responses, according to background information in a Research Letter appearing in the October 23/30 issue of JAMA. Simon Kessner, of the University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and colleagues conducted a study to test whether oxytocin enhances the placebo response in an experimental placebo analgesia model.

Between January and September 2012, the researchers randomly assigned 80 healthy male volunteers to 40 IU of intranasal oxytocin or saline. The researchers and participants were blinded to study drug identity. After 45 minutes, placebo analgesia was assessed using the following standard technique. Two identical inert ointments were applied to 2 sites on each participant’s forearm. The ointments were described as an anesthetic that reduces pain (placebo) and an inert control cream (control). In the 15 minutes following application that the participant expected the anesthetic to take effect, the researchers calibrated the  intensity at which a 20-second painful heat stimulus was perceived by each individual to rate as a 60 on a scale ranging from 0 (no pain) to 100 (unbearable pain). During the subsequent test phase, a series of 10 of those calibrated stimuli was applied to each of the 2 sites in randomized order. The primary outcome was the placebo analgesic response, defined as the reduction of perceived pain intensity on the placebo site compared with the control site in the oxytocin and saline groups.

Despite identical stimulation on both sites, the difference in pain ratings at the placebo and pain sites were greater in the oxytocin group than in the saline group due to lower pain ratings at the placebo site.

“To our knowledge, our study provides the first experimental evidence that placebo responses can be pharmacologically enhanced by the application of intranasal oxytocin,” the authors write. “Further studies are needed to replicate our findings in larger clinical populations, identify the underlying mechanisms, and explore moderating variables such as sex or aspects of patient-physician communication.”

(doi:10.l001/jama.2013.277446; 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, OCTOBER 22, 2013

Media Advisory: To contact Jacob A. Udell, M.D., M.P.H., F.R.C.P.C., call Nicole Bodnar at 416-978-5811 or email Nicole.Bodnar@utoronto.ca. To contact editorial author Kathleen M. Neuzil, M.D., M.P.H., call Monica Graham at 206-302-6072 or email mgraham@path.org.

Receiving an influenza vaccination was associated with a lower risk of major adverse cardiovascular events such as heart failure or hospitalization for heart attack, with the greatest treatment effect seen among patients with recent acute coronary syndrome (ACS; such as heart attack or unstable angina), according to a meta-analysis published in the October 23/30 issue of JAMA.

“Among nontraditional cardiovascular risk factors, there remains interest in a potential association between respiratory tract infections, of which influenza and influenza-like illnesses are common causes, and subsequent cardiovascular events,” according to background information in the article. Several epidemiological studies have suggested a strong inverse relationship between influenza vaccination and the risk of fatal and nonfatal cardiovascular events.

Jacob A. Udell, M.D., M.P.H., F.R.C.P.C., of the University of Toronto, and colleagues conducted a meta-analysis of all randomized clinical trials (RCTs) of influenza vaccine that studied cardiovascular events as efficacy or safety outcomes to determine if influenza vaccination is associated with prevention of cardiovascular events. The researchers identified five published and 1 unpublished RCTs of 6,735 patients (average age, 67 years; 51 percent women; 36 percent with a cardiac history; average follow-up time, 7.9 months) that met inclusion criteria for the study. Analyses were stratified by subgroups of patients with and without a history of acute coronary syndrome (ACS) within 1 year of randomization.

In the 5 published RCTs, 95 of 3,238 patients treated with influenza vaccine (2.9 percent) developed a major adverse cardiovascular event compared with 151 of 3,231 patients (4.7 percent) treated with placebo or control within 1 year of follow-up, an absolute risk difference favoring flu vaccine of 1.74 percent. The addition of the unpublished data did not materially change the results (2.9 percent influenza vaccine vs. 4.6 percent placebo or control).

In a subgroup analysis of 3 RCTs of patients with pre-existing coronary artery disease (CAD), the risk of major adverse cardiovascular events among patients with a history of recent ACS was especially lower with vaccine (10.3 percent influenza vaccine vs. 23.1 percent placebo or control), an absolute-risk difference of 12.9 percent, compared to patients with stable CAD (6.9 percent influenza vaccine vs. 7.4 percent placebo or control). Results were similar with the addition of unpublished data.

“Within this global meta-analysis of RCTs that studied patients with high cardiovascular risk, influenza vaccination was associated with a lower risk of major adverse cardiovascular events within 1 year. Influenza vaccination was particularly associated with cardiovascular prevention in patients with recent ACS. Future research with an adequately powered multicenter trial to confirm the efficacy of this low-cost, annual, safe, easily administered, and well-tolerated therapy to reduce cardiovascular risk beyond current therapies is warranted,” the authors conclude.

(doi:10.l001/jama.2013.279206; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Dr. Udell is supported by a Canadian Institutes for Health Research and Canadian Foundation for Women’s Health postdoctoral research fellowship award. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

There will also be a digital news release available for this study, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, October 22 at this link.

Editorial: Influenza Vaccination in 2013-2014 – Achieving 100 percent Participation

In an accompanying editorial, Kathleen M. Neuzil, M.D., M.P.H., of PATH, Seattle, discusses the importance of improving influenza vaccination coverage.

“There are proven ways to increase vaccination coverage, including expanding access through nontraditional settings (e.g., pharmacy, workplace, school venues), improving the use of evidence-based practices at medical sites (e.g., standing orders, reminder or recall notification), and using immunization registries. One of the most consistent and relevant findings of operational research is that recommendation for vaccination from physicians and other health care professionals is a strong predictor of vaccine acceptance and receipt among patients. While few are in a position to develop new influenza vaccines, all health care practitioners can recommend influenza vaccine to their patients. Doing so will help achieve the goal of 100 percent vaccination for the 2013-2014 influenza season.”

(doi:10.l001/jama.2013.279207; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Neuzil reports receiving grant funding from the Bill & Melinda Gates Foundation and Centers for Disease Control and Prevention.

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

Media Advisory: To contact Lisa R. Metsch, Ph.D., call Stephanie Berger at 212-305-4372 or email sb2247@columbia.edu. To contact editorial co-author Jason S. Haukoos, M.D., M.Sc., call Jenny Bertrand at 303-520-9591 or email Jennifer.Bertrand@dhha.org.

Brief risk-reduction counseling at the time of a rapid human immunodeficiency virus (HIV) test was not effective for reducing new sexually transmitted infections (STIs) during the subsequent 6 months among persons at risk for HIV, according to a study in the October 23/30 issue of JAMA.

In the United States, approximately 1.1 million people are estimated to be living with HIV infection. The incidence of HIV infection is considered to have remained steady over the last decade, with about 50,000 new infections occurring annually. About l in 5 people living with HIV is thought to be undiagnosed. The U.S. Preventive Services Task Force recently recommended that all persons age 15 to 65 years be screened for HIV, according to background information in the article. A major issue regarding HIV testing of such a large population is the effectiveness of HIV risk-reduction counseling at the time of testing, because counseling involves considerable time, personnel, and financial costs.

Lisa R. Metsch, Ph.D., of Columbia University’s Mailman School of Public Health, New York, and colleagues conducted a trial to assess the effectiveness of counseling in reducing STI incidence among STI clinic patients. From April to December 2010, Project AWARE randomized 5,012 patients from 9 STI clinics in the United States to receive either brief patient-centered HIV risk-reduction counseling with a rapid HIV test or the rapid HIV test with information only. Participants were assessed for multiple STIs at both the beginning of the study and 6-month follow-up. The core elements of the counseling that the patients received included a focus on the patient’s specific HIV/STI risk behavior and negotiation of realistic and achievable risk-reduction steps. The prespecified outcome was a cumulative incidence of any of the measured STIs over 6 months. All participants were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum (syphilis), herpes simplex virus 2, and HIV. Women were also tested for Trichomonas vaginalis.

The researchers found no difference in 6-month composite STI incidence by study group: STI incidence was 250 of 2,039 (12.3 percent) in the counseling group and 226 of 2,032 (11.1 percent) in the information group. This pattern was consistent at all sites. Analyses by age group, race/ethnicity, and sex (for heterosexuals) also demonstrated no effect of counseling on STI rates.

“Despite the historical emphasis on risk-reduction counseling as integral to the HIV testing process, no contemporary data exist on the effectiveness of such counseling. The results of Project AWARE help fill this gap,” the authors write.

“Overall, these study findings lend support for reconsidering the role of counseling as an essential adjunct to HIV testing. This inference is further buttressed by the additional costs associated with counseling at the time of testing: without evidence of effectiveness, counseling cannot be considered an efficient use of resources. Posttest counseling for persons testing HIV-positive remains essential, both for addressing psychological needs and for providing and ensuring follow-through with medical care and support. A more focused approach to providing information at the time of testing may allow clinics to use resources more efficiently to conduct universal testing, potentially detecting more HIV cases earlier and linking and engaging HIV-infected people in care.”

(doi:10.l001/jama.2013.280034; 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: Eliminating Prevention Counseling to Improve HIV Screening

“In an era of shrinking resources, clinicians and policy makers cannot ignore data that inform efficient clinical practice,” write Jason S. Haukoos, M.D., M.Sc., of the Denver Health Medical Center, and Mark W. Thrun, M.D., of Denver Public Health, in an accompanying editorial.

“Maximizing identification of individuals with undiagnosed HIV infection and reducing viral transmission will require consistent and extensive HIV testing with emphasis, for those identified with HIV infection, on linkage to care, treatment, and adherence. Although utilization of prevention counseling in the context of these post-HIV testing efforts remains to be characterized, results of the AWARE trial support the notion that prevention counseling in conjunction with HIV testing is not effective and should not be included as a routine part of practice.”

(doi:10.l001/jama.2013.280035; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: Dr. Haukoos is supported in part by the National Institute of Allergy and Infectious Diseases and the Agency for Healthcare Research and Quality. Please see the article for additional information, including financial disclosures.

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EMBARGOED FOR EARLY RELEASE: 6:00 A.M. (CT) THURSDAY, OCTOBER 17, 2013

Media Advisory: To contact Jennifer F. Kawwass, M.D., call Janet Christenbury at 404-727-8599 or email Jmchris@emory.edu. To contact editorial author Evan R. Myers, M.D., M.P.H., call Rachel Harrison at 919-419-5069 or email rachel.harrison@duke.edu.

Between 2000 and 2010 in the United States the number of donor eggs used for in vitro fertilization increased, and outcomes for births from those donor eggs improved, according to a study published by JAMA. The study is being released early online to coincide with its presentation at the American Society for Reproductive Medicine and the International Federation of Fertility Societies joint annual meeting.

During the past several decades, the number of live births to women in their early 40s in the United States has increased steadily. The prevalence of oocyte (egg) donation for in vitro fertilization (IVF) has increased in the United States, but little information is available regarding maternal or infant outcomes to improve counseling and clinical decision making, according to background information in the article.

Jennifer F. Kawwass, M.D., of the Emory University School of Medicine, Atlanta, and colleagues examined trends in use of donor oocytes in the United States and assessed perinatal outcomes. The study used data from the Centers for Disease Control and Prevention’s National Assisted Reproductive Technology (ART) Surveillance System (NASS); fertility centers are mandated to report their data to the system, which includes data on more than 95 percent of all IVF cycles performed in the United States. Good perinatal outcome was defined as a single live-born infant delivered at 37 weeks or later weighing 5.5 lbs. or more.

The researchers found that at 443 clinics (93 percent of all U.S. fertility centers) the annual number of donor oocyte cycles performed in the United States increased from 10,801 in 2000 to 18,306 in 2010, as did the percentage of such cycles that involved frozen oocytes or embryos (vs. fresh) (26.7 percent to 40.3 percent) and that involved elective single-embryo transfer (vs. transfer of multiple embryos) (0.8 percent to 14.5 percent). Good perinatal outcomes increased from 18.5 percent to 24.4 percent. Average age remained stable at 28 years for donors and 41 years for recipients. Recipient age was not associated with likelihood of good perinatal outcome.

“Use of donor oocytes is an increasingly common treatment for infertile women with diminished ovarian reserve for whom the likelihood of good perinatal outcome appears to be independent of recipient age. To maximize the likelihood of a good perinatal outcome, the American Society of Reproductive Medicine recommendations suggesting transfer of a single embryo in women younger than 35 years should be considered. Additional studies evaluating the mechanisms by which race/ethnicity, infertility diagnosis, and day of embryo culture affect perinatal outcomes in both autologous [donor and recipient are the same person] and donor IVF pregnancies are warranted to develop preventive measures to increase the likelihood of obtaining a good perinatal outcome among ART users,” the authors write.

(doi:10.1001/jama.2013.280924; 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: Outcomes of Donor Oocyte Cycles in Assisted Reproduction

Evan R. Myers, M.D., M.P.H., of Duke University School of Medicine, Durham, N.C., comments on the findings of this study in an accompanying editorial.

“Given the promising data presented by Kawwass et al on perinatal outcomes after use of donor oocytes, the use of oocyte donors is likely to at least remain constant and may even increase. More complete data on both short- and long-term outcomes of donation are needed so donors can make truly informed choices and, once those data are available, mechanisms can be put in place to ensure that the donor recruitment and consent process at clinics is conducted according to the highest ethical standards.”

(doi:10.1001/jama.2013.280925; 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, OCTOBER 15, 2013

Media Advisory: To contact Bjorn Pasternak, M.D., email bjp@ssi.dk.

In an analysis that included more than 40,000 women exposed to the nausea medication metoclopramide in pregnancy, use of this drug was not associated with significantly increased risk of major congenital malformations overall, spontaneous abortion, and stillbirth, according to a study in the October 16 issue of JAMA.

More than 50 percent of pregnant women experience nausea and vomiting, typically early in their pregnancy. The care of most women is managed conservatively, but 10 percent to 15 percent of those with nausea and vomiting will eventually receive drug treatment. Metoclopramide is often recommended if treatment with an antihistamine or vitamin B6 has failed. Despite metoclopramide being one of the most commonly used prescription medications in pregnancy, data on the safety of its use in pregnancy are limited, according to background information in the article.

Bjorn Pasternak, M.D., Ph.D., of the Statens Serum Institut, Copenhagen, and colleagues conducted a study to investigate associations between metoclopramide use in pregnancy and serious adverse outcomes. The study included 1,222,503 pregnancies in Denmark from 1997-2011 and compared outcomes for women who used metoclopramide to those who did not.

In a group that included women exposed and unexposed (control group) to metoclopramide, there were 28,486 live-born infants exposed to metoclopramide in the first trimester of pregnancy and 113,698 unexposed infants. Of these, 721 exposed (25.3 per 1,000 births) and 3,024 unexposed infants (26.6 per 1,000 births) were diagnosed with any major malformation during the first year of life. In analyses of individual malformation categories, there were no associations between metoclopramide use in the first trimester and any of the 20 malformations, including neural tube defects, cleft lip, cleft palate and limb reduction.

The researchers also observed no increased risk of spontaneous abortion, stillbirth, preterm birth, low birth weight, and fetal growth restriction associated with metoclopramide use in pregnancy.

“These safety data may help inform decision making when treatment with metoclopramide is considered in pregnancy,” the authors conclude.

(doi:10.l001/jama.2013.278343; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by a Danish Medical Research Council grant. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, OCTOBER 15, 2013

Media Advisory: To contact corresponding author James S. Goodwin, M.D., call Raul Reyes at 409-747-0794 or email rareyes@utmb.edu.

“No organization recommends prostate-specific antigen (PSA) screening in men older than 75 years. Nevertheless, testing rates remain high,” write Elizabeth Jaramillo, M.D., of the University of Texas Medical Branch, Galveston, and colleagues in a Research Letter appearing in the October 16 issue of JAMA. The authors examined whether PSA screening rates would vary substantially among primary care physicians (PCPs) and if the variance would depend on which PCP patients used.

Using complete Medicare Part A and B data for Texas, the researchers selected PCPs whose patient panels included at least 20 men 75 years or older without a prior diagnosis of prostate cancer. Primary care physicians were identified as generalist physicians who saw a man on 3 or more occasions in 2009. PSA screening rates for 2010 were estimated. The sample included 1,963 PCPs and 61,351 patients. Overall, 41.1 percent of the men received PSA screening and 28.8 percent received PSA screening ordered by their PCPs. Both rates declined with patient age.

The authors found high variability among PCPs in PSA screening, with a 10-fold difference in rates between the highest and lowest deciles (divided into ten groups) of PCPs. In addition, which PCP a man saw explained approximately 7 times more of the variance in PSA screening than did the measurable patient characteristics.

“The high variability among PCPs in ordering PSA screening for older men requires additional study to understand its causes. It has been suggested that overtesting rates be included as quality measures of PCPs. Medicare data can be used to generate such measures.”

(doi:10.l001/jama.2013.277514; 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, OCTOBER 15, 2013

Media Advisory: To contact corresponding author David J. Cohen, M.D., M.Sc., call Kerry O’Connor at 816-932-8646 or email koconnor@saint-lukes.org.

For patients with diabetes and coronary artery disease in more than one artery, treatment with coronary artery bypass graft surgery provided slightly better health status and quality of life between 6 months and 2 years than procedures using drug-eluting stents, although beyond 2 years the difference disappeared, according to a study in the October 16 issue of JAMA.

Although previous studies have demonstrated that coronary artery bypass graft (CABG) surgery is generally preferred over percutaneous coronary intervention (PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries) for patients with diabetes mellitus and coronary artery disease in more than one artery, these studies were based largely on older data from when angioplasty and stents were different. Recently, the FREEDOM trial demonstrated that for this group of patients, CABG surgery resulted in lower rates of death and heart attack but a higher risk of stroke when compared with PCI using drug-eluting stents. Whether there are differences in health status assessed from the patient’s perspective is unknown, according to background information in the article.

Mouin S. Abdallah, M.D., M.Sc., of Saint Luke’s Mid America Heart Institute, Kansas City, and colleagues conducted a substudy of the FREEDOM trial to assess functional status and quality of life. Between 2005 and 2010, 1,900 patients from 18 countries with diabetes mellitus and multivessel coronary artery disease were randomized to undergo either CABG surgery (n = 947) or PCI (n = 953) as an initial treatment strategy. Of these, a total of 1,880 patients had baseline health status assessed (935 CABG, 945 PCI) and comprised the primary analytic sample.

The researchers found that at 2-year follow-up, measures of angina frequency, physical limitations, and quality-of-life indicated greater benefit of CABG compared to PCI. Beyond 2 years, the 2 revascularization strategies provided generally similar patient-reported outcomes.

The primary results of the FREEDOM trial demonstrated that for diabetic patients with multivessel coronary artery disease, CABG led to a benefit over PCI for the composite endpoint of death, myocardial infarction, or stroke, driven by reductions in both all-cause mortality and myocardial infarction. Although both revascularization strategies led to substantial and sustained improvements in quality of life and functional status in the FREEDOM trial, angina relief was slightly better with CABG than PCI, especially among patients with the most severe angina at baseline, the authors write.

These findings suggest that CABG could be preferred as the initial revascularization strategy for such patients. “Given the increased rate of stroke, as well as the well-recognized longer recovery period with CABG surgery, however, some patients who do not wish to face these acute risks may still choose the less invasive PCI strategy. For such patients, our study provides reassurance that there are not major differences in long-term health status and quality of life between the 2 treatment strategies. Nonetheless, it is important for patients to recognize that the similar late quality-of-life outcomes with PCI and CABG in the FREEDOM trial were achieved with higher rates of antianginal medication use and the need for more frequent repeat revascularization procedures among the PCI group.”

(doi:10.l001/jama.2013.279208; 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. Cordis and Boston Scientific provided the stents; Eli Lilly provided abciximab and an unrestricted research grant; and Sanofi-Aventis and Bristol-Myers Squibb provided clopidogrel. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR EARLY RELEASE: 7 A.M. (CT) WEDNESDAY, OCTOBER 9, 2013

Andrea Morelli, M.D., of the University of Rome, Italy, and colleagues conducted a study to investigate the effect of the short-acting beta-blocker esmolol on the heart rate of patients with severe septic shock and high risk of death.

Septic shock is associated with adverse effects on cardiac function. Beta-blocker therapy controls heart rate and may improve cardiovascular performance, but concerns remain that this therapy may lead to cardiovascular decompensation (inability of the heart to maintain adequate circulation), according to background information in the article.

The randomized phase 2 study was conducted in a university hospital intensive care unit (ICU) between November 2010 and July 2012. It recruited patients in septic shock with a heart rate of 95/min or higher requiring high-dose norepinephrine to maintain an average arterial pressure of 65 mm Hg or higher. The researchers randomly assigned 77 patients to receive a continuous infusion of esmolol to maintain heart rate between 80 beats per minute (BPM) and 94 BPM for the duration of their ICU stay and 77 patients to standard treatment. The primary outcome was a reduction in heart rate below the predefined threshold of 95 BPM and maintain a heart rate between 80 and 94 BPM over a 96-hour period.

The researchers found that the target range for heart rate was achieved in all patients in the esmolol group, which was significantly lower throughout the intervention period than what was achieved in the control group. In addition, the esmolol group had a 28-day mortality rate of 49.4 percent vs. 80.5 percent in the control group. Overall survival was higher in the esmolol group.

There was no clinically relevant differences between groups in other investigated cardiopulmonary variables nor in rescue therapy requirements.

“Further investigation of the effects of esmolol on clinical outcomes is warranted,” the authors write.

(doi:10.l001/jama.2013.278477; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Andrea Morelli, M.D., email Andrea.Morelli@uniroma1.it.

Please Note: The presentation of this study at the meeting will be available after the embargo at this link: https://www.esicm.org/news-article/lives2013hottopics.

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

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EMBARGOED FOR EARLY RELEASE: 7 A.M. (CT) WEDNESDAY, OCTOBER 9, 2013

Laurent Papazian, M.D., Ph.D., of Hôpital Nord, Marseille, France, and colleagues conducted a study to determine whether statin therapy decreased day-28 mortality among intensive care unit patients with ventilator-associated pneumonia.

Observational studies have reported that statins improve outcomes of various infections. Ventilator-associated pneumonia (VAP) is the most common infection in the intensive care unit (ICU) and is diagnosed in approximately 8 to 28 percent of ICU patients receiving mechanical ventilation. Ventilator-associated pneumonia is associated with increased mortality rates and high health care costs. New treatments are needed to improve the outcomes of VAP, according to background information in the article.

The trial, performed in 26 intensive care units in France from January 2010 to March 2013, randomized 300 patients to receive simvastatin (60 mg) or placebo, started on the same day as antibiotic therapy and given until ICU discharge, death, or day 28, whichever occurred first.

The study was stopped for futility at the first scheduled interim analysis after enrollment of the 300 patients. The researchers found that day-28 mortality was not lower in the simvastatin group (21.2 percent) than in the placebo group (15.2 percent). There were no differences in day-14, ICU, or hospital mortality rates, or in duration of mechanical ventilation.

“These findings do not support the use of statins [for] improving VAP outcomes,” the authors conclude.

(doi:10.l001/jama.2013.280031; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Laurent Papazian, M.D., Ph.D.,, email Laurent.Papazian@ap-hm.fr.

Please Note: The presentation of this study at the meeting will be available after the embargo at this link: https://www.esicm.org/news-article/lives2013hottopics.

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EMBARGOED FOR EARLY RELEASE: 7 A.M. (CT) WEDNESDAY, OCTOBER 9, 2013

Djillali Annane, M.D., Ph.D., of Raymond Poincare Hospital, Garches, France, and colleagues conducted a study to compare the effects of 2 types of intravenous fluids on survival for critically ill patients in an intensive care unit.

Thousands of patients in intensive care units (ICUs) throughout the world are treated every day with intravenous fluids, mainly to restore effective blood volume and perfusion of organs. Fluid therapy includes a broad variety of products that are categorized as crystalloids and colloids: crystalloids are salts; colloids are salts and gelatin, starch or protein. Compared with crystalloids, colloid solutions expand blood volume and last longer. However, colloids may increase illness and death in critically ill patients and many physicians considered crystalloids the best fluid therapy in this population, according to background information in the article.

The trial included 2,857 ICU patients who required fluid resuscitation for sepsis or trauma, or hypovolemic (decreased blood volume) shock for patients without sepsis or trauma at 57 intensive care units in France, Belgium, North Africa, and Canada. Recruitment into the trial started in February 2003 and ended in August 2012 with follow-up until November 2012. Patients were randomly assigned to crystalloids (n = 1,443) or colloids (n = 1,414) for all fluid intervention (except fluid maintenance) throughout their ICU stay. The primary outcome was death within 28 days.

The study reports no difference in outcomes between groups; there were 359 deaths (25.4 percent) among patients treated with colloids vs. 390 deaths (27.0 percent) among patients treated with crystalloids. At 90 days, there were 434 deaths (30.7 percent) among patients treated with colloids vs. 493 deaths (34.2 percent) among patients treated with crystalloids.

“In conclusion, among ICU patients with hypovolemia, the use of colloids compared with crystalloids did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy,” the authors write.

(doi:10.l001/jama.2013.280502; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Djillali Annane, M.D., Ph.D.,, email Djillali.Annane@rpc.aphp.fr.

Please Note: The presentation of this study at the meeting will be available after the embargo at this link: https://www.esicm.org/news-article/lives2013hottopics.

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EMBARGOED FOR EARLY RELEASE: 7 A.M. (CT) WEDNESDAY, OCTOBER 9, 2013

Zudin A. Puthucheary, M.R.C.P., of University College London, England, and colleagues conducted a study to characterize and evaluate the time course and pathophysiology of acute muscle loss in critical illness.

“Survivors of critical illness experience significant skeletal muscle weakness and physical disability, which can persist for at least 5 years. Muscle wasting contributes substantially to weakness acquired in the intensive care unit, but its time course and underlying pathophysiological mechanisms remain poorly characterized and not well understood,” according to background information in the article.

The study included 63 critically ill patients who were prospectively recruited within 24 hours of intensive care unit (ICU) admission from August 2009 to April 2011 at a university teaching and a community hospital in England. Muscle loss was determined through serial ultrasound measurement of the rectus femoris (a muscle in the quadriceps) cross-sectional area (CSA) on days 1,3,7, and 10.

The researchers found reductions in the rectus femoris CSA observed at day 10 (-17.7 percent). Decrease in the rectus femoris CSA was greater in patients who experienced multiorgan failure compared with single organ failure: -15.7 vs. -3.0 percent by day 7; -8.7 percent vs. -1.8 percent by day 3.

In addition, muscle protein synthesis was depressed to levels equivalent to the healthy fasted state on day 1. It increased to rates similar to the healthy fed state by day 7; but the net balance remained negative (i.e., destructive metabolism). “Importantly, these overall effects occurred despite the administration of enteral nutrition. Unexpectedly, higher protein delivery in the first week was associated with greater muscle wasting,” the authors write.

“Early interventions to enhance anabolism [a constructive phase of muscle building metabolism] may be required in addition to those aimed at reducing catabolism if muscle wasting is to be limited or prevented.”

(doi:10.l001/jama.2013.278481; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Zudin A. Puthucheary, M.R.C.P., email zudin.puthucheary.09@ucl.ac.uk.

Please Note: The presentation of this study at the meeting will be available after the embargo at this link: https://www.esicm.org/news-article/lives2013hottopics.

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EMBARGOED FOR EARLY RELEASE: 10:15 A.M. (CT) TUESDAY, OCTOBER 8, 2013

Bruno Mourvillier, M.D., of the Université Paris Diderot, Sorbonne Paris Cité, Paris, and colleagues conducted a study to examine whether treatment with hypothermia would improve the functional outcome of comatose patients with bacterial meningitis compared with standard care.

Among adults with bacterial meningitis, the death rate and frequency of neurologic complications are high, indicating the need for new therapeutic approaches. Clinical trials of patients with trauma who were treated with hypothermia have shown a decrease of intracranial pressure, suggesting a potential benefit of this technique in bacterial meningitis, according to background information in the article.

The randomized trial conducted in 49 intensive care units in France between February 2009 and November 2011 assessed 130 patients for eligibility and randomized 98 comatose adults with community acquired bacterial meningitis to the hypothermia group, where patients received a loading dose of 39°F cold saline and were cooled to 90°F to 93°F for 48 hours, or standard care.

The trial was stopped early because of concerns over excess mortality in the hypothermia group (25 of 49 patients [51 percent]) compared with the control group (15 of 49 patients [31 percent]). At 3 months, 86 percent in the hypothermia group compared with 74 percent in the control group had an unfavorable outcome (as gauged via the Glasgow Outcome Scale [a functional assessment inventory]).

“In conclusion, our trial does not support the use of hypothermia in adults with severe meningitis. Moderate hypothermia did not improve outcome in patients with severe bacterial meningitis and may even be harmful. Our results may have important implications for future trials on hypothermia in patients presenting with septic shock or stroke. Careful evaluation of safety issues in these future and ongoing trials are needed,” the authors write.

(doi:10.l001/jama.2013.280506; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Bruno Mourvillier, M.D., email bruno.mourvillier@bch.aphp.fr.

Please Note: The presentation of this study at the meeting will be available after the embargo at this link: https://www.esicm.org/news-article/lives2013presidentsession.

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

Media Advisory: To contact Justin E. Bekelman, M.D., call Holly Auer at 215-349-5659 or email holly.auer@uphs.upenn.edu.

Justin E. Bekelman, M.D., of the University of Pennsylvania Perelman School of Medicine, Philadelphia, and colleagues conducted a study to examine whether single-fraction radiation treatment, shown to be as effective as multiple-fraction treatment with less potential for harm, has been incorporated into routine clinical practice for Medicare beneficiaries with prostate cancer and at what cost savings. Single-fraction radiotherapy is where a large dose of radiation is given in one session; with multiple-fraction radiotherapy, radiation is delivered in smaller doses over a longer period of time.

“Palliative radiotherapy, comprising l or more fractions (i.e., treatments) of daily radiation, is the mainstay of treatment for painful bone metastases. In 2005, a U.S.-based randomized trial demonstrated no difference in pain relief between single- and multiple-fraction radiotherapy for uncomplicated bone metastases, confirming results from international trials,” according to background information in the article appearing in the October 9 issue of JAMA.

As reported in the Research Letter, the authors selected patients age 65 years or older with prostate cancer and bone metastases and subsequent courses of radiotherapy from January 2006 through December 2009 from the Surveillance, Epidemiology and End Results (SEER)-Medicare database. For each patient, the researchers identified the initial outpatient course of radiotherapy following the first diagnosis of bone metastasis (index course) and determined the dates and number of radiotherapy fractions based on Medicare claims for radiation delivery (Medicare reimburses each radiotherapy fraction individually).

Of 3,050 patients included in the study, 3.3 percent had single-fraction radiotherapy and 50.3 percent received more than 10 fractions.  Average 45-day radiotherapy-related expenditures were a relative 62 percent lower for patients treated with single relative to multiple fractions ($1,873 for single vs. $4,967 for multiple fractions).

“Despite evidence demonstrating comparable pain relief for single-fraction treatment, only 3.3 percent of Medicare beneficiaries with bone metastases from prostate cancer received single-fraction treatment. Patients who received single-fraction radiotherapy had poorer prognoses, perhaps reflecting the perception that single-fraction treatment should be reserved for patients with limited life expectancy or poor performance status. However, single-fraction treatment has substantial benefits for patient-centric palliative care, including greater quality of life and convenience, reduced travel time, and lower treatment costs,” the authors conclude.

(doi:10.l001/jama.2013.277081; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by grants from the National Cancer Institute and American Cancer Society, and with funding from the Leonard Davis Institute for Health Economics. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Bekelman reported receiving honoraria from the American Society for Clinical Oncology; and travel expenses from the Radiation Oncology Institute. Dr. Epstein reported receiving institutional grant support from the Institute for Health Technology Studies. No other disclosures were reported.

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