EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 8, 2016

Media Advisory: To contact Adam M. Leventhal, Ph.D., email Zen Vuong at zvuong@usc.edu or call 213-740-5277.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.14649

In a study appearing in the November 8 issue of JAMA, Adam M. Leventhal, Ph.D., of the University of Southern California Keck School of Medicine, Los Angeles, and colleagues examined associations of e-cigarette vaping with subsequent smoking frequency and heavy smoking among adolescents.

E-cigarette vaping is reported by 37 percent of U.S. 10th-grade adolescents and is associated with subsequent initiation of combustible cigarette smoking. Whether individuals who vape and transition to combustible cigarettes are experimenting or progress to more frequent and heavy smoking is unknown. In addition, because some adolescents use e-cigarettes as a smoking cessation aid, adolescent smokers who vape could be more likely to reduce their smoking levels over time.

This study consisted of an analysis of data from surveys administered to 10th grade students in ten public high schools in Los Angeles County during the fall (baseline for this report) and spring (6-month follow-up) of 2014-2015. Surveys included e-cigarette and combustible cigarette use questions from prior research, which were used to determine baseline vaping and baseline and follow-up past 30-day smoking frequency and heaviness.

Students with complete vaping and smoking data at baseline and follow-up constituted the analytic sample (n = 3,084; 54 percent girls; baseline average age, 15.5 years). The prevalence rates of past 30-day vaping and smoking were low overall. Smoking frequency at follow-up was proportionately greater with successively higher levels of baseline vaping. Similar trends were found for smoking heaviness.

Adjusting for baseline smoking, each increment higher on the 4-level baseline vaping frequency continuum was associated with proportionally higher odds of smoking at a greater level of frequency and heaviness by follow-up. The positive association between baseline vaping and follow-up smoking frequency was stronger among baseline nonsmokers than baseline infrequent and frequent smokers; similar trends were found for smoking heaviness.

“The role of nicotine and generalizability of these results to other locations and ages, longer follow-up periods, and non-self-report assessments are unknown and merit further inquiry. The transition from vaping to smoking may warrant particular attention in tobacco control policy,” the authors write.

(doi:10.1001/jama.2016.14649; the study is available pre-embargo at the For the Media website)

Editor’s Note: This research was supported by grants from the National Institutes of Health. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 1, 2016

Media Advisory: To contact Seena Fazel, M.D., email seena.fazel@psych.ox.ac.uk.

 
To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.15380

Among released prisoners in Sweden, rates of violent reoffending were lower during periods when individuals were dispensed antipsychotics, psychostimulants, and drugs for addictive disorders, compared with periods in which they were not dispensed these medications, according to a study appearing in the November 1 issue of JAMA.

There were more than 10 million prisoners worldwide in 2015, with approximately 2.2 million in the United States alone. Despite reported decreases in violence in many countries, reoffending rates remain high. From 2005 through 2010, more than one-third of released prisoners in the United States and the United Kingdom were reconvicted of a new crime within 2 years. Most programs to reduce reoffending focus on psychosocial interventions, but their effect sizes are weak to moderate. As psychiatric and substance use disorders, which increase reoffending rates, are overrepresented among jail and prison populations, treatment with appropriate psychotropic medications offers an alternative strategy to reduce reoffending, although there is uncertainty about whether pharmacological treatments reduce reoffending risk.

Seena Fazel, M.D., of the University of Oxford, England, and colleagues examined the associations between major classes of psychotropic medications and violent reoffending. The study included all released prisoners in Sweden from July 2005 to December 2010, through linkage of population-based registers. Rates of violent reoffending during medicated periods (dispensed prescription of psychotropic medications [antipsychotics, antidepressants, psychostimulants, drugs used in addictive disorders, and antiepileptic drugs]) were compared with rates during nonmedicated periods. Prison-based psychological treatments were also included in the analysis.

The study included 22,275 released prisoners (average age, 38 years; 92 percent male). During follow-up (median, 4.6 years), 4,031 individuals (18 percent) had 5,653 violent reoffenses. The researchers found that three classes of psychotropic medications were associated with substantial reductions in violent reoffending: antipsychotics, a 42 percent reduction; psychostimulants, 38 percent; and drugs used in addictive disorders, a 52 percent reduction. In contrast, antidepressants and antiepileptics were not significantly associated with violent reoffending rates.

Analyses also demonstrated that completion of psychological treatments targeting general criminal attitudes and substance abuse was associated with reductions in violent reoffending. The associations with these psychological programs were not stronger than those for medications. “These findings may have implications for risk management, because prison psychological programs need appropriate facilities, require sufficiently trained and supervised therapists, and are likely to be relatively expensive. Provision of medication after prison release needs evaluation as a possibly cost-effective crime reduction alternative. Because prisoners with psychiatric disorders benefit from both pharmacological and psychological treatments, research should investigate whether combining therapies improves outcomes,” the authors write.

“The absolute numbers of prisoners with psychiatric disorders are large worldwide, and most individuals who could benefit from psychotropic treatment do not receive it after prison release. The magnitudes of the associations reported in this study may warrant correctional services to review policies for released prisoners. Evidence-based provision of psychotropic medications to released prisoners may have the potential to make substantial improvements to public health and safety, particularly in countries that are undergoing decarceration [reducing the number of persons imprisoned or the rate of imprisonment].”

(doi:10.1001/jama.2016.15380; the study is available pre-embargo at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 1, 2016

Media Advisory: To contact Malini DeSilva, M.D., M.P.H., email Vineeta Sawkar at vineeta.s.sawkar@healthpartners.com.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.14432

In an analyses that included more than 300,000 births, tetanus, diphtheria, and acellular pertussis (Tdap) vaccine administration during pregnancy was not significantly associated with increased risk for microcephaly or for structural birth defects in offspring, according to a study appearing in the November 1 issue of JAMA.

In 2012, the U.S. Advisory Committee on Immunization Practices recommended that Tdap vaccine be administered during every pregnancy, ideally between 27 and 36 weeks’ gestation. Previously, Tdap was recommended for unvaccinated pregnant women since 2010 in California and since 2011 across the United States. Cases of microcephaly (an abnormally small head due to failure of brain growth) in Brazil increased substantially during 2015, likely associated with maternal Zika virus infections. However, these cases overlapped with the November 2014 initiation of Brazil’s maternal Tdap program. Previous small observational studies reported no increased risks for birth defects following maternal Tdap vaccination; none focused on microcephaly.

In this study, Malini DeSilva, M.D., M.P.H., of HealthPartners Institute, Minneapolis, and colleagues included data from live births at 7 Vaccine Safety Datalink sites (Northern California, Southern California, Colorado, Minnesota, Oregon, Washington, and Wisconsin) from January 2007 through September 2013 and compared prevalence of structural birth defects between infants born to women who received Tdap during pregnancy and unvaccinated women. Analyses of maternal Tdap vaccination from 27 to 36 weeks’ gestation were limited to 2010-2013 for California sites and to 2012-2013 for other sites. Any structural defect, selected major structural defects, and microcephaly alone were identified from diagnostic codes assigned at medical visits during the first year of life.

Analyses included 324,463 live births. The researchers found that maternal Tdap was not significantly associated with increased risk for microcephaly for vaccinations occurring at less than 14 weeks’ gestation (n = 3,321), between 27 and 36 weeks’ gestation (n = 20,568), or during any week of pregnancy (n = 41,654). Adjusted analyses were similar for any structural birth defect and selected major structural defects.

The authors note that the findings are potentially limited by incomplete data on Tdap vaccinations (making it possible to misclassify women’s immunization status), diagnosed structural birth defects, and important covariates (including maternal alcohol use), as well as inability to study birth defects resulting in pregnancy loss or elective termination.

“The findings support recommendations for routine Tdap administration during pregnancy,” the researchers write.

(doi:10.1001/jama.2016.14432; the study is available pre-embargo at the For the Media website)

Editor’s Note: This work was funded by the Centers for Disease Control and Prevention. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) THURSDAY, OCTOBER 27, 2016

Media Advisory: To contact Manisha Juthani-Mehta, M.D., email Ziba Kashef at ziba.kashef@yale.edu or call 203-436-9317. To contact editorial author Lindsay E. Nicolle, M.D., F.R.C.P.C., email Chris Rutkowski at Chris.Rutkowski@umanitoba.ca or call 204-474-9514.

To place an electronic embedded link to these articles in your story  These links will be live at the embargo time: http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.16141  http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.16140

Among older women residing in nursing homes, administration of cranberry capsules compared with placebo resulted in no significant difference in presence of bacteriuria plus pyuria (presence of bacteria and white blood cells in the urine, a sign of urinary tract infection [UTI]), or in the number of episodes of UTIs over l year, according to a study published online by JAMA. The study is being released to coincide with its presentation at IDWeek 2016.

Urinary tract infection is the most commonly diagnosed infection among nursing home residents. Bacteriuria is prevalent in 25 percent to 50 percent of women living in nursing homes, and pyuria is present in 90 percent of those with bacteriuria. Cranberry capsules are an understudied, nonantimicrobial prevention strategy used in this population. Manisha Juthani-Mehta, M.D., of the Yale School of Medicine, New Haven, Conn., and colleagues randomly assigned 185 women (average age, 86 years; with or without bacteriuria plus pyuria at study entry) residing in nursing homes to two oral cranberry capsules, each capsule containing 36 mg of the active ingredient proanthocyanidin (i.e., 72 mg total, equivalent to 20 ounces of cranberry juice) or placebo administered once a day.

Of the 185 study participants (31 percent with bacteriuria plus pyuria at study entry), 147 completed the study. Overall adherence was 80 percent. After adjustment for various factors, there was no significant difference in the presence of bacteriuria plus pyuria between the treatment group vs the control group (29.1 percent vs 29.0 percent). There were also no significant differences in number of symptomatic UTIs (10 episodes in the treatment group vs 12 in the control group), rates of death (17 vs 16 deaths), hospitalization, antibiotics administered for suspected UTIs, or total antimicrobial utilization.

“Many studies of cranberry products have been conducted over several decades with conflicting evidence of its utility for UTI prevention. The results have led to the recommendation that cranberry products do not prevent UTI overall but may be effective in older women. This trial did not show a benefit of cranberry capsules in terms of a lower presence of bacteriuria plus pyuria among older women living in nursing homes,” the authors write.

(doi:10.1001/jama.2016.16141; the study is available pre-embargo at the For the Media website)

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

Editorial: Cranberry for Prevention of Urinary Tract Infection? – Time to Move on

“The continuing promotion of cranberry use to prevent recurrent UTI in the popular press or online advice seems inconsistent with the reality of repeated negative studies or positive studies compromised by methodological shortcomings. Any continued promotion of the use of cranberry products seems to go beyond available scientific evidence and rational reasoning,” writes Lindsay E. Nicolle, M.D., F.R.C.P.C., of the University of Manitoba, Winnipeg, Manitoba, Canada, in an accompanying editorial.

“Some of this conviction is likely an interest of individuals or groups to promote the use of natural health products for clinical benefits, allowing avoidance of medical interventions and, potentially, giving women who experience recurrent UTI an element of personal control in managing their problem. The current emphasis on antimicrobial stewardship and limiting antimicrobial use whenever possible also may have some influence in the continued endorsement of cranberry juice or tablets as a nonantimicrobial strategy for management of UTI.”

“Recurrent UTI is a common problem that is distressing to patients and because it is so frequent and costly for the health care system. It is time to identify other potential approaches for management. This certainly must include a wiser use of antimicrobial therapy for syndromes of recurrent UTI in women in long-term care facilities. Other possible interventions to explore in this and other populations may include, among other approaches, adherence inhibitors or immunologic interventions. Intellectual discussions and clinical trial activity should be redirected to identify and evaluate other innovative antimicrobial and nonantimicrobial approaches. It is time to move on from cranberries.”

(doi:10.1001/jama.2016.16140; the editorial is available pre-embargo at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 12:30 P.M. (ET) FRIDAY, OCTOBER 28, 2016

Media Advisory: To contact Rafael Harpaz, M.D., M.P.H., email Ian Branam at yfi1@cdc.gov or call 404-639-0316.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.16477

In a study published online by JAMA, Rafael Harpaz, M.D., M.P.H., of the U.S. Centers for Disease Control and Prevention, Atlanta, and colleagues analyzed data from the 2013 National Health Interview Survey (NHIS; an annual health survey conducted via household interviews) to estimate the prevalence of self-reported immunosuppressed adults in the United States. The study is being released to coincide with its presentation at IDWeek 2016.

The number of immunosuppressed adults in the United States is unknown but thought to be increasing because of both greater life expectancy among immunosuppressed adults due to improvements in medical management, as well as new indications for immunosuppressive treatments. Immunosuppression increases the risks and severity of primary or reactivation infections; its prevalence has implications for food and water safety, tuberculosis control, vaccine programs, infection control strategies, outbreak preparedness, travel medicine, and other facets of public health.

In 2013, NHIS respondents were asked whether they had ever been told by a “doctor or other health professional” that their immune system was weakened. Those responding yes were asked follow-up questions to assess whether that status was current (i.e., at time of response) and to report additional evidence of immunosuppression. Those reporting use of immunosuppressive medications or treatments or occurrence of immunosuppressive medical conditions (i.e., hematopoietic cancers or human immunodeficiency virus [HIV] infection) were considered immunosuppressed in this analysis, but those reporting only frequent colds or infections or attributing immunosuppression solely to chronic diseases or to solid cancers (i.e., in absence of immunosuppressive treatments) were not.

The total 2013 NHIS household response rate was 76 percent, consisting of 41,355 eligible households. Of 34,426 eligible adult respondents within these households, 4.2 percent (n = 1,442) had been told at some time by a health professional that their immune system was weakened. Of these, 2.8 percent (n = 951) reported current immunosuppression and additional evidence of immunosuppression, translating to an estimated U.S. prevalence of 2.7 percent. Prevalence was highest among women, whites, and persons age 50 to 59 years.

“This study was not designed to explore the attributable causes of immunosuppression, although prevalence is likely driven by frequency and chronicity (e.g., life-long immunosuppression due to HIV infection, treatment for autoimmune conditions, or solid organ transplantation vs short-term cancer chemotherapy). The higher prevalence of immunosuppression among women may reflect their higher risk for autoimmune conditions. Age-specific immunosuppression increased with age, in parallel with the epidemiology of prevalent conditions that require immunosuppressive treatments, but it is unclear why it peaked at ages 50 to 59 years,” the authors write.

“This study addresses an underappreciated phenomenon and serves as a call for additional data from other sources to complement and fill the gaps in the study. Tracking immunosuppression over time is particularly important given the hundreds of clinical trials now under way to assess the use of immunosuppressive treatments for prevention or mitigation of common chronic diseases in highly prevalent risk groups.”

(doi:10.1001/jama.2016.16477; the study is available pre-embargo at the For the Media website)

Editor’s Note: This work was funded by the U.S. Centers for Disease Control and Prevention. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, OCTOBER 25, 2016

Media Advisory: To contact the U.S. Preventive Services Task Force, email the Media Coordinator at Newsroom@USPSTF.net or call 202-572-2044.

To place an electronic embedded link to this report in your story  This link will be live at the embargo time: http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.14697

The U.S. Preventive Services Task Force (USPSTF) recommends providing interventions during pregnancy and after birth to support breastfeeding. The report appears in the October 25 issue of JAMA.

This is a B recommendation, indicating that there is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial.

There is convincing evidence that breastfeeding provides substantial health benefits for children and adequate evidence that breastfeeding provides moderate health benefits for women. However, nearly half of all mothers in the United States who initially breastfeed stop doing so by 6 months, and there are significant disparities in breastfeeding rates among younger mothers and in disadvantaged communities. To update its 2008 recommendation, the USPSTF reviewed the evidence on the effectiveness of interventions to support breastfeeding on breastfeeding initiation, duration, and exclusivity. The USPSTF also briefly reviewed the literature on the effects of these interventions on child and maternal health outcomes.

The USPSTF is an independent, volunteer panel of experts that makes recommendations about the effectiveness of specific preventive care services such as screenings, counseling services, and preventive medications.

Interventions

Primary care clinicians can support women before and after childbirth by providing interventions directly or by referral to help them make an informed choice about how to feed their infants and to be successful in their choice. Interventions include promoting the benefits of breastfeeding, providing practical advice and direct support on how to breastfeed, and providing psychological support. Interventions can be categorized as professional support, peer support, and formal education, although none of these categories are mutually exclusive, and interventions may be combined within and between categories. Interventions may also involve a woman’s partner, other family members, and friends.

Effectiveness of Interventions to Change Behavior

Adequate evidence indicates that interventions to support breastfeeding increase the duration and rates of breastfeeding, including exclusive breastfeeding.

Harms of Interventions to Change Behavior

There is adequate evidence to bound the potential harms of interventions to support breastfeeding as no greater than small, based on the nature of the intervention, the low likelihood of serious harms, and the available information from studies reporting few harms.

Implementation

Not all women choose to or are able to breastfeed. Clinicians should, as with any preventive service, respect the autonomy of women and their families to make decisions that fit their specific situation, values, and preferences.

Summary

The USPSTF found adequate evidence that interventions to support breastfeeding, including professional support, peer support, and formal education, change behavior and that the harms of these interventions are no greater than small. The USPSTF concludes with moderate certainty that interventions to support breastfeeding have a moderate net benefit for women and their children.

(doi:10.1001/jama.2016.14697; the full report is available pre-embargo to the media at the For the Media website)

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

Note: More information about the U.S. Preventive Services Task Force, its process, and its recommendations can be found on the newsroom page of its website.

# # #

EMBARGOED FOR RELEASE: 5:45 P.M. (ET) MONDAY, OCTOBER 17, 2016

Media Advisory: To contact Thue Bisgaard, M.D., D.M.Sc., email thue.bisgaard@gmail.com; to contact Dunja Kokotovic, M.B., email dunja.kokotovic@hotmail.com. To contact editorial author Kamal M. F. Itani, M.D., email Gina DiGravio-Wilczewski at ginad@bu.edu.

To place electronic embedded links to these articles in your story  These links will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.15217  http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.15722

Among patients undergoing incisional hernia repair, the use of mesh to reinforce the repair was associated with a lower risk of hernia recurrence over 5 years compared with when mesh was not used, although with long-term follow-up, the benefits attributable to mesh were offset in part by mesh-related complications, according to a study published online by JAMA. The study is being released to coincide with its presentation at the American College of Surgeons Clinical Congress 2016.

Elective incisional hernia repair is one of the most commonly performed general surgical operations.  In the United States alone, there were about 190,000 inpatient abdominal wall hernia repairs performed in 2012. Prosthetic mesh is frequently used to reinforce the repair; it’s done in at least half of the abdominal wall hernia repairs performed in the United States. The benefits of mesh for reducing the risk of hernia recurrence or the long-term risks of mesh-related complications are not known.

Dunja Kokotovic, M.B., and Frederik Helgstrand, M.D., D.M.Sc., of Zealand University Hospital, Køge, Denmark, and Thue Bisgaard, M.D., D.M.Sc., of Hvidovre Hospital, Hvidovre, Denmark, conducted a study that included 3,242 patients with elective incisional hernia repairs in Denmark from January 2007 to December 2010. The researchers compared outcomes for hernia repair using mesh performed by either open or laparoscopic techniques vs open repair without use of mesh.

Among the patients (average age, 59 years; 53 percent women), 1,119 underwent open mesh repair (35 percent), 366 had open nonmesh repair (11 percent), and 1,757 had laparoscopic mesh repair (54 percent). The median follow-up after open mesh repair was 59 months; after nonmesh open repair, 62 months; and after laparoscopic mesh repair, was 61 months. The researchers found that the risk of the need for repair for recurrent hernia following these initial hernia operations was lower for patients with open mesh repair (12 percent; risk difference, -4.8 percent) and for patients with laparoscopic mesh repair (10.6 percent; risk difference, -6.5 percent) compared with nonmesh repair (17.1 percent).

For the entirety of the follow-up duration, there were a progressively increasing number of mesh-related complications (such as bowel obstruction, bowel perforation, bleeding, late abscess) for both open and laparoscopic procedures. At 5 years of follow-up, the cumulative incidence of mesh-related complications was 5.6 percent for patients who underwent open mesh hernia repair and 3.7 percent for patients who underwent laparoscopic mesh repair. The long-term repair-related complication rate for patients with an initial nonmesh repair was 0.8 percent (open nonmesh repair vs open mesh repair: risk difference, 5.3 percent; open nonmesh repair vs laparoscopic mesh repair: risk difference, 3.4 percent).

“Mesh implantation prevented the need for subsequent reoperation in relatively few patients, suggesting that the benefits associated with the use of mesh are partially off­set by long-term complications associated with its use. This observation, however, should be interpreted with caution because of the risk of selection bias. Larger, more complicated hernias are likely to be repaired with mesh, and small, simple hernias with little likelihood of long-term problems tend to be repaired without mesh,” the authors write.

“The present study highlights the need to assess the long-term safety of interventions before making definitive conclusions about their benefits. Demonstration of long-term safety is required for drugs in the United States but not for some devices, such as hernia meshes, which are not subject to similarly strict documentation. In the United States, most hernia mesh is approved for use by the 510(k) mechanism. This requires only that these materials have similarity to existing products on the market without the need for clinical trials to demonstrate safety or efficacy. Thus, the complete spectrum for the risks and benefits of mesh used to reinforce hernia repair is not known because there are very few clinical trial data reporting hernia outcomes as they pertain to mesh utilization. This highlights the need for more long-term studies of mesh repair using high-quality registries such as the one in Denmark.”

(doi:10.1001/jama.2016.15217; the study is available pre-embargo to the media at the For the Media website)

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

Editorial: New Findings in Ventral Incisional Hernia Repair

“Although the study by Kokotovic and colleagues is one of the most comprehensive long-term studies in hernia surgery, many questions remain about the optimal approach for repairing ventral hernia,” writes Kamal M. F. Itani, M.D., of the VA Boston Health Care System, Boston University, West Roxbury, Mass., in an accompanying editorial.

“To provide more rigorous data to better understand optimal approaches to this common clinical problem, surgeons will need to design large multicenter pragmatic trials with long-term follow-up. When commercial entities want to test a product, they should fund an independent research group to conduct the trial to avoid the perception of bias. Because hernia is so common and the evidence base supporting its treatment is so limited, there is a pressing need to design, fund, and conduct these trials.”

(doi:10.1001/jama.2016.15722; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, OCTOBER 18, 2016

Media Advisory: To contact David R. Flum, M.D., M.P.H., call Brian Donohue at 206-543-7856 or email bdonohue@uw.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.12040

In a study appearing in the October 18 issue of JAMA, David R. Flum, M.D., M.P.H., of the University of Washington, Seattle, and colleagues assessed working status and change in productivity in the first 3 years following bariatric surgery for severe obesity.

Obesity is associated with sick leave, disability, and work-place injuries. Bariatric surgery is an effective treatment for patients with severe obesity. Evidence is limited regarding the relationship between bariatric surgery and work productivity.  This analysis included adults with severe obesity undergoing bariatric surgery who were recruited (February 2005-February 2009) at 10 U.S. centers for the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study. Participants completed a work productivity and activity impairment questionnaire presurgery and annually postsurgery. Work status among nonretirees and past-week work absenteeism (missed work due to health) and presenteeism (impaired work due to health) among employed participants were assessed.

Of 2,019 nonretired participants, 89 percent had work factors data at 1 or more follow-up assessment(s) and were included in the analysis. Baseline median age was 45 years; median body mass index was 46; 80 percent were women. Weight loss was 28 percent at 3 years. Prevalence of employment or disability did not significantly change throughout follow-up. However, unemployment increased from presurgery to year 3 (3.7 percent for presurgery vs 5.6 percent for year 3 postsurgery).

Of 1,265 employed participants, 86 percent were included in the work productivity sample. Prevalence of absenteeism was lower at year 1 (10.4 percent) vs presurgery (15.2 percent), but did not significantly differ from presurgery at year 2 or 3. Prevalence of presenteeism was lower than presurgery at all post­surgery times but increased from years 1 to 3. Improvements in physical function and depressive symptoms were independently associated with lower risks of postsurgery absenteeism and presenteeism, whereas postsurgery initiation or continuation of psychiatric treatment vs no treatment presurgery or postsurgery was associated with higher risks. Greater weight loss was independently associated with lower risk of postsurgery presenteeism only.

“In this large cohort of adults who underwent bariatric surgery, patients maintained working status and decreased impairment due to health while working. The small increase in unemployment by year 3 may reflect a secular trend in unemployment during the time of the study; the annual average rate of unemployment increased from 4.5 percent in 2007 to 8 percent in 2012. The reduction in presenteeism following surgery may be explained by weight loss, improved physical function, or reduction in depressive symptoms. The increase in presenteeism between years 1 and 3 may reflect an adaptation to a new health state or deterioration of initial presurgery to postsurgery improvements,” the authors write.

(doi:10.1001/jama.2016.12040; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) WEDNESDAY, OCTOBER 12, 2016

Media Advisory: To contact Jeffrey L. Carson, M.D., call Jennifer Forbes at 732-235-6356 or email mullenjf@rwjms.rutgers.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.9185

In a report published online by JAMA, Jeffrey L. Carson, M.D., of Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J., and colleagues provide recommendations for the AABB (previously known as the American Association of Blood Banks) for the target hemoglobin level for red blood cell (RBC) transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion.

More than 100 million units of blood are collected worldwide each year, and approximately 13 million RBC units are collected in the United States, yet the indication for RBC transfusion and the optimal length of RBC storage prior to transfusion are uncertain. For RBC transfusion thresholds, the authors summarized and analyzed the results of 31 randomized clinical trials (RCTs) that included 12,587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dl) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dl). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes. For RBC storage duration, 13 RCTs included 5,515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes.

Summary of Findings

It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dl is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dl (strong recommendation, moderate quality evidence).

A restrictive RBC transfusion threshold of 8 g/dl is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dl is likely comparable with 8 g/dl, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion-dependent anemia (not recommended due to insufficient evidence).

Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: <10 days) RBC units (strong recommendation, moderate quality evidence).

“Transfusion is a common therapeutic intervention for which there is considerable variation in clinical practice. If clinicians continue to adopt a restrictive transfusion strategy of 7 g/dl to 8 g/dl, the number of RBC transfusions would continue to decrease. In addition, standard practice should be to initiate a transfusion with 1 unit of blood rather than 2 units. This would have potentially important implications for the use of blood transfusions and minimize the risks of infectious and noninfectious complications,” the authors write.

“Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.”

(doi:10.1001/jama.2016.9185; the study is available pre-embargo to the media at the For the Media website)

Editor’s Note: Support for guideline development was provided by the AABB. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, OCTOBER 11, 2016

Media Advisory: To contact Elizabeth D. Kantor, Ph.D., call Nicole McNamara at 646-227-3633 or email mcnamarn@mskcc.org. To contact editorial author Pieter A. Cohen, M.D., call David Cecere at 617- 591-4044 or email dcecere@challiance.org.

To place an electronic embedded link to these articles in your story  These links will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.14403; http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.14252

A nationally representative survey indicates that supplement use among U.S. adults remained stable from 1999-2012, with more than half of adults reporting use of supplements, while use of multivitamins decreased during this time period, according to a study appearing in the October 11 issue of JAMA.

Dietary supplement products are commonly used by adults in the United States, with prior research indicating an increase in use between the 1980s and mid-2000s. Despite extensive research conducted on the role of dietary supplements in health, little is known about recent trends in supplement use. Elizabeth D. Kantor, Ph.D., of Memorial Sloan Kettering Cancer Center, New York, and colleagues used data from the National Health and Nutrition Examination Survey (NHANES) to examine trends in supplement use among U.S. adults from 1999 through 2012, with a focus on use of any supplement products and multivitamins/multiminerals (MVMM; defined as a product containing 10 or more vitamins and/or minerals), as well as use of individual vitamins, minerals, and nonvitamin, nonmineral supplements. Participants were surveyed over 7 continuous 2-year cycles.

A total of 37,958 adults were included in the study (average age, 46 years; women, 52 percent), with a response rate of 74 percent. Overall, the use of supplements remained stable between 1999 and 2012, with 52 percent of U.S. adults reporting use of any supplements in 2011-2012. Use of MVMM decreased, with 37 percent reporting use in 1999-2000 and 31 percent reporting use in 2011-2012. Vitamin D supplementation from sources other than MVMM increased from 5.1 percent to 19 percent and use of fish oil supplements increased from 1.3 percent to 12 percent over the study period, whereas use of a number of other supplements decreased, including vitamins C, E, and selenium.

Trends varied across age, sex, race/ethnicity, and education.

“With the present data, it is clear that the use of supplements among U.S. adults has stabilized. This stabilization appears to be the balance of several opposing trends, with a major contributing downward factor being the decrease in use of MVMM,” the authors write.

(doi:10.1001/jama.2016.14403; the study is available pre-embargo to the media at the For the Media website)

Editor’s Note: This study was supported by grants from the National Cancer Institute of the National Institutes of Health. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: The Supplement Paradox – Negligible Benefits, Robust Consumption

“What are the conclusions from this new analysis? It is now well documented that more than half of U.S. adults use supplements. Physicians should include supplements when they review medications with all patients and also consider supplements when symptoms raise the possibility of a supplement-related adverse effect. It is now known that many supplements contain pharmaceutically active botanicals, which can have important clinical effects,” writes Pieter A. Cohen, M.D., of the Cambridge Health Alliance, Cambridge, and Harvard Medical School, Boston, in an accompanying editorial.

“For example, red yeast rice, yohimbe, and caffeine all have pharmacological effects, and although ephedra has been banned, a variety of synthetic drugs have replaced ephedra as stimulants in many sports and weight loss supplements. Reporting suspected adverse effects of supplements is also critical. The FDA relies on physicians and consumers to report adverse events via MedWatch to remove hazardous supplements from the marketplace.”

“The current study by Kantor et al should also lead funders and legislators to reconsider their priorities with respect to supplements. Given the current regulatory framework, even high-quality research appears to have only modest effects on supplement use. Future efforts should focus on developing regulatory reforms that provide consumers with accurate information about the efficacy and safety of supplements and on improving mechanisms for identifying products that are causing more harm than good.”

(doi:10.1001/jama.2016.14252; the study is available pre-embargo to the media at the For the Media website)

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

Embed the JAMA Report video: Copy and paste the link below to embed the related JAMA Report video on your website.

<div style="display:none">
use this as template for single videos 
</div>

<!--
By use of this code snippet, I agree to the Brightcove Publisher T and C 
found at https://accounts.brightcove.com/en/terms-and-conditions/. 
-->

<script language="JavaScript" type="text/javascript" src="http://admin.brightcove.com/js/BrightcoveExperiences.js"></script>

<object id="myExperience5131845279001" class="BrightcoveExperience">
  <param name="bgcolor" value="#FFFFFF" />
  <param name="width" value=“640" />
  <param name="height" value=“360" />
  <param name="playerID" value="1377024934001" />
  <param name="playerKey" value="AQ~~,AAAAyT9oH9k~,DTe1zot21E1nSpajEYjJB2xxrjlZGznd" />
  <param name="isVid" value="true" />
  <param name="isUI" value="true" />
  <param name="dynamicStreaming" value="true" />
  
  <param name="@videoPlayer" value="5131845279001" />
</object>

<!-- 
This script tag will cause the Brightcove Players defined above it to be created as soon
as the line is read by the browser. If you wish to have the player instantiated only after
the rest of the HTML is processed and the page load is complete, remove the line.
-->
<script type="text/javascript">brightcove.createExperiences();</script>

<!-- End of Brightcove Player -->

# # #

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, OCTOBER 11, 2016

Media Advisory: To contact Keith Willett, M.B.B.S., F.R.C.S., email keith.willett@nhs.net. To contact editorial author David W. Sanders, M.D., M.Sc., F.R.C.S.C., email Crystal Mackay at crystal.mackay@schulich.uwo.ca.

To place an electronic embedded link to these articles in your story  These links will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.14719  http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.14819

Among older adults with an unstable ankle fracture, the use of a modified casting technique known as close contact casting (a molded below-knee cast with minimal padding) resulted in similar functional outcomes at 6 months compared with surgery, and with fewer wound complications and reduced intervention costs, according to a study appearing in the October 11 issue of JAMA.

The number of older adults sustaining ankle fractures is increasing. Treatment of unstable fractures is either surgical or nonsurgical (using externally applied casts). Neither method yields an entirely satisfactory outcome in older adults. Traditional casting techniques are associated with poor fracture alignment and healing, as well as plaster-related sores. Surgery is often complicated by poor implant fixation (bone healing), wound problems, and infection. A modified casting technique has been developed, close contact casting, which uses minimal padding compared with traditional casting and achieves fracture reduction by distributing contact pressure by close anatomic fit.

Keith Willett, M.B.B.S., F.R.C.S., of the University of Oxford, United Kingdom, and colleagues randomly assigned 620 adults older than 60 years with acute, unstable ankle fracture to surgery (n = 309) or casting (n = 311). Casts were applied in the operating room under general or spinal anesthesia by a trained surgeon.

Among the 620 adults (average age, 71 years; 74 percent women) who were randomized, 96 percent completed the study. Nearly all participants (93 percent) received assigned treatment; 52 of 275 (19 percent) who initially received casting later converted to surgery. At 6 months, casting resulted in measures of ankle function equivalent to that with surgery. Infection and wound breakdown were more common with surgery (10 percent vs 1 percent), as were additional operating room procedures (6 percent vs 1 percent).

Radiologic malunion (abnormal healing of a fracture) was more common in the casting group (15 percent vs 3 percent for surgery). Casting required less operating room time compared with surgery. There were no significant differences in other secondary outcomes: quality of life, pain, ankle motion, mobility, and patient satisfaction.

“Close contact casting was delivered successfully for most participants, substantially reducing the number of patients requiring invasive surgical procedures at the outset and additional operations during a 6-month period,” the authors write.

The researchers add that close contact casting may be an appropriate treatment for older adults with unstable ankle fracture.

(doi:10.1001/jama.2016.14719; the study is available pre-embargo to the media at the For the Media website)

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

Editorial: Close Contact Casting vs Surgery for Unstable Ankle Fractures

“The results reported by Willett et al demonstrate that most unstable ankle fractures in older patients can be treated with a cast without the need for surgery,” writes David W. Sanders, M.D., M.Sc., F.R.C.S.C., of Western University, London, Ontario, Canada, in an accompanying editorial.

“However, many patients who were initially treated by casting subsequently required repeat casting or surgery. Further studies are needed to help identify which patients will not benefit from casting. Although close contact casting may be unfamiliar to some orthopedic surgeons, it can avoid surgery for older patients with ankle fractures, yet result in equivalent functional outcomes. This technique is worth considering when treating this challenging clinical problem.”

(doi:10.1001/jama.2016.14819; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, OCTOBER 11, 2016

Media Advisory: To contact Fredric Blavin, Ph.D., call Stu Kantor at 202-261-5709 or email skantor@urban.org.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.14765

In a study appearing in the October 11 issue of JAMA, Fredric Blavin, Ph.D., of The Urban Institute, Washington, D.C., estimated the association between Medicaid expansion in 2014 and hospital finances by assessing differences between hospitals in states that expanded Medicaid and in states that did not expand Medicaid.

The Affordable Care Act expanded Medicaid eligibility for millions of low-income adults. The choice for states to expand Medicaid could affect the financial health of hospitals by decreasing the proportion of patient volume and unreimbursed expenses attributable to uninsured patients while increasing revenue from newly covered patients. However, whether Medicaid expansion has been associated with improved hospital profits is uncertain, particularly for hospitals that received generous support from state or local government for providing uncompensated care.

This study included data from the American Hospital Association Annual Survey and the Health Care Cost Report Information System from the U.S. Centers for Medicare & Medicaid Services for nonfederal general medical or surgical hospitals in fiscal years 2011 through 2014. The sample included between 1,200 and 1,400 hospitals per fiscal year in 19 states that expanded Medicaid in early 2014 and between 2,200 and 2,400 hospitals per fiscal year in 25 states that did not expand Medicaid (with sample size varying depending on the outcome measured).

Expansion of Medicaid was associated with a decline of $2.8 million in average annual uncompensated care costs per hospital. In addition, hospitals in states with Medicaid expansion experienced a $3.2 million increase in average annual Medicaid revenue per hospital, relative to hospitals in states without Medicaid expansion. Medicaid expansion was also significantly associated with improved excess margins (a profitability indicator that includes all other sources of income, not just those from patient care) (1.1 percentage points), but not improved operating margins.

“For states still considering Medicaid expansion, these findings suggest that expansion may be associated with improvements in hospitals’ payer mix and overall financial outlook. However, changes in financial outcomes for hospitals in any specific state will likely depend on a host of factors, such as the state’s pre-ACA income and coverage distribution, Medicaid eligibility thresholds, Medicaid reimbursement levels, and the subsidies hospitals receive for providing uncompensated care,” the author writes.

“Further study is needed to assess longer-term implications of this policy change on hospitals’ overall finances.”

(doi:10.1001/jama.2016.14765; the study is available pre-embargo to the media at the For the Media website)

Editor’s Note: This study was supported by the Robert Wood Johnson Foundation. The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, OCTOBER 11, 2016

Media Advisory: To contact Ali Torkamani, Ph.D., email Anna Andersen at aanders@scripps.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.11445

In a study appearing in the October 11 issue of JAMA, Ali Torkamani, Ph.D., of Scripps Translational Science Institute, La Jolla, Calif., and colleagues report preliminary results from a family-based, postmortem genetic testing study.

Approximately 11,000 individuals younger than 45 years in the United States die suddenly and unexpectedly each year from conditions including sudden infant death, pulmonary embolism, ruptured aortic aneurysm, and sudden cardiac death (SCD). Sometimes the cause of death is not determined, even after a clinical autopsy, leaving living relatives with an inaccurate or ambiguous family health history. Moreover, the rate of clinical autopsy has declined from approximately 50 percent fifty years ago to less than 10 percent in 2008, contributing further to uncertain family health histories. This uncertainty may be partially resolved with postmortem genetic testing (“molecular autopsy”).  Initial studies, limited to cardiac channelopathy and epilepsy genes, have yielded molecular diagnoses in approximately 25 percent of cases. A more comprehensive molecular autopsy program, expanded beyond SCD, has the potential to provide more accurate family health information to a wider spectrum of afflicted families.

For this study, exome sequencing was performed on blood or tissue samples collected from deceased persons age 45 years or younger, with sudden unexpected death, referred to Scripps Translational Science Institute by the medical examiner between October 2014 and November 2015. Exome sequencing of saliva samples from parents, when available, was also performed. Mutations were categorized as likely cause of death (mutation previously reported or expected in an SCD-related gene); plausible cause of death (mutation of unknown significance in an SCD gene); or speculative cause of death (mutation previously reported in other disorders).

Twenty-five cases were sequenced, with 9 including both parents of the deceased. Clinical autopsies discovered the likely cause of death in 5 cases. A likely cause of death was identified by molecular autopsy in 4 cases (16 percent), a plausible cause in 6 (24 percent), and a speculative cause in 7 (28 percent); no mutations were identified in 8 (32 percent). The likely genetic cause of death was corroborated with clinical autopsy findings in 2 of 5 cases. All other clinical autopsy findings (3 cases) could be linked to a plausible or speculative genetic cause. Seventy percent (7/10 cases) of likely and plausible pathogenic mutations were inherited from relatives who did not die suddenly.

The authors note that these speculative and plausible findings cannot definitively be linked to sudden death.

“The ambiguity associated with some of these genetic findings should be balanced against the potential for clinical follow-up, active surveillance, or preventive interventions in living relatives. Although molecular autopsies may help identify genetic causes of sudden unexpected death, a comprehensive and systematic effort to collect and share genetic and phenotypic data is needed to more precisely define pathogenic variants and provide quantifiable risks to living relatives.”

(doi:10.1001/jama.2016.11445; the study is available pre-embargo to the media at the For the Media website)

Editor’s Note: This work is supported by a National Institutes of Health and National Center for Advancing Translational Sciences clinical and translational science award and grants from Scripps Genomic Medicine. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, OCTOBER 4, 2016

Media Advisory: To contact Cindy L. Amundsen, M.D., call Amara Omeokwe at 919-681-4239 or email amara.omeokwe@duke.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.14617

In a study appearing in the October 4 issue of JAMA, Cindy L. Amundsen, M.D., of Duke University, Durham, N.C., and colleagues assessed whether injection of onabotulinumtoxinA (Botox A) is superior to sacral neuromodulation (use of an implanted electrode for bladder control) in controlling episodes of refractory urgency urinary incontinence in women.

Urgency urinary incontinence is a sudden need to void resulting in uncontrollable urine loss. This disruptive condition is common and increases with age, from 17 percent of women older than 45 years to 27 percent older than 75 years in the United States. Women with refractory (not responsive to treatment) urgency urinary incontinence are treated with onabotulinumtoxinA and sacral neuromodulation (involves the implantation of a small electrode tip near the sacral nerve, which controls voiding function in the lower spine; the implanted device stimulates the nerve to act as a sort of pacemaker for the bladder) with limited comparative information.

For this study, conducted at nine U.S. medical centers, the researchers randomly assigned women with refractory urgency urinary incontinence to an injection of onabotulinumtoxinA (n = 192) or sacral neuromodulation (n = 189). Of the 364 women (average age, 63 years) in the intention-to-treat population, 190 in the onabotulinumtoxinA group had a statistically significant greater reduction in 6-month average number of episodes of urgency incontinence per day than did the 174 in the sacral neuromodulation group (-3.9 vs -3.3 episodes per day). Participants treated with onabotulinumtoxinA showed greater improvement in an overactive bladder questionnaire for symptom bother, treatment satisfaction and treatment endorsement than treatment with sacral neuromodulation.

However, there was no significant difference for quality of life or for measures of treatment preference, convenience, or adverse effects. OnabotulinumtoxinA did increase the risk of urinary tract infections and need for self-catheterizations.

“Overall, these findings make it uncertain whether onabotulinumtoxinA provides a clinically important net benefit compared with sacral neuromodulation,” the authors write.

(doi:10.1001/jama.2016.14617; the study is available pre-embargo to the media at the For the Media website)

Editor’s Note: This work was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the NIH Office of Research on Women’s Health at National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, OCTOBER 4, 2016

Media Advisory: To contact Paul S. Chan, M.D., call Laurel Gifford at 816-502-8532 or email lgifford@saint-lukes.org.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.14380

In a study appearing in the October 4 issue of JAMA, Paul S. Chan, M.D., of Saint Luke’s Mid America Heart Institute, Kansas City, and colleagues evaluated the association of hypothermia treatment with survival to hospital discharge and with favorable neurological survival at hospital discharge among patients with in-hospital cardiac arrest.

Therapeutic hypothermia, or targeted temperature management, is recommended for comatose patients following both out-of-hospital and in-hospital cardiac arrest. Nevertheless, therapeutic hypothermia has only been shown to improve overall survival and rates of favorable neurological survival in patients with out-of-hospital cardiac arrest due to ventricular fibrillation. Whether this treatment improves survival for patients with in-hospital cardiac arrest is unknown. As in-hospital cardiac arrest affects approximately 200,000 individuals annually in the United States, there is a need to understand whether therapeutic hypothermia is associated with improved survival for these patients.

With the use of the national Get With the Guidelines-Resuscitation registry, the researchers identified 26,183 patients successfully resuscitated from an in-hospital cardiac arrest between March 2002 and December 2014, and either treated or not treated with hypothermia at 355 U.S. hospitals.

Overall, 1,568 of 26,183 patients with in-hospital cardiac arrest (6 percent) were treated with therapeutic hypothermia; 1,524 of these patients were matched to 3,714 non-hypothermia-treated patients. After adjustment, therapeutic hypothermia was associated with lower in-hospital survival (27.4 percent vs 29.2 percent), and this association was similar for nonshockable cardiac arrest rhythms (22.2 percent vs 24.5 percent) and shockable cardiac arrest rhythms (41.3 percent vs 44.1 percent). Therapeutic hypothermia was also associated with lower rates of favorable neurological survival for the overall study group (hypothermia-treated group, 17 percent; non-hypothermia-treated group, 20.5 percent) and for both rhythm types.

When follow-up was extended to 1 year, there remained no survival advantage with therapeutic hypothermia treatment.

“Collectively, these findings do not support current use of therapeutic hypothermia for patients with in-hospital cardiac arrest,” the authors write.

“These observational findings warrant a randomized clinical trial to assess efficacy of therapeutic hypothermia for in-hospital cardiac arrest.”

(doi:10.1001/jama.2016.14380; the study is available pre-embargo to the media at the For the Media website)

Editor’s Note: Dr. Chan is supported by a grant from the National Heart, Lung, and Blood Institute. The Get With the Guidelines-Resuscitation registry is sponsored by the American Heart Association. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, OCTOBER 4, 2016

Media Advisory: To contact co-author Nicholas J. Wareham, M.B.B.S., Ph.D., email nick.wareham@mrc-epid.cam.ac.uk.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.14568

In a study appearing in the October 4 issue of JAMA, Luca A. Lotta, M.D., Ph.D., of the University of Cambridge, U.K., and colleagues examined the associations with type 2 diabetes and coronary artery disease of low-density lipoprotein cholesterol (LDL-C)-lowering genetic variants. Treatment with statins, the pharmacological agents of choice for LDL-C-lowering therapy in cardiovascular prevention, is associated with weight gain and a higher incidence of new-onset type 2 diabetes.

The researchers conducted a meta-analyses of genetic association studies, and included 50,775 individuals with type 2 diabetes and 270,269 controls and 60,801 individuals with coronary artery disease and 123,504 controls. Data collection took place in Europe and the United States between 1991 and 2016.

The authors found that LDL-C-lowering genetic variants at the gene NPC1L1 were inversely associated with coronary artery disease and directly associated with type 2 diabetes. For a given reduction in LDL-C, genetic variants were associated with a similar reduction in coronary artery disease risk. However, associations with type 2 diabetes were heterogeneous (dissimilar), indicating gene-specific associations with metabolic risk of LDL-C-lowering alleles.

“In this meta-analysis, exposure to LDL-C-lowering genetic variants in or near the NPC1L1 gene was associated with a higher risk of type 2 diabetes,” the authors write.

“The results of this study show that multiple LDL-C­ lowering mechanisms, including those mediated by the molecular targets of available LDL-C-lowering drugs (i.e., statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors), are associated with adverse metabolic consequences and increased type 2 diabetes risk.”

“In general, unlike the association of LDL-C-lowering alleles [an alternative form of a gene] with cardiovascular risk, the association of these alleles with metabolic risk appears to be specific to particular genes, which in turn might suggest that the adverse consequences of lipid-lowering agents on diabetes risk could be specific to a particular drug target. This may have clinical implications for the future of lipid-lowering therapy in the context of the increasing number of approved drugs acting on different molecular targets. The overall safety profile of these drugs, including the magnitude of risk of new-onset type 2 diabetes, may be relevant to the choice of specific agent for subsets of the patient population (e.g., those at high risk for type 2 diabetes who are candidates for lipid-lowering therapy),” the researchers write.

(doi:10.1001/jama.2016.14568; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 27, 2016

Media Advisory: To contact Michael D. Hill, M.D., M.Sc., call Marta Cyperling at 403-210-3835 or email mcyperli@ucalgary.ca.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.13647

In an analysis that included nearly 1,300 patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy (intra-arterial use of a micro-catheter or other device to remove a blood clot) plus medical therapy (use of a clot dissolving agent) compared with medical therapy alone was associated with less disability at 3 months, according to a study appearing in the September 27 issue of JAMA.

Five randomized trials have demonstrated the benefit of second-generation endovascular recanalization therapies over medical therapy alone among patients with acute ischemic stroke due to large vessel occlusions (blockage). However, uncertainties remain about the benefit and risk of endovascular intervention when under taken more than 6 hours after symptom onset. Michael D. Hill, M.D., M.Sc., of the University of Calgary, Calgary, Canada, and colleagues conducted a meta-analysis of the data from these 5 randomized trials (1,287 patients enrolled at 89 international sites). Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled.

The researchers found that compared with medical therapy alone, earlier treatment with endovascular thrombectomy plus medical therapy was associated with lower degrees of disability at 3 months. Benefit was greatest with time from symptom onset to arterial puncture for thrombectomy of less than 2 hours and became nonsignificant after 7.3 hours.

Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability and less functional independence, but no change in mortality.

The authors note that within 7.3 hours, “functional outcomes were better the sooner after symptom onset that endovascular reperfusion was achieved, emphasizing the importance of programs to enhance patient awareness, out-of-hospital care, and in-hospital management to shorten symptom onset-to-treatment times.”

“The results of this study reinforce guideline recommendations to pursue endovascular treatment when arterial puncture can be initiated within 6 hours of symptom onset, and provide evidence that potentially supports strengthening of recommendations for treatment from 6 through 7.3 hours after symptom onset.”

(doi:10.1001/jama.2016.13647; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 27, 2016

Media Advisory: To contact Marc S. Sabatine, M.D., M.P.H., call Johanna Younghans at 617- 525-6373 or email jyounghans@partners.org.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.13985

In a study appearing in the September 27 issue of JAMA, Marc S. Sabatine, M.D., M.P.H., of Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues evaluated the association between lowering low-density lipoprotein cholesterol (LDL-C) and relative cardiovascular risk reduction across different statin and nonstatin therapies.

Low-density lipoprotein cholesterol is a well-established risk factor for cardiovascular disease. The clinical benefit of lowering LDL-C with statins remains widely accepted. In contrast, the comparative clinical benefit of nonstatin therapies that reduce LDL-C remains uncertain. For this study, the authors conducted a review and meta-analysis of 49 trials that met criteria for inclusion. The study included a total of 312,175 participants with 39,645 major vascular events and 9 different interventions to lower LDL-C.

The interventions were divided into 4 groups: (1) statins; (2) nonstatin therapies that ultimately work predominantly through upregulation of LDL receptor expression (i.e., diet, bile acid sequestrants, ileal bypass, and ezetimibe); (3) interventions that do not reduce LDL-C levels primarily through upregulation of LDL receptor expression (i.e., fibrates, niacin, cholesteryl ester transfer protein [CETP] inhibitors); and (4) PCSK9 inhibitors, which upregulate LDL-C clearance through the LDL receptor, but for which dedicated cardiovascular outcome trials have not yet been completed (and were considered separately to evaluate how the data to date compare with established therapies that upregulate LDL receptor expression).

The authors found that there was a similar association between absolute reductions in LDL-C and lower relative risks for major vascular events (a composite of cardiovascular death, acute heart attack or other acute coronary syndrome, coronary revascularization, or stroke) across therapies that lead to upregulation of LDL receptor expression. Each 1-mmol/L (39 mg/dL) reduction in LDL-C was associated with a 23 percent relative reduction in the risk of major vascular events. There was also a significant linear association between achieved LDL-C and the rate of cardiovascular outcomes over the range of LDL-C studied.

“The implications of these results deserve careful consideration in light of the strength of the available trial evidence for different types of therapies. As per current guidelines, when tolerated, statins should be the first-line therapy given the large reductions observed for LDL-C, the excellent safety profile, the demonstrated clinical benefit, and low cost (now that most are generic). However, the data in the present meta-regression analysis raise the possibility that other interventions, especially those that ultimately act predominantly through upregulation of LDL receptor expression, may provide additional options and may potentially be associated with the same relative clinical benefit per each 1-mmol/L reduction in LDL-C,” the authors write.

(doi:10.1001/jama.2016.13985; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 27, 2016

Media Advisory: To contact Kanu Okike, M.D., M.P.H., email okike@post.harvard.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.11014

In a study appearing in the September 27 issue of JAMA, Kanu Okike, M.D., M.P.H., of the Kaiser Moanalua Medical Center, Honolulu, and colleagues examined if bias with single-blind peer review might be greatest in the setting of author or institutional prestige.

Most medical journals practice single-blind review (authors’ identities known to reviewers), but double-blind review (authors’ identities masked to reviewers) may improve the quality of reviews. This study was conducted at Clinical Orthopaedics and Related Research, an orthopedic journal that allows authors to select single-blind or double-blind peer review. Potential reviewers were informed that a study on peer review would occur in the coming year, and allowed to opt out.

Between June 2014 and August 2015, reviewers were randomly assigned to receive single-blind or double-blind versions of an otherwise identical fabricated manuscript, which was indicated as being written by 2 past presidents of the American Academy of Orthopaedic Surgeons from prominent institutions. Five subtle errors were included to determine differences in how critically the manuscript was examined. The primary outcome was recommendation of acceptance or rejection.

The authors found that reviewers (n = 119) were more likely to recommend acceptance when the prestigious authors’ names and institutions were visible (single-blind review) than when they were redacted (double-blind review) (87 percent vs 68 percent) and also gave higher ratings for the methods and other categories. There was no difference in the number of errors detected.

The researchers note that the study was conducted at a single orthopaedic journal; generalizability to other journals and other fields of medicine is unknown.

(doi:10.1001/jama.2016.11014; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) THURSDAY, SEPTEMBER 22, 2016

Media Advisory: To contact Victor R. Fuchs, Ph.D., email Adam Gorlick at agorlick@stanford.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.14398

In a Viewpoint published online by JAMA, Victor R. Fuchs, Ph.D., Henry J. Kaiser Professor Emeritus, Stanford University, Stanford, Calif., discusses the narrowing life-expectancy gap between the U.S. black and white populations and points out categories of disease and death that could further narrow the gap.

“In recent decades the U.S. black population has experienced substantial gains in life expectancy, now becoming closer to the life expectancy of the white population. Between 1995 and 2014, the increase in black life expectancy at birth was more than double the white increase: a gain of 6.0 years from 69.6 years to 75.6 years for black people compared with a gain of 2.5 years from 76.5 years to 79.0 for white people,” Dr. Fuchs writes.

In a study of changes in black-white differences in life expectancy from 1999 to 2013, Kochanek et al found that the gap in life-expectancy closed by 2.3 years, from 5.9 to 3.6 years, and that gains in just 5 causes (cardiovascular disease, cancer, human immunodeficiency virus (HIV), unintentional injuries, and perinatal conditions) accounted for almost 60 percent of the decrease in the black-white life expectancy gap.

Dr. Fuchs writes that to make a significant contribution to reducing the current gap between black and white life expectancy, a cause must have substantial number of deaths and a significantly higher age-adjusted death rate for blacks than for whites. Eleven causes of death meet those 2 criteria: HIV; homicide; essential hypertension & hypertensive renal disease; nephritis, nephrotic syndrome, and nephrosis; cancer of prostate; diabetes mellitus; septicemia; cancer of breast; cerebrovascular disease; cancer of colon, rectum, anus; and diseases of the heart. “With a goal of reducing the 17 percent differential in black-white all-cause deaths, it appears that progress in just a few causes probably will not be enough; progress in many causes will be required.”

“The very high black-white ratio for age-adjusted homicide deaths suggests another opportunity for reducing the racial gap in all-cause deaths, but realization of the opportunity depends more on public health measures such as gun control than on medical care. Essential hypertension, prostate cancer, kidney disease (nephritis, nephrotic syndrome, nephrosis), and septicemia all have high black-white age-adjusted mortality ratios and a substantial number of total deaths, posing a challenge to research, prevention, diagnosis, and therapeutic interventions. Continued progress in preventing and treating heart disease in black men could also make a substantial contribution because of the large number of these men who die young relative to white men and black women.”

“In 1944, Gunner Myrdahl, Nobel Prize winner in Economics, wrote that black-white differences were arguably the United States’ biggest problem. Major advances in life expectancy that bring blacks closer to whites is a significant contribution to its solution.”

(doi:10.1001/jama.2016.14398; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 20, 2016

Media Advisory: To contact John M. Jakicic, Ph.D., email Anthony Moore at amm114@pitt.edu.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.12858

Among overweight or obese young adults, the addition of a wearable technology device (that provided feedback on physical activity) to a standard behavioral intervention resulted in less weight loss over 24 months, according to a study appearing in the September 20 issue of JAMA.

Effective long-term treatments are needed to address the obesity epidemic. There is wide availability of commercial technologies for physical activity and diet. These technologies include wearable devices to monitor physical activity, with many also including an interface to monitor diet. These technologies may provide a method to improve longer-term weight loss; however, there are limited data on the effectiveness of such technologies for modifying health behaviors long term.

John M. Jakicic, Ph.D., of the University of Pittsburgh, and colleagues randomly assigned study participants to a standard behavioral weight loss intervention (n = 233) or technology-enhanced weight loss intervention (n = 237). Participants (body mass index [BMI], 25 to <40; age range, 18-35 years; 29 percent nonwhite; 77 percent women) were placed on a low-calorie diet, prescribed increases in physical activity, and had group counseling sessions. At 6 months, the interventions added telephone counseling sessions, text message prompts, and access to study materials on a website. Also at 6 months, participants randomized to the standard intervention group initiated self-monitoring of diet and physical activity using a website, and those randomly assigned to the enhanced intervention group were provided with a wearable device and accompanying web interface to monitor diet and physical activity. The trial was conducted between October 2010 and October 2012.

Seventy-five percent of participants completed the study. The researchers found that weight change at 24 months differed significantly by intervention group. Estimated average weights for the enhanced intervention group were 212 lbs. at study entry and 205 lbs. at 24 months, resulting in an average weight loss of about 7.7 lbs. Corresponding values for the standard intervention group were 210 lbs. at baseline and 197 lbs. at 24 months, for an average loss of 13 lbs. At 24 months, weight loss was 5.3 lbs. lower in the enhanced intervention group compared with the standard intervention group.

Both groups had significant improvements in body composition, fitness, physical activity, and diet, with no significant difference between groups.

“Devices that monitor and provide feedback on physical activity may not offer an advantage over standard behavioral weight loss approaches,” the authors write.

The researchers add that the reason for the difference in weight loss between the groups warrants further investigation.

(doi:10.1001/jama.2016.12858; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 20, 2016

Media Advisory: To contact Robert J. Boyle, M.D., Ph.D., email r.boyle@nhs.net. To contact editorial author Matthew Greenhawt, M.D., M.B.A., M.Sc., email Hollon Kohtz at Hollon.Kohtz@childrenscolorado.org.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.12623

In a study appearing in the September 20 issue of JAMA, Robert J. Boyle, M.D., Ph.D., of Imperial College London, and colleagues examined the evidence that timing of allergenic food introduction during infancy influences risk of allergic or autoimmune disease.

Infant feeding guidelines have moved away from advising parents to delay the introduction of allergenic food, but most guidelines do not yet advise early feeding of such foods. Timing of introduction of allergenic foods to the infant diet may influence the risk of allergic or autoimmune disease, but the evidence for this has not been comprehensively examined.

For this study, the researchers conducted a systematic review and meta-analysis of intervention trials and observational studies that evaluated timing of allergenic food introduction during the first year of life and reported allergic or autoimmune disease or allergic sensitization. Of 16,289 original titles screened, data were extracted from 204 titles reporting 146 studies.

The authors found evidence that timing of introduction of certain allergenic foods to the infant diet was associated with risk of allergic disease but not risk of autoimmune disease. There was moderate-certainty evidence that introduction of egg to the infant diet at age 4 to 6 months was associated with reduced egg allergy and introduction of peanut at age 4 to 11 months was associated with reduced peanut allergy compared with later introduction of these foods. Absolute risk reduction for a population with 5.4 percent incidence of egg allergy was 24 cases per 1,000 population. Absolute risk reduction for a population with 2.5 percent incidence of peanut allergy was 18 cases per 1,000 population.

There was low-certainty evidence that fish introduction before age 6 to 12 months was associated with reduced allergic rhinitis and very low-certainty evidence that fish introduction before age 6 to 9 months was associated with reduced allergic sensitization. There was high-certainty evidence that timing of gluten introduction was not associated with celiac disease risk, and timing of allergenic food introduction was not associated with other outcomes.

The authors note that these systematic review findings should not automatically lead to new recommendations to feed egg and peanut to all infants. “The imprecise effect estimates, issues regarding indirectness, and inconclusive trial sequential analysis findings all need to be considered, together with a careful assessment of the safety and acceptability of early egg and peanut introduction in different populations.”

(doi:10.1001/jama.2016.12623; the study is available pre-embargo to the media at the For the Media website)

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

Editorial: Early Allergen Introduction for Preventing Development of Food Allergy

“The rigorous, comprehensive meta-analysis by Ierodiakonou and colleagues is an important addition to the evidence regarding food allergy prevention,” writes Matthew Greenhawt, M.D., M.B.A., M.Sc., of Children’s Hospital Colorado, Aurora, in an accompanying editorial.

“Their conclusions highlight that the 2008 guidelines to not delay introduction were correct. Delay of introduction of these foods may be associated with some degree of potential harm, and early introduction of selected foods appears to have a well-defined benefit. These important points should resonate with allergy specialists, primary care physicians, and other health care professionals who care for infants, as well as obstetricians caring for pregnant mothers, all of whom are important stakeholders in effectively conveying the message that guidance to delay allergen introduction is outdated.”

(doi:10.1001/jama.2016.12715; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 20, 2016

Media Advisory: To contact Hilary D. Marston, M.D., M.P.H., email niaidnews@niaid.nih.gov.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.11764

Antimicrobial resistance poses significant challenges for current clinical care, and the modified use of antimicrobial agents and public health interventions, coupled with new antimicrobial strategies, may help reduce the effect of multidrug-resistant organisms in the future, according to a study appearing in the September 20 issue of JAMA.

Antibiotics have revolutionized the practice of medicine by enabling breakthroughs across the spectrum of clinical medicine, including safer childbirth, surgical procedures and organ transplantation. However, antimicrobial resistance (AMR) threatens to impede and even reverse some of this progress. In the United States, AMR organisms cause more than 2 million infections and are associated with approximately 23,000 deaths each year. In Europe, AMR is associated with approximately 25,000 deaths annually.

Anthony S. Fauci, M.D., Hilary D. Marston, M.D., M.P.H., of the National Institutes of Health, Bethesda, Md., and colleagues conducted a study to identify factors associated with AMR, the current epidemiology of important resistant organisms, and possible solutions to the AMR problem. Databases were searched for articles and entries related to AMR, focusing on epidemiology, clinical effects of AMR, discovery of novel agents to treat AMR bacterial infections, and nonpharmacological strategies to eliminate or modify AMR bacteria. In addition, selected health policy reports and public health guidance documents were reviewed. Of 217 articles, databases, and reports identified, 103 were selected for review.

The authors summarize that the increase in AMR has been driven by a diverse set of factors, including inappropriate antibiotic prescribing and sales, use of antibiotics outside of the health care sector, and genetic factors intrinsic to bacteria. The problem has been exacerbated by inadequate economic incentives for pharmaceutical development of new antimicrobial agents. A range of specific AMR concerns, including carbapenem- and colistin-resistant gram-negative organisms, pose a clinical challenge. Alternative approaches to address the AMR threat include new methods of antibacterial drug identification and strategies that neutralize virulence factors.

“Since bacterial resistance to antibiotics is inevitable, researchers must respond with innovative strategies to identify and develop new drug candidates, vaccines, and other prophylactic immune interventions and create novel treatment methods that are less likely than typical antibiotics to result in resistance,” the researchers write.

“Although advances in biomedical research hold promise for efforts to prevent and treat AMR, many of these technologies are in the earliest stages of discovery. Meanwhile, effective action can slow the spread and mitigate the negative effects of resistant bacteria today. Medical professionals and facilities have an important role to play, through implementation of antimicrobial stewardship programs, reduction in inappropriate prescribing, immunization against bacterial and viral pathogens, and robust infection control measures including enhanced surveillance for resistant organisms.”

“National plans, such as the President’s National Strategy for Combating Antibiotic Resistant Bacteria, lay out more comprehensive approaches, drawing on contributions from health care practitioners, biomedical researchers, and the pharmaceutical and agricultural sectors (among others). Analogous international efforts, overseen by the World Health Organization, are also under way. These programs require committed and concerted implementation to realize their promise. Without a coordinated response, the postantibiotic age presaged by so many is a distinct and unwelcome possibility,” the authors conclude.

(doi:10.1001/jama.2016.11764; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 20, 2016

Media Advisory: To contact Bradley D. Stein, M.D., Ph.D., email Warren Robak at robak@rand.org.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.10542

In a study appearing in the September 20 issue of JAMA, Bradley D. Stein, M.D., Ph.D., of RAND Corporation, Pittsburgh, and colleagues examined patient censuses of buprenorphine prescribers to determine whether patient limits have been a barrier to buprenorphine treatment.

Buprenorphine, a medication effective in treating individuals with opioid use disorders, can be prescribed in the United States by addiction specialists or by physicians who complete an 8-hour course and obtain a U.S. Drug Enforcement Administration waiver. Waivered prescribers have been restricted to treating up to 30 patients with an opioid use disorder concurrently; after a year, physicians could request that the limit be increased to 100 patients. Policy makers have prioritized increasing capacity to provide buprenorphine to fight the opioid epidemic but lack adequate information about how to do so effectively.

The researchers used a database that contains pharmacy retail transactions from more than 80 percent of pharmacies nationwide, including high-volume national chain pharmacies, resulting in information on approximately 90 percent of prescriptions filled at retail pharmacies in the United States. Data from 7 states with the most buprenorphine-waivered physicians (California, Florida, Massachusetts, Michigan, New York, Pennsylvania, Texas) were analyzed.

The study included 3,234 buprenorphine prescribers with 245,016 patients receiving a new prescription of buprenorphine from 2010-2013. The authors found that the monthly patient censuses for buprenorphine-prescribing physicians were substantially below patient limits; more than 20 percent treated 3 or fewer patients, and fewer than 10 percent treated more than 75 patients. The median treatment duration (53 days) was lower than expected given clinical recommendations of maintenance treatment for up to 12 months and evidence linking longer treatment to better outcomes.

“Novice prescribers cite insufficient access to more experienced prescribers and insufficient access to substance abuse counseling for patients as barriers to treating more patients. Such barriers might be addressed by web-based or tele-counseling for patients and by programs providing mentoring and telephone consultation from more experienced prescribers. Strategies to help current prescribers treat more patients safely and effectively could complement policy initiatives designed to increase access to treatment by increasing patient limits and number of waivered prescribers,” the authors write.

(doi:10.1001/jama.2016.10542; the study is available pre-embargo to the media at the For the Media website)

Editor’s Note: The work was supported by a grant from the National Institute on Drug Abuse of the National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 20, 2016

Media Advisory: To contact Jacques-Eric Gottenberg, M.D., Ph.D., email jacques-eric.gottenberg@chru-strasbourg.fr.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.13512

Among patients with rheumatoid arthritis previously treated with anti-tumor necrosis factor (TNF) drugs but with insufficient response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was a second anti-TNF medication, according to a study appearing in the September 20 issue of JAMA.

Tumor necrosis factor α (TNF-α) inhibitors have improved the quality of life for patients with rheumatoid arthritis who show insufficient response to the agent methotrexate. However, as many as one-third of patients have persistent disease activity and insufficient response to anti-TNF agents, and there is little guidance on choosing the next treatment.

Jacques-Eric Gottenberg, M.D., Ph.D., of the Universite de Strasbourg, Strasbourg, France, and colleagues randomly assigned 300 patients with rheumatoid arthritis with persistent disease activity and an insufficient response to anti-TNF therapy to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment. The choice of the biologic prescribed within each randomized group was left to the treating clinician.

Of the 300 randomized patients, 269 (90 percent) completed the study. At week 24, 101 of 146 patients (69 percent) in the non-TNF group and 76 (52 percent) in the second anti-TNF group achieved a good or moderate response. A measure of disease activity was lower in the non-TNF group than in the second anti-TNF group. At weeks 24 and 52, more patients in the non-TNF group vs the second anti-TNF group showed low disease activity (45 percent vs 28 percent at week 24; and 41 percent vs 23 percent at week 52).

“Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but considered for a second medication due to inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks. However, a second anti-TNF drug to treat these patients was often effective in producing a clinical improvement,” the authors conclude.

(doi:10.1001/jama.2016.13512; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) MONDAY, SEPTEMBER 19, 2016

Media Advisory:  For media inquiries, email press@cms.hhs.gov.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.12717

In a study published online by JAMA, Laura A. Dummit, M.S.P.H., of The Lewin Group, Falls Church, Va., and colleagues evaluated whether Bundled Payments for Care Improvement (BPCI) was associated with a greater reduction in Medicare payments without loss of quality of care for lower extremity joint (primarily hip and knee) replacement episodes initiated in BPCI-participating hospitals that are accountable for total episode payments (for the hospitalization and Medicare-covered services during the 90 days after discharge).

The Centers for Medicare & Medicaid Services (CMS) launched the BPCI initiative in 2013 to test whether linking payments for services provided during an episode of care can reduce Medicare payments, while maintaining or improving quality. Hospitals, physician group practices, postacute care providers such as skilled nursing facilities and home health agencies, and other entities were invited to participate in BPCI, which holds them accountable for Medicare payments for services provided during an episode of care triggered by a hospitalization. As with other alternative payment models, BPCI is designed to reward clinicians and facilities that deliver care more efficiently and effectively.

For this study, the researchers estimated the change in outcomes for Medicare fee-for-service beneficiaries who had a lower extremity joint replacement at a BPCI-participating hospital between the baseline (October 2011 through September 2012) and intervention (October 2013 through June 2015) periods and beneficiaries with the same surgical procedure at matched comparison hospitals.

There were 29,441 lower extremity joint replacement episodes in the baseline period and 31,700 in the intervention period at 176 BPCI-participating hospitals, compared with 29,440 episodes in the baseline period (768 hospitals) and 31,696 episodes in the intervention period (841 hospitals) at matched comparison hospitals. The authors found that average Medicare payments for a lower extremity joint replacement hospitalization and the 90-day postdischarge period declined $1,166 more for Medicare beneficiaries with episodes initiated in a BPCI-participating hospital than for beneficiaries in a comparison hospital. The lower Medicare payments were primarily due to reduced use of institutional postacute care. Claims-based quality measures, including unplanned readmissions, emergency department visits, and mortality, were not statistically different between the BPCI and comparison populations.

“This analysis of lower extremity joint replacement episodes, which account for more than 450,000 Medicare hospitalizations per year, significantly extends the evidence on the use of payment incentives to reduce spending for episodes of care, while maintaining or improving quality,” the researchers write.

“Further studies are needed to assess longer-term follow-up as well as patterns for other types of clinical care.”

(doi:10.1001/jama.2016.12717; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 13, 2016

Media Advisory: To contact Vivian S. Lee, M.D., Ph.D., M.B.A., email Julie Kiefer at julie.kiefer@hsc.utah.edu. To contact editorial co-author Thomas H. Lee, M.D., M.Sc., email Jon Siegal at PressGaney@mslgroup.com.

To place an electronic embedded link to this study and editorial in your story  These links will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.12226  http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.11698

Implementing an analytic tool that allocates clinical care costs and quality measures to individual patient encounters was associated with significant improvements in value of care for 3 designated outcomes—total joint replacement, laboratory testing among medical inpatients, and sepsis management, according to a study appearing in the September 13 issue of JAMA.

Fee-for-service payment models reward care volume over value. Under fee-for-service models, health care costs are increasing at a rate of 5.3 percent annually, accounted for 17.7 percent of the U.S. gross domestic product in 2014, and are projected to increase to 19.6 percent of the gross domestic product by 2024. Value-based payment models and alternative payment models incentivize the provision of efficient, high-quality, patient-centered care through financial penalties and rewards. Under alternative payment models, clinicians will theoretically deliver higher-quality care that results in better outcomes, fewer complications, and reduced health care spending. To implement alternative payment models effectively, physicians must understand actual care costs (not charges) and outcomes achieved for individual patients with defined clinical conditions—the level at which they can most directly influence change.

Vivian S. Lee, M.D., Ph.D., M.B.A., of the University of Utah, Salt Lake City, and colleagues measured quality and outcomes relative to cost from 2012 to 2016 at University of Utah Health Care. Clinical improvement projects included total hip and knee joint replacement, hospitalist (physicians who practice in the inpatient setting) laboratory utilization, and management of sepsis. Physicians were given access to a tool with information about outcomes, costs (not charges), and variation and partnered with process improvement experts.

From July 1, 2014 to June 30, 2015, there were 1.7 million total patient visits, including 34,000 inpatient discharges. For total joint replacement, a composite quality index was 54 percent at baseline (n = 233 encounters) and 80 percent 1 year into the implementation (n = 188 encounters). Compared with the baseline year, average direct costs were 7 percent lower in the implementation year and 11 percent lower in the post-implementation year.

The initiative to reduce hospitalist laboratory testing was associated with 11 percent lower costs, with no significant change in length of stay and a lower 30-day readmission rate. A sepsis intervention was associated with reduced average times to anti-infective administration following fulfillment of systemic inflammatory response syndrome criteria in patients with infection (7.8 hours to 3.6 hours).

“Implementation of a multifaceted value-driven outcomes tool to identify high variability in costs and outcomes in a large single health care system was associated with reduced costs and improved quality for 3 selected clinical projects. There may be benefit for individual physicians to understand actual care costs (not charges) and outcomes achieved for individual patients with defined clinical conditions,” the authors write.

(doi:10.1001/jama.2016.12226; the study is available pre-embargo to the media at the For the Media website)

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

Editorial: From Volume to Value in Health Care

Michael E. Porter, Ph.D., of Harvard Business School, Boston, and Thomas H. Lee, M.D., M.Sc., of Press Ganey, Wakefield, Mass., comment on the findings of this study in an accompanying editorial.

“The study by Lee and colleagues in this issue of JAMA is an impressive and important step forward, not just for the University of Utah Health Care system but for the rest of U.S. health care and other health care systems around the world that are focused on value. The findings offer proof of concept that improving value by patient condition can lead to lower costs and better quality—at the same time. There is much to be done and the road is long, but the report by Lee and colleagues points out how the path begins.”

(doi:10.1001/jama.2016.11698; the editorial is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 13, 2016

Media Advisory: To contact Gillian D. Sanders, Ph.D., call Ellen de Graffenreid at 919-660-1922 or email ellen.degraffenreid@duke.edu. To contact editorial author Mark S. Roberts, M.D., M.P.P., email Allison Hydzik at hydzikam@upmc.edu.

To place an electronic embedded link to this study and editorial in your story  These links will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.12195  http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.12844

The Second Panel on Cost-Effectiveness in Health and Medicine reviewed the current status of the field of cost-effectiveness analysis and developed a new set of recommendations, with major changes including the recommendation to perform analyses from 2 reference case perspectives and to provide an impact inventory to clarify included consequences, according to an article appearing in the September 13 issue of JAMA.

In 1993, the U.S. Public Health Service convened a panel of 13 nongovernment scientists and scholars with expertise in economics, clinical medicine, ethics, and statistics to review the state of cost-effectiveness analysis and to develop recommendations for its conduct and use in health and medicine. The primary goals were to improve the quality of cost-effectiveness analyses and promote comparability across studies. In 1996, the original Panel on Cost-Effectiveness in Health and Medicine published its findings in a series of articles in JAMA and in a book. The panel emphasized that the growing field of cost-effectiveness analysis provided an opportunity to rationalize health policy if the technique and its application were well understood and implemented. Since publication of the report, researchers have advanced the methods of cost-effectiveness analysis, and policy makers have experimented with its application. The need to deliver health care efficiently and the importance of using analytic techniques to understand the clinical and economic consequences of strategies to improve health have increased in recent years.

Gillian D. Sanders, Ph.D., of the Duke Clinical Research Institute, Durham, N.C., Peter J. Neumann, Sc.D., of the Center for the Evaluation of Value and Risk in Health, Tufts Medical Center, Boston, and colleagues representing the Second Panel on Cost-Effectiveness in Health and Medicine, reviewed the state of the field and provided recommendations to improve the quality of cost-effectiveness analyses. The panel developed recommendations by consensus. These recommendations were then reviewed by invited external reviewers and through a public posting process.

Among the Key Recommendations:

— The concept of a “reference case” and a set of standard methodological practices that all cost-effectiveness analyses should follow to improve quality and comparability;

— All cost-effectiveness analyses should report two reference case analyses: one based on a health care sector perspective and another based on a societal perspective;

— Use of an “impact inventory,” which is a structured table that contains consequences (both inside and outside the formal health care sector), intended to clarify the scope and boundaries of the two reference case analyses.

“The goal of the Second Panel was to promote the continued evolution of cost-effectiveness analysis and its use to support judicious, efficient, and fair decisions regarding the use of health care resources,” the authors write.

“Cost-effectiveness analysis can help inform decisions about how to apply new or existing tests, therapies, and preventive and public health interventions so that they represent a judicious use of resources. It also can help to fill gaps in the evidence about the estimated population-level public health effect of such interventions, and can support decisions to disinvest in older interventions for which there are more cost-effective alternatives. Cost-effectiveness analysis provides a framework for comparing the relative value of different interventions, along with information that can help decision makers sort through alternatives and decide which ones best serve their programmatic and financial needs.”

(doi:10.1001/jama.2016.12195; the study is available pre-embargo to the media at the For the Media website)

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

Editorial: The Next Chapter in Cost-effectiveness Analysis

“This chapter in the development of a solid methodological foundation for the use of cost-effectiveness analysis [CEA] is an informative, rigorous, and welcome addition. The Second Panel has updated the specific recommendations to incorporate a significant amount of important advances that have resolved many methodological questions posed by the first panel,” writes Mark S. Roberts, M.D., M.P.P., of the University of Pittsburgh Graduate School of Public Health, in an accompanying editorial.

“Although this work represents an important step along the way to enhancing the applicability and acceptance of CEA as a tool that can inform policy decisions, it is not sufficient. Hopefully the next chapter will include expanded use of CEA as 1 of many inputs for decisions about health care resources. An important task toward that goal will be the education of decision makers, including politicians, that the amount of resources to spend on health care is not unlimited, and that CEA can be an important tool in making resource allocation decisions more transparent and explicit, rather than hidden and ad hoc.”

(doi:10.1001/jama.2016.12844; the editorial is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 13, 2016

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

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.10349

In a study appearing in the September 13 issue of JAMA, Jouke T. Annema, M.D., Ph.D., of the Academic Medical Center, Amsterdam, and colleagues examined five-year survival after endosonography vs mediastinoscopy for mediastinal nodal staging of lung cancer.

Accurate mediastinal nodal staging is crucial in the management of non-small cell lung cancer (NSCLC) because it directs therapy and has prognostic value. The Assessment of Surgical Staging vs Endosonographic Ultrasound in Lung Cancer (ASTER) trial compared mediastinoscopy (surgical staging) with an endosonographic staging strategy (which combined the use of endobronchial and transesophageal ultrasound followed by mediastinoscopy if negative). The endosonographic strategy was significantly more sensitive for diagnosing mediastinal nodal metastases than surgical staging (94 percent endosonographic strategy vs 79 percent surgical strategy). If mediastinal staging is improved, more patients should receive optimal treatment and might survive longer.

This analysis evaluated survival in ASTER. Of 241 patients with potentially resectable NSCLC, 123 were randomized to endosonographic staging and 118 to surgical staging in 4 tertiary referral centers. Survival data were obtained through patient records, death registers, or contact with general practitioners. Survival data at 5 years were obtained for 237 of 241 patients. The prevalence of mediastinal nodal metastases was 54 percent in the endosonographic strategy group and 44 percent in the surgical strategy group. Survival at 5 years was 35 percent for the endosonographic strategy vs 35 percent for the surgical strategy. The estimated median survival was 31 months for the endosonographic strategy vs 33 months for the surgical strategy.

“Why did improved mediastinal staging not lead to improved survival? Missing data occurred in less than 2 percent and therefore are an unlikely source of bias. However, ASTER was powered to detect a difference in diagnostic sensitivity, not survival, as reflected by the wide confidence intervals. If a survival difference between the strategies exists, it is likely to be small and a larger sample size may be needed to detect it. However, randomized trials to detect a survival difference based on staging strategy are not likely to be conducted as the endosonographic strategy is now advised in clinical guidelines,” the authors write.

(doi:10.1001/jama.2016.10349; the study is available pre-embargo to the media at the For the Media website)

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

# # #

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 13, 2016

Media Advisory: To contact Josep Rodes-Cabau, M.D., call Jean-François Huppé at 418-656-7785 or email Jean-Francois.Huppe@dc.ulaval.ca.

To place an electronic embedded link to this study in your story  This link will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.12347

Among patients undergoing transcatheter aortic valve replacement, younger age, male sex, history of diabetes mellitus, and moderate to severe residual aortic regurgitation were significantly associated with an increased risk of infective endocarditis, and patients who developed endocarditis had high rates of in-hospital mortality and 2-year mortality, according to a study appearing in the September 13 issue of JAMA.

Infective endocarditis (an infection caused by bacteria that enter the bloodstream and settle in the heart valve or heart lining) following surgical valve replacement occurs in 1 percent to 6 percent of patients and is associated with a high risk of illness and death. Transcatheter aortic valve replacement (TAVR) has emerged as a therapeutic option for patients with aortic stenosis (narrowing) who are considered to be at high or prohibitive surgical risk. Limited data exist on clinical characteristics and outcomes of patients who had infective endocarditis after undergoing TAVR.

Josep Rodes-Cabau, M.D., of Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada and colleagues analyzed data from the Infectious Endocarditis after TAVR International Registry, which included patients with definite infective endocarditis after TAVR from 47 centers from Europe, North America, and South America between June 2005 and October 2015. A total of 250 cases of infective endocarditis occurred in 20,006 patients after TAVR (incidence, 1.1 percent per person-year; median age, 80 years; 64 percent men). Median time from TAVR to infective endocarditis was 5.3 months.

The characteristics associated with higher risk of progressing to infective endocarditis after TAVR was younger age (78.9 years vs 81.8 years), male sex (62 percent vs 50 percent), diabetes mellitus (42 percent vs 30 percent), and moderate to severe aortic regurgitation (22 percent vs 15 percent). Health care-associated infective endocarditis was present in 53 percent of patients. Enterococci species and Staphylococcus aureus were the most frequently isolated microorganisms (25 percent and 23 percent, respectively). The in-hospital mortality rate was 36 percent, and surgery was performed in 15 percent of patients during the infective endocarditis episode. In-hospital mortality was associated with heart failure and acute kidney injury. The 2-year mortality rate was 67 percent.

“The rate of infective endocarditis after TAVR observed in the present study is similar to that reported for surgical prosthetic valve endocarditis, therefore, supports the lack of reduction in the rate of prosthetic valve infective endocarditis after TAVR despite less invasive nature of TAVR compared with surgical valve replacement. This study confirms the high rate of morbidity and mortality of infective endocarditis after TAVR and provides novel information about the timing, causative organisms, and predictive factors of infective endocarditis in this particular population. This information may help the clinicians identify patients at higher risk and aid in implementing appropriate preventive measures,” the authors write.

(doi:10.1001/jama.2016.12347; the study is available pre-embargo to the media at the For the Media website)

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

# # #