EMBARGOED FOR RELEASE: 1 P.M. (ET) FRIDAY, APRIL 21, 2017

Media Advisory: To contact Aminu K. Bello, Ph.D., email Tony Kirby at tony@tonykirby.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.2017.4046

JAMA

Survey results representing 125 countries indicate there is significant variability in the current capacity for kidney care across the world, including important gaps in services, workforce and available technologies, such as facilities for kidney disease detection and management, according to a study published by JAMA. The study is being released to coincide with its presentation at the International Society of Nephrology Global Kidney Policy Forum.

Kidney disease is a substantial worldwide clinical and public health problem. Acute kidney injury (AKI) and chronic kidney disease (CKD) are linked to high health care costs, poor quality of life, and serious adverse health outcomes (including cardiovascular disease, kidney failure requiring kidney replacement therapy, infection, depression, and death). However, information about available care worldwide is limited.

Aminu K. Bello, Ph.D., of the University of Alberta, Edmonton, Canada, and colleagues analyzed the results of a multinational questionnaire survey conducted from May to September 2016 by the International Society of Nephrology (ISN) in 130 ISN-affiliated countries with sampling of key stakeholders (national nephrology society leadership, policy makers, and patient organization representatives).

Responses were received from 125 of 130 countries (96 percent), representing an estimated 93 percent (6.8 billion) of the world’s population. The researchers found that there was wide variation for kidney care in country readiness, capacity, and response in terms of service delivery, financing, workforce, information systems, and leadership and governance. Overall, 95 percent of countries had facilities for hemodialysis, 76 percent for peritoneal dialysis, and 75 percent for kidney transplantation. In contrast, 94 percent of countries in Africa had facilities for hemodialysis, 45 percent for peritoneal dialysis, and 34 percent for kidney transplantation. For CKD monitoring in primary care, serum creatinine with estimated glomerular filtration rate was reported as always available in 18 percent of countries, and proteinuria measurements in 8 percent of countries.

Hemodialysis was funded publicly and free at the point of care delivery in 42 percent of countries; peritoneal dialysis, in 51 percent of countries, and transplantation services in 49 percent of countries. The number of nephrologists was variable and was low (less than 10 per million population) in Africa, the Middle East, South Asia, and Oceania and South East Asia regions. Health information system (renal registry) availability was limited, particularly for AKI (eight countries [7 percent]) and nondialysis CKD (9 countries [8 percent]). International AKI and CKD guidelines were reportedly accessible in 45 percent and 52 percent of countries, respectively. There was relatively low capacity for clinical studies in developing nations.

“The status of kidney health care as suggested by this study indicates that the health systems of many countries face substantial challenges in closing the large gaps that are reported to currently exist in meeting the health needs of people with AKI and CKD around the world,” the authors write. “Assuming the responses accurately reflect the status of kidney care in the respondent countries, the findings may be useful to inform efforts to improve the quality of kidney care worldwide.”

For more details and to read the full study, please visit the For The Media website.

(doi:10.1001/jama.2017.4046)

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

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For more information, contact JAMA Network Media Relations at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, APRIL 18, 2017

Media Advisory: To contact Gail Hayward, D.Phil., M.R.C.G.P., email gail.hayward@phc.ox.ac.uk.

Related video: There is a JAMA Report video story on this study available for use in your report. Broadcast-quality downloadable video files, B-roll, scripts and other images are available under embargo at this link. Please contact JAMA Network Media Relations at mediarelations@jamanetwork.org if there are questions.

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JAMA

In patients with a sore throat that didn’t require immediate antibiotics, a single capsule of the corticosteroid dexamethasone didn’t increase the likelihood of complete symptom resolution after 24 hours, and although more patients taking the steroid reported feeling completely better after 48 hours, a role for steroids to treat sore throats in primary care is uncertain, according to a study published by JAMA.

Acute sore throat is one of the most common symptoms among patients presenting to primary care. Adults in the United States made an estimated 92 million visits to doctors for sore throats between 1997 and 2010, an average of 6.6 million visits annually. Antibiotics are prescribed at 60 percent of UK primary care sore throat consultations, despite national guidelines advising against prescriptions. There is a need to find alternative strategies that reduce symptoms and antibiotic consumption.

Gail Hayward, D.Phil., M.R.C.G.P., of the University of Oxford, United Kingdom, and colleagues randomly assigned adults with sore throat not requiring immediate antibiotics to a single oral dose of 10 mg of dexamethasone or placebo. The trial was conducted in 42 family practices in South and West England.

Of 565 eligible randomized participants (median age, 34 years), 288 received dexamethasone and 277 placebo. The researchers found that at 24 hours, participants receiving dexamethasone were not more likely than those receiving placebo to have complete symptom resolution. Results were similar among those who were not offered an antibiotic prescription and those who were offered a delayed antibiotic prescription. At 48 hours, more participants receiving dexamethasone than placebo (35 percent versus 27 percent) had complete symptom resolution, which was also observed in patients not offered delayed antibiotics. There were no significant differences in other outcomes such as days missed from work or school and adverse events.

The authors note that uncertainty remains about the role of oral corticosteroids for patients presenting in primary care with sore throat. “Corticosteroids may have clinical benefit in addition to antibiotics for severe sore throat, for example, to reduce hospital admissions of those patients who are unable to swallow fluids or medications. There have been no trials of corticosteroid use involving these patient groups.”

(doi:10.1001/jama.2017.3417; 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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, APRIL 18, 2017

Media Advisory: To contact Simone N. Vigod, M.D., M.Sc., F.R.C.P.C., email Lindsay Jolivet at lindsay.jolivet@wchospital.ca. To contact Brian M. D’Onofrio, Ph.D., email Kevin Fryling at kfryling@iu.edu.

Related material: The editorial, “Disentangling Maternal Depression and Antidepressant Use During Pregnancy as Risks for Autism in Children,” by Tim F. Oberlander, M.D., F.R.C.P.C., University of British Columbia, Vancouver, and Lonnie Zwaigenbaum, M.Sc., M.D., F.R.C.P.C., University of Alberta, Edmonton, also is available at the For The Media website.

To place an electronic embedded link to these studies in your story  These links will be live at the embargo time: http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2017.3415  http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2017.3413

JAMA

Two studies published by JAMA examine the risk of autism and other adverse birth outcomes among women who use antidepressants during pregnancy.

Previous studies suggesting a higher risk of childhood autism spectrum disorder associated with antidepressant exposure during pregnancy may have been skewed by other factors that can influence the outcomes. Simone N. Vigod, M.D., M.Sc., F.R.C.P.C., of Women’s College Hospital, Toronto, and colleagues evaluated the association between serotonergic antidepressant exposure (a selective serotonin reuptake inhibitor or selective norepinephrine reuptake inhibitor medication) during pregnancy and childhood autism spectrum disorder, using a variety of methods to address those potential confounding factors.

The study included 35,906 births at an average gestational age of 38.7 weeks (average maternal age, 27 years; average duration of follow-up was 5 years). In the 2,837 pregnancies (7.9 percent) exposed to antidepressants, 2 percent of children were diagnosed with autism spectrum disorder. The researchers found that children exposed to serotonergic antidepressants were at higher risk for autism spectrum disorder compared with unexposed children, but after adjusting for confounding, the difference was no longer statistically significant. The association was also not significant when exposed children were compared with unexposed siblings.

“Although a causal relationship cannot be ruled out, the previously observed association may be explained by other factors,” the authors write.

For more details and to read the full study, please visit the For The Media website.

(doi:10.1001/jama.2017.3415)

In another study, Brian M. D’Onofrio, Ph.D., of Indiana University, Bloomington, and colleagues evaluated alternative hypotheses for associations between first-trimester antidepressant exposure and birth and neurodevelopmental problems. Previous studies may not have adequately accounted for confounding.

The study included 1,580,629 Swedish offspring (1.4 percent [n = 22,544] with maternal first-trimester self-reported antidepressant use) born between 1996 and 2012 and followed up through 2013.

The researchers found that after accounting for measured pregnancy, maternal and paternal traits, and all (unmeasured) stable familial characteristics shared by siblings, maternal antidepressant use during the first trimester of pregnancy, compared with no exposure, was associated with a small increased risk of preterm birth but no increased risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder (ADHD).

“These results are consistent with the hypothesis that genetic factors, familial environmental factors, or both account for the population-wide associations between first-trimester antidepressant exposure and these outcomes,” the authors write.

For more details and to read the full study, please visit the For The Media website.

(doi:10.1001/jama.2017.3413)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, APRIL 18, 2017

Media Advisory: To contact Michael J. Pencina, Ph.D., email Amara Omeokwe at amara.omeokwe@duke.edu.

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JAMA

Fewer people could be recommended for primary prevention statin therapy, including many younger adults with high long-term cardiovascular disease risk, if physicians adhere to the 2016 U.S. Preventive Services Task Force (USPSTF) recommendations for statin therapy compared with the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, according to a study published by JAMA.

The 2013 ACC/AHA guidelines substantially expanded the population eligible for statin therapy by basing recommendations on an elevated 10-year risk of atherosclerotic cardiovascular disease (ASCVD). The 2016 USPSTF recommendations for primary prevention statin therapy  increased the estimated ASCVD risk threshold for patients (including those with diabetes) and required the presence of at least one cardiovascular risk factor (i.e., hypertension, diabetes, dyslipidemia, or smoking) in addition to elevated risk.

Michael J. Pencina, Ph.D., of Duke University, Durham, N.C., and colleagues used National Health and Nutrition Examination Survey (NHANES) data (2009-2014) to assess statin eligibility under the 2016 USPSTF recommendations vs the 2013 ACC/AHA cholesterol guidelines among a nationally representative sample of 3,416 U.S. adults ages 40 to 75 years with fasting lipid data and triglyceride levels of 400 mg/dl or less, without prior cardiovascular disease (CVD).

The researchers found that if fully implemented, the USPSTF recommendations would be associated with statin initiation in 16 percent of adults without prior CVD, in addition to the 22 percent of adults already taking lipid-lowering therapy; in comparison, the ACC/AHA guidelines would be associated with statin initiation in an additional 24 percent of patients. Among the 8.9 percent of individuals in the primary prevention population who would be recommended for statins by ACC/AHA guidelines but not by USPSTF recommendations, 55 percent would be adults ages 40 to 59 years with an average 30-year cardiovascular risk greater than 30 percent, and 28 percent would have diabetes.

“If these estimates are accurate and assuming these proportions can be projected to the U.S. population, there could be an estimated 17.1 million vs 26.4 million U.S. adults with a new recommendation for statin therapy, based on the USPSTF recommendations vs the ACC/AHA guideline recommendations, respectively—an estimated difference of 9.3 million individuals,” the authors write.

“Alternative approaches to augmenting risk-based cholesterol guidelines, including those that explicitly incorporate potential benefit of therapy, should be considered.”

(doi:10.1001/jama.2017.3416; 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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, APRIL 11, 2017

Media Advisory: To contact Rebecca F. Gottesman, M.D., Ph.D., email Vanessa McMains at vmcmain1@jhmi.edu.

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.2017.3090

JAMA

Among adults who entered a study more than 25 years ago, an increasing number of midlife vascular risk factors, such as obesity, high blood pressure, diabetes, high cholesterol and smoking, were associated with elevated levels of brain amyloid (protein fragments linked to Alzheimer disease) later in life, according to a study published by JAMA.

Midlife vascular risk factors have been associated with late-life dementia. Whether these risk factors directly contribute to brain amyloid deposition is less well understood. Rebecca F. Gottesman, M.D., Ph.D., of the Johns Hopkins University School of Medicine, Baltimore, and colleagues examined data from 346 participants without dementia at study entry who have been evaluated for vascular risk factors and markers since 1987-1989 and with PET scans in 2011-2013 as part of the Atherosclerosis Risk in Communities (ARIC)-PET Amyloid Imaging Study. Positron emission tomography image analysis was completed in 2015. Vascular risk factors at ARIC study entry (age 45-64 years; risk factors included body mass index 30 or greater, current smoking, hypertension, diabetes, and total cholesterol 200 mg/dL or greater) were evaluated in models that included age, sex, race, APOE genotype, and educational level.

The availability of imaging biomarkers for brain amyloid allows the study of individuals before the development of dementia and thereby allows consideration of the relative contributions of vascular disease and amyloid to cognition, as well as the contribution of vascular disease to amyloid deposition.

The researchers found that a cumulative number of midlife vascular risk factors were associated with elevated brain amyloid. Relationships between vascular risk factors and brain amyloid did not differ by race. The results were not supportive of a significant difference in association among people who were or were not carriers of an APOE ε4 allele (a variant of a gene associated with increased risk for Alzheimer disease). Late-life vascular risk factors were not associated with late-life brain amyloid deposition.

“These data support the concept that midlife, but not late-life, exposure to these vascular risk factors is important for amyloid deposition,” the authors write. “These findings are consistent with a role of vascular disease in the development of AD.”
(doi:10.1001/jama.2017.3090)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, APRIL 11, 2017

Media Advisory: To contact Paul G. Shekelle, M.D., Ph.D., email Nikki Baker at nikki.baker@va.gov.

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.2017.3086

JAMA

Among patients with acute low back pain, spinal manipulation therapy was associated with modest improvements in pain and function at up to 6 weeks, with temporary minor musculoskeletal harms, according to a study published by JAMA.

Back pain is among the most common symptoms prompting patients to seek care. Lifetime prevalence estimates of low back pain exceed 50 percent. Treatments for acute back pain include analgesics, muscle relaxants, exercises, physical therapy, heat, spinal manipulative therapy (SMT) and others, with none established as superior to others. Paul G. Shekelle, M.D., Ph.D., of the West Los Angeles Veterans Affairs Medical Center, Los Angeles, and colleagues conducted a review and meta-analysis of previous studies to assess the effectiveness and harms associated with spinal manipulation compared with other nonmanipulative therapies for adults with acute (six weeks or less) low back pain.

Of 26 eligible randomized clinical trials (RCTs) identified, 15 RCTs (1,711 patients) provided moderate-quality evidence that SMT has a statistically significant association with improvements in pain. Twelve RCTs (1,381 patients) produced moderate-quality evidence that SMT has a statistically significant association with improvements in function. No RCT reported any serious adverse event. Minor transient adverse events such as increased pain, muscle stiffness, and headache were reported 50 percent to 67 percent of the time in large case series of patients treated with SMT. Heterogeneity (differences) in study results was large, and was not explained by type of clinician performing SMT, type of manipulation, study quality, or whether SMT was given alone or as part of a package of therapies.

The authors write that the size of the benefit of SMT for acute low back pain is about the same as the benefit from nonsteroidal anti-inflammatory drugs, according to the Cochrane review on this topic.

(doi:10.1001/jama.2017.3086; the study is available pre-embargo at the For the Media website)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, APRIL 11, 2017

Media Advisory: To contact Jan Bollen, L.L.M., M.D., email jan@janbollen.be.

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.2017.0729

JAMA

An estimated 10 percent of all patients undergoing euthanasia in Belgium could potentially donate at least one organ, according to a study published by JAMA.

The practice of organ donation after euthanasia is controversial and currently only allowed in Belgium and the Netherlands. It requires patients to undergo euthanasia in the hospital, and organ donation is performed after circulatory death. Donation after euthanasia could potentially help ease the shortage of organs for transplantation. It is unknown how many of these patients would be medically suitable to donate organs. Jan Bollen, L.L.M., M.D., of Maastricht University Medical Center, Maastricht, the Netherlands, and colleagues calculated the number of potential organ donors among persons undergoing euthanasia by excluding patients because of certain criteria (age, medical condition).

In 2015, 2,023 patients underwent euthanasia in Belgium and 1,288 people were on the Belgian organ transplantation waiting list. The researchers found that an estimated maximum of 10 percent of all patients undergoing euthanasia could potentially donate at least one organ, with 684 organs potentially available for donation. In 2015, 260 deceased donor kidneys were donated; if 400 kidneys were donated by patients undergoing euthanasia, the potential number of kidneys available for donation could more than double.

The authors note that medical suitability only implies that a patient is a possible organ donor. “Whether the patient is also willing to donate, and is willing to die in hospital, must be carefully ascertained.”

“Even if only a small percentage of the patients undergoing euthanasia donated an organ, donation after euthanasia could potentially help reduce the waitlists for organ donation. Nevertheless, it is essential that the primary goal of organ donation after euthanasia remains the same as for any patient donating an organ—to enable patients to carry out their last will of donating organs to help other people, after their own death.”

(doi:10.1001/jama.2017.0729; the study is available pre-embargo at the For the Media website)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, APRIL 4, 2017

Media Advisory: To contact Olivier Baud, M.D., Ph.D., email olivier.baud@rdb.aphp.fr.

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.2017.2692

JAMA

The administration of low-dose hydrocortisone to extremely preterm infants was not associated with any adverse effects on neurodevelopmental outcomes at 2 years of age, according to a study published by JAMA.

Early low-dose hydrocortisone treatment in very preterm infants has been reported to improve survival without bronchopulmonary dysplasia (a form of chronic lung disease), but its safety with regard to neurodevelopment remains to be assessed. Olivier Baud, M.D., Ph.D., of Robert Debre Children’s Hospital, Paris, and colleagues analyzed data from the PREMILOC trial, in which infants born between 24 0/7 weeks and 27 6/7 weeks of gestation and before 24 hours of postnatal age were randomly assigned to receive either placebo or low-dose hydrocortisone  injection.

Of neonates screened, 523 were assigned to hydrocortisone (n = 256) or placebo (n = 267) and 406 survived to 2 years of age. A total of 379 patients (93 percent) were evaluated at a median corrected age of 22 months. The researchers found no statistically significant difference in patients without neurodevelopmental impairment (73 percent in the hydrocortisone group vs 70 percent in the placebo group), with mild neurodevelopmental impairment (20 percent in the hydrocortisone group vs 18 percent in the placebo group), or with moderate to severe neurodevelopmental impairment (7 percent in the hydrocortisone group vs 11 percent in the placebo group). The incidence of cerebral palsy or other major neurological impairments was not significantly different between groups.

“Further randomized studies are needed to provide definitive assessment of the neurodevelopmental safety of hydrocortisone in extremely preterm infants,” the authors write.

(doi:10.1001/jama.2017.2692; the study is available pre-embargo at the For the Media website)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, APRIL 4, 2017

Media Advisory: To contact Amanda H. Cook, M.A., email Kristin Samuelson at kristin.samuelson@northwestern.edu.

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.2017.0627

JAMA

Cognitively average elderly adults demonstrated greater annual whole-brain cortical volume loss over 18 months compared with SuperAgers, adults 80 years and older with memory ability at least as good as that of average middle-age adults, according to a study published by JAMA.

SuperAgers have a significantly thicker brain cortex than their same-age peers with average-for-age memory, which is unusual as age-related cortical atrophy is considered “normal” and often associated with cognitive decline in nondemented older adults. Amanda H. Cook, M.A., of Northwestern University, Chicago, and colleagues quantitated rates of cortical volume change over 18 months in 24 SuperAgers and 12 cognitively average elderly adults to examine if SuperAgers may resist age-related brain atrophy.

The researchers found that both groups demonstrated statistically significant average annual percent whole-brain cortical volume loss (SuperAgers, 1.06 percent; cognitively average elderly, 2.24 percent). However, the annual percentage change in whole-brain cortical volume loss was significantly greater in cognitively average elderly compared with SuperAgers.

The authors note that the possibility that SuperAgers were endowed with larger brains throughout life cannot be ruled out.

“As SuperAgers represent a rare cognitive phenotype, study findings require validation in larger samples with broader representation of demographic and socioeconomic features. The functional effect of the lesser decline of cortical volume in SuperAgers over 18 months is difficult to surmise. However, the between-group unadjusted difference in annual percentage change of 1.2 percent is similar in magnitude to the difference demonstrated in previous studies between nondemented and demented adults older than 50 years, suggesting that differences of this magnitude may have functional consequences. The factors that underlie the rate of age-related cortical volume loss are unknown; however, research on SuperAgers provides unique opportunities for exploring their biological foundations,” the authors write.

(doi:10.1001/jama.2017.0627; the study is available pre-embargo at the For the Media website)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 28, 2017

Media Advisory: To contact Aaron Reuben, M.E.M., email Karl Bates at karl.bates@duke.edu.

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.2017.1712

JAMA

Children who had higher blood lead levels at age 11 were more likely to have lower cognitive function, IQ and socioeconomic status when they were adults at age 38, according to a study published by JAMA.

Exposure to lead in childhood may adversely affect brain health and disrupt cognitive development. It is unknown if this disruption results in cognitive decline and altered socioeconomic trajectories by midlife. Aaron Reuben, M.E.M., of Duke University, Durham, N.C., and colleagues conducted a study that included participants of the Dunedin Multidisciplinary Health and Development Study, an investigation of health and behavior of individuals born between April 1972 and March 1973 in Dunedin, New Zealand. Childhood lead exposure ascertained as blood lead levels were measured at age 11 years. High blood lead levels were observed among children from all socioeconomic status levels in this group.

Of 1,037 original participants, 1,007 were alive at age 38 years, of whom 565 (56 percent) had been lead tested at age 11 years. Among the findings:

— Childhood blood lead level was associated with lower adult IQ scores nearly three decades later, reflecting cognitive decline following childhood lead exposure.

— Childhood blood lead level was associated with lower adult socioeconomic status, reflecting downward social mobility following childhood lead exposure.

— The relationship between childhood lead exposure and downward social mobility by midlife was partially but significantly mediated by cognitive decline following childhood lead exposure.

“The results indicate that childhood exposures to lead can be linked with cognitive and socioeconomic outcomes detectable more than 3 decades later,” the authors write. “For communities that have experienced collective lead exposure events and for countries where lead exposures are still routinely above health standards, the findings raise questions about the reasonable duration and magnitude of public responses. Just as the problem of toxic lead exposure in homes appears to persist, so too do the poor outcomes associated with such exposure. Short-lived public responses to community lead exposure may not be enough.”

(doi:10.1001/jama.2017.1712)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 28, 2017

Media Advisory: To contact Joan Lappe, Ph.D., R.N., email Cindy Workman at CindyWorkman@creighton.edu.

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.2017.2115

JAMA

Among healthy postmenopausal women, supplementation with vitamin D₃ and calcium compared with placebo did not result in a significantly lower risk of cancer after four years, according to a study published by JAMA.

About 40 percent of the U.S. population will have a cancer diagnosis at some point during their lives. Evidence suggests that low vitamin D status may increase the risk of cancer, and considerable interest exists in the potential role of vitamin D for prevention of cancer. Joan Lappe, Ph.D., R.N., of the Creighton University Schools of Nursing and Medicine, Omaha, and colleagues randomly assigned 2,303 healthy postmenopausal women 55 years or older (average age, 65 years) to the treatment group (n=1,156; 2,000 IU/d of vitamin D₃ and 1,500 mg/d of calcium) or to the placebo group (n=1,147). Duration of treatment was four years. The researchers examined the incidence of all-type cancer (excluding nonmelanoma skin cancers).

A new diagnosis of cancer was confirmed in 109 participants, 45 (3.89 percent) in the vitamin D₃ + calcium group and 64 (5.58 percent) in the placebo group (difference, 1.69 percent). Incidence over four years was 0.042 in the treatment group and 0.060 in the placebo group. There was no statistically significant difference between the treatment groups in incidence of breast cancer.

Adverse events potentially related to the study included kidney stones (16 participants in the treatment group and 10 in the placebo group) and elevated serum calcium levels (six in the treatment group and two in the placebo group).

The authors write that one explanation for lack of statistically significant differences between the treatment groups in all-type cancer incidence is that the study group had higher baseline vitamin D (serum 25-hydroxyvitamin D) levels compared with the U.S. population.

“Further research is necessary to assess the possible role of vitamin D in cancer prevention.”

(doi:10.1001/jama.2017.2115; the study is available pre-embargo at the For the Media website)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 28, 2017

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.2017.1462

JAMA

The U.S. Preventive Services Task Force (USPSTF) has concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for celiac disease in asymptomatic persons. The report appears in the March 28 issue of JAMA.

This is an I statement, indicating that evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

Celiac disease is caused by an immune response in persons who are genetically susceptible to dietary gluten, a protein complex found in wheat, rye, and barley. Ingestion of gluten by persons with celiac disease causes inflammatory damage to the small intestine, which can cause gastrointestinal and nongastrointestinal illness. The estimated prevalence among U.S. adults ranges from 0.40% to 0.95%.

To issue a new recommendation, the USPSTF reviewed the evidence on the accuracy of screening for celiac disease in asymptomatic adults, adolescents, and children; the potential benefits and harms of screening vs not screening and targeted vs universal screening; and the benefits and harms of treatment of screen-detected celiac disease.

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.

Detection

The USPSTF found inadequate evidence regarding the accuracy of screening tests for celiac disease in asymptomatic populations.

Benefits of Early Detection and Intervention or Treatment

The USPSTF found inadequate evidence on the effectiveness of screening for celiac disease in asymptomatic adults, adolescents, and children with regard to morbidity, mortality, or quality of life. The USPSTF also found inadequate evidence on the effectiveness of targeted screening in persons who are at increased risk for celiac disease (e.g., persons with family history or other risk factors), or on the effectiveness of treatment of screen-detected, asymptomatic celiac disease to improve morbidity, mortality, or quality of life compared with no treatment or treatment initiated after clinical diagnosis.

Harms of Early Detection and Intervention or Treatment

The USPSTF found inadequate evidence on the harms of screening for or treatment of celiac disease.

Summary

The USPSTF found inadequate evidence on the accuracy of screening for celiac disease, the potential benefits and harms of screening vs not screening or targeted vs universal screening, and the potential benefits and harms of treatment of screen-detected celiac disease.

(doi:10.1001/jama.2017.1462; the full report is available pre-embargo to the media at the For the Media website)

JAMA encourages use of the following summary video with the embed code credit below:

Screening for Celiac Disease: USPSTF Recommendation Statement

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[Credit: Video courtesy of The JAMA Network ®; © 2017 American Medical Association]

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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 28, 2017

Media Advisory: To contact Andreas Obermair, M.D., email obermair@powerup.com.au.

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JAMA

Researchers found similar rates of disease-free survival and no difference in overall survival among women who received a laparoscopic or abdominal total hysterectomy for stage I endometrial cancer, according to a study published by JAMA.

Endometrial cancer is the most common gynecological cancer in developed countries. Standard treatment involves removal of the uterus, tubes, ovaries and lymph nodes. Laparoscopic hysterectomy is associated with less morbidity and results in better recovery than open operations, but it is not known if the operation results in survival outcomes equivalent to abdominal hysterectomy. Andreas Obermair, M.D., of the University of Queensland, Herston, Australia, and colleagues randomly assigned 760 women with stage I endometrial cancer to either total abdominal hysterectomy (TAH; n = 353) or total laparoscopic hysterectomy (TLH; n = 407).

Disease-free survival at 4.5 years was 81.6 percent with total laparoscopic hysterectomy vs 81.3 percent with total abdominal hysterectomy (between-group difference, 0.3 percent), meeting the prespecified criteria for equivalence (a margin of seven percent or less). There was no statistically significant between-group difference in recurrence of endometrial cancer (7.9 percent in the TAH group vs 8.1 percent in the TLH group) or in overall survival (6.8 percent in the TAH group vs 7.4 percent in the TLH group).

“These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer,” the authors write.

(doi:10.1001/jama.2017.2068)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 28, 2017

Media Advisory: To contact Emily S. Jungheim, M.D., M.S.C.I., email Diane Williams at williamsdia@wustl.edu.

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JAMA

Women with insurance coverage for in vitro fertilization (IVF) were more likely to attempt IVF again and had a higher probability of live birth than women who self-paid for IVF, according to a study published by JAMA.

Because IVF is expensive and often cost-prohibitive, some states mandate IVF insurance coverage. Emily S. Jungheim, M.D., M.S.C.I., of the Washington University in St. Louis School of Medicine, and colleagues examined the cumulative probability of live birth among women with and without IVF insurance coverage at the Fertility and Reproductive Medicine Center at Washington University, a center located near the border between Illinois, which mandates IVF coverage, and Missouri, which does not. Women initiating IVF from 2001 through 2010 were included and observed through 2014.

Of the 1,572 women in the sample, 56 percent had IVF insurance coverage (40 percent mandated, 60 percent nonmandated) and 44 percent were self-pay. The two groups did not differ medically, but patients with coverage were younger. The researchers found that IVF coverage status was not associated with probability of live birth in individual cycles. However, the proportion returning for a second cycle if unsuccessful in the first cycle was 0.703 among women with coverage compared with 0.516 among self-paying women. The average cumulative live birth probability after four cycles for women with coverage, 0.585, was significantly higher than that for self-paying women, 0.505. The difference in cumulative live birth rates adjusting for patient risk factors between insured and self-pay patients after four cycles narrowed to 0.054, but was still significant.

“These findings demonstrate legislation mandating IVF insurance coverage may improve the delivery and outcomes of fertility treatments,” the authors write.

(doi:10.1001/jama.2017.0727; the study is available pre-embargo at the For the Media website)

Editor’s Note: This work was supported by a grant from the Women’s Reproductive Health Research Program of the National Institutes of Health. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 21, 2017

Media Advisory: To contact Daniel A. Barocas, M.D., M.P.H., email Craig Boerner at craig.boerner@Vanderbilt.Edu. To contact Ronald C. Chen, M.D., M.P.H., email Laura Oleniacz at loleniac@email.unc.edu.

To place an electronic embedded link to these studies in your story  These links will be live at the embargo time: http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2017.1704  http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2017.1652

JAMA

Two studies published by JAMA examine the adverse effects and quality of life as reported by men with localized prostate cancer who chose treatment, observation or active surveillance.

In one study, Daniel A. Barocas, M.D., M.P.H., of Vanderbilt University Medical Center, Nashville, and colleagues included 2,550 men (average age, 64 years) with localized prostate cancer who received treatment with radical prostatectomy (n=1,523; 60 percent), external beam radiation therapy (EBRT; n=598; 24 percent), or chose active surveillance (n=429; 17 percent). Patient-reported outcomes were collected via survey at enrollment and 6, 12, and 36 months after enrollment.

The researchers found that radical prostatectomy was associated with a greater decrease in sexual function and urinary incontinence than either EBRT or active surveillance after three years and was associated with fewer urinary irritative symptoms than active surveillance; however, no meaningful differences existed in either bowel or hormonal function beyond 12 months or in other domains of health-related quality-of-life measures.

“This information may facilitate patient counseling regarding the expected harms of contemporary treatments and their possible effect on quality of life,” the authors write.
In another study, Ronald C. Chen, M.D., M.P.H., of the University of North Carolina at Chapel Hill, and colleagues included 1,141 men with newly diagnosed prostate cancer to compare quality of life (QOL) after radical prostatectomy (n=469; 41 percent), external beam radiotherapy (n= 249; 22 percent), and brachytherapy (n=109; 9.6 percent) vs active surveillance (n=314; 28 percent). Median age was 66 to 67 years across groups. Quality of life was assessed by surveys at baseline (pretreatment) and 3, 12, and 24 months after the treatment date, with scores given on measures of function of various domains.

The researchers found that compared with active surveillance, average sexual dysfunction scores worsened by three months for patients who received radical prostatectomy, external beam radiotherapy, and brachytherapy. Compared with active surveillance at three months, worsened urinary incontinence was associated with radical prostatectomy; acute worsening of urinary obstruction and irritation with external beam radiotherapy and brachytherapy; and worsened bowel symptoms with external beam radiotherapy. By 24 months, average scores between treatment groups vs active surveillance were not significantly different in most domains.

“These findings can be used to promote treatment decisions that incorporate individual preferences,” the authors write.

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 21, 2017

Media Advisory: To contact J. Bradley Layton, Ph.D., email David Pesci at dpesci@email.unc.edu.

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JAMA

Televised direct-to-consumer advertising for testosterone therapies increased across U.S. metropolitan areas between 2009 and 2013, and exposure to these ads was associated with greater testosterone testing, new use of testosterone therapies, and use without recent testing, according to a study published by JAMA.

Testosterone therapies were originally approved to treat hypogonadism (a condition in which the body doesn’t produce enough testosterone) resulting from the disruption of the pituitary-hypothalamus-gonadal axis. Now many men take or are prescribed testosterone for age-related reduced testosterone levels or nonspecific symptoms without pathological hypogonadism. Testosterone initiation increased substantially in the United States from 2000 to 2013, especially among men without clear indications. Direct-to-consumer advertising (DTCA) also increased during this time.

Bradley Layton, Ph.D., of the University of North Carolina at Chapel Hill, and colleagues examined associations between televised DTCA and testosterone testing and initiation in 75 designated market areas (DMAs) in the United States. Monthly testosterone advertising ratings were linked to DMA-level testosterone use data from 2009-2013 derived from commercial insurance claims. Associations between DTCA and testosterone testing, initiation, and initiation without recent baseline tests were estimated. Initiation of testosterone gels, patches, injections, or implants was defined as pharmacy dispensing or in-office receipt identified through procedure codes of testosterone following six months without prior testosterone receipt.

Of 17,228,599 commercially insured men in the 75 DMAs, 1,007,990 (average age, 50 years) had new serum testosterone tests and 283,317 (average age, 52 years) initiated testosterone treatment. Advertising intensity varied by geographic region and time, with the highest intensity seen in the southeastern United States and with months ranging from no ad exposures to an average of 13.6 exposures per household. Nonbranded advertisements were common prior to 2012, with branded advertisements becoming more common during and after 2012. Each household advertisement exposure was associated with a monthly increase in rates of new testosterone testing, initiation, and initiation without a recent test.

“Although the average increase in testosterone rates associated with a single ad exposure was less than 1 percent, advertisements were widespread and frequent during the study period; with cumulative ad exposures of close to 200 in some DMAs, DTCA was associated with substantial overall increases in testosterone testing and initiation,” the authors write.

“While other studies have demonstrated associations between DTCA and increasing medication use, this study demonstrates increases in potentially inappropriate use and increasing initiation during a time when most testosterone use was of questionable value for age-related testosterone decreases without strong evidence of benefit,” the researchers write. “This study complements many others that suggest the contribution that DTCA may make in the early adoption of recently approved treatments whose risk-benefit profile may be quite unclear.”

(doi:10.1001/jama.2016.21041; the study is available pre-embargo at the For the Media website)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 21, 2017

Media Advisory: To contact Maria Makrides, B.Sc., B.N.D., Ph.D., email maria.makrides@sahmri.com.

JAMA

Longer-term follow-up of a randomized trial found strong evidence for the lack of benefit of prenatal DHA supplementation on IQ in children at 7 years of age, according to a study published by JAMA.

The sale of prenatal supplements with docosahexaenoic acid (DHA) continues to increase, despite little evidence of benefit to offspring neurodevelopment. Maria Makrides, B.Sc., B.N.D., Ph.D., of the South Australian Health and Medical Research Institute, Adelaide, Australia and colleagues randomized pregnant women to receive 800 mg of DHA daily or a placebo during the last half of pregnancy and found no group differences in cognitive, language, and motor development at 18 months of age. At 4 years of age there was no benefit of DHA supplementation in general intelligence, language, and executive functioning, and a possible negative effect on parent-rated behavior and executive functioning. This follow-up was designed to evaluate the effect of prenatal DHA on intelligence quotient (IQ) at 7 years, the earliest age at which adult performance can be indicated.

Of those eligible, 543 children (85 percent) participated in the 7-year follow-up. Average IQ of the DHA and control groups did not differ (98.31 for the DHA group vs 97.32 for the control group). Direct assessments consistently demonstrated no significant differences in language, academic abilities, or executive functioning.  Although perceptual reasoning was slightly higher in the DHA group, parent-reported behavioral problems and executive dysfunction were worse with prenatal DHA supplementation.

The authors note that the small but consistent negative effects of prenatal DHA on behavior and executive functioning at 7 and 4 years may reflect true effects, although effect sizes were small and neurodevelopmental diagnoses did not differ between groups.

(doi:10.1001/jama.2016.21303; the study is available pre-embargo at the For the Media website)

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

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EMBARGOED FOR RELEASE: 2 P.M. (ET) TUESDAY, MARCH 21, 2017

Media Advisory: To contact corresponding author Victor J. Dzau, M.D., of the National Academy of Medicine, email Jennifer Walsh at jwalsh@nas.edu.

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JAMA

A new publication from the National Academy of Medicine identifies eight policy directions as vital to the nation’s health and fiscal future, including action priorities and essential infrastructure needs that represent major opportunities to improve health outcomes and increase efficiency and value in the health system, according to the article published online by JAMA.

The U.S. health and health care system is at a critical juncture. Discussions about repeal of the Affordable Care Act (ACA) introduce considerable uncertainty into the health care marketplace and for the 20 million people newly insured during the past six years, but the range of health and health care challenges spans far beyond the coverage provisions of the ACA. Initiatives directed to certain strategic and infrastructure priorities are vital to achieve better health at lower cost.

The National Academy of Medicine convened more than 150 of the nation’s leading health and policy experts to author 19 articles that addressed pressing policy challenges and opportunities, and offered specific recommendations for achieving progress. Summarized in this publication are the most potentially transformative crosscutting policy directions identified from those assessments, indicated as action priorities and infrastructure needs essential to addressing these priorities. These strategies and priorities are offered to assist the new administration and others leading change throughout health and health care at national, state, local, and institutional levels.

Summary of Findings

The U.S. health system faces major challenges. Health care costs remain high at $3.2 trillion spent annually, of which an estimated 30 percent is related to waste, inefficiencies, and excessive prices; health disparities are persistent and worsening; and the health and financial burdens of chronic illness and disability are straining families and communities. Promising opportunities and knowledge to achieve change exist. Across the 19 discussion papers examined, eight policy directions were identified as vital to the nation’s health and fiscal future, including four action priorities and four essential infrastructure needs.

Action Priorities

— Pay for value—deliver better health and better results for all

— Empower people—democratize action for health

— Activate communities—collaborate to mobilize resources for health progress

— Connect care—implement seamless digital interfaces for best care

Essential Infrastructure Needs

— Measure what matters most—use consistent core metrics to sharpen focus and performance

— Modernize skills—train the workforce for 21st-century health care and biomedical science

—  Accelerate real-world evidence—derive evidence from each care experience

— Advance science—forge innovation-ready clinical research processes and partnerships

The action priorities recurred across the articles as direct and strategic opportunities to advance a more efficient, equitable, and patient- and community-focused health system. The essential infrastructure needs were the most commonly cited foundational elements to ensure progress.

“As the new U.S. administration and Congress chart the future of health and health care for the United States, and as health leaders across the country contemplate future directions for their programs and initiatives, their leadership and strategic investment in these priorities will be essential for achieving significant progress,” the authors write.

(doi:10.1001/jama.2017.1964)

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

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EMBARGOED FOR RELEASE: 4 A.M. (ET) TUESDAY, MARCH 21, 2017

Media Advisory: To contact Hannah Wunsch, M.D., M.Sc., email Sybil Millar at sybil.millar@sunnybrook.ca.

 
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JAMA

Patients with septic shock admitted to hospitals affected by the 2011 shortage of the drug norepinephrine had a higher risk of in-hospital death, according to a study published online by JAMA. The study is being released to coincide with its presentation at the 37th International Symposium on Intensive Care and Emergency Medicine.

Drug shortages are an increasing problem, but their effect on patient care and outcomes has rarely been reported. In February 2011, the U.S. Food and Drug Administration (FDA) announced a severe nationwide shortage of norepinephrine caused by production interruptions at three drug manufacturers that persisted until February 2012. Norepinephrine is recommended as the first-line vasopressor (a drug that constricts [narrows] blood vessels, increasing blood pressure) for treatment of hypotension (abnormally low blood pressure) due to septic shock.

Hannah Wunsch, M.D., M.Sc., of Sunnybrook Health Sciences Centre, Toronto, and colleagues assessed changes to patient care and outcomes associated with the 2011 shortage of norepinephrine. The study included 26 U.S. hospitals with a baseline rate of norepinephrine use of at least 60 percent for patients with septic shock. The study group included adults with septic shock admitted to study hospitals between July 2008 and June 2013 (n = 27,835). Hospital-level norepinephrine shortage was defined as any quarterly (3-month) interval in 2011 during which the hospital rate of norepinephrine use decreased by more than 20 percent from baseline.

Among the patients with septic shock in hospitals that demonstrated at least one quarter of norepinephrine shortage in 2011, norepinephrine use declined from 77 percent of patients before the shortage to a low of 56 percent in the second quarter of 2011; phenylephrine was the most frequently used alternative vasopressor during this time. Compared with hospital admission with septic shock during quarters of normal use, hospital admission during quarters of shortage was associated with an increased rate of in-hospital mortality (9,283 of 25,874 patients [35.9 percent] vs 777 of 1,961 patients [39.6 percent], respectively; absolute risk increase = 3.7 percent).

The authors write that several factors may explain the observed associations between norepinephrine shortage and increased patient mortality, including that other specific vasopressors selected to replace norepinephrine may result in worse outcomes for patients with septic shock, and that observable decreases in norepinephrine use in the setting of shortage may be a marker of related unmeasured factors that affected patient outcomes, such as the absence of a dedicated shortage pharmacist to optimize distribution of limited supplies, delayed administration of vasopressors, or lack of clinician familiarity with dosing of alternative vasopressor agents.

(doi:10.1001/jama.2017.2841; the study is available pre-embargo at the For the Media website)

Editor’s Note: This study was supported by funds from the Herbert and Florence Irving Scholars Program at Columbia University. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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For more information, contact JAMA Network Media Relations at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 14, 2017

Media Advisory: To contact Ying Xian, M.D., Ph.D., email Sarah Avery at sarah.avery@duke.edu.

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.2017.1371

JAMA

Inadequate use of anticoagulation therapies was prevalent among patients with atrial fibrillation who experienced a stroke, according to a study appearing in the March 14 issue of JAMA.

Atrial fibrillation (AF) is an independent risk factor for stroke, increases stroke risk by a factor of 4 to 5, and accounts for 10 percent to 15 percent of all ischemic strokes. While the burden of AF-related stroke is high, AF is a potentially treatable risk factor. Numerous studies have demonstrated that vitamin K antagonists, such as warfarin, or non-vitamin K antagonist oral anticoagulants (NOACs), reduce the risk of ischemic stroke. Based on these data, current guidelines recommend adjusted-dose warfarin or NOACs over aspirin for stroke prevention in high-risk patients with AF.

Ying Xian, M.D., Ph.D., of the Duke University Medical Center, Durham, N.C., and colleagues conducted a study that included 94,474 patients who had an acute ischemic stroke and known history of AF admitted to hospitals participating in the Get With the Guidelines-Stroke program.

Of these patients:

• 84 percent were not receiving therapeutic anticoagulation prior to stroke
• 30 percent were not receiving any antithrombotic treatment prior to stroke
• 6 percent were receiving therapeutic warfarin
• 8 percent were receiving NOACs
• 40 percent were receiving antiplatelet therapy only

Therapeutic anticoagulation was associated with lower odds of moderate or severe stroke and lower odds of in-hospital mortality.

“Atrial fibrillation is a highly prevalent and important, but treatable, risk factor for stroke. Despite numerous international guideline recommendations, many patients fail to receive proper treatment for stroke prevention,” the authors write.

(doi:10.1001/jama.2017.1371; the study is available pre-embargo at the For the Media website)

Editor’s Note: This work was supported by an award from the Patient-Centered Outcomes Research Institute. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 14, 2017

Media Advisory: To contact Justine M. Naylor, Ph.D., email Justine.Naylor@sswahs.nsw.gov.au.

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.2017.1224

JAMA

Among patients with osteoarthritis undergoing total knee replacement and who have not experienced a significant early complication, the use of inpatient rehabilitation compared with a monitored home-based program did not improve mobility at 26 weeks after surgery, according to a study appearing in the March 14 issue of JAMA.

From 1980 to 2010, the prevalence of total knee replacement in the United States increased 11-fold. Formal rehabilitation programs, including inpatient programs, are often assumed to optimize recovery. Inpatient programs, however, have not been compared with any outpatient or home-based programs. Justine M. Naylor, Ph.D., of the University of New South Wales, Liverpool, Australia and colleagues randomly assigned patients with osteoarthritis undergoing total knee arthroplasty (replacement) to receive 10 days of hospital inpatient rehabilitation followed by an 8-week clinician-monitored home-based program (n = 81) or the home-based program alone (n = 84). There were 87 patients in an observational group, which included only the home-based program.

Among the measures analyzed, there was no significant difference in the 6-minute walk test between the inpatient rehabilitation and either of the two home program groups, nor in patient-reported pain and function, or quality of life. The number of postdischarge complications for the inpatient group was 12 vs nine among the home group, and there were no adverse events reported that were a result of trial participation.

“These findings do not support inpatient rehabilitation for this group of patients,” the authors write.

(doi:10.1001/jama.2017.1224; 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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 14, 2017

Media Advisory: To contact M. Sean Esplin, M.D., email Jess Gomez at jess.gomez@imail.org.

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JAMA

The use of two measures, fetal fibronectin (a protein) levels and transvaginal cervical length, had low predictive accuracy for spontaneous preterm birth among women who have not given birth before, according to a study appearing in the March 14 issue of JAMA.

Preterm birth, affecting approximately 1.2 percent of the deliveries in the United States, was responsible for 35 percent of the world’s 3.1 million annual neonatal deaths in 2006. Current strategies to identify women at risk are largely based on prior pregnancy outcomes, but risk assessment in women pregnant for the first time is difficult. The combination of transvaginal cervical length and fetal fibronectin levels to identify women at risk has been studied, with conflicting results.

Sean Esplin, M.D., of Intermountain Healthcare, Salt Lake City, and colleagues conducted a study that included 9,410 women without prior childbirth who had transvaginal cervical length and vaginal fetal fibronectin levels reviewed at two study visits four or more weeks apart.

Among these women, 474 (5 percent) had spontaneous preterm births, 335 (3.6 percent) had medically indicated preterm births, and 8,601 (91 percent) had term births. The researchers found that fetal fibronectin levels and transvaginal cervical length had poor predictive performance as screening tests for spontaneous preterm birth before 37 weeks. The most commonly used clinical cutoff for transvaginal cervical length (threshold of 25 mm or less) identified a minority (23 percent) of spontaneous preterm births before 37 weeks. The addition of fetal fibronectin levels to transvaginal cervical length measurement did not increase the predictive performance of transvaginal cervical length alone. Fetal fibronectin levels of 50 ng/mL or greater at 16 to 22 weeks identified 30 of 410 women (7.3 percent) with spontaneous preterm birth and 31 of 384 (8.1 percent) at 22 to 30 weeks.

“These findings do not support routine use of these tests in such women,” the authors write.

(doi:10.1001/jama.2017.1373; 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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 14, 2017

Media Advisory: To contact Matthew D. Snape, M.D., email matthew.snape@paediatrics.ox.ac.uk.

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JAMA

Immune responses to Ebola vaccines at one year after vaccination are examined in a new study appearing in the March 14 issue of JAMA.

The Ebola virus vaccine strategies evaluated by the World Health Organization in response to the 2014-2016 outbreak in West Africa included a heterologous primary and booster vaccination schedule of the adenovirus type 26 vector vaccine encoding Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia virus Ankara vector vaccine, encoding glycoproteins from Ebola, Sudan, Marburg, and Tai Forest viruses nucleoprotein (MVA-BN-Filo). These vaccines both used a ‘viral-vector’ approach, where a benign virus is modified to safely express key proteins of the target virus, in this case Ebola. This schedule has been shown to induce immune responses that persist for eight months after primary immunization, with 100 percent of vaccine recipients retaining Ebola virus glycoprotein-specific antibodies. A vaccine that provides durable immune responses is important in maintaining sustained protection against disease, both during outbreaks and outside of an outbreak for at-risk populations.

Matthew D. Snape, M.D., of the University of Oxford, United Kingdom, and colleagues conducted a trial that was performed in Oxford and enrolled healthy participants ages 18 to 50 years, who were randomized to four groups, each with 18 participants (3 placebo and 15 active vaccine). Of 75 active vaccine recipients, 64 attended follow-up at day 360. No serious adverse events were recorded from day 240 through day 360. All of the active vaccine recipients maintained Ebola virus-specific immunoglobulin G responses at day 360. To the authors’ knowledge, this is the longest duration follow-up for any heterologous primary and booster Ebola vaccine schedule.

“Immunity after heterologous primary and booster vaccination with Ad26.ZEBOV and MVA-BN-Filo persisted at 1 year. Although no correlate of protection has yet been established, Ebola virus glycoprotein-specific antibodies appear to play an important role in immunity. A strategy of preemptive use of an AD26.ZEBOV followed by MVA-BN-Filo immunization schedule in at-risk populations (where durability of immune response is likely to be of primary importance) may offer advantages over reactive use of single-dose vaccine regimens,” the authors write.

The researchers note that a limitation of the study is that it was conducted in a European population. “Immune responses may differ in a sub-Saharan African population; these vaccine candidates are being assessed in this region. Additional research is also warranted to explore the persistence of immunity beyond 1 year following immunization and response to booster doses of vaccine.”

(doi:10.1001/jama.2016.20644; 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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 7, 2017

Media Advisory: To contact Renata Micha, R.D., Ph.D., email Siobhan Gallagher at Siobhan.Gallagher@tufts.edu.

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JAMA

Nearly half of all deaths due to heart disease, stroke, and type 2 diabetes in the U.S. in 2012 were associated with suboptimal consumption of certain dietary factors, according to a study appearing in the March 7 issue of JAMA.

Dietary habits influence many risk factors for cardiometabolic health, including heart disease, stroke, and type 2 diabetes, which collectively pose substantial health and economic burdens. In the United States, associations of individual dietary factors with specific cardiometabolic diseases are not well established.

Renata Micha, R.D., Ph.D., of the Tufts Friedman School of Nutrition Science and Policy, Boston, and colleagues developed a model that used data from the National Health and Nutrition Examination Surveys (1999-2002; n = 8,104; 2009-2012; n = 8,516); estimated associations of diet and disease from studies and clinical trials; and estimated disease-specific national mortality from the National Center for Health Statistics. The researchers examined mortality due to heart disease, stroke, and type 2 diabetes in 2012 and the consumption of 10 foods/nutrients associated with cardiometabolic diseases: fruits, vegetables, nuts/seeds, whole grains, unprocessed red meats, processed meats, sugar-sweetened beverages (SSBs), polyunsaturated fats, seafood omega-3 fats, and sodium.

In 2012,702,308 cardiometabolic deaths occurred in U.S. adults. Of these, an estimated 45 percent (n=318,656 due to heart disease, stroke, and type 2 diabetes) were associated with suboptimal intakes of the 10 dietary factors. By sex, larger diet-related proportional mortality was estimated in men than in women, consistent with generally unhealthier dietary habits in men. Suboptimal diet was also associated with larger proportional mortality at younger vs older ages, among blacks and Hispanics vs whites, and among individuals with low and medium education vs high education.

The largest numbers of estimated diet-related cardiometabolic deaths were related to high sodium, low nuts/seeds, high processed meats, low seafood omega-3 fats, low vegetables, low fruits, and high SSBs. Between 2002 and 2012, as a percentage of annual cardiometabolic deaths, diet-associated mortality declined for polyunsaturated fats (-21 percent), nuts (-18 percent), and SSBs (-14.5 percent); remained relatively stable for whole grains, fruits, vegetables, seafood omega-3 fats, and processed meats; and increased for sodium (+5.8 percent) and unprocessed red meats (+14 percent).

“These results should help identify priorities, guide public health planning, and inform strategies to alter dietary habits and improve health,” the authors write.

(doi:10.1001/jama.2017.0947; 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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 7, 2017

Media Advisory: To contact Jian Zhang, M.D., Dr.P.H., email Jennifer Wise at jwise@georgiasouthern.edu.

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JAMA

Although weight gain has continued among U.S. adults, fewer report trying to lose weight, according to a study appearing in the March 7 issue of JAMA.

Socially acceptable body weight is increasing. If more individuals who are overweight or obese are satisfied with their weight, fewer might be motivated to lose unhealthy weight. Jian Zhang, M.D., Dr.P.H., of Georgia Southern University, Statesboro, and colleagues used data from the National Health and Nutrition Examination Survey (NHANES) to assess the trend in the percentage of adults who were overweight or obese and trying to lose weight during three periods: from 1988-1994, 1999-2004, and 2009-2014. Participants ages 20 to 59 years who were overweight (a body mass index [BMI] of 25 to less than 30) or obese (BMI 30 or greater) were included. The question of interest was “During the past 12 months, have you tried to lose weight?”

The study included 27,350 adults. Overweight and obesity prevalence increased throughout the study period, from 53 percent in 1988-1994 to 66 percent in 2009-2014. The percentages of adults who were overweight or obese and trying to lose weight declined during the same period, from 56 percent in 1988-1994 to 49 percent in 2009-2014. The largest decline occurred among black women, from 66 percent in 1988-1994 to 55 percent in 2009-2014. Black women also had the highest prevalence of obesity, and more than half of black women (55 percent) were obese in the 2009-2014 survey. Adjusted prevalence rates showed a significantly declining trend of reporting efforts to lose weight among white men and women, and black women.

The authors write that fewer adults trying to lose weight may be due to body weight misperception reducing the motivation to engage in weight loss efforts, or primary care clinicians not discussing weight issues with patients. Also, the longer adults live with obesity, the less they may be willing to attempt weight loss, in particular if they had attempted weight loss multiple times without success.

(doi:10.1001/jama.2016.20036; the study is available pre-embargo at the For the Media website)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 7, 2017

Media Advisory: To contact Eduardo Villamor, M.D., Dr.P.H., email Laurel Thomas-Gnagey at ltgnagey@umich.edu.

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JAMA

Among Swedish women, being overweight or obese early in pregnancy was associated with increased rates of cerebral palsy in children, according to a study appearing in the March 7 issue of JAMA.

Despite advances in obstetric and neonatal care, the prevalence of cerebral palsy has increased from 1998 through 2006 in children born at full term. Few preventable factors are known to affect the risk of cerebral palsy. Maternal overweight and obesity are associated with increased risks of preterm delivery, asphyxia-related neonatal complications, and congenital malformations, which in turn are associated with increased risks of cerebral palsy. It is uncertain whether risk of cerebral palsy in offspring increases with maternal overweight and obesity severity and what could be possible mechanisms.

Eduardo Villamor, M.D., Dr.P.H., of the University of Michigan, Ann Arbor, and colleagues conducted a study that included women with children born in Sweden from 1997 through 2011. Using national registries, children were followed for a cerebral palsy diagnosis through 2012.

Of 1,423,929 children included (average gestational age, 39.8 weeks), 3,029 were diagnosed with cerebral palsy over a median 7.8 years of follow-up. Analysis of the data indicated that maternal overweight (body mass index [BMI] of 25 to 29.9) and increasing grades of obesity (BMI 30 or greater) were associated with increasing rates of cerebral palsy. Results were statistically significant for children born at full term, who comprised 71 percent of all children with cerebral palsy, but not for preterm infants. An estimated 45 percent of the association between maternal BMI and rates of cerebral palsy in full-term children was mediated through asphyxia-related neonatal complications.

The authors note that although the effect of maternal obesity on cerebral palsy may seem small compared with other risk factors, the association is of public health relevance due to the large proportion of women who are overweight or obese. “The number of women with a BMI of 35 or more globally doubled from approximately 50 to 100 million from 2000 through 2010. In the United States, approximately half of all pregnant women have overweight or obesity at the first prenatal visit. Considering the high prevalence of obesity and the continued rise of its most severe forms, the finding that maternal overweight and obesity are related to rates of cerebral palsy in a dose-response manner may have serious public health implications.”

(doi:10.1001/jama.2017.0945; 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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, MARCH 7, 2017

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

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JAMA
The U.S. Preventive Services Task Force (USPSTF) has concluded that the current evidence is insufficient to assess the balance of benefits and harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women for the early detection and treatment of a range of gynecologic conditions. This statement does not apply to specific disorders for which the USPSTF already recommends screening (i.e., screening for cervical cancer with a Papanicolaou smear, screening for gonorrhea and chlamydia). The report appears in the March 7 issue of JAMA.

This is an I statement, indicating that evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

Many conditions that can affect women’s health are often evaluated through pelvic examination. These include but are not limited to malignant diseases, infectious diseases, and other benign conditions. Although the pelvic examination is a common part of the physical examination, it is unclear whether performing screening pelvic examinations in asymptomatic women reduces the risk of illness or death. To issue a new recommendation, the USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women 18 years and older who are not at increased risk for any specific gynecologic condition.

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.

Detection

The USPSTF found inadequate evidence on the accuracy of pelvic examination to detect a range of gynecologic conditions. Limited evidence from studies evaluating the use of screening pelvic examination alone for ovarian cancer detection generally reported low positive predictive values. Very few studies on screening for other gynecologic conditions with pelvic examination alone have been conducted, and the USPSTF found that these studies have limited generalizability to the current population of asymptomatic women seen in primary care settings in the United States.

Benefits of Screening

The USPSTF found inadequate evidence on the benefits of screening for a range of gynecologic conditions with pelvic examination. No studies were identified that evaluated the benefit of screening with pelvic examination on all-cause mortality, disease-specific morbidity or mortality, or quality of life.

Harms of Screening

The USPSTF found inadequate evidence on the harms of screening for a range of gynecologic conditions with pelvic examination. A few studies reported on false-positive rates for ovarian cancer, and false-negative rates. Among women who had abnormal findings on pelvic examination, five percent to 36 percent went on to have surgery. Very few studies reported false-positive and false-negative rates for other gynecologic conditions. No studies quantified the amount of anxiety associated with screening pelvic examinations.

Summary

Overall, the USPSTF found inadequate evidence on screening pelvic examinations for the early detection and treatment of a range of gynecologic conditions in asymptomatic, nonpregnant adult women.

(doi:10.1001/jama.2017.0807; 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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 28, 2017

Media Advisory: To contact Lucie M. Turcotte, M.D., M.P.H., M.S., email Caroline Marin at crmarin@umn.edu.

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 JAMA

Although the risk of subsequent malignancies for survivors of childhood cancer diagnosed in the 1990s remains increased, the risk is lower compared with those diagnosed in the 1970s, a decrease that is associated with a reduction in therapeutic radiation dose, according to a study appearing in the February 28 issue of JAMA.

The Childhood Cancer Survivor Study and other groups of childhood cancer survivors have reported extensively on the incidence of and risk factors for subsequent neoplasms (tumors). Therapeutic radiation has been strongly associated with development of subsequent tumors; however, links have also been identified between specific chemotherapeutic agents and the development of tumors. With this information, childhood cancer treatment has been modified over time with the hope of reducing subsequent tumor risk, while maintaining or improving 5-year survival.

Lucie M. Turcotte, M.D., M.P.H., M.S., of the University of Minnesota Medical School, Minneapolis, and colleagues conducted a study that included 23,603 five-year cancer survivors (average age at diagnosis, 7.7 years) from pediatric hospitals in the United States and Canada between 1970-1999, with follow-up through December 2015.

During an average follow-up of 20.5 years, 1,639 survivors experienced 3,115 subsequent neoplasms. The most common subsequent malignancies were breast and thyroid cancers. Proportions of individuals receiving radiation decreased (77 percent for 1970s vs 33 percent for 1990s), as did median dose. Fifteen-year cumulative incidence of subsequent malignancies decreased by decade of diagnosis (2.1 percent for 1970s, 1.7 percent for 1980s, 1.3 percent for 1990s). Relative rates declined with each 5-year increment for subsequent malignancies. Radiation dose changes were associated with reduced risk for subsequent malignancies, meningiomas (a tumor that arises from the membranes that surround the brain and spinal cord), and nonmelanoma skin cancers.

“The current analysis, including more than 23,000 survivors of childhood cancer treated over 3 decades, demonstrated that the cumulative incidence rates of subsequent neoplasms, subsequent malignant neoplasms, meningiomas, and nonmelanoma skin cancers were lower among survivors treated in more recent treatment eras and that modifications of primary cancer therapy were associated with these declines,” the authors write.

(doi:10.1001/jama.2017.0693; 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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 28, 2017

Media Advisory: To contact David Gaist, M.D., Ph.D., email dgaist@health.sdu.dk.

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JAMA

An increased incidence in Denmark of subdural hematoma (a bleed located within the skull, but outside the brain) from 2000 to 2015 appears to be associated with the increased use of antithrombotic drugs, such as low-dose aspirin, vitamin K antagonists (e.g., warfarin), clopidogrel, and oral anticoagulants, according to a study appearing in the February 28 issue of JAMA.

David Gaist, M.D., Ph.D., of Odense University Hospital and the University of Southern Denmark, Odense, Denmark and colleagues conducted a study that included 10,010 patients, ages 20 to 89 years, with a first-ever subdural hematoma diagnosis from 2000 to 2015 who were matched to 400,380 individuals from the general population (controls). Subdural hematoma incidence and antithrombotic drug use was identified using population-based regional data and national data from Denmark.

Among the patients with subdural hematoma (average age, 69 years), 47 percent were taking antithrombotic medications. The researchers found that low-dose aspirin was associated with a small risk, use of clopidogrel and a direct oral anticoagulant with a moderate risk, and use of a vitamin K antagonist (VKA) with a higher risk of subdural hematoma. With the exception of low-dose aspirin combined with dipyridamole (an antiplatelet drug), which was associated with a risk similar to use of low-dose aspirin alone, concurrent use of more than one antithrombotic drug was related to substantially higher subdural hematoma risk, which was particularly marked for combined treatment of a VKA with an antiplatelet drug, e.g., low-dose aspirin or clopidogrel.

The prevalence of antithrombotic drug use increased in the general population from 2000 to 2015, as did the overall subdural hematoma incidence rate. The largest increase in incidence of subdural hematoma was among patients older than 75 years.

“The present data add 1 more piece of evidence to the complex risk-benefit equation of antithrombotic drug use. It is known that these drugs result in net benefits overall in patients with clear therapeutic indications,” the authors write.

(doi:10.1001/jama.2017.0639; 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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 28, 2017

Media Advisory: To contact Dana Dabelea, M.D., Ph.D., email Tonya Ewers at tonya.ewers@ucdenver.edu.

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JAMA

Among teenagers and young adults who had been diagnosed with diabetes during childhood or adolescence, the prevalence of diabetes-related complications was higher among those with type 2 than with type 1, but complications were frequent in both groups, according to a study appearing in the February 28 issue of JAMA.

The increased prevalence of type 2 diabetes among children and adolescents has been relatively recent in most populations, beginning in the early to mid-1990s. Additionally, a long-term increase in type 1 diabetes has been observed both worldwide and in the United States. These recent trends in type 1 and 2 diabetes diagnosed in young individuals raise the question of whether the pattern of complications differs by diabetes type at similar ages and diabetes duration.

Dana Dabelea, M.D., Ph.D., of the Colorado School of Public Health, Aurora, and colleagues estimated the prevalence of multiple diabetes-related complications among 2,018 study participants with type 1 and type 2 diabetes diagnosed at younger than 20 years. Of the participants, 1,746 had type 1 diabetes and 272 had type 2. Average diabetes duration was 7.9 years (both groups).

The researchers found that approximately one in three teenagers and young adults with type 1 diabetes (32 percent) and almost 3 of 4 of those with type 2 diabetes (72 percent) had a complication. Patients with type 2 diabetes vs those with type 1 had higher age-adjusted prevalence for:

• diabetic kidney disease (19.9 percent vs 5.8 percent)
• retinopathy (9.1 percent vs 5.6 percent)
• peripheral neuropathy (17.7 percent vs 8.5 percent)
• arterial stiffness (47.4 percent vs 11.6 percent)
• hypertension (21.6 percent vs 10.1 percent)

After adjustment for established risk factors measured over time, participants with type 2 diabetes vs those with type 1 had significantly higher odds of diabetic kidney disease, retinopathy, and peripheral neuropathy but no significant difference in the odds of arterial stiffness and hypertension.

“These findings support early monitoring of youth with diabetes for development of complications,” the authors write.

(doi:10.1001/jama.2017.0686; 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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 28, 2017

Media Advisory: To contact Kenneth D. Mandl, M.D., M.P.H., email Keri Stedman at Keri.Stedman@childrens.harvard.edu.

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.2016.19579

JAMA

The total payments insurance companies pay for knee and hip implants were twice as high as the average selling prices at which hospitals purchased the implants from manufacturers, resulting in hundreds of millions of dollars of additional insurance claims, according to a study appearing in the February 28 issue of JAMA.

Total knee arthroplasty (TKA; replacement) and total hip arthroplasty (THA) are common procedures with charges ranking first and eighth among all procedures in the United States. The cost of the implant device is typically the largest expense associated with these procedures, but insurance companies pay without knowledge of either price or even the device model.

Yi-Ju Tseng, Ph.D., and Kenneth D. Mandl, M.D., M.P.H., of Boston Children’s Hospital, conducted a study that included 40,372 patients with primary TKAs and 23,570 patients with primary THAs in 2011-2015. The patients were younger than 65 years of age. The average selling price (ASP; paid from surgical centers to manufacturers) was $5,023 for knee implants and the average insurance payment was $10,605. The ASP was $5,620 for hip implants and the average insurance payment was $11,751.

Based on the differences between the ASP and the average insurance payments, the cumulative differences in payment for patients in this insurance database were estimated at $225.3 million for total knee replacement and $199.7 million for total hip replacement.

“Insurance companies pay for implants without knowing the brand or model, and device pricing by manufacturers is not publicly reported. Availability of such information would allow price negotiation between insurance companies, hospitals, and manufacturers and may lower implant prices,” the authors write.

(doi:10.1001/jama.2016.19579; the study is available pre-embargo at the For the Media website)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 21, 2017

Media Advisory: To contact Simon Gilbody, Ph.D., email Rachel Richardson at rachelrichardson1@gmail.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.2017.0130

JAMA

Among older adults with subthreshold depression (insufficient levels of depressive symptoms to meet diagnostic criteria), collaborative care compared with usual care resulted in an improvement in depressive symptoms after four months, although it is of uncertain clinical importance, according to a study appearing in the February 21 issue of JAMA.

Depression is the second leading cause of disability worldwide, and one in seven older people meet criteria for depression.  Effective therapeutic strategies are needed in older people with depressive symptoms. Simon Gilbody, Ph.D., of the University of York, England, and colleagues randomly assigned 705 adults age 65 years or older with subthreshold depression to collaborative care (n=344) or usual primary care (control; n=361). Collaborative care was coordinated by a case manager who assessed functional impairments relating to mood symptoms. Participants were offered behavioral activation and completed an average of six weekly sessions.

Collaborative care resulted in lower scores vs usual care at 4-month follow-up on measures of self-reported depression severity. The proportion of participants meeting criteria for depression were lower for collaborative care (17.2 percent) than usual care (23.5 percent) at 4-month follow-up, and at 12-month follow-up (15.7 percent vs 27.8 percent).

“Although differences persisted through 12 months, findings are limited by attrition, and further research is needed to assess longer-term efficacy,” the authors write.

(doi:10.1001/jama.2017.0130; the study is available pre-embargo at the For the Media website)

Editor’s Note: This project was funded by the UK National Institute of Health Research Health Technology Assessment Programme. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 21, 2017

Media Advisory: To contact Tara Lagu, M.D., M.P.H., email Brendan Monahan at Brendan.Monahan@baystatehealth.org.

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JAMA

An analysis of 28 commercial physician-rating websites finds that search mechanisms are cumbersome, and reviews scarce, according to a study appearing in the February 21 issue of JAMA.

Patients are increasingly seeking information about physicians online. Nearly 60 percent report that online reviews are important when choosing a physician. Because publicly reported quality data are not reported at the physician level, patients must consult physician-rating websites to find such reviews. Tara Lagu, M.D., M.P.H., of Baystate Medical Center, Springfield, Mass., and colleagues identified 28 physician-rating websites that met criteria for inclusion in the study. The researchers then used publicly available lists of registered and active physicians to identify a random sample of 600 physicians from three metropolitan areas (Boston, Portland, Ore.; and Dallas) and searched each website for reviews and calculated average and median number of reviews per physician per site.

The authors found that few sites allowed the user to search by clinical condition, sex of physician, hospital affiliation, languages spoken, or insurance accepted. Across the 28 websites, there were 8,133 quantitative reviews for the 600 physicians. Among physicians with at least one review on any site, the median number was 7 reviews per physician across all sites. One-third of sampled physicians did not have a review on any site.

The researchers write that despite certain study limitations, “these results demonstrate that it is difficult for a prospective patient to find (for any given physician on any commercial physician-rating website) a quantity of reviews that would accurately relay the experience of care with that physician.”

“Methods that use systematic data collection (e.g., surveys) may have a greater chance of amassing a sufficient quantity and quality of reviews to allow patients to make inferences about patient experience of care.”

(doi:10.1001/jama.2016.18553; the study is available pre-embargo at the For the Media website)

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 21, 2017

JAMA

An article in the Arts and Medicine section of JAMA reports the experience of a tattoo artist who works with women to design imagery to conceal their mastectomy scars. The article is available here, and images of a postmastectomy tattoo and the application process are below.

Botanical imagery in a tattoo after mastectomy and surgical
reconstruction.

Stages of tattoo application process after bilateral mastectomy and deep inferior epigastric artery perforator flap reconstruction.

EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 14, 2017

Media Advisory: To contact Julie Nangia, M.D., email Allison Huseman at Allison.Huseman@bcm.edu. To contact Hope S. Rugo, M.D., email Elizabeth Fernandez at Elizabeth.Fernandez@ucsf.edu.

Related material: Images of scalp cooling and photographic results of two patients treated with scalp cooling are available below.

To place an electronic embedded link to these studies in your story  These links will be live at the embargo time: http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.20939  http://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.21038

JAMA

Two studies in the February 14 issue of JAMA examine hair loss among women with breast cancer who received scalp cooling before, during and after chemotherapy.

Chemotherapy may result in hair loss (alopecia), which women rate as one of the most distressing adverse effects of chemotherapy. Scalp cooling is hypothesized to reduce blood flow to hair follicles and reduce uptake of chemotherapeutic agents. Modern methods to prevent hair loss use devices that circulate fluid in a cooling cap using refrigeration. A cap is placed on the patient prior to chemotherapy and does not have to be changed or removed until the treatment is completed. Although scalp cooling devices have been used to prevent alopecia, efficacy has not been assessed in a randomized clinical trial.

In one study, Julie Nangia, M.D., of the Baylor College of Medicine, Houston, and colleagues randomly assigned 182 women with breast cancer undergoing chemotherapy to scalp cooling (n = 119) or control (n = 63). Scalp cooling was done 30 minutes prior to and during and 90 minutes after each chemotherapy infusion. Hair preservation was assessed at the end of four cycles of chemotherapy. One interim analysis was planned to allow the study to stop early for efficacy.

At the time of the interim analysis, 142 participants were evaluable. The researchers found that patients who received scalp cooling were significantly more likely than patients who did not receive scalp cooling to have less than 50 percent hair loss (with 51 percent of those in the scalp cooling group retaining their hair, compared with 0 percent of those in the control group). There were no significant differences in changes in any of the measures of quality of life between the groups. Only adverse events related to device use were collected; 54 adverse events were reported in the cooling group, none serious.

“Further research is needed to assess longer-term efficacy and adverse effects,” the authors write.

In another study, Hope S. Rugo, M.D., of the University of California, San Francisco, and colleagues included women with breast cancer receiving chemotherapy (106 patients in the scalp cooling group and 16 in the control group; 14 matched by both age and chemotherapy regimen). Scalp cooling was initiated 30 minutes prior to each chemotherapy cycle, with scalp temperature maintained at 3°C (37°F) throughout chemotherapy and for 90 minutes to 120 minutes afterward.

Image of scalp cooling:

From Rugo et al article, photographic results of two patients treated with scalp cooling (details available in paper):

Although scalp cooling has been available for several decades in Europe, use has been limited in the United States because of several factors, including insufficient prospective efficacy data with current chemotherapy regimens.

Among the 122 patients in the study, the average duration of chemotherapy was 2.3 months. Hair loss of 50 percent or less was seen in 67 of 101 patients (66 percent) evaluable for alopecia in the scalp cooling group vs 0 of 16 patients (0 percent) in the control group. Three of five quality-of-life measures were significantly better one month after the end of chemotherapy in the scalp cooling group. Of patients who underwent scalp cooling, 27 percent reported feeling less physically attractive compared with 56 percent of patients in the control group. Of the 106 patients in the scalp cooling group, four (3.8 percent) experienced the adverse event of mild headache and three (2.8 percent) discontinued scalp cooling due to feeling cold.

“Further research is needed to assess outcomes after patients receive anthracycline [a class of drugs used in chemotherapy] regimens, longer-term measures of alopecia, and adverse effects,” the authors write.

Editor’s Note for Nangia et al study: This work was supported by Paxman Coolers Ltd., which contracted with Baylor College of Medicine to conduct the study. Dr. Lacouture is supported in part by a grant from the National Cancer Institute. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editor’s Note for Rugo et al study: The study was funded partially by Dignitana AB, the Lazlo Tauber Family Foundation, the Anne Moore Breast Cancer Research Fund, and the Friedman Family Foundation. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 14, 2017

Media Advisory: To contact Sekar Kathiresan, M.D., email Julie Cunningham at julie.cunningham@mgh.harvard.edu.

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.2016.21042

JAMA

A genetic predisposition to higher waist-to-hip ratio adjusted for body mass index (a measure of abdominal adiposity [fat]) was associated with an increased risk of type 2 diabetes and coronary heart disease, according to a study appearing in the February 14 issue of JAMA.

Obesity, typically defined on the basis of body mass index (BMI), is a leading cause of type 2 diabetes and coronary heart disease (CHD). However, for any given BMI, body fat distribution can vary substantially; some individuals store proportionally more fat around their visceral organs (abdominal adiposity) than on their thighs and hip. In observational studies, abdominal adiposity has been associated with type 2 diabetes and CHD. Whether these associations represent causal relationships remains uncertain.

Sekar Kathiresan, M.D., of Massachusetts General Hospital, Harvard Medical School, Boston, and colleagues examined whether a genetic predisposition to increased waist-to-hip ratio adjusted for BMI was associated with cardiometabolic quantitative traits (i.e., lipids, insulin, glucose, and systolic blood pressure), type 2 diabetes and CHD.

Estimates for cardiometabolic traits were based on a combined data set consisting of summary results from 4 genome-wide association studies conducted from 2007 to 2015, including up to 322,154 participants, as well as individual-level, cross-sectional data from the UK Biobank collected from 2007-2011, including 111,986 individuals.

The researchers found that genetic predisposition to higher waist-to-hip ratio adjusted for BMI was associated with increased levels of quantitative risk factors (lipids, insulin, glucose, and systolic blood pressure) as well as a higher risk for type 2 diabetes and CHD.

“These results permit several conclusions. First, these findings lend human genetic support to previous observations associating abdominal adiposity with cardiometabolic disease,” the authors write. “Second, these results suggest that body fat distribution, beyond simple measurement of BMI, could explain part of the variation in risk of type 2 diabetes and CHD noted across individuals and subpopulations. … Third, waist-to-hip ratio adjusted for BMI might prove useful as a biomarker for the development of therapies to prevent type 2 diabetes and CHD.”

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 14, 2017

Media Advisory: To contact Stephen R. Durham, M.D., email s.durham@imperial.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.2016.21040

JAMA

Among patients with moderate to severe seasonal allergic rhinitis, two years of immunotherapy tablets was not significantly different from placebo in improving nasal symptoms at 3-year follow-up, according to a study appearing in the February 14 issue of JAMA.

The prevalence of allergic rhinitis in the United States has been estimated at 15 percent based on physician diagnosis and at 30 percent based on self-reported nasal symptoms. Rhinitis has major effects on quality of life, sleep, and work and school performance. Three years of continuous treatment with subcutaneous (injection) immunotherapy and sublingual (tablets) immunotherapy has been shown to improve symptoms for at least two years following discontinuation of treatment. It is unknown whether a shorter course of immunotherapy provides long-term benefits, while reducing overall costs, patient inconvenience, and adverse events.

Stephen R. Durham, M.D., of Imperial College London, and colleagues randomly assigned 106 adults with moderate to severe seasonal allergic rhinitis to receive two years of sublingual immunotherapy (n=36; daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections); subcutaneous immunotherapy (n=36; monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets); matched double-placebo (n=34). Nasal allergen challenge was performed before treatment, at one and two years of treatment, and at three years (1 year after treatment discontinuation).

Among 106 randomized participants, 92 completed the study at three years. The researchers found that treatment for two years with grass pollen sublingual immunotherapy was not sufficient to achieve an allergic response improvement at 3-year follow-up.

“International guidelines regarding immunotherapy recommend a minimum of 3 years of treatment with both delivery methods [subcutaneous, sublingual]. If a 2-year regimen had demonstrated long-term benefits in addition to efficacy, this could have represented cost savings in terms of clinical resources and improved convenience for the patient. Because this was not observed, clinicians should be advised to follow established guidelines that recommend at least 3 years treatment,” the authors write.

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

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 7, 2017

Media Advisory: To contact Mary E. Lacy, M.P.H., email David Orenstein at david_orenstein@brown.edu.

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.2016.21035

JAMA

Using standard hemoglobin A_1c criteria resulted in identifying 40 percent fewer cases of prediabetes and 48 percent fewer cases of diabetes among African Americans with sickle cell trait compared with those without, while glucose-based methods resulted in a similar prevalence regardless of sickle cell trait status, according to a study in the February 7 issue of JAMA.

Hemoglobin A_1c (HbA_1c) reflects past glucose concentrations, but this relationship may differ between those with sickle cell trait (SCT) and those without it. Sickle cell trait is a condition in which a person has only one copy of the gene for sickle cell but does not have sickle cell disease (which requires two copies of the sickle cell gene). Correct interpretation of HbA_1c values in individuals with SCT is important because it directly affects efforts that use HbA_1c for screening, diagnosis, and monitoring of diabetes and prediabetes. Sickle cell trait is the most common hemoglobin variant in the United States, with 8 to 10 percent of black people affected by SCT compared with less than one percent of white people.

Mary E. Lacy, M.P.H., of the Brown University School of Public Health, Providence, R.I., and colleagues evaluated the association between SCT and HbA_1c for given levels of fasting or 2-hour glucose levels among African Americans using data collected from 7,938 participants in two community-based cohorts, the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS).

The analytic sample included 4,620 participants (367 [7.9 percent] with SCT). The researchers found that at the same fasting or 2-hour glucose concentration, HbA_1c was significantly lower among participants with vs without SCT. Also, differences in HbA_1c concentration by SCT status were greater at higher glucose concentrations. The prevalence of prediabetes and diabetes was significantly lower among participants with SCT when defined using HbA_1c values (29 percent vs 49 percent for prediabetes and 3.8 percent vs 7.3 percent for diabetes).

“These results could have clinically significant implications. As a screening tool, an HbA_1c value that systematically underestimates long-term glucose levels may result in a missed opportunity for intervention,” the authors write. “Because black people typically have a higher prevalence of diabetes and experience a number of diabetic complications at higher rates than white people, the cost of inaccurately assessing risk and treatment response is high.”

(doi:10.1001/jama.2016.21035; 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.

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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, FEBRUARY 7, 2017

Media Advisory: To contact Allison W. Kurian, M.D., M.Sc., email Krista Conger at kristac@stanford.edu.

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.2016.16918

JAMA

In a study appearing in the February 7 issue of JAMA, Allison W. Kurian, M.D., M.Sc., of the Stanford University School of Medicine, Stanford, Calif., and colleagues examined the use of genetic counseling and testing among patients with newly diagnosed breast cancer.

Testing of two breast cancer-associated genes, BRCA1 and BRCA2, has been available for 20 years but new technology and less restrictive patent laws have made certain tests available at much lower costs, yet little is known about recent patient experience with genetic testing and counseling. This study included women ages 20 through 79 years, diagnosed with stages 0 to II breast cancer, who were mailed surveys two months after surgical operation. Survey questions addressed how much patients wanted genetic testing (not at all, a little bit, somewhat, quite a bit, very much); and whether patients talked about testing with any “doctor or other health professional,” had a session with a genetic counseling expert, or had testing.

A total of 2,529 women (71 percent) responded to the survey. Among the findings: most patients (66 percent) reported wanting genetic testing and 29 percent reported having it. Yet only 40 percent of all high-risk women and 62 percent of tested high-risk women reported having a genetic counseling session. Only 53 percent of high-risk patients had a genetic test, “representing a missed opportunity to prevent ovarian and other cancer deaths among mutation carriers and their families,” the authors write.

They add that clinical need for genetic testing may not be adequately recognized by physicians. High-risk patients reported lack of a physician’s recommendation, not expense, as their primary reason for not testing.

High-risk patients most vulnerable to under-testing included Asians and older women, despite evidence that many such patients carry mutations.

“The findings emphasize the importance of cancer physicians in the genetic testing process. Priorities include improving physicians’ communication skills and assessments of patients’ risk and desire for testing, and optimizing triage to genetic counselors.”

(doi:10.1001/jama.2016.16918; 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.

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