Loss of consciousness is a common presenting symptom in patients after subarachnoid hemorrhage (SAH) due to brain aneurysm. Corresponding author Stephan A. Mayer, M.D., of the Ichan School of Medicine at Mount Sinai in New York, and coauthors suggest loss of consciousness may be an indicator of a severe bleeding event and therefore a predictor of death or poor functional outcome a year later, according to an article published online by JAMA Neurology.
To read the full article and an accompanying editorial by R. Loch Macdonald, M.D., Ph.D., of the University of Toronto, Canada, plus hear an audio interview with the authors, please visit the For The Media website.
(JAMA Neurol. Published online November 9, 2015. doi:10.1001/jamaneurol.2015.3188. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: An author made a conflict of interest disclosure. Funding/support disclosures also were made. Please see the article 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 emailmediarelations@jamanetwork.org.
EMBARGOED FOR RELEASE: 11A.M. (ET), MONDAY, NOVEMBER 9, 2015
Media Advisory: To contact corresponding author Ulla Uusitalo, Ph.D., call Anne DeLotto Baier at 813-974-3303 or email abaier@health.usf.edu. To contact corresponding editorial author George M. Weinstock, Ph.D., call Joyce Peterson 207-288-6058 or email joyce.peterson@jax.org.
Probiotic exposure during the first 27 days of an infant’s life may be associated with reduced risk of islet autoimmunity among children at increased genetic risk for type 1 diabetes, although further studies are needed before any recommendations for probiotics can be made, according to an article published online by JAMA Pediatrics.
Probiotics are live organisms that may confer health benefits. Animal studies have looked at manipulation of gut microbiota by probiotics and the risk of developing type 1 diabetes (T1DM) related to autoimmunity.
Ulla Uusitalo, Ph.D., of the University of South Florida, Tampa, and coauthors examined the association between supplemental probiotic use during the first year of life and islet autoimmunity. Islet autoimmunity occurs when antibodies attack islet cells in the pancreas that produce insulin.
The authors report the results of The Environmental Determinants of Diabetes in the Young (TEDDY) study, which started in 2004 with children from six clinical centers, three in the United States (Colorado, Georgia/Florida and Washington) and three in Europe (Finland, Germany and Sweden).
The children were followed-up for T1DM-related autoantibodies with blood samples drawn every three months between 3 and 48 months of age and every six months thereafter to determine persistent islet autoimmunity. Questionnaires and diaries were used to detail infant feeding, including probiotic supplementation and infant formula use.
A final study sample consisted of 7,473 children who ranged in age from 4 to 10 years old. Probiotic supplementation from dietary supplements or infant formula varied by country and was most pervasive in Finland and Germany during the first year of a child’s life.
Receiving probiotics through a dietary supplement or fortified infant formula, or both, by 27 days of age may be associated with a reduced risk of islet autoimmunity compared with those children who first received probiotics after 27 days of age or not at all. Early probiotic exposure appeared to be associated with a 60 percent decrease in the risk of islet autoimmunity among children with the highest-risk HLA genotype DR3/4 but not among other genotypes.
An association does not imply causality and further research needs to be done, the study notes.
“Early exposure to supplemental probiotics may decrease the risk of IA [islet autoimmunity] among children at elevated risk of T1DM. … These results have to be confirmed before making recommendations on the use of probiotic supplementation,” the study concludes.
(JAMA Pediatr. Published online November 9, 2015. doi:10.1001/jamapediatrics.2015.2757. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: The study includes funding/support disclosures. Please see article for additional information, including other authors, author contributions and affiliations, etc.
Editorial: A Glimpse of Microbial Power in Preventive Medicine
In a related editorial, George M. Weinstock, Ph.D., of the Jackson Laboratory for Genomic Medicine, Farmington, Conn., writes: “This protective association between early probiotic use and T1DM-related IA awaits further randomized clinical trials. … While probiotic use in children is not that common in the United States, statistics in the current study show it to be more widespread in the study’s other participating sites of Finland, Germany and Sweden. This is an area in its infancy but likely to have a large impact on the medicine of the future.”
(JAMA Pediatr. Published online November 9, 2015. doi:10.1001/jamapediatrics.2015.3246. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see article for additional information, including other authors, author contributions and affiliations, etc.
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Mihai Gheorghiade, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, and colleagues randomly assigned 456 patients with worsening chronic HF and reduced left ventricular ejection fraction (a measure of how well the left ventricle of the heart pumps with each beat) to receive placebo or 1 of 4 daily target doses of the medication vericiguat for 12 weeks. This JAMA study is being released to coincide with its presentation at the American Heart Association’s Scientific Sessions 2015.
More than 1 million hospitalizations for heart failure (HF) occur annually in the United States alone, and more than 80 percent of these hospitalized patients have worsening chronic HF. Despite an often rapid and substantial in-hospital improvement in HF signs and symptoms with standard therapy, approximately 25 percent of patients are rehospitalized within 30 days and 30 percent of patients may die within 1 year.
This phase 2 study, which included patients from across Europe, North America, and Asia, was conducted to determine the optimal dose and tolerability of the drug vericiguat to reduce elevated natriuretic peptide levels. Natriuretic peptides are produced by the heart in response to high pressures inside the heart, which is typical in heart failure. Elevated levels are seen in the setting of worsening heart failure and correlate with severity of symptoms and risk of death.
Overall, 351 patients (77 percent) completed treatment with the study drug with valid 12-week N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and no major protocol deviation. In the primary analysis, change in NT-proBNP levels from baseline to week 12 was not significantly different between the pooled vericiguat group and placebo. The secondary analysis suggested a dose-response relationship, such that higher vericiguat doses were associated with greater reductions in NT-proBNP level. Rates of any adverse event were 77 percent and 71 percent among the placebo and 10-mg vericiguat groups, respectively.
“Among patients with worsening chronic HF and reduced LVEF, compared with placebo, vericiguat did not have a statistically significant effect on change in NT-proBNP level at 12 weeks but was well-tolerated. Further clinical trials of vericiguat based on the dose-response relationship in this study are needed to determine the potential role of this drug for patients with worsening chronic HF,” the authors write.
Editor’s Note: This study was funded by affiliates of Bayer and Merck, Sharp & Dohme, a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
Anna Svatikova, M.D., Ph.D., of the Mayo Clinic, Rochester, Minn., and colleagues randomly assigned 25 healthy volunteers (age 18 years or older) to consume a can (480 mL; 16 fl. oz.) of a commercially available energy drink (Rockstar; Rockstar Inc) and placebo drink within 5 minutes, in random order on 2 separate days, maximum 2 weeks apart. The placebo drink, selected to match the nutritional constituents of the energy drink, was similar in taste, texture, and color but lacked caffeine and other stimulants of the energy drink (240 mg of caffeine, 2,000 mg of taurine, and extracts of guarana seed, ginseng root, and milk thistle). This JAMA study is being released to coincide with its presentation at the American Heart Association’s Scientific Sessions 2015.
Energy drink consumption has been associated with serious cardiovascular events, possibly related to caffeine and other stimulants. The researchers examined the effect of energy drink consumption on hemodynamic changes, such as blood pressure and heart rate. Participants were fasting and abstained from caffeine and alcohol 24 hours prior to each study day. Serum levels of caffeine, plasma glucose, and norepinephrine (noradrenaline) were measured and blood pressure and heart rate were obtained at baseline and 30 minutes after drink ingestion.
Caffeine levels remained unchanged after the placebo drink, but increased significantly after energy drink consumption. Consumption of the energy drink elicited a 6.2 percent increase in systolic blood pressure; diastolic blood pressure increased by 6.8 percent; average blood pressure increased after consumption of the energy drink by 6.4 percent. There was no significant difference in heart rate increase between the 2 groups. The average norepinephrine level increased from 150 pg/mL to 250 pg/mL after consumption of the energy drink and from 140 pg/mL to 179 pg/mL after placebo (change rate: 74 percent vs 31 percent, respectively).
“These acute hemodynamic and adrenergic changes may predispose to increased cardiovascular risk,” the authors write. “Further research in larger studies is needed to assess whether the observed acute changes are likely to increase cardiovascular risk.”
Editor’s Note: This research was supported by a grant from the Mayo Foundation and the National Center for Advancing Translational Sciences, National Institutes of Health. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
EMBARGOED FOR RELEASE: 9:00 A.M. (ET) MONDAY, NOVEMBER 9, 2015
Media Advisory: To contact Nihar R. Desai, M.D., M.P.H., call Karen Peart at 203-432-1326 or email karen.peart@yale.edu. To contact editorial author Robert A. Harrington, M.D., email Tracie White at traciew@stanford.edu.
Nihar R. Desai, M.D., M.P.H., of the Yale School of Medicine, New Haven, Conn., and colleagues examined trends in percutaneous coronary intervention use, patient selection, and procedural appropriateness following the introduction of Appropriate Use Criteria. This JAMA study is being released to coincide with its presentation at the American Heart Association’s Scientific Sessions 2015.
In 2009, the American College of Cardiology and the American Heart Association, along with other professional societies, released Appropriate Use Criteria for Coronary Revascularization to critically examine and improve patient selection for percutaneous coronary intervention (PCI; commonly known as coronary angioplasty, a non-surgical procedure used to open narrow or blocked coronary arteries) as well as address concerns about potential overuse. Prior studies demonstrated that 1 in 6 nonacute PCIs were classified as inappropriate, indicating that the benefits of the procedure were unlikely to outweigh the risks. National trends in the appropriateness of PCI have not been examined since the introduction of the Appropriate Use Criteria, according to background information in the article.
This analysis included patients undergoing PCI between July 2009 and December 2014 at hospitals continuously participating in the National Cardiovascular Data Registry CathPCI registry over the study period. The researchers determined the proportion of nonacute PCIs classified as inappropriate at the patient and hospital level using the 2012 Appropriate Use Criteria for coronary revascularization.
A total of 2.7 million PCI procedures from 766 hospitals were included. Annual PCI volume of acute indications was consistent over the study period, but the volume of nonacute PCIs decreased from 89,704 in 2010 to 59,375 in 2014. The proportion of nonacute PCIs classified as inappropriate decreased from 26 percent to 13 percent, and the absolute number of inappropriate PCIs decreased from 21,781to 7,921. Hospital-level variation in the proportion of PCIs classified as inappropriate persisted over the study period (median, 13 percent in 2014).
Among patients undergoing nonacute PCI, there were significant increases in angina severity, use of antianginal medications prior to PCI, and high-risk findings on noninvasive testing, but only modest increases in multivessel coronary artery disease.
“This analysis provides details about changes in the clinical profiles of patients undergoing PCI and suggests that the observed reductions in inappropriate PCI in part reflect improvements in patient selection and clinical decision making as well as better documentation of the key elements used to determine procedural appropriateness,” the authors write. “These findings may indicate that clinicians are doing a better job of identifying and limiting nonacute PCI procedures to those patients most likely to benefit from revascularization.”
“Collectively, these findings suggest that the practice of interventional cardiology has evolved since the introduction of Appropriate Use Criteria in 2009.”
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Appropriate Use Criteria for Coronary Revascularization and the Learning Health System
“As reported by Desai et al, the use of the National Cardiovascular Data Registry has allowed temporal review of the PCI appropriate use criteria,” writes Robert A. Harrington, M.D., of Stanford University, Stanford, Calif., in an accompanying editorial.
“However, these data analyses are retrospective. What is needed is a national system that allows immediate real-time decision support for clinical activities fully integrated with clinical research capabilities that use constantly accumulating data and sophisticated data analytics, including randomization when appropriate. Only at that point will the continuously learning health care system be a reality.”
To place an electronic embedded link to this study in your story This link for the study will be live at the embargo time: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2015.13919
Josep Rodes-Cabau, M.D., of Laval University, Quebec City, Canada, and colleagues randomly assigned 171 patients with an indication for atrial septal defect (ASD) closure and no history of migraine to receive dual antiplatelet therapy (aspirin + clopidogrel [the clopidogrel group], n = 84) or single antiplatelet therapy (aspirin + placebo [the placebo group], n = 87) for 3 months following transcatheter ASD closure. This JAMA study is being released to coincide with its presentation at the American Heart Association’s Scientific Sessions 2015.
An atrial septal defect is a hole in the part of the septum (wall) that separates the upper chambers of the heart. Occurrence of new-onset migraine attacks has been reported in approximately 15 percent of patients following transcatheter ASD closure, with the majority of initial episodes occurring within the days to weeks following the procedure. Aspirin is often prescribed for 6 months following the procedure. Preliminary studies have suggested an association with a lower incidence and severity of migraine headaches following ASD closure when ticlopidine or clopidogrel is added to aspirin treatment.
The researchers found that patients in the clopidogrel group had a reduced average number of monthly migraine days within the 3 months following the procedure (0.4 days) vs the placebo group (1.4 days) and a lower incidence of migraine attacks (9.5 percent for the clopidogrel group vs 22 percent for the placebo group). Among patients with migraines, those in the clopidogrel group had less-severe migraine attacks (zero patients with moderately or severely disabling migraine attacks vs 37 percent [7 patients] in the placebo group). No significant increase in adverse events was observed with the use of dual vs single antiplatelet therapy.
“Further studies are needed to assess generalizability and durability of this effect,” the authors write.
Editor’s Note: This study was funded by unrestricted grants from Sanofi and St. Jude Medical and a grant from the Foundation of the Quebec Heart and Lung Institute. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
Myeong-Ki Hong, M.D., Ph.D., of the Yonsei University College of Medicine, Seoul, Korea and colleagues randomly assigned 1,400 patients with long coronary lesions to receive intravascular ultrasound-guided (n = 700) or angiography-guided (n = 700) everolimus-eluting stent implantation. This JAMA study is being released to coincide with its presentation at the American Heart Association’s Scientific Sessions 2015.
Even though recent guidelines recommend the use of intravascular ultrasound (IVUS) to optimize stent implantation for select patients, the effect of IVUS-guided drug-eluting (releasing) stent implantation on clinical outcomes remains uncertain because of the limited number of properly powered randomized trials.
For this trial, one-year follow-up was complete in 1,323 patients (94.5 percent). Major adverse cardiac events (including cardiac death, target lesion-related heart attack, or ischemia-driven target lesion revascularization) at 1 year occurred in 39 patients (5.8 percent) undergoing angiography-guided and in 19 patients (2.9 percent) undergoing IVUS-guided stent implantation (a 2.9 percent absolute reduction and 48 percent relative reduction). The difference was driven by a lower risk of ischemia-driven target lesion revascularization in patients undergoing IVUS-guided (17 [2.5 percent]) compared with angiography-guided (33 [5 percent]) stent implantation.
Cardiac death and target lesion-related heart attack were not significantly different between the 2 groups. For cardiac death, there were 3 patients (0.4 percent) in the IVUS-guided group and 5 patients (0.7 percent) in the angiography-guided group. Target lesion-related heart attack occurred in 1 patient in the angiography-guided stent implantation group.
“Our findings suggest better clinical outcomes for major adverse cardiac events with IVUS-guided stent implantation compared with angiography-guided stent implantation, particularly for diffuse long lesions,” the authors write.
Editor’s Note: This study was supported by the Cardiovascular Research Center (Seoul, Korea) and funded by Abbott Vascular Inc. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
In a study examining the effect of financial incentives to improve lipid levels among patients in primary care practices, shared financial incentives for physicians and patients, but not incentives to physicians or patients alone, resulted in a modest reduction of low-density lipoprotein cholesterol (LDL-C) levels after 12 months, according to a study in the November 10 issue of JAMA. This issue, a cardiovascular disease theme issue, coincides with the American Heart Association’s Scientific Sessions 2015.
Cardiovascular disease is the leading cause of death in the United States, and studies indicate that taking statins to lower cholesterol reduces the risk of heart attack by about 30 percent. Despite proven benefits, the relatively low cost, once-a-day dosing, and few adverse effects, the population effectiveness of statins is limited for several reasons, including physicians underprescribing statins or failing to intensify treatment when indicated, and poor medication adherence among patients. Financial incentives to physicians or patients are increasingly used, but their effectiveness is not well established, according to background information in the article.
David A. Asch, M.D., and Kevin G. Volpp, M.D., Ph.D., of the University of Pennsylvania, Philadelphia, and colleagues conducted a study in which primary care physicians were randomly assigned to one of four groups: control, physician incentives, patient incentives, or shared physician-patient incentives. Physicians in the physician incentives group were eligible to receive up to $1,024 per enrolled patient meeting LDL-C goals. Patients in the patient incentives group were eligible for the same amount, distributed through daily lotteries tied to medication adherence. Physicians and patients in the shared incentives group shared these incentives. Physicians and patients in the control group received no incentives tied to outcomes, but all patient participants received up to $355 each for trial participation.
The clinical trial was conducted in 3 health care delivery systems in the northeastern United States. Three hundred forty eligible primary care physicians (PCPs) were enrolled from a pool of 421. Of 25,627 potentially eligible patients of those PCPs, 1,503 were enrolled.
After 12 months, the average reduction in LDL-C levels for patients was:
25.1 mg/dL for patients in the control group;
25.1 mg/dL for patients in the patient incentives group;
27.9 mg/dL for patients in the physician incentives group;
33.6 mg/dL for patients in the shared physician-patient incentives group.
Only patients in the shared physician-patient incentives group achieved reductions in LDL-C levels statistically different from those in the control group (difference of 8.5 mg/dl). “This outcome is supported by the finding that 49 percent of the patients in the shared patient and physician incentive group achieved the LDL-C goal in comparison with 36 percent to 40 percent in the other 3 groups. The superiority of a shared approach makes sense because success at LDL-C reduction is likely to be driven by both provision of medication by physicians and patient adherence to that medication. Consistent with this hypothesis, patients in the shared group were more likely to receive medication intensification and to adhere to medication use than patients in other groups.”
The author note that the reduction in LDL-C levels achieved by the patients in the shared physician-patient incentives group were modest, and that further information is needed to understand whether this approach represents good value.
Editor’s Note: This study received support from the National Institute on Aging. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
In a multiethnic, middle-aged and older study population, the prevalence of myocardial scars (evidence of a heart attack) was nearly 8 percent, of which nearly 80 percent were unrecognized by electrocardiography or clinical evaluation, according to a study in the November 10 issue of JAMA. This issue, a cardiovascular disease theme issue, coincides with the American Heart Association’s Scientific Sessions 2015.
Ischemic heart disease is an important public health concern, but a considerable proportion of myocardial infarctions (MIs; heart attacks) are clinically unrecognized. Given the aging of the U.S. population, it is important to understand the prevalence, risk factors, and prognosis of unrecognized MI. In patients who survive a heart attack, normal contractile (having the property of contracting) tissue is replaced by noncontractile fibrosis (formation of excess fibrous connective tissue in a reparative process) (scar). Myocardial scarring leads to abnormal heart function and poor prognosis. The prevalence of and factors associated with unrecognized MI and scar have not been previously defined using contemporary methods in a multiethnic U.S. population, according to information in the article.
David A. Bluemke, M.D., Ph.D., of the National Institute of Biomedical Imaging and Bioengineering, Bethesda, Md., and colleagues examined the prevalence of myocardial scar using cardiac magnetic resonance (CMR; considered a standard of reference for defining the presence of myocardial scar). Participants were multiethnic, 45 through 84 years of age and free of clinical cardiovascular disease (CVD) at study entry in 2000-2002. In the 10th year examination (2010-2012), 1,840 participants (average age, 68 years; 52 percent men) underwent CMR imaging with gadolinium to detect myocardial scar. Cardiovascular disease risk factors and coronary artery calcium (CAC) scores were measured at study entry and year 10.
The overall prevalence of myocardial scar by CMR was 7.9 percent (146 of 1,840). The prevalence of previously unrecognized myocardial scar was 6.2 percent, whereas 1.7 percent had clinically recognized MI. Thus, 78 percent (114 of 146) of myocardial scars were unrecognized by clinical or electrocardiography (ECG) evaluation. Men had a higher prevalence of myocardial scar than women (12.9 percent vs 2.5 percent).
Of individual risk factors, age, male sex, CAC score, body mass index, current smoking, and use of antihypertensive medications at study entry were associated with higher odds of myocardial scar.
“The clinical significance of unrecognized myocardial scar remains to be defined, although prior myocardial scar has been noted pathologically in more than 70 percent of patients with sudden cardiac death but without prior known coronary artery disease,” the authors write. “Further studies are needed to understand the clinical consequences of these undetected scars.”
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Although frequent laboratory monitoring of patients with heart failure following initiation of mineralocorticoid receptor antagonists is supported by the results of large clinical trials and recommended in guidelines, there appears to be low rates of monitoring in clinical practice, according to a study in the November 10 issue of JAMA. This issue, a cardiovascular disease theme issue, coincides with the American Heart Association’s Scientific Sessions 2015.
Mineralocorticoid receptor antagonists (MRAs) are a cornerstone of heart failure therapy but carry a risk of hyperkalemia (elevated potassium in the blood). Clinical guidelines recommend close monitoring of kidney function and electrolyte (including potassium) levels throughout the course of therapy. No large studies have examined whether laboratory monitoring occurs routinely in community practice. Adrian F. Hernandez, M.D., M.H.S., of the Duke University School of Medicine, Durham, N.C., and colleagues analyzed a group of patients (10,443 Medicare beneficiaries) with heart failure who had initiated MRA therapy (eplerenone or spironolactone). The researchers examined the frequency of measurement of serum creatinine and potassium levels before and after MRA initiation.
The researchers found that combined, 756 patients (7 percent) received appropriate testing before and after MRA initiation. After initiation of MRA therapy, 13 percent and 30 percent of patients received appropriate testing in early and extended follow-up, respectively. In contrast, 55 percent and 22 percent received no testing in early or extended follow-up, respectively. Atrial fibrillation, anemia, chronic kidney disease, chronic obstructive pulmonary disease, hypothyroidism, osteoporosis, and use of diuretics were associated with a greater likelihood of appropriate laboratory testing during all periods.
“The landmark trials of MRAs in heart failure showed MRAs significantly reduced mortality and cardiovascular readmission compared with placebo. However, an analysis of community practice found similar outcomes among patients treated or not treated with an MRA. One possible explanation may be less rigorous monitoring outside clinical trial settings, which may increase risks of adverse events associated with MRAs,” the authors write.
“Closing the gap between the efficacy and effectiveness of MRAs in heart failure will require clinicians to address this issue. Quality improvement initiatives to improve appropriate laboratory monitoring are needed.”
Editor’s Note: This project was supported in part by a grant from the Agency for Healthcare Research and Quality. Dr. Cooper was supported by a grant from the National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
Author Interview: An author audio interview will be available when the embargo lifts on the JAMA Oncology website: http://bit.ly/1gk4gY2
JAMA Oncology
Oral premalignant lesions (OPLs) are considered risk factors for the development of oral cancer. In an article published online by JAMA Oncology, William N. William Jr., M.D., of the University of Texas MD Anderson Cancer Center, Houston, Scott M. Lippman, M.D., of the University of California, San Diego, and coauthors report the results of a randomized clinical trial that tested if the epidermal growth factor receptor inhibitor erlotinib would reduce oral cancer development in patients with high-risk OPLs defined by specific loss of heterozygosity (LOH) profiles. They also looked at LOH as a prognostic marker in OPLs. The authors note, that to their knowledge, the Erlotinib Prevention of Oral Cancer (EPOC) randomized clinical trial is the first molecularly based precision medicine trial design in cancer prevention, and the first study of OPLs to use cancer as the primary end point.
To read the whole study and a related editorial, plus hear an author audio interview, please visit the For The Media website.
(JAMA Oncol. Published online November 5, 2015. doi:10.1001/jamaoncol.2015.4364. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made conflict of interest disclosures. The work was financially supported by OSI Pharmaceuticals. OSI Pharmaceuticals also provided drug supply. 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) SUNDAY, NOVEMBER 8, 2015
Media Advisory: To contact M.G. Myriam Hunink, M.D., Ph.D., email m.hunink@erasmusmc.nl. To contact editorial author Mary McGrae McDermott, M.D., email Marla Paul at marla-paul@northwestern.edu.
Among patients with peripheral artery disease and intermittent claudication (cramping pain in the legs due to poor circulation in the arteries, aggravated by walking), a combination therapy of endovascular revascularization (an invasive procedure to improve blood flow in an artery) followed by supervised exercise resulted in greater improvement in walking distances and health-related quality-of-life measures at one year compared with supervised exercise only, according to a study in the November 10 issue of JAMA. This issue, a cardiovascular disease theme issue, coincides with the American Heart Association’s Scientific Sessions 2015.
Intermittent claudication is the classic symptomatic form of peripheral artery disease (PAD), affecting approximately 20 to 40 million people worldwide and increasing rapidly with the aging world population. Patients with claudication experience significant functional disability often resulting in a sedentary lifestyle and reduced quality of life. Supervised exercise is recommended as a first-line treatment. A combination therapy of endovascular revascularization plus supervised exercise may be beneficial, but few data comparing the two therapies are available, according to background information in the article.
M.G. Myriam Hunink, M.D., Ph.D., of the Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues randomly assigned 212 patients with PAD and intermittent claudication to endovascular revascularization plus supervised exercise (n = 106) or supervised exercise only (n = 106). The primary measured outcome for the study was the difference in maximum treadmill walking distance at 12 months between the groups.
The researchers found that endovascular revascularization plus supervised exercise (combination therapy) was associated with greater improvement in maximum walking distance compared with the supervised exercise only group, and in pain-free walking distance. Also, the combination therapy group demonstrated significantly greater improvement in health-related quality-of-life.
“The present study reopens the debate for revascularization in patients with claudication, in particular in terms of an approach using endovascular revascularization first. By improving lower extremity blood flow, early percutaneous revascularization of the target lesion gives an impulse to patient mobility and quality of life in the short-term. This, in turn, facilitates subsequent exercising and allows the patient to profit from the long-term benefits of an additional supervised exercise program,” the authors write.
Editor’s Note: All study funding was provided by the Netherlands Organisation for Health Research and Development. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
Editorial: Erasing Disability in Peripheral Artery Disease
The results of this trial (ERASE) underscore once again the benefits of supervised treadmill exercise for patients with peripheral artery disease, writes Mary McGrae McDermott, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, and Senior Editor, JAMA, in an accompanying editorial.
“Randomized trial evidence already convincingly demonstrates that supervised treadmill exercise improves walking performance compared with no exercise. The ERASE trial newly demonstrates that supervised exercise also improves lower extremity outcomes after endovascular revascularization. Current reimbursement strategies in the United States provide significant incentives for clinicians to offer endovascular revascularizations to patients with peripheral artery disease, whereas supervised exercise remains expensive and inaccessible to patients. Reducing disability from peripheral artery disease in the 21st century requires strategies to ensure that effective exercise programs are accessible for all patients with peripheral artery disease.”
Author Interview: An author audio interview will be available when the embargo lifts on the JAMA Psychiatry website: http://jama.md/1CAHnJb
JAMA Psychiatry
Physicians in training are at high risk for suicidal ideation (thoughts) during their internship year. In an article published online by JAMA Psychiatry, Constance Guille, M.D., of the Medical University of South Carolina, Charleston, and coauthors examined the effectiveness of a web-based cognitive behavioral therapy program delivered before the start of the medical internship year to prevent suicidal ideation in medical interns. Results of the randomized clinical trial at two university hospitals with 199 medical interns suggest the interns were amenable to the intervention and the intervention was associated with a reduced likelihood of suicidal ideation during the internship year.
To read the whole study and a related editorial, plus hear an author audio interview, please visit the For The Media website.
(JAMA Psychiatry. Published online November 4, 2015. doi:10.1001/jamapsychiatry.2015.1880. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: The authors made project funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial
disclosures, funding and support, etc.
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Between 1999-2012, overall prescription drug use increased among U.S. adults, with this increase seen for the majority of but not all drug classes, according to a study in the November 3 issue of JAMA.
Use of prescription drugs represents a major expenditure in the United States, and research suggests that use of prescription drugs is increasing. Yet much of the information about prescription use is derived from pharmacy databases or expenditure data, neither of which directly captures use at the population level. It is important to document patterns of prescription drug use to inform both clinical practice and research, according to background information in the article.
Elizabeth D. Kantor, Ph.D., M.P.H., formerly of the Harvard T.H. Chan School of Public Health, Boston, and colleagues evaluated trends in prescription drug use using nationally representative data from the National Health and Nutrition Examination Survey (NHANES). Participants included 37,959 U.S. adults, age 20 years and older. Seven NHANES cycles were included (1999-2000 to 2011-2012), and the sample size per cycle ranged from 4,861 to 6,212. Within each NHANES cycle, use of prescription drugs in the prior 30 days was assessed overall and by drug class.
The researchers found that the prevalence of prescription drug use increased from 51 percent in 1999-2000 to 59 percent in 2011-2012, while the prevalence of polypharmacy (use of five or more prescription drugs) increased from 8 percent to 15 percent. Use of medications for hypertension increased (20 percent-27 percent), as did medications to treat hyperlipidemia, a trend largely driven by statins (7 percent-17 percent). Use of antidepressants also increased (7 percent-13 percent). Among the 18 drug classes used by more than 2.5 percent of the population at any point over the study period, the prevalence of use increased in 11 drug classes.
Prescription drug use increased significantly among persons 40 to 64 years of age and also among those 65 years and older, but not among adults 20 to 39 years old.
The most commonly used individual drug in 2011-2012 was simvastatin (7.9 percent), increasing from 2.0 percent in 1999-2000. The remaining top 10 drugs included lisinopril, levothyroxine, metoprolol, metformin, hydrochlorothiazide, omeprazole, amlodipine, atorvastatin, and albuterol; all of the top 10 most commonly used drugs increased over the study period except atorvastatin.
“Eight of the 10 most commonly used drugs in 2011-2012 are used to treat components of the cardiometabolic syndrome, including hypertension, diabetes, and dyslipidemia. Another is a proton-pump inhibitor used for gastroesophageal reflux, a condition more prevalent among individuals who are overweight or obese. Thus, the increase in use of some agents may reflect the growing need for treatment of complications associated with the increase in overweight and obesity,” the authors write.
Editor’s Note: Elizabeth D. Kantor, Ph.D., M.P.H., is now with the Memorial Sloan Kettering Cancer Center, New York. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 3, 2015
Media Advisory: To contact Saleh A. Almenawer, M.D., call Veronica McGuire at 905-525-9140, ext. 22169 or email vmcguir@mcmaster.ca. To contact editorial co-author Joanna M. Wardlaw, M.D., F.R.C.R., email joanna.wardlaw@ed.ac.uk.
In a meta-analysis of randomized clinical trials for the treatment of acute ischemic stroke, an endovascular intervention (such as use of a very small catheter to remove a blood clot) compared to standard medical care (administration of a clot dissolving agent) was associated with improved functional outcomes and higher rates of functional independence at 90 days, but no significant difference in symptomatic intracranial hemorrhage (bleeding in the brain) or all-cause mortality, according to a study in the November 3 issue of JAMA.
The current standard therapy for acute ischemic stroke is intravenous administration of tissue plasminogen activator (tPA). Although intravenous tPA improves survival and functional outcomes when administered as early as possible after onset of ischemic stroke, its use is limited by the narrow therapeutic time window (<4.5 hours), and by several contraindications. As few as 10 percent of patients presenting with ischemic stroke can be eligible for treatment with intravenous tPA. The limitations of its use have led to interest in endovascular therapy for acute ischemic stroke. Endovascular intervention improves blood flow but clinical studies examining this therapy have yielded variable results, warranting further examination, according to background information in the article.
Saleh A. Almenawer, M.D., of McMaster University, Hamilton, Ontario, Canada, and colleagues conducted a meta-analysis that included data from 8 trials involving 2,423 patients with acute ischemic stroke (average age, 67 years; 47 percent women), including 1,313 who underwent endovascular thrombectomy and 1,110 who received standard medical care with tPA. For this analysis, endovascular therapy was defined as the intra-arterial use of a microcatheter or other device for mechanical thrombectomy (clot removal), with or without the use of a chemical thrombolytic (clot busting) agent.
The researchers found that endovascular therapy was associated with a significant treatment benefit across measures of functional outcomes. Functional independence at 90 days occurred among 45 percent of the patients in the endovascular therapy group vs 32 percent of the patients in the standard medical care group. Compared with standard medical care, endovascular thrombectomy was associated with significantly higher rates of angiographic revascularization at 24 hours but no significant difference in rates of symptomatic intracranial hemorrhage (5.7 percent vs 5.1 percent) or all-cause mortality at 90 days (218 deaths [16 percent] vs 201 deaths [18 percent]).
“This meta-analysis synthesizes evidence from multicenter randomized clinical trials, and may help inform the design and execution of future studies examining the efficacy of endovascular therapy for acute ischemic stroke. Additional trials are needed to systematically study the relationship of patient-, disease-, and treatment-related variables with outcomes following mechanical thrombectomy, and to identify the ideal patient to undergo endovascular therapy.”
Editor’s Note: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Editorial: Thrombectomy for Acute Ischemic Stroke
“Thrombectomy appears to improve functional outcome for selected patients with internal carotid artery or middle cerebral artery main stem thrombus who have limited comorbidities and who are younger than 80 years. For these patients, intravenous recombinant tissue plasminogen activator should be initiated quickly (if the patient has no contraindications) while rapidly preparing for thrombectomy. Perfusion imaging is not essential,” write Joanna M. Wardlaw, M.D., F.R.C.R., and Martin S. Dennis, M.D., F.R.C.P., of the University of Edinburgh, United Kingdom, in an accompanying editorial.
“However, clinicians should realize that thrombectomy is not necessarily safer than standard medical care, with similar risks of symptomatic intracranial hemorrhage and all-cause mortality reported by Badhiwala et al, along with potential procedural risks.”
“Additional rigorous trials would help to define which additional patients might benefit from thrombectomy and, by how much, including consideration of the effects of comorbidities, advanced age, limits of extractable thrombus location or extent and the latest time window (probably >6 hours). Studies also are needed to determine how to implement thrombectomy in routine practice, including testing the thorny question of who should perform the procedure, and whether the balance of benefit, cost, and service efficiency favor treating just those patients who individually will gain most or treating all patients with a reasonable chance of some worthwhile benefit.”
Although gonorrhea susceptibility to the antibiotic cefixime has been improving in recent years, suggesting a halt of a drift towards antibiotic resistance, data for 2014 indicates a worsening of susceptibility, according to a study in the November 3 issue of JAMA.
Gonorrhea is a common sexually transmitted disease that, if untreated, can cause a number of reproductive and general health complications. Treatments for gonorrhea have been repeatedly jeopardized by antimicrobial resistance. To ensure effective treatment, the U.S. Centers for Disease Control and Prevention (CDC) periodically updates guidelines based on resistance trends. Following declining cephalosporin susceptibility in several countries, the CDC updated its treatment recommendation in 2010 from single-dose cephalosporin (injectable ceftriaxone or oral cefixime) to a higher dose of ceftriaxone or cefixime plus a second antimicrobial. In 2012, the CDC again updated treatment guidelines and recommended ceftriaxone-based combination therapy as the single recommended therapy.
Robert D. Kirkcaldy, M.D., M.P.H., of the CDC, Atlanta, and colleagues examined recent gonorrhea susceptibility trends (when antibiotics are effective at killing or stopping the growth of a certain bacteria in the laboratory, the bacteria is known as susceptible to antibiotics) to third generation cephalosporin antibiotics (injectable ceftriaxone or oral cefixime). The researchers analyzed data from the CDC’s Gonococcal Isolate Surveillance Project, a system that monitors antimicrobial susceptibility in urethral (opening through which urine is discharged) isolates from men with gonorrhea treated at U.S. public clinics for sexually transmitted disease.
During 2006-2014, 51,144 isolates were collected in 34 cities. The percentage of participants treated with 250 mg of ceftriaxone intramuscularly increased from 8.7 percent in 2006 to 96.6 percent in 2014. The percentage of isolates with reduced cefixime susceptibility increased from 0.1 percent in 2006 to 1.4 percent in 2011, and then declined to 0.4 percent in 2013. In 2014, the percentage of resistant isolates increased to 0.8 percent.
“Although this improvement in susceptibility appears temporally correlated with treatment guideline changes, we cannot establish a causal relationship,” the authors write. “The 2014 data, however, suggest that improvements in susceptibility may be short-lived.”
“The increased prevalence of reduced cefixime susceptibility in 2014 highlights the need to maintain surveillance, search for new therapeutics, and ensure that gonorrhea is treated according to the CDC’s guidelines.”
Editor’s Note: The Gonococcal Isolate Surveillance Project is funded by the CDC. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
Although the absolute risk was low, researchers found an increased risk of childhood-onset epilepsy among children in Denmark who had a hospital-diagnosed pertussis infection, compared with the general population, according to a study in the November 3 issue of JAMA.
Pertussis, an acute respiratory tract infection, is among the most common vaccine-preventable childhood diseases in developed countries. Worldwide, an estimated 16 million cases occur each year; almost 50,000 pertussis cases were reported in the United States in 2012. Pertussis is characterized by spasms of coughing and a protracted course. During the acute phase, pertussis is associated with seizures in infants, but the likelihood of developing epilepsy has not been known. Epilepsy is the most common neurologic childhood disorder, and its cause is poorly understood, according to background information in the article.
Morten Olsen, M.D., Ph.D., of the Aarhus University Hospital, Aarhus N, Denmark, and colleagues used population-based medical registries covering all Danish hospitals to identify all patients with pertussis born between 1978 and 2011, followed up through 2011. A database was used to identify 10 individuals from the general population for each patient with pertussis, matched on sex and year of birth.
The researchers identified 4,700 patients with pertussis (48 percent male), of whom 53 percent were diagnosed before age 6 months. In the pertussis cohort, 90 children were diagnosed with epilepsy, compared with 511 children in the comparison cohort. The cumulative incidence of epilepsy at age 10 years was 1.7 percent for patients in the pertussis cohort and 0.9 percent for members of the comparison cohort. Patients older than 3 years when diagnosed with pertussis were not at increased risk of epilepsy compared with the general population.
The authors write that potential mechanisms underlying the observed association include hypoxic brain damage from coughing, perhaps via increased intrathoracic and intra-abdominal pressure and central nervous system hemorrhages.
Editor’s Note: The study was supported by grants from the Program for Clinical Research Infrastructure established by the Lundbeck Foundation and the Novo Nordisk Foundation. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, NOVEMBER 3, 2015
Media Advisory: To contact Louise Kuhn, Ph.D., call Stephanie Berger at 212-305-4372 or email sb2247@columbia.edu. To contact editorial author Ram Yogev, M.D., call Julie Pesch at 312-227-4261 or email jpesch@luriechildrens.org.
Louise Kuhn, Ph.D., of Columbia University, New York, and colleagues evaluated whether HIV-infected children in South Africa who had achieved viral suppression with one treatment could transition to efavirenz-based therapy without risk of viral failure. The study appears in the November 3 issue of JAMA.
Implementation of pediatric antiretroviral treatment (ART) programs in sub-Saharan Africa has resulted in significant reductions in morbidity and mortality among children infected with human immunodeficiency virus (HIV), changing a rapidly fatal disease into a chronic condition. For infants and young children, ritonavir-boosted lopinavir-based therapy is recommended as first-line ART. In adults and older children, efavirenz is recommended as part of first-line ART. Advantages of this regimen include once-daily dosing, simplification of co-treatment for tuberculosis, preservation of ritonavir-boosted lopinavir for second-line treatment, and alignment of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz in children exposed to nevirapine for prevention of mother-to-child transmission.
This study, conducted at a hospital in Johannesburg, South Africa, included HIV-infected children 3 years of age or older exposed to nevirapine for prevention of mother-to-child transmission and who had plasma HIV RNA of less than 50 copies/ml during ritonavir-boosted lopinavir-based therapy. Participants were randomly assigned to switch to efavirenz-based therapy (n = 150) or continue ritonavir-boosted lopinavir-based therapy (n = 148). The children were followed up to 48 weeks after randomization.
The researchers found that switching to efavirenz-based therapy compared with continuing ritonavir-boosted lopinavir-based therapy did not result in significantly higher rates of viral rebound (i.e., HIV RNA >50 copies/mL) or viral failure (i.e., confirmed HIV RNA >1000 copies/mL). “This therapeutic approach may offer advantages in children such as these.”
“There is little guidance available as to what clinicians ought to do when confronted with a child older than 3 years who has begun treatment with ritonavir-boosted lopinavir. As a result, it has been left to individual interpretation, and there are anecdotal reports of clinicians switching to efavirenz in the absence of data to support such a practice. This study provides evidence to support the safety and efficacy of switching to efavirenz, the recommended drug for children older than 3 years, among children with viral suppression,” the authors write.
Editor’s Note: The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Editorial: Antiretroviral Therapy for Nevirapine-Exposed Children With HIV Infection
Ram Yogev, M.D., of Lurie Children’s Hospital, Chicago, comments on the findings of this study in an accompanying editorial.
“The study by Coovadia et al is an important contribution in the evolving science of how to treat perinatally HIVinfected children. Even when combination ART controls the viral load, HIV-related complications remain (e.g., cardiovascular disease), and strategies to improve patient outcomes are needed that include early treatment and chemoprophylaxis as well as research on vaccines and an effective cure.”
A reduced risk for childhood asthma at the age of six was associated with exposure to dogs or farm animals during a child’s first year of life, according to an article published online by JAMA Pediatrics.
Childhood asthma is a global health concern. A number of environmental factors have been associated with either increased or decreased risk of asthma.
Tove Fall, Ph.D., of Uppsala University, Sweden, and coauthors looked at the association between animal exposure and asthma in a nationwide study that included all of the more than 1 million children born in Sweden from 2001 through 2010. Registry data was used for information on dog and farm animals, as well as asthma medication and diagnosis.
The analyses included 376,638 preschool-age (53,460 exposed to dogs and 1,729 exposed to farm animals) and 276,298 school-age children (22,629 exposed to dogs and 958 exposed to farm animals). Of those children, 18,799 children (5 percent) in the preschool-age group had an asthmatic event before baseline and 28,511 cases of asthma were recorded during follow-up. In the group of school-age children, 11,585 children (4.2 percent) had an asthmatic event during the seventh year of life.
Dog exposure during the first year of life was associated with a 13 percent decreased risk of asthma in school-age children. Farm animal exposure was associated with a 52 percent reduced risk of asthma in school-aged children and 31 percent reduced risk in preschool-age children respectively, the results indicate.
The authors note their results were independent of parental asthma or whether the child was first-born. Some study limitations were mentioned.
“For what we believe to be the first time in a nationwide setting, we provide evidence of a reduced risk of childhood asthma in 6-year-old children exposed to dogs and farm animals. This information might be helpful in decision making for families and physicians on the appropriateness and timing of early animal exposure,” the study concludes.
(JAMA Pediatr. Published online November 2, 2015. doi:10.1001/jamapediatrics.2015.3219. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made conflict of interest and funding/support disclosures. Please see article for additional information, including other authors, author contributions and affiliations, etc.
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EMBARGOED FOR RELEASE: 11A.M. (ET), MONDAY, NOVEMBER 2, 2015
Media Advisory: To contact corresponding author Laura Widman, Ph.D., call Matt Shipman at 919-515-6386 or email matt_shipman@ncsu.edu. To contact corresponding editorial author Vincent Guilamo-Ramos, Ph.D., M.P.H., L.C.S.W., R.N., call Robert Polner at 212-998-2337 or email robert.polner@nyu.edu.
Talking about sex with parents, especially mothers, had an effect on safer sex behavior among adolescents, especially girls, according to an article published online by JAMA Pediatrics.
Risky sexual behavior among adolescents is a serious public health problem because of the risk of sexually transmitted infections and unintended pregnancies. Communication between parents and adolescents is one factor that could positively affect safer sex behavior among teens, including the use of contraception and condoms. However, such open communication about sex does not always take place because embarrassment and inaccurate knowledge can get in the way.
Laura Widman, Ph.D., of North Carolina State University, Raleigh, and coauthors reviewed medical literature and pooled data from 30 years of research with more than 25,000 adolescents from 52 articles to examine the effect of parent-adolescent sexual communication on safer sex behavior among youth.
The data indicate a small but significant positive effect of parent-adolescent sexual communication associated with safer sex behavior. That association was stronger for girls and stronger for adolescents who discussed sexual topics with their mothers. The association between parent communication and adolescents’ contraceptive and condom use was significantly stronger for girls than boys, the study reports.
“Results of this study confirm that parent-adolescent sexual communication is a protective factor for youth, and a focus on communication remains justified in future intervention efforts,” the study concludes.
(JAMA Pediatr. Published online November 2, 2015. doi:10.1001/jamapediatrics.2015.2731. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made funding/support disclosures. Please see article for additional information, including other authors, author contributions and affiliations, etc.
Editorial: Parent-Adolescent Communication about Contraception, Condom Use
In a related editorial, Vincent Guilamo-Ramos, Ph.D., M.P.H., L.C.S.W., R.N., of New York University, and coauthors write: “In summary, the meta-analysis by Widman et al provides evidence that parent-adolescent communication is associated with adolescent use of contraceptives and condoms. Most research has focused on parental influences in delaying sexual debut. Sexually active youths also benefit from parental discussions regarding sexual and reproductive health outcomes. Youth want to hear from their parents and overwhelmingly say that parents matter. Hence, public health efforts should support the unique role that parents can play in sexual decision making among adolescents.”
(JAMA Pediatr. Published online November 2, 2015. doi:10.1001/jamapediatrics.2015.3109. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see article for additional information, including other authors, author contributions and affiliations, etc.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), MONDAY, NOVEMBER 2, 2015
Media Advisory: To contact study corresponding author Tewodros Eguale, M.D., Ph.D., call Chris Chipello at 514-398-4201 or email chris.chipello@mcgill.ca. To contact corresponding commentary author Chester B. Good, M.D., call Sheila Tunney at 412-360-1479 or email Sheila.Tunney@va.gov.
Off-label use of prescription drugs was associated with adverse drug events in a study of patients in Canada, especially off-label use lacking strong scientific evidence, according to an article published online by JAMA Internal Medicine.
Off-label prescribing of drugs is common and has been identified as a potentially important contributor to preventable adverse drug events (ADEs).
Tewodros Eguale, M.D., Ph.D., of McGill University, Montreal, Canada, and now of MCPHS University (Massachusetts College of Pharmacy and Health Sciences), Boston, and coauthors looked at the off-label use of prescription drugs and its effect on ADEs in 46,021 patients who received 151,305 prescribed drugs from primary care clinics in Quebec, Canada. Electronic health records documented treatment indications and outcomes. Prescriptions dispensed from 2005 through 2009 were followed up and examined. The authors looked at off-label prescription drug use with and without strong scientific evidence.
The authors identified 3,484 ADEs in the 46,021 study patients. The overall incidence rate of ADEs for all drugs was 13.2 per 10,000 person-months. The rate of ADEs for off-label use (19.7 per 10,000 person-months) was higher than for on-label use (12.5 per 10,000 person-months), according to the results.
Off-label use that lacked strong scientific evidence had a higher ADE rate (21.7 per 10,000 person-months) compared with on-label use and off-label use with strong scientific evidence (13.2 per 10,000 person-months) had about the same risk for ADEs as on-label use, the study reports.
The risk for ADEs grew as the number of prescription drugs the patient used increased, according to the authors. For example, patients using eight or more drugs had more than a 5-fold increased risk for ADEs compared with patients who used one to two drugs.
The authors note a number of study limitations, which include missed medication-related symptoms by physicians and patients who don’t tell physicians about all their symptoms. The study also did not measure the cost of ADEs.
“Off-label drug use, and particularly off-label use without strong scientific evidence, is a risk factor for ADEs. Hence, physicians and physician organizations should recognize the enormity of the problem and be active participants in the promotion of cautious prescribing of drugs for off-label uses lacking strong scientific evidence. Future EHRs should be designed to enable postmarketing surveillance of treatment indications and treatment outcomes to monitor the safety of on- and off-label uses of drugs,” the authors conclude.
(JAMA Intern Med. Published online November 2, 2015. doi:10.1001/jamainternmed.2015.6058. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
Commentary: Turning Up the Heat on Off-Label Prescribing
In a related commentary, Chester B. Good, M.D., M.P.H., and Walid F. Gellad, M.D., M.P.H., of the Veterans Affairs Pittsburgh Heathcare System, write: “Egulae and colleagues have provided compelling evidence that off-label prescribing is frequently inappropriate and that prescribing in these circumstances increases the risk for an adverse event substantially. The FDA and the courts must carefully consider these findings as they contemplate guidance that would relax regulations to permit promotion of drugs beyond their labeled indications.”
(JAMA Intern Med. Published online November 2, 2015. doi:10.1001/jamainternmed.2015.6068. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
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Patients with chronic rhinosinusitis (sinus infection) who decided to continue medical therapy rather than undergo surgery had little change in productivity, with results suggesting that medical therapy may help these patients maintain their level of productivity, according to a study published online by JAMA Otolaryngology-Head & Neck Surgery.
Chronic rhinosinusitis (CRS) significantly reduces daily productivity, and the degree of lost work is associated with the severity of quality-of-life (QOL) impairment. It is estimated that lost productivity related to CRS costs society in excess of $13 billion per year in the United States. Although endoscopic sinus surgery (ESS) is an effective intervention for select patients with CRS, some patients make a preference-sensitive decision to continue with medical therapy as opposed to undergoing surgery. Given that continued medical therapy is a viable treatment option for refractory (difficult to treat) CRS, it is important to define the effect on productivity level to inform patients of expected outcomes, according to background information in the article.
Luke Rudmik, M.D., M.Sc., of the University of Calgary, Canada, and colleagues examined the change in productivity costs in patients with refractory CRS whose initial appropriate medical therapy failed and selected to continue medical therapy rather than have surgery. Absenteeism, presenteeism, and lost leisure time were quantified to define annual lost productive time, which was measured at enrollment (baseline) and at a minimum of 6 months after treatment.
Thirty-eight patients with refractory CRS who selected continued medical therapy had an average baseline annual productivity cost of $3,464 per patient. After continued medical therapy for an average of 12.8 months, productivity costs were $2,730 (before vs after continued medical therapy productivity cost). Average annual absenteeism was reduced from 5 days to 2 days. Average annual presenteeism (17 days reduced to 15 days) and average annual household days lost (7 days reduced to 6) were maintained at baseline levels.
“Patients with refractory CRS often make treatment decisions based on their degree of QOL and productivity impairment,” the authors write. “This prospective study evaluated the productivity outcomes in a select group of patients with refractory CRS who made a decision to continue medical therapy rather than undergoing ESS. Patients who continued medical therapy had mild reductions in their baseline productivity (92 percent). Although the results need to be validated with a larger sample, outcomes from this study suggest that continued medical therapy can maintain baseline productivity level in this select cohort of patients with CRS. These outcomes may be used to improve patient-centered care for CRS by informing the appropriate patients of their expected outcomes from continued medical therapy.”
(JAMA Otolaryngol Head Neck Surg. Published online October 29, 2015. doi:10.1001/.jamaoto.2015.2321. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: This study was supported by grants from 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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The use of superlatives to describe cancer drugs in news articles as “breakthrough,” “revolutionary,” “miracle” or in other grandiose terms was common even when drugs were not yet approved, had no clinical data or not yet shown overall survival benefits, according to an article published online by JAMA Oncology.
The omission of medical context or the use of inflated descriptions can lead to misunderstandings among readers. Vinay Prasad, M.D., M.P.H., of the Oregon Health & Science University, Portland, and coauthors examined the use of modest and superlative descriptors in news articles regarding cancer drugs.
The authors searched for 10 superlatives (breakthrough, game changer, miracle, cure, home run, revolutionary, transformative, life saver, groundbreaking and marvel) in conjunction with the term “cancer drug” in a Google news search earlier this year between June 21 and June 25. The authors found 94 articles from 66 news outlets with 97 superlative mentions meeting the study criteria and referring to 36 specific drugs. Half of the drugs described had not yet received approval from the U.S. Food and Drug Administration for at least one indication.
The most common class of drugs referenced was targeted therapy (17 of 36), nine cytotoxic drugs, five immunotherapy checkpoint inhibitors, three cancer vaccines, one radiotherapy and one gene therapy. Superlatives were used most often to refer to targeted therapy and an immunologic checkpoint inhibitor. For 5 of the 36 drugs (14 percent), superlatives were used in the absence of clinical data, according to the results.
Most of the 97 superlatives were used by journalists (55 percent); physicians (27 percent); industry experts (9 percent); patients (8 percent) and one member of Congress (1 percent). In 55 percent of the cases, the superlative was used by the author of the article without any other attribution.
“A range of speakers used superlatives but the majority were journalists (55 percent), who may not have the expertise to identify the most promising medical therapies, or what magnitude of benefit warrants a superlative. The use of superlatives is common in cancer research news articles. Some of this use may be questioned,” the authors conclude.
(JAMA Oncol. Published online October 29, 2015. doi:10.1001/jamaoncol.2015.3931. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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Patient self-esteem measures appear to be unconnected to a positive outcome after face-lift surgery because patients felt they looked almost nine years younger but there was no change in self-esteem, according to an article published by JAMA Facial Plastic Surgery.
Face-lift surgery can restore the appearance of youth to an aging face. As with all cosmetic surgery, psychosocial factors weigh heavily in both the decision to have surgery as well as defining the outcomes of the procedure. With the number of face-lift procedures steadily increasing by nearly 30 percent since 1997, it is increasingly important to understand the psychosocial effects of this popular procedure.
Andrew Jacono, M.D., of the New York Center for Facial Plastic and Laser Surgery, New York, and coauthors used a self-esteem scale to look at the outcome of face-lift surgery as perceived by the patient to understand the association between self-esteem and the results of aesthetic facial rejuvenation.
The study included 59 patients undergoing face-lift surgery from July through October 2013; of the 59 patients, 50 completed the six-month post-operative questionnaire. All but two of the patients were women with an average age of 58.
Patients with low self-esteem had a statistically significant increase in self-esteem scores after surgery, while those with high preoperative self-esteem showed a statistically significant decrease in self-esteem scores. The group with average preoperative self-esteem showed a nonsignificant increase six months after surgery, according to the results. However, the overall difference between the average preoperative and postoperative self-esteem scores was not statistically significant.
While patients felt they looked nearly nine years younger that perceived change in youthful appearance did not correlate with changes in self-esteem, the authors report.
“These findings underscore the complex nature of the human psyche as it relates to aesthetic surgery and demonstrates that patients exhibit a wide spectrum of psychological reactions after face-lift surgery,” the study concludes.
(JAMA Facial Plast Surg. Published October 29, 2015. doi:10.1001/jamafacial.2015.1460. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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Among more than 1,500 adults who underwent cardiac surgery, those who were divorced, separated, or widowed were more likely to have died or develop a new functional disability after the surgery compared with the married participants, according to a study published online by JAMA Surgery.
Chances of survival after major surgery may be better among married vs unmarried persons, but little is known regarding the association between marital status and postoperative function. Characterizing the association between marital status and postoperative function may be useful for counseling patients and identifying at-risk groups that may benefit from targeted interventions aimed at improving functional recovery.
Mark D. Neuman, M.D., M.Sc., and Rachel M. Werner, M.D., Ph.D., of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia used data from the University of Michigan Health and Retirement Study, which has enrolled 29,053 adults 50 years of age or older since 1998. The study participants undergo interviews every 2 years regarding health, functioning, medical care, and family structure. The sample for this analysis included surviving participants who reported having undergone cardiac surgery in the interval since the preceding interview and deceased participants for whom proxies reported a cardiac surgery since the last interview.
The study included 1,576 participants; at the time of study entry, 65 percent were married, 12 percent were divorced or separated, 21 percent were widowed, and 2 percent were never married. Married participants were more likely to be male and to demonstrate lower levels of other illnesses and disability before surgery. At the postsurgery interview, 19 percent of married participants, 29 percent of divorced or separated individuals, 34 percent of widowed participants, and 20 percent of participants who had never been married had either died or developed a new disability (unable to perform independently an activity of daily living such as dressing, walking, eating).
Marital status was significantly associated with death or a new functional disability. Participants who were divorced, separated, or widowed had an approximately 40 percent greater odds of dying or developing a new functional disability during the first 2 years after cardiac surgery compared with the married participants.
“These findings extend prior work suggesting postoperative survival advantages for married people and may relate to the role of social supports in influencing patients’ choices of hospitals and their self-care,” the authors write. They add that their findings suggest “that marital status is a predictor of survival and functional recovery after cardiac surgery. Further research is needed to define the mechanisms linking marital status and postoperative outcomes.”
(JAMA Surgery. Published online October 28, 2015. doi:10.1001/jamasurg.2015.3240. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: This work was supported by the National Institutes of Health, Bethesda, Md. No conflict of interest disclosures were reported.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), WEDNESDAY, OCTOBER 28, 2015
Media Advisory: To contact corresponding author Mark Olfson, M.D., M.P.H., call Rachel Yarmolinsky at 646-774-5353 or email Yarmoli@nyspi.columbia.edu. To contact corresponding editorial author John J. McGrath, M.D., Ph.D., email j.mcgrath@uq.edu.au.
Adults with schizophrenia were more than 3.5 times as likely to die as adults in the general U.S. population, particularly from cardiovascular and respiratory diseases, and that implicates tobacco as a modifiable risk factor, according to an article published online by JAMA Psychiatry.
Many factors, including economic disadvantage, negative health behaviors, and difficulty accessing and adhering to medical treatments are believed to contribute to premature death among individuals with schizophrenia. Smoking, limited physical activity, obesity, elevated blood glucose level, hypertension and dyslipidemia are more common in individuals with schizophrenia than in the general population.
Mark Olfson, M.D., M.P.H.., of Columbia University, New York, and coauthors describe the overall and cause-specific death rates and standardized mortality ratios (SMRs, which are used to compare death rates in populations) for adults with schizophrenia compared with the U.S. general population. The authors identified a national group of more than 1.1 million Medicaid patients with schizophrenia (between the ages of 20 to 64) and 74,003 deaths, of which 65,553 had a known cause.
Among the 65,553 deaths with a known cause, 55,741 were from natural causes, which include a variety of diseases, and 9,812 were due to unnatural deaths, which included suicide, homicide assault and accidents, both poisoning and nonpoisoning, according to the results.
Cardiovascular disease had the highest mortality rate (403.2 per 100,000 person-years) and accounted for almost one-third of all natural deaths (n=19,381). Cancer accounted for about 1 in 6 deaths. Among the other natural causes of death, chronic obstructive pulmonary disease (COPD), diabetes, influenza and pneumonia had the highest mortality rates, study results indicate.
Unnatural causes of death accounted for about 1 in 7 deaths with known causes (n=9,812), with suicide accounting for about one-quarter of the unnatural deaths (n=2,498). Accidents accounted for more than twice as many deaths (n=5,753) as suicide.
Nonsuicidal substance-induced death, mostly from alcohol or other drugs, also was a leading cause of death (95.2 per 100,000 person-years).
Limitations noted by the authors include not having information about key health risk factors such as smoking status, body mass index and substance abuse.
“The results from this study confirm a marked excess of deaths in schizophrenia, particularly from cardiovascular and respiratory disease, that is evident in early adulthood and persists into later life. Especially high risks of mortality were observed from diseases for which tobacco use is a key risk factor. These findings support efforts to train mental health care professionals in tobacco use prevention and treatment and in implementation of policies that incentivize smoking control interventions in settings treating patients with schizophrenia,” the study concludes.
(JAMA Psychiatry. Published online October 28, 2015. doi:10.1001/jamapsychiatry.2015.1737. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: An author made a conflict of interest disclosure. This research was supported by a grant from the Agency for Healthcare Research and Quality and by the New York State Psychiatric Institute. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: An Urgent Call to Address the Deadly Consequences of Serious Mental Disorders
In a related editorial, John J. McGrath, M.D., Ph.D., of the Queensland Centre for Mental Health Research, the Park Centre for Mental Health, Australia, and coauthors write: “The article by Olfson and colleagues in this issue of JAMA Psychiatry is reminder of how we are failing to meet the needs of people with schizophrenia. … The findings by Olfson and colleagues highlight the need to focus on interventions that target lifestyle risk factors such as smoking and poor diet, treat medical risk factors such as hypertension and hypercholesterolemia, and assertively manage physical comorbidities such as diabetes mellitus and cardiovascular disease.”
(JAMA Psychiatry. Published online October 28, 2015. doi:10.1001/jamapsychiatry.2015.1981. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made fund/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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Immune dysfunction underlies the development of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Immunosuppressive therapy is a risk factor for nonmelanoma skin cancer (NMSC). Frank I. Scott, M.D., M.S.C.E., of the University of Pennsylvania, Philadelphia, and coauthors looked at the risk of a second NMSC in Medicare patients with RA or IBD who received immunosuppressive agents including methotrexate, anti-tumor necrosis factor therapy or thiopurines after an initial NMSC. Among 9,460 individuals (6,841 with RA and 2,788 with IBD) the rate of a second NMSC per 1,000 person-years was 58.2 in patients with RA and 58.9 in patients with IBD.
(JAMA Dermatology. Published online October 28, 2015. doi:10.1001/jamadermatol.2015.3029. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made conflict of interest and funding/support disclosures. 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, OCTOBER 27, 2015
Media Advisory: To contact Jiemin Ma, Ph.D., M.H.S., email David Sampson at david.sampson@cancer.org. To contact editorial author J. Michael McGinnis, M.D., M.P.P., email Jennifer Walsh at jwalsh@nas.edu.
An analysis of deaths in the United States between 1969 and 2013 finds an overall decreasing trend in the age-standardized death rate for all causes combined and for heart disease, cancer, stroke, unintentional injuries, and diabetes, although the rate of decrease appears to have slowed for heart disease, stroke, and diabetes, according to a study in the October 27 issue of JAMA.
A comprehensive examination of long-term trends in mortality is important for health planning and priority setting and for identifying modifiable factors that may contribute to the trends. Jiemin Ma, Ph.D., M.H.S., of the American Cancer Society, Atlanta, and colleagues analyzed U.S. national vital statistics data from 1969 through 2013 to determine total and annual percent change in age-standardized death rates and years of potential life lost before age 75 years for all causes combined and for the leading causes.
Between 1969 and 2013, the age-standardized death rate for all causes combined decreased from 1,279 per 100,000 population to 730 (43 percent reduction) – an average annual decrease of 1.3 percent. Five of the six leading causes of death experienced an overall decline in death rates during this time period. The rate of death (per 100,000) decreased for stroke by 77 percent; for heart disease, by 68 percent; for unintentional injuries, by 40 percent; for cancer, by 18 percent; and for diabetes, by 17 percent. The death rate for chronic obstructive pulmonary disease (COPD) increased by 101 percent during this period. However, during the last time segment in the analysis, the death rate for COPD in men began to decrease and the declines in rates slowed for heart disease, stroke, and diabetes. For example, the annual decline for heart disease slowed from 3.9 percent during the 2000-2010 period to 1.4 percent during the 2010-2013 period.
Between 1969 and 2013, age-standardized years of potential life lost per 1,000 decreased from 1.9 to 1.6 for diabetes (14.5 percent reduction); a 41 percent reduction for cancer; 48 percent for unintentional injuries; 68 percent for heart disease; and 75 percent for stroke. For COPD, the rate for years of potential life lost did not decrease over this time interval.
The researchers write that the progress against heart disease and stroke is attributed to improvements in control of hypertension and hyperlipidemia, smoking cessation, and medical treatment. “The reduction in cancer deaths since the early 1990s is also an outcome of tobacco control efforts, as well as advances in early detection and treatment. Notably, the years-of-potential-life lost rate from cancer has been decreasing since 1969, preceding the decline in cancer death rates by about 20 years. This may reflect the importance of smoking cessation in substantially reducing premature mortality. The overall decrease in the death rate for unintentional injuries has been largely attributed to continuous declines in motor vehicle–related deaths.”
The authors note that the observed recent slowing of the decline in death rates for obesity-related diseases (e.g., heart disease, stroke, and diabetes) may reflect the lagged consequences of increased obesity prevalence since the 1980s.
“Further disease-specific studies are needed to investigate these trends. Regardless of the changes in death rates, the increasing numbers of old persons in the United States and growth of the U.S. population will pose a considerable challenge for health care delivery in the coming decades, in view of the shortage of primary care physicians and geriatricians, increasing cost of health care, and the lag between healthy life and life expectancies.”
Editor’s Note: This work was supported by the Intramural Research Department of the American Cancer Society. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Editorial: Mortality Trends and Signs of Health Progress in the United States
“Death rate may have at one time served as a sufficient measure of health system performance, but assessment now requires more textured insights, including those that reflect the improving capacity to measure health status, risk prevalence, and service access, effectiveness, and affordability,” writes J. Michael McGinnis, M.D., M.P.P., of the National Academy of Medicine, Washington D.C., in an accompanying editorial.
“What is needed is a set of national vital health indicators that is broader than mortality, but still a limited number, tightly constructed, standardized, and reliably available at all levels from local to national. Earlier this year, an Institute of Medicine Committee on Core Metrics for Better Health at Lower Cost, released its report, Vital Signs: Core Metrics for Health and Health Care Progress. The Committee recommended 15 core measures across 4 domains—healthy people, quality care, affordable care, and engaged people—which could be assembled from a manageable set of standardized measures to be collected system-wide. Whether through adoption of this or some other expanded notion of what should constitute the nation’s truly vital signs, the time has arrived to match the capacity with the potential and the need.”
Among black adults with asthma treated with an inhaled corticosteroid, adding a long-acting beta-agonist did not improve the time to an asthma exacerbation compared with adding the anticholinergic tiotropium, according to a study in the October 27 issue of JAMA.
National treatment recommendations suggest increasing inhaled corticosteroid (ICS) dose or adding a long-acting beta-agonist (LABA) to asthma patients with poor asthma control on low-dose ICS. However, asthma experts and the U.S. Food and Drug Administration have questioned the safety of LABA therapy, noting possible increases in serious events, including hospitalizations and death. Data suggest that LABA risks, if they exist, may disproportionately affect black populations and that black individuals may not benefit from LABAs to the same degree as individuals of other races. Investigations in predominantly white populations have attempted to determine if long-acting anticholinergics (a class of drugs that inhibit the transmission of certain nerve impulses, reducing spasms of smooth muscles, such as in the lungs) can substitute for LABAs in asthma, according to background information in the article.
Michael E. Wechsler, M.D., M.Sc., of National Jewish Health, Denver, and Elliot Israel, M.D., of Brigham and Women’s Hospital, Boston, and colleagues randomly assigned black adults with moderate to severe asthma to receive ICS plus either once-daily tiotropium (n = 532) or twice-daily LABAs (n = 538). Patients completed monthly questionnaires and were followed up for up to 18 months. Patients also underwent genetic testing. Some studies have suggested that a genetic variation may be associated with increased rates of adverse outcomes when LABAs are used for asthma, especially among black patients.
The researchers found that the primary outcome, time to first exacerbation, did not differ significantly between groups. In addition, LABA + ICS was not superior to tiotropium + ICS for secondary outcomes that addressed additional dimensions of asthma control, such as patient-reported outcomes (quality of life, asthma control, symptom index, symptom-free days), spirometry (a test of the air capacity of the lungs), rescue medication use, and asthma deteriorations.
Genetic variants were not associated with differential responses to therapy.
“These findings do not support the superiority of LABA + ICS compared with tiotropium + ICS for black patients with asthma,” the authors write.
“Although we could not detect a difference in exacerbations between either combination therapy, we found that, despite combination therapy, this population experienced a high rate of exacerbations. Additional targeted interventions and further study are needed to reduce the rate of asthma exacerbations in this population.”
Editor’s Note: This project was supported by a grant from the Agency for Healthcare Research and Quality. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
In a study of federal marketplace insurance plans, nearly 15 percent completely lacked in-network physicians for at least 1 specialty, a practice found among multiple states and issuers, raising concerns regarding patient access to specialty care, according to a study in the October 27 issue of JAMA.
Nearly 12 million individuals have enrolled in coverage through the Affordable Care Act’s insurance marketplaces. The U.S. Department of Health and Human Services regulates plans, applying a “reasonable access” standard to ensure access to “a sufficient number and type of providers.” Concerns remain about network adequacy, according to background information in the article.
Stephen C. Dorner, M.Sc., of the Harvard T. H. Chan School of Public Health, Boston, and colleagues examined physician networks in 34 states offering plans through the federal marketplace during 2015 open enrollment; this analysis included 135 plans. Using plans’ online directories, the authors searched for in-network specialist physicians for various specialties.
Using a 100 mile and 50 mile search radius, 18 (13 percent) and 19 (14 percent), respectively, of 135 plans were specialist-deficient plans (plans without a specialist physician). Endocrinology, rheumatology, and psychiatry were most commonly excluded, and an additional 7-14 plans had fewer than 5 in-network physicians in those specialties. There was no significant difference in the proportion of specialist deficient plans across insurance plan premium levels. Nine of 34 states (24 percent) had at least 1 specialist-deficient plan. Twelve different insurers had at least 1 specialist-deficient plan.
Beneficiaries of specialist-deficient plans had high out-of-network costs; 5 of 19 (26 percent) plans did not cover out-of-network services, whereas 11 of the remaining 14 plans (79 percent) required cost-sharing of 50 percent or more. Nine of 19 (47 percent) did not cover medications prescribed by out-of-network physicians. There was no significant difference in premiums between specialist-deficient plans and other plans.
Regarding plans that lack in-network physicians for at least 1 specialty, “this likely violates network adequacy requirements, raising concerns regarding patient access to specialty care,” the authors write. “Such plans precipitate high out-of-pocket costs and may lead to adverse selection (i.e., sicker individuals choosing plans with broader networks), which is similar to concerns over restrictive drug formularies.”
Editor’s Note: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Sommers reported currently serving part-time as a senior advisor to the U.S. Department of Health and Human Services. No other disclosures were reported.
Among a survey of youth 12 to 17 years of age, the majority who self-reported ever experimenting with tobacco started with a flavored product, and most current tobacco users reported use of flavored products, according to a study published by JAMA.
Most tobacco use begins during youth and young adulthood. Recent declines in prevalence of cigarette smoking among youth have coincided with increased use of e-cigarettes and hookahs. Although flavors other than menthol are prohibited in cigarettes in the United States, flavored noncigarette tobacco products are widely available and may appeal to youth, according to background information in the article.
Bridget K. Ambrose, Ph.D., M.P.H., of the Center for Tobacco Products, U.S. Food and Drug Administration, Silver Spring, Md., and colleagues examined flavored tobacco use among U.S. youth using data from the Population Assessment of Tobacco and Health Study, a household-based, nationally representative study of 45,971 adults and youth (12-17 years) in the United States. Youth responded to questions about ever and past 30-day use of tobacco products including cigarettes, e-cigarettes, hookahs, cigars, pipe tobacco, all types of smokeless tobacco, dissolvable tobacco, bidis, and kreteks. For each product ever used, youth answered whether the first product they used was flavored (e.g., “Was the first e-cigarette you used flavored to taste like menthol, mint, clove, spice, candy, fruit, chocolate, alcohol [such as wine or cognac], or other sweets?”).
Of the 13,651 youth enrolled and included in this analysis, 51 percent were male, 55 percent non-Hispanic white, 14 percent non-Hispanic black, and 23 percent Hispanic; average age was 14.5 years. The majority of youth ever-users reported that the first product they had used was flavored, including 89 percent of ever hookah users, 81 percent of ever e-cigarette users, 65 percent of ever users of any cigar type, and 50 percent of ever cigarette smokers. For past 30-day youth tobacco use, the overall proportion of flavored product use was 80 percent among users of any product and 89 percent among hookah users, 85 percent among e-cigarette users, 72 percent among users of any cigar type, and 60 percent among cigarette smokers. Youth consistently reported product flavoring as a reason for use across all product types, including e-cigarettes, hookahs, cigars, smokeless tobacco, and snus pouches.
“Consistent with national school-based estimates, this study confirms widespread appeal of flavored products among youth tobacco users. In addition to continued proven tobacco control and prevention strategies, efforts to decrease use of flavored tobacco products among youth should be considered,” the authors write.
Editor’s Note: Funded by the National Institute on Drug Abuse, National Institutes of Health, and the U.S. FDA, Department of Health and Human Services. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
EMBARGOED FOR RELEASE: 11 A.M. (ET), WEDNESDAY, OCTOBER 26, 2015
Media Advisory: To contact corresponding author Shadi Yaghi, M.D., call David Orenstein at 401-863-1862 or email david_orenstein@brown.edu. To contact editorial author Nicole R. Gonzales, M.D., call Deborah Mann Lake at 713-500-3304 or email Deborah.M.Lake@uth.tmc.edu.
Treating brain hemorrhage (symptomatic intracerebral hemorrhage, sICH) after clot-busting thrombolysis for stroke was not associated with a reduced likelihood of in-hospital death or expansion of the hematoma but shortening time to diagnosis and treatment may be key to improving outcomes, according to an article published online by JAMA Neurology.
Intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) can improve outcomes for patients with ischemic stroke treated within 4½ hours of the onset of symptoms. The most serious complication of thrombolysis is sICH, which was reported in 6 percent of patients with stroke in the National Institute of Neurological Disorders and Stroke rtPA trials. Although it is an infrequent complication, sICH is associated with a high mortality rate near 50 percent.
Shadi Yaghi, M.D., of Brown University, Providence, R.I., and colleagues analyzed data from 10 stroke centers across the United States to understand the natural history of thrombolysis-related sICH and to focus on the efficacy of various treatments used. The authors looked at outcomes for in-hospital death and hematoma expansion.
There were 3,894 patients treated with rtPA between January 2009 and April 2014; among them 128 patients (3.3 percent) had sICH. Of those 128 patients, 38.2 percent (49 patients) received any treatment for sICH and 28.9 percent (37 patients) had their code status changed to comfort measures within the first 24 hours after sICH diagnosis.
The authors report the most commonly used treatment was the frozen blood product cryoprecipitate (31.3 percent [40 of 128]). The median time from initiation of rtPA therapy to sICH diagnosis was 470 minutes and the median time from sICH diagnosis to treatment of sICH was 112 minutes.
The in-hospital mortality rate was 52.3 percent (67 of 128 patients) and 26.8 percent of patients (22 of 82) had hematoma expansion. A change in code status to comfort measures after sICH diagnosis was the only factor associated with increased in-hospital death, according to the results.
The authors note the effects of therapy may be underestimated because few patients received each of the sICH treatments.
“In this study, treatment of postthrombolysis sICH did not significantly reduce the likelihood of in-hospital mortality or hematoma expansion. Shortening the time to diagnosis and treatment may be a key variable in improving outcomes of patients with sICH,” the study concludes.
(JAMA Neurol. Published online October 26, 2015. doi:10.1001/jamaneurol.2015.2371. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Can We Make Thrombolysis Safer?
In a related editorial, Tiffany Cossey, M.D., and Nicole R. Gonzales, M.D., of The University of Texas Health Science Center at Houston, write: “Although sICH may be an uncommon occurrence, the known risk weighs heavily on the decision of clinicians to administer tPA [intravenous tissue plasminogen activator], as well as on the decisions of patients and families regarding treatment. It is worthwhile to dedicate efforts to minimizing the risk of this complication for both the direct and indirect benefits.”
((JAMA Neurol. Published online October 26, 2015. doi:10.1001/jamaneurol.2015.2900. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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EMBARGOED FOR RELEASE: 11A.M. (ET), MONDAY, OCTOBER 26, 2015
Media Advisory: To contact corresponding author Adam J. Zolotor, M.D., Dr.P.H., call Donna Parker at 919-260-7854 or email donna_parker@med.unc.edu. To contact corresponding editorial author Joanne N. Wood, M.D., M.S.H.P., call Joey McCool Ryan at 267-426-6070 or email MCCOOL@email.chop.edu. An author audio interview will be live when the embargo lifts on the JAMA Pediatrics website: http://bit.ly/1OP08fv
A program to prevent abusive head trauma (AHT), also known as shaken baby syndrome, was associated with a decline in calls to a nurse advice line but not with a significant change in AHT rates in North Carolina, according to an article published online by JAMA Pediatrics.
AHT is a rare, but severe, form of child maltreatment with severe consequences that can include death or long-term neurological, development and cognitive issues. Infant crying is the most significant trigger of AHT.
Adam J. Zolotor, M.D., Dr.P.H., of the University of North Carolina, Chapel Hill, and coauthors describe the AHT prevention program, the Period of PURPLE Crying, which was delivered to 88 percent of the parents of newborns (n=405,060) in North Carolina from June 2009 through September 2012. The intervention, which was developed by the National Center on Shaken Baby Syndrome, teaches parents about normal infant crying. The intervention included education provided by a nurse, a DVD and a booklet, with messages reinforced by primary care physicians and through a media campaign.
The authors measured changes to the number of after-hours calls to a nurse advice line for infant crying before and after the intervention was implemented. They also analyzed AHT rates over time in North Carolina and in five comparison states.
The authors report that two years after the intervention was implemented, parental telephone calls to the nurse advice line declined by 20 percent for children younger than 3 months and by 12 percent for children 3 to 12 months.
However, there was no significant effect on North Carolina’s state-level AHT rates. North Carolina had average AHT rates of 34.01 per 100,000 person-years before the intervention and 36.04 after the intervention, according to the results. The comparison states had average AHT rates of 33.22 per 100,000 person-years before the intervention and 33.41 after the intervention.
Limitations of the study include that while 88 percent of parents of newborns received the AHT prevention education, it is unknown if those people not exposed to the intervention were at highest risk for AHT. Also, the authors do not know whether perpetrators of AHT were exposed to the program.
“It may be that the intervention was ineffective, the study was underpowered, the follow-up was too brief or a decrease in cases may have been obscured by unmeasured confounding. Future research should use the most robust methods available to establish a causal relationship between prevention programs and AHT,” the study concludes.
(JAMA Pediatr. Published online October 26, 2015. doi:10.1001/jamapediatrics.2015.2690. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made conflict of interest and funding/support disclosures. Please see article for additional information, including other authors, author contributions and affiliations, etc.
Editorial: Challenges in Prevention of Abusive Head Trauma
In a related editorial, Joanne N. Wood, M.D., M.S.H.P., of The Children’s Hospital of Pennsylvania, Philadelphia, writes: “The negative findings from this large, rigorous evaluation study by Zolotor et al raise questions about the effectiveness of AHT prevention programs and highlight the challenges in AHT prevention. … We have made progress in understanding AHT prevention, but we still have much to learn. As Zolotor et al conclude, the high costs of AHT to children, families and society demand that we must not give up.”
(JAMA Pediatr. Published online October 26, 2015. doi:10.1001/jamapediatrics.2015.3023. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: The author made a conflict of interest disclosure. Please see article for additional information, including other authors, author contributions and affiliations, etc.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), MONDAY, OCTOBER 26, 2015
Media Advisory: To contact study corresponding author Jeremy B. Sussman, M.D., M.S., call Kara Gavin at 734-516-5362 or email kegavin@umich.edu. To contact research letter corresponding author Tanner J. Caverly, M.D., M.P.H., call Kara Gavin at 734-516-5362 or email kegavin@umich.edu. To contact corresponding commentary author Enrico Mossello, M.D., Ph.D., email enrico.mossello@unifi.it.
Medication Deintensification in Older Patients with Low HbA1c or Blood Pressure
Among older patients with diabetes whose treatment has resulted in very low hemoglobin A1c (HbA1c) levels or blood pressure values, only 27 percent or fewer underwent medication deintensification, a lost opportunity to reduce overtreatment, according to an article published online by JAMA Internal Medicine.
New guidelines and the Choosing Wisely campaign recommend less aggressive treatment for older patients and those with limited life expectancy, such as a target HbA1c level of 7.5 percent or 8.0 percent. Another report recommends older patients seek to achieve a systolic blood pressure (SBP) of 150 mm Hg and no longer try to reach a level below 140 mm Hg. However, little is known about the process of medication deintensification, including how often it happens and for whom.
Jeremy B. Sussman, M.D., M.S., of the Veterans Affairs Center for Clinical Management Research, Ann Arbor, Mich., and coauthors describe the frequency of medication deintensification among older adults with diabetes using data from the U.S Veterans Health Administration. Participants included 211,667 patients older than 70 receiving active treatment in 2012. Active treatment was defined as blood pressure-lowering medications other than angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or glucose-lowering medications other than metformin hydrochloride.
More than half of the 211,667 participants actively treated for blood pressure had moderately low (SBP of 120 to 129 mm Hg or diastolic blood pressure [DBP] less than 65 mm Hg) or very low (SBP less than 120 mm Hg or DBP less than 65 mm Hg) blood pressure levels. Treatment was deintensified in 16 percent of the 25,955 patients with moderately low blood pressure levels and in 18.8 percent of the 81,226 patients with very low blood pressure levels. Of the patients with very low blood pressure levels whose treatment was not deintensified, only 0.2 percent had a follow-up blood pressure measurement that was elevated (≥ 140/90 mm Hg), according to the results.
The actively treated HbA1c group included 179,991 individuals. Treatment was deintensified in 20.9 percent of the 23,769 patients with moderately low HbA1c (6.0 percent to 6.4 percent) levels and in 27 percent of the 12,917 patients with very low HbA1c (less than 6.0 percent). Of the patients with very low HbA1c whose treatment was not deintensified, fewer than 0.8 percent had a follow-up elevated HbA1c (≥ 7.5 percent), the results indicate.
The authors acknowledge several reasons why low blood pressure or HbA1c levels have a weak association with medication deintensification. Those reasons include requiring a shift in how treatment is understood by patients and explained by health care professionals. Also, guidelines and performance measures are more focused on preventing underuse than overuse.
“Future performance management systems should consider how to create incentives against both overuse and underuse to motivate appropriate treatment, including deintensification of treatment that is personalized to individual needs, risks and benefits. In addition, health care professionals should assess the harms of intensive therapy just as they do the benefits. These changes may require new clinical decision support tools, new performance measures and, most important, a new perspective focusing on personalized, appropriate care,” the authors conclude.
(JAMA Intern Med. Published online October 26, 2015. doi:10.1001/jamainternmed.2015.5110. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Partial funding for this work was provided by the Veterans Health Administration’s Office of Informatics and Analytics. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
Research Letter: Appropriate Prescribing for Patients with Diabetes
A research letter Tanner J. Caverly, M.D., M.P.H., of the Ann Arbor Veterans Affairs Center for Clinical Management Research, Michigan, and coauthors examined the beliefs of primary care health-care professionals (PCPs) as to how receptive they might be to recommendations for limiting medications for some older patients, including a hypothetical scenario involving a 77-year-old man with diabetes at risk for hypoglycemia. The authors surveyed Department of Veterans Affairs PCPs, including physicians, nurse practitioners and physician assistants. Of 1,222 eligible PCPs, 594 returned usable surveys. The results indicate that almost half of the PCPs reported that they would not worry about the harms of tight glycemic control for an older patient at risk for hypoglycemia. Nearly one-quarter of PCPs reported they would worry that deintensifying medication for the man in the hypothetical situation could leave them vulnerable to future malpractice claims.
(JAMA Intern Med. Published online October 26, 2015. doi:10.1001/jamainternmed.2015.5950. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
Commentary: Targeting Vascular Risk Factors in Older Adults: From Polypill to Personalized Prevention
A related commentary by Enrico Mossello, M.D., Ph.D., of the University of Florence and Careggi Teaching Hospital, Florence, Italy, also is available.
(JAMA Intern Med. Published online October 26, 2015. doi:10.1001/jamainternmed.2015.5941. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), THURSDAY, OCTOBER 22, 2015
Media Advisory: To contact corresponding author Quoc-Dien Trinh, M.D., call Johanna Younghans at 617-525-6373 or email jyounghans@partners.org. To contact commentary author Otis W. Brawley, M.D., M.A.C.P., call David Sampson at 213-407-9950 or email david.sampson@cancer.org.
Older black men with localized prostate cancer were more likely to have poorer quality care, incur higher costs and have worse postoperative outcomes than white men but that did not translate to worse overall or cancer-specific survival, according to an article published online by JAMA Oncology.
Prostate cancer is a frequently diagnosed cancer among men in the United States with an estimated 233,000 new cases in 2014. The treatment of prostate cancer is driven, in part, by the severity of disease at presentation. Definitive therapy for localized prostate cancer with the intention of curing it is radical prostatectomy (RP, removal of the prostate gland), radiotherapy or a combination thereof.
Quoc-Dien Trinh, M.D., of Brigham and Women’s Hospital, Harvard Medical School, Boston, and coauthors looked at the effect of race on quality of care and survival of men receiving RP for localized prostate cancer. They used data from the Surveillance, Epidemiology and End Results (SEER)-Medicare database for 26,482 men 65 or older with localized prostate cancer who underwent radical prostatectomy: 2,020 black men (7.6 percent) and 24,462 non-Hispanic white men (92.4 percent).
While the authors found no difference in cancer-specific or overall death between black and white men with localized prostate cancer, the authors note several other findings:
_ 59.4 percent of black men underwent RP within 90 days vs. 69.5 percent of white men.
_ Black men had a seven-day treatment delay compared with white men in the top 50 percent of patients.
_ Black men were less likely to undergo lymph node dissection.
_ Black men were more likely to have postoperative visits to the emergency department or be readmitted to the hospital compared with white men.
_ The top 50 percent of black patients had higher incremental annual costs for surgery, spending $1,185 more compared to white patients.
Limitations to the study include that it was comprised only of Medicare enrollees 65 or older and the authors acknowledge that most men being treated with RP are younger and have private health insurance, so the findings may not be generalizable to the general population of men having RP.
“We provide robust evidence for the existence of a substantial difference in the quality of surgical care of PCa (localized prostate cancer) in blacks. Because the unfavorable quality of care did not translate into worse overall and cancer-specific survival in our sample, the commonly perceived detrimental survival in black patients with PCa may be the sequelae of barriers and selection bias in definitive treatment. Public and professional awareness needs to be raised to address these concerning issues and identify their underlying causes,” the authors conclude.
(JAMA Oncol. Published online October 22, 2015. doi:10.1001/jamaoncol.2015.3384. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Commentary: The Meaning of Race in Prostate Cancer Treatment
In a related commentary, Otis W. Brawley, M.D., M.A.C.P., of the American Cancer Society and Emory University, Atlanta, writes: “The black patients in this study have insurance and access to care and were deemed healthy enough for surgery, but there was still a disparity in quality of that care. … This study documents clear evidence that quality of care differs by race. … Race is an important sociopolitical categorization as quality of care differs. The reason is debatable. Is it racism on the part of physicians? I personally doubt it. My hypothesis is that a higher proportion of black men have physicians who do not routinely perform radical prostatectomies and a higher proportion of blacks are treated at hospitals that have a low volume of prostate surgery. It is widely established that physicians and hospitals that have high volumes of radical prostatectomy have better outcomes. … It is my belief that quality health care is a basic human right. While many blacks get superb health care, being black in America means one is less likely to receive quality care and more likely to have a bad outcome. Schmid and colleagues show this in localized prostate cancer, and it is likely true for other diseases.”
(JAMA Oncol. Published online October 22, 2015. doi:10.1001/jamaoncol.2015.3615. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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For more information, contact JAMA Network Media Relations at 312-464-JAMA (5262) or emailmediarelations@jamanetwork.org.
The National Academy of Medicine announced today the election as a member Howard Bauchner, M.D., Editor in Chief, JAMA and The JAMA Network. Election to the Academy is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.
The National Academy of Medicine, formerly the Institute of Medicine, announced the election of 70 regular members and 10 international members during its annual meeting. “Our newly elected members represent the brightest, most influential, and passionate people in health, science, and medicine in our nation and internationally,” said NAM President Victor J. Dzau. “They are at the top of their fields and are committed to service. The expertise they bring to the organization will help us respond to today’s most pressing health-related challenges and inform the future of health, science, and medicine. It is my privilege to welcome these distinguished individuals to the National Academy of Medicine.”
New members are elected by current active members through a selective process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care, and public health. Established originally as the Institute of Medicine in 1970 by the National Academy of Sciences, the National Academy of Medicine addresses critical issues in health, science, medicine, and related policy.
Additional information about the National Academy of Medicine can be found at http://nam.edu/.
EMBARGOED FOR RELEASE: 11 A.M. (ET), WEDNESDAY, OCTOBER 21, 2015
Media Advisory: To contact corresponding author Bridget F. Grant, Ph.D., call the NIAAA Press Office at 301-443-3860 or email NIAAAPressOffice@mail.nih.gov
The estimated prevalence of adults who used marijuana in the past year more than doubled in the United States between 2001 and 2013 to 9.5 percent, according to an article published online by JAMA Psychiatry.
Laws and attitudes about marijuana are changing, with 23 states having medical marijuana laws and four of these states having also legalized marijuana for recreational use.
Bridget F. Grant, Ph.D., of the National Institute on Alcohol Abuse and Alcoholism, Rockville, Md., and coauthors used nationally representative data on past-year prevalence rates of marijuana use, marijuana use disorder and marijuana use disorder among marijuana users in the United States. Data came from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III).
The prevalence of past-year marijuana use climbed to 9.5 percent of adults in 2012-2013 from 4.1 percent in 2001-2002, with increases particularly notable among women and individuals who were black, Hispanic, living in the South, middle-aged or older, the authors report.
The prevalence of a diagnosis of a past-year marijuana use disorder (abuse or dependence) also increased to 2.9 percent in 2012-2013 from 1.5 percent in 2001-2002, which means nearly 3 of every 10 Americans who used marijuana in the past year had a diagnosis of a marijuana use disorder (approximately 6.8 million Americans). Groups with notable increases included individuals ages 45 to 64 and those individuals who were black or Hispanic, with the lowest incomes or living in the South.
Among marijuana users, the prevalence of marijuana use disorder decreased to 30.6 percent in 2012-2013 from 35.6 percent in 2001-2002. Because there was no increase in the risk for marijuana use disorder found among users, in fact there was a decrease, the increase in prevalence of marijuana use disorders can be attributed to the increase in marijuana users between the two surveys, the authors note.
“In summary, while many in the United States think prohibition of recreational marijuana should be ended, this study and others suggest caution and the need for public education about the potential harms in marijuana use, including the risk for addiction. As is the case with alcohol, many individuals can use marijuana without becoming addicted. However, the clear risk for marijuana use disorders among users (approximately 30 percent) suggests that as the number of U.S. users grows, so will the numbers of those experiencing problems related to such use. This information is important to convey in a balanced manner to health care professionals, policy makers and the public,” the study concludes.
(JAMA Psychiatry. Published online October 21, 2015. doi:10.1001/jamapsychiatry.2015.1858. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: The study includes funding/support disclosures. 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, OCTOBER 20, 2015
Media Advisory: To contact corresponding author Robert A. Smith, Ph.D., of the American Cancer Society, email David Sampson at david.sampson@cancer.org. To contact editorial co-author Nancy L. Keating, M.D., M.P.H., email David Cameron at David_Cameron@hms.harvard.edu.
Among the changes in the American Cancer Society’s updated breast cancer screening guideline is that women with an average risk of breast cancer should undergo regular, annual screening mammography beginning at age 45 years, with women having an opportunity to choose to begin annual screening as early as age 40; women 55 years and older should transition to screening every other year (vs annual), but still have the opportunity to continue with annual screening; and routine screening clinical breast examination is no longer recommended, according to an article in the October 20 issue of JAMA.
Breast cancer is the most common cancer in women worldwide. In the United States, it is estimated that approximately 230,000 women will be diagnosed with breast cancer in 2015. Breast cancer continues to rank second, after lung cancer, as a cause of cancer death in women in the U.S., and is a leading cause of premature mortality for women. Even though death from breast cancer has declined steadily since 1990, largely due to improvements in early detection and treatment, an estimated 40,300 women in the U.S. will die of breast cancer in 2015. Early detection is associated with reduced breast cancer illness and death, according to background information in the article.
Since the last American Cancer Society (ACS) breast cancer screening update for average-risk women was published in 2003, new evidence has accumulated from long-term follow-up of randomized controlled trials and observational studies of organized, population-based screening programs. Evan R. Myers, M.D., M.P.H., of the Duke Evidence Synthesis Group, Duke Clinical Research Institute, Durham, N.C., and colleagues conducted a systematic review of the breast cancer screening literature to update the American Cancer Society 2003 breast cancer screening guideline for women at average risk for breast cancer (this study appears in JAMA); Diana L. Miglioretti, Ph.D., of the University of California Davis School of Medicine, and colleagues performed an analysis of Breast Cancer Surveillance Consortium mammography registry data to address questions related to screening intervals (this study appears in JAMA Oncology). Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms.
The 2015 recommendations for breast cancer screening for women at average risk:
Women should undergo regular screening mammography starting at age 45.
Women 45 to 54 years of age should be screened annually.
Women 55 years and older should transition to biennial screening or have the opportunity to continue screening annually.
Women should have the opportunity to begin annual screening between the ages of 40 and 44 years.
Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer.
Clinical breast examination is not recommended for breast cancer screening among average-risk women at any age.
“The ACS endorses beginning annual screening mammography at age 45 years and transitioning to biennial screening at age 55 years, while retaining the option to continue annual screening, which some women may elect based on personal preference, clinical guidance, or both,” the authors write. “After careful examination of the burden of disease among women aged 40 to 54 years, the guideline development group (GDG) concluded that the lesser, but not insignificant, burden of disease for women aged 40 to 44 years and the higher cumulative risk of adverse outcomes no longer warranted a direct recommendation to begin screening at age 40 years.”
Regarding no longer recommending periodic clinical breast examination (CBE), the researchers write that “the absence of clear evidence that CBE contributed significantly to breast cancer detection prior to or after age 40 years led the GDG to conclude that it could no longer be recommended for average-risk women at any age.”
“This guideline is intended to provide guidance to the public and clinicians, and it is especially designed for use in the context of a clinical encounter. Women should be encouraged to be aware of and to discuss their family history and medical history with a clinician, who should periodically ascertain whether a woman’s risk factor profile has changed. If the woman has an average risk of developing breast cancer, the ACS encourages a discussion of screening around the age of 40 years. The ACS also recommends that women be provided with information about risk factors, risk reduction, and the benefits, limitations, and harms associated with mammography screening.”
“In conclusion, the ACS recommendations are made in the context of maximizing reductions in breast cancer mortality and reducing years of life lost while minimizing the associated harms among the population of women in the United States. The ACS recognizes that the balance of benefits and harms will be close in some instances and that the spectrum of women’s values and preferences will lead to varying decisions. The intention of this new guideline is to provide both guidance and flexibility for women about when to start and stop screening mammography and how frequently to be screened for breast cancer.”
Editor’s Note: The American Cancer Society supported the development of this guideline through the use of general funds. Dr. Oeffinger was supported in part through a Cancer Center Support Grant from the National Institutes of Health/National Cancer Institute. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
Editorial: New Guidelines for Breast Cancer Screening in U.S. Women
“Will the new ACS guideline make it easier for clinicians and women to make decisions about screening mammography? In some ways, the messages from ACS and the U.S. Preventive Services Task Force (USPSTF), 2 major guidelines, are now more consistent. Both guidelines agree that for average-risk women younger than 45 years, the harms of mammography screening likely outweigh the benefits,” write Nancy L. Keating, M.D., M.P.H., of Harvard Medical School, Boston, and Lydia E. Pace, M.D., M.P.H., of Brigham and Women’s Hospital, Boston, in an accompanying editorial.
“For women older than 55 years, biennial mammography is likely to provide the best balance of benefits to harms. The new ACS recommendation to stop screening older women with life expectancies of less than 10 years is practical and consistent with the increasing emphasis on functional vs chronologic age. The more challenging decisions are for women aged 45 to 54 years, for whom ACS recommends annual screening, but for whom the USPSTF recommends no routine screening (age 45-49 years) or biennial screening (age 50-54 years). In communicating with patients, clinicians will have to balance the ACS’ recommendation for more frequent screening against the fact that younger women experience a lower absolute benefit from screening mammography.”
EMBARGOED FOR RELEASE: 11 A.M. (ET), TUESDAY, OCTOBER 20, 2015
Media Advisory: To contact corresponding author Diana L. Miglioretti, Ph.D., call Dorsey Griffith at 916-734-9118 or email dgriffith@ucdavis.edu. To contact corresponding editorial author Wendy Y. Chen, M.D., M.P.H., call John Noble at 617-632-4090 or email johnW_Noble@dfci.harvard.edu.
Author Interview: An author audio interview will be available when the embargo lifts on the JAMA Oncology website: http://bit.ly/1gk4gY2
Premenopausal women diagnosed with breast cancer following a biennial screening mammogram were more likely to have bigger more advanced tumors than women screened annually, while postmenopausal women not using hormone therapy had a similar proportion of tumors with less favorable prognostic characteristics regardless of whether their screening mammogram was biennial or annual, according to an article published online by JAMA Oncology.
Screening mammography intervals remain under debate in the United States. However, mammography accuracy has improved, new breast cancer treatments have been developed, and interest has increased in tailoring screening recommendations to individual risk to maximize the balance of benefits vs. harms.
Diana L. Miglioretti, Ph.D., of the University of California-Davis School of Medicine, and coauthors compared the proportion of less vs. more favorable tumor prognostic characteristics in women with breast cancer who had annual vs. biennial screening mammograms by age, menopausal status and postmenopausal hormone therapy (HT) use. The authors update previous analyses by using narrower intervals for defining annual (11–14 months) and biennial (23-26 months) screening.
The authors used data from Breast Cancer Surveillance Consortium facilities and included a total of 15,440 women (ages 40 to 85) with breast cancer diagnosed within one year of an annual or within two years of a biennial screening mammogram.
The authors defined less favorable prognostic characteristics as tumors that were stage IIB or higher, bigger than 15 millimeters, positive lymph nodes and any one or more of these characteristics.
Among the 15,440 women with breast cancer, most were 50 or older (13,182 or 85.4 percent), white (12,063 or 78.1 percent) and postmenopausal (9,823 or 63.6 percent). Women who had biennial screening mammograms were more likely to be in the youngest (40 to 49) or oldest (70 to 85) age groups and less likely than women screened annually to have a family history of breast cancer.
Premenopausal women (2,027 or 13.1 percent) had higher proportions of ductal carcinoma in situ (DCIS) vs. invasive cancers and invasive tumors with less favorable prognostic characteristics than postmenopausal women. Among premenopausal women, women screened biennially vs. annually had a higher proportion of stage IIB or higher tumors (25.7 percent vs. 19.8 percent), tumors greater than 15 millimeters (65.3 percent vs. 54.6 percent) and node-positive disease (36.6 percent vs. 31.3 percent), the results show.
Differences in these tumor characteristics among postmenopausal women were small and inconsistent, regardless of HT use, and the differences in women taking postmenopausal HT were not statistically significant, the study reports. The proportions of tumors with less favorable prognostic characteristics were not significantly larger for postmenopausal women not taking HT who were screened biennially or annually.
The authors note their study did not measure breast cancer mortality so they do not know if increases in the proportions of less favorable tumors with biennial vs. annual screening would result in differences in breast cancer mortality.
“Our findings suggest that menopausal status may be more important than age when considering breast cancer screening intervals, which is biologically plausible. … Our findings of a lower proportion of less favorable tumors with more frequent screening in premenopausal women, and no statistically significant difference in the proportion of less favorable tumors in postmenopausal women by screening interval, add to evidence about the potential benefits and harms of screening that policymakers can use to set guidelines about screening intervals and women can use when making personal screening decisions with their clinicians,” the authors conclude.
(JAMA Oncol. Published online October 20, 2015. doi:10.1001/jamaoncol.2015.3084. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: An author made a conflict of interest disclosure. This research was supported by the American Cancer Society. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Measuring the Effectiveness of Mammography
In a related commentary, Wendy Y. Chen, M.D., M.P.H., of Brigham and Women’s Hospital and the Dana Farber Cancer Institute, Harvard Medical School, Boston, writes: “Although the authors do not endorse annual or biennial screening, they imply that biennial screening would be acceptable for postmenopausal women but inferior for premenopausal women owing to their findings of a higher proportion of ‘less favorable’ cancers with biennial screening in that subgroup. … This study and others have clearly demonstrated that with less frequent mammography, the tumors will be bigger and have a slightly more advanced stage. However, with our better understanding of tumor biology and improvements in targeted therapy, the best way to optimize the risk and/or benefit of screening may not be to maximize the chances of finding a smaller tumor. Instead, efforts should be focused on a better understanding of how screening interacts with tumor biology with a better understanding of the types of interval cancers and sojourn times and how these characteristics differ by age and/or menopausal status.”
(JAMA Oncol. Published online October 20, 2015. doi:10.1001/jamaoncol.2015.3286. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Among patients with acute, low back pain presenting to an emergency department, neither the nonsteroidal anti-inflammatory drug (NSAID) naproxen combined with oxycodone/acetaminophen or the muscle relaxant cyclobenzaprine provided better pain relief or improvement in functional outcomes than naproxen combined with placebo, according to a study in the October 20 issue of JAMA.
Low back pain (LBP) is responsible for 2.4 percent of visits to U.S. emergency departments, resulting in more than 2.5 million visits annually. These patients are usually treated with NSAIDs, acetaminophen, opioids, or skeletal muscle relaxants, often in combination. Pain outcomes for these patients are generally poor.
Benjamin W. Friedman, M.D., M.S., of the Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, N.Y., and colleagues randomly assigned 323 patients who presented to an emergency department with nontraumatic, nonradicular LBP of 2 weeks’ duration or less to receive a 10-day course of naproxen + placebo (n = 107); naproxen + cyclobenzaprine (5 mg) (n = 108); or naproxen + oxycodone, 5 mg/acetaminophen, 325 mg (n = 108). Participants were instructed to take 1 or 2 of these tablets every 8 hours, as needed for LBP; naproxen, 500 mg, was to be taken twice a day. Patients also received a standardized 10-minute LBP educational session prior to discharge.
The researchers found that neither naproxen combined with oxycodone/acetaminophen nor naproxen combined with cyclobenzaprine provided better pain relief or better improvement in functional outcomes than naproxen combined with placebo. Measures of pain, functional impairment, and use of health care resources were not different between the study groups at 7 days or at 3 months after the emergency department visit.
Regardless of allocation, nearly two-thirds of patients demonstrated clinically significant improvement in LBP and function 1 week later. However, 40 percent of the cohort reported moderate or severe pain, half reported functionally impairing LBP, and nearly 60 percent were still using medication for their LBP 1 week later. By 3-month follow-up, nearly one-fourth of the cohort reported moderate or severe pain and use of medications for LBP. Three months after the emergency department visit, regardless of study group, opioid use for LBP was uncommon, with fewer than 3 percent of patients reporting use of an opioid within the previous 72 hours.
“These findings do not support the use of these additional medications in this setting,” 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.
An analysis of more than 1.9 million mother and infant pairs finds that preeclampsia was significantly associated with noncritical heart defects in offspring, and preeclampsia with onset before 34 weeks was associated with critical heart defects; however, the absolute risk of congenital heart defects was low, according to a study in the October 20 issue of JAMA.
Congenital heart defects are the most common anomalies in infants, affecting every 8 births per 1,000, and are a major cause of infant illness and death, despite significant advancements in medical care. The causes and risk factors for congenital heart defects are mostly unknown. Some studies have shown that the pathology of preeclampsia (a disorder of pregnancy characterized by high blood pressure and excess protein in the urine) begins early and possibly even at the start of pregnancy, around the time of fetal heart morphogenesis. Despite the plausible link, evidence that preeclampsia is associated with congenital heart defects has largely been absent, according to background information in the article.
Nathalie Auger, M.D., M.Sc., F.R.C.P.C., of the University of Montreal, Quebec, Canada and colleagues conducted an analysis of live births before discharge (1989-2012) for the entire province of Quebec, comprising a quarter of Canada’s population. All women who delivered an infant with or without heart defects in any Quebec hospital were included (n = 1,942,072 neonates). The researchers examined the presence of any critical or noncritical congenital heart defect detected in infants at birth, comparing prevalence in those exposed and not exposed to preeclampsia. In general, critical heart defects lead to significant mortality and morbidity if not diagnosed promptly after birth; for noncritical defects, mortality and morbidity are much lower.
The overall prevalence of heart defects was 8.9 per 1,000 infants. Prevalence was higher for infants of women with preeclampsia than without preeclampsia (16.7 vs 8.6 per 1,000). Risk was elevated for defects affecting all general structures of the heart, including the aorta, pulmonary artery, valves, ventricles, and septa. Infants of women with preeclampsia had no increased prevalence of critical heart defects but did have an increased prevalence of noncritical heart defects compared with infants of non-preeclamptic women. Compared with infants of women with late-onset preeclampsia, those with early onset (<34 weeks) had greater prevalence of critical and noncritical heart defects. The absolute risk of congenital heart defects was low.
“Our results help advance the current understanding of the pathophysiology of preeclampsia and congenital heart defects. The relationship between them supports the notion that these disorders share common risk factors and etiology, beginning very early in pregnancy and involving a long cascade of events affecting the development of fetal heart structures throughout gestation,” the authors write.
“Prevention of both preeclampsia and heart defects may well depend on the ability to elucidate these pathways more clearly in future research. Until then, clinicians should be alert to the possibility that preeclampsia may increase the risk of heart defects in fetuses, although more research is needed in other settings to confirm our findings before modification of clinical practice.”
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Among women who received the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine during pregnancy, there was no increased risk of adverse events in the mothers or adverse birth outcomes in newborns for women who had received a tetanus-containing vaccine in the previous 5 years, according to a study in the October 20 issue of JAMA.
Pertussis (whooping cough) is a vaccine-preventable illness that has been increasing in incidence over the past decade in the United States. Neonates (a baby from birth to four weeks) and infants are at increased risk of pertussis-related hospitalization and death compared with older children and adults. The Advisory Committee on Immunization Practices recommends the Tdap vaccine for pregnant women during each pregnancy, regardless of prior immunization status. However, safety data on repeated Tdap vaccination in pregnancy has been lacking, according to background information in the article.
Lakshmi Sukumaran, M.D., M.P.H., of the Centers for Disease Control and Prevention, Atlanta, and colleagues conducted a study that included 29,155 pregnant women, ages 14 through 49 years, using data from 2007 to 2013 from 7 Vaccine Safety Datalink sites in California, Colorado, Minnesota, Oregon, Washington, and Wisconsin. The authors examined outcomes for women who received Tdap in pregnancy following a prior tetanus-containing vaccine less than 2 years before, 2 to 5 years before, and more than 5 years before.
The researchers found no significant differences in rates of acute adverse events in the mothers (fever, allergy, and local reactions) or adverse birth outcomes in neonates (small for gestational age, preterm delivery, and low birth weight) when comparing women who were vaccinated with Tdap during pregnancy regardless of the length of time since a prior tetanus-containing vaccine.
“Our findings should reassure patients and clinicians who might be hesitant to give Tdap vaccine to pregnant women who recently received a Tdap or other tetanus-containing vaccination,” the authors write.
The researchers add that future studies are needed to determine if there are differences in other important adverse pregnancy outcomes, such as stillbirth and spontaneous abortion, when Tdap is given in pregnancy in close intervals from prior tetanus-containing vaccines.
Editor’s Note: This work was supported by the Centers for Disease Control and Prevention and a grant from the National Institute of Allergy and Infectious Diseases. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
Although some studies have suggested that transfusion of stored red blood cell (RBC) concentrates may be harmful, as blood undergoes several physiological changes during storage, an analysis of patients who underwent cardiac surgery in Sweden over a 16-year period found no association between duration of RBC storage and risk of death or serious complications, according to a study in the October 20 issue of JAMA.
Ulrik Sartipy, M.D., Ph.D., of Karolinska University Hospital, Stockholm, Sweden and colleagues identified all patients in Sweden who underwent coronary artery bypass graft surgery, heart valve surgery, or both between 1997 and 2012. Transfusion data were obtained from a nationwide register of blood transfusions. Linkage with national health data registers provided vital status and adverse outcomes. Blood services in Sweden are part of the public health care system and follow national guidelines, whereby the oldest available blood unit of the appropriate blood type is allocated first.
During the study period, 47,071 patients were transfused in connection with cardiac surgery in 9 Swedish hospitals. Of these patients, 37 percent exclusively received RBCs stored less than 14 days; 27 percent, RBCs stored 14-27 days; 9 percent, RBCs stored 28-42 days; and 28 percent, RBCs of mixed age. Compared with recipients of RBCs stored for less than 14 days, there was no association between transfusion of RBCs stored 14-27 days or 28-42 days and 30-day, 2-year and 10-year mortality. There was no association with risk of selected serious complications.
“These results complement recent randomized trials in providing further reassurance of the safety of current blood storage practices,” 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.
The JAMA Neurology feature “Images in Neurology” features the case of a 25-year-old right-handed physical education student who was buried by an avalanche during a ski tour and endured 15 minutes of hypoxia (oxygen deficiency). He developed involuntary myoclonic jerking (brief, involuntary twitching of muscles) of the mouth induced by talking and of the legs by walking. Weeks later when he was trying to solve Sudoku puzzles he developed clonic seizures (rapid contractions of muscles) of the left arm. The seizures stopped when the Sudoku puzzle was discontinued. Berend Feddersen, M.D., Ph.D., of the University of Munich, Germany, and coauthors suggest oxygen deficiency most likely caused some damage to the brain. The patient stopped solving Sudoku puzzles and has been seizure free for more than five years.
(JAMA Neurol. Published online October 19, 2015. doi:10.1001/jamaneurol.2015.2828. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made a conflict of interest disclosures. 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: 11A.M. (ET), MONDAY, OCTOBER 19, 2015
Media Advisory: To contact corresponding author P. Brian Smith, M.D. M.P.H., M.H.S., call Samiha Khanna at 919-419-5069 or email samiha.khanna@duke.edu. To contact corresponding editorial author Pablo J. Sanchez, M.D., call Gina Bericchia at 614-355-0495 or email mediarelations@nationwidechildrens.org.
Invasive methicillin-susceptible Staphylococcus aureus (S aureus) infection (MSSA) caused more infections and more deaths in hospitalized infants than invasive methicillin-resistant S aureus infection (MRSA), which suggests measures to prevent S aureus infections should include MSSA in addition to MRSA, according to an article published online by JAMA Pediatrics.
P. Brian Smith, M.D., M.P.H., M.H.S., of the Duke University School of Medicine, Durham, N.C., and coauthors compared demographics and mortality of infants with MRSA and MSSA at 348 neonatal intensive care units (NICUs) around the United States to determine the annual proportion of S aureus infections that were MRSA and to contrast the risk of death after invasive MRSA and MSSA infections.
The authors identified 3,888 of 887,910 infants (0.4 percent) with 3,978 invasive S aureus infections. Infections were more commonly caused by MSSA (2,868 of 3,978 or 72.1 percent) than MRSA (1,110 of 3,978 or 27.9 percent).
Overall, invasive S aureus infections had an incidence of 44.8 infections per 10,000 infants, according to the results. The annual incidence of invasive S aureus infection increased from 1997 through 2006 and then declined modestly from 2007 through 2012.
The study indicates invasive S aureus infections were more common in infants born at less than 1,500 grams (3,061 of 136,797 or 223.8 per 10,000 infants) than in infants born at 1,500 grams or higher (915 of 748,715 or 12.2 per 10,000 infants).
More infants with invasive MSSA infections (n=237) died before hospital discharge than infants with invasive MRSA infections (n=110). However, the proportions of infants who died after invasive MSSA and MRSA infections were similar at 237 of 2,474 (9.6 percent) and 110 of 926 (11.9 percent). The adjusted risk of death before hospital discharge and the risk of death at seven and 30 days after invasive infection were similar between infants with invasive MSSA infection and invasive MRSA infection, the results indicate.
“The absolute numbers of infections and deaths due to MSSA exceed those due to MRSA. Consideration should be given to expanding hospital infection control efforts targeting MRSA to include MSSA as well. Future studies to better define the relationship between MSSA colonization and subsequent infection will help to clarify the importance of such interventions for preventing MSSA disease,” the study concludes.
(JAMA Pediatr. Published online October 19, 2015. doi:10.1001/jamapediatrics.2015.2380. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: The authors made conflict of interest and funding/support disclosures. Please see article for additional information, including other authors, author contributions and affiliations, etc.
Editorial: Spreading the Benefits of Infections Prevention in the NICU
In a related editorial, Pablo J. Sanchez, M.D., of the Nationwide Children’s Hospital, Ohio State University, Columbus, and coauthors write: “In conclusion, the key to minimizing morbidity and mortality from any organism (S aureus included) must be prevention of horizontal transmission that can result in NICU outbreaks. We know that horizontal transmission occurs via the hands of health care workers, so hand hygiene as part of standard and transmission-based precautions remains the mainstay of prevention. Hand hygiene is cost-effective and easy to perform. … The common goal must remain prevention of transmission, and the most effective prevention strategy is already in our hands.”
(JAMA Pediatr. Published online October 19, 2015. doi:10.1001/jamapediatrics.2015.2980. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see article for additional information, including other authors, author contributions and affiliations, etc.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), MONDAY, OCTOBER 19, 2015
Media Advisory: To contact study corresponding author J. Michael McWilliams, M.D., Ph.D., call David Cameron at 617-432-0441 or email David_Cameron@hms.harvard.edu. To contact corresponding commentary author James D. Reschovsky, Ph.D., call Christal Stone Valenzano, MPH at 202-250-3520 or email cstone@mathematica-mpr.com.
Physician-hospital integration appears to be associated with increased spending and prices for outpatient care but without the accompanying changes in utilization that might suggest more efficient care from better coordination and economies of scale, according to an article published online by JAMA Internal Medicine.
Hospital employment of physicians and ownership of physician practices has increased in the past decade. Financial integration with physicians can boost hospital referrals for health care systems and for physicians, the resources and economies of scale of a hospital can be attractive compared with independent practice. The price-increasing effects of hospital mergers are well documented but less is known about the effect of consolidation among physicians and between physicians and hospitals.
J. Michael McWilliams, M.D., Ph.D., of Harvard Medical School, Boston, and coauthors looked at the association between changes in physician-hospital integration from 2008 through 2012 and changes in commercial spending and prices. Physician-hospital integration was measured using Medicare claims data in metropolitan statistical areas (MSAs). The study sample included nearly 7.4 million nonelderly enrollees in preferred-provider organizations or point-of-service plans from a commercial database.
The authors report that physician-hospital integration increased by an average of 3.3 percentage points from 2008 to 2012 among 240 MSAs. Increased physician-hospital integration in MSAs was associated with an average increase of $75 per enrollee in annual outpatient spending from 2008 to 2012. Average annual spending per enrollee in 2012 was $2,407 for outpatient care. This increase in outpatient spending without an increase in utilization suggests that the spending increase was driven almost entirely by price increases. Changes in physician-hospital integration were not associated with significant changes in inpatient spending, according to the results.
“Changes in the structure of health care provider markets and in spending should be monitored, particularly as payment systems shift away from fee-for-service, and may require additional regulatory measures to control,” the authors conclude.
(JAMA Intern Med. Published online October 19, 2015. doi:10.1001/jamainternmed.2015.4610. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: An author made a conflict of interest disclosure. This study was supported by a grant from Changes in Health Care Financing and Organization, from the Robert Wood Johnson Foundation. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
Commentary: Hospital Acquisition of Physician Groups
In a related commentary, James D. Reschovsky, Ph.D., and Eugene Rich, M.D., of Mathematica Policy Research, Washington, D.C., write: “Given the possibilities for better-integrated care, the purchase of physician groups by hospitals would be expected to improve efficiencies and save costs. But overall this does not seem to be the case. The article by Neprash and colleagues in this issue of JAMA Internal Medicine shows that hospital purchase of physician practices was linked to greater net costs between 2008 and 2012. This confirms previous research, but for the first time, the findings are based on national commercial insurance data.”
(JAMA Intern Med. Published online October 19, 2015. doi:10.1001/jamainternmed.2015.6183. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
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Use of a qualification test within a retinal practice appeared to be effective in predicting which patients with intermediate age-related macular degeneration (AMD) would be good candidates to initiate use of a home monitoring device for progression to more severe AMD, according to a study published online by JAMA Ophthalmology.
Choroidal neovascularization (CNV; creation of abnormal blood vessels) from AMD left untreated or unmanaged after substantial vision loss has occurred remains a leading cause of irreversible blindness in people age 50 years or older throughout much of the world. In the United States, approximately 8 million people have intermediate AMD or monocular advanced AMD of whom 1.3 million people will develop advanced AMD during the ensuing 5 years. Patients with intermediate AMD using a home monitoring device (includes looking at a computer screen and using a mouse) have less loss of visual acuity, on average, at detection of choroidal neovascularization than do individuals using standard care monitoring techniques (such as viewing a grid on a piece of paper). Patients must establish a baseline set of responses during a limited series of initial home testing to monitor AMD progression using this device. There is little known about the proportion of patients with high-risk non-neovascular AMD who may be able to incorporate the device successfully into their home monitoring regimen, according to background information in the article.
The developers of the home device designed an in-office qualification test to identify individuals most likely to be able to use the device successfully. Neil M. Bressler, M.D., of the Johns Hopkins University School of Medicine, Baltimore, and Editor, JAMA Ophthalmology, and colleagues studied 131 participants within a university-based retina practice with intermediate AMD in at least one eye who completed an in-clinic qualification test for the home monitoring device. The qualification test protocol included a short explanation by the study coordinator, explanatory tutorial administered through the device, a trial or practice test administered through the device (an opportunity to mark areas of artificial distortion), an opportunity for the participant to ask the coordinator questions, and the actual qualification test.
A total of 129 participants had reliable qualification test results; 91 participants (70 percent) who completed this test attained a score that suggested they would be able to successfully use the home device. Among the 91 participants who could initiate home testing, 83 did so, including 80 participants (88 percent) who established a baseline value that could be used as a reference for future monitoring. Younger participants were more likely to qualify for home testing. Visual acuity at study enrollment did not appear to be associated with successful qualification.
“These data support the likelihood that a larger percentage of individuals at high risk of progressing to CNV from AMD who successfully complete a qualification test to use this home monitoring device will be able to establish a baseline value for subsequent monitoring at home. These individuals can continue to increase their chance of detecting neovascular AMD between scheduled office visits while the lesion is relatively small and associated with visual acuity that is relatively good,” the authors write.
(JAMA Ophthalmol. Published online October 15, 2015.doi:10.1001/jamaopthalmol.2015.3684; Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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A study of young women in China undergoing cosmetic surgery on their eyelids and noses suggests feelings of self-esteem and self-efficacy (confidence in one’s abilities) were lower before surgery but increased in the months after surgery, according to an article published by JAMA Facial Plastic Surgery.
The number of patients undergoing facial cosmetic surgery in China has increased markedly in the past decade. As more young women seek these procedures more research is investigating the psychosocial profile of these patients.
Jincai Fan, M.D., of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, and coauthors examined the association of patient psychological traits, the decision to undergo cosmetic surgery and the effectiveness of surgery on the psychological conditions of these young women.
The study enrolled 161 cosmetic surgery patients (CSPs), 355 general population controls (GPCs) and 268 facial appearance raters (FARs). Patient data were obtained from questionnaires preoperatively and six months after surgery. Front-view facial images also were taken and show to FARs.
The authors report self-esteem and self-efficacy scores were lower preoperatively in young women compared with women in the general population who had not visited a plastic surgeon, but those scores increased to nearly normal levels six months after surgery.
While there was no significant difference between cosmetic surgery patients and women from the general population in the objective assessment of facial appearance by the FARs, the average scores for cosmetic surgery patients’ self-assessments were lower for the eyes, nose and overall facial appearance.
The authors note a number of limitations to the study, which include generalizability.
“Self-esteem and self-efficacy mediate the negative effects of self-assessment on the decision of young women to undergo facial cosmetic surgery. The impairment of self-esteem and self-efficacy may indicate the need for preoperative psychological intervention,” the study concludes.
(JAMA Facial Plast Surg. Published October 15, 2015. doi:10.1001/jamafacial.2015.1381. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: This work was supported by a grant from the Doctorial Innovation Fund of Peking Union Medical College. Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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Patients newly diagnosed with cancer were less likely to participate in clinical trials if their annual household income was below $50,000, according to an article published online by JAMA Oncology.
Joseph M. Unger, Ph.D., of the Fred Hutchinson Cancer Research Center, Seattle, and coauthors used data from a survey of adult patients with new diagnoses of breast, lung or colorectal cancer. All patients were enrolled prior to making a treatment decision and then followed for six months to assess whether they participated in a clinical trial.
Of the 1,581 patients who were eligible, 1,262 (80 percent) with annual income data were available for the analysis. Patients were predominantly younger than 65, female and not African American.
The authors report patients with annual household income below $50,000 had 32 percent lower odds of trial participation than higher income patients (12 percent vs. 17 percent). Trial participation decreased as annual household income decreased from $50,000 or higher to between $20,000 and $49,999 and to less than $20,000 (17 percent vs. 13 percent vs. 11 percent, respectively).
“The identification of patient income level as an independent predictor of trial participation is important for multiple reasons. If income is associated with health status, then improving representativeness of lower-income patients in trials would improve the generalizability of study outcomes. Also, greater participation of lower-income patients would allow trials to be conducted more quickly, speeding the development of new treatments. Crucially, since clinical trial treatments represent the newest available treatments, access to this vital resource should be available to individuals of all income levels,” the authors conclude.
(JAMA Oncol. Published online October 15, 2015. doi:10.1001/jamaoncol.2015.3924. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: This work was supported by grants from the Breast Cancer Research Foundation and the National Institutes of Health, National Cancer Institute Community Oncology Research Program Research Base. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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In a study that included 231 hospitals and more than 12.6 million patient encounters, researchers found that patients at safety-net hospitals tend to have fewer resources and present with greater severity of illness, and that these hospitals have higher mortality and readmission rates and higher cost associated with surgical care.
“However, these inferior outcomes persisted after adjusting for patient characteristics and hospital procedure volume, suggesting that intrinsic qualities of safety-net hospitals lead to surgical care that is inferior and more expensive,” writes Shimul A. Shah, M.D., M.H.C.M., of the University of Cincinnati School of Medicine, and colleagues in a study published online by JAMA Surgery.
The authors note that unadjusted reimbursement penalties based on these performance measures may exacerbate disparities in care. “Whether the goal is to reduce health care expenditures or improve quality of care, special attention needs to be devoted to safety-net hospitals that are in a unique financial position and care for a vulnerable patient population.”
To read the whole study, please visit the For the Media website.
(JAMA Surgery. Published online October 14, 2015. doi:10.1001/jamasurg.2015.3209. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), WEDNESDAY, OCTOBER 14, 2015
Media Advisory: To contact corresponding author Lieve Brochez, M.D., Ph.D., email lieve.brochez@ugent.be. To contact corresponding editorial writer June K. Robinson, M.D., call Marla Paul at 312-503-8928 or email marla-paul@northwestern.edu.
Total-body examination found a higher absolute number of skin cancers but lesion-directed screening performed by a dermatologist appeared to be an acceptable alternative screening method in a Belgian study, according to an article published online by JAMA Dermatology.
The incidence of melanoma and nonmelanoma skin cancer (NMSC) has been on the rise worldwide. Early detection is believed to result in better cure rates and subsequently more cost-effective treatment.
Lieve Brochez, M.D., Ph.D., of University Hospital Ghent, Belgium, and coauthors compared dermatologist-conducted lesion-directed screening (LDS) with standard total-body examination (TBE) in two communities in Belgium. Those individuals invited for LDS had a lesion that met one or more of the listed criteria: the ABCD rule (A, asymmetry; B, borders; C, colors; and D, differential structures), ugly duckling sign (looks different from a patient’s other moles); a new lesion lasting longer than four weeks; or red nonhealing lesions.
The participation rate was 17.9 percent (1,668 of 9,325) in the TBE group compared with 3.3 percent (314 of 9,484) in the LDS group. In total, 1,982 people were screened and 47 skin cancers (2.4 percent) were confirmed, including nine melanomas, 37 basal cell carcinomas and one squamous cell carcinoma or Bowen disease.
The skin cancer detection rate per 100 participants did not differ between the two groups with a 2.3 percent rate (39 of 1,668) in the TBE group and 3.2 percent (8 of 248) in the LDS group, according to the results. In the group invited for TBE, more skin cancers were detected given the higher participation rate of 0.4 percent (39 of 9,325) for TBE compared with 0.1 percent (8 of 9,484) for LDS.
Conducting a TBE took on average just less than four minutes (232 seconds) and a LDS examination was about 41 seconds, which the authors note makes the LDS 5.6 times less time consuming than TBE.
“When performed by dermatologists, LDS is an acceptable alternative screening method, especially in health care systems with limited budgets or long waiting lists. The effectiveness of skin cancer screening by nondermatologists warrants further study,” the study concludes.
(JAMA Dermatology. Published online October 14, 2015. doi:10.1001/jamadermatol.2015.2680. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: The skin cancer screening was supported by a research grant from the LEO Foundation. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Cost-Effectice Melanoma Screening
In a related editorial, June K. Robinson, M.D., JAMA Dermatology editor and of the Northwestern University Feinberg School of Medicine, Chicago, and Allan C. Halpern, M.D., of Memorial Sloan Kettering Cancer Center, New York, write: “A major logistic barrier for melanoma screening is access to expert skin cancer diagnosis. The Belgian study points to an intriguing strategy for achieving screening efficiency by moving the screening process outside usual office-based practice. In the Belgian study, the examiners were dermatologists, but the economics and size of the dermatology workforce make this an impractical approach in the United States.” (JAMA Dermatology. Published online October 14, 2015. doi:10.1001/jamadermatol.2015.2681. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: This study was supported by a grant from the National Cancer Institute. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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Counties that implemented Garrett Lee Smith Memorial Suicide Prevention Program activities had lower rates of suicide attempts among young people ages 16 to 23 than counties that did not, according to an article published online by JAMA Psychiatry.
Suicide prevention is a major public health priority. Since 2005, the Garrett Lee Smith Memorial Suicide Prevention Program (the GSL program) has funded grants for suicide prevention activities awarded to states, tribal communities and college campuses in the United States. Programs supported by the GLS program have generally been comprehensive in scope and multifaceted, with activities that include education, mental health awareness, screening, and training events for gatekeepers to better recognize suicide risk, ask about risk, intervene and help suicidal individuals get assistance.
Christine Walrath, Ph.D., of ICF International, New York, and coauthors conducted a study of community-based suicide prevention programs for young people across 46 states and 12 tribal communities. The study compared 466 counties implementing the GLS program between 2006 and 2009 (the intervention counties) with 1,161 counties not exposed to the GLS program (the control group counties). The analysis used 57,000 respondents in the intervention and 84,000 in the control group. Suicide attempt rates for each county were obtained from the National Survey on Drug Use and Health.
The authors report counties implementing GLS program activities had lower suicide attempt rates the year after implementation among young people ages 16 to 23, which the authors estimate resulted in 4.9 fewer suicide attempts per 1,000 youths.
“Although causality cannot be definitely inferred from our study owing to a lack of random assignment, these results suggest that more than 79,000 attempts were avoided between 2008 and 2011 following implementation of the GLS program. … These findings have significant implications for public health policy – specifically, suicide prevention programs and the ways to reduce morbidity and mortality associated with suicidal behaviors – and suggest that community-based programs (such as the GLS program) provide a pathway toward fewer suicide attempts and deaths,” the study concludes.
(JAMA Psychiatry. Published online October 14, 2015. doi:10.1001/jamapsychiatry.2015.1933. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: An author made a conflict of interest disclosure. The cross-site evaluation was supported trhough a Substance Abuse and Mental Health Services Administration contract to ICF Macro. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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CHICAGO – The JAMA Network will launch a new journal, JAMA Cardiology, and has named Robert O. Bonow, M.D., Max and Lilly Goldberg Distinguished Professor of Cardiology at the Northwestern University Feinberg School of Medicine, Chicago, as editor in chief.
“JAMA Cardiology represents another important addition to the JAMA family. Progress in preventing and treating cardiovascular disease has been substantial. Yet much work remains. Like other journals in the JAMA family, this journal will include original research, opinion pieces, and short and long review articles. Bob Bonow is the perfect inaugural editor in chief, a world renowned cardiologist with vast research and clinical experience. He has assembled an outstanding group of senior editors and editorial board members,” said Howard Bauchner, M.D., editor in chief of JAMA and the JAMA Network.
When JAMA Cardiology premieres in early 2016, it will be the 12th journal in the JAMA Network, which includes JAMA and 10 other specialty journals. All JAMA Cardiology content – research, reviews and opinions – will be published online each week on Wednesday and then published in a monthly print and online issue. JAMA Cardiology will focus on all aspects of cardiovascular medicine, including epidemiology and prevention, diagnostic testing, interventional and pharmacologic therapeutics, translational research, health care policy and outcomes, and global health.
“Extending the JAMA Network editorial franchise to serve the worldwide cardiology community—serving physicians engaged in advancing both the science and practice of cardiology—is a rare opportunity and pleasure. Supported by the strength of the JAMA Network and first-rate, forward-thinking editorial leadership, JAMA Cardiology will be a leader in the field beginning in 2016,” said Thomas J. Easley, publisher of JAMA and the JAMA Network.
As the journal’s founding editor, Dr. Bonow brings extensive experience to his new role. In addition to serving as the Goldberg Distinguished Professor of Cardiology, he is vice chairman of the Department of Medicine at the Northwestern University Feinberg School of Medicine and director of the department’s Center for Cardiovascular Innovation. From 1992 to 2011, he served as chief of the Division of Cardiology at Northwestern Memorial Hospital, where he is currently an attending physician. Dr. Bonow is recognized for his research and teaching in a variety of cardiac diseases, including coronary artery disease, valvular heart disease, and heart failure. He has published more than 500 articles and 100 book chapters and is one of the four principal editors of Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. Dr. Bonow is past president of the American Heart Association and a Master of the American College of Cardiology and Master of the American College of Physicians. Among his honors are the National Institutes of Health Director’s Award and the U.S. Public Health Service Commendation Medal and Outstanding Service Medal. He received his M.D. degree from the University of Pennsylvania School of Medicine.
“I am very excited to join the JAMA leadership team and to serve as editor in chief as we launch JAMA Cardiology. I look forward to the development of a cutting-edge journal in cardiovascular medicine that will serve both the research and clinical communities, with the goals to advance science, educate our readers, inform the practice of cardiology, and influence health care policy,” said Dr. Bonow.
Existing institutional customers will have free online access to JAMA Cardiology in 2016. Individual physicians and other health care professionals can purchase an online subscription or access content for free on the JAMA Network Reader.
EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, OCTOBER 13, 2015
Media Advisory: To contact Beth Han, M.D., Ph.D., M.P.H., call Bradford Stone at 240-276-2140 or email Bradford.Stone@SAMHSA.hhs.gov. To contact editorial co-author Lewis S. Nelson, M.D., call Rob Magyar at 212-404-3591 or email Robert.magyar@nyumc.org.
From 2003 to 2013, the percentage of nonmedical use of prescription opioids decreased among adults in the U.S., while the prevalence of prescription opioid use disorders, frequency of use, and related deaths increased, according to a study in the October 13 issue of JAMA.
Since 1999, the United States has experienced increases in illness and death associated with nonmedical use of prescription opioids, which is being called a U.S. epidemic. During this period, emergency department visits and drug overdose deaths involving these drugs have increased rapidly. To fully understand the current status of the epidemic and who is currently most affected, an examination of nationally representative U.S. surveillance data is needed.
Beth Han, M.D., Ph.D., M.P.H., of the Substance Abuse and Mental Health Services Administration, Rockville, Md., and colleagues examined the prevalence of nonmedical use and use disorders (dependence on or abuse of alcohol, marijuana, cocaine, hallucinogens, heroin, inhalants, or nonmedical use of prescription pain relievers, sedatives, or stimulants) and related risk factors with data from 472,200 persons who participated in the 2003-2013 National Surveys on Drug Use and Health. Mortality was based on the 2003-2013 National Vital Statistics System’s Multiple Cause of Death Files.
Among adults age 18 through 64 years, the prevalence of nonmedical use of prescription opioids decreased from 5.4 percent in 2003 to 4.9 percent in 2013, but the prevalence of prescription opioid use disorders increased from 0.6 percent in 2003 to 0.9 percent in 2013. The 12-month prevalence of high-frequency use (200 days or more) also increased from 0.3 percent in 2003 to 0.4 percent in 2013.
Mortality assessed by drug overdose death rates involving prescription opioids increased from 4.5 per 100,000 in 2003 to 7.8 per 100,000 in 2013. The average number of days of nonmedical use of prescription opioids increased from 2.1 in 2003 to 2.6 in 2013. The prevalence of having prescription opioid use disorders among nonmedical users increased to 15.7 percent in 2010, 16.1 percent in 2011, 17 percent in 2012, and 16.9 percent in 2013, from 12.7 percent in 2003.
“We found a significant decrease in the percentage of nonmedical use of prescription opioids, as well as significant increases in the prevalence of prescription opioid use disorders, high-frequency use, and related mortality among adults aged 18 through 64 years in the United States over the past decade. Furthermore, the increases identified in this study occurred in the context of increasing heroin use and heroin-related overdose deaths in the United States, supporting a need to address nonmedical use of prescription opioid and heroin abuse in a coordinated and comprehensive manner,” the authors write.
“Receiving treatment for substance use disorders is particularly critical. Most adults with prescription opioid use disorders or other substance use disorders neither receive treatment nor perceive a need for treatment. In 2013, more than three-fourths of adults aged 18 through 64 years who had prescription opioid use disorders did not receive any substance use treatment. Particularly, policy and societal barriers prevent broad dissemination, access, and adoption of highly effective medication-assisted therapies for people with prescription opioid use disorders.”
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Addressing the Opioid Epidemic
“If the observed decrease in rates of new opioid users reported by Han et al is sustained, understanding the reasons behind this change is important. These are likely multifactorial and may include the use of prescribing guidelines for chronic pain, rationalizing expectations of physicians and patients for pain control and functional outcome, media attention on the consequences of addiction, and regulatory and legal efforts. It is encouraging that the culture around prescription opioids is starting to change, especially when considering the marketing of a plethora of new opioids for the treatment of chronic pain, none of which has been shown to be safe and effective over the long term,” writes Lewis S. Nelson, M.D., of the New York University School of Medicine, and colleagues.
“The chronic, relapsing nature of opioid addiction means most patients are never ‘cured,’ and the best outcome is long-term recovery. The lifelong implications of this disease far outweigh the limited benefits of opioids in the treatment of chronic pain, and in many cases the risks inherent in the treatment of acute pain with opioids. The encouraging finding of declining opioid initiation rates should be tempered by the increasing rates of nonmedical opioid use disorders and the limited utilization of treatment programs. Although multifaceted approaches are needed to successfully address the opioid epidemic, an important step is to start at the beginning and keep opioid-naive patients opioid naive.”
During the decade from 2004 to 2013, use of treatment remained low for individuals with opioid use disorders, according to a study in the October 13 issue of JAMA.
During the last decade, nonmedical use of opioid analgesics and heroin increased substantially in the United States. In the early 2000s, less than one-sixth of individuals with opioid use disorders (OUDs) received any treatment, and use of office-based treatment was rare. It is unknown whether treatment patterns have changed in recent years. Brendan Saloner, Ph.D., and Shankar Karthikeyan, M.P.P., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, used data from the 2004-2013 rounds of the National Survey of Drug Use and Health, a nationally representative annual survey of individuals age 12 years or older, to identify individuals with opioid abuse or dependence symptoms and if they received treatment for OUD in the prior 12 months. The sample was divided into two 5-year periods (2004-2008 vs 2009-2013) to provide reliable estimates.
In the combined sample, the researchers identified 6,770 respondents with OUDs. The adjusted rates for the percentage of individuals with OUDs receiving treatment were similar (18.8 percent in 2004-2008 vs 19.7 percent in 2009-2013).
The average number of treatment settings visited increased during the study period. The most common setting in both periods was self-help groups. More than half of individuals receiving treatment during both periods also visited outpatient treatment. Use of inpatient treatment increased from 37.5 percent in 2004-2008 to 52 percent in 2009-2013, and office-based treatment increased from 25 percent to 35 percent.
“Individuals in treatment received care in more settings, with the greatest increases in inpatient treatment and at physician’s offices. Although physician’s offices may provide access to buprenorphine, medication-assisted treatments are often unavailable in inpatient settings, which could hinder patient recovery,” 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.
Early physical therapy for recent-onset low back pain resulted in statistically significant improvement in disability compared to usual care, but the improvement was modest and did not achieve a difference considered clinically important at the individual patient level, according to a study in the October 13 issue of JAMA.
Lifetime prevalence of low back pain (LBP) is about 70 percent and accounts for 2 percent to 5 percent of all physician visits. The effect of early physical therapy for LBP is unclear. Guidelines advise delaying referral to physical therapy or other specialists for a few weeks to permit spontaneous recovery. Findings from recent observational studies suggest that some patients may benefit from early physical therapy.
Julie M. Fritz, Ph.D., P.T., of the University of Utah, Salt Lake City, and colleagues randomly assigned 220 patients with recent-onset LBP to early physical therapy (n = 108; consisted of 4 physical therapy sessions [manipulation and exercise]), or usual care (n = 112; no additional interventions during the first 4 weeks). All participants received back pain related education. One-year follow-up was completed by 207 participants (94 percent).
For the primary study outcome, early physical therapy showed improvement compared to usual care on a measure of disability after 3 months. A significant difference was not found for disability between groups at 1-year follow-up. There was no improvement in pain intensity at 4-week, 3-month, or 1-year follow-up. Most differences between groups were modest. There were no differences in health care utilization at any point.
“We found that patients in both groups improved rapidly. Rapid and substantial improvement by most patients with acute LBP limits treatment effects in early intervention studies. We detected a modest difference favoring early physical therapy that was better than the natural history of acute LBP for the primary outcome at 3-month follow-up. However, the between-group difference did not achieve the threshold for minimum clinically important difference. Furthermore, differences were mostly undetectable by 1 year,” 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.
JAMA Neurology is publishing a collection of articles related to multiple sclerosis, a chronic disabling neurological disease.
The articles include:
The original investigation Equivalence of Generic Glatiramer Acetate in Multiple Sclerosis is a randomized clinical trial by Jeffrey Cohen, M.D., of the Cleveland Clinic, and coauthors that examined whether the generic drug was equivalent to the brand drug. The article is accompanied by the editorial Equivalence of Glatiramer Acetate Generics with Branded Glatiramer Acetate in Efficacy and Cost for the Treatment of Multiple Sclerosis by Dennis Bourdette, M.D., of Oregon Health & Science University, Portland, and Daniel Hartung, Pharm.D., M.P.H., of Oregon State University/Oregon Health & Science University, Portland. (JAMA Neurol. Published online October 12, 2015. doi:10.1001/jamaneurol.2015.2154 and doi:10.1001/jamaneurol.2015.2605)
The original investigation Association of Vitamin D Levels with Multiple Sclerosis Activity and Progression in Patients Receiving Interferon Beta-1b by Kathryn C. Fitzgerald, Sc.M., of the Harvard T.H. Chan School of Public Health, Boston, and coauthors assessed the association between 25-hydroxyvitamin D levels, disease course and prognosis in patients with relapsing-remitting multiple sclerosis treated with interferon beta-1b. (JAMA Neurol. Published online October 12, 2015. doi:10.1001/jamaneurol.2015.2742)
The original investigation Association of Deep Gray Matter Damage with Cortical and Spinal Cord Degeneration in Primary Progressive Multiple Sclerosis by Matilde Inglese, M.D., Ph.D., of the Ichan School of Medicine at Mount Sinai, New York, and coauthors investigated the association of magnetic resonance imaging measures of cortical, deep gray matter and spinal cord damage and their effect on clinical disability. (JAMA Neurol. Published online October 12, 2015. doi:10.1001/jamaneurol.2015.1897.)
The viewpoint article Targeting Central Nervous System B Cells in Progression of Multiple Sclerosis by Martin S. Weber, M.D., of the University Medical Centre, Georg August University, Germany, and coauthors. (JAMA Neurol. Published online October 12, 2015. doi:10.1001/jamaneurol.2015.2869)
Uninjured athletes reported concussion-like symptoms in a new study that suggests symptom reporting in the absence of recent concussion is related to male or female sex and preexisting conditions, which can include prior treatment for a psychiatric condition or substance abuse, according to an article published online by JAMA Pediatrics.
Every state in the U.S. has passed legislation pertaining to sport-related concussion. In general, the laws mandate that injured student athletes be evaluated by a qualified health care professional before they can return to participating in sports. Decisions about returning to activity are based on symptom reporting.
Grant L. Iverson, Ph.D., of Harvard Medical School, Boston, and coauthors sought to clarify factors associated with concussion-like symptoms in uninjured adolescents using data from more than 30,000 student athletes. It is important for clinicians to understand factors that may be associated with baseline symptom reporting so they can properly make decisions about when athletes may return to activity.
The authors found symptom reporting was more common in girls than boys and that in the absence of a recent concussion, 19 percent of boys and 28 percent of girls reported a group of symptoms similar to postconcussional syndrome.
Preexisting psychiatric, developmental (e.g., attention-deficit/hyperactivity disorder [ADHD] and learning disability) and neurological factors (e.g., migraines) were associated with higher rates of reporting symptoms that resemble postconcussional syndrome at baseline.
Prior treatment of a prior psychiatric condition was the strongest indicator for symptom reporting in boys, followed by a history of migraines. For girls, the indicators were prior treatment of a psychiatric condition or substance abuse and ADHD.
While prior concussions were modestly associated with increased risk for reporting clusters of symptoms, they were less so than preexisting developmental and psychiatric factors.
“When managing a student athlete with a concussion, it has been widely noted that the athlete should be ‘asymptomatic’ at rest and with exercise before returning to sports, and sometimes athletes are kept out of school for prolonged periods while they wait for symptoms to resolve, which could have negative consequences for their academic, social and emotional functioning and contribute to symptom reporting. These results reinforce that ‘asymptomatic’ status after concussion can be difficult to define,” the study concludes.
(JAMA Pediatr. Published online October 12, 2015. doi:10.1001/jamapediatrics.2015.2374. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: An author made conflict of interest disclosures. Funding/support disclosures also were made. Please see article for additional information, including other authors, author contributions and affiliations, etc.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), MONDAY, OCTOBER 12, 2015
Media Advisory: To contact study corresponding author Abiy Agiro, Ph.D., call Jill Becher at 414-234-1573 or email Jill.Becher@anthem.com. To contact corresponding commentary author Ralph Gonzales, M.D., M.S.P.H., call Laura Kurtzman at 415-476-3163 or email Laura.Kurtzman@ucsf.edu.
An analysis of seven clinical services with minimal benefit to patients identified as part of the Choosing Wisely campaign found significant declines in two services: the use of imaging for headaches and cardiac imaging in low risk patients, according to an article published online by JAMA Internal Medicine.
Reducing the use of unnecessary medical procedures and treatments is important in controlling health care expenditures. Choosing Wisely includes more than 70 lists of about 400 recommendations of frequently used medical practices or procedures that are of minimal clinical benefit to patients.
Abiy Agiro, Ph.D., of HealthCore, Wilmington, Del., and coauthors examined the frequency and trends of some of the earliest Choosing Wisely recommendations from 2012 using medical and pharmacy claims from Anthem-affiliated Blue Cross and Blue Shield health care plans for about 25 million members.
The authors identified seven services: imaging tests for headache with uncomplicated conditions; cardiac imaging for members without a history of cardiac conditions; preoperative chest x-rays with unremarkable history and physical examination results; low back pain imaging without red-flag conditions; human papillomavirus (HPV) testing for women younger than 30; antibiotics for acute sinusitis; and prescription nonsteroidal anti-inflammatory drugs (NSAIDs) for members with select chronic conditions (hypertension, heart failure or chronic kidney disease).
The authors found:
Use of imaging for headache decreased from 14.9 percent to 13.4 percent
Cardiac imaging decreased from 10.8 percent to 9.7 percent
Use of NSAIDs increased from 14.4 percent to 16.2 percent
HPV testing in younger women increased from 4.8 percent to 6.0 percent
Antibiotics for sinusitis remained stable decreasing only from 84.5 percent to 83.7 percent
Use of pre-operative chest x-rays (ending utilization 91.5 percent) and imaging for low back pain (53.7 percent utilization throughout the study) remained high with no significant changes.
Although four of the seven had statistically significant changes, which is unsurprising given the large sample size, the clinical significance is uncertain, the authors note.
The authors acknowledge limitations because the study was based on administrative claims data that do not adequately capture the clinical circumstances that led to the service being ordered so the recommendation may be appropriate for an individual patient
“The relatively small use changes suggest that additional interventions are necessary for wider implementation of Choosing Wisely recommendations in general practice. Some of the additional interventions needed include data feedback, physician communication training, systems interventions (e.g., clinical decision support in electronic medical records), clinician scorecards, patient-focused strategies and financial incentives,” the authors conclude.
(JAMA Intern Med. Published online October 5, 2015. doi:10.1001/jamainternmed.2015.5441. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: The authors made conflict of interest disclosures. Research support was provded by Anthem. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
Commentary: Changing Clinician Behavior When Less is More
In a related commentary, Ralph Gonzales, M.D., M.S.P.H., and Adithya Cattamanchi, M.D., M.A.S., of the University of California, San Francisco, write: “As we have described, frameworks exist to guide delivery systems and clinician groups in developing and testing strategies to facilitate reducing the ordering of low-value tests and treatments. Further efforts to compel delivery systems to commit to Choosing Wisely are needed to leverage the grassroots/front-line cultural shifts that the campaign has stimulated before the impact wanes.”
(JAMA Intern Med. Published online October 5, 2015. doi:10.1001/jamainternmed.2015.5987. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
Viewpoint: Producing Evidence to Reduce Low-Value Care
In a related Viewpoint, David H. Howard, Ph.D., of Emory University, Atlanta, and Cary P. Gross, M.D., of the Yale University School of Medicine, New Haven, Conn., write: “A comprehensive initiative to fund trials comparing established medical treatments with less costly alternatives should complement ongoing efforts to reduce low-value care through physicians stewardship and innovations in health care. There is a need for evidence that will guide decisions about clinical care. Instead of asking, “Does evidence affect practice?” we ought to be asking, “How can we produce more of it?”
(JAMA Intern Med. Published online October 12, 2015. doi:10.1001/jamainternmed.2015.5453. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: The authors made conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
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Contamination of the skin and clothing of health care workers happened frequently during the removal of gloves or gowns in a simulation study published by JAMA Internal Medicine that used fluorescent lotion and black light. The study by Curtis J. Donskey, M.D., of the Cleveland Veterans Affairs Medical Center, and coauthors included health care workers at four northeast Ohio hospitals who participated in personal protective equipment (PPE) removal simulations. Other health care personnel at one medical center participated in an intervention that included education and practice in removal of contaminated PPE.
The authors report that of 435 glove and gown removal simulations, contamination of skin or clothing with fluorescent lotion happened in 200 (46 percent). The intervention reduced skin and clothing contamination during glove and gown removal (60 percent before the intervention vs. 18.9 percent after) that was sustained after one and three months.
“These findings highlight the urgent need for additional studies to determine effective strategies to minimize the risk of contamination during PPE removal, to improve PPE design and to identify optimal methods for training of personnel in PPE use,” the authors write.
To read the whole study and a related commentary by Michelle Doll, M.D., and Gonzalo M. Bearman, M.D., M.P.H., of Virginia Commonwealth University, Richmond, please visit the For The Media website.
(JAMA Intern Med. Published online October 12, 2015. doi:10.1001/jamainternmed.2015.4535. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: An author made a conflict of interest disclosure. This work was supported by a Veterans Affairs Merit Review grant from the Department of Veterans Affairs, the Cleveland Veterans Affairs Geriatric Research, Education and Clinical Center and a grant from STERIS. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
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A small study of 16 patients published by JAMA Facial Plastic Surgery found a 75 percent rate (12 of 16) of concussions associated with isolated mandible fractures. Lindsay Sobin, M.D., of Boston Children’s Hospital, and coauthors suggest patients with isolated mandible fractures may benefit from being screened for concussion and referred to a concussion clinic.
To read the whole study and a related commentary, please visit the For The Media website.
(JAMA Facial Plast Surg. Published October 8, 2015. doi:10.1001/jamafacial.2015.1339. Available pre-embargo to the media at https://media.jamanetwork.com.)
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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Two decades of follow-up of more than 100,000 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study finds that higher intake of bioavailable carotenoids, particularly lutein/zeaxanthin and α-carotene, are associated with a reduced risk of advanced age-related macular degeneration (AMD), according to an article published online by JAMA Ophthalmology.
“Because other carotenoids may also have a protective role, a public health strategy of increasing the consumption of a wide variety of fruits and vegetables rich in carotenoids could be most beneficial and is compatible with current dietary guidelines,” writes Juan Wu, M.S., of the Harvard T. H. Chan School of Public Health, Boston, and colleagues
To read the whole study, please visit the For the Media website.
(JAMA Ophthalmol. Published online October 8, 2015. doi:10.1001/jamaopthalmol.2015.3590)
Editor’s Note: This study was supported by grants from 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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First-born individuals in a sample of adults in the United Kingdom were more likely to be nearsighted than later-born individuals in a family, and the association was larger before adjusting for educational exposure, suggesting that reduced parental investment in the education of children with later birth orders may be partly responsible, according to a study published online by JAMA Ophthalmology.
Myopia (nearsightedness) is increasing in prevalence in younger generations in many parts of the world and is an important public health issue. Major known risk factors for myopia are genetic background, time spent outdoors, and time spent doing “near” work (including educational activities). A prior analysis suggested myopia was more common in first-born children in a family compared with later-born children. One potential cause of the association between birth order and myopia is parental investment in education; on average, parents have been reported to direct more of their available resources to earlier-born children, resulting in better educational attainment in earlier-born than later-born individuals. Thus, parents may expose their earlier-born children to a more myopia-predisposing environment, according to background information in the article.
Jeremy A. Guggenheim, Ph.D., of Cardiff University, Cardiff, U.K., and colleagues conducted an analysis of UK Biobank participants who were 40 to 69 years of age, were of white ethnicity, had a vision assessment and no history of eye disorders (n = 89,120). The researchers determined the odds for myopia and by birth order, adjusting for age and sex, and education.
First-born individuals were approximately 10% more likely to be myopic or about 20% more likely to have high (more severe) myopia than later-born individuals. After adjusting for either of 2 measures of educational exposure— highest educational qualification or age at completion of full-time education—the association between birth order and myopia was lessened (by approximately 25%) and no dose-response relationship was evident.
“Greater educational exposure in earlier-born children may expose them to a more myopiagenic [factors causing myopia] environment; for example, more time doing near work and less time spent outdoors. Our findings that statistical adjustment for indices of educational exposure partially attenuated the magnitude of the association between birth order and myopia, and completely removed the evidence for a dose-response relationship, therefore support the idea that reduced parental investment in children’s education for offspring of later birth order contributed to the observed birth order vs myopia association and produced the observed dose-response relationship,” the authors write.
“These results add to the extensive literature implicating a role for education in the etiology of myopia, although a causal relationship cannot be confirmed using observational data.”
(JAMA Ophthalmol. Published online October 8, 2015. doi:10.1001/jamaopthalmol.2015.3556; Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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Despite manufacturing and legislative changes to improve workplace hygiene, the risk of occupational bladder cancer appears to be on the rise in some industries, although the profile of at-risk occupations has changed over time, according to an article published online by JAMA Oncology.
Bladder cancer is a common cancer and most tumors arise following exposure to carcinogens that enter the circulation through inhalation, ingestion or skin contact. The two most frequent routes are through tobacco smoking and occupation.
James W.F. Catto, M.B.Ch.B., Ph.D., F.R.C.S., of the University of Sheffield, England, and coauthors reviewed the medical literature and examined contemporary risks of occupational bladder cancer. Their review included 263 articles reporting on 31.4 million people. The authors used Nordic Occupational Classification and International Standard Classifications of Occupations.
The authors’ meta-analysis reported increased bladder cancer risk in 42 of 61 occupational classes and increased risk of bladder cancer-specific mortality in 16 of 40 occupational classes. Reduced incidence risk and mortality risk were seen in 6 of 61 and 2 of 40 classes, respectively. Risk varied with sex and was greatest in men, although it varied over time, according to the results.
Overall, the highest bladder cancer risks were for workers exposed to aromatic amines (tobacco, dye and rubber workers, hairdressers, printers and leather workers) and polycystic aromatic hydrocarbons (chimney sweeps, nurses, waiters, aluminum workers, seamen and oil/petroleum workers). The lowest risks were seen in agricultural sector workers.
The highest risks of death from bladder cancer occurred in workers exposed to heavy metals and polycystic aromatic hydrocarbons (metal workers, aluminum workers, electricians and mechanics), to diesel and combustion products (military and public safety workers) and those exposed to aromatic amines (domestic assistants and cleaners, rubber workers, painters and hairdressers).
While there appeared to be increased risk of bladder cancer, it appears to be increasing faster in women than in men, according to the authors. This increasing risk could be due to improved detection mechanisms and screening. The authors also suggest the increase among women may be due to an increase in the number of women in the workforce and the emergence of carcinogens in occupations dominated by women.
The authors noted several study limitations including that risk was divided according to occupational title or class rather than tasks and they were unable to adjust for smoking, the most common carcinogen.
“Efforts to reduce the impact of BC [bladder cancer] on workers should be targeted to occupations at risk of mortality,” the authors conclude.
(JAMA Oncol. Published online October 1, 2015. doi:10.1001/jamaoncol.2015.3209. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Need for Further Preventive Measures for Occupational Bladder Cancer
In a related commentary, Elisabete Weiderpass, M.D., M.Sc., Ph.D., of the Institute of Population-Based Cancer Research, Oslo, Norway, and Harri Vainio, M.D., Ph.D., Finnish Institute of Occupational Health, Helsinki, Finland, write: “In summary, this meta-analysis revealed that bladder cancer incidence and mortality are still elevated in many occupational groups, despite recent improvements in occupational hygiene, as observed in particular in Western countries. Bladder cancer continues to vary considerable by occupation, sex and calendar time – all indications that prevention is possible, and warranted. Workers around the world have the right to demand and get a safe and carcinogen-free workplace.”
(JAMA Oncol. Published online October 8, 2015. doi:10.1001/jamaoncol.2015.3270. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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EMBARGOED FOR RELEASE: 11 A.M. (ET) THURSDAY, OCTOBER 8, 2015
Media Advisory: To contact Joshua D. Schiffman, M.D., call Linda Aagard at 801-587-7639 or email linda.aagard@hci.utah.edu. To contact editorial author Mel Greaves, Ph.D., email Mel.Greaves@icr.ac.uk.
Multiple copies of a cancer-suppression gene may play a role in why elephants have a lower-than-expected rate of cancer, findings that have the potential to provide a better understanding of the mechanisms related to cancer suppression, including in humans, according to a study published online by JAMA.
The mechanisms that prevent accumulation of genetic damage and subsequent uncontrolled proliferation of somatic cells (any cell in the body that is not involved in reproduction) remain poorly understood. Understanding the cellular mechanism of cancer suppression in animals could benefit humans at high risk of cancer. Joshua D. Schiffman, M.D., of the University of Utah School of Medicine, Salt Lake City, and colleagues investigated the cancer rate in different mammals, including elephants, identified potential molecular mechanisms of cancer resistance, and compared response to DNA damage in elephants with that in healthy human controls and patients with Li-Fraumeni syndrome (LFS; a genetic syndrome with a high lifetime risk of cancer).
A comprehensive survey of necropsy data (information on disease and cause of death) was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes (a type of white blood cell that plays a role in immunity and defending the body against disease) from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11).
The authors write that a greater number of cells and cell divisions increases the chance of accumulating mutations resulting in malignant transformation. If all mammalian cells are equally susceptible to oncogenic mutations, then cancer risk should increase with body size (number of cells) and species life span (number of cell divisions), although it has been observed that cancer incidence across animals does not appear to increase as theoretically expected for larger body size and life span.
For this study, the researchers found that across mammals, cancer mortality did not increase with body size and/or maximum life span (e.g., for rock hyrax, 1 percent; African wild dog, 8 percent; lion, 2 percent). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.8 percent, compared with humans, who have 11 percent to 25 percent cancer mortality.
While humans have 1 copy (2 alleles [one of a pair of alternative forms of a gene]) of TP53 (a crucial tumor suppressor gene, mutated in the majority of human cancers), African elephants have at least 20 copies (40 alleles). Patients with LFS inherit only 1 functioning TP53 allele and may have a lifetime risk of cancer approaching 90 percent to 100 percent. TP53 plays a central role in response to DNA damage through apoptosis (a form of cell death) and cell cycle arrest. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status. The multiple copies of TP53 and the enhanced p53-mediated apoptosis observed in elephants may have evolved to offer such cancer protection.
“Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression,” 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.
Editorial: Evolutionary Adaptations to Cancer Risk
“It is not clear what lessons the study of elephants by Abegglen and colleagues has for informing cancer risk in humans. Perhaps the main message from this innovative investigation is to bring into focus the question of why humans appear to be so ill-adapted to cancer, given the average size and life span? The human genome is replete with footprints of positive selection in the not too distant historical past. Humans may have acquired, in one particular respect, an extra cancer suppressor gene variant early on in evolutionary history approximately 1.8 million years ago,” writes Mel Greaves, Ph.D., of the Institute of Cancer Research, London, in an accompanying editorial.
“However, in other respects, as aging occurs, modern humans appear to be exceptionally vulnerable to cancer, especially in more developed societies. The explanation for this dilemma may involve other factors that greatly increase cancer risk. For instance, most human cancers (approximately 75 percent – 90 percent) are associated with lifestyles that are not found among animals, such as smoking, reproductive, dietary, and sunsoaking habits. These behaviors are relatively recently acquired by humans, over a few hundred years, and the risks they impart far exceed prior and otherwise effective cancer suppressor mechanisms that were inherited from primate ancestors. Contrariwise, humans have inadvertently become maladapted via mismatches between current lifestyles and inherent genetics that was adaptively forged in a very different ancestral environment.”
Editor’s Note: The author’s research is supported by a grant from the Wellcome Trust. The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Among immunocompromised patients admitted to the intensive care unit with hypoxemic (inadequate oxygenation of the blood) acute respiratory failure, early noninvasive ventilation compared with oxygen therapy alone did not reduce the risk of death at 28 days, according to a study appearing in JAMA. The study is being released to coincide with its presentation at the 28th annual congress of the European Society of Intensive Care Medicine.
The number of patients living with immune deficiencies is increasing steadily. These patients are at high risk for life-threatening complications, including acute respiratory failure warranting admission to the intensive care unit (ICU). Mortality in this situation has ranged from 40 percent to 90 percent and remains high, despite improvements in recent years. Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure. However, its effectiveness has been unclear, according to background information in the article.
Elie Azoulay, M.D., Ph.D., of Saint-Louis University Hospital, Paris, and colleagues had 374 critically ill immunocompromised patients randomly assigned to early noninvasive ventilation (n = 191) or oxygen therapy alone (n = 183). Of these patients, 317 (85 percent) were receiving treatment for hematologic malignancies or solid tumors. The trial was conducted at 28 ICUs in France and Belgium.
On day 28 after randomization, 46 deaths (24 percent) had occurred in the noninvasive ventilation group vs 50 (27 percent) in the oxygen group. Oxygenation failure occurred in 155 patients overall (41 percent), 38 percent in the noninvasive ventilation group and 45 percent in the oxygen group. There were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays.
“In this multicenter randomized trial enrolling critically ill immunocompromised patients with acute respiratory failure, early noninvasive ventilation, compared with oxygen therapy alone, did not reduce the primary outcome of day-28 all-cause mortality, either overall or in any of the prespecified subgroups,” the authors write. “However, study power was limited.”
Editor’s Note: The study was sponsored by 2 grants from the nonprofit organizations Legs Poix (Chancellerie des Universites de Paris) and the OUTCOMEREA study group. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Editorial: The Changing Landscape of Noninvasive Ventilation in the Intensive Care Unit
Bhakti K. Patel, M.D., and John P. Kress, M.D., of the University of Chicago, comment on this subject in an accompanying editorial.
“With additional efforts to continue to reduce the percentage of critically ill patients who require invasive mechanical ventilation, alternative strategies for noninvasive ventilation that minimize face mask leak, improve oxygenation, and decrease work of breathing with alternative interfaces such as high-flow nasal cannula will need further investigation.”
EMBARGOED FOR RELEASE: 11 A.M. (ET), WEDNESDAY, OCTOBER 7, 2015
Media Advisory: To contact Junaid A. Bhatti, M.B.B.S., M.Sc., Ph.D., call Laura Bristow at 416-480-4040 or email Laura.Bristow@sunnybrook.ca. To contact commentary co-author Amir A. Ghaferi, M.D., M.S., email Kara Gavin at kegavin@med.umich.edu.
A study of a large group of adults who underwent bariatric surgery finds that the risk for self-harm emergencies increased after the surgery, according to a study published online by JAMA Surgery.
Morbid obesity is an epidemic in affluent countries; approximately 6 percent of Americans are morbidly obese. Mental health problems are prevalent in morbidly obese patients and those undergoing bariatric surgery. Self-harm behaviors, including suicidal ideation and past suicide attempts, are frequent in bariatric surgery candidates. It is unclear, however, whether these behaviors are mitigated or aggravated by surgery, according to background information in the article.
Junaid A. Bhatti, M.B.B.S., M.Sc., Ph.D., of the Sunnybrook Research Institute, Toronto, and colleagues studied 8,815 adults from Ontario, Canada, who underwent bariatric surgery to compare the risk of self-harm behaviors before and after surgery. Follow-up for each patient was 3 years prior to surgery and 3 years after surgery. The researchers categorized 4 distinct mechanisms of self-harm behaviors: medications, alcohol, poisoning by toxic chemicals, and physical trauma.
A total of 111 patients had 158 self-harm emergencies during follow-up. The researchers write that although a few patients had self-harm emergencies, the risk of these emergencies increased significantly (by approximately 50 percent) after surgery. Nearly all events occurred in patients who had a history of a mental health disorder. Intentional self-poisoning by medications was the most common mechanism of attempted suicide.
The authors write that the published literature provides differing reasons for the association between bariatric surgery and the subsequent risk of self-harm, including changes in alcohol metabolism after surgery; surgery might lead to a substitution of substance misuse for food; increased stress and anxiety in postoperative patients; and the effect of surgery on the levels of neurohormones, possible mediators of the likelihood of depression and suicidal behaviors. “Findings from this study advocate a better understanding of these and other theories through future research of potential mechanisms of self-harm in patients undergoing bariatric surgery.”
“These adverse events undermine the overall benefits of bariatric surgery. The study findings could be useful for bariatric surgeons and emergency physicians in postoperative follow-up. Additional clinical implications include active postoperative screening for self-harm risk among patients who have undergone bariatric surgery and are presenting for follow up. Patient and surgery factors could help identify vulnerable patients. Overall, these findings imply that more work is needed to understand why self-harm behaviors increase in the postoperative period and how these risks might be reduced.”
(JAMA Surgery. Published online October 7, 2015. doi:10.1001/jamasurg.2015.3414. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Commentary: Bariatric Surgery – More Than Just an Operation
“The study has 2 important findings. First, the preoperative incidence of self-harm emergencies in patients undergoing bariatric surgery is twice the population average and increases by an additional 50 percent in the postoperative period. The identification of patients with an increased risk of such adverse outcomes remains an elusive goal,” write Amir A. Ghaferi, M.D., M.S., and Carol Lindsay-Westphal, Ph.D., of the Ann Arbor Veterans Administration Healthcare System, Ann Arbor, Mich.
“Second, most self-harm emergencies occur in the second and third postoperative years. There is currently no minimum standard for psychological follow-up. Although stringent criteria are in place for insurance and programmatic approval to undergo surgery, the postoperative follow-up rates in general have been poor.”
“The study by Bhatti and colleagues underscores the unique vulnerability of patients undergoing bariatric surgery and forces us to look closely at why suicide rates are more than 4 times higher in these patients than the general population. Bariatric surgery is more than just an operation—it is time we recognize and treat it is as such.”
(JAMA Surgery. Published online October 7, 2015. doi:10.1001/jamasurg.2015.3396. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Dr. Ghaferi reported receiving salary support from Blue Cross Blue Shield of Michigan as the director of the Michigan Bariatric Surgery Collaborative. No other disclosures were reported.
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EMBARGOED FOR RELEASE: 8 A.M. (ET) WEDNESDAY, OCTOBER 7, 2015
Media Advisory: To contact Paul Young, F.C.I.C.M., email paul.young@ccdhb.org.nz. To contact editorial co-author John A. Kellum, M.D., email Anita Srikameswaran at srikamav@upmc.edu.
There was no significant difference in the incidence of acute kidney injury or failure for intensive care unit (ICU) patients who received a buffered crystalloid or saline for fluid therapy, according to a study appearing in JAMA. The study is being released to coincide with its presentation at the 28th annual congress of the European Society of Intensive Care Medicine.
The administration of intravenous fluids to increase intravascular volume or maintain hydration is a frequent intervention in the ICU, although the choice of fluid remains controversial. Globally, 0.9 percent sodium chloride (saline) is the most commonly used resuscitation fluid. However, despite its widespread use, emerging data provide uncertainty about the safety of saline in patients who are critically ill, with a concern that the high chloride content may contribute to the development of acute kidney injury (AKI), according to background information in the article.
One alternative to saline is a buffered crystalloid solution with an electrolyte composition that more closely resembles that of plasma, such as the prototype compound sodium lactate solutions or proprietary “buffered” or “balanced” crystalloid solutions. Observational data suggest that buffered crystalloids may be associated with a decreased risk of AKI and of death compared with saline. Paul Young, F.C.I.C.M., of the Medical Research Institute of New Zealand, Wellington, and colleagues studied 2,278 patients who were receiving treatment in 4 ICUs in New Zealand and requiring crystalloid fluid therapy. Of these patients, 1,152 of 1,162 patients (99 percent) receiving buffered crystalloid and 1,110 of 1,116 patients (99.5 percent) receiving saline were analyzed.
In the buffered crystalloid group, 102 of 1,067 patients (9.6 percent) developed AKI within 90 days after enrollment compared with 94 of 1,025 patients (9.2 percent) in the saline group. In the buffered crystalloid group, renal replacement therapy (dialysis) was used in 38 of 1,152 patients (3.3 percent) compared with 38 of 1,110 patients (3.4 percent) in the saline group. Overall, 7.6 percent of patients in the buffered crystalloid group and 8.6 percent of patients in the saline group died in the hospital.
“Further large randomized clinical trials are needed to assess efficacy in higher-risk populations and to measure clinical outcomes such as mortality,” the authors write.
Editor’s Note: This study was funded by the Health Research Council of New Zealand through a Research Partnership for Health Delivery grant and by Baxter Healthcare Corporation. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
Editorial: Assessing Toxicity of Intravenous Crystalloids in Critically Ill Patients
In an accompanying editorial, John A. Kellum, M.D., of the University of Pittsburgh, and Andrew D. Shaw, M.B., F.R.C.A., of the Vanderbilt University School of Medicine, Nashville, comment on the findings of this study.
“The results of the trial by Young et al provide reassurance that neither 0.9 percent saline nor a low-chloride electrolyte solution appears to be particularly hazardous when the total dose used in patients at low to moderate risk is about 2 L. This is an important contribution to the care of patients in the ICU. However, the large body of ‘circumstantial’ evidence that points to a harm signal for saline—with scant, if any, evidence of comparative benefit—should behoove intensivists and other clinicians to proceed with caution when ordering intravenous fluids.”
Author Interview: Pneumatic Compression Devices in Patients With Lymphedema
An author audio interview will be available for the study The Cutaneous, Net Clinical, and Health Economic Benefits of Advanced Pneumatic Compression Devices in Patients With Lymphedema. The article examines the impact of an advanced pneumatic compression device (APCD) on cutaneous and other clinical outcomes and health economic costs in a representative privately insured population of lymphedema patients.
The author audio interview will be available when the embargo lifts on the JAMA Dermatology website.
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For more information, contact JAMA Network Media Relations at 312-464-JAMA (5262) or emailmediarelations@jamanetwork.org.
Women who served in Vietnam have higher odds of posttraumatic stress disorder (PTSD) than women stationed during that era in the United States, and this effect appears to be associated with wartime exposures including sexual discrimination or harassment and job performance pressures, according to an article published online by JAMA Psychiatry.
During the Vietnam era, approximately 5,000 to 7,500 American women served in the U.S. military in Vietnam, at least 2,000 were stationed at nearby bases in Japan, the Philippines, Guam, Korea and Thailand, and 250,000 were in the United States. Most of the deployed women were nurses, although others filled clerical, medical and personnel positions. Although women were excluded from combat, women in Vietnam were still in a war theater and many of those stationed near Vietnam were exposed to casualties and other stressors.
Kathryn Magruder, Ph.D., M.P.H., of the Johnson Veterans Affairs Medical Center, Charleston, S.C., and coauthors report the main findings from the Department of Veterans Affairs (VA) Cooperative Study 579, the Health of Vietnam-Era Women’s Study (HealthVIEWS).
Among the 4,219 women (48.3 percent) who completed a survey and telephone interview, 1,956 served in Vietnam, 657 were near Vietnam and 1,606 served in the United States. Most of the women who served in Vietnam and in the United States were in the Army, while most of the women who served near Vietnam were in the Air Force. Women in Vietnam were more likely to be nurses.
The lifetime prevalence of PTSD was 20.1 percent for women in Vietnam, 11.5 percent for women near Vietnam and 14.1 percent for women in the United States. The prevalence for current PTSD active within the past year was 15.9 percent for women in Vietnam, 8.1 percent for women near Vietnam and 9.1 percent for women stationed in the U.S., the study reports.
Wartime exposure increased the odds of PTSD, especially exposure to sexual harassment and job performance pressure, according to the results. Sexual discrimination or harassment, which is not thought of as a unique war zone exposure, was higher among deployed women and related to PTSD in every model of analysis.
The authors acknowledge their findings differ from another national study of PTSD among Vietnam-era women veterans. They also note nonrespondents to the study, including those who have died, may have had a different PTSD prevalence.
“Because current PTSD is still present in many of these women decades after their military service, clinicians who treat them should continue to screen for PTSD symptoms and be sensitive to their noncombat wartime experiences,” the study concludes.
(JAMA Psychiatry. Published online October 7, 2015. doi:10.1001/jamapsychiatry.2015.1786. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: This study was supported by the Department of Veterans Affairs (VA), Veterans Health Administration, VA Office of Research and Development, Cooperative Studies Program. 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), WEDNESDAY, OCTOBER 7, 2015
Media Advisory: To contact corresponding author Sarah Arron, M.D., Ph.D., call Elizabeth Fernandez at 415-514-1592 or email Elizabeth.Fernandez@ucsf.edu. To contact corresponding editorial writer Aaron J. Blashill, Ph.D., call Beth Downing Chee at 619-594-4563 or email bchee@mail.sdsu.edu.
Gay and bisexual men indoor tan more frequently and report higher rates of skin cancer than heterosexual men, according to an article published online by JAMA Dermatology.
Skin cancer is the most common cancer in the United States, with approximately 5 million Americans treated annually. Data suggest sexual minority (self-reported homosexual, gay or bisexual) men may be more likely to engage in indoor tanning and to develop skin cancer. Indoor tanning is strongly associated with body image and appearance concerns. No study has assessed skin cancer prevalence or indoor tanning behaviors by sexual orientation in women, according to the study background.
Sarah Arron, M.D., Ph.D., of the University of California, San Francisco, and coauthors investigated the prevalence of a history of skin cancer and a history of indoor tanning among sexual minority men and women compared with heterosexuals. The authors used data from California Health Interview Surveys (CHISs) and the National Health Interview Survey (NHIS). The study included 78,487 heterosexual men, 3,083 sexual minority men, 107,976 heterosexual women and 3,029 sexual minority women.
Data from the state (2001-2005 CHISs) indicate skin cancer prevalence was higher among sexual minority men (4.3 percent) compared with heterosexual men (2.7 percent). National data (2013 NHIS) showed comparably higher rates of skin cancer among sexual minority men (6.7 percent) compared with heterosexual men (3.2 percent). When it comes to indoor tanning, sexual minority men were more likely than heterosexual men to report having tanned indoors.
Sexual minority women were less likely than heterosexual women to report having had nonmelanoma skin cancer or having tanned indoors, according to the study.
“Our study highlights disparities by sexual orientation in skin cancer history and indoor tanning, a known behavioral risk factor for skin cancer. This finding may inform practice by increasing awareness among practitioners and the larger medical community and by raising the need for better public health efforts, specifically, targeting risk behaviors among sexual minority men,” the authors conclude.
(JAMA Dermatology. Published online October 7, 2015. doi:10.1001/jamadermatol.2015.3126. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: The authors made funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Skin Cancer Risk in Gay and Bisexual Men
In a related editorial, Aaron J. Blashill, Ph.D., of San Diego State University, and Sherry Pagoto, Ph.D., of the University of Massachusetts Medical School, Worcester, write: “Skin cancer risk reduction in sexual minority men is an area in urgent need of research. … Further research is also needed to determine where sexual minority men engage in indoor tanning (i.e., salon vs. nonsalon locations) and to describe the nature of their tanning habits. Finally, skin cancer prevention interventions are also needed to reduce risk behavior in this population. Physicians can improve care and lend insights about this population by assessing sexual orientation as part of routine care and entering it into electronic medical records. Ultimately, reducing health disparities in sexual minorities will also require recognizing and eliminating bias and stigma in both research and clinical practice.”
(JAMA Dermatology. Published online October 7, 2015. doi:10.1001/jamadermatol.2015.3125. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Some investigator time was supported by a grant from the National Institute of Mental Health. 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), WEDNESDAY, OCTOBER 7, 2015
Media Advisory: To contact corresponding author Eleni Linos, M.D., Dr.P.H., call Elizabeth Fernandez at 415-514-1592 or email Elizabeth.Fernandez@ucsf.edu.
Online advertising may be a feasible way to deliver targeted prevention messages related to indoor tanning and skin cancer, according to an article published online by JAMA Dermatology.
Skin cancer is more common than all other cancers combined and indoor tanning is a preventable risk factor that accounts for more than 450,000 new malignant neoplasms (cancers) each year. Awareness of the dangers of tanning beds is one factor that can lead to behavior change.
Eleni Linos, M.D., Dr.P.H., of the University of California, San Francisco, and coauthors used Google’s advertising service to disseminate skin cancer prevention messages to Internet users conducting searches related to tanning beds.
Google AdWords is a pay-per-click advertising service that places three-line, 105-character advertisements next to Google search results. Google Nonprofits provided free advertising. The advertisements were divided into three thematic groups: appearance (i.e., tanning causes wrinkles, prevent skin aging and tanning makes you ugly); health (i.e., protect your skin, tanning causes cancer and prevent skin cancer); and education (i.e., the truth of tanning beds, the truth behind UV light, and know what tanning beds do).
The authors report that each month Google processes an average of more than 75,000 searches with the terms tanning, tanning bed and tanning salon. The authors’ advertisements were shown 235,913 times and clicked more than 2,000 times. A clock-through ratio of 1 percent is considered adequate for commercial advertisements.
“However, the effect of these advertisements on health behavior remains unknown. Further studies of this approach are needed to explore the characteristics of messages that generate views and clicks, and ultimately to determine whether this type of intervention successfully changes behavior,” the authors conclude.
(JAMA Dermatology. Published online October 7, 2015. doi:10.1001/jamadermatol.2015.3998. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: This study was supported in part by Google for Nonprofits, which provided an AdWords grant to fund advertisements. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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Among children and adults hospitalized with community-acquired pneumonia, those with influenza-associated pneumonia, compared with those with pneumonia not associated with influenza, had lower odds of having received an influenza vaccination, according to a study published online by JAMA.
In the United States, seasonal influenza epidemics are responsible for an estimated average of 226,000 hospitalizations and between 3,000 and 49,000 deaths each year. Pneumonia, the leading infectious cause of hospitalization and death in the United States, is a relatively common and serious complication of influenza. Whether influenza vaccines can decrease the risk of influenza-associated hospitalizations for community acquired pneumonia remains unclear, according to background information in the article.
In an observational multicenter study of hospitalizations for community-acquired pneumonia conducted from January 2010 through June 2012 at 4 U.S. sites, Carlos G. Grijalva, M.D., M.P.H., of the Vanderbilt University School of Medicine, Nashville, Tenn., and colleagues used data from patients 6 months or older with laboratory-confirmed influenza infection and verified vaccination status during the influenza seasons. Odds ratios were calculated, comparing the odds of vaccination between influenza-positive (case) and influenza-negative (control) patients with pneumonia, controlling for various factors.
Overall, 2,767 patients hospitalized for pneumonia were eligible for the study; 162 (5.9 percent) had laboratory-confirmed influenza. Twenty-eight of 162 cases (17 percent) with influenza-associated pneumonia and 766 of 2,605 controls (29 percent) with influenza-negative pneumonia had been vaccinated. The estimated vaccine effectiveness was 57 percent, meaning that the odds of influenza vaccination among cases hospitalized with influenza-associated pneumonia was 57 percent lower than among noninfluenza pneumonia controls.
The authors note that the estimated odds ratio of vaccination between cases and controls, and derived vaccine effectiveness from this study, could be used to inform subsequent estimations of the national number of hospitalizations for pneumonia averted by influenza vaccination.
Editor’s Note: This study was funded by the Influenza Division in the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
EMBARGOED FOR RELEASE: 11 A.M. (ET) MONDAY, OCTOBER 5, 2015
Media Advisory: To contact Alexander J. Kallen, M.D., M.P.H., call Melissa Brower at 404-639-4718 or email mbrower@cdc.gov. To contact editorial author Mary K. Hayden, M.D., call Charlie Jolie at 312-217-1864 or email Charles_L_Jolie@rush.edu.
The overall incidence in 2012-2013 was relatively low of a serious, highly drug-resistant group of bacteria (Carbapenem-resistant Enterobacteriaceae [CRE]) that are an important cause for health-care associated infections, according to a study published online by JAMA. Most CRE cases were associated with prior hospitalizations and discharge to long-term care settings.
Carbapenem-resistant Enterobacteriaceae are a worldwide clinical and public health problem. These multidrug-resistant organisms cause infections associated with high mortality and limited treatment options. Assessment of the U.S. epidemiology of CRE is needed to inform national prevention efforts, according to background information in the article.
Alexander J. Kallen, M.D., M.P.H., of the U.S. Centers for Disease Control and Prevention, Atlanta, and colleagues conducted a population- and laboratory-based active surveillance of CRE in 2012-2013 among individuals living in 1 of 7 U.S. metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, and Oregon. Cases of CRE were defined as carbapenem-nonsusceptible (excluding ertapenem) and extended-spectrum cephalosporin-resistant Escherichia coli, Enterobacter aerogenes, Enterobocter cloacae complex, Klebsiella pneumoniae, or Klebsiella oxytoca that were recovered from sterile-site or urine cultures during 2012-2013.
Among 599 CRE cases in 481 individuals, 520 (87 percent) were isolated from urine and 68 (11 percent) from blood. The median age was 66 years. The overall annual CRE incidence rate per 100,000 population was 2.93. The authors note that this estimate is substantially lower than the incidence of infections due to other pathogens traditionally associated with health care exposures, including methicillin-resistant Staphylococcus aureus (25.1 per 100,000 population), invasive candidiasis (13.3-26.2 per 100,000), and Clostridium difficile (147.2 per 100,000).
Most cases occurred in individuals with prior hospitalizations (75 percent) or indwelling devices (73 percent; such as urinary catheter, central venous catheter); 56 percent of admitted cases resulted in a discharge to a long-term care setting. Death occurred in 51 cases (9 percent), including in 27.5 percent of cases with CRE isolated from normally sterile sites.
The CRE standardized incidence ratio was significantly higher than predicted for the sites in Georgia (1.65), Maryland (1.44), and New York (1.42), and significantly lower than predicted for the sites in Colorado (0.53), New Mexico (0.41), and Oregon (0.28).
“The fact that heterogeneity exists (with respect to the incidence and the types of CRE found in these different surveillance areas) further highlights the need to understand the local epidemiology to tailor prevention efforts in individual regions of the United States. The frequency with which individuals with CRE are transferred between facilities emphasizes the need for regional control efforts in all the facilities,” the authors write.
“In summary, the results of this investigation further inform local efforts to prevent CRE transmission. The low CRE incidence in the catchment areas, compared with other more established resistant organisms, highlights that CRE are emerging and suggests that control interventions implemented now could have a substantial effect.”
Editor’s Note: This work was supported by the Emerging Infections Program and the National Center for Emerging and Zoonotic Infectious Diseases at the U.S. Centers for Disease Control and Prevention. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Editorial: Measuring Carbapenem-Resistant Enterobacteriaceae in the United States
“The study by Guh et al represents an important step forward for CRE control in the United States,” writes Mary K. Hayden, M.D., of Rush University Medical Center, Chicago.
“Expansion of surveillance to more geographic regions, including rural settings and metropolitan areas known to have high prevalence of CRE, would provide a more complete picture of the U.S. burden. Molecular characterization of isolates would also inform prevention efforts. Whether the resources needed for this work will be made available is unclear.”
“In the meantime, physicians, infection control practitioners, and public health workers will continue to rely on the Multi-site Gram-negative Surveillance Initiative [used for this study] and other surveillance networks to measure the extent of CRE and estimate the effects of prevention efforts.”
Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Hayden reported receiving grants from the U.S. Centers for Disease Control and Prevention.
EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, OCTOBER 6, 2015
Media Advisory: To contact James Fleshman, M.D., call Craig Civale at 214-820-6251 or email Craig.Civale@baylorhealth.edu. To contact Andrew R. L. Stevenson, M.B.B.S., F.R.A.C.S., email admin@ausces.com. To contact editorial co-author Scott A. Strong, M.D., call Pat Tremmel at 847-491-4892 or email p-tremmel@northwestern.edu.
Compared to open resection (surgical removal) for rectal cancer, minimally invasive laparoscopic-assisted resection did not provide better cancer outcomes, according to two studies in the October 6 issue of JAMA.
Treatment of curable, locally advanced (stage II or III) rectal cancer relies on surgical resection as the core feature of a treatment process. Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete, particularly for patients with more advanced-stage disease. There are concerns that not all the cancer can be removed with minimally invasive techniques. James Fleshman, M.D., of Baylor University Medical Center, Dallas, and colleagues conducted a trial in which 486 patients with clinical stage II or Ill rectal cancer were randomly assigned to laparoscopic or open resection to examine whether laparoscopic resection is noninferior (not worse than) to open resection, as determined by several measures of the adequacy of cancer removal. A 6 percent noninferiority margin was chosen as being a clinically important difference. . The trial was conducted at 35 institutions in the United States and Canada and sponsored by the American College of Surgeons and the National Cancer Institute.
Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis. They underwent surgery by surgeons with experience and proven expertise in the operations they were performing. Pre-determined measures of overall surgical success occurred in 82 percent of laparoscopic resection cases and 87 percent of open resection cases. “Laparoscopic resection failed to meet the criterion for noninferiority for pathologic outcomes compared with open resection and was thus potentially inferior,” the authors write. In terms of cancer control, the laparoscopic procedure was not shown to be as good as the traditional, open operation.
Operative time was significantly longer for laparoscopic resection. Hospital length of stay, readmission within 30 days, and severe complications were not significantly different.
The researchers write that one explanation for their findings is that proctectomy (resection of the rectum) is challenging, and it can be even more difficult to work in the deep pelvis with in-line rigid instruments used in laparoscopic surgery. Access to this very difficult area of the body might be better with the open procedure. .
“Pending clinical oncologic outcomes [such as survival or cancer recurrence rates], the findings do not support the use of laparoscopic resection in these patients.”
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
In another study using the same design as the Fleshman study, Andrew R. L. Stevenson, M.B.B.S., F.R.A.C.S., of the University of Queensland, Brisbane, Australia, and colleagues conducted a phase 3 trial that included 475 patients with T1-T3 rectal cancer who were randomized to open laparotomy and rectal resection (n = 237) or laparoscopic rectal resection (n = 238) at 24 sites in Australia and New Zealand.
Proponents of the laparoscopic technique suggest that a similar tumor resection with better short-term outcomes can be achieved with minimal access surgery. Because of anatomical constraints, laparoscopic rectal resection may not be better because of limitations in performing an adequate cancer resection, according to background information in the article.
For this trial, the primary outcome of a successful resection (a composite of oncological factors, with a noninferiority margin of 8 percent) was achieved in 194 patients (82 percent) in the laparoscopic surgery group and in 208 patients (89 percent) in the open surgery group and was the same as that of the Fleshman study. Non inferiority was not shown for the laparoscopic resection, meaning that it was not shown to be as good as the open operation for rectal cancer. In fact, a post hoc test for superiority suggested that open surgery was better. Additional analysis with adjustment for baseline prognostic factors, including pathological grade, did not significantly change the overall treatment effect.
There were no differences between the two groups in hospital length of stay, intensive care unit stay or analgesic requirement.
“We were unable to establish noninferiority of laparoscopic rectal cancer surgery in this large randomized trial,” the authors write. “Even though our trial was not designed to demonstrate whether one method of rectal dissection was superior to the other, the inability to establish noninferiority suggests that surgeons should be cautious when considering the suitability of a laparoscopic approach for a patient with rectal cancer.”
Editor’s Note: The study was supported by grants from the Colorectal Surgical Society of Australia and New Zealand Foundation and the National Health and Medical Research Council. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Editorial: Minimally Invasive Approaches to Rectal Cancer and Diverticulitis
The large, randomized, multicenter trials reported in this issue of JAMA substantiate recent findings from similar randomized trials that a laparoscopic resection may not be oncologically justified in many patients requiring proctectomy for rectal cancer, write Scott A. Strong, M.D., and Nathaniel J. Soper, M.D., of the Northwestern University Feinberg School of Medicine, Chicago.
“The studies do not signal a moratorium on these approaches, but surgeons must proceed in a judicious manner to ensure that patients are informed about the benefits and risks associated with minimally invasive and open operations.”
“Although the surgical management of patients with rectal cancer and diverticulitis has greatly improved, many questions persist and new ones continually arise that can be answered only with well-designed, rigorously conducted clinical trials. The utility of less intrusive strategies and minimally invasive approaches will undoubtedly expand as technologies evolve, but they must be responsibly incorporated into surgical practice based on evidence rather than subjective reasons.”
A supervised exercise program and self-management advice, like those commonly given with physical therapy, did not improve activity limitation or quality of life compared with advice alone after removal of immobilization for patients with an uncomplicated ankle fracture, according to a study in the October 6 issue of JAMA.
Ankle fracture is a common injury and is treated with reduction (realignment), sometimes with surgical fixation, followed by a period of immobilization while the fracture heals. The benefits of rehabilitation after immobilization for ankle fracture has been unclear, according to background information in the article.
Anne M. Moseley, Ph.D., of the University of Sydney, Australia, and colleagues randomly allocated 214 patients with isolated ankle fracture presenting to fracture clinics in 7 Australian hospitals to rehabilitation (n = 106) or advice alone (n = 108), following removal of their immobilization cast. Rehabilitation consisted of a supervised exercise program (individually tailored, prescribed, monitored, and progressed by a physical therapist) and advice about self-management. Participants in the advice group were provided with a single session of self-management advice about exercise and return to activity.
There was follow-up for 170 patients (79 percent) at 6 months. Activity limitation and quality of life were assessed at study entry and at 1, 3 and 6 months. At study entry, participants had significant activity limitation and low quality of life. The researchers found that the rehabilitation program and self-management advice did not improve activity limitation or quality of life compared with advice alone. The treatment effects were not associated with fracture severity, age or sex.
“We have previously shown that recovery of activity limitation after ankle fracture is rapid in the first 6 months and that adding passive stretch or manual therapy to a supervised exercise program did not enhance the benefits of exercise alone,” the authors write. “It is possible that the lack of treatment effect we observed in this trial is attributable to the fact that rehabilitation cannot accelerate this rapid recovery. These findings and the findings of the present trial suggest that routine care for patients after isolated ankle fracture should include self-management advice at the time of removal of immobilization but not a supervised exercise program [like those typically provided in a physical therapy program].”
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
EMBARGOED FOR RELEASE: 11 A.M. (ET), MONDAY, OCTOBER 5, 2015
Media Advisory: To contact corresponding author Carlos Rodriguez-Galindo, M.D., call Irene Sege at 617-919-3110 or email irene.sege@childrens.harvard.edu.
Ethnic, racial and socioeconomic disparities appear to exist among children with retinoblastoma, a once uniformly fatal but now treatable eye cancer, and those disparities are associated with greater risks for advanced disease and undergoing enucleation (removal of the eye), according to an article published online by JAMA Pediatrics.
Retinoblastoma is a rare childhood cancer with about 9,000 cases diagnosed yearly worldwide. When diagnosed early, salvaging the eye and preserving vision are possible with relatively minimal therapy. Although disparities in access to health care have been well discussed for adult cancers, little is known about pediatric cancers.
Carlos Rodriguez-Galindo, M.D., of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, and coauthors reviewed 18 Surveillance, Epidemiology and End Results (SEER) registries from 2000 through 2010. The authors identified 830 cases of retinoblastoma for children up to 9 years old and examined the effects of socioeconomic status, race and ethnicity on the extent of disease and outcomes.
Among the 830 children, Hispanic children had a higher percentage of extraocular (outside of the eye or advanced disease) compared with non-Hispanic children 33 percent (86 of 261) vs. 20 percent (102 of 510). Among 771 children whose extent of disease could be determined, 188 (24.4 percent) of them presented with extraocular disease. The percentage of extraocular cases was higher in counties with low socioeconomic status indicators including higher poverty, lower educational attainment, higher levels of crowding, higher unemployment, higher language isolation and higher percentage of immigrants, according to the results.
Ocular outcomes were known for 822 children and 574 of these children (69.8 percent) underwent enucleation at some point in treatment. Hispanic children were 41 percent more likely to undergo enucleation than non-Hispanic white children, according to the study. The percentage of enucleation was higher among Hispanic compared with non-Hispanic children 74.5 percent (202 of 271) vs. 67.5 percent (372 of 551). Higher rates of enucleation also were associated with low educational attainment and a higher level of crowding.
The five-year relative survival rate was 97.7 percent.
The authors acknowledge limitations inherent to the use of SEER registry and census data and to extrapolating indicators to investigate social determinants of health in this specific population.
“Low socioeconomic status affects disease extent and ocular outcomes, presumably by limiting access to primary and cancer-directed care,” the study notes.
(JAMA Pediatr. Published online October 5, 2015. doi:10.1001/jamapediatrics.2015.2360. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see article for additional information, including other authors, author contributions and affiliations, etc.
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Students who lived in states with an antibullying law that includes at least one U.S. Department of Education-recommended legislative component had lower odds of reporting bullying and cyberbullying compared with students in states whose laws had no such provisions, according to an article published online by JAMA Pediatrics.
Currently, 49 states have antibullying laws in place, although there has been very little empirical examination of their effectiveness.
Mark L. Hatzenbuehler, Ph.D., of the Columbia University Mailman School of Public Health, New York, and coauthors used data from 25 states to evaluate the effectiveness of antibullying legislation in reducing students’ risk of being bullied and cyberbullied.
Data on antibullying legislation came from the Department of Education (DOE), which had recommended a framework for antibullying laws that was disseminated to schools across the country. In a 2011 report, the DOE reviewed the extent to which state antibullying laws adhered to those recommendations and found substantial heterogeneity across state policies. The report identified 16 components divided into four broad categories: definitions of the policy, district policy development and review, mandated procedures, and strategies for communication, training and legal support. Policy variables from 25 states were linked to data from the Youth Risk Behavior Surveillance System on bullying and cyberbullying.
The final study sample included 59,472 students in 9th through the 12th grades in public and private schools. The authors report students in states with at least one DOE legislative component in the antibullying law had 24 percent lower odds of reporting bullying and 20 percent lower odds of reporting cyberbullying.
Three individual components of antibullying legislation were consistently associated with decreased odds of being bullied and cyberbullied: statement of scope, description of prohibited behaviors, and requirements for districts to develop and implement local policies, the study reports.
The authors caution they can only infer about associations between antibullying policies and rates of being bullied because the data were cross-sectional and they cannot test causal associations.
“Bullying is a multifaceted phenomenon that requires a multipronged approach. Although antibullying policies by themselves cannot completely eradicate bullying, these data suggest that such policies represent an important part of a comprehensive strategy for preventing bullying among youth,” the study concludes.
(JAMA Pediatr. Published online October 5, 2015. doi:10.1001/jamapediatrics.2015.2411. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: This study was supported in part by a grant from the Center for Injury Epidemiology and Prevention at Columbia University and a Research Core grant from the University of Iowa Injury Prevention Research Center. Both centers were funded by the National Center for Injury Prevention and Control, Centers for Disease Control and Prevention. Please see article for additional information, including other authors, author contributions and affiliations, etc.
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A two-drug antihypertensive treatment that included a beta-blocker was associated with increased risk for major adverse cardiovascular events (MACEs) and death in a study of Danish patients who underwent noncardiac surgery, according to an article published online by JAMA Internal Medicine.
Use of β-blockers during noncardiac surgery is being reevaluated because of concerns about the validity of some prior studies.
Mads E. Jørgensen, M.B., of Gentofte Hospital, University of Copenhagen, Denmark and coauthors examined in-hospital records and out-of-hospital pharmacotherapy use in Danish patients with uncomplicated hypertension treated with at least two antihypertensive drugs (β-blockers, thiazides, calcium antagonists or renin-angiotensin system [RAS] inhibitors) undergoing noncardiac surgery between 2005 and 2011. The authors looked at 30-day risk of MACEs and all-cause mortality.
A total of 55,320 hypertensive patients underwent noncardiac surgery in Denmark between 2005 and 2011; baseline clinical characteristics were similar between the 14,644 patients treated with β-blockers and the 40,676 patients treated with other antihypertensive drugs.
The study reports the 30-day incidence of MACEs was 1.32 percent and mortality was 1.93 percent in patients treated with β-blockers compared with 0.84 percent and 1.32 percent, respectively, in patients treated with other drugs.
β-blocker use was associated with increased risks of MACEs in two-drug combinations with RAS inhibitors, calcium antagonists and thiazides. The results were similar for all-cause mortality. Risk of MACEs associated with β-blocker use seemed especially pronounced for patients at least 70 years old, for men and for patients undergoing acute surgery, according to the results.
The authors acknowledge study limitations that include the misclassification of some patients as hypertensive and an incomplete exclusion of patients with complicated hypertension.
“This association was seen irrespective of the antihypertensive drug combination and was consistent across subgroups. This observation may suggest that perioperative management of patients with hypertension should receive specific attention in clinical practice and future guidelines, but additional randomized clinical trials on this question may be warranted,” the authors conclude.
(JAMA Intern Med. Published online October 5, 2015. doi:10.1001/jamainternmed.2015.5346. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), MONDAY, OCTOBER 5, 2015
Media Advisory: To contact study corresponding author Kristin N. Ray. M.D., M.S., call Andrea Kunicky at 412-692-6254 or email andrea.kunicky@chp.edu. To contact Editor’s Note authors Joseph S. Ross, M.D., M.H.S., or Mitchell Katz, M.D., email mediarelations@jamanetwork.org
Racial/ethnic minorities and unemployed individuals had a longer total time burden (time spent traveling to, waiting for and receiving ambulatory medical care) in a nationally representative study, although patients’ face-to-face time with physicians tended not to vary, according to an article published online by JAMA Internal Medicine.
The Institute of Medicine has identified timeliness of care as a key quality aspect. Racial and socioeconomic disparities exist in the receipt of timely appointments and interventions. Disparities in time burden have received less attention.
Kristin N. Ray, M.D., M.S., of the University of Pittsburgh School of Medicine, and colleagues used data from the American Time Use Survey from 2005 to 2013 to identify those people reporting clinic time, which is time waiting for or obtaining medical care. For 3,787 survey respondents with clinic time, the authors determined associated travel time and total time, which is the sum of clinic time and travel time. Then the authors compared the time estimates with time spent with a physician collected from 2006 to 2010 by the National Ambulatory Medical Care Survey (n=150,022).
The results indicate that patients spent on average 123 minutes obtaining medical care, including 86 minutes of clinic time and 38 minutes of travel time.
Clinic time was longer for racial/ethnic minorities, individuals with less education and those who are unemployed. For example, clinic time for non-Hispanic whites was 80 minutes compared with 99 minutes for non-Hispanic black patients and 105 minutes for Hispanic patients. Clinic time was 94 minutes for unemployed individuals vs. 72 minutes for those with the highest hourly income.
Travel time also was longer for racial/ethnic minorities and unemployed individuals. For example, travel time for non-Hispanic whites was 36 minutes vs. 45 minutes for non-Hispanic black and Hispanic patients, while unemployed individuals had 41 minutes of travel time compared with 34 minutes for those with the highest hourly income, according to the results.
Face-to-face time with physicians averaged 20.5 minutes and did not vary by patient race/ethnicity, neighborhood income or rural/urban status, the authors report.
The authors note their study is limited by data that does not include health status, reasons for visits, severity of illness, insurance status or site of care, such as an emergency department or physician office.
“For individuals, excess time burden may create a disincentive to seeking care. Given that racial/ethnic minorities and unemployed persons disproportionally receive care at community health centers, the differences in clinic time may reflect the struggles of these centers to manage clinical appointments efficiently, as well as the consequences of obtaining care in walk-in clinics or emergency departments where appointments are not scheduled,” the authors conclude.
Editor’s Note: No Time to Wait
In a related commentary, Joseph S. Ross, M.D., M.H.S., an associate editor of JAMA Internal Medicine, and Mitchell H. Katz M.D., a deputy editor of JAMA Internal Medicine, write: “This study characterizes a problem we all know to exist. We need additional work to assure the timeliness and equitability of care through effective interventions to shorten the time spent waiting. ”
(JAMA Intern Med. Published online October 5, 2015. doi:10.1001/jamainternmed.2015.4468. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: The study was supported in part by grants from the California HealthCare Foundation, the Health Resources and Services Administration National Research Service Award for Primary Medical Care, the Agency for Healthcare Research and Quality and the National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), THURSDAY, OCTOBER 1, 2015
Media Advisory: To contact corresponding author Rebecca Sutphen, M.D., call Anne DeLotto Baier at 813-974-3303 or email abaier@health.usf.edu. To contact corresponding editorial author Steven Narod, M.D., call Rebecca Cheung at 416-300-5346 or email rebecca.cheung@wchospital.ca.
Most women who underwent BRCA genetic testing did not receive genetic counseling by trained genetics professionals and the lack of clinician recommendation was the most commonly reported reason in a study of commercially insured women, according to an article published online by JAMA Oncology.
Women with susceptibility to hereditary breast and ovarian cancer (HBOC) face high lifetime risks of 24 percent to 86 percent for breast cancer and 16 percent to 67 percent for ovarian cancer. Professional guidelines delineate clinical criteria based on personal and family history and recommend, for women who meet the criteria, consultation with a professionally trained, board-certified genetics clinician for genetic counseling.
Rebecca Sutphen, M.D., of the University of South Florida Morsani College of Medicine, Tampa, and coauthors examined the factors associated with use of BRCA testing, assessed whether delivery of genetic counseling and testing services adheres to professional guidelines, and measured the impact on patient reported outcomes.
In collaboration with the commercial health insurer Aetna, the American BRCA Outcomes and Utilization of Testing (ABOUT) study analyzed data from 11,159 women whose clinicians ordered BRCA testing between December 2011 and December 2012. Aetna mailed study packet questionnaires to women and 34.7 percent of them completed it. Aetna’s commercial health plans cover genetic counseling services by a professional genetics clinician either in person or by telephone, according to the study background.
The majority of women (an estimated 53.3 percent) undergoing BRCA testing did not have a personal history of breast or ovarian cancer; an estimated 43.3 percent had a personal history of breast cancer; 2.9 percent had a personal history of ovarian cancer; and 0.5 percent had a personal history of breast and ovarian cancer.
Among 3,628 women whose physicians ordered comprehensive BRCA testing, most were white non-Hispanic (69 percent), college-educated (81.4 percent) and married (75.8 percent) with higher incomes (55.4 percent). Of these women, authors report 16.4 percent (596) did not meet testing criteria. Mutations were identified in 161 (5.3 percent) women who had comprehensive testing. About 36.8 percent (1,334) of the 3,628 women reported receiving genetic counseling from a genetics professional, and the lowest rates (130[12.3 percent]) were among patients of obstetricians/gynecologists. The most common reason reported by women for not receiving this service was the lack of a clinician recommendation.
The women who did receive genetic counseling by a trained genetics professional displayed greater knowledge of BRCA and expressed greater understanding and satisfaction, according to the results.
Limitations to the study include that the authors were unable to directly obtain additional information from ordering providers about the potential underlying causes for the suboptimal genetic counseling referral patterns and relatively high rate of inappropriate test requests.
“These findings demonstrate important gaps in clinical genetic services. Recently mandated coverage of genetic counseling services as a preventive service without patient cost sharing should contribute to improving clinical genetics services and associated outcomes in the future,” the study concludes.
(JAMA Oncol. Published online October 1, 2015. doi:10.1001/jamaoncol.2015.3048. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: An author made a financial disclosure. The research was supported with funds received through the Aetna Foundation as well as in-kind support from Aetna, University of South Florida, Facing Our Risk of Cancer empowered, Inc., (FORCE) and the American Cancer Society. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Genetic Testing for BRCA Mutations Today and Tomorrow
In a related editorial, Steven Narod, M.D., of the Women’s College Research Institute, Toronto, writes: “The article by Armstrong et al tells an interesting story, but it is a story of the recent past told from a particular point of view, and given the rapid pace of change, it is a story that may not be a relevant guide for the future. It is disingenuous to think that we can maintain the status quo in terms of universal 1-on-1 pretest counseling if we are to fully realize the technical advances in genetic sequencing and apply these to the practice of personalized medicine. We should test as widely as possible to find as many carriers as we can. To do this, we need to find adequate alternatives to 1-on-1 counseling and focus our attention on those with positive test results. We need to expand our research programs to gain a better understanding of the meaning of each test result.”
(JAMA Oncol. Published online October 1, 2015. doi:10.1001/jamaoncol.2015.3269. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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CHICAGO – Jay F. Piccirillo, M.D., F.A.C.S., C.P.I., professor of otolaryngology and vice chairman for research at the Washington University School of Medicine in St. Louis, has been named the next editor in chief of JAMA Otolaryngology-Head & Neck Surgery, one of ten specialty journals in the JAMA Network.
On January 1, Dr. Piccirillo, who currently serves on the editorial board of JAMA Otolaryngology-Head & Neck Surgery, will replace Paul A. Levine, M.D., who has been editor in chief since 2005 of the journal formerly known as the Archives of Otolaryngology-Head & Neck Surgery. Dr. Levine is professor and chair of the Department of Otolaryngology – Head and Neck Surgery at the University of Virginia School of Medicine, Charlottesville.
“I am thrilled to assume the editor in chief position at JAMA-Otolaryngology Head & Neck Surgery and continue the great work of the previous editors, including Drs. Paul Levine and Michael Johns,” said Dr. Piccirillo. “I also look forward to working with the great JAMA Network medical publishing team led by Howard Bauchner, and my otolaryngology colleagues who serve on the editorial board and serve as reviewers.”
Dr. Piccirillo is a Professor of Otolaryngology at the Washington University School of Medicine, where he is Vice Chair for Research; Director of the Clinical Outcomes Research Office for the Department of Otolaryngology – Head & Neck Surgery; and a board-certified otolaryngologist. Dr. Piccirillo’s research and teaching interests include tinnitus, rhinosinusitis, head and neck cancer, and clinical research methods and statistics. He has published more than 130 peer-reviewed journal articles and is an attending physician at Barnes-Jewish Hospital and St. Louis Children’s Hospital. Dr. Piccirillo graduated from the University of Vermont College of Arts & Sciences and the College of Medicine.
“I could not be more pleased to welcome Jay Piccirillo, a fine clinician and superb investigator, as the new editor in chief of JAMA Otolaryngology-Head & Neck Surgery. This is also the time to thank Paul Levine for his service, commitment, and wisdom these past 10 years,” said Howard Bauchner, M.D., editor in chief of JAMA and the JAMA Network.
“Dr. Piccirillo is an outstanding choice to take JAMA Otolaryngology-Head & Neck Surgery into the next decade and assist with the continuing changes that make this journal so valuable to our specialty,” said Dr. Levine.
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The chronic inflammatory skin condition psoriasis was associated with the risk of major depression, although the risk was unrelated to the severity of the disorder, according to an article published online by JAMA Dermatology.
Psoriasis affects 3 percent to 4 percent of the U.S. population, and the psychological impact of psoriasis can be substantial. The identification of depression among patients with psoriasis is especially important because major depression is associated with decreased quality of life and increased all-cause mortality.
Roger S. Ho, M.D., M.S., M.P.H., of the New York University School of Medicine, New York, and coauthors examined the relationship between psoriasis and major depression in a nationally representative group, after adjusting for cardiovascular risk because prior research has suggested both depression and psoriasis are associated with cardiovascular disease. The authors analyzed data for participants in the National Health and Nutrition Examination Survey (NHANES) from 2009 through 2012. Diagnosis of major depression was based on a health questionnaire.
Authors identified 351 (2.8 percent) cases of psoriasis and 968 (7.8 percent) cases of major depression among 12,382 U.S. residents. There were 58 (16.5 percent) patients with psoriasis who met the criteria for a diagnosis of major depression. The average patient questionnaire score was higher among patients with a history of psoriasis than those patients without, according to the results.
Further analyses suggested the risk of major depression was not different between patients with limited vs. extensive psoriasis. A history of cardiovascular events did not affect the risk of major depression for patients with psoriasis. However, more patients with psoriasis (23.6 percent) reported that any symptoms of depression caused daily functional impairment, compared with patients without psoriasis (15.4 percent), according to the results.
The authors note limitations to the study, including the use cross-sectional data that prevents the establishment of a temporal relationship (which came first) between depression and psoriasis.
“Therefore, our study supports that all patients with psoriasis, regardless of severity, are at risk for depressive symptoms and may benefit from depression screening,” the authors conclude.
(JAMA Dermatology. Published online September 30, 2015. doi:10.1001/jamadermatol.2015.3605. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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Training on skin self-examination (SSE) to aid early detection could be extra beneficial for patients with melanoma and their partners who report having low relationship quality because it gives them activities to do together, according to an article published online by JAMA Dermatology.
Melanoma remains a significant public health concern with an estimated 73,000 new cases of invasive melanoma and more than 9,900 deaths expected to occur in 2015. Melanoma is a treatable cancer with a high survival rate if it is detected early. Individuals previously diagnosed with melanoma are 10 times more likely to develop additional melanomas, which makes them an important population on which to focus early detection. Melanomas detected during SSE are more likely to have favorable outcomes. However, many areas on the body are difficult to examine by oneself so a skin-check partner is beneficial.
JAMA Dermatology Editor June K. Robinson, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, and coauthors examined for whom a SSE training intervention works best in a sample of pairs of melanoma patients and their partners (a cohabitating spouse or committed partner or a noncohabitating friend, child, parent, sibling or other relative).
The study, which included 494 patients with melanoma and their skin-check partners, was conducted at Northwestern Medicine ambulatory care dermatology offices from June 2011 to April 2014. Of the patients, 395 were randomly assigned to the intervention and 99 patients served as a control group to receive customary care. Both patients and their partners were an average age of 55.
In the intervention, patients and their skin-check partners received skills training to assess moles, along with a ruler and a lighted magnifying lens, a laminated card with the ABCDE (Assess Border, Color, Diameter and Evolution of pigmented lesions) rules and a map of the body. During a clinical visit, the dermatologist also invited the partner to join in looking at the patient’s back as part of the intervention. Patients and their partners in the control group received no such skills training and were not invited by the dermatologist to review the patient’s back during a clinic visit.
The authors report the intervention increased patient SSE self-efficacy scores, which gauge confidence in performing SSE. Partner motivation did not affect patient SSE self-efficacy. However, there was an effect from relationship variables (happiness and activities performed with the partner) on how the intervention affected patient SSE self-efficacy, with the greatest benefit of SSE education identified in those pairs who spend the least time together and have the least happiness, according to the study.
“While dermatologists are most likely not going to be able to change relationship quality, pairs who were given an activity – partner-assisted SSE – to perform together did so; thus, pairs with low relationship quality increased their activities performed with their partner. Since these individuals showed the largest increase in patient SSE self-efficacy after they received the SSE training, dermatologists or health care professionals should consider recommending SSE training for these individuals and their partners,” the authors conclude.
The authors note limitations in their study, including reliance on self-reports.
(JAMA Dermatology. Published online September 30, 2015. doi:10.1001/jamadermatol.2015.2819. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: This study was supported by a grant from the National Cancer Institute. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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A cognitive-behavioral prevention program for depression among at-risk youth showed benefit more than 6 years after the implementation of the intervention, according to an article published online by JAMA Psychiatry.
Depression is the leading cause of disability worldwide and commonly begins in adolescence. Adolescents whose parents have a history of depression are at risk for developing depression and functional impairment. The long-term effects of prevention programs on adolescent depression and functioning has not been known, according to background information in the article.
David A. Brent, M.D., of the University of Pittsburgh School of Medicine, and colleagues randomly assigned 316 participants (13 to17 years of age at enrollment with at least 1 parent with current or prior depressive episodes [index parent]) to a cognitive-behavioral prevention (CBP) program (n = 159; 8 weekly 90-minute group sessions followed by 6 monthly continuation sessions) or usual care (n = 157; any family-initiated mental health treatment). The study was conducted at four sites.
Over a follow-up period of 75 months (with 88 percent retention), youths assigned to CBP had a lower incidence of depression. The CBP program’s overall significant effect was driven by a lower incidence of depressive episodes during the first 9 months after enrollment. The CBP program’s benefit was seen in youths whose index parent was not depressed at enrollment; benefit was also noted on depression incidence, depression-free days, and developmental competence (i.e., educational and occupational attainment, romantic relationships, family and peers relationships and life satisfaction). The effects on developmental competence were mediated via the CBP program’s effect on depression-free days.
“Overall, these findings demonstrate the effectiveness of CBP for preventing depression and promoting competence, but they also highlight 3 potential improvements to CBP. First, the main beneficial effect on the onset of new depression episodes occurred over the course of the intervention, suggesting that booster sessions might help extend these effects on new onsets even further in time. Second, CBP was not effective if the index parent was depressed at baseline, highlighting the possible importance of treating parental depression, either prior to or concomitant with their children’s participation in the CBP program,” the authors write.
“Third, CBP is focused exclusively on the adolescent. Interventions that also improve parenting and the quality of the parent-child relationship have been shown to have long-lasting benefits on a range of both externalizing and internalizing symptoms. Nevertheless, the current findings showed that CBP forms the basis of a promising intervention and that the prevention of depression is possible and can have longer-term developmental consequences.”
(JAMA Psychiatry. Published online September 30, 2015. doi:10.1001/jamapsychiatry.2015.1559. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), WEDNESDAY, SEPTEMBER 30, 2015
Media Advisory: To contact Russ S. Kotwal, M.D., M.P.H., call Steven Galvan at 210-539-5470 or email steven.galvan2.civ@mail.mil. To contact Todd E. Rasmussen, M.D., call Lori Salvatore at 301-619-2736 or email lori.b.salvatore.civ@mail.mil.
A mandate in 2009 that prehospital helicopter transport of critically injured combat casualties occur in 60 minutes or less (golden hour policy) has resulted in a reduction in time between critical injury and definitive care for combat casualties in Afghanistan and an improvement in survival, according to a study published online by JAMA Surgery.
Minimizing time between critical injury and definitive care has long been a hallmark and metric of trauma systems, particularly in war, where devastating injuries result in death occurring predominantly before hospital arrival. In 2009, Secretary of Defense Robert M. Gates mandated a standard of 60 minutes or less, from call to arrival at the treatment facility, for prehospital helicopter transport of U.S. military casualties with critical injuries, cutting in half the previous goal of 2 hours.
Russ S. Kotwal, M.D., M.P.H., of the United States Army Institute of Surgical Research, Joint Base San Antonio-Ft. Sam Houston, and colleagues compared morbidity and mortality outcomes for casualties before vs after the mandate and for those who underwent prehospital helicopter transport in 60 minutes or less vs. more than 60 minutes. The analysis included battlefield data for 21,089 U.S. military casualties that occurred during the Afghanistan conflict from September 2001 to March 2014.
For the total casualty population, the percentage killed in action (16 percent [386 of 2,411] vs 9.9 percent [964 of 9,755]) and the case fatality rate ([CFR] 13.7 (469 of 3,429] vs 7.6 (1,344 of 17,660) were higher before vs. after the mandate, while the percentage died of wounds ([DOW] 4.1 percent vs 4.3 percent) remained unchanged. Decline in CFR after the mandate was associated with an increasing percentage of casualties transported in 60 minutes or less, with projected vs actual CFR equating to 359 lives saved.
Among 4,542 casualties with detailed data, there was a decrease in median transport time after the mandate (90 min vs 43 min) and an increase in missions achieving prehospital helicopter transport in 60 minutes or less (24.8 percent vs 75.2 percent). When adjusted for injury severity score and time period, the percentage killed in action was lower for those critically injured who received a blood transfusion and were transported in 60 minutes or less, while the percentage died of wounds was lower among those critically injured initially treated by combat support hospitals.
“In summary, as transport time decreased and capabilities increased, casualties who would previously have been in the killed in action mortality group survived outright or survived long enough that they shifted to the DOW mortality group, and casualties who would previously have been in the DOW mortality group were also surviving. Decreasing the time from injury to arrival at the treatment facility challenged the full measure of the trauma system with more critically injured casualties who then benefited from the care they received,” the authors write.
(JAMA Surgery. Published online September 30, 2015. doi:10.1001/jamasurg.2015.3104. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: No conflict of interest disclosures were reported. Please see the article for additional information, including financial disclosures, funding and support, etc.
Commentary: The Power of Advanced Capability and Informed Policy
“Reduction in the percentage killed in action following the 2009 policy change provides evidence of the effect of an enhanced capability during the ‘golden hour’ after injury,” writes Todd E. Rasmussen, M.D., of the U.S. Combat Casualty Care Research Program, U.S. Army, Fort Detrick, Md.
“Although the notion of a golden hour is not new, this study assembled injury management data from the U.S. Department of Defense Trauma Registry, autopsy data from the Armed Forces Medical Examiner, and previously classified data pertaining to evacuation times to provide insight into what can be accomplished during this acute phase of care. Findings of a reduced percentage killed in action also confirm previous studies suggesting the effectiveness of point-of-injury care and the care provided by enhanced en route platforms.”
(JAMA Surgery. Published online September 30, 2015. doi:10.1001/jamasurg.2015.3111. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: No conflict of interest disclosures were reported. Please see the article for additional information, including financial disclosures, funding and support, etc.
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A cognitive behavior therapy intervention that targeted both depression and heart failure self-care was effective for depression but not for heart failure self-care or physical functioning compared to enhanced usual care, according to an article published online by JAMA Internal Medicine.
Major depression is a common co-existing illness in heart failure (HF). Depression and inadequate self-care are common and interrelated problems that increase the risks of hospitalization and death in patients with HF. Self-care in HF includes behaviors that maintain physical functioning and prevent acute exacerbations, such as following a low-sodium diet, exercising and taking prescribed medications, according to background information in the article
Kenneth E. Freedland, Ph.D., of the Washington University School of Medicine, St. Louis, and colleagues randomly assigned 158 outpatients with heart failure and major depression to cognitive behavior therapy (CBT) delivered by experienced therapists plus usual care (UC; n = 79) or UC alone (n = 79). Usual care was enhanced in both groups with a structured HF education program delivered by a cardiac nurse. The intervention treatment followed standard CBT manuals and a supplemental manual on CBT for cardiac patients. The intensive phase of the intervention consisted of up to 6 months of weekly 1-hour sessions. Sessions tapered to biweekly and then monthly between the end of intensive (weekly) treatment and 6 months post-randomization.
One hundred thirty-two (84 percent) of the participants completed the 6-month posttreatment assessments; 60 (76 percent) of the UC and 58 (73 percent) of the CBT participants completed every follow-up assessment. Six-month depression scores were lower in the CBT than the UC group. CBT did not improve HF self-care or physical functioning, but it did improve anxiety, fatigue, social functioning, and quality of life, and additional analysis suggested that the intervention might help to decrease the hospitalization rate in clinically depressed patients.
The authors note that major depression in heart failure may respond to CBT even if antidepressant therapy is unsuccessful.
“The results suggest that CBT is superior to usual care for depression in patients with HF,” the researchers write. “Further research is needed on interventions to improve depression, self-care, physical functioning, and quality of life in patients with HF and comorbid major depression.
(JAMA Intern Med. Published online September 28, 2015. doi:10.1001/jamainternmed.2015.5220. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: This study was conducted with support from the National Heart, Lung, and Blood Institute. No conflict of interest disclosures were reported.
Editor’s Note: Reframing Depression Treatment in Heart Failure
Patrick G. O’Malley, M.D., M.P.H., Deputy Editor, JAMA Internal Medicine, writes that the good news is that the CBT in this study “did significantly improve emotional health and overall quality of life, and the improvement in depressive symptoms associated with CBT was larger than observed in pharmacotherapy trials for depression in patients with heart disease.”
“This is supportive evidence for a shift in practice away from so much pharmacotherapy and more use of psychotherapy to achieve better mental health and overall quality-of-life outcomes in patients with heart failure. In reframing how we think about the management of depression in patients with heart failure, we should be talking more and prescribing less.”
Editor’s Note: No conflict of interest disclosures were reported.
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While autoimmune cerebellar ataxia (a loss of muscle coordination) can lead to severe disability with some patients becoming wheelchair-bound, there are factors that may help to predict better immunotherapy response and neurological outcomes, according to an article published online by JAMA Neurology.
Autoimmune cerebellar ataxia in adults, which usually comes on rapidly and progresses quickly, can be divided into disorders that are paraneoplastic (triggered by cancer in the body) or nonparaneoplastic (non-cancer-related autoimmune disorders of the central nervous system). The disabling neurological effects can include speech that is not clearly articulated, gait and balance disorders, and loss of muscle control in the limbs. Little has been published regarding treatment responses and neurologic outcomes among patients with autoimmune cerebellar ataxia. However, at least 17 autoantibodies have been reported as causally linked to autoimmune cerebellar ataxia.
Andrew McKeon, M.D., of the Mayo Clinic, Rochester, Minn., and coauthors reviewed medical records at the Mayo Clinic to examine treatment responses and outcomes in 118 adults with autoimmune cerebellar ataxia who were seropositive for at least one neural autoantibody, had received at least one immunotherapy or cancer therapy, and had neurologist-reported outcomes from 1989 through 2013.
Results indicate the median (midpoint) age at onset of neurologic symptoms was 58, nearly three-quarters of the patients were women, and the median duration from symptom onset to last follow-up was 25 months. Among the patients, 63 had paraneoplastic ataxic disorders and 55 patients had nonparaneoplastic ataxic disorders. Also, 81 patients were seropositive for NNC [neuronal nuclear and/or cytoplasmic] antibodies; 22 patients for neural PMP [plasma membrane protein] receptor or ion channel antibodies; and 15 patients for antibodies from both categories.
Overall, 54 patients (45.8 percent) had physician-reported neurologic improvement with immunotherapy (n=51) or cancer therapy (n=3), according to the study results. Analyses suggest factors that may predict better immunotherapy response and neurologic outcomes include a nonparaneoplastic disorder, the detection of at least one or more PMP antibodies or the detection of GAD 65 [glutamic acid decarboxylase 65-kDa isoform] antibodies.
Regardless of the response to immunotherapy, the final ambulatory outcomes regarding the use of gait aids to get around were 56 patients used a wheelchair, 26 patients had walkers and seven patients used canes. Among the remaining 29 patients, 25 of them required no gait aid but had an abnormal gait and four patients had normal gait, the study reports.
“Although autoimmune ataxia is usually severe, treatment responses can be gratifying, particularly in patients with nonparaneoplastic disorders and in those harboring autoantibodies directed against GAD65 or neural PMPs,” the study concludes.
(JAMA Neurol. Published online September 28, 2015. doi:10.1001/jamaneurol.2015.2378. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: An author made a conflict of interest disclosure. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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Use of a decision aid helped primary care clinicians and patients with moderate to severe depression select antidepressants together but had no discernible effect on depression control and medication use and adherence, according to an article published online by JAMA Internal Medicine.
Depression is a common, debilitating, and costly chronic mental illness affecting an estimated 17 percent of Americans. Pharmacotherapy is a primary treatment, but the efficacy of antidepressants is reduced by low patient adherence rates and premature discontinuation. Annie LeBlanc, Ph.D., of the Mayo Clinic, Rochester, Minn., and colleagues studied the effect of the Depression Medication Choice (DMC) encounter decision aid on quality of the decision-making process and depression outcomes. This aid was designed to help patients and clinicians consider available antidepressants and the extent to which they improved depression and other issues important to patients.
Primary care practices in 10 rural, suburban, and urban primary care practices across Minnesota and Wisconsin were randomly allocated to treatment of depression with or without use of the DMC decision aid, which consisted of a series of cards, each highlighting the effect of the available options on an issue of importance to patients for use during face-to-face consultations.
The study included 117 clinicians and 301 patients with moderate to severe depression considering treatment with an antidepressant. Compared with usual care, use of DMC significantly improved patients’ decisional comfort, knowledge, satisfaction, and involvement. It also improved clinicians’ decisional comfort and satisfaction. There were no differences in encounter duration, medication adherence, or improvement of depression control between groups.
“Further work in this area is necessary. The ideal decision support should include nonpharmacological options. A larger and longer trial to study the effect of the decision aid on adherence to therapy in patients selected because of nonadherence may be more informative. Larger studies are needed to identify subgroups (i.e., socioeconomic status) that may benefit more from using the decision aid. Identifying the amount and type of support needed to effectively embed the use of this decision aid in the routines of primary care practices to support its longitudinal use also remains to be determined,” the authors write.
(JAMA Intern Med. Published online September 28, 2015. doi:10.1001/jamainternmed.2015.5214. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: This study was funded by the Agency for Healthcare and Quality Research under the American Recovery and Reinvestment Act of 2009. No conflict of interest disclosures were reported.
Commentary: The Role of Decision Aids in Depression Care
“While better clinical outcomes are typically the bottom line for most interventions, certain patient-centered outcomes may have an independent intrinsic value,” writes Kurt Kroenke, M.D., of the Regenstrief Institute Inc., Indianapolis, in a commentary.
“For example, 79 percent of the patients in the trial expressed a preference for either being the principal decision maker or sharing medical decisions with their clinician. One wonders how often in a busy clinical setting, when there is a choice among medications to treat a disease, the clinician actually discusses the pros and cons of different options. It may be less important for short-term use of drugs to treat acute conditions. However, for medications prescribed for chronic use, informed patient input may be especially desirable. Decision aids could either be used routinely or targeted toward certain patients based on their decision-making preference, sociodemographic characteristics, and history of medication intolerance or prior treatment failures.”
(JAMA Intern Med. Published online September 28, 2015. doi:10.1001/jamainternmed.2015.5243. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: No conflict of interest disclosures were reported.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), MONDAY, SEPTEMBER 28, 2015
Media Advisory: To contact corresponding author Normand G. Boulé, Ph.D., call Jocelyn Love at 780-492-8804 or email jocelyn.love@ualberta.ca.
To place an electronic embedded link to this study in your story Links will be live at the embargo time: http://archpedi.jamanetwork.com/article.aspx?doi=10.1001/jamapediatrics.2015.2186
JAMA Pediatrics
A review of the medical literature suggests the diabetes medication metformin may be associated with a small increase in height in children and adolescents in randomized clinical trials providing the largest cumulative metformin doses, according to an article published online by JAMA Pediatrics.
There has been increasing off-label use of metformin in children and adolescents, often as part of the management of polycystic ovary syndrome, but also for impaired glucose tolerance, nonalcoholic fatty liver disease and obesity.
Normand G. Boulé, Ph.D., of the University of Alberta, Canada, and coauthors included 10 studies with a total of 562 children and adolescents at baseline; 59 percent were female (n=330); the average age within the studies ranged from nearly 8 to 16; and the average body mass index (BMI) ranged from 18.4 to 41. Participants used metformin from three to 48 months.
Overall, height changes were not significantly different between metformin users and control group participants in the studies, the authors report. However, further analyses stratified according to the cumulative metformin dose (in milligrams per day times the number of days of treatment) showed about a one-centimeter increase in height with metformin use in the five studies providing the largest cumulative metformin doses but not in the five studies providing the lowest doses compared with the control group.
The authors note limitations to their study, which include their inability to obtain height data from many studies, even though this information had been collected for the reporting of BMI.
“While an approximate 1-cm increase in height may appear small, it is likely underestimated given that many studies were of short duration and included older adolescents, potentially after epiphyseal growth plate closure. … Our results also suggest a need for additional longer-term studies in younger participants because preliminary evidence suggests that these individuals may experience greater increases in height compared with a control group,” the study concludes.
(JAMA Pediatr. Published online September 28, 2015. doi:10.1001/jamapediatrics.2015.2186. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see article for additional information, including other authors, author contributions and affiliations, etc.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), MONDAY, SEPTEMBER 28, 2015
Media Advisory: To contact study corresponding author Constance D. Lehman, M.D., Ph.D., call Rebecca Hughes at 206-287-2055 or email hughes.r@ghc.org or call Katie Marquedant at 617-726-0337 or email KMarquedant@partners.org. To contact commentary author Joshua J. Fenton, M.D., M.P.H., call Dorsey Griffith at 916-734-9118 or email dgriffith@ucdavis.edu.
Computer-aided detection (CAD) in screening mammography was not associated with improved diagnostic accuracy in a study that analyzed results from a large Breast Cancer Surveillance Consortium database of digital screening mammograms, according to an article published online by JAMA Internal Medicine.
CAD for mammography is intended to help radiologists identify subtle cancers that might otherwise be missed. The U.S. Food and Drug Administration approved CAD for mammography in 1998 and the Centers for Medicare and Medicaid Services (CMS) increased reimbursement for CAD in 2002. Measuring the true impact of CAD on the accuracy of mammographic interpretation has been challenging.
Constance D. Lehman, M.D., Ph.D., of the Massachusetts General Hospital, Boston, and coauthors measured the performance of digital screening mammography with and without CAD in U.S. community practice. The authors included more than 625,000 mammograms interpreted by 271 radiologists with CAD (n=495,818) or without (n=129,807) from 2003 through 2009 among 323,973 women. Linkages with tumor registries identified 3,159 breast cancers in the 323,973 women within one year of the screening.
The authors analyzed mammography performance based on sensitivity (the ability of a test to correctly identify those who do have the disease), specificity (the ability of a test to correctly identify those who do not have the disease) and cancer detection rates per 1,000 women.
The authors report screening performance with CAD was not associated with improvement based on the metrics they assessed. Sensitivity was 85.3 percent with CAD and 87.3 percent without CAD, while specificity was 91.6 percent with CAD and 91.4 percent without CAD. The authors also found no difference in the overall cancer detection rate (4.1 cancers per 1,000 women screened with and without CAD) or in the invasive cancer detection rate (2.9 vs. 3.0 cancers per 1,000 women screened with CAD or without), according to the results. Although the detection rate for ductal carcinoma in situ (DCIS) was slightly higher in patients whose mammograms were assessed with CAD compared to those without (1.2 vs. 0.9 cancers per 1,000 women), finding more low-grade DCIS may offer no improved outcomes for women in screening programs.
In subset analyses among 107 radiologists who interpreted mammograms both with and without CAD, performance was not improved with CAD and CAD was associated with decreased sensitivity (missing breast cancers).
“In the era of Choosing Wisely and clear commitments to support technology that brings added value to the patient experience, while aggressively reducing waste and containing costs, CAD is a technology that does not seem to warrant added compensation beyond coverage of the mammographic examination. The results of our comprehensive study lend no support for continued reimbursement for CAD as a method to increase mammography performance or improve patient outcomes,” the authors conclude.
(JAMA Intern Med. Published online September 28, 2015. doi:10.1001/jamainternmed.2015.5231. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: An author made a conflict of interest disclosure. Funding/support was also detailed. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
Commentary: Is it Time to Stop Paying for Computer-Aided Mammography
In a related commentary, Joshua J. Fenton, M.D., M.P.H., of the University of California, Davis Health System, Sacramento, writes: “If the CMS [Centers for Medicare and Medicaid Services] were to consider a proposal for new CAD coverage at this time, the current evidence base would not support approval. Thus, we should question whether society should continue to pay for CAD use. … Congress should therefore rescind the Medicare benefit for CAD use. … The lesson of CAD is that broad societal investment in new medical technologies should occur only after large-sample evaluations prove their real-world effectiveness and justify their costs.”
(JAMA Intern Med. Published online September 28, 2015. doi:10.1001/jamainternmed.2015.5319. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures.
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EMBARGOED FOR RELEASE: 11 A.M. (ET), THURSDAY, SEPTEMBER 24, 2015
Media Advisory: To contact corresponding author Angel Arnaout, M.D., M.Sc. call Lois Ross at 613-737-8899 x73687 or email loross@ohri.ca. To contact corresponding editorial Constance D. Lehman, M.D., Ph.D., call Katie Marquedant at 617-726-0337 or email kmarquedant@mgh.harvard.edu.
The use of preoperative breast magnetic resonance imaging (MRI) increased eight-fold over a 10-year period among women newly diagnosed with breast cancer in Ontario, Canada, according to an article published online by JAMA Oncology.
Current guidelines recommend bilateral mammography as the primary imaging technique and, if necessary, preoperative ultrasonography. There has been growing use of preoperative breast MRI because of the potential that it might find hidden disease not seen with traditional breast imaging. However, breast MRI can lead to higher false-positive rates and it is expensive. Previous studies also suggest preoperative MRI fails to improve surgical outcomes, breast cancer recurrence rates or survival, according to study background information.
Angel Arnaout, M.D., M.Sc., of The Ottawa Hospital and the University of Ottawa, Ontario, Canada, and coauthors evaluated patterns of preoperative MRI use in new diagnosed breast cancer and the factors associated with it. The authors used administrative healthcare databases in Ontario over 14 geographic regions. Study participants included 53,015 women with primary operable breast cancer treated from 2003 to 2012.
The authors report that 14.8 percent of women (7,824 of 53,015) had preoperative MRI; most patients (65 percent) underwent breast-conserving surgery. The use of preoperative MRI increased eight-fold across all stages during the 10-year period, from 3 percent of patients newly diagnosed with breast cancer in 2003 to 24 percent of patients in 2012.
Patient-related factors associated with higher preoperative MRI use were younger age, higher socioeconomic status and higher comorbidity score. Health system and clinician factors related to increased preoperative MRI included surgery in a teaching hospital and fewer years of surgeon experience, according to the results.
Analyses suggest that preoperative breast MRI was associated with a higher likelihood of postdiagnosis breast imaging, breast biopsies and imaging to look for distant metastatic disease, as well as mastectomy, contralateral prophylactic mastectomy (when a healthy breast is also removed) and more than a 30-day wait for surgery
The authors suggest influences that may have contributed to the growth of preoperative MRI are increased availability of MRI scanners, rising patient demand and institutional pressure to use expensive capital equipment.
Even with a single-payer universal health insurance system, geographic variability existed in preoperative MRI use, according to the study.
Study limitations include the use of claims-based registry data, which do not include clinical indications for the preoperative MRI or any of the procedure outcomes. Administrative billing data also do not provide details on whether actual treatment decisions were changed based on test results.
“Irrespective of the reasons for increased pMRI [preoperative MRI] use, in an era of ever-increasing focus on cost containment in health care, consideration must also be given to the unintended consequences of those who undergo pMRI. The increased sensitivity of breast MRI is achieved at the cost of lower specificity; in practice, this translates into more confirmatory imaging and biopsies needed to rule out a diagnosis of cancer,” the authors write.
The authors conclude: “Preoperative breast MRI use has increased substantially in routine clinical practice and is associated with a significant increase in ancillary investigations, wait time to surgery, mastectomies and contralateral prophylactic mastectomies.”
(JAMA Oncol. Published online September 24, 2015. doi:10.1001/jamaoncol.2015.3018. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Financial support for this project has been obtained from the 2013 University of Ottawa, Department of Medicine, Patient Safety Grant. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Rethinking Preoperative Breast MRI
In a related editorial, Habib Rahbar, M.D., University of Washington, Seattle, and Constance D. Lehman, M.D., Ph.D., Massachusetts General Hospital, Boston, write: “This study adds to the growing body of evidence that the use of MRI in the preoperative setting is associated with more aggressive surgery of the affected breast. … It may be that advanced imaging, such as MRI, is unlikely to lead to better outcomes in the context of treatment paradigms developed in settings of conventional imaging. High-quality diagnostic mammography supported the transition from mastectomy to breast-conserving surgery and radiation for patients with unifocal disease. Similarly, MRI may support the next advance in treatment options that are more targeted to the individual patient’s disease burden. Because MRI can detect occult disease with high sensitivity, future research might explore its role in novel treatment approaches, such as whether it can identify patients for whom multiple lumpectomies for multicentric disease (in lieu of mastectomy) or for whom lumpectomy without radiation for unifocal low-risk disease are appropriate. It is this role in precision diagnostics and risk-stratification that advanced imaging techniques may hold the greatest promise, and for which MRI should be studied in future prospective trials.”
(JAMA Oncol. Published online September 24, 2015. doi:10.1001/jamaoncol.2015.3029. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: An author made a conflict of interest disclosure. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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In a nationally representative sample of adults 70 years or older, moderate or more severe hearing impairment was associated with an increased risk of death, with greater impairment increasing the risk, compared to older adults without hearing impairment, according to a study published online by JAMA Otolaryngology-Head & Neck Surgery.
Hearing impairment (HI) is common in older adults; its prevalence doubles with every decade of life, affecting two-thirds of adults older than 70 years, and has been shown to be associated with various negative health outcomes. Using combined data from the January 2005 to December 2006 and January 2009 to December 2010 cycles of the National Health and Nutrition Examination Survey (NHANES), Kevin J. Contrera, M.P.H., of the Johns Hopkins University School of Medicine, Baltimore, and colleagues studied 1,666 adults 70 years or older who had undergone audiometric testing. Severity of HI was defined per World Health Organization criteria.
Compared with individuals without HI (n = 527), individuals with HI (n = 1,139) were more likely to be older, male, white, former smokers, less educated, and have a history of cardiovascular disease and stroke. In an age-adjusted model, moderate or more severe HI was associated with a 54 percent increased risk of death, and mild HI with a 27 percent increased risk of death, compared with individuals without HI. After further adjustment for demographic characteristics and cardiovascular risk factors, the results suggested that HI may be associated with a 39 percent and 21 percent increased risk of death in individuals with moderate or more severe HI and mild HI, respectively, compared with individuals without HI.
Analysis restricted to individuals 80 years or younger yielded results also suggestive of a positive association between HI and mortality.
The authors write that potential mechanisms for these findings include causal connections of HI with cognitive, mental, and physical function.
“Future studies are required to explore the basis of the association of HI with mortality and to determine whether therapies to rehabilitate hearing can reduce mortality.”
(JAMA Otolaryngol Head Neck Surg. Published online September 24, 2015. doi:10.1001/.jamaoto.2015.1762. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 22, 2015
Media Advisory: To contact Jeffrey L. Cummings, M.D., Sc.D., email Janice Guhl at Guhlj@ccf.org. To contact editorial co-author Anne Corbett, Ph.D., email anne.corbett@kcl.ac.uk.
In a preliminary 10-week randomized trial, patients with probable Alzheimer disease who received the combination medication dextromethorphan-quinidine demonstrated less occurrences and severity of agitation, compared to patients who received placebo, according to a study in the September 22/29 issue of JAMA.
Agitation and aggression are highly prevalent in patients with dementia and are associated with distress for patients and caregivers, greater risk of institutionalization, and accelerated progression to severe dementia and death. Nonpharmacological interventions are recommended as first-line therapy, but many patients fail to respond. Although many classes of psychotropic drugs are prescribed for agitation, safety concerns and modest or unproven efficacy limit their use, according to background information in the article.
The combination of the drugs dextromethorphan hydrobromide and quinidine sulfate is approved for the treatment of pseudobulbar affect (a neurologic disorder characterized by episodes of emotional displays such as crying), and there is evidence suggesting a potential benefit of these drugs for agitation. Jeffrey L. Cummings, M.D., Sc.D., of the Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues randomly assigned 220 patients to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127) in stage 1. In stage 2, patients receiving dextromethorphan-quinidine continued; those receiving placebo were stratified by response and re-randomized to dextromethorphan-quinidine (n = 59) or placebo (n = 60). The 10 week trial was conducted at 42 study sites.
A total of 194 patients (88 percent) completed the study. Analysis combining stages 1 (all patients) and 2 (re-randomized placebo nonresponders) showed significantly reduced measures of agitation (occurrence and severity of symptoms). Patients treated with only dextromethorphan-quinidine had an average 51 percent reduction in the measure of agitation from baseline to week 10, compared with 26 percent for those treated with only placebo.
Adverse events included falls (8.6 percent for dextromethorphan-quinidine vs 3.9 percent for placebo), diarrhea (5.9 percent vs 3.1 percent, respectively), and urinary tract infection (5.3 percent vs 3.9 percent, respectively). Serious adverse events occurred in 7.9 percent with dextromethorphan-quinidine vs 4.7 percent with placebo. Dextromethorphan-quinidine was not associated with cognitive impairment or sedation.
“These preliminary findings require confirmation in additional clinical trials with longer treatment duration,” the authors write.
Editor’s Note: This study was funded by Avanir Pharmaceuticals Inc. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.
Editorial: Dextromethorphan and Quinidine for Treating Agitation in Patients With Alzheimer Disease Dementia
Pending further evidence, there is a reasonably strong case to prioritize dextromethorphan-quinidine as an off-label treatment for agitation, possibly as a safer alternative to atypical antipsychotics, writes Anne Corbett, Ph.D., of King’s College London, and colleagues in an accompanying editorial.
“However, while further studies are conducted to verify the efficacy and safety of this approach, it will be important to achieve a robust international expert consensus regarding the prioritization of potential treatments for agitation in patients with dementia to improve the consistency of clinical practice. This approach also must understand and incorporate patient and caregiver views regarding the evaluation of risk and benefits in relation to these treatments.”
Most veterans undergoing general surgical operations of low complexity preferred telehealth (video or telephone) follow-up than visiting a clinic, and data suggested that telehealth visits may help identify veterans requiring in-person assessment or further care, according to a study published online by JAMA Surgery.
There is increasing interest in telehealth as a means to improve access to care and decrease costs associated with patients traveling for traditional face-to-face encounters. This is especially important in the Veterans Health Administration patient population. Michael A. Vella, M.D., of the Veterans Affairs Medical Center and Vanderbilt University, Nashville, and colleagues conducted a study to measure the quality of telehealth visits and the preferences for post-operative general surgical care among veterans with regard to telephone, video, and in-person postoperative visits.
From May to July 2014, the researchers selected a sample of veterans undergoing operations of low complexity amenable to postoperative telehealth evaluation. Each eligible veteran was evaluated at 3 sequential visits: telephone, in-person, and video that addressed 4 domains (general recovery, follow-up needs, wound care needs, and complications). After completing all 3 types of visits, veterans were asked about their preferences regarding them.
Thirty-five veterans agreed to participate, and 23 veterans completed all 3 types of visits. There was 100 percent agreement across all 3 types of visits in the domains of general recovery and follow-up needs. Percentage of agreement for wound needs and complications was 96 percent, reflecting a possible infection reported during a telephone call that was not present during the in-person clinic or video visit. One veteran had a wound infection that was detected during telephone and video visits and confirmed during the in-person visit. There were no instances in which a wound or postoperative complication was not detected by telephone or video.
The majority of veterans (69 percent) preferred a telehealth visit (39 percent preferred the telephone, and 30 percent preferred video). Veterans who preferred telehealth visits traveled farther than those who preferred in-person visits (162 vs 75 miles).
“The data suggest that telehealth visits, either by telephone or video, can identify veterans requiring in-person assessment or further care. A telehealth follow-up program with further evaluation of patient outcomes is being trialed at our facility. This has implications for waitlist management, costs, and access to care for veterans and the Veterans Affairs health care system,” the authors write.
(JAMA Surgery. Published online September 23, 2015. doi:10.1001/jamasurg.2015.2660. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 22, 2015
Media Advisory: To contact Clara K. Chow, M.B.B.S., Ph.D., email cchow@georgeinstitute.org.au. To contact editorial co-author Zubin J. Eapen, M.D., M.H.S., call Sarah Avery at 919-660-1306 or email sarah.avery@duke.edu.
A simple, low-cost automated program of semi-personalized mobile phone text messages supporting lifestyle change led to improvement in low-density lipoprotein cholesterol (LDL-C) levels, blood pressure, body mass index, and smoking status in patients with coronary heart disease, according to a study in the September 22/29 issue of JAMA.
Globally, cardiovascular disease is the leading cause of death and disease burden. Cardiovascular disease prevention, including lifestyle modification, is important but underutilized. Mobile phone text messages to remind, encourage, and motivate patients regarding the adoption of healthy lifestyles might be useful, but there has been limited scientific evaluation of these interventions, according to background information in the article.
Clara K. Chow, M.B.B.S., Ph.D., of the George Institute for Global Health, University of Sydney, Australia, and colleagues randomly assigned patients with proven coronary heart disease to receive 4 text messages per week for 6 months in addition to usual care (intervention group; n = 352) or usual care (control group; n=358). Text messages provided advice, motivational reminders, and support to change lifestyle behaviors. Messages for each participant were selected from a bank of messages according to baseline characteristics (e.g., smoking) and delivered via an automated computerized message management system. The average age of the patients was 58 years; 53 percent were current smokers.
At six months, levels of LDL-C were lower in intervention participants (79 mg/dL vs 84 mg/dL), as was systolic blood pressure (128 mm Hg vs 136 mm Hg) and body mass index. After six months, there was also a lower percentage (26 percent vs 43 percent) of smokers in the intervention group, who also reported an increase in physical activity. The proportion of patients achieving 3 of 5 guideline target levels of risk factors were substantially higher in the intervention group vs the control group (63 percent vs. 34 percent).
The majority of participants reported the text messages to be useful (91 percent), easy to understand (97 percent), and appropriate in frequency (86 percent).
“The duration of these effects and hence whether they result in improved clinical outcomes remain to be determined,” the authors conclude.
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Can Mobile Health Applications Facilitate Meaningful Behavior Change?
Zubin J. Eapen, M.D., M.H.S., and Eric D. Peterson, M.D., M.P.H., of the Duke Clinical Research Institute, Durham, N.C., (Dr. Peterson is also Associate Editor, JAMA) comment in an accompanying editorial.
“Health care needs to be challenged to make its evaluation as nimble as that of technology. The U.S. health care system needs to be capable of testing novel low-risk interventions such as text messaging in the context of routine clinical care. Creating an agile and clinically integrated research framework that rigorously evaluates all interventions—drug, device, or digital—is a collective responsibility and challenge for both app developers and health care practitioners. Solving this dilemma can enable the development and use of pragmatic, scalable, and evidence-based solutions that can address a massive problem like cardiovascular disease.”
EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 22, 2015
Media Advisory: To contact Thomas S. Valley, M.D., email Kara Gavin at kegavin@med.umich.edu. To contact Jeremy M. Kahn, M.D., M.S., call Allison Hydzik at 412-647-9975 or email hydzikam@upmc.edu.
Among Medicare beneficiaries hospitalized with pneumonia, intensive care unit (ICU) admission of patients which appeared to be discretionary was associated with improved survival and no significant differences in Medicare spending or hospital costs, compared with patients admitted to general wards, according to a study in the September 22/29 issue of JAMA.
Observational studies examining the relationship between ICU admission frequency and patient outcomes often suggest that greater ICU use does not achieve better outcomes. However, these results are likely influenced by factors such as indication, because sicker patients are more likely to be admitted to the ICU. Among patients whose need for intensive care is uncertain, the relationship of ICU admission with mortality and costs has been unknown, according to background information in the article.
Thomas S. Valley, M.D., of the University of Michigan, Ann Arbor, and colleagues examined the association between ICU admission and outcomes, 30-day mortality and costs, among elderly patients hospitalized for pneumonia. The study included Medicare beneficiaries (older than 64 years of age) admitted to 2,988 acute care hospitals in the United States with pneumonia from 2010 to 2012.
Among 1,112,394 Medicare beneficiaries with pneumonia, 328,404 (30 percent) were admitted to the ICU. Patients (n = 553,597) living closer than the median differential distance (less than 3.3 miles) to a hospital with high ICU admission were significantly more likely to be admitted to the ICU than patients living farther away (n = 558,797) (36 percent for patients living closer vs 23 percent for patients living farther).
For the 13 percent of patients whose ICU admission decision appeared to be discretionary (dependent only on distance), ICU admission was associated with a significantly lower adjusted 30-day mortality (14.8 percent for ICU admission vs 20.5 percent for general ward admission), yet there were no significant differences in Medicare spending or hospital costs for the hospitalization.
The authors write that contrary to the study’s prespecified hypothesis, “these findings suggest that ICU admission for borderline patients (those for whom ICU admission depends on the hospital to which they present) is associated with reduced mortality without a considerable increase in costs.”
“A randomized trial may be warranted to assess whether more liberal ICU admission policies improve mortality for patients with pneumonia.”
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Assessing the Value of Intensive Care
The findings of this study “argue against active efforts to reduce ICU admissions through triage guidelines or bed supply reductions, at least for older patients with pneumonia,” write Ian J. Barbash, M.D., and Jeremy M. Kahn, M.D., M.S., of the University of Pittsburgh School of Medicine, in an accompanying editorial.
“In the current health care system, more judicious use of the ICU may well lead to higher mortality in some patient populations. Indeed, the greatest lesson from this study may be that low-value health care is difficult to find. Reducing health care spending by preventing ICU readmissions will require addressing the difficult questions about rationing ICU care and the degree to which the nation can afford to make intensive care available to anyone at any time. While this conversation is underway, the task at hand is to study why the intensive care saves lives, and then use this information to make hospital care as safe and effective for all patients, regardless of where in the hospital they receive care.”
EMBARGOED FOR RELEASE: 11 A.M. (ET) TUESDAY, SEPTEMBER 22, 2015
Media Advisory: To contact Timothy J. Fendler, M.D., M.S., call Laurel Gifford at 816-502-8532 or email lgifford@saint-lukes.org. To contact editorial co-author Derek C. Angus, M.D., M.P.H., call Allison Hydzik at 412-647-9975 or email hydzikam@upmc.edu.
Although do-not-resuscitate (DNR) orders after in-hospital cardiac arrest were generally aligned with patients’ likelihood of favorable neurological survival, almost two-thirds of patients with the worst prognosis did not have DNR orders, according to a study in the September 22/29 issue of JAMA.
Do-not-resuscitate orders are often established for patients whose prognosis is poor. One such example is in-hospital cardiac arrest, which affects nearly 200,000 patients in the United States annually, with rates of favorable neurological survival (i.e., survival without severe cognitive disability) of less than 20 percent. Accordingly, this poor prognosis frequently prompts discussions about DNR status among resuscitated patients and their families. It is not known if real-world decisions for DNR orders after successful resuscitation from in-hospital cardiac arrest are aligned with patients’ likelihood of favorable neurological survival, according to background information in the article.
From a registry (Get With The Guidelines-Resuscitation), Timothy J. Fendler, M.D., M.S., of Saint Luke’s Mid America Heart Institute, Kansas City, and colleagues identified 26,327 patients with return of spontaneous circulation (ROSC) after in-hospital cardiac arrest between April 2006 and September 2012 at 406 U.S. hospitals. Using a previously validated prognostic tool, each patient’s likelihood of favorable neurological survival (i.e., without severe neurological disability) was calculated. The proportion of patients with DNR orders within each prognosis score group and the association between DNR status and actual favorable neurological survival were examined.
Overall, 5,944 (23 percent) patients had DNR orders within 12 hours of ROSC. Among patients with the best prognosis, 7 percent had DNR orders even though their predicted rate of favorable neurological survival was 65 percent. Among patients with the worst expected prognosis, 36 percent had DNR orders even though their predicted rate for favorable neurological survival was 4 percent. The actual rate of favorable neurological survival was higher for patients without DNR orders (31 percent) than it was for those with DNR orders (2 percent).
“In this national registry of in-hospital cardiac arrest, we found that DNR orders after successful resuscitation were generally aligned with patients’ likelihood for favorable neurological survival, with increasing rates of DNR orders as a patient’s likelihood to survive without neurological disability decreased. Nevertheless, almost two-thirds of patients with the worst prognosis did not have DNR orders, even though only 4.0 percent of patients within this [group] had favorable neurological survival. Moreover, patients who had DNR orders despite a good prognosis had significantly lower survival and less resource use than patients without DNR orders who had a similar prognosis after ROSC,” the authors write
“Among patients with a low likelihood of favorable neurological survival after in-hospital cardiac arrest, our findings highlight the potential to improve DNR decision making.”
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Editorial: Successful Resuscitation From In-Hospital Cardiac Arrest – What Happens Next?
“In summary, when a cardiac arrest occurs in hospital, health care teams are good at rushing in to provide robust resuscitative efforts,” writes Derek C. Angus, M.D., M.P.H., of the University of Pittsburgh, and Associate Editor, JAMA, in an accompanying editorial.
“However, after successful ROSC, just as after the initial response to any disaster, it is clear the work has only just begun. Hopefully in the future, standardized delivery of high-quality evidence-based resuscitation guidelines for cardiac arrest will be followed by equally high-quality standard approaches to ensure patients and families are supported optimally, regardless of prognosis.”
EMBARGOED FOR RELEASE: 11 A.M (ET), MONDAY, SEPTEMBER 21, 2015
Media Advisory: To contact corresponding author J. David Spence, M.D., call Tristan Michelle Joseph at 519-661-2111 x80387 or email tristan.joseph@schulich.uwo.ca. To contact corresponding editorial author Ralph L. Sacco, M.D., call Lisa Worley at 305-243-5184 or email lworley2@med.miami.edu.
Preventing carotid artery occlusion (blockage) may not be a valid indication for stenting because the risk of progression to occlusion appears to be below the risk of carotid stenting or endarterectomy (surgical removal of plaque from an artery), according to an article published online by JAMA Neurology.
Increasing evidence indicates that with intensive medical therapy most patients with asymptomatic carotid stenosis (ACS) are more likely to be harmed than to benefit from carotid endarterectomy or carotid stenting. Many of these procedures are performed with the objective to prevent carotid occlusion because the underlying assumption is that carotid occlusion would carry a high risk of stroke.
J. David Spence, M.D., of Western University, Ontario, Canada, and coauthors looked at the risk resulting from progression to occlusion among patients with ACS. They assessed the role of severity of carotid stenosis or the presence of contralateral (on the opposite side of the body) occlusion as factors that may predict the risk of stroke or death after occlusion of a previously asymptomatic carotid stenosis.
The authors analyzed data collected from patients at stroke prevention clinics from 1990 through 1995 or from 1995 through 2012. The authors measured ipsilateral stroke (on the same side of the body as the carotid artery blockage), transient ischemic attack, death from ipsilateral stroke or death from unknown cause.
The study reports that among 3,681 patients, 316 patients were asymptomatic before the initial occlusion. The average age of patients was 66, most patients were men and most had high blood pressure and hyperlipidemia. Most new occlusions (254 of 316) occurred before 2002, when medical therapy was less intensive.
Only one patient (0.3 percent) had a stroke at the time of the occlusion and only three patients (0.9 percent) had an ipsilateral stroke during follow-up. Analyses suggest that neither severity of stenosis nor contralateral occlusion predicted the risk of ipsilateral stroke or transient ischemic attack, death from stroke or death from unknown cause.
“Patients with carotid stenosis are at high risk of death, but as indicated in Table 2, most of the deaths are not from stroke. Carotid stenting or endarterectomy can therefore not be expected to improve those outcomes,” the study notes.
Study limitations include that authors did not perform brain imaging unless patients had a stroke and they did not study patients who became symptomatic and had interventions for that reason.
“The risk of ipsilateral stroke at the time of carotid occlusion was well below the risk of carotid stenting or carotid endarterectomy, and the percent stenosis or contralateral occlusion did not identify patients who would benefit from intervention. Preventing carotid occlusion may not be a valid indication for intervention,” the study concludes.
(JAMA Neurol. Published online September 21, 2015. doi:10.1001/jamaneurol.2015.1843. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: An author made a funding/support disclosure. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Are Current Risks of Asymptomatic Carotid Stenosis Exaggerated?
In a related editorial, Seemant Chaturvedi, M.D., and Ralph L. Sacco, M.D., M.S., of the University of Miami Miller School of Medicine, write: “In this issue of JAMA Neurology, Yang et al add some ‘fuel to the fire’ regarding the debate concerning the best treatment for asymptomatic carotid stenosis. … As a single-center study, the analysis by Yang et al has limitations. … All these limitations could have led to underestimations in the risk of stroke. … Ultimately, whether the improvements in aggressive medical therapy are sufficient to reduce the rationale for CEA (carotid endarterectomy) or CAS (carotid artery stenting) in asymptomatic patients will need to be determined by contemporary randomized clinical trials.”
(JAMA Neurol. Published online September 21, 2015. doi:10.1001/jamaneurol.2015.2196. Available pre-embargo to the media at https://media.jamanetwork.com.)
Editor’s Note: Authors made conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
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