The 50 most-cited articles in Annals of Internal Medicine, 2016

DESCRIPTION: Update of the 2009 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for breast cancer. METHODS: The USPSTF reviewed the evidence on the following: effectiveness of breast cancer screening in reducing breast cancer-specific and all-cause mortality, as well as the incidence of advanced breast cancer and treatment-related morbidity; harms of breast cancer screening; test performance characteristics of digital breast tomosynthesis as a primary screening strategy; and adjunctive screening in women with increased breast density. In addition, the USPSTF reviewed comparative decision models on optimal starting and stopping ages and intervals for screening mammography; how breast density, breast cancer risk, and comorbidity level affect the balance of benefit and harms of screening mammography; and the number of radiation-induced breast cancer cases and deaths associated with different screening mammography strategies over the course of a woman's lifetime. POPULATION: This recommendation applies to asymptomatic women aged 40 years or older who do not have…

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of chronic insomnia disorder in adults. METHODS: This guideline is based on a systematic review of randomized, controlled trials published in English from 2004 through September 2015. Evaluated outcomes included global outcomes assessed by questionnaires, patient-reported sleep outcomes, and harms. The target audience for this guideline includes all clinicians, and the target patient population includes adults with chronic insomnia disorder. This guideline grades the evidence and recommendations by using the ACP grading system, which is based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RECOMMENDATION 1: ACP recommends that all adult patients receive cognitive behavioral therapy for insomnia (CBT-I) as the initial treatment for chronic insomnia disorder. (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 2: ACP recommends that clinicians use a shared…

BACKGROUND: Little is known about how physician time is allocated in ambulatory care. OBJECTIVE: To describe how physician time is spent in ambulatory practice. DESIGN: Quantitative direct observational time and motion study (during office hours) and self-reported diary (after hours). SETTING: U.S. ambulatory care in 4 specialties in 4 states (Illinois, New Hampshire, Virginia, and Washington). PARTICIPANTS: 57 U.S. physicians in family medicine, internal medicine, cardiology, and orthopedics who were observed for 430 hours, 21 of whom also completed after-hours diaries. MEASUREMENTS: Proportions of time spent on 4 activities (direct clinical face time, electronic health record [EHR] and desk work, administrative tasks, and other tasks) and self-reported after-hours work. RESULTS: During the office day, physicians spent 27.0% of their total time on direct clinical face time with patients and 49.2% of their time on EHR and desk work. While in the examination room with patients, physicians spent 52.9% of the time on direct clinical face time and 37.0% on EHR and desk work. The 21…

BACKGROUND: The metabolic defects of nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes mellitus (T2DM) seem to be specifically targeted by pioglitazone. However, information about its long-term use in this population is limited. OBJECTIVE: To determine the efficacy and safety of long-term pioglitazone treatment in patients with NASH and prediabetes or T2DM. DESIGN: Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT00994682). SETTING: University hospital. PARTICIPANTS: Patients (n = 101) with prediabetes or T2DM and biopsy-proven NASH were recruited from the general population and outpatient clinics. INTERVENTION: All patients were prescribed a hypocaloric diet (500-kcal/d deficit from weight-maintaining caloric intake) and then randomly assigned to pioglitazone, 45 mg/d, or placebo for 18 months, followed by an 18-month open-label phase with pioglitazone treatment. MEASUREMENTS: The primary outcome was a reduction of at least 2 points in the nonalcoholic fatty liver disease activity score in 2 histologic categories without worsening of…

DESCRIPTION: Update of the 2009 USPSTF recommendation on aspirin use to prevent cardiovascular disease (CVD) events and the 2007 recommendation on aspirin and nonsteroidal anti-inflammatory drug use to prevent colorectal cancer (CRC). METHODS: The USPSTF reviewed 5 additional studies of aspirin for the primary prevention of CVD and several additional analyses of CRC follow-up data. The USPSTF also relied on commissioned systematic reviews of all-cause mortality and total cancer incidence and mortality and a comprehensive review of harms. The USPSTF then used a microsimulation model to systematically estimate the balance of benefits and harms. POPULATION: This recommendation applies to adults aged 40 years or older without known CVD and without increased bleeding risk. RECOMMENDATIONS: The USPSTF recommends initiating low-dose aspirin use for the primary prevention of CVD and CRC in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily…

BACKGROUND: Clinicians and patients need updated evidence on the comparative effectiveness and safety of diabetes medications to make informed treatment choices. PURPOSE: To evaluate the comparative effectiveness and safety of monotherapy (thiazolidinediones, metformin, sulfonylureas, dipeptidyl peptidase-4 [DPP-4] inhibitors, sodium-glucose cotransporter 2 [SGLT-2] inhibitors, and glucagon-like peptide-1 [GLP-1] receptor agonists) and selected metformin-based combinations in adults with type 2 diabetes. DATA SOURCES: English-language studies from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, indexed from inception through March 2015 (MEDLINE search updated through December 2015). STUDY SELECTION: Paired reviewers independently identified 179 trials and 25 observational studies of head-to-head monotherapy or metformin-based combinations. DATA EXTRACTION: Two reviewers independently assessed study quality and serially extracted data and graded the strength of evidence. DATA SYNTHESIS: Cardiovascular mortality was lower for metformin versus sulfonylureas;…

DESCRIPTION: The American Diabetes Association (ADA) published the 2016 Standards of Medical Care in Diabetes (Standards) to provide clinicians, patients, researchers, payers, and other interested parties with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care. METHODS: The ADA Professional Practice Committee performed a systematic search on MEDLINE to revise or clarify recommendations based on new evidence. The committee assigns the recommendations a rating of A, B, or C, depending on the quality of evidence. The E rating for expert opinion is assigned to recommendations based on expert consensus or clinical experience. The Standards were reviewed and approved by the Executive Committee of the ADA Board of Directors, which includes health care professionals, scientists, and laypersons. Feedback from the larger clinical community was incorporated into the 2016 revision. RECOMMENDATIONS: The synopsis focuses on 8 key areas that are important to primary care providers. The recommendations highlight individualized care to manage the…

Background: Trends in the prevalence of chronic kidney disease (CKD) are important for health care policy and planning. Objective: To update trends in CKD prevalence. Design: Repeated cross-sectional study. Setting: NHANES (National Health and Nutrition Examination Survey) for 1988 to 1994 and every 2 years from 1999 to 2012. Participants: Adults aged 20 years or older. Measurements: Chronic kidney disease (stages 3 and 4) was defined as an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73 m2, estimated with the Chronic Kidney Disease Epidemiology Collaboration equation from calibrated serum creatinine measurements. An expanded definition of CKD also included persons with an eGFR of at least 60 mL/min/1.73 m2 and a 1-time urine albumin-creatinine ratio of at least 30 mg/g. Results: The unadjusted prevalence of stage 3 and 4 CKD increased from the late 1990s to the early 2000s. Since 2003 to 2004, however, the overall prevalence has largely stabilized (for example, 6.9% prevalence in 2003 to 2004 and in 2011 to 2012). There was little difference in adjusted…

BACKGROUND: To date, evidence for the efficacy of fecal microbiota transplantation (FMT) in recurrent Clostridium difficile infection (CDI) has been limited to case series and open-label clinical trials. OBJECTIVE: To determine the efficacy and safety of FMT for treatment of recurrent CDI. DESIGN: Randomized, controlled, double-blind clinical trial. (ClinicalTrials.gov: NCT01703494). SETTING: Two academic medical centers. PATIENTS: 46 patients who had 3 or more recurrences of CDI and received a full course of vancomycin for their most recent acute episode. INTERVENTION: Fecal microbiota transplantation with donor stool (heterologous) or patient's own stool (autologous) administered by colonoscopy. MEASUREMENTS: The primary end point was resolution of diarrhea without the need for further anti-CDI therapy during the 8-week follow-up. Safety data were compared between treatment groups via review of adverse events (AEs), serious AEs (SAEs), and new medical conditions for 6 months after FMT. Fecal microbiota analyses were performed on patients' stool before and after FMT and also on…

BACKGROUND: In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years. PURPOSE: To review studies of the effectiveness of breast cancer screening in average-risk women. DATA SOURCES: MEDLINE and Cochrane databases to 4 June 2015. STUDY SELECTION: English-language randomized, controlled trials and observational studies of screening with mammography, magnetic resonance imaging, and ultrasonography that reported breast cancer mortality, all-cause mortality, or advanced breast cancer outcomes. DATA EXTRACTION: Investigators extracted and confirmed data and dual rated study quality; discrepancies were resolved through consensus. DATA SYNTHESIS: Fair-quality evidence from a meta-analysis of mammography trials indicated relative risks (RRs) for breast cancer mortality of 0.92 for women aged 39 to 49 years (95% CI, 0.75 to 1.02) (9 trials; 3 deaths prevented per 10,000 women over 10 years); 0.86 for those aged 50 to 59 years (CI, 0.68 to 0.97) (7 trials; 8 deaths prevented…

Electronic practice data are increasingly being used to provide feedback to encourage practice improvement. However, evidence suggests that despite decades of experience, the effects of such interventions vary greatly and are not improving over time. Guidance on providing more effective feedback does exist, but it is distributed across a wide range of disciplines and theoretical perspectives. Through expert interviews; systematic reviews; and experience with providing, evaluating, and receiving practice feedback, 15 suggestions that are believed to be associated with effective feedback interventions have been identified. These suggestions are intended to provide practical guidance to quality improvement professionals, information technology developers, educators, administrators, and practitioners who receive such interventions. Designing interventions with these suggestions in mind should improve their effect, and studying the mechanisms underlying these suggestions will advance a stagnant literature.

BACKGROUND: In 2014, only 26 states and the District of Columbia chose to implement the Patient Protection and Affordable Care Act (ACA) Medicaid expansions for low-income adults. OBJECTIVE: To evaluate whether the state Medicaid expansions were associated with changes in insurance coverage, access to and utilization of health care, and self-reported health. DESIGN: Comparison of outcomes before and after the expansions in states that did and did not expand Medicaid. SETTING: United States. PARTICIPANTS: Citizens aged 19 to 64 years with family incomes below 138% of the federal poverty level in the 2010 to 2014 National Health Interview Surveys. MEASUREMENTS: Health insurance coverage (private, Medicaid, or none); improvements in coverage over the previous year; visits to physicians in general practice and specialists; hospitalizations and emergency department visits; skipped or delayed medical care; usual source of care; diagnoses of diabetes, high cholesterol, and hypertension; self-reported health; and depression. RESULTS: In the second half of 2014, adults in expansion states…

BACKGROUND: In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years. PURPOSE: To review studies of screening in average-risk women with mammography, magnetic resonance imaging, or ultrasonography that reported on false-positive results, overdiagnosis, anxiety, pain, and radiation exposure. DATA SOURCES: MEDLINE and Cochrane databases through December 2014. STUDY SELECTION: English-language systematic reviews, randomized trials, and observational studies of screening. DATA EXTRACTION: Investigators extracted and confirmed data from studies and dual-rated study quality. Discrepancies were resolved through consensus. DATA SYNTHESIS: Based on 2 studies of U.S. data, 10-year cumulative rates of false-positive mammography results and biopsies were higher with annual than biennial screening (61% vs. 42% and 7% vs. 5%, respectively) and for women aged 40 to 49 years, those with dense breasts, and those using combination hormone therapy. Twenty-nine studies using different…

BACKGROUND: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. OBJECTIVE: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers. DESIGN: Prospective observational cohort study. (ClinicalTrials .gov: NCT00518440). SETTING: 31 liver disease and transplant centers in the United States. PATIENTS: Consecutively enrolled patients-without prior advanced liver disease-with ALF (n = 2070). MEASUREMENTS: Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013). RESULTS: Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the…

BACKGROUND: Acute respiratory tract infection (ARTI) is the most common reason for antibiotic prescription in adults. Antibiotics are often inappropriately prescribed for patients with ARTI. This article presents best practices for antibiotic use in healthy adults (those without chronic lung disease or immunocompromising conditions) presenting with ARTI. METHODS: A narrative literature review of evidence about appropriate antibiotic use for ARTI in adults was conducted. The most recent clinical guidelines from professional societies were complemented by meta-analyses, systematic reviews, and randomized clinical trials. To identify evidence-based articles, the Cochrane Library, PubMed, MEDLINE, and EMBASE were searched through September 2015 using the following Medical Subject Headings terms: "acute bronchitis," "respiratory tract infection," "pharyngitis," "rhinosinusitis," and "the common cold." HIGH-VALUE CARE ADVICE 1: Clinicians should not perform testing or initiate antibiotic therapy in patients with bronchitis unless pneumonia is suspected. HIGH-VALUE CARE ADVICE 2:…

Background: Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID). Objective: To evaluate elbasvir-grazoprevir in treating HCV infection in PWID. Design: Randomized, placebo-controlled, double-blind trial. (ClinicalTrials.gov: NCT02105688). Setting: Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States. Patients: 301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80% adherent to visits for opioid agonist therapy (OAT). Intervention: The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks. Measurements: The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events. Results: The SVR12 was 91.5% (95% CI, 86.8% to 95.0%) in the ITG and…

Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of gout. Methods: Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials; systematic reviews; and large observational studies published between January 2010 and March 2016. Clinical outcomes evaluated included pain, joint swelling and tenderness, activities of daily living, patient global assessment, recurrence, intermediate outcomes of serum urate levels, and harms. Target Audience and Patient Population: The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute or recurrent gout. Recommendation 1: ACP recommends that clinicians choose corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or colchicine to treat patients with acute gout. (Grade: strong recommendation, high-quality evidence). Recommendation 2: ACP recommends that clinicians use low-dose colchicine when using…

BACKGROUND: Substance use, a leading cause of illness and death, is underidentified in medical practice. OBJECTIVE: The Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool was developed to address the need for a brief screening and assessment instrument that includes all commonly used substances and fits into clinical workflows. The goal of this study was to assess the performance of the TAPS tool in primary care patients. DESIGN: Multisite study, conducted within the National Drug Abuse Treatment Clinical Trials Network, comparing the TAPS tool with a reference standard measure. (ClinicalTrials.gov: NCT02110693). SETTING: 5 adult primary care clinics. PARTICIPANTS: 2000 adult patients consecutively recruited from clinic waiting areas. MEASUREMENTS: Interviewer- and self-administered versions of the TAPS tool were compared with a reference standard, the modified World Mental Health Composite International Diagnostic Interview (CIDI), which measures problem use and substance use disorder (SUD). RESULTS: Interviewer- and self-administered versions of the…

Greater integration of medication-assisted treatment (MAT) for opioid use disorder (OUD) in U.S. primary care settings would expand access to treatment for this condition. Models for integrating MAT into primary care vary in structure. This article summarizes findings of a technical report for the Agency for Healthcare Research and Quality describing MAT models of care for OUD, based on a literature review and interviews with key informants in the field. The report describes 12 representative models of care for integrating MAT into primary care settings that could be considered for adaptation across diverse health care settings. Common components of existing care models include pharmacotherapy with buprenorphine or naltrexone, provider and community education, coordination and integration of OUD treatment with other medical and psychological needs, and psychosocial services and interventions. Models vary in how each component is implemented. Decisions about adopting MAT models of care should be individualized to address the unique milieu of each implementation setting.

BACKGROUND: The best treatment options for binge-eating disorder are unclear. PURPOSE: To summarize evidence about the benefits and harms of psychological and pharmacologic therapies for adults with binge-eating disorder. DATA SOURCES: English-language publications in EMBASE, the Cochrane Library, Academic OneFile, CINAHL, and ClinicalTrials.gov through 18 November 2015, and in MEDLINE through 12 May 2016. STUDY SELECTION: 9 waitlist-controlled psychological trials and 25 placebo-controlled trials that evaluated pharmacologic (n = 19) or combination (n = 6) treatment. All were randomized trials with low or medium risk of bias. DATA EXTRACTION: 2 reviewers independently extracted trial data, assessed risk of bias, and graded strength of evidence. DATA SYNTHESIS: Therapist-led cognitive behavioral therapy, lisdexamfetamine, and second-generation antidepressants (SGAs) decreased binge-eating frequency and increased binge-eating abstinence (relative risk, 4.95 [95% CI, 3.06 to 8.00], 2.61 [CI, 2.04 to 3.33], and 1.67 [CI, 1.24 to 2.26], respectively). Lisdexamfetamine (mean difference…

BACKGROUND: The risk for chronic kidney disease (CKD) among obese persons without obesity-related metabolic abnormalities, called metabolically healthy obesity, is largely unexplored. OBJECTIVE: To investigate the risk for incident CKD across categories of body mass index in a large cohort of metabolically healthy men and women. DESIGN: Prospective cohort study. SETTING: Kangbuk Samsung Health Study, Kangbuk Samsung Hospital, Seoul, South Korea. PARTICIPANTS: 62 249 metabolically healthy, young and middle-aged men and women without CKD or proteinuria at baseline. MEASUREMENTS: Metabolic health was defined as a homeostasis model assessment of insulin resistance less than 2.5 and absence of any component of the metabolic syndrome. Underweight, normal weight, overweight, and obesity were defined as a body mass index less than 18.5 kg/m2, 18.5 to 22.9 kg/m2, 23 to 24.9 kg/m2, and 25 kg/m2 or greater, respectively. The outcome was incident CKD, defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. RESULTS: During 369 088 person-years of follow-up, 906 incident…

BACKGROUND: Controversy persists about optimal mammography screening strategies. OBJECTIVE: To evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer. DESIGN: Collaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality. SETTING: United States. PATIENTS: Average-risk U.S. female population and subgroups with varying risk, breast density, or comorbidity. INTERVENTION: Eight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years. MEASUREMENTS: Benefits (breast cancer-specific mortality reduction, breast cancer deaths averted, life-years, and quality-adjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens. RESULTS: Biennial…

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness of treatment with second-generation antidepressants versus nonpharmacologic treatments for major depressive disorder in adults. METHODS: This guideline is based on a systematic review of published, English-language, randomized, controlled trials from 1990 through September 2015 identified using several databases and through hand searches of references of relevant studies. Interventions evaluated include psychotherapies, complementary and alternative medicines (including acupuncture, ω-3 fatty acids, S-adenosyl-L-methionine, St. John's wort [Hypericum perforatum]), exercise, and second-generation antidepressants. Evaluated outcomes included response, remission, functional capacity, quality of life, reduction of suicidality or hospitalizations, and harms. The target audience for this guideline includes all clinicians, and the target patient population includes adults with major depressive disorder. This guideline…

BACKGROUND: Pharmacologic interventions are often prescribed for insomnia disorder. PURPOSE: To assess the benefits, harms, and comparative effectiveness of pharmacologic treatments for adults with insomnia disorder. DATA SOURCES: Several electronic databases (2004-September 2015), reference lists, and U.S. Food and Drug Administration (FDA) documents. STUDY SELECTION: 35 randomized, controlled trials of at least 4 weeks' duration that evaluated pharmacotherapies available in the United States and that reported global or sleep outcomes; 11 long-term observational studies that reported harm information; FDA review data for nonbenzodiazepine hypnotics and orexin receptor antagonists; and product labels for all agents. DATA EXTRACTION: Data extraction by single investigator confirmed by a second reviewer; dual-investigator assessment of risk of bias; consensus determination of strength of evidence. DATA SYNTHESIS: Eszopiclone, zolpidem, and suvorexant improved short-term global and sleep outcomes compared with placebo, although absolute effect sizes were small (low- to…

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in the United States. PURPOSE: To update a systematic review about the benefits of aspirin for the primary prevention of cardiovascular events in adults aged 40 years or older and to evaluate effect modification in subpopulations. DATA SOURCES: MEDLINE, PubMed, Cochrane Central Register of Controlled Trials (January 2008 to January 2015), and Cochrane Database of Systematic Reviews. STUDY SELECTION: Two investigators independently reviewed 3396 abstracts and 65 articles according to prespecified criteria. All included trials evaluated aspirin for the primary prevention of cardiovascular events. DATA EXTRACTION: Two investigators assessed study quality; data were abstracted by 1 reviewer and checked by a second. DATA SYNTHESIS: Two good-quality and 9 fair-quality randomized, controlled trials were identified. In analyses of all doses, aspirin reduced the risk for nonfatal myocardial infarction (MI) (relative risk [RR], 0.78 [95% CI, 0.71 to 0.87]) but not nonfatal stroke; aspirin showed little or no benefit for…

BACKGROUND: Financial incentive designs to increase physical activity have not been well-examined. OBJECTIVE: To test the effectiveness of 3 methods to frame financial incentives to increase physical activity among overweight and obese adults. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov: NCT 02030119). SETTING: University of Pennsylvania. PARTICIPANTS: 281 adult employees (body mass index ≥27 kg/m2). INTERVENTION: 13-week intervention. Participants had a goal of 7000 steps per day and were randomly assigned to a control group with daily feedback or 1 of 3 financial incentive programs with daily feedback: a gain incentive ($1.40 given each day the goal was achieved), lottery incentive (daily eligibility [expected value approximately $1.40] if goal was achieved), or loss incentive ($42 allocated monthly upfront and $1.40 removed each day the goal was not achieved). Participants were followed for another 13 weeks with daily performance feedback but no incentives. MEASUREMENTS: Primary outcome was the mean proportion of participant-days that the 7000-step goal was achieved…

BACKGROUND: Acupuncture has been used for chronic constipation, but evidence for its effectiveness remains scarce. OBJECTIVE: To determine the efficacy of electroacupuncture (EA) for chronic severe functional constipation (CSFC). DESIGN: Randomized, parallel, sham-controlled trial. (ClinicalTrials.gov: NCT01726504). SETTING: 15 hospitals in China. PARTICIPANTS: Patients with CSFC and no serious underlying pathologic cause for constipation. INTERVENTION: 28 sessions of EA at traditional acupoints or sham EA (SA) at nonacupoints over 8 weeks. MEASUREMENTS: The primary outcome was the change from baseline in mean weekly complete spontaneous bowel movements (CSBMs) during weeks 1 to 8. Participants were followed until week 20. RESULTS: 1075 patients (536 and 539 in the EA and SA groups, respectively) were enrolled. The increase from baseline in mean weekly CSBMs during weeks 1 to 8 was 1.76 (95% CI, 1.61 to 1.89) in the EA group and 0.87 (CI, 0.73 to 0.97) in the SA group (between-group difference, 0.90 [CI, 0.74 to 1.10]; P < 0.001). The change from baseline in mean weekly CSBMs during…

BACKGROUND: Prior mortality studies have concluded that elevated body mass index (BMI) may improve survival. These studies were limited because they did not measure adiposity directly. OBJECTIVE: To examine associations of BMI and body fat percentage (separately and together) with mortality. DESIGN: Observational study. SETTING: Manitoba, Canada. PARTICIPANTS: Adults aged 40 years or older referred for bone mineral density (BMD) testing. MEASUREMENTS: Participants had dual-energy x-ray absorptiometry (DXA), entered a clinical BMD registry, and were followed using linked administrative databases. Adjusted, sex-stratified Cox models were constructed. Body mass index and DXA-derived body fat percentage were divided into quintiles, with quintile 1 as the lowest, quintile 5 as the highest, and quintile 3 as the reference. RESULTS: The final cohort included 49 476 women (mean age, 63.5 years; mean BMI, 27.0 kg/m2; mean body fat, 32.1%) and 4944 men (mean age, 65.5 years; mean BMI, 27.4 kg/m2; mean body fat, 29.5%). Death occurred in 4965 women over a median of 6.7 years and 984 men over a…

BACKGROUND: The balance between potential aspirin-related risks and benefits is critical in primary prevention. PURPOSE: To evaluate the risk for serious bleeding with regular aspirin use in cardiovascular disease (CVD) primary prevention. DATA SOURCES: PubMed, MEDLINE, Cochrane Central Register of Controlled Trials (2010 through 6 January 2015), and relevant references from other reviews. STUDY SELECTION: Randomized, controlled trials; cohort studies; and meta-analyses comparing aspirin with placebo or no treatment to prevent CVD or cancer in adults. DATA EXTRACTION: One investigator abstracted data, another checked for accuracy, and 2 assessed study quality. DATA SYNTHESIS: In CVD primary prevention studies, very-low-dose aspirin use (≤100 mg daily or every other day) increased major gastrointestinal (GI) bleeding risk by 58% (odds ratio [OR], 1.58 [95% CI, 1.29 to 1.95]) and hemorrhagic stroke risk by 27% (OR, 1.27 [CI, 0.96 to 1.68]). Projected excess bleeding events with aspirin depend on baseline assumptions. Estimated excess major bleeding events were 1.39 (CI, 0.70 to 2.28)…

BACKGROUND: Frailty assessment may inform surgical risk and prognosis not captured by conventional surgical risk scores. PURPOSE: To evaluate the evidence for various frailty instruments used to predict mortality, functional status, or major adverse cardiovascular and cerebrovascular events (MACCEs) in older adults undergoing cardiac surgical procedures. DATA SOURCES: MEDLINE and EMBASE (without language restrictions), from their inception to 2 May 2016. STUDY SELECTION: Cohort studies evaluating the association between frailty and mortality or functional status at 6 months or later in patients aged 60 years or older undergoing major or minimally invasive cardiac surgical procedures. DATA EXTRACTION: 2 reviewers independently extracted study data and assessed study quality. DATA SYNTHESIS: Mobility, disability, and nutrition were frequently assessed domains of frailty in both types of procedures. In patients undergoing major procedures (n = 18 388; 8 studies), 9 frailty instruments were evaluated. There was moderate-quality evidence to assess mobility or disability and very-low- to…

BACKGROUND: The fecal immunochemical test (FIT) is a common method for colorectal cancer (CRC) screening, yet its acceptability and performance over several rounds of annual testing are largely unknown. OBJECTIVE: To assess FIT performance characteristics over 4 rounds of annual screening. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Northern and Southern California. PATIENTS: 323 349 health plan members aged 50 to 70 years on their FIT mailing date in 2007 or 2008 who completed the first round of FIT and were followed for up to 4 screening rounds. MEASUREMENTS: Screening participation, FIT positivity (≥20 µg of hemoglobin/g), positive predictive values for adenoma and CRC, and FIT sensitivity for detecting CRC obtained from Kaiser Permanente electronic databases and cancer registries. RESULTS: Of the patients invited for screening, 48.2% participated in round 1. Of those who remained eligible, 75.3% to 86.1% participated in subsequent rounds. Median follow-up was 4.0 years, and 32% of round 1 participants crossed over to endoscopy over 4 screening rounds-7.0% due…

BACKGROUND: Studies of cardiac disease among adult survivors of childhood cancer have generally relied on self-reported or registry-based data. OBJECTIVE: To systematically assess cardiac outcomes among survivors of childhood cancer. DESIGN: Cross-sectional study. SETTING: St. Jude Children's Research Hospital. PATIENTS: 1853 adult survivors of childhood cancer, aged 18 years or older, who received cancer-related cardiotoxic therapy at least 10 years earlier. MEASUREMENTS: Baseline history and physical examination, fasting metabolic and lipid panels, echocardiography, electrocardiography, and 6-minute walk test. RESULTS: One half of the survivors (52.3%) were men with a median age of 8 years (range, 0 to 24 years) at cancer diagnosis and 31 years (range, 18 to 60 years) at evaluation. Cardiomyopathy was present in 7.4% survivors (newly identified at the time of evaluation in 4.7%), coronary artery disease in 3.8% (newly identified in 2.2%), valvular regurgitation or stenosis in 28.0% (newly identified in 24.8%), and conduction or rhythm abnormalities in 4.4% (newly identified in…

BACKGROUND: Few remedies effectively treat long-term pain and disability from knee osteoarthritis. Studies suggest that Tai Chi alleviates symptoms, but no trials have directly compared Tai Chi with standard therapies for osteoarthritis. OBJECTIVE: To compare Tai Chi with standard physical therapy for patients with knee osteoarthritis. DESIGN: Randomized, 52-week, single-blind comparative effectiveness trial. (ClinicalTrials.gov: NCT01258985). SETTING: An urban tertiary care academic hospital. PATIENTS: 204 participants with symptomatic knee osteoarthritis (mean age, 60 years; 70% women; 53% white). INTERVENTION: Tai Chi (2 times per week for 12 weeks) or standard physical therapy (2 times per week for 6 weeks, followed by 6 weeks of monitored home exercise). MEASUREMENTS: The primary outcome was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 12 weeks. Secondary outcomes included physical function, depression, medication use, and quality of life. RESULTS: At 12 weeks, the WOMAC score was substantially reduced in both groups (Tai Chi, 167 points [95%…

Background: About half of the United States has legislation requiring radiology facilities to disclose mammographic breast density information to women, often with language recommending discussion of supplemental screening options for women with dense breasts. Objective: To examine variation in breast density assessment across radiologists in clinical practice. Design: Cross-sectional and longitudinal analyses of prospectively collected observational data. Setting: 30 radiology facilities within the 3 breast cancer screening research centers of the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. Participants: Radiologists who interpreted at least 500 screening mammograms during 2011 to 2013 (n = 83). Data on 216 783 screening mammograms from 145 123 women aged 40 to 89 years were included. Measurements: Mammographic breast density, as clinically recorded using the 4 Breast Imaging Reporting and Data System categories (heterogeneously dense and extremely dense categories were considered "dense" for analyses), and patient age, race,…

BACKGROUND: Ranking of interventions is one of the most appealing elements of network meta-analysis. There is, however, little evidence about the reliability of these rankings. PURPOSE: To empirically evaluate the extent of uncertainty in intervention rankings from network meta-analysis. DATA SOURCES: Two previous systematic reviews that involved searches of the Cochrane Library, MEDLINE, and Embase up to July 2012 for articles that included networks of at least 3 interventions. STUDY SELECTION: 58 network meta-analyses involving 1308 randomized trials and 404 interventions with available aggregated outcome data. DATA ANALYSIS: Each network was analyzed with a Bayesian approach. For each intervention, the surface under the cumulative ranking curve (SUCRA) and its 95% credible interval (95% CrI) were estimated. Through use of the SUCRA values, the interventions were then rank-ordered between 0% (worst) and 100% (best). DATA SYNTHESIS: The median width of the 95% CrIs of the SUCRA was 65% (first to third quartile, 38% to 80%). In 28% of networks, there was a 50% or greater probability…

BACKGROUND: Women screened with digital mammography may receive false-positive and false-negative results and subsequent imaging and biopsies. How these outcomes vary by age, time since the last screening, and individual risk factors is unclear. OBJECTIVE: To determine factors associated with false-positive and false-negative digital mammography results, additional imaging, and biopsies among a general population of women screened for breast cancer. DESIGN: Analysis of registry data. SETTING: Participating facilities at 5 U.S. Breast Cancer Surveillance Consortium breast imaging registries with linkages to pathology databases and tumor registries. PATIENTS: 405,191 women aged 40 to 89 years screened with digital mammography between 2003 and 2011. A total of 2963 were diagnosed with invasive cancer or ductal carcinoma in situ within 12 months of screening. MEASUREMENTS: Rates of false-positive and false-negative results and recommendations for additional imaging and biopsies from a single screening round; comparisons by age, time since the last screening, and risk factors. RESULTS:…

BACKGROUND: Unintentional overdose involving opioid analgesics is a leading cause of injury-related death in the United States. OBJECTIVE: To evaluate the feasibility and effect of implementing naloxone prescription to patients prescribed opioids for chronic pain. DESIGN: 2-year nonrandomized intervention study. SETTING: 6 safety-net primary care clinics in San Francisco, California. PARTICIPANTS: 1985 adults receiving long-term opioid therapy for pain. INTERVENTION: Providers and clinic staff were trained and supported in naloxone prescribing. MEASUREMENTS: Outcomes were proportion of patients prescribed naloxone, opioid-related emergency department (ED) visits, and prescribed opioid dose based on chart review. RESULTS: 38.2% of 1985 patients receiving long-term opioids were prescribed naloxone. Patients prescribed higher doses of opioids and with an opioid-related ED visit in the past 12 months were independently more likely to be prescribed naloxone. Patients who received a naloxone prescription had 47% fewer opioid-related ED visits per month in the 6 months after receipt of the…

BACKGROUND: N-acetylcysteine, sodium bicarbonate, statins, and ascorbic acid have been studied for reducing contrast-induced nephropathy (CIN). PURPOSE: To evaluate the comparative effectiveness of interventions to reduce CIN in adults receiving contrast media. DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and Scopus databases through June 2015. Risk of bias and overall strength of evidence (SOE) of studies were assessed. STUDY SELECTION: Randomized, controlled trials of N-acetylcysteine, sodium bicarbonate, statins, or ascorbic acid that used intravenous (IV) or intra-arterial contrast media and defined CIN with enough data for meta-analysis. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality. DATA SYNTHESIS: Low-dose N-acetylcysteine plus IV saline compared with IV saline (risk ratio [RR], 0.75 [95% CI, 0.63 to 0.89]; low SOE), N-acetylcysteine plus IV saline compared with IV saline in patients receiving low-osmolar contrast media (RR, 0.69 [CI, 0.58 to 0.84]; moderate SOE), and statins plus N-acetylcysteine plus IV saline…

BACKGROUND: Use of interferon and ribavirin to treat chronic hepatitis C virus (HCV) infection in kidney transplant recipients is limited because of the risk for allograft rejection and poor tolerability. OBJECTIVE: To evaluate the safety and efficacy of the interferon- and ribavirin-free regimen ledipasvir-sofosbuvir in kidney transplant recipients with chronic genotype 1 or 4 HCV infection. DESIGN: Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT02251717). SETTING: 5 sites in Europe. PATIENTS: Treatment-naive or -experienced kidney transplant recipients with chronic genotype 1 or 4 HCV infection, with or without compensated cirrhosis, and with an estimated glomerular filtration rate (eGFR) of 40 mL/min or greater were randomly assigned 1:1 to receive ledipasvir (90 mg) and sofosbuvir (400 mg) for 12 or 24 weeks. MEASUREMENTS: The primary end point was sustained virologic response at 12 weeks after therapy ended (SVR12). RESULTS: Among 114 patients, the median age was 53 years, 58% were male, 91% had genotype 1 infection, 69% were treatment naive, and 15% had…

BACKGROUND: Diagnosis of chronic hepatitis C virus (HCV) infection requires both a positive HCV antibody screen and confirmatory nucleic acid testing (NAT). Testing for hepatitis C virus core antigen (HCVcAg) is a potential alternative to NAT. PURPOSE: To evaluate the accuracy of diagnosis of active HCV infection among adults and children for 5 HCVcAg tests compared with NAT. DATA SOURCES: EMBASE, PubMed, Web of Science, Scopus, and Cochrane Database of Systematic Reviews from 1990 through 31 March 2016. STUDY SELECTION: Case-control, cross-sectional, cohort, or randomized trials that compared any of 5 HCVcAg tests with an NAT reference standard. DATA EXTRACTION: 2 independent reviewers extracted data and assessed quality using an adapted QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. DATA SYNTHESIS: 44 studies evaluated 5 index tests. Studies for the Abbott ARCHITECT HCV Ag assay had the highest quality, whereas those for the Ortho HCV Ag enzyme-linked immunosorbent assay (ELISA) had the lowest quality. From bivariate analyses, the sensitivity and specificity…

DESCRIPTION: Update of the 2009 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for major depressive disorder (MDD) in children and adolescents. METHODS: The USPSTF reviewed the evidence on the benefits and harms of screening; the accuracy of primary care-feasible screening tests; and the benefits and harms of treatment with psychotherapy, medications, and collaborative care models in patients aged 7 to 18 years. POPULATION: This recommendation applies to children and adolescents aged 18 years or younger who do not have a diagnosis of MDD. RECOMMENDATION: The USPSTF recommends screening for MDD in adolescents aged 12 to 18 years. Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for MDD in children aged 11 years or younger. (I statement).

BACKGROUND: Estimates of risk for radiation-induced breast cancer from mammography screening have not considered variation in dose exposure or diagnostic work-up after abnormal screening results. OBJECTIVE: To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening while considering exposure from screening and diagnostic mammography and dose variation among women. DESIGN: 2 simulation-modeling approaches. SETTING: U.S. population. PATIENTS: Women aged 40 to 74 years. INTERVENTION: Annual or biennial digital mammography screening from age 40, 45, or 50 years until age 74 years. MEASUREMENTS: Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality (harms) per 100,000 women screened. RESULTS: Annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancer cases (95% CI, 88 to 178) leading to 16 deaths (CI, 11 to 23), relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were…

BACKGROUND: Conflicting evidence exists regarding potential cardiovascular risks associated with high levels of calcium intake. PURPOSE: To update and reanalyze 2 systematic reviews to examine the effects of calcium intake on cardiovascular disease (CVD) among generally healthy adults. DATA SOURCES: MEDLINE; Cochrane Central Register of Controlled Trials; Scopus, including EMBASE; and previous evidence reports from English-language publications from 1966 to July 2016. STUDY SELECTION: Randomized trials and prospective cohort and nested case-control studies with data on dietary or supplemental intake of calcium, with or without vitamin D, and cardiovascular outcomes. DATA EXTRACTION: Study characteristics and results extracted by 1 reviewer were confirmed by a second reviewer. Two raters independently assessed risk of bias. DATA SYNTHESIS: Overall risk of bias was low for the 4 randomized trials (in 10 publications) and moderate for the 27 observational studies included. The trials did not find statistically significant differences in risk for CVD events or mortality between groups…

BACKGROUND: The performance of different diagnostic strategies for pulmonary embolism (PE) in patient subgroups is unclear. PURPOSE: To evaluate and compare the efficiency and safety of the Wells rule with fixed or age-adjusted d-dimer testing overall and in inpatients and persons with cancer, chronic obstructive pulmonary disease, previous venous thromboembolism, delayed presentation, and age 75 years or older. DATA SOURCES: MEDLINE and EMBASE from 1 January 1988 to 13 February 2016. STUDY SELECTION: 6 prospective studies in which the diagnostic management of PE was guided by the dichotomized Wells rule and quantitative d-dimer testing. DATA EXTRACTION: Individual data of 7268 patients; risk of bias assessed by 2 investigators with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. DATA SYNTHESIS: The proportion of patients in whom imaging could be withheld based on a "PE-unlikely" Wells score and a negative d-dimer test result (efficiency) was estimated using fixed (≤500 µg/L) and age-adjusted (age × 10 µg/L in patients aged >50 years) d-dimer thresholds;…

BACKGROUND: Whether hospitals with the highest risk-standardized readmission rates (RSRRs) subsequently experienced the greatest improvement after passage of the Medicare Hospital Readmissions Reduction Program (HRRP) is unknown. OBJECTIVE: To evaluate whether passage of the HRRP was followed by acceleration in improvement in 30-day RSRRs after hospitalizations for acute myocardial infarction (AMI), congestive heart failure (CHF), or pneumonia and whether the lowest-performing hospitals had faster acceleration in improvement after passage of the law than hospitals that were already performing well. DESIGN: Pre-post analysis stratified by hospital performance groups. SETTING: U.S. acute care hospitals. PATIENTS: 15 170 008 Medicare patients discharged alive from 2000 to 2013. INTERVENTION: Passage of the HRRP. MEASUREMENTS: 30-day readmission rates after hospitalization for AMI, CHF, or pneumonia for hospitals in the highest-performance (0% penalty), average-performance (>0% and <0.50% penalty), low-performance (≥0.50% and <0.99% penalty), and lowest-performance (≥0.99% penalty)…

BACKGROUND: Cancer is the second leading cause of death in the United States. PURPOSE: To conduct systematic reviews of aspirin and 1) total cancer mortality and incidence in persons eligible for primary prevention of cardiovascular disease (CVD) and 2) colorectal cancer (CRC) mortality and incidence in persons at average CRC risk. DATA SOURCES: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials through January 2015 and relevant references from other reviews. STUDY SELECTION: Trials comparing oral aspirin versus placebo or no treatment in adults aged 40 years or older were included. Two investigators independently reviewed abstracts and articles against inclusion and quality criteria. DATA EXTRACTION: Data from 20 good- or fair-quality trials were abstracted by one reviewer and checked by another. DATA SYNTHESIS: In CVD primary prevention trials, cancer mortality (relative risk [RR], 0.96 [95% CI, 0.87 to 1.06]) (10 trials; n = 103 787) and incidence (RR, 0.98 [CI, 0.93 to 1.04]) (6 trials; n = 72 926) were similar in aspirin and control groups over 3.6 to 10.1…

BACKGROUND: Mediterranean diets may be healthier than typical Western diets. PURPOSE: To summarize the literature comparing a Mediterranean diet with unrestricted fat intake with other diets regarding their effects on health outcomes in adults. DATA SOURCES: Ovid MEDLINE, CINAHL, and the Cochrane Library from 1990 through April 2016. STUDY SELECTION: Controlled trials of 100 or more persons followed for at least 1 year for mortality, cardiovascular, hypertension, diabetes, and adherence outcomes, as well as cohort studies for cancer outcomes. DATA EXTRACTION: Data extracted by 1 investigator was verified by another. Two reviewers assessed risk of bias and strength of evidence. DATA SYNTHESIS: Two primary prevention trials found no difference in all-cause mortality between diet groups. One large primary prevention trial found that a Mediterranean diet resulted in a lower incidence of major cardiovascular events (hazard ratio [HR], 0.71 [95% CI, 0.56 to 0.90]), breast cancer (HR, 0.43 [CI, 0.21 to 0.88]), and diabetes (HR, 0.70 [CI, 0.54 to 0.92]). Pooled analyses of primary…

The latest guidelines from the American College of Cardiology and American Heart Association, released in fall 2013, provide a long-anticipated update to the recommendations of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). The guidelines incorporate a new risk score for atherosclerotic cardiovascular disease that includes stroke as well as coronary heart disease. After publication, the new pooled cohort equations (PCEs) were evaluated in 15 studies from the United States and Europe, most of which used cohorts that were more contemporary than those used in developing the guidelines. In almost all of these external validation cohorts, the PCEs overestimated the observed risk. This narrative review provides an update of the published reports, an overview of the strengths and weaknesses of these validation efforts, and a discussion of possible reasons for the discrepancies. These issues may be useful in a recalibration process designed to better match…

Physicians have unique opportunities to help prevent firearm violence. Concern has developed that federal and state laws or regulations prohibit physicians from asking or counseling patients about firearms and disclosing patient information about firearms to others, even when threats to health and safety may be involved. This is not the case. In this article, the authors explain the statutes in question, emphasizing that physicians may ask about firearms (with rare exceptions), may counsel about firearms as they do about other health matters, and may disclose information to third parties when necessary. The authors then review circumstances under which questions about firearms might be most appropriate if they are not asked routinely. Such circumstances include instances when the patient provides information or exhibits behavior suggesting an acutely increased risk for violence, whether to himself or others, or when the patient possesses other individual-level risk factors for violence, such as alcohol abuse. The article summarizes the literature on current physician practices in…

Climate change could have a devastating effect on human and environmental health. Potential effects of climate change on human health include higher rates of respiratory and heat-related illness, increased prevalence of vector-borne and waterborne diseases, food and water insecurity, and malnutrition. Persons who are elderly, sick, or poor are especially vulnerable to these potential consequences. Addressing climate change could have substantial benefits to human health. In this position paper, the American College of Physicians (ACP) recommends that physicians and the broader health care community throughout the world engage in environmentally sustainable practices that reduce carbon emissions; support efforts to mitigate and adapt to the effects of climate change; and educate the public, their colleagues, their community, and lawmakers about the health risks posed by climate change. Tackling climate change is an opportunity to dramatically improve human health and avert dire environmental outcomes, and ACP believes that physicians can play a role in achieving this goal.