The 50 most-cited articles in Annals of Internal Medicine, 2019

Background: Microplastics are ubiquitous in natural environments. Ingestion of microplastics has been described in marine organisms, whereby particles may enter the food chain. Objective: To examine human feces for the presence of microplastics to determine whether humans involuntarily ingest them. Design: Prospective case series in which participants completed a food diary and sampled stool according to step-by-step instructions. Setting: Europe and Asia. Participants: Eight healthy volunteers aged 33 to 65 years. Measurements: After chemical digestion, Fourier-transform infrared microspectroscopy was used to analyze the presence and shape of 10 common types of microplastic in stool samples. Results: All 8 stool samples tested positive for microplastics. A median of 20 microplastics (50 to 500 µm in size) per 10 g of human stool were identified. Overall, 9 plastic types were detected, with polypropylene and polyethylene terephthalate being the most abundant. Limitations: There were few participants, and each provided only 1 sample. The origin and fate of microplastics in the…

Background: Although physician burnout is associated with negative clinical and organizational outcomes, its economic costs are poorly understood. As a result, leaders in health care cannot properly assess the financial benefits of initiatives to remediate physician burnout. Objective: To estimate burnout-associated costs related to physician turnover and physicians reducing their clinical hours at national (U.S.) and organizational levels. Design: Cost-consequence analysis using a mathematical model. Setting: United States. Participants: Simulated population of U.S. physicians. Measurements: Model inputs were estimated by using the results of contemporary published research findings and industry reports. Results: On a national scale, the conservative base-case model estimates that approximately $4.6 billion in costs related to physician turnover and reduced clinical hours is attributable to burnout each year in the United States. This estimate ranged from $2.6 billion to $6.3 billion in multivariate probabilistic sensitivity analyses. At an organizational level, the annual economic…

Description: This update of the 2010 International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding (UGIB) refines previous important statements and presents new clinically relevant recommendations. Methods: An international multidisciplinary group of experts developed the recommendations. Data sources included evidence summarized in previous recommendations, as well as systematic reviews and trials identified from a series of literature searches of several electronic bibliographic databases from inception to April 2018. Using an iterative process, group members formulated key questions. Two methodologists prepared evidence profiles and assessed quality (certainty) of evidence relevant to the key questions according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Group members reviewed the evidence profiles and, using a consensus process, voted on recommendations and determined the strength of recommendations as strong or conditional. Recommendations: Preendoscopic management: The…

Background: Whether health care provider burnout contributes to lower quality of patient care is unclear. Purpose: To estimate the overall relationship between burnout and quality of care and to evaluate whether published studies provide exaggerated estimates of this relationship. Data Sources: MEDLINE, PsycINFO, Health and Psychosocial Instruments (EBSCO), Mental Measurements Yearbook (EBSCO), EMBASE (Elsevier), and Web of Science (Clarivate Analytics), with no language restrictions, from inception through 28 May 2019. Study Selection: Peer-reviewed publications, in any language, quantifying health care provider burnout in relation to quality of patient care. Data Extraction: 2 reviewers independently selected studies, extracted measures of association of burnout and quality of care, and assessed potential bias by using the Ioannidis (excess significance) and Egger (small-study effect) tests. Data Synthesis: A total of 11 703 citations were identified, from which 123 publications with 142 study populations encompassing 241 553 health care providers were selected. Quality-of-care…

Background: Substitutive hospital-level care in a patient's home may reduce cost, health care use, and readmissions while improving patient experience, although evidence from randomized controlled trials in the United States is lacking. Objective: To compare outcomes of home hospital versus usual hospital care for patients requiring admission. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT03203759). Setting: Academic medical center and community hospital. Patients: 91 adults (43 home and 48 control) admitted via the emergency department with selected acute conditions. Intervention: Acute care at home, including nurse and physician home visits, intravenous medications, remote monitoring, video communication, and point-of-care testing. Measurements: The primary outcome was the total direct cost of the acute care episode (sum of costs for nonphysician labor, supplies, medications, and diagnostic tests). Secondary outcomes included health care use and physical activity during the acute care episode and at 30 days. Results: The adjusted mean cost of the acute care episode…

Heterogeneity of treatment effect (HTE) refers to the nonrandom variation in the magnitude or direction of a treatment effect across levels of a covariate, as measured on a selected scale, against a clinical outcome. In randomized controlled trials (RCTs), HTE is typically examined through a subgroup analysis that contrasts effects in groups of patients defined "1 variable at a time" (for example, male vs. female or old vs. young). The authors of this statement present guidance on an alternative approach to HTE analysis, "predictive HTE analysis." The goal of predictive HTE analysis is to provide patient-centered estimates of outcome risks with versus without the intervention, taking into account all relevant patient attributes simultaneously. The PATH (Predictive Approaches to Treatment effect Heterogeneity) Statement was developed using a multidisciplinary technical expert panel, targeted literature reviews, simulations to characterize potential problems with predictive approaches, and a deliberative process engaging the expert panel. The authors distinguish 2 categories of…

Background: The large observed variability in hemophilia prevalence prevents robust estimation of burden of disease. Objective: To estimate the prevalence and prevalence at birth of hemophilia and the associated life expectancy disadvantage. Design: Random-effects meta-analysis of registry data. Setting: Australia, Canada, France, Italy, New Zealand, and the United Kingdom. Participants: Male patients with hemophilia A or B. Measurements: Prevalence of hemophilia as a proportion of cases to the male population, prevalence of hemophilia at birth as a proportion of cases to live male births by year of birth, life expectancy disadvantage as a 1 - ratio of prevalence to prevalence at birth, and expected number of patients worldwide based on prevalence in high-income countries and prevalence at birth. Results: Prevalence (per 100 000 males) is 17.1 cases for all severities of hemophilia A, 6.0 cases for severe hemophilia A, 3.8 cases for all severities of hemophilia B, and 1.1 cases for severe hemophilia B. Prevalence at birth (per 100 000 males) is 24.6 cases for all severities of…

Background: The potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain. Objective: To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists (VKAs) for thrombotic APS. Design: 3-year, open-label, randomized noninferiority trial. (EU Clinical Trials Register: EUDRA [European Union Drug Regulatory Authorities] code 2010-019764-36). Setting: 6 university hospitals in Spain. Participants: 190 adults (aged 18 to 75 years) with thrombotic APS. Intervention: Rivaroxaban (20 mg/d or 15 mg/d, according to renal function) versus dose-adjusted VKAs (target international normalized ratio, 2.0 to 3.0, or 3.1 to 4.0 in patients with a history of recurrent thrombosis). Measurements: The primary efficacy outcome was the proportion of patients with new thrombotic events; the primary safety outcome was major bleeding. The prespecified noninferiority margin for risk ratio (RR) was 1.40. Secondary outcomes included time to thrombosis, type of thrombosis, changes in biomarker levels, cardiovascular death, and nonmajor…

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Description: Dietary guideline recommendations require consideration of the certainty in the evidence, the magnitude of potential benefits and harms, and explicit consideration of people's values and preferences. A set of recommendations on red meat and processed meat consumption was developed on the basis of 5 de novo systematic reviews that considered all of these issues. Methods: The recommendations were developed by using the Nutritional Recommendations (NutriRECS) guideline development process, which includes rigorous systematic review methodology, and GRADE methods to rate the certainty of evidence for each outcome and to move from evidence to recommendations. A panel of 14 members, including 3 community members, from 7 countries voted on the final recommendations. Strict criteria limited the conflicts of interest among panel members. Considerations of environmental impact or animal welfare did not bear on the recommendations. Four systematic reviews addressed the health…

Background: Mavacamten, an orally administered, small-molecule modulator of cardiac myosin, targets underlying biomechanical abnormalities in obstructive hypertrophic cardiomyopathy (oHCM). Objective: To characterize the effect of mavacamten on left ventricular outflow tract (LVOT) gradient. Design: Open-label, nonrandomized, phase 2 trial. (ClinicalTrials.gov: NCT02842242). Setting: 5 academic centers. Participants: 21 symptomatic patients with oHCM. Intervention: Patients in cohort A received mavacamten, 10 to 20 mg/d, without background medications. Those in cohort B received mavacamten, 2 to 5 mg/d, with β-blockers allowed. Measurements: The primary end point was change in postexercise LVOT gradient at 12 weeks. Secondary end points included changes in peak oxygen consumption (pVO2), resting and Valsalva LVOT gradients, left ventricular ejection fraction (LVEF), and numerical rating scale dyspnea score. Results: In cohort A, mavacamten reduced mean postexercise LVOT gradient from 103 mm Hg (SD, 50) at baseline to 19 mm Hg (SD, 13) at 12 weeks (mean change, -89.5 mm Hg [95% CI,…

Letters5 November 2019The Accuracy of Google Translate for Abstracting Data From Non–English-Language Trials for Systematic ReviewsJeffrey L Jackson, MD, MPH, Akira Kuriyama, MD, MPH, Andreea Anton, MD, April Choi, MD, Jean-Pascal Fournier, MD, PhD, Anne-Kathrin Geier, MD, MPH, Frederique Jacquerioz, MD, MPH, Dmitry Kogan, MD, Cecilia Scholcoff, MD, MPH, and Rao Sun, MD, PhDJeffrey L Jackson, MD, MPHMedical College of Wisconsin, Milwaukee, Wisconsin (J.L.J., A.A., D.K., C.S.), Akira Kuriyama, MD, MPHKurashiki Central Hospital, Okayama, Japan (A.K.), Andreea Anton, MDMedical College of Wisconsin, Milwaukee, Wisconsin (J.L.J., A.A., D.K., C.S.), April Choi, MDRutgers New Jersey Medical School, Newark, New Jersey (A.C.), Jean-Pascal Fournier, MD, PhDUniversité de Nantes, Nantes, France (J.F.), Anne-Kathrin Geier, MD, MPHUniversity of Leipzig, Leipzig, Germany (A.G.), Frederique Jacquerioz, MD, MPHHôpital Universitaire de Genéve, Geneva, Switzerland (F.J.), Dmitry Kogan, MDMedical College of Wisconsin, Milwaukee, Wisconsin (J.L.J., A.A., D.K., C.S.), Cecilia Scholcoff, MD, MPHMedical…

Background: The health benefits and risks of dietary supplement use are controversial. Objective: To evaluate the association among dietary supplement use, levels of nutrient intake from foods and supplements, and mortality among U.S. adults. Design: Prospective cohort study. Setting: NHANES (National Health and Nutrition Examination Survey) data from 1999 to 2010, linked to National Death Index mortality data. Participants: 30 899 U.S. adults aged 20 years or older who answered questions on dietary supplement use. Measurements: Dietary supplement use in the previous 30 days and nutrient intake from foods and supplements. Outcomes included mortality from all causes, cardiovascular disease (CVD), and cancer. Results: During a median follow-up of 6.1 years, 3613 deaths occurred, including 945 CVD deaths and 805 cancer deaths. Ever-use of dietary supplements was not associated with mortality outcomes. Adequate intake (at or above the Estimated Average Requirement or the Adequate Intake level) of vitamin A, vitamin K, magnesium, zinc, and copper was associated with reduced all-cause or…

Background: The suicide case-fatality rate (CFR)-the proportion of suicidal acts that are fatal-depends on the distribution of methods used in suicidal acts and the probability of death given a particular method (method-specific CFR). Objective: To estimate overall and method-specific suicide CFRs and the distribution of methods used in suicidal acts by demographic characteristics. Design: Cross-sectional study. Setting: United States, 2007 to 2014. Participants: Suicide deaths (n = 309 377 records from the National Vital Statistics System) and nonfatal suicide attempts requiring treatment in an emergency department (ED) (n = 1 791 638 records from the Nationwide Emergency Department Sample) or hospitalization (n = 1 556 871 records from the National [Nationwide] Inpatient Sample) among persons aged 5 years or older. Measurements: Rates of suicide deaths and nonfatal suicide attempts, overall and method-specific CFRs, and distribution of methods used, by sex, age group, region, and urbanization. Results: Overall, 8.5% of suicidal acts were fatal (14.7% for males vs. 3.3% for…

Description: The European Commission Initiative for Breast Cancer Screening and Diagnosis guidelines (European Breast Guidelines) are coordinated by the European Commission's Joint Research Centre. The target audience for the guidelines includes women, health professionals, and policymakers. Methods: An international guideline panel of 28 multidisciplinary members, including patients, developed questions and corresponding recommendations that were informed by systematic reviews of the evidence conducted between March 2016 and December 2018. GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests by enhancing transparency. Questions and recommendations, expressed as strong or conditional, focused on outcomes that matter to women and provided a rating of the certainty of evidence. Recommendations: This synopsis of the European Breast Guidelines provides recommendations regarding organized screening programs for women aged 40 to 75 years who are at…

Pharmacoepidemiologic and pharmacoeconomic analysis of health care databases has become a vital source of evidence to support health care decision making and efficient management of health care organizations. However, decision makers often consider studies done in nonrandomized health care databases more difficult to review than randomized trials because many design choices need to be considered. This is perceived as an important barrier to decision making about the effectiveness and safety of medical products. Design flaws in longitudinal database studies are avoidable but can be unintentionally obscured in the convoluted prose of methods sections, which often lack specificity. We propose a simple framework of graphical representation that visualizes study design implementations in a comprehensive, unambiguous, and intuitive way; contains a level of detail that enables reproduction of key study design variables; and uses standardized structure and terminology to simplify review and communication to a broad audience of decision makers. Visualization of design details will make…

Obstructive sleep apnea (OSA) is very common but is frequently undiagnosed. Symptoms include loud snoring, nocturnal awakening, and daytime sleepiness. Motor vehicle accidents due to drowsy driving are a particular concern. Evaluation and treatment should focus on symptomatic patients, both to alleviate symptoms and to potentially decrease cardiovascular risk. In recent years, a strategy of home sleep apnea testing followed by initiation of autotitrating continuous positive airway pressure therapy in the home has greatly reduced barriers to diagnosis and treatment and has also facilitated routine management of OSA by primary care providers.

Background: Adrenal incidentalomas are mostly benign nonfunctioning adrenal tumors (NFATs) or adenomas causing mild autonomous cortisol excess (MACE), but their natural history is unclear. Purpose: To summarize the follow-up data of adults with NFAT or MACE to determine the proportions of tumor growth, malignant transformation, and incident changes in hormone function; the prevalence of incident cardiometabolic comorbid conditions; and mortality. Data Sources: MEDLINE, Embase, Cochrane, and Scopus (January 1990 to February 2019) and bibliographies of identified articles, without language restriction. Study Selection: Studies that included 20 or more conservatively managed patients with NFAT or MACE and reported outcomes at baseline and after at least 12 months of follow-up. Data Extraction: Pairs of reviewers extracted outcomes and assessed methodological quality. Data Synthesis: Thirty-two studies reported outcomes of 4121 patients with NFAT or MACE, 61.5% of whom were women; the mean age was 60.2 years, and mean follow-up was 50.2 months. Mean tumor growth was 2 mm over 52.8…

Background: The hypothesized link between the measles, mumps, rubella (MMR) vaccine and autism continues to cause concern and challenge vaccine uptake. Objective: To evaluate whether the MMR vaccine increases the risk for autism in children, subgroups of children, or time periods after vaccination. Design: Nationwide cohort study. Setting: Denmark. Participants: 657 461 children born in Denmark from 1999 through 31 December 2010, with follow-up from 1 year of age and through 31 August 2013. Measurements: Danish population registries were used to link information on MMR vaccination, autism diagnoses, other childhood vaccines, sibling history of autism, and autism risk factors to children in the cohort. Survival analysis of the time to autism diagnosis with Cox proportional hazards regression was used to estimate hazard ratios of autism according to MMR vaccination status, with adjustment for age, birth year, sex, other childhood vaccines, sibling history of autism, and autism risk factors (based on a disease risk score). Results: During 5 025 754 person-years of follow-up, 6517…

Background: Randomized trials demonstrate no benefit from antibiotic treatment exceeding the shortest effective duration. Objective: To examine predictors and outcomes associated with excess duration of antibiotic treatment. Design: Retrospective cohort study. Setting: 43 hospitals in the Michigan Hospital Medicine Safety Consortium. Patients: 6481 general care medical patients with pneumonia. Measurements: The primary outcome was the rate of excess antibiotic treatment duration (excess days per 30-day period). Excess days were calculated by subtracting each patient's shortest effective (expected) treatment duration (based on time to clinical stability, pathogen, and pneumonia classification [community-acquired vs. health care-associated]) from the actual duration. Negative binomial generalized estimating equations (GEEs) were used to calculate rate ratios to assess predictors of 30-day rates of excess duration. Patient outcomes, assessed at 30 days via the medical record and telephone calls, were evaluated using logit GEEs that adjusted for patient characteristics and probability…

Background: Delirium is common in hospitalized patients and is associated with worse outcomes. Antipsychotics are commonly used; however, the associated benefits and harms are unclear. Purpose: To conduct a systematic review evaluating the benefits and harms of antipsychotics to treat delirium in adults. Data Sources: PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception to July 2019 without language restrictions. Study Selection: Randomized controlled trials (RCTs) of antipsychotic versus placebo or another antipsychotic, and prospective observational studies reporting harms. Data Extraction: One reviewer extracted data and assessed strength of evidence (SOE) for critical outcomes, with confirmation by another reviewer. Risk of bias was assessed independently by 2 reviewers. Data Synthesis: Across 16 RCTs and 10 observational studies of hospitalized adults, there was no difference in sedation status (low and moderate SOE), delirium duration, hospital length of stay (moderate SOE), or mortality between haloperidol and second-generation antipsychotics versus placebo. There was…

Background: Studies report inconsistent performance of fecal immunochemical tests (FITs) for colorectal cancer (CRC) and advanced adenomas. Purpose: To summarize performance characteristics of FITs for CRC and advanced adenomas in average-risk persons undergoing screening colonoscopy (reference standard) and to identify factors affecting these characteristics. Data Sources: Ovid MEDLINE, PubMed, Embase, and the Cochrane Library from inception through October 2018; reference lists of studies and reviews. Study Selection: Two reviewers independently screened records to identify published English-language prospective or retrospective observational studies that evaluated FIT sensitivity and specificity for colonoscopic findings in asymptomatic, average-risk adults. Data Extraction: Two authors independently extracted data and evaluated study quality. Data Synthesis: Thirty-one studies (120 255 participants; 18 FITs) were included; all were judged to have low to moderate risk of bias. Performance characteristics depended on the threshold for a positive result. A threshold of 10 µg/g…

Health care applications of artificial intelligence (AI) have recently emerged. Artificial intelligence approaches, such as deep learning, rely on vast amounts of data and complex model structures ...

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Dietary guidelines generally recommend limiting intake of red and processed meat. However, the quality of evidence implicating red and processed meat in adverse health outcomes remains unclear. Purpose: To evaluate the association between red and processed meat consumption and all-cause mortality, cardiometabolic outcomes, quality of life, and satisfaction with diet among adults. Data Sources: EMBASE (Elsevier), Cochrane Central Register of Controlled Trials (Wiley), Web of Science (Clarivate Analytics), CINAHL (EBSCO), and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019, without language restrictions, as well as bibliographies of relevant articles. Study Selection: Cohort studies with at least 1000 participants that reported an association between unprocessed red or processed meat intake and outcomes of interest. Data Extraction: Teams of 2 reviewers independently extracted data and assessed risk of bias. One investigator assessed…

Background: Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors has been associated with Fournier gangrene (FG), a rare urologic emergency characterized by necrotizing infection of the external genitalia, perineum, and perianal region. Objective: To describe and compare reported cases of FG in diabetic adults receiving treatment with SGLT2 inhibitors or other antiglycemic agents. Design: Descriptive case series. Setting: U.S. Food and Drug Administration (FDA) Adverse Event Reporting System and published case reports. Patients: Adults receiving SGLT2 inhibitors or other antiglycemic agents. Measurements: Clinical and laboratory data. Results: The FDA identified 55 unique cases of FG in patients receiving SGLT2 inhibitors between 1 March 2013 and 31 January 2019. The patients ranged in age from 33 to 87 years; 39 were men, and 16 were women. Time to onset after initiation of SGLT2-inhibitor therapy ranged from 5 days to 49 months. All patients had surgical debridement and were severely ill. Reported complications included diabetic ketoacidosis (n = 8), sepsis or septic shock (n…

Background: Administering antimicrobial agents before obtaining blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear how this strategy affects diagnostic sensitivity. Objective: To determine the sensitivity of blood cultures obtained shortly after initiation of antimicrobial therapy in patients with severe manifestations of sepsis. Design: Patient-level, single-group, diagnostic study. (ClinicalTrials.gov: NCT01867905). Setting: 7 emergency departments in North America. Participants: Adults with severe manifestations of sepsis, including systolic blood pressure less than 90 mm Hg or a serum lactate level of 4 mmol/L or more. Intervention: Blood cultures were obtained before and within 120 minutes after initiation of antimicrobial treatment. Measurements: Sensitivity of blood cultures obtained after initiation of antimicrobial therapy. Results: Of 3164 participants screened, 325 were included in the study (mean age, 65.6 years; 62.8% men) and had repeated blood cultures drawn after initiation of antimicrobial therapy (median time, 70…

Description: The purpose of this guidance statement is to provide advice to clinicians on breast cancer screening in average-risk women based on a review of existing guidelines and the evidence they include. Methods: This guidance statement is derived from an appraisal of selected guidelines from around the world that address breast cancer screening, as well as their included evidence. All national guidelines published in English between 1 January 2013 and 15 November 2017 in the National Guideline Clearinghouse or Guidelines International Network library were included. In addition, the authors selected other guidelines commonly used in clinical practice. Web sites associated with all selected guidelines were checked for updates on 10 December 2018. The AGREE II (Appraisal of Guidelines for Research and Evaluation II) instrument was used to evaluate the quality of guidelines. Target Audience and Patient Population: The target audience is all clinicians, and the target patient population is all asymptomatic women with average risk for breast cancer. Guidance Statement 1: In…

Generalized anxiety disorder (GAD) is a common and disabling illness that is often underdiagnosed and undertreated. Patients with GAD are at increased risk for suicide as well as cardiovascular-related events and death. Most patients can be diagnosed and managed by primary care physicians. Symptoms include chronic, pervasive anxiety and worry accompanied by nonspecific physical and psychological symptoms (restlessness, fatigue, difficulty concentrating, irritability, muscle tension, or sleep disturbances). Effective treatments include psychotherapy (often cognitive behavioral therapy) and pharmacotherapy, such as selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors.

Background: Prior studies evaluating risk for severe urinary tract infections (UTIs) with sodium-glucose cotransporter-2 (SGLT-2) inhibitors have reported conflicting findings. Objective: To assess whether patients initiating use of SGLT-2 inhibitors were at increased risk for severe UTI events compared with those initiating use of dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 receptor (GLP-1) agonists. Design: Population-based cohort study. Setting: 2 large, U.S.-based databases of commercial claims (March 2013 to September 2015). Participants: Within each database, 2 cohorts were created and matched 1:1 on propensity score. Patients were aged 18 years or older, had type 2 diabetes mellitus, and were initiating use of SGLT-2 inhibitors versus DPP-4 inhibitors (cohort 1) or GLP-1 agonists (cohort 2). Measurements: The primary outcome was a severe UTI event, defined as a hospitalization for primary UTI, sepsis with UTI, or pyelonephritis; the secondary outcome was outpatient UTI treated with antibiotics. Hazard ratios (HRs) were estimated in each propensity…

Background: The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear. Purpose: To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults. Data Sources: PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists. Study Selection: English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease. Data Extraction: Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. Data Synthesis: Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were…

Background: The long-term cardiovascular risk of isolated elevated office blood pressure (BP) is unclear. Purpose: To summarize the risk for cardiovascular events and all-cause mortality associated with untreated white coat hypertension (WCH) and treated white coat effect (WCE). Data Sources: PubMed and EMBASE, without language restriction, from inception to December 2018. Study Selection: Observational studies with at least 3 years of follow-up evaluating the cardiovascular risk of WCH or WCE compared with normotension. Data Extraction: 2 investigators independently extracted study data and assessed study quality. Data Synthesis: 27 studies were included, comprising 25 786 participants with untreated WCH or treated WCE and 38 487 with normal BP followed for a mean of 3 to 19 years. Compared with normotension, untreated WCH was associated with an increased risk for cardiovascular events (hazard ratio [HR], 1.36 [95% CI, 1.03 to 2.00]), all-cause mortality (HR, 1.33 [CI, 1.07 to 1.67]), and cardiovascular mortality (HR, 2.09 [CI, 1.23 to 4.48]); the risk for WCH was attenuated in…

Background: Preliminary data suggest that preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) may improve risk prediction in patients undergoing noncardiac surgery. Objective: To determine whether preoperative NT-proBNP has additional predictive value beyond a clinical risk score for the composite of vascular death and myocardial injury after noncardiac surgery (MINS) within 30 days after surgery. Design: Prospective cohort study. Setting: 16 hospitals in 9 countries. Patients: 10 402 patients aged 45 years or older having inpatient noncardiac surgery. Measurements: All patients had NT-proBNP levels measured before surgery and troponin T levels measured daily for up to 3 days after surgery. Results: In multivariable analyses, compared with preoperative NT-proBNP values less than 100 pg/mL (the reference group), those of 100 to less than 200 pg/mL, 200 to less than 1500 pg/mL, and 1500 pg/mL or greater were associated with adjusted hazard ratios of 2.27 (95% CI, 1.90 to 2.70), 3.63 (CI, 3.13 to 4.21), and 5.82 (CI, 4.81 to 7.05) and corresponding incidences of the…

Background: Suicide is a growing public health problem, with the national rate in the United States increasing by 30% from 2000 to 2016. Purpose: To assess the benefits and harms of nonpharmacologic and pharmacologic interventions to prevent suicide and reduce suicide behaviors in at-risk adults. Data Sources: MEDLINE, EMBASE, PsycINFO, and other databases from November 2011 through May 2018. Study Selection: Systematic reviews (SRs) and randomized controlled trials (RCTs) that assessed nonpharmacologic or pharmacologic therapies for adults at risk for suicide. Data Extraction: One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy. Data Synthesis: Eight SRs and 15 RCTs were included. The evidence for psychological interventions suggests that cognitive behavioral therapy (CBT) reduces suicide attempts, suicidal ideation, and hopelessness compared with treatment as usual (TAU). Limited evidence suggests that dialectical behavior therapy (DBT) reduces suicidal ideation compared with wait-list control or…

The PATH (Predictive Approaches to Treatment effect Heterogeneity) Statement was developed to promote the conduct of, and provide guidance for, predictive analyses of heterogeneity of treatment effects (HTE) in clinical trials. The goal of predictive HTE analysis is to provide patient-centered estimates of outcome risk with versus without the intervention, taking into account all relevant patient attributes simultaneously, to support more personalized clinical decision making than can be made on the basis of only an overall average treatment effect. The authors distinguished 2 categories of predictive HTE approaches (a "risk-modeling" and an "effect-modeling" approach) and developed 4 sets of guidance statements: criteria to determine when risk-modeling approaches are likely to identify clinically meaningful HTE, methodological aspects of risk-modeling methods, considerations for translation to clinical practice, and considerations and caveats in the use of effect-modeling approaches. They discuss limitations of these methods and enumerate research priorities for advancing methods…

Letters3 September 2019The Limitations of Poor Broadband Internet Access for Telemedicine Use in Rural America: An Observational StudyColeman Drake, PhD, Yuehan Zhang, ScM, Krisda H. Chaiyachati, MD, MPH, MSHP, and Daniel Polsky, PhDColeman Drake, PhDUniversity of Pittsburgh, Pittsburgh, Pennsylvania (C.D.), Yuehan Zhang, ScMUniversity of Pennsylvania, Philadelphia, Pennsylvania (Y.Z., K.H.C.), Krisda H. Chaiyachati, MD, MPH, MSHPUniversity of Pennsylvania, Philadelphia, Pennsylvania (Y.Z., K.H.C.), and Daniel Polsky, PhDJohns Hopkins University, Baltimore, Maryland (D.P.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-0283 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Fewer than 10% of U.S. physicians practice in rural communities, where 25% of Americans live (1). Yet, rural Americans may need more health care as they become increasingly older and sicker relative to their urban counterparts (2). Telemedicine has been proposed as a solution to improve access to…

Background: Little is known about the relative harms of edible and inhalable cannabis products. Objective: To describe and compare adult emergency department (ED) visits related to edible and inhaled cannabis exposure. Design: Chart review of ED visits between 1 January 2012 and 31 December 2016. Setting: A large urban academic hospital in Colorado. Participants: Adults with ED visits with a cannabis-related International Classification of Diseases, Ninth or 10th Revision, Clinical Modification (ICD-9-CM or ICD-10-CM), code. Measurements: Patient demographic characteristics, route of exposure, dose, symptoms, length of stay, disposition, discharge diagnoses, and attribution of visit to cannabis. Results: There were 9973 visits with an ICD-9-CM or ICD-10-CM code for cannabis use. Of these, 2567 (25.7%) visits were at least partially attributable to cannabis, and 238 of those (9.3%) were related to edible cannabis. Visits attributable to inhaled cannabis were more likely to be for cannabinoid hyperemesis syndrome (18.0% vs. 8.4%), and visits attributable to edible cannabis were more…

Transgender persons are a diverse group whose gender identity differs from their sex recorded at birth. Some choose to undergo medical treatment to align their physical appearance with their gender identity. Barriers to accessing appropriate and culturally competent care contribute to health disparities in transgender persons, such as increased rates of certain types of cancer, substance abuse, mental health conditions, infections, and chronic diseases. Thus, it is important that clinicians understand the specific medical issues that are relevant to this population.

Letters18 February 2020Geographic Variation in Prevalence of Adult Obesity in China: Results From the 2013–2014 National Chronic Disease and Risk Factor SurveillanceXiao Zhang, MD, PhD, Mei Zhang, MD, PhD, Zhenping Zhao, MD, Zhengjing Huang, MPH, Qian Deng, MD, PhD, Yichong Li, MD, PhD, An Pan, MD, PhD, Chun Li, MD, Zhihua Chen, MD, Maigeng Zhou, MD, PhD, Chao Yu, PhD, Alfred Stein, PhD, Peng Jia, PhD*, and Limin Wang, MPH*Xiao Zhang, MD, PhDNational Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China (X.Z., M.Z., Z.Z., Z.H., Q.D., Y.L., C.L., Z.C., M.Z., L.W.), Mei Zhang, MD, PhDNational Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China (X.Z., M.Z., Z.Z., Z.H., Q.D., Y.L., C.L., Z.C., M.Z., L.W.), Zhenping Zhao, MDNational Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China (X.Z., M.Z., Z.Z., Z.H., Q.D., Y.L., C.L., Z.C., M.Z.,…

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Cancer incidence has continuously increased over the past few centuries and represents a major health burden worldwide. Purpose: To evaluate the possible causal relationship between intake of red and processed meat and cancer mortality and incidence. Data Sources: Embase, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL, and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019 without language restrictions. Study Selection: Cohort studies that included more than 1000 adults and reported the association between consumption of unprocessed red and processed meat and cancer mortality and incidence. Data Extraction: Teams of 2 reviewers independently extracted data and assessed risk of bias; 1 reviewer evaluated the certainty of evidence, which was confirmed or revised by the senior reviewer. Data Synthesis: Of 118 articles (56 cohorts) with more than 6 million participants, 73 articles were eligible for the…

Background: Both pharmacologic and nonpharmacologic interventions are used to treat neuropsychiatric symptoms in persons with dementia. Purpose: To summarize the comparative efficacy of pharmacologic and nonpharmacologic interventions for treating aggression and agitation in adults with dementia. Data Sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, and PsycINFO between inception and 28 May 2019 without language restrictions; gray literature; and reference lists scanned from selected studies and systematic reviews. Study Selection: Randomized controlled trials comparing interventions for treating aggression and agitation in adults with dementia. Data Extraction: Pairs of reviewers independently screened studies, abstracted data, and appraised risk of bias. Data Synthesis: After screening of 19 684 citations, 163 studies (23 143 patients) were included in network meta-analyses. Analysis of interventions targeting aggression and agitation (148 studies [21 686 patients]) showed that multidisciplinary care (standardized mean difference [SMD], -0.5 [95%…

Background: Identifying reliable predictors of long-term weight loss (LTWL) could lead to improved weight management. Objective: To identify some predictors of LTWL. Design: The DPP (Diabetes Prevention Program) was a randomized controlled trial that compared weight loss with metformin, intensive lifestyle intervention (ILS), or placebo. Its Outcomes Study (DPPOS) observed patients after the masked treatment phase ended. (ClinicalTrials.gov: NCT00004992 and NCT00038727). Setting: 27 DPP and DPPOS clinics. Participants: Of the 3234 randomly assigned participants, 1066 lost at least 5% of baseline weight in the first year and were followed for 15 years. Measurements: Treatment assignment, personal characteristics, and weight. Results: After 1 year, 289 (28.5%) participants in the metformin group, 640 (62.6%) in the ILS group, and 137 (13.4%) in the placebo group had lost at least 5% of their weight. After the masked treatment phase ended, the mean weight loss relative to baseline that was maintained between years 6 and 15 was 6.2% (95% CI, 5.2% to 7.2%) in the metformin group, 3.7%…

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Studying dietary patterns may provide insights into the potential effects of red and processed meat on health outcomes. Purpose: To evaluate the effect of dietary patterns, including different amounts of red or processed meat, on all-cause mortality, cardiometabolic outcomes, and cancer incidence and mortality. Data Sources: Systematic search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and ProQuest Dissertations & Theses Global from inception to April 2019 with no restrictions on year or language. Study Selection: Teams of 2 reviewers independently screened search results and included prospective cohort studies with 1000 or more participants that reported on the association between dietary patterns and health outcomes. Data Extraction: Two reviewers independently extracted data, assessed risk of bias, and evaluated the certainty of evidence using GRADE (Grading of Recommendations Assessment, Development and…

Background: Optimal long-term osteoporosis drug treatment (ODT) is uncertain. Purpose: To summarize the effects of long-term ODT and ODT discontinuation and holidays. Data Sources: Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies. Study Selection: 48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB). Data Extraction: Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy. Data Synthesis: Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both…

Background: Treatment decisions commonly have to be made in intensive care units (ICUs). These decisions are difficult for surrogate decision makers and often lead to decisional conflict, psychological distress, and treatments misaligned with patient preferences. Objective: To determine whether a decision aid about prolonged mechanical ventilation improved prognostic concordance between surrogate decision makers and clinicians compared with a usual care control. Design: Multicenter, parallel, randomized, clinical trial. (ClinicalTrials.gov: NCT01751061). Setting: 13 medical and surgical ICUs at 5 hospitals. Participants: Adult patients receiving prolonged mechanical ventilation and their surrogates, ICU physicians, and ICU nurses. Intervention: A Web-based decision aid provided personalized prognostic estimates, explained treatment options, and interactively clarified patient values to inform a family meeting. The control group received information according to usual care practices followed by a family meeting. Measurements: The primary outcome was improved concordance on 1-year…

Description: The purpose of this guidance statement is to guide clinicians on colorectal cancer screening in average-risk adults. Methods: This guidance statement is derived from a critical appraisal of guidelines on screening for colorectal cancer in average-risk adults and the evidence presented in these guidelines. National guidelines published in English between 1 June 2014 and 28 May 2018 in the National Guideline Clearinghouse or Guidelines International Network library were included. The authors also included 3 guidelines commonly used in clinical practice. Web sites were searched for guideline updates in December 2018. The AGREE II (Appraisal of Guidelines for Research and Evaluation II) instrument was used to evaluate the quality of guidelines. Target Audience and Patient Population: The target audience is all clinicians, and the target patient population is adults at average risk for colorectal cancer. Guidance Statement 1: Clinicians should screen for colorectal cancer in average-risk adults between the ages of 50 and 75 years. Guidance Statement 2: Clinicians should…

Background: MIV-711 is a novel selective cathepsin K inhibitor with beneficial effects on bone and cartilage in preclinical osteoarthritis models. Objective: To evaluate the efficacy, safety, and tolerability of MIV-711 in participants with symptomatic, radiographic knee osteoarthritis. Design: 26-week randomized, double-blind, placebo-controlled phase 2a study with a 26-week open-label safety extension substudy. (EudraCT: 2015-003230-26 and 2016-001096-73). Setting: Six European sites. Participants: 244 participants with primary knee osteoarthritis, Kellgren-Lawrence grade 2 or 3, and pain score of 4 to 10 on a numerical rating scale (NRS). Intervention: MIV-711, 100 (n = 82) or 200 (n = 81) mg daily, or matched placebo (n = 77). Participants (46 who initially received 200 mg/d and 4 who received placebo) received 200 mg of MIV-711 daily during the extension substudy. Measurements: The primary outcome was change in NRS pain score. The key secondary outcome was change in bone area on magnetic resonance imaging (MRI). Other secondary end points included cartilage thickness on…

Background: Effects of oral anticoagulation in chronic kidney disease (CKD) are uncertain. Purpose: To evaluate the benefits and harms of vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) in adults with CKD stages 3 to 5, including those with dialysis-dependent end-stage kidney disease (ESKD). Data Sources: English-language searches of MEDLINE, EMBASE, and Cochrane databases (inception to February 2019); review bibliographies; and ClinicalTrials.gov (25 February 2019). Study Selection: Randomized controlled trials evaluating VKAs or NOACs for any indication in patients with CKD that reported efficacy or bleeding outcomes. Data Extraction: Two authors independently extracted data, assessed risk of bias, and rated certainty of evidence. Data Synthesis: Forty-five trials involving 34 082 participants who received anticoagulation for atrial fibrillation (AF) (11 trials), venous thromboembolism (VTE) (11 trials), thromboprophylaxis (6 trials), prevention of dialysis access thrombosis (8 trials), and cardiovascular disease other than AF (9 trials) were included.…

Background: Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown. Objective: To assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis. Design: Prospective propensity score (PS)-matched cohort. Setting: Swedish registers, 2005 to 2013. Participants: A PS-matched cohort of 16 668 adults (8334 who initiated statin use [6554 lipophilic and 1780 hydrophilic] and 8334 nonusers) among 63 279 eligible adults. Measurements: Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs). Results: Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], -4.8 percentage points [95% CI, -6.2 to -3.3 percentage points]; adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0%…

Background: Many people who inject drugs (PWID) are denied treatment for hepatitis C virus (HCV) infection, even if they are receiving opioid agonist therapy (OAT). Research suggests that HCV in PWID may be treated effectively, but optimal models of care for promoting adherence and sustained virologic response (SVR) have not been evaluated in the direct-acting antiviral (DAA) era. Objective: To determine whether directly observed therapy (DOT) and group treatment (GT) are more effective than self-administered individual treatment (SIT) in promoting adherence and achieving SVR among PWID receiving OAT. Design: Three-group, randomized controlled trial conducted from October 2013 to April 2017. (ClinicalTrials.gov: NCT01857245). Setting: Three OAT programs in Bronx, New York. Participants: Persons aged 18 years and older with genotype 1 HCV infection who were willing to receive HCV therapy on site in the OAT program. Of 190 persons screened, 158 were randomly assigned to a study group and 150 initiated treatment: DOT (n = 51), GT (n = 48), and SIT (n = 51). Intervention: 2 intensive…

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Few randomized trials have evaluated the effect of reducing red meat intake on clinically important outcomes. Purpose: To summarize the effect of lower versus higher red meat intake on the incidence of cardiometabolic and cancer outcomes in adults. Data Sources: EMBASE, CENTRAL, CINAHL, Web of Science, and ProQuest from inception to July 2018 and MEDLINE from inception to April 2019, without language restrictions. Study Selection: Randomized trials (published in any language) comparing diets lower in red meat with diets higher in red meat that differed by a gradient of at least 1 serving per week for 6 months or more. Data Extraction: Teams of 2 reviewers independently extracted data and assessed the risk of bias and the certainty of the evidence. Data Synthesis: Of 12 eligible trials, a single trial enrolling 48 835 women provided the most credible, though still low-certainty, evidence that diets lower in red meat may have little or no effect on all-cause mortality…

Letters3 September 2019Measles, Mumps, Rubella Vaccination and AutismAnders Hviid, DrMedSci, Jørgen Vinsløv Hansen, PhD, Morten Frisch, DrMedSci, and Mads Melbye, DrMedSciAnders Hviid, DrMedSciStatens Serum Institut, Copenhagen, Denmark (A.H., J.V.H., M.F., M.M.), Jørgen Vinsløv Hansen, PhDStatens Serum Institut, Copenhagen, Denmark (A.H., J.V.H., M.F., M.M.), Morten Frisch, DrMedSciStatens Serum Institut, Copenhagen, Denmark (A.H., J.V.H., M.F., M.M.), and Mads Melbye, DrMedSciStatens Serum Institut, Copenhagen, Denmark (A.H., J.V.H., M.F., M.M.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0383 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Mawson suggests that we should have compared the risk for autism between fully vaccinated and completely unvaccinated groups of children or between children who only received the MMR vaccine and their completely unvaccinated counterparts. Figure 3 of our article does compare the risk for autism in MMR-vaccinated and…