Showing papers in "Annals of Internal Medicine in 2015"

The PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions: Checklist and Explanations

Abstract: The PRISMA statement is a reporting guideline designed to improve the completeness of reporting of systematic reviews and meta-analyses. Authors have used this guideline worldwide to prepare their reviews for publication. In the past, these reports typically compared 2 treatment alternatives. With the evolution of systematic reviews that compare multiple treatments, some of them only indirectly, authors face novel challenges for conducting and reporting their reviews. This extension of the PRISMA (Preferred Reporting Items for Systematic Reviews and Metaanalyses) statement was developed specifically to improve the reporting of systematic reviews incorporating network meta-analyses.

Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): explanation and elaboration.

Abstract: The TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) Statement includes a 22-item checklist, which aims to improve the reporting of studies developing, validating, or updating a prediction model, whether for diagnostic or prognostic purposes. The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study regardless of the study methods used. This explanation and elaboration document describes the rationale; clarifies the meaning of each item; and discusses why transparent reporting is important, with a view to assessing risk of bias and clinical usefulness of the prediction model. Each checklist item of the TRIPOD Statement is explained in detail and accompanied by published examples of good reporting. The document also provides a valuable reference of issues to consider when designing, conducting, and analyzing prediction model studies. To aid the editorial process and help peer reviewers and, ultimately, readers and systematic reviewers of prediction model studies, it is recommended that authors include a completed checklist in their submission. The TRIPOD checklist can also be downloaded from www.tripod-statement.org.

Sedentary Time and Its Association With Risk for Disease Incidence, Mortality, and Hospitalization in Adults: A Systematic Review and Meta-analysis

Abstract: Background: The magnitude, consistency, and manner of association between sedentary time and outcomes independent of physical activity remain unclear. Purpose: To quantify the association between sedentary time and hospitalizations, all-cause mortality, cardiovascular disease, diabetes, and cancer in adults independent of physical activity. Data sources: English-language studies in MEDLINE, PubMed, EMBASE, CINAHL, Cochrane Library, Web of Knowledge, and Google Scholar databases were searched through August 2014 with hand-searching of in-text citations and no publication date limitations. Study selection: Studies assessing sedentary behavior in adults, adjusted for physical activity and correlated to at least 1 outcome. Data extraction: Two independent reviewers performed data abstraction and quality assessment, and a third reviewer resolved inconsistencies. Data synthesis: Forty-seven articles met our eligibility criteria. Meta-analyses were performed on outcomes for cardiovascular disease and diabetes (14 studies), cancer (14 studies), and all-cause mortality (13 studies). Prospective cohort designs were used in all but 3 studies; sedentary times were quantified using self-report in all but 1 study. Significant hazard ratio (HR) associations were found with all-cause mortality (HR, 1.240 [95% CI, 1.090 to 1.410]), cardiovascular disease mortality (HR, 1.179 [CI, 1.106 to 1.257]), cardiovascular disease incidence (HR, 1.143 [CI, 1.002 to 1.729]), cancer mortality (HR, 1.173 [CI, 1.108 to 1.242]), cancer incidence (HR, 1.130 [CI, 1.053 to 1.213]), and type 2 diabetes incidence (HR, 1.910 [CI, 1.642 to 2.222]). Hazard ratios associated with sedentary time and outcomes were generally more pronounced at lower levels of physical activity than at higher levels. Limitation: There was marked heterogeneity in research designs and the assessment of sedentary time and physical activity. Conclusion: Prolonged sedentary time was independently associated with deleterious health outcomes regardless of physical activity. Primary funding source: None.

Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD): The TRIPOD Statement

Abstract: Prediction models are developed to aid health care providers in estimating the probability or risk that a specific disease or condition is present (diagnostic models) or that a specific event will occur in the future (prognostic models), to inform their decision making. However, the overwhelming evidence shows that the quality of reporting of prediction model studies is poor. Only with full and clear reporting of information on all aspects of a prediction model can risk of bias and potential usefulness of prediction models be adequately assessed. The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for the reporting of studies developing, validating, or updating a prediction model, whether for diagnostic or prognostic purposes. This article describes how the TRIPOD Statement was developed. An extensive list of items based on a review of the literature was created, which was reduced after a Web-based survey and revised during a 3-day meeting in June 2011 with methodologists, health care professionals, and journal editors. The list was refined during several meetings of the steering group and in e-mail discussions with the wider group of TRIPOD contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed essential for transparent reporting of a prediction model study. The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study regardless of the study methods used. The TRIPOD Statement is best used in conjunction with the TRIPOD explanation and elaboration document. To aid the editorial process and readers of prediction model studies, it is recommended that authors include a completed checklist in their submission (also available at www.tripod-statement.org).

Sedentary Time and Its Association With Risk for Disease Incidence, Mortality, and Hospitalization in Adults

Abstract: Physical activity has many health-enhancing benefits, but it may not be enough to reduce the risk for disease and illness. This systematic review and meta-analysis evaluated the association between...

The Effectiveness and Risks of Long-Term Opioid Therapy for Chronic Pain: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop

Abstract: Prescriptions of opioid medications for chronic pain have increased dramatically, as have opioid overdoses, abuse, and other harms and uncertainty about long-term effectiveness This review found s

Platelet Transfusion: A Clinical Practice Guideline From the AABB

Abstract: Platelet transfusions are administered to prevent or treat bleeding in patients with quantitative or qualitative platelet disorders The AABB (formerly, the American Association of Blood Banks) dev

Cognitive Behavioral Therapy for Chronic Insomnia: A Systematic Review and Meta-analysis

Abstract: Background Because psychological approaches are likely to produce sustained benefits without the risk for tolerance or adverse effects associated with pharmacologic approaches, cognitive behavioral therapy for insomnia (CBT-i) is now commonly recommended as first-line treatment for chronic insomnia. Purpose To determine the efficacy of CBT-i on diary measures of overnight sleep in adults with chronic insomnia. Data sources Searches of MEDLINE, EMBASE, PsycINFO, CINAHL, the Cochrane Library, and PubMed Clinical Queries from inception to 31 March 2015, supplemented with manual screening. Study selection Randomized, controlled trials assessing the efficacy of face-to-face, multimodal CBT-i compared with inactive comparators on overnight sleep in adults with chronic insomnia. Studies of insomnia comorbid with medical, sleep, or psychiatric disorders were excluded. Data extraction Study characteristics, quality, and data were assessed independently by 2 reviewers. Main outcome measures were sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), and sleep efficiency (SE%). Data synthesis Among 292 citations and 91 full-text articles reviewed, 20 studies (1162 participants [64% female; mean age, 56 years]) were included. Approaches to CBT-i incorporated at least 3 of the following: cognitive therapy, stimulus control, sleep restriction, sleep hygiene, and relaxation. At the posttreatment time point, SOL improved by 19.03 (95% CI, 14.12 to 23.93) minutes, WASO improved by 26.00 (CI, 15.48 to 36.52) minutes, TST improved by 7.61 (CI, -0.51 to 15.74) minutes, and SE% improved by 9.91% (CI, 8.09% to 11.73%). Changes seemed to be sustained at later time points. No adverse outcomes were reported. Limitation Narrow inclusion criteria limited applicability to patients with comorbid insomnia and other sleep problems, and accuracy of estimates at later time points was less clear. Conclusion CBT-i is an effective treatment for adults with chronic insomnia, with clinically meaningful effect sizes. Primary funding source None. (PROSPERO registration number: CRD42012002863).

Adalimumab Induction Therapy for Crohn Disease Previously Treated with Infliximab

Abstract: Background: Adalimumab, a fully human tumor necrosis factor (TNF) antagonist, is an effective treatment for patients with Crohn disease who are naive to the chimeric TNF antagonist, infliximab. No anti-TNF agent has been evaluated prospectively in patients with Crohn disease who had responded to another anti-TNF agent and then lost that response or were intolerant of the agent. Objective: To determine whether adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who have symptoms despite infliximab therapy or who cannot take infliximab because of adverse events. Design: 4-week, randomized, double-blind, placebo-controlled trial (November 2004 to December 2005). Setting: 52 sites in the United States, Canada, and Europe. Patients: 325 adults 18 to 75 years of age who had a history of Crohn disease for 4 months or more that was moderate to severe at baseline (Crohn’s Disease Activity Index [CDAI] score, 220 to 450 points). Intervention: Patients were randomly assigned to receive induction doses of adalimumab, 160 mg and 80 mg, at weeks 0 and 2, respectively, or placebo at the same time points. Measurements: The primary end point was induction of remission at week 4. Decreases in CDAI score by 70 or more and 100 or more points (secondary end points) were also measured. Results: A total of 301 patients completed the trial. Twenty-one percent (34 of 159) of patients in the adalimumab group versus 7% (12 of 166) of those in the placebo group achieved remission at week 4 (P 0.001). The absolute difference in clinical remission rates was 14.2 percentage points (95% CI, 6.7 to 21.6 percentage points). A 70-point response occurred at week 4 in 52% (82 of 159) of patients in the adalimumab group versus 34% (56 of 166) of patients in the placebo group (P 0.001). The absolute difference in 70-point response rates was 17.8 percentage points (CI, 7.3 to 28.4 percentage points). Two of 159 patients in the adalimumab group and 4 of 166 patients in the placebo group discontinued treatment because of adverse events. No patients in the adalimumab group and 4 of 166 patients in the placebo group had a serious infection. Limitations: The trial did not directly compare alternative active treatments and did not evaluate maintenance of response or longterm immunogenicity of adalimumab. Conclusion: Adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who cannot tolerate infliximab or have symptoms despite receiving infliximab therapy.

Comparative Effectiveness of Pharmacologic Interventions for Knee Osteoarthritis: A Systematic Review and Network Meta-analysis

Abstract: Background The relative efficacy of available treatments of knee osteoarthritis (OA) must be determined for rational treatment algorithms to be formulated. Purpose To examine the efficacy of treatments of primary knee OA using a network meta-analysis design, which estimates relative effects of all treatments against each other. Data sources MEDLINE, EMBASE, Web of Science, Google Scholar, Cochrane Central Register of Controlled Trials from inception through 15 August 2014, and unpublished data. Study selection Randomized trials of adults with knee OA comparing 2 or more of the following: acetaminophen, diclofenac, ibuprofen, naproxen, celecoxib, intra-articular (IA) corticosteroids, IA hyaluronic acid, oral placebo, and IA placebo. Data extraction Two reviewers independently abstracted study data and assessed study quality. Standardized mean differences were calculated for pain, function, and stiffness at 3-month follow-up. Data synthesis Network meta-analysis was performed using a Bayesian random-effects model; 137 studies comprising 33,243 participants were identified. For pain, all interventions significantly outperformed oral placebo, with effect sizes from 0.63 (95% credible interval [CrI], 0.39 to 0.88) for the most efficacious treatment (hyaluronic acid) to 0.18 (CrI, 0.04 to 0.33) for the least efficacious treatment (acetaminophen). For function, all interventions except IA corticosteroids were significantly superior to oral placebo. For stiffness, most of the treatments did not significantly differ from one another. Limitation Lack of long-term data, inadequate reporting of safety data, possible publication bias, and few head-to-head comparisons. Conclusion This method allowed comparison of common treatments of knee OA according to their relative efficacy. Intra-articular treatments were superior to nonsteroidal anti-inflammatory drugs, possibly because of the integrated IA placebo effect. Small but robust differences were observed between active treatments. All treatments except acetaminophen showed clinically significant improvement from baseline pain. This information, along with the safety profiles and relative costs of included treatments, will be helpful for individualized patient care decisions. Primary funding source Agency for Healthcare Research and Quality.

Grazoprevir–Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial

Abstract: BACKGROUND Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection. OBJECTIVE To evaluate the safety and efficacy of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) in treatment-naive patients. DESIGN Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02105467). SETTING 60 centers in the United States, Europe, Australia, Scandinavia, and Asia. PATIENTS Cirrhotic and noncirrhotic treatment-naive adults with genotype 1, 4, or 6 infection. INTERVENTION Oral, once-daily, fixed-dose grazoprevir 100 mg/elbasvir 50 mg for 12 weeks, stratified by fibrosis and genotype. Patients were randomly assigned 3:1 to immediate or deferred therapy. MEASUREMENTS Proportion of patients in the immediate-treatment group achieving unquantifiable HCV RNA 12 weeks after treatment (SVR12); adverse events in both groups. RESULTS Among 421 participants, 194 (46%) were women, 157 (37%) were nonwhite, 382 (91%) had genotype 1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299 of 316 (95% [95% CI, 92% to 97%]) achieved SVR12, including 144 of 157 (92% [CI, 86% to 96%]) with genotype 1a, 129 of 131 (99% [CI, 95% to 100%]) with genotype 1b, 18 of 18 (100% [CI, 82% to 100%]) with genotype 4, 8 of 10 (80% [CI, 44% to 98%]) with genotype 6, 68 of 70 (97% [CI, 90% to 100%]) with cirrhosis, and 231 of 246 (94% [CI, 90% to 97%]) without cirrhosis. Virologic failure occurred in 13 patients (4%), including 1 case of breakthrough infection and 12 relapses, and was associated with baseline NS5A polymorphisms and emergent NS3 or NS5A variants or both. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo groups, respectively (difference <0.05 percentage point [CI, -5.4 to 3.1 percentage points]); none were considered drug related. The most common adverse events in the active group were headache (17%), fatigue (16%), and nausea (9%). LIMITATION The study lacked an active-comparator control group and included relatively few genotype 4 and 6 infections. CONCLUSION Grazoprevir-elbasvir achieved high SVR12 rates in treatment-naive cirrhotic and noncirrhotic patients with genotype 1, 4, or 6 infection. This once-daily, all-oral, fixed-combination regimen represents a potent new therapeutic option for chronic HCV infection. PRIMARY FUNDING SOURCE Merck & Co.

An analysis of calibration and discrimination among multiple cardiovascular risk scores in a modern multiethnic cohort.

Abstract: Accurate risk prediction is a vital component in the primary prevention of atherosclerotic cardiovascular disease. This study evaluated the performance of 4 commonly used risk prediction tools and ...

The Michigan Appropriateness Guide for Intravenous Catheters (MAGIC): Results From a Multispecialty Panel Using the RAND/UCLA Appropriateness Method

Abstract: Use of peripherally inserted central catheters (PICCs) has grown substantially in recent years. Increasing use has led to the realization that PICCs are associated with important complications, including thrombosis and infection. Moreover, some PICCs may not be placed for clinically valid reasons. Defining appropriate indications for insertion, maintenance, and care of PICCs is thus important for patient safety. An international panel was convened that applied the RAND/UCLA Appropriateness Method to develop criteria for use of PICCs. After systematic reviews of the literature, scenarios related to PICC use, care, and maintenance were developed according to patient population (for example, general hospitalized, critically ill, cancer, kidney disease), indication for insertion (infusion of peripherally compatible infusates vs. vesicants), and duration of use (≤5 days, 6 to 14 days, 15 to 30 days, or ≥31 days). Within each scenario, appropriateness of PICC use was compared with that of other venous access devices. After review of 665 scenarios, 253 (38%) were rated as appropriate, 124 (19%) as neutral/uncertain, and 288 (43%) as inappropriate. For peripherally compatible infusions, PICC use was rated as inappropriate when the proposed duration of use was 5 or fewer days. Midline catheters and ultrasonography-guided peripheral intravenous catheters were preferred to PICCs for use between 6 and 14 days. In critically ill patients, nontunneled central venous catheters were preferred over PICCs when 14 or fewer days of use were likely. In patients with cancer, PICCs were rated as appropriate for irritant or vesicant infusion, regardless of duration. The panel of experts used a validated method to develop appropriate indications for PICC use across patient populations. These criteria can be used to improve care, inform quality improvement efforts, and advance the safety of medical patients.

Screening for High Blood Pressure in Adults: U.S. Preventive Services Task Force Recommendation Statement

Abstract: This updated guideline from the U.S. Preventive Services Task Force addresses methods for and timing of hypertension screening in adults.

Restrictions for Medicaid Reimbursement of Sofosbuvir for the Treatment of Hepatitis C Virus Infection in the United States.

Abstract: The aim of this study was to systematically evaluate state Medicaid policies for the treatment of hepatitis C virus (HCV) infection with sofosbuvir in the United States. Medicaid reimbursement criteria for sofosbuvir were evaluated in all 50 states and the District of Columbia. The authors searched state Medicaid Web sites between 23 June and 7 December 2014 and extracted data in duplicate. Any differences were resolved by consensus. Data were extracted on whether sofosbuvir was covered and the criteria for coverage based on the following categories: liver disease stage, HIV co-infection, prescriber type, and drug or alcohol use. Of the 42 states with known Medicaid reimbursement criteria for sofosbuvir, 74% limit sofosbuvir access to persons with advanced fibrosis (Meta-Analysis of Histologic Data in Viral Hepatitis [METAVIR] fibrosis stage F3) or cirrhosis (F4). One quarter of states require persons co-infected with HCV and HIV to be receiving antiretroviral therapy or to have suppressed HIV RNA levels. Two thirds of states have restrictions based on prescriber type, and 88% include drug or alcohol use in their sofosbuvir eligibility criteria, with 50% requiring a period of abstinence and 64% requiring urine drug screening. Heterogeneity is present in Medicaid reimbursement criteria for sofosbuvir with respect to liver disease staging, HIV co-infection, prescriber type, and drug or alcohol use across the United States. Restrictions do not seem to conform with recommendations from professional organizations, such as the Infectious Diseases Society of America and the American Association for the Study of Liver Diseases. Current restrictions seem to violate federal Medicaid law, which requires states to cover drugs consistent with their U.S. Food and Drug Administration labels.

Normal-Weight Central Obesity: Implications for Total and Cardiovascular Mortality

Abstract: Whether measures of central obesity, such as waist-to-hip ratio (WHR), provide additional information beyond body mass index (BMI) in defining mortality risks is unclear. This study examined data f...

Behavioral and Pharmacotherapy Interventions for Tobacco Smoking Cessation in Adults, Including Pregnant Women: U.S. Preventive Services Task Force Recommendation Statement.

Abstract: This guideline from the U.S. Preventive Services Task Force addresses behavioral and pharmacotherapy interventions for tobacco smoking cessation in adults, including pregnant women.

Combination antifungal therapy for invasive aspergillosis a randomized trial

Abstract: Background Invasive aspergillosis (IA) is associated with poor outcomes in patients with hematologic malignancies (HMs) and hematopoietic cell transplantation (HCT). Small studies suggest a role for combination antifungal therapy. Objective To assess the safety and efficacy of voriconazole and anidulafungin compared with voriconazole monotherapy for treatment of IA. Design Randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov: NCT00531479). Setting 93 international sites. Patients 454 patients with HM or HCT and suspected or documented IA were randomly assigned to treatment with voriconazole and anidulafungin or placebo. Primary analysis was done in the modified intention-to-treat population of 277 patients in whom IA was confirmed. Measurements The primary outcome was 6-week mortality; secondary outcomes included 12-week mortality, mortality in major subgroups, and safety measures. Results Mortality rates at 6 weeks were 19.3% (26 of 135) for combination therapy and 27.5% (39 of 142) for monotherapy (difference, -8.2 percentage points [95% CI, -19.0 to 1.5]; P = 0.087). Secondary mortality outcomes favored combination therapy. Multivariable regression analysis suggested that maximum galactomannan value, Karnofsky score, and baseline platelet count had prognostic significance. Most patients (218 of 277 [78.7%]) had IA diagnosis established by radiographic findings and maximum galactomannan positivity. In a post hoc analysis of this dominant subgroup, 6-week mortality was lower in combination therapy than monotherapy (15.7% [17 of 108] vs. 27.3% [30 of 110]; difference, -11.5 percentage points [CI, -22.7 to -0.4]; P = 0.037). Safety measures, including hepatotoxicity, were not different. Limitations Mortality at 6 weeks was higher than expected, and the difference in mortality was lower than expected, which reduced power to detect a treatment effect. Enrollment was restricted to patients with HM or HCT, which limited generalizability. Conclusion Compared with voriconazole monotherapy, combination therapy with anidulafungin led to higher survival in subgroups of patients with IA. Limitations in power preclude definitive conclusions about superiority. Primary funding source Pfizer.

Cigarette Smoking Prevalence Among Adults With HIV Compared With the General Adult Population in the United States: Cross-sectional Surveys

Abstract: Background: The negative health effects of cigarette smoking and HIV infection are synergistic. Objective: To compare the prevalence of current cigarette smoking and smoking cessation between adults with HIV receiving medical care and adults in the general population. Design: Nationally representative cross-sectional surveys. Setting: United States. Patients: 4217 adults with HIV who participated in the Medical Monitoring Project and 27 731 U.S. adults who participated in the National Health Interview Survey in 2009. Measurements: The main exposure was cigarette smoking. The outcome measures were weighted prevalence of cigarette smoking and quit ratio (ratio of former smokers to the sum of former and current smokers). Results: Of the estimated 419 945 adults with HIV receiving medical care, 42.4% (95% CI, 39.7% to 45.1%) were current cigarette smokers, 20.3% (CI, 18.6% to 22.1%) were former smokers, and 37.3% (CI, 34.9% to 39.6%) had never smoked. Compared with the U.S. adult population, in which an estimated 20.6% of adults smoked cigarettes in 2009, adults with HIV were nearly twice as likely to smoke (adjusted prevalence difference, 17.0 percentage points [CI, 14.0 to 20.1 percentage points]) but were less likely to quit smoking (quit ratio, 32.4% vs. 51.7%). Among adults with HIV, factors independently associated with greater smoking prevalence were older age, non-Hispanic white or non-Hispanic black race, lower educational level, poverty, homelessness, incarceration, substance use, binge alcohol use, depression, and not achieving a suppressed HIV viral load. Limitation: Cross-sectional design with some generalizability limitations. Conclusion: Adults with HIV were more likely to smoke and less likely to quit smoking than the general adult population. Tobacco screening and cessation strategies are important considerations as part of routine HIV care.

Predictors of Pregnancy Outcomes in Patients With Lupus: A Cohort Study

Abstract: Background Since systemic lupus erythematosus (SLE) affects women of reproductive age, pregnancy is a major concern

Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis.

Abstract: BACKGROUND Guidelines recommend statins as first-line therapy for dyslipidemia. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new lipid-lowering approach. PURPOSE To assess the efficacy and safety of PCSK9 antibodies in adults with hypercholesterolemia. DATA SOURCES MEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through 4 April 2015. STUDY SELECTION Phase 2 or 3 randomized, controlled trials (RCTs) comparing treatment using PCSK9 antibodies with no anti-PCSK9 therapy in adults with hypercholesterolemia. DATA EXTRACTION Two investigators independently extracted data on study characteristics and lipid and clinical outcomes, and rated risk of bias of trials. Prespecified primary end points were all-cause and cardiovascular mortality. DATA SYNTHESIS Twenty-four RCTs comprising 10 159 patients were included. Compared with no antibody, treatment with PCSK9 antibodies led to marked reductions in low-density lipoprotein cholesterol levels (mean difference, -47.49% [95% CI, -69.64% to -25.35%]; P < 0.001] and other atherogenic lipid fractions, and it reduced all-cause mortality (odds ratio [OR], 0.45 [CI, 0.23 to 0.86]; P = 0.015; heterogeneity P = 0.63; I2 = 0%) and cardiovascular mortality (OR, 0.50 [CI, 0.23 to 1.10]; P = 0.084; heterogeneity P = 0.78; I2 = 0%). The rate of myocardial infarction was significantly reduced with use of PCSK9 antibodies (OR, 0.49 [CI, 0.26 to 0.93]; P = 0.030; heterogeneity P = 0.45; I2 = 0%), and increases in the serum creatine kinase level were reduced (OR, 0.72 [CI, 0.54 to 0.96]; P = 0.026; heterogeneity P = 0.65; I2 = 0%). Serious adverse events did not increase with administration of PCSK9 antibodies. LIMITATION Results were derived from study-level data rather than patient-level data, and clinical outcome data are rare. CONCLUSION PCSK9 antibodies seem to be safe and effective for adults with dyslipidemia. PRIMARY FUNDING SOURCE CRC 1116 Masterswitches in Myocardial Ischemia, German Research Council DFG.

Performance of Lung-RADS in the National Lung Screening Trial: a retrospective assessment.

Abstract: The definitions used to classify low-dose computed tomography findings may markedly influence the benefits and harms of lung cancer screening. This analysis of data from a large screening trial fou...

Cost-Effectiveness and Budget Impact of Hepatitis C Virus Treatment With Sofosbuvir and Ledipasvir in the United States

Abstract: Background The recently approved drugs, sofosbuvir and ledipasvir, for chronic hepatitis C virus (HCV) treatment are more efficacious and safer but are substantially more expensive than the old standard-of-care (oSOC). It remains unclear whether and in which patients their improved efficacy justifies their increased cost.

Diagnostic and Predictive Accuracy of Blood Pressure Screening Methods With Consideration of Rescreening Intervals: A Systematic Review for the U.S. Preventive Services Task Force

Abstract: This systematic review for the U.S. Preventive Services Task Force evaluates the benefits and harms of screening for high blood pressure (BP) in adults and summarizes evidence on screening interval...

Fecal microbiota transplantation for clostridium difficile infection a systematic review

Abstract: BACKGROUND The role of fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) is not well-known. PURPOSE To assess the efficacy, comparative effectiveness, and harms of FMT for CDI. DATA SOURCES MEDLINE (1980 to January 2015), Cochrane Library, and ClinicalTrials.gov, followed by hand-searching references from systematic reviews and identified studies. STUDY SELECTION Any study of FMT to treat adult patients with CDI; case reports were only used to report harms. DATA EXTRACTION Data were extracted by 1 author and verified by another; 2 authors independently assessed risk of bias and strength of evidence. DATA SYNTHESIS Two randomized, controlled trials (RCTs); 28 case-series studies; and 5 case reports were included. Two RCTs and 21 case-series studies (516 patients receiving FMT) reported using FMT for patients with recurrent CDI. A high proportion of treated patients had symptom resolution; however, the role of previous antimicrobials is unclear. One RCT comparing FMT with 2 control groups (n = 43) reported resolution of symptoms in 81%, 31%, and 23% of the FMT, vancomycin, or vancomycin-plus-bowel lavage groups, respectively (P < 0.001 for both control groups vs. FMT). An RCT comparing FMT route (n = 20) reported no difference between groups (60% in the nasogastric tube group and 80% in the colonoscopy group; P = 0.63). Across all studies for recurrent CDI, symptom resolution was seen in 85% of cases. In 7 case-series studies of patients with refractory CDI, symptom resolution ranged from 0% to 100%. Among 7 patients treated with FMT for initial CDI, results were mixed. LIMITATION Most studies were uncontrolled case-series studies; only 2 RCTs were available for analysis. CONCLUSION Fecal microbiota transplantation may have a substantial effect with few short-term adverse events for recurrent CDI. Evidence is insufficient on FMT for refractory or initial CDI treatment and on whether effects vary by donor, preparation, or delivery method. PRIMARY FUNDING SOURCE U.S. Department of Veterans Affairs.

Combined Diet and Physical Activity Promotion Programs to Prevent Type 2 Diabetes Among Persons at Increased Risk: A Systematic Review for the Community Preventive Services Task Force

Abstract: Background Trials have demonstrated the efficacy of rigorous diet and physical activity promotion (D&PA) programs for adults at increased risk for type 2 diabetes to reduce diabetes incidence and improve measures of glycemia.

Rapid-Response Systems as a Patient Safety Strategy

Abstract: Rapid-response systems (RRSs) are a popular intervention in U.S. hospitals and are supported by accreditors and quality improvement organizations. The purpose of this review is to evaluate the effe...

Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3

Abstract: The Good Publication Practice (GPP) guideline provides recommendations for individuals and organizations that contribute to the publication of research results sponsored or supported by pharmaceuti...

Efficacy of Commercial Weight-Loss Programs: An Updated Systematic Review

Abstract: BACKGROUND Commercial and proprietary weight-loss programs are popular obesity treatment options, but their efficacy is unclear. PURPOSE To compare weight loss, adherence, and harms of commercial or proprietary weight-loss programs versus control/education (no intervention, printed materials only, health education curriculum, or <3 sessions with a provider) or behavioral counseling among overweight and obese adults. DATA SOURCES MEDLINE and the Cochrane Database of Systematic Reviews from inception to November 2014; references identified by program staff. STUDY SELECTION Randomized, controlled trials (RCTs) of at least 12 weeks' duration; prospective case series of at least 12 months' duration (harms only). DATA EXTRACTION Two reviewers extracted information on study design, population characteristics, interventions, and mean percentage of weight change and assessed risk of bias. DATA SYNTHESIS We included 45 studies, 39 of which were RCTs. At 12 months, Weight Watchers participants achieved at least 2.6% greater weight loss than those assigned to control/education. Jenny Craig resulted in at least 4.9% greater weight loss at 12 months than control/education and counseling. Nutrisystem resulted in at least 3.8% greater weight loss at 3 months than control/education and counseling. Very-low-calorie programs (Health Management Resources, Medifast, and OPTIFAST) resulted in at least 4.0% greater short-term weight loss than counseling, but some attenuation of effect occurred beyond 6 months when reported. Atkins resulted in 0.1% to 2.9% greater weight loss at 12 months than counseling. Results for SlimFast were mixed. We found limited evidence to evaluate adherence or harms for all programs and weight outcomes for other commercial programs. LIMITATION Many trials were short (<12 months), had high attrition, and lacked blinding. CONCLUSION Clinicians could consider referring overweight or obese patients to Weight Watchers or Jenny Craig. Other popular programs, such as Nutrisystem, show promising weight-loss results; however, additional studies evaluating long-term outcomes are needed. PRIMARY FUNDING SOURCE None. ( PROSPERO CRD4201-4007155).