Showing papers in "Annals of Internal Medicine in 2013"

SPIRIT 2013 statement: defining standard protocol items for clinical trials.

Abstract: The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline.

Abstract: The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed clinical practice guidelines in 2012 to provide guidance on the evaluation, management, and treatment of chronic kidney ...

Assessing Bias in Studies of Prognostic Factors

Abstract: Previous work has identified 6 important areas to consider when evaluating validity and bias in studies of prognostic factors: participation, attrition, prognostic factor measurement, confounding measurement and account, outcome measurement, and analysis and reporting. This article describes the Quality In Prognosis Studies tool, which includes questions related to these areas that can inform judgments of risk of bias in prognostic research.A working group comprising epidemiologists, statisticians, and clinicians developed the tool as they considered prognosis studies of low back pain. Forty-three groups reviewing studies addressing prognosis in other topic areas used the tool and provided feedback. Most reviewers (74%) reported that reaching consensus on judgments was easy. Median completion time per study was 20 minutes; interrater agreement (κ statistic) reported by 9 review teams varied from 0.56 to 0.82 (median, 0.75). Some reviewers reported challenges making judgments across prompting items, which were addressed by providing comprehensive guidance and examples. The refined Quality In Prognosis Studies tool may be useful to assess the risk of bias in studies of prognostic factors.

Are Metabolically Healthy Overweight and Obesity Benign Conditions?: A Systematic Review and Meta-analysis

Abstract: Recent interest has focused on a unique subgroup of overweight and obese individuals who have normal metabolic features despite increased adiposity. Normal-weight individuals with adverse metabolic status have also been described. However, it remains unclear whether metabolic phenotype modifies the morbidity and mortality associated with higher body mass index (BMI).

Conceptual and Technical Challenges in Network Meta-analysis

Abstract: The increase in treatment options creates an urgent need for comparative effectiveness research. Randomized, controlled trials comparing several treatments are usually not feasible, so other methodological approaches are needed. Meta-analyses provide summary estimates of treatment effects by combining data from many studies. However, an important drawback is that standard meta-analyses can compare only 2 interventions at a time. A new meta-analytic technique, called network meta-analysis (or multiple treatments meta-analysis or mixed-treatment comparison), allows assessment of the relative effectiveness of several interventions, synthesizing evidence across a network of randomized trials. Despite the growing prevalence and influence of network meta-analysis in many fields of medicine, several issues need to be addressed when constructing one to avoid conclusions that are inaccurate, invalid, or not clearly justified. This article explores the scope and limitations of network meta-analysis and offers advice on dealing with heterogeneity, inconsistency, and potential sources of bias in the available evidence to increase awareness among physicians about some of the challenges in interpretation.

Sodium–Glucose Cotransporter 2 Inhibitors for Type 2 Diabetes: A Systematic Review and Meta-analysis

Abstract: Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs. Purpose To assess the efficacy and safety of SGLT2 inhibitors in adults with type 2 diabetes. Data sources MEDLINE, EMBASE, and the Cochrane Library from inception through April 2013 without language restrictions; regulatory authorities' reports; and gray literature. Study selection Randomized trials comparing SGLT2 inhibitors with placebo or other medication for type 2 diabetes. Data extraction Three reviewers extracted or checked data for study characteristics, outcomes of interest, and risk of bias, and 3 reviewers summarized strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Data synthesis Sodium-glucose cotransporter 2 inhibitors were compared with placebo in 45 studies (n = 11 232) and with active comparators in 13 studies (n = 5175). They had a favorable effect on hemoglobin A1c level (mean difference vs. placebo, -0.66% [95% CI, -0.73% to -0.58%]; mean difference vs. active comparators, -0.06% [CI, -0.18% to 0.05%]). Sensitivity analyses incorporating unpublished data showed similar effect estimates. Compared with other agents, SGLT2 inhibitors reduced body weight (mean difference, -1.80 kg [CI, -3.50 to -0.11 kg]) and systolic blood pressure (mean difference, -4.45 mm Hg [CI, -5.73 to -3.18 mm Hg]). Urinary and genital tract infections were more common with SGLT2 inhibitors (odds ratios, 1.42 [CI, 1.06 to 1.90] and 5.06 [CI, 3.44 to 7.45], respectively). Hypoglycemic risk was similar to that of other agents. Results for cardiovascular outcomes and death were inconclusive. An imbalance in incidence of bladder and breast cancer was noted with dapagliflozin compared with control. Limitation Most trials were rated as high risk of bias because of missing data and last-observation-carried-forward methods. Conclusion Sodium-glucose cotransporter 2 inhibitors may improve short-term outcomes in adults with type 2 diabetes, but effects on long-term outcomes and safety are unclear. Primary funding source None.

Eradication of Hepatitis C Virus Infection and the Development of Hepatocellular Carcinoma: A Meta-analysis of Observational Studies

Abstract: Background Hepatitis C virus (HCV) is a leading cause of hepatocellular carcinoma (HCC). In the United States, this form of cancer occurs in approximately 15 000 persons annually. A systematic review of the evidence is needed to assess the benefits of treatment of HCV-infected persons on development of HCC. Purpose To systematically review observational studies to determine the association between response to HCV therapy and development of HCC among persons at any stage of fibrosis and those with advanced liver disease. Data sources MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science, and the Database of Abstracts of Reviews and Effectiveness from inception through February 2012. Study selection English-language observational studies that compared therapy-derived sustained virologic response (SVR) with no response to therapy among HCV-infected persons, targeted an adult population, and had an average follow-up of at least 2 years. Data extraction Two investigators independently extracted data into uniform relative risk measures. The Grading of Recommendations Assessment, Development and Evaluation framework was used to determine the quality of the evidence. Data synthesis Thirty studies fulfilled the inclusion criteria, and 18 provided adjusted effect estimates that were used to calculate pooled relative risks. Among HCV-infected persons, SVR was associated with reduced risk for HCC (relative risk for all persons, 0.24 [95% CI, 0.18 to 0.31], moderate-quality evidence; advanced liver disease hazard ratio, 0.23 [CI, 0.16 to 0.35], moderate-quality evidence). Limitation In the meta-analyses, some variables could not be controlled for because of the observational design of the included studies. Conclusion Sustained virologic response after treatment among HCV-infected persons at any stage of fibrosis is associated with reduced HCC. The evidence was determined to be of moderate quality.

Eradication of Hepatitis C Virus Infection and the Development of Hepatocellular Carcinoma

Abstract: Hepatitis C virus (HCV) is a leading cause of hepatocellular carcinoma (HCC). This systematic review summarized moderate-quality evidence from 30 observational studies examining the risk for HCC am...

The Patient-Centered Medical Home: A Systematic Review

Abstract: The patient-centered medical home (PCMH) model seeks to meet the health care needs of patients and improve patient and staff experiences, outcomes, safety, and system efficiency. This review of PCM...

Opportunistic Screening for Osteoporosis Using Abdominal Computed Tomography Scans Obtained for Other Indications

Abstract: Osteoporosis is prevalent and treatable and conveys a considerable lifetime fracture risk, yet it remains substantially underdiagnosed and undertreated (1-4). Currently, nearly half of all female Medicare beneficiaries have never undergone bone mineral density (BMD) testing (5), and more than 80% of all persons with a major osteoporosis-related fracture do not have BMD testing or receive pharmacologic agents to reduce fracture risk (6). Furthermore, because normal BMD and mild osteopenia confer a very low risk for osteoporosis (7), efficient and cost-effective stratification of the unscreened population into groups at low and high risk for osteoporosis and fractures is desirable. Central dual-energy x-ray absorptiometry (DXA) of the hips and lumbar spine is widely recognized as the reference standard for diagnosing osteoporosis (8, 9), but it is underutilized. Safe and cost-effective alternatives to increase detection of this condition are needed. More than 80 million computed tomography (CT) scans were performed in the United States in 2011 (10), most of which carry potentially useful information about BMD. Retrieval of BMD data available on body CT examinations ordered for other indications requires no additional cost, patient time, equipment, software, or radiation exposure, and these data can be retrospectively acquired. It could therefore expand population screening efforts for osteoporosis. In a recent feasibility study of adults who underwent osteoporosis screening with DXA and colorectal cancer screening with CT colonography, we showed that a single CT measurement of vertebral attenuation was equivalent to the more complex dedicated quantitative CT (QCT) assessment but was considerably easier to obtain (10). The purpose of this study was to evaluate CT-derived BMD assessment compared with DXA screening by using CT scans that were performed for other clinical indications in a larger patient population, focusing on the L1 level because it is easily identified as the first non-rib-bearing vertebra and is included on all abdominal and thoracic CT scans in routine practice.

Discontinuation of statins in routine care settings: a cohort study.

Abstract: Background Systematic data on discontinuation of statins in routine practice of medicine are limited. Objective To investigate the reasons for statin discontinuation and the role of statin-related events (clinical events or symptoms believed to have been caused by statins) in routine care settings. Design A retrospective cohort study. Setting Practices affiliated with Brigham and Women's Hospital and Massachusetts General Hospital in Boston. Patients Adults who received a statin prescription between 1 January 2000 and 31 December 2008. Measurements Information on reasons for statin discontinuations was obtained from a combination of structured electronic medical record entries and analysis of electronic provider notes by validated software. Results Statins were discontinued at least temporarily for 57 292 of 107 835 patients. Statin-related events were documented for 18 778 (17.4%) patients. Of these, 11 124 had statins discontinued at least temporarily; 6579 were rechallenged with a statin over the subsequent 12 months. Most patients who were rechallenged (92.2%) were still taking a statin 12 months after the statin-related event. Among the 2721 patients who were rechallenged with the same statin to which they had a statin-related event, 1295 were receiving the same statin 12 months later, and 996 of them were receiving the same or a higher dose. Limitations Statin discontinuations and statin-related events were assessed in practices affiliated with 2 academic medical centers. Utilization of secondary data could have led to missing or misinterpreted data. Natural-language-processing tools used to compensate for the low (30%) proportion of reasons for statin discontinuation documented in structured electronic medical record fields are not perfectly accurate. Conclusion Statin-related events are commonly reported and often lead to statin discontinuation. However, most patients who are rechallenged can tolerate statins long-term. This suggests that many of the statin-related events may have other causes, are tolerable, or may be specific to individual statins rather than the entire drug class. Primary funding source National Library of Medicine, Diabetes Action Research and Education Foundation, and Chinese National Key Program of Clinical Science.

Promoting a culture of safety as a patient safety strategy: a systematic review.

Abstract: Developing a culture of safety is a core element of many efforts to improve patient safety and care quality. This systematic review identifies and assesses interventions used to promote safety culture or climate in acute care settings. The authors searched MEDLINE, CINAHL, PsycINFO, Cochrane, and EMBASE to identify relevant English-language studies published from January 2000 to October 2012. They selected studies that targeted health care workers practicing in inpatient settings and included data about change in patient safety culture or climate after a targeted intervention. Two raters independently screened 3679 abstracts (which yielded 33 eligible studies in 35 articles), extracted study data, and rated study quality and strength of evidence. Eight studies included executive walk rounds or interdisciplinary rounds; 8 evaluated multicomponent, unit-based interventions; and 20 included team training or communication initiatives. Twenty-nine studies reported some improvement in safety culture or patient outcomes, but measured outcomes were highly heterogeneous. Strength of evidence was low, and most studies were pre-post evaluations of low to moderate quality. Within these limits, evidence suggests that interventions can improve perceptions of safety culture and potentially reduce patient harm.

Screening for Lung Cancer With Low-Dose Computed Tomography: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation

Abstract: Early-stage lung cancer is associated with lower mortality than late-stage disease; thus, early detection and treatment may be beneficial. This systematic review updates evidence on the effectivene...

Screening for Hepatitis C Virus Infection in Adults: U.S. Preventive Services Task Force Recommendation Statement

Abstract: The USPSTF now recommends screening for hepatitis C virus (HCV) infection in all asymptomatic persons at high risk for infection and recommends offering 1-time screening for adults born between 194...

Management of Obstructive Sleep Apnea in Adults: A Clinical Practice Guideline From the American College of Physicians

Abstract: In this guideline on the diagnosis of obstructive sleep apnea in adults, the American College of Physicians recommends a sleep study for patients with unexplained daytime sleepiness, polysomnograph...

Treatment of idiopathic pulmonary fibrosis with Ambrisentan: A parallel, randomized trial

Abstract: BACKGROUND Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor. OBJECTIVE To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression. DESIGN Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300). SETTING Academic and private hospitals. PARTICIPANTS Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans. INTERVENTION Ambrisentan, 10 mg/d, or placebo. MEASUREMENTS Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function. RESULTS The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point. LIMITATION The study was terminated early. CONCLUSION Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations. PRIMARY FUNDING SOURCE Gilead Sciences.

GeoSentinel Surveillance of Illness in Returned Travelers, 2007–2011

Abstract: Background International travel continues to increase, particularly to Asia and Africa. Clinicians are increasingly likely to be consulted for advice before travel or by ill returned travelers.

Medication Reconciliation During Transitions of Care as a Patient Safety Strategy: A Systematic Review

Abstract: Medication reconciliation identifies and resolves unintentional discrepancies between patients' medication lists across transitions in care. The purpose of this review is to summarize evidence about the effectiveness of hospital-based medication reconciliation interventions. Searches encompassed MEDLINE through November 2012 and EMBASE and the Cochrane Central Register of Controlled Trials through July 2012. Eligible studies evaluated the effects of hospital-based medication reconciliation on unintentional discrepancies with nontrivial risks for harm to patients or 30-day postdischarge emergency department visits and readmission. Two reviewers evaluated study eligibility, abstracted data, and assessed study quality. Eighteen studies evaluating 20 interventions met the selection criteria. Pharmacists performed medication reconciliation in 17 of the 20 interventions. Most unintentional discrepancies identified had no clinical significance. Medication reconciliation alone probably does not reduce postdischarge hospital utilization but may do so when bundled with interventions aimed at improving care transitions.

Mortality After Prison Release: Opioid Overdose and Other Causes of Death, Risk Factors, and Time Trends From 1999 to 2009

Abstract: Former prisoners are at increased risk for death, particularly from drug-related causes. Researchers documented that, in Washington state from 1999 to 2009, the leading cause of death after prison ...

Lifestyle Interventions for Patients With and at Risk for Type 2 Diabetes: A Systematic Review and Meta-analysis

Abstract: BACKGROUND The effect of multifaceted lifestyle interventions on clinically oriented outcomes across a spectrum of metabolic risk factors and abnormal glucose is unclear. PURPOSE To systematically review the effectiveness of lifestyle interventions on minimizing progression to diabetes in high-risk patients or progression to clinical outcomes (such as cardiovascular disease and death) in patients with type 2 diabetes. DATA SOURCES 5 electronic databases (1980 to June 2013), reference lists, and gray literature. STUDY SELECTION Two reviewers independently identified randomized, controlled trials of lifestyle interventions (≥3 months' duration) that included exercise, diet, and at least 1 other component; the comparator was standard care. DATA EXTRACTION One reviewer extracted and a second verified data. Two reviewers independently assessed methodological quality. DATA SYNTHESIS Nine randomized, controlled trials with patients who were at risk for diabetes and 11 with patients who had diabetes were included. Seven studies reported that lifestyle interventions decreased the risk for diabetes from the end of intervention up to 10 years after it. In patients with diabetes, 2 randomized, controlled trials (which included pharmacotherapy) reported no improvement in all-cause mortality (risk ratio, 0.75 [95% CI, 0.53 to 1.06]). Composite outcomes for cardiovascular disease were too heterogeneous to pool. One trial reported improvement in microvascular outcomes at 13-year follow-up. LIMITATION Most trials focused on surrogate measures (such as weight change, blood pressure, and lipids) for which clinical relevance was unclear. CONCLUSION Comprehensive lifestyle interventions effectively decrease the incidence of type 2 diabetes in high-risk patients. In patients who already have type 2 diabetes, there is no evidence of reduced all-cause mortality and insufficient evidence to suggest benefit on cardiovascular and microvascular outcomes. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion: a systematic review and meta-analysis

Abstract: Background Recombinant human bone morphogenetic protein-2 (rhBMP-2) is used as a bone graft substitute in spinal fusion, which unites (fuses) bones in the spine. The accuracy and completeness of journal publications of industry-sponsored trials on the effectiveness and harms of rhBMP-2 has been called into question. Purpose To independently assess the effectiveness and harms of rhBMP-2 in spinal fusion and reporting bias in industry-sponsored journal publications. Data sources Individual-patient data (IPD) from 17 industry-sponsored studies; related internal documents; and searches of MEDLINE (1996 to August 2012), other databases, and reference lists. Study selection Randomized, controlled trials (RCTs) and cohort studies of rhBMP-2 versus any control and uncontrolled studies of harms. Data extraction Effectiveness outcomes in IPD were recalculated using consistent definitions. Study characteristics and results were abstracted by 1 investigator and confirmed by another. Two investigators independently assessed quality using predefined criteria. Data synthesis Thirteen RCTs and 31 cohort studies were included. For lumbar spine fusion, rhBMP-2 and iliac crest bone graft were similar in overall success, fusion, and other effectiveness measures and in risk for any adverse event, although rates were high across interventions (77% to 93% at 24 months from surgery). For anterior lumbar interbody fusion, rhBMP-2 was associated with nonsignificantly increased risk for retrograde ejaculation and urogenital problems. For anterior cervical spine fusion, rhBMP-2 was associated with increased risk for wound complications and dysphagia. At 24 months, the cancer risk was increased with rhBMP-2 (risk ratio, 3.45 [95% CI, 1.98 to 6.00]), but event rates were low and cancer was heterogeneous. Early journal publications misrepresented the effectiveness and harms through selective reporting, duplicate publication, and underreporting. Limitations Outcome assessment was not blinded, and ascertainment of harms in trials was poor. No trials were truly independent of industry sponsorship. Conclusion In spinal fusion, rhBMP-2 has no proven clinical advantage over bone graft and may be associated with important harms, making it difficult to identify clear indications for rhBMP-2. Earlier disclosure of all relevant data would have better informed clinicians and the public than the initial published trial reports did. Primary funding source Yale University and Medtronic.

Screening and Behavioral Counseling Interventions in Primary Care to Reduce Alcohol Misuse: U.S. Preventive Services Task Force Recommendation Statement

Abstract: Description: Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening and behavioral counseling interventions in primary care to reduce alcohol misuse. Methods: The USPSTF reviewed new evidence on the effectiveness of screening for alcohol misuse for improving health outcomes, the accuracy of various screening approaches, the effectiveness of various behavioral counseling interventions for improving intermediate or long-term health outcomes, the harms of screening and behavioral counseling interventions, and influences from the health care system that promote or detract from effective screening and counseling interventions for alcohol misuse. Population: These recommendations apply to adolescents aged 12 to 17 years and adults aged 18 years or older. These recommendations do not apply to persons who are actively seeking evaluation or treatment of alcohol misuse. Recommendation: The USPSTF recommends that clinicians screen adults aged 18 years or older for alcohol misuse and provide persons engaged in risky or hazardous drinking with brief behavioral counseling interventions to reduce alcohol misuse. (Grade B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening and behavioral counseling interventions in primary care settings to reduce alcohol misuse in adolescents. (I statement)

Electronic Patient Portals: Evidence on Health Outcomes, Satisfaction, Efficiency, and Attitudes

Abstract: Patient portals tied to electronic health record systems give patients secure access to health information and methods for communication and information sharing. This systematic review found mixed ...

Electronic Patient Portals: Evidence on Health Outcomes, Satisfaction, Efficiency, and Attitudes: A Systematic Review

Abstract: Background Patient portals tied to provider electronic health record (EHR) systems are increasingly popular. Purpose To systematically review the literature reporting the effect of patient portals on clinical care. Data sources PubMed and Web of Science searches from 1 January 1990 to 24 January 2013. Study selection Hypothesis-testing or quantitative studies of patient portals tethered to a provider EHR that addressed patient outcomes, satisfaction, adherence, efficiency, utilization, attitudes, and patient characteristics, as well as qualitative studies of barriers or facilitators, were included. Data extraction Two reviewers independently extracted data and addressed discrepancies through consensus discussion. Data synthesis From 6508 titles, 14 randomized, controlled trials; 21 observational, hypothesis-testing studies; 5 quantitative, descriptive studies; and 6 qualitative studies were included. Evidence is mixed about the effect of portals on patient outcomes and satisfaction, although they may be more effective when used with case management. The effect of portals on utilization and efficiency is unclear, although patient race and ethnicity, education level or literacy, and degree of comorbid conditions may influence use. Limitation Limited data for most outcomes and an absence of reporting on organizational and provider context and implementation processes. Conclusion Evidence that patient portals improve health outcomes, cost, or utilization is insufficient. Patient attitudes are generally positive, but more widespread use may require efforts to overcome racial, ethnic, and literacy barriers. Portals represent a new technology with benefits that are still unclear. Better understanding requires studies that include details about context, implementation factors, and cost.

Screening for HIV: U.S. Preventive Services Task Force Recommendation Statement

Abstract: The recommendations from the U.S. Preventive Services Task Force recommend screening for HIV infection in all adolescents and adults aged 15 to 65 years, younger adolescents and older adults who ha...

Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial.

Abstract: BACKGROUND Many patients with rheumatoid arthritis (RA) do not achieve adequate and safe responses with disease-modifying antirheumatic drugs (DMARDs). Tofacitinib is a novel, oral, Janus kinase inhibitor that treats RA. OBJECTIVE To evaluate the efficacy and safety of tofacitinib in combination with nonbiologic DMARDs. DESIGN 1-year, double-blind, randomized trial (ClinicalTrials.gov: NCT00856544). SETTING 114 centers in 19 countries. PATIENTS 792 patients with active RA despite nonbiologic DMARD therapy. INTERVENTION Patients were randomly assigned 4:4:1:1 to oral tofacitinib, 5 mg or 10 mg twice daily, or placebo advanced to tofacitinib, 5 mg or 10 mg twice daily. MEASUREMENTS Primary end points were 20% improvement in American College of Rheumatology (ACR20) criteria; Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6; DAS28-4(ESR)-defined remission, change in Health Assessment Questionnaire Disability Index (HAQ-DI) score, and safety assessments. RESULTS Mean treatment differences for ACR20 response rates (month 6) for the 5-mg and 10-mg tofacitinib groups compared with the combined placebo groups were 21.2% (95% CI, 12.2% to 30.3%; P < 0.001) and 25.8% (CI, 16.8% to 34.8%; P < 0.001), respectively. The HAQ-DI scores (month 3) and DAS28-4(ESR) less than 2.6 response rates (month 6) were also superior in the tofacitinib groups versus placebo. The incidence rates of serious adverse events for patients receiving 5-mg tofacitinib, 10-mg tofacitinib, or placebo were 6.9, 7.3, or 10.9 events per 100 patient-years of exposure, respectively. In the tofacitinib groups, 2 cases of tuberculosis, 2 cases of other opportunistic infections, 3 cardiovascular events, and 4 deaths occurred. Neutrophil counts decreased, hemoglobin and low- and high-density lipoprotein cholesterol levels increased, and serum creatinine levels had small increases in the tofacitinib groups. LIMITATIONS Placebo groups were smaller and of shorter duration. Patients received primarily methotrexate. The ability to assess drug combinations other than tofacitinib plus methotrexate was limited. CONCLUSION Tofacitinib improved disease control in patients with active RA despite treatment with nonbiologic DMARDs, primarily methotrexate. PRIMARY FUNDING SOURCE Pfizer.

Screening for Cognitive Impairment in Older Adults: A Systematic Review for the U.S. Preventive Services Task Force

Abstract: This review examined the diagnostic accuracy of brief cognitive screening instruments and the benefits and harms of pharmacologic and nonpharmacologic interventions for early cognitive impairment. ...

Screening for intimate partner violence and abuse of elderly and vulnerable adults: U.S. preventive services task force recommendation statement.

Abstract: This U.S. Preventive Services Task Force updates its 2004 statement on screening for family and intimate partner violence. It recommends screening women of childbearing age for intimate partner vio...

Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force

Abstract: This systematic review for the U.S. Preventive Services Task Force updates evidence on the benefits and harms of vitamin and mineral supplements for primary prevention of cardiovascular disease and...

Cognitive impairment associated with atrial fibrillation: a meta-analysis

Abstract: Background Atrial fibrillation (AF) has been linked with an increased risk of cognitive impairment and dementia.