Daniel E Jonas

Systematic Review: Comparative Effectiveness and Harms of Disease-Modifying Medications for Rheumatoid Arthritis

Context Which disease-modifying antirheumatic drugs (DMARDs) best reduce symptoms, improve function, and prevent radiographic progression in patients with rheumatoid arthritis? Contribution This systematic review of trials that compared DMARDs in adults with rheumatoid arthritis found few direct comparisons of different agents but no important differences among synthetic DMARDs or antitumor necrosis factor drugs. Combination therapy improved response rates and functional outcomes in patients whose monotherapy failed. Numbers and types of short-term adverse events were similar among DMARDs. Implication Of several monotherapies for adults with rheumatoid arthritis, no regimen is clearly superior. Combination therapies improve response rates in some patients previously receiving monotherapy. The Editors Rheumatoid arthritis is an autoimmune disease that affects more than 2 million adults in the United States. Disease onset generally occurs between 30 and 55 years of age, and women are affected more often than men. Disease hallmarks are inflammation of the synovium, progressive bone erosion, joint malalignment and destruction, and subsequent weakness of surrounding tissues and muscles. Presentations range from mild to severe, although the typical patient has a progressive course leading to functional limitations. Treatment aims at controlling pain and inflammation and slowing or arresting the progression of joint destruction. Therapies generally used in the United States include corticosteroids; synthetic disease-modifying antirheumatic drugs (DMARDs), such as hydroxychloroquine, leflunomide, methotrexate, and sulfasalazine; and biological DMARDs, such as abatacept, adalimumab, anakinra, etanercept, infliximab, and rituximab. The American College of Rheumatology (ACR) recommends beginning DMARD therapy within 3 months of diagnosis (1). Often, treatment with a single DMARD does not adequately control symptoms, leading clinicians to consider various combination strategies. Experts do not agree about the comparative benefits of different combination therapies. Many questions remain about the risks of these agents across a spectrum of adverse events from relatively minor side effects to severe and possibly life-threatening problems. Given this uncertainty, the Agency for Healthcare Research and Quality (AHRQ) commissioned a systematic review to compare the benefits and safety of rheumatoid arthritis drugs (2). Methods We developed and followed a standardized protocol for all steps of the review. The full technical report (2) describes study methods in detail and gives evidence tables of individual studies. Literature Search We searched MEDLINE, EMBASE, The Cochrane Library, and the International Pharmaceutical Abstracts for studies from 1980 to September 2007. Search terms included Medical Subject Headings or keywords when appropriate. We combined terms for rheumatoid arthritis with 11 drugs of interest (corticosteroid, methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, etanercept, infliximab, adalimumab, abatacept, anakinra, and rituximab). We limited electronic searches to studies involving adults and humans and studies in English. We manually searched reference lists of review articles and letters to the editor. In addition, we searched the Center for Drug Evaluation and Research database (September 2007) to identify unpublished research submitted to the U.S. Food and Drug Administration. In early to mid-2006, the Oregon Scientific Resource Center invited pharmaceutical manufacturers to submit dossiers on all published and unpublished studies on a specific drug. Five companies (Abbott, Amgen, Bristol-Myers Squibb, Centocor, and Genentech) provided dossiers. Study Selection Two persons, each blinded to the others results, independently reviewed titles, abstracts, and sometimes full text to identify studies meeting preestablished criteria. To assess efficacy regarding symptoms, quality of life, functional capacity, and radiographic progression, we included head-to-head controlled trials and prospective cohort studies comparing any of the therapies. For harms (specific adverse events, rates of adverse events, and discontinuation attributable to adverse events) and subgroups, we also examined data from retrospective observational studies and placebo-controlled trials. For efficacy and harm data, we selected studies with 100 or more participants and at least 12 weeks of follow-up. Finally, if we found no evidence about efficacy from direct head-to-head comparison studies, we included evidence from fair- or good-quality meta-analyses that indirectly compared placebo-controlled trial data across drugs. Data Abstraction and Quality Assessment Trained reviewers abstracted each study by using a Web-based system (SRS 4.0, TrialStat, Ottawa, Ontario, Canada). A senior reviewer read each abstracted article and evaluated completeness of data extraction. We recorded intention-to-treat results if available. We assessed the internal validity (quality) of trials on the basis of predefined criteria from the U.S. Preventive Services Task Force (rating of good, fair, or poor) (3) and the National Health Service Centre for Reviews and Dissemination (4). Elements of internal validity for trials included randomization, allocation concealment, similarity of compared groups at baseline, intention-to-treat analysis, and overall and differential loss to follow-up. To assess the quality of observational studies, we used criteria outlined by Deeks and colleagues (5). Items assessed included sample selection, adjustment for confounders, methods of outcomes assessment, length of follow-up, and statistical analysis. Data Synthesis We primarily synthesized the literature qualitatively; we reported some quantitative syntheses from fair- to good-quality meta-analyses. Drug comparisons that were not quantitatively analyzed in meta-analyses had insufficient data or noncomparable study samples and did not merit additional quantitative analyses. We examined data within 3 main drug classes (corticosteroids, synthetic DMARDs, and biological DMARDs) and between drug classes and combination therapies. Strength of Evidence Ratings We rated the strength of the available evidence in a 3-part hierarchy (high, moderate, and low) (2) based on a modified Grading of Recommendations, Assessment, Development, and Evaluation approach (6, 7). Grades reflect the strength of evidence for a given comparison with respect to specific outcomes, such as 20% improvement in ACR response criteria (ACR 20), radiographic changes, or adverse events. Role of the Funding Source Agency for Healthcare Research and Quality staff participated in formulating initial study questions and reviewed methods, data analysis, and the draft report. The funding source did not participate in the literature search, determination of study eligibility, or evaluation of individual studies. Results Characteristics of Reviewed Studies We identified 2395 citations (Figure). Working from 635 articles retrieved for full review, we included 143 published articles reporting on 101 studies (Table 1). Of the 101 included studies, 49 (48.5%) were supported by pharmaceutical companies, 20 (19.8%) by governmental or independent funds, and 11 (10.9%) by a combination of pharmaceutical and governmental funding. We could not determine the source of support for 21 (20.8%) studies. Table 1. Summary of Head-to-Head Reviewed Studies, by Drug Comparison* Figure. Study flow diagram. Numbers of included articles and included studies differ because some studies have multiple publications. RCT = randomized, controlled trial. Comparative Effectiveness and Harms We found few fair- or good-quality head-to-head trials for each drug comparison (Table 1). Most trials were efficacy trials in highly selected populations with few comorbid conditions. Most trials used ACR 20, disease activity scores to measure clinical improvement, and Sharp or Sharpvan der Heijde scores to measure radiologic progression of the disease. Trials examining quality of life used the Health Assessment Questionnaire (HAQ) or Medical Outcomes Study Short Form 36 (SF-36). Table 2 summarizes results. Table 2. Summary of Comparative Findings on Efficacy and Harms of Rheumatoid Arthritis Drugs Monotherapy versus Monotherapy Synthetic DMARDs One good systematic review that included a meta-analysis of 2 trials suggested that more patients receiving methotrexate achieved ACR 20 at 1 year than did patients receiving leflunomide (odds ratio, 1.43 [95% CI, 1.15 to 1.77]). The ACR 20 benefit was lower and more uncertain at 2 years (odds ratio, 1.28 [CI, 0.98 to 1.67]) (8). However, patients receiving methotrexate showed less improvement in health-related quality of life than did patients receiving leflunomide (odds ratio for SF-36 physical component, 3.00 [CI, 5.41 to 0.59]). Radiographic outcomes over 2 years seemed similar. For leflunomide versus sulfasalazine, data are limited to 1 trial (9) involving 358 participants with 2-year follow-up (10, 11). Leflunomide yielded more patients achieving ACR 20, ACR 50, and greater improvement in functional capacity (ACR 20, 82% vs. 60% [P= 0.008]; ACR 50, 52% vs. 25% [P= 0.040]; HAQ, 0.50 vs. 0.29 [P 0.030]). Radiographic changes were similar for the 2 drugs (Larsen score change at 2 years, 0.010 for either drug) (9). Three trials involving 479 participants and lasting up to 52 weeks compared methotrexate with sulfasalazine and found similar response rates in ACR 20, disease activity scores, or functional capacity (1214). Two trials included patients with disease for longer than 1 year and used a lower dose of weekly methotrexate (7.5 mg) than that generally used in the United States (13, 14). The overall attrition rate for these studies ranged from 19% to 28.5%. We found no statistically significant differences in frequency of serious adverse events for leflunomide, methotrexate, and sulfasalazine in 3 efficacy trial

Transitional care interventions to prevent readmissions for persons with heart failure: a systematic review and meta-analysis.

Heart failure (HF) is a leading cause of hospitalization and health care costs in the United States (1). Up to 25% of patients hospitalized with HF are readmitted within 30 days (25). Readmissions after an index hospitalization for HF are related to various conditions. An analysis of Medicare claims data from 2007 to 2009 found that 35% of readmissions within 30 days were for HF; the remainder were for diverse indications (for example, renal disorders, pneumonia, and arrhythmias) (2). To reduce rehospitalization of Medicare patients, in October 2012, the Centers for Medicare & Medicaid Services began decreasing reimbursements to hospitals with excessive risk-standardized readmission (6). This policy incentivizes hospitals to develop programs to reduce readmission rates for persons with HF. Despite advances in the quality of acute and chronic HF disease management, knowledge gaps remain about effective interventions to support the transition of care for persons with HF. Interventions designed to prevent readmissions among populations transitioning from one care setting to another are often called transitional care interventions (7, 8). They aim to avoid poor outcomes caused by uncoordinated care, such as preventable readmissions (9). Although no clear set of components defines transitional care interventions, they focus on patient or caregiver education, medication reconciliation, and coordination among health professionals involved in the transition. We conducted a systematic review of transitional care interventions for persons with HF for the Effective Health Care Program of the Agency for Healthcare Research and Quality (AHRQ) (10). We included a broad range of intervention types (Table 1) applicable to adults transitioning from hospital to home that aimed to prevent readmissions. Although 30-day readmissions are the focus of quality measures, we also included readmissions measured over 3 to 6 months because these are common, costly, and potentially preventable (5). The full technical report addressed 5 questions (Appendix Table 1). For this article, we focused on readmission and mortality outcomes. Table 1. Transitional Care Interventions Appendix Table 1. Scope and Key Questions* Methods We developed and followed a standard protocol. A technical report that details methods and includes complete search strategies and additional evidence tables is available at www.effectivehealthcare.ahrq.gov/reports/final.cfm. Data Sources and Searches We searched MEDLINE, the Cochrane Library, and CINAHL for English-language and human-only studies published from 1 July 2007 to late October 2013, and we used a previous technology assessment on a similar topic to identify randomized, controlled trials (RCTs) published before 1 July 2007 (11). An experienced Evidence-based Practice Center librarian conducted the searches, and a second librarian reviewed them. We manually searched reference lists of pertinent reviews, included trials, and background articles on this topic to look for relevant citations our searches might have missed. We searched for relevant unpublished studies using ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. Study Selection We developed inclusion and exclusion criteria with respect to populations, interventions, comparators, outcomes, timing, settings, and study designs (Appendix Table 2). We included studies of adults recruited during or within 1 week of an index hospitalization for HF that compared a transitional care intervention with another eligible intervention or with usual care (that is, routine or standard care, as defined by the primary studies). We required that interventions include 1 or more of the following components: education of patient or caregiver delivered before or after discharge, planned or scheduled outpatient clinic visits (primary care or multidisciplinary heart failure [MDS-HF] clinic), home visits, telemonitoring, structured telephone support (STS), transition coach or case management, or interventions to increase provider continuity. We required studies to report a readmission rate, mortality rate, or the composite outcome (all-cause readmission or mortality). In the full report, we also assessed emergency department visits, acute care visits, hospital days of subsequent readmissions, quality of life, functional status, and caregiver or self-care burden (10). Appendix Table 2. Inclusion and Exclusion Criteria for Studies of Transitional Care Interventions for Patients Hospitalized for HF Data Extraction and Risk-of-Bias Assessment One team member extracted relevant data from each article, and a second team member reviewed all data extractions for completeness and accuracy. We used predefined criteria based on the AHRQ Methods Guide for Comparative Effectiveness Reviews (12) to rate studies as having low, medium, high, or unclear risk of bias. Two reviewers independently assessed risk of bias for each study, and disagreements were resolved by consensus. Data Synthesis and Analysis We categorized intervention types primarily on the basis of the method and environment of delivery, as defined in Table 1. One investigator categorized the intervention, and a second team member reviewed the categorization. Disagreements were resolved by consensus. Given heterogeneity of the clinic-based interventions, we subcategorized these by clinic setting: MDS-HF, nurse-led HF, or primary care. We used DerSimonianLaird random-effects models (13) for meta-analyses of outcomes reported by multiple studies that were sufficiently similar to justify combining results. We ran meta-analyses of trials that reported the number of deaths or number of persons readmitted in each group (and not total readmissions per group). When only the total number of readmissions per group was available, we contacted authors for additional data. When we could not obtain the number of persons readmitted, we did not include the results in meta-analyses; instead, we included the results in qualitative syntheses and considered them when grading the strength of evidence (SOE). For readmission and mortality rates, we calculated risk ratios (RRs). We stratified analyses for each intervention category by outcome timing and separated rates reported at 30 days from those after 30 days (that is, rates reported over 3 to 6 months were combined). We did not include studies rated as high or unclear risk of bias in our main analyses but included them in sensitivity analyses, which are available in the technical report (10); we describe them here only when they differed from primary analyses. We assessed statistical heterogeneity using the chi-square and I 2 statistics (14, 15). We calculated the number needed to treat (NNT) for readmission and mortality outcomes when we had statistically significant findings based on our primary analyses of trials rated as low or medium risk of bias, and we found at least low SOE for benefit. The NNT was derived from the RR and median usual care event rate using methods described in the Cochrane Handbook (16). We conducted meta-analyses using Stata, version 11.1 (StataCorp, College Station, Texas). We did meta-analysis stratified by intensity in each intervention category when variation existed. The results of these subgroup analyses are available in the main report (10); we describe them here only when we found a difference in efficacy based on level of intensity. Given the heterogeneity of included interventions, we could not develop a single measure of intensity that could be applied to all intervention categories. For most interventions, we defined intensity as the duration, frequency, or periodicity of patient contact and categorized each intervention as low-, medium-, or high-intensity. We reserved the low-intensity category for interventions that included 1 episode of patient contact or few resources. We graded SOE as high, moderate, low, or insufficient based on guidance established for the Evidence-based Practice Center program (17). The approach incorporates 4 key domains: risk of bias, consistency, directness, and precision. When only 1 study reported an outcome of interest, we usually graded the SOE as insufficient (primarily due to unknown consistency and imprecision); however, when similar interventions had consistent results at other time points, we graded the SOE as low. Two reviewers assessed each domain for each outcome, and differences were resolved by consensus. Role of the Funding Source The AHRQ funded this review, and AHRQ staff participated in the development of the scope of the work and reviewed draft manuscripts. Approval from AHRQ was required before the manuscript could be submitted for publication, but the authors are solely responsible for the content and the decision to submit it for publication. Results Searches of all sources identified 2419 potentially relevant citations. We included 47 RCTs (Appendix Figure 1). Trial characteristics are shown in Appendix Table 3. Most trials compared a transitional care intervention with usual care; 2 directly compared more than 1 intervention (both rated high risk of bias) (18, 19). In general, trials included adults with a mean age of 70 years who were hospitalized with a primary diagnosis of HF. Most reported HF disease severity based on the New York Heart Association classification and included persons with moderate to severe HF. Twenty-nine trials reported mean ejection fraction. Of these, 27 enrolled persons with a mean ejection fraction less than 0.50 and 7 trials specified a reduced ejection fraction as an inclusion criterion. Across most trials, the majority of patients were prescribed an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. The percentages of patients who were prescribed -blockers at discharge varied widely across trials. Trials were conducted in a range of settings: academic medical centers, Department of Veterans Affairs hospitals,

Systematic Review: Enhancing the Use and Quality of Colorectal Cancer Screening

BACKGROUND National guideline groups recommend screening and discussion of screening options for persons at average risk for colorectal cancer (CRC). However, emerging evidence suggests that CRC screening is simultaneously underused, overused, and misused and that adequate patient-provider discussions about screening are infrequent. PURPOSE To summarize evidence on factors that influence CRC screening and strategies that increase the appropriate use and quality of CRC screening and CRC screening discussions. DATA SOURCES MEDLINE, the Cochrane Library, and the Cochrane Central Register of Controlled Trials were searched for English-language publications describing studies conducted in the United States from January 1998 through September 2009. STUDY SELECTION Two reviewers independently selected studies that addressed the study questions and met eligibility criteria. DATA EXTRACTION Information on study design, setting, intervention, outcomes, and quality were extracted by one reviewer and double-checked by another. Reviewers assigned a strength-of-evidence grade for intervention categories by using criteria plus a consensus process. DATA SYNTHESIS Reviewers found evidence of simultaneous underuse, overuse, and misuse of CRC screening as well as inadequate clinical discussions about CRC screening. Several patient-level factors were independently associated with lower screening rates, including having low income or less education, being uninsured, being Hispanic or Asian, being less acculturated into the United States, or having limited access to care. Evidence that interventions that included patient reminders or one-on-one interactions (that is, between patients and nonphysician clinic staff), eliminated structural barriers (for example, simplifying access to fecal occult blood test cards), or made system-level changes (for example, using systematic screening as opposed to opportunistic screening) were effective in enhancing use of CRC screening was strong. Evidence on how best to enhance discussions about CRC screening options is limited. No studies focused on reducing overuse, and very few focused on misuse. LIMITATIONS Reporting and publication bias may have affected our findings. The independent effect of individual elements of multicomponent interventions was often uncertain. CONCLUSION Although CRC screening is underused overall, important problems of overuse and misuse also exist. System- and policy-level interventions that target vulnerable populations are needed to reduce underuse. Interventions aimed at reducing barriers by making the screening process easier are likely to be effective. Studies aimed at reducing overuse and misuse and at enhancing the quality and frequency of discussions about CRC screening options are needed. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Outcomes and costs of community health worker interventions: A systematic review

Objectives:We conducted a systematic review on outcomes and costs of community health worker (CHW) interventions. CHWs are increasingly expected to improve health outcomes cost-effectively for the underserved. Research Design:We searched Medline, Cochrane Collaboration resources, and the Cumulative Index to Nursing and Allied Health Literature for studies conducted in the United States and published in English from 1980 through November 2008. We dually reviewed abstracts, full-text articles, data abstractions, quality ratings, and strength of evidence grades and resolved disagreements by consensus. Results:We included 53 studies on outcomes of CHW interventions and 6 on cost or cost-effectiveness. For outcomes, limited evidence (5 studies) suggests that CHW interventions can improve participant knowledge compared with alternative approaches or no intervention. We found mixed evidence for participant behavior change (22 studies) and health outcomes (27 studies). Some studies suggested that CHW interventions can result in greater improvements in participant behavior and health outcomes compared with various alternatives, but other studies suggested that CHW interventions provide no statistically different benefits than alternatives. We found low or moderate strength of evidence suggesting that CHWs can increase appropriate health care utilization for some interventions (30 studies). Six studies with economic information yielded insufficient data to evaluate the cost-effectiveness of CHW interventions relative to other interventions. Conclusions:CHWs can improve outcomes for underserved populations for some health conditions. The effectiveness of CHWs in many health care areas requires further research that addresses the methodologic limitations of prior studies and that contributes to translating research into practice.

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis

OBJECTIVE To evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with major depressive disorder (MDD) and 2 or more prior antidepressant treatment failures (often referred to as treatment-resistant depression [TRD]). These patients are less likely to recover with medications alone and often consider nonpharmacologic treatments such as rTMS. DATA SOURCES We searched MEDLINE, EMBASE, the Cochrane Library, PsycINFO, and the International Pharmaceutical Abstracts for studies comparing rTMS with a sham-controlled treatment in TRD patients ages 18 years or older. STUDY SELECTION We included 18 good- or fair-quality TRD studies published from January 1, 1980, through March 20, 2013. DATA EXTRACTION We abstracted relevant data, assessed each studys internal validity, and graded strength of evidence for change in depressive severity, response rates, and remission rates. RESULTS rTMS was beneficial compared with sham for all outcomes. rTMS produced a greater decrease in depressive severity (high strength of evidence), averaging a clinically meaningful decrease on the Hamilton Depression Rating Scale (HDRS) of more than 4 points compared with sham (mean decrease = -4.53; 95% CI, -6.11 to -2.96). rTMS resulted in greater response rates (high strength of evidence); those receiving rTMS were more than 3 times as likely to respond as patients receiving sham (relative risk = 3.38; 95% CI, 2.24 to 5.10). Finally, rTMS was more likely to produce remission (moderate strength of evidence); patients receiving rTMS were more than 5 times as likely to achieve remission as those receiving sham (relative risk = 5.07; 95% CI, 2.50 to 10.30). Limited evidence and variable treatment parameters prevented conclusions about which specific treatment options are more effective than others. How long these benefits persist remains unclear. CONCLUSIONS For MDD patients with 2 or more antidepressant treatment failures, rTMS is a reasonable, effective consideration.

Interventions to prevent post-traumatic stress disorder: a systematic review.

CONTEXT Traumatic events are prevalent worldwide; trauma victims seek help in numerous clinical and emergency settings. Using effective interventions to prevent post-traumatic stress disorder (PTSD) is increasingly important. This review assessed the efficacy, comparative effectiveness, and harms of psychological, pharmacologic, and emerging interventions to prevent PTSD. EVIDENCE ACQUISITION The following sources were searched for research on interventions to be included in the review: MEDLINE; Cochrane Library; CINAHL; EMBASE; PILOTS (Published International Literature on Traumatic Stress); International Pharmaceutical Abstracts; PsycINFO; Web of Science; reference lists of published literature; and unpublished literature (January 1, 1980 to July 30, 2012). Two reviewers independently selected studies, extracted data or checked accuracy, assessed study risk of bias, and graded strength of evidence. All data synthesis occurred between January and September 2012. EVIDENCE SYNTHESIS Nineteen studies covered various populations, traumas, and interventions. In meta-analyses of three trials (from the same team) for people with acute stress disorder, brief trauma-focused cognitive behavioral therapy was more effective than supportive counseling in reducing the severity of PTSD symptoms (moderate-strength); these two interventions had similar results for incidence of PTSD (low-strength); depression severity (low-strength); and anxiety severity (moderate-strength). PTSD symptom severity after injury decreased more with collaborative care than usual care (single study; low-strength). Debriefing did not reduce incidence or severity of PTSD or psychological symptoms in civilian traumas (low-strength). Evidence about relevant outcomes was unavailable for many interventions or was insufficient owing to methodologic shortcomings. CONCLUSIONS Evidence is very limited regarding best practices to treat trauma-exposed individuals. Brief cognitive behavioral therapy may reduce PTSD symptom severity in people with acute stress disorder; collaborative care may help decrease symptom severity post-injury.

Review and special articleInterventions to Prevent Post-Traumatic Stress Disorder: A Systematic Review

CONTEXT Traumatic events are prevalent worldwide; trauma victims seek help in numerous clinical and emergency settings. Using effective interventions to prevent post-traumatic stress disorder (PTSD) is increasingly important. This review assessed the efficacy, comparative effectiveness, and harms of psychological, pharmacologic, and emerging interventions to prevent PTSD. EVIDENCE ACQUISITION The following sources were searched for research on interventions to be included in the review: MEDLINE; Cochrane Library; CINAHL; EMBASE; PILOTS (Published International Literature on Traumatic Stress); International Pharmaceutical Abstracts; PsycINFO; Web of Science; reference lists of published literature; and unpublished literature (January 1, 1980 to July 30, 2012). Two reviewers independently selected studies, extracted data or checked accuracy, assessed study risk of bias, and graded strength of evidence. All data synthesis occurred between January and September 2012. EVIDENCE SYNTHESIS Nineteen studies covered various populations, traumas, and interventions. In meta-analyses of three trials (from the same team) for people with acute stress disorder, brief trauma-focused cognitive behavioral therapy was more effective than supportive counseling in reducing the severity of PTSD symptoms (moderate-strength); these two interventions had similar results for incidence of PTSD (low-strength); depression severity (low-strength); and anxiety severity (moderate-strength). PTSD symptom severity after injury decreased more with collaborative care than usual care (single study; low-strength). Debriefing did not reduce incidence or severity of PTSD or psychological symptoms in civilian traumas (low-strength). Evidence about relevant outcomes was unavailable for many interventions or was insufficient owing to methodologic shortcomings. CONCLUSIONS Evidence is very limited regarding best practices to treat trauma-exposed individuals. Brief cognitive behavioral therapy may reduce PTSD symptom severity in people with acute stress disorder; collaborative care may help decrease symptom severity post-injury.

Ticagrelor versus Genotype-Driven Antiplatelet Therapy for Secondary Prevention after Acute Coronary Syndrome: A Cost-Effectiveness Analysis

BACKGROUND Clopidogrels effectiveness is likely reduced significantly for prevention of thrombotic events after acute coronary syndrome (ACS) in patients exhibiting a decreased ability to metabolize clopidogrel into its active form. A genetic mutation responsible for this reduced effectiveness is detectable by genotyping. Ticagrelor is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel in a recent secondary prevention trial. In 2011, clopidogrel will lose its patent protection and likely will be substantially less expensive than ticagrelor. OBJECTIVE To determine the cost-effectiveness of ticagrelor compared with a genotype-driven selection of antiplatelet agents. METHODS A hybrid decision tree/Markov model was used to estimate the 5-year medical costs (in 2009 US

Systematic Review: Effective Characteristics of Nursing Homes and Other Residential Long-Term Care Settings for People with Dementia

) and outcomes for a cohort of ACS patients enrolled in Medicare receiving either genotype-driven or ticagrelor-only treatment. Outcomes included life years and quality-adjusted life years (QALYs) gained. Data comparing the clinical performance of ticagrelor and clopidogrel were derived from the Platelet Inhibition and Patient Outcomes trial. RESULTS The incremental cost-effectiveness ratio (ICER) for universal ticagrelor was

Conjoint Analysis Versus Rating and Ranking for Values Elicitation and Clarification in Colorectal Cancer Screening

10,059 per QALY compared to genotype-driven treatment, and was most sensitive to the price of ticagrelor and the hazard ratio for death for ticagrelor compared with clopidogrel. The ICER remained below