Screening for Atrial Fibrillation: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Atrial fibrillation (AF), the most common arrhythmia, increases the risk of stroke. Objective: To review the evidence on screening for AF in adults without prior stroke to inform the US Preventive Services Task Force. Data Sources: PubMed, Cochrane Library, and trial registries through October 5, 2020; references, experts, and literature surveillance through October 31, 2021. Study Selection: Randomized clinical trials (RCTs) of screening among asymptomatic persons without known AF or prior stroke; test accuracy studies; RCTs of anticoagulation among persons with AF; systematic reviews; and observational studies reporting harms. Data Extraction and Synthesis: Two reviewers assessed titles/abstracts, full-text articles, and study quality and extracted data; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures: Detection of undiagnosed AF, test accuracy, mortality, stroke, stroke-related morbidity, and harms. Results: Twenty-six studies (N = 113 784) were included. In 1 RCT (n = 28 768) of twice-daily electrocardiography (ECG) screening for 2 weeks, the likelihood of a composite end point (ischemic stroke, hemorrhagic stroke, systemic embolism, all-cause mortality, and hospitalization for bleeding) was lower in the screened group over 6.9 years (hazard ratio, 0.96 [95% CI, 0.92-1.00]; P = .045), but that study had numerous limitations. In 4 RCTs (n = 32 491), significantly more AF was detected with intermittent and continuous ECG screening compared with no screening (risk difference range, 1.0%-4.8%). Treatment with warfarin over a mean of 1.5 years in populations with clinical, mostly persistent AF was associated with fewer ischemic strokes (pooled risk ratio [RR], 0.32 [95% CI, 0.20-0.51]; 5 RCTs; n = 2415) and lower all-cause mortality (pooled RR, 0.68 [95% CI, 0.50-0.93]) compared with placebo. Treatment with direct oral anticoagulants was also associated with lower incidence of stroke (adjusted odds ratios range, 0.32-0.44) in indirect comparisons with placebo. The pooled RR for major bleeding for warfarin compared with placebo was 1.8 (95% CI, 0.85-3.7; 5 RCTs; n = 2415), and the adjusted odds ratio for major bleeding for direct oral anticoagulants compared with placebo or no treatment ranged from 1.38 to 2.21, but CIs did not exclude a null effect. Conclusions and Relevance: Although screening can detect more cases of unknown AF, evidence regarding effects on health outcomes is limited. Anticoagulation was associated with lower risk of first stroke and mortality but with increased risk of major bleeding, although estimates for this harm are imprecise; no trials assessed benefits and harms of anticoagulation among screen-detected populations.

Correction to: Comparative Effectiveness of Combining MTX with Biologic Drug Therapy Versus Either MTX or Biologics Alone for Early Rheumatoid Arthritis in Adults: a Systematic Review and Network Meta-analysis.

This article has been amended to include open access.

Defining treatment-resistant depression.

BACKGROUND: Varying conceptualizations of treatment-resistant depression (TRD) have made translating research findings or systematic reviews into clinical practice guidelines challenging and inconsistent. METHODS: We conducted a review for the Centers for Medicare & Medicaid Services and the Agency for Healthcare Research and Quality to clarify how experts and investigators have defined TRD and to review systematically how well this definition comports with TRD definitions in clinical trials through July 5, 2019. RESULTS: We found that no consensus definition existed for TRD. The most common TRD definition for major depressive disorder required a minimum of two prior treatment failures and confirmation of prior adequate dose and duration. The most common TRD definition for bipolar disorder required one prior treatment failure. No clear consensus emerged on defining adequacy of either dose or duration. Our systematic review found that only 17% of intervention studies enrolled samples meeting the most frequently specified criteria for TRD. Depressive outcomes and clinical global impressions were commonly measured; functional impairment and quality-of-life tools were rarely used. CONCLUSIONS: Two key steps are critical to advancing TRD research: (a) Developing a consensus definition of TRD that addresses how best to specify the number of prior treatment failures and the adequacy of dose and duration; and (b) identifying a core package of outcome measures that can be applied in a standardized manner. Our recommendations about stronger approaches to designing and conducting TRD research will foster better evidence to translate into clearer guidelines for treating patients with this serious condition.

Comparative Effectiveness of Combining MTX with Biologic Drug Therapy Versus Either MTX or Biologics Alone for Early Rheumatoid Arthritis in Adults: a Systematic Review and Network Meta-analysis.

BACKGROUND: Comparative effectiveness of early rheumatoid arthritis (RA) treatments remains uncertain. PURPOSE: Compare benefits and harms of biologic drug therapies for adults with early RA within 1 year of diagnosis. DATA SOURCES: English language articles from the 2012 review to October 2017 identified through MEDLINE, Cochrane Library and International Pharmaceutical Abstracts, gray literature, expert recommendations, reference lists of published literature, and supplemental evidence data requests. STUDY SELECTION: Two persons independently selected studies based on predefined inclusion criteria. DATA EXTRACTION: One reviewer extracted data; a second reviewer checked accuracy. Two independent reviewers assigned risk of bias ratings. DATA SYNTHESIS: We identified 22 eligible studies with 9934 participants. Combination therapy with tumor necrosis factor (TNF) or non-TNF biologics plus methotrexate (MTX) improved disease control, remission, and functional capacity compared with monotherapy of either MTX or a biologic. Network meta-analyses found higher ACR50 response (50% improvement) for combination therapy of biologic plus MTX than for MTX monotherapy (relative risk range 1.20 [95% confidence interval (CI), 1.04 to 1.38] to 1.57 [95% CI, 1.30 to 1.88]). No significant differences emerged between treatment discontinuation rates because of adverse events or serious adverse events. Subgroup data (disease activity, prior therapy, demographics, serious conditions) were limited. LIMITATIONS: Trials enrolled almost exclusively selected populations with high disease activity. Network meta-analyses were derived from indirect comparisons relative to MTX due to the dearth of head-to-head studies comparing interventions. No eligible data on biosimilars were found. CONCLUSIONS: Qualitative and network meta-analyses suggest that the combination of MTX with TNF or non-TNF biologics reduces disease activity and improves remission when compared with MTX monotherapy. Overall adverse event and discontinuation rates were similar between treatment groups. REGISTRATION: PROSPERO (available at http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017079260 ).

Comparative Benefits and Harms of Complementary and Alternative Medicine Therapies for Initial Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis.

OBJECTIVES: To report the comparative benefits and harms of exercise and complementary and alternative medicine (CAM) treatments with second-generation antidepressants (SGA) for major depressive disorder (MDD). DESIGN: Systematic review and meta-analysis. SETTINGS: Outpatient clinics. SUBJECTS: Adults, aged 18 years and older, with MDD receiving an initial treatment attempt with SGA. INTERVENTIONS: Any CAM or exercise intervention compared with an SGA. OUTCOME MEASURES: Treatment response, remission, change in depression rating, adverse events, treatment discontinuation, and treatment discontinuation due to adverse events. RESULTS: We found 22 randomized controlled trials for direct comparisons and 127 trials for network meta-analyses, including trials of acupuncture, omega-3 fatty acids, S-adenosyl methionine, St. John's wort, and exercise. For most treatment comparisons, we found no differences between treatment groups for response and remission. However, the risk of bias of these studies led us to conclude that the strength of evidence for these findings was either low or insufficient. The risk of treatment harms and treatment discontinuation attributed to adverse events was higher for selective serotonin receptor inhibitors than for St. John's wort. CONCLUSIONS: Although we found little difference in the comparative efficacy of most CAM therapies or exercise and SGAs, the overall poor quality of the available evidence base tempers any conclusions that we might draw from those trials. Future trials should incorporate patient-oriented outcomes, treatment expectancy, depressive severity, and harms assessments into their designs; antidepressants should be administered over their full dosage ranges; and larger trials using methods to reduce sampling bias are needed.

Preventing and De-escalating Aggressive Behavior Among Adult Psychiatric Patients: A Systematic Review of the Evidence.

OBJECTIVE: The project goal was to compare the effectiveness of strategies to prevent and de-escalate aggressive behaviors among psychiatric patients in acute care settings, including interventions for reducing use of seclusion and restraint. METHODS: Relevant databases were systematically reviewed for comparative studies of violence prevention and de-escalation strategies involving adult psychiatric patients in acute care settings. Studies (trials and cohort studies) were required to report on aggression or seclusion or restraint outcomes. Both risk of bias, an indicator of quality of individual studies, and strength of evidence (SOE) for each outcome were independently assessed by two study personnel. RESULTS: Seventeen primary studies met inclusion criteria. Evidence was limited for benefits and harms; information about characteristics that might modify the interventions' effectiveness, such as race or ethnicity, was especially limited. All but one study had a medium or high risk of bias and thus presented worrisome limitations. For prevention, risk assessment reduced both aggression and use of seclusion and restraint (low SOE), and multimodal interventions reduced the use of seclusion and restraint (low SOE). SOE for all other interventions, whether aimed at preventing or de-escalating aggression, and for modifying characteristics was insufficient. CONCLUSIONS: Available evidence about strategies for preventing and de-escalating aggressive behavior among psychiatric patients is very limited. Two preventive strategies, risk assessment and multimodal interventions consistent with the Six Core Strategies principles, may effectively lower aggressive behavior and use of seclusion and restraint, but more research is needed on how best to prevent and de-escalate aggressive behavior in acute care settings.

Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review.

BACKGROUND: The emerging dual imperatives of personalized medicine and technologic advances make population screening for preventable conditions resulting from genetic alterations a realistic possibility. Lynch syndrome is a potential screening target due to its prevalence, penetrance, and the availability of well-established, preventive interventions. However, while population screening may lower incidence of preventable conditions, implementation without evidence may lead to unintentional harms. We examined the literature to determine whether evidence exists that screening for Lynch-associated mismatch repair (MMR) gene mutations leads to improved overall survival, cancer-specific survival, or quality of life. Documenting evidence and gaps is critical to implementing genomic approaches in public health and guiding future research. MATERIALS AND METHODS: Our 2014-2015 systematic review identified studies comparing screening with no screening in the general population, and controlled studies assessing analytic validity of targeted next-generation sequencing, and benefits or harms of interventions or screening. We conducted meta-analyses for the association between early or more frequent colonoscopies and health outcomes. RESULTS: Twelve studies met our eligibility criteria. No adequate evidence directly addressed the main question or the harms of screening in the general population. Meta-analyses found relative reductions of 68% for colorectal cancer incidence (relative risk: 0.32, 95% confidence interval: 0.23-0.43, three cohort studies, 590 participants) and 78% for all-cause mortality (relative risk: 0.22, 95% confidence interval: 0.09-0.56, three cohort studies, 590 participants) for early or more frequent colonoscopies among family members of people with cancer who also had an associated MMR gene mutation. CONCLUSION: Inadequate evidence exists examining harms and benefits of population-based screening for Lynch syndrome. Lack of evidence highlights the need for data that directly compare benefits and harms.

Folic Acid Supplementation for the Prevention of Neural Tube Defects: An Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Neural tube defects are among the most common congenital anomalies in the United States. Periconceptional folic acid supplementation is a primary care-relevant preventive intervention. Objective: To review the evidence on folic acid supplementation for preventing neural tube defects to inform the US Preventive Services Task Force for an updated Recommendation Statement. Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries through January 28, 2016, with ongoing surveillance through November 11, 2016; references; experts. Study Selection: English-language studies of folic acid supplementation in women. Excluded were poor-quality studies; studies of prepubertal girls, men, women without the potential for childbearing, and neural tube defect recurrence; and studies conducted in developing countries. Data Extraction and Synthesis: Two investigators independently reviewed abstracts, full-text articles, and risk of bias of included studies. One investigator extracted data and a second checked accuracy. Because of heterogeneity, data were not pooled. Main Outcomes and Measures: Neural tube defects, harms of treatment (twinning, respiratory outcomes). Results: A total of 24 studies (N > 58 860) were included. In 1 randomized clinical trial from Hungary initiated in 1984, incidence of neural tube defects for folic acid supplementation compared with trace element supplementation was 0% vs 0.25% (Peto odds ratio [OR], 0.13 [95% CI, 0.03-0.65]; n = 4862). Odds ratios from cohort studies recruiting participants between 1984 and 1996 demonstrated beneficial associations and ranged from 0.11 to 0.27 (n = 19 982). Three of 4 case-control studies with data from 1976 through 1998 reported ORs ranging from 0.6 to 0.7 (n > 7121). Evidence of benefit led to food fortification in the United States beginning in 1998, after which no new prospective studies have been conducted. More recent case-control studies drawing from data collected after 1998 have not demonstrated a protective association consistently with folic acid supplementation, with ORs ranging from 0.93 to 1.4 and confidence intervals spanning the null (n > 13 990). Regarding harms, 1 trial (OR, 1.40 [95% CI, 0.89-2.21]; n = 4767) and 1 cohort study (OR, 1.04 [95% CI, 0.91-1.18]; n = 2620) found no statistically significant increased risk of twinning. Three systematic reviews found no consistent evidence of increased risk of asthma (OR, 1.06 [95% CI, 0.99-1.14]; n = 14 438), wheezing, or allergy. Conclusions and Relevance: In studies conducted before the initiation of food fortification in the United States in 1998, folic acid supplementation provided protection against neural tube defects. Newer postfortification studies have not demonstrated a protective association but have the potential for misclassification and recall bias, which can attenuate the measured association of folic acid supplementation with neural tube defects.

The Effectiveness of Total Worker Health Interventions: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.

BACKGROUND: The Total Worker Health (TWH) program of the National Institute for Occupational Safety and Health aims to advance worker well-being by integrating injury and illness prevention efforts with work-related safety and health hazard efforts. PURPOSE: To evaluate evidence on the benefits and harms of integrated TWH interventions. DATA SOURCES: MEDLINE, Cochrane Library, and PsycINFO (January 1990 through September 2015); clinical trial registries; and reference lists. STUDY SELECTION: English-language studies that enrolled employed adults and compared integrated interventions with usual work practice, no intervention, or another intervention. DATA EXTRACTION: Dual abstraction and risk-of-bias (ROB) assessment. DATA SYNTHESIS: Ten of the 15 included studies had high ROB, primarily because of selection and attrition bias. Findings graded as having low strength of evidence (SOE) supported the effectiveness of TWH interventions for improving smoking cessation, as measured by self-reported 7-day abstinence over 22 to 26 weeks (2 randomized, controlled trials [RCTs]; n = 737), and increasing consumption of fruits and vegetables over 26 to 104 weeks (3 RCTs; n = 6056); results apply to populations of blue-collar manufacturing and construction workers. Findings graded as having low SOE supported the effectiveness of TWH interventions for reducing sedentary work behavior in office workers over 16 to 52 weeks (2 RCTs; n = 262). Evidence was insufficient or lacking for other outcomes of interest, such as rates of work injuries, quality of life, and harms. LIMITATION: Small, diverse body of evidence with many methodological limitations; possible publication bias. CONCLUSION: Integrated TWH interventions might improve health behaviors (for example, reduce tobacco use and sedentary behavior and improve diet) of workers, but effects of these interventions on injuries and overall quality of life are not known. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Comparative Benefits and Harms of Antidepressant, Psychological, Complementary, and Exercise Treatments for Major Depression: An Evidence Report for a Clinical Practice Guideline From the American College of Physicians.

BACKGROUND: Primary care patients and clinicians may prefer options other than second-generation antidepressants for the treatment of major depressive disorder (MDD). The comparative benefits and harms of antidepressants and alternative treatments are unclear. PURPOSE: To compare the benefits and harms of second-generation antidepressants and psychological, complementary and alternative medicine (CAM), and exercise treatments as first- and second-step interventions for adults with acute MDD. DATA SOURCES: English-, German-, and Italian-language studies from multiple electronic databases (January 1990 to September 2015); trial registries and gray-literature databases were used to identify unpublished research. STUDY SELECTION: Two investigators independently selected comparative randomized trials of at least 6 weeks' duration on health outcomes of adult outpatients; nonrandomized studies were eligible for harms. DATA EXTRACTION: Reviewers abstracted data on study design, participants, interventions, and outcomes; rated the risk of bias; and graded the strength of evidence. A senior reviewer confirmed data and ratings. DATA SYNTHESIS: 45 trials met inclusion criteria. On the basis of moderate-strength evidence, cognitive behavioral therapy (CBT) and antidepressants led to similar response rates (relative risk [RR], 0.90 [95% CI, 0.76 to 1.07]) and remission rates (RR, 0.98 [CI, 0.73 to 1.32]). In trials, antidepressants had higher risks for adverse events than most other treatment options; no information from nonrandomized studies was available. The evidence was too limited to make firm conclusions about differences in the benefits and harms of antidepressants compared with other treatment options as first-step therapies for acute MDD. For second-step therapies, different switching and augmentation strategies provided similar symptom relief. LIMITATION: High dropout rates, dosing inequalities, small sample sizes, and poor assessment of adverse events limit confidence in the evidence. CONCLUSION: Given their similar efficacy, CBT and antidepressants are both viable choices for initial treatment of MDD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis.

STUDY QUESTION: What are the benefits and harms of second generation antidepressants and cognitive behavioral therapies (CBTs) in the initial treatment of a current episode of major depressive disorder in adults? METHODS: This was a systematic review including qualitative assessment and meta-analyses using random and fixed effects models. Medline, Embase, the Cochrane Library, the Allied and Complementary Medicine Database, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature were searched from January 1990 through January 2015. The 11 randomized controlled trials included compared a second generation antidepressant CBT. Ten trials compared antidepressant monotherapy with CBT alone; three compared antidepressant monotherapy with antidepressant plus CBT. SUMMARY ANSWER AND LIMITATIONS: Meta-analyses found no statistically significant difference in effectiveness between second generation antidepressants and CBT for response (risk ratio 0.91, 0.77 to 1.07), remission (0.98, 0.73 to 1.32), or change in 17 item Hamilton Rating Scale for Depression score (weighted mean difference, -0.38, -2.87 to 2.10). Similarly, no significant differences were found in rates of overall study discontinuation (risk ratio 0.90, 0.49 to 1.65) or discontinuation attributable to lack of efficacy (0.40, 0.05 to 2.91). Although more patients treated with a second generation antidepressant than receiving CBT withdrew from studies because of adverse events, the difference was not statistically significant (risk ratio 3.29, 0.42 to 25.72). No conclusions could be drawn about other outcomes because of lack of evidence. Results should be interpreted cautiously given the low strength of evidence for most outcomes. The scope of this review was limited to trials that enrolled adult patients with major depressive disorder and compared a second generation antidepressant with CBT, and many of the included trials had methodological shortcomings that may limit confidence in some of the findings. WHAT THIS STUDY ADDS: Second generation antidepressants and CBT have evidence bases of benefits and harms in major depressive disorder. Available evidence suggests no difference in treatment effects of second generation antidepressants and CBT, either alone or in combination, although small numbers may preclude detection of small but clinically meaningful differences. Funding, competing interests, data sharing This project was funded under contract from the Agency for Healthcare Research and Quality by the RTI-UNC Evidence-based Practice Center. Detailed methods and additional information are available in the full report, available at http://effectivehealthcare.ahrq.gov/.

Medication therapy management interventions in outpatient settings: a systematic review and meta-analysis.

IMPORTANCE: Medication therapy management (MTM) services (also called clinical pharmacy services) aim to reduce medication-related problems and their downstream outcomes. OBJECTIVE: To assess the effect of MTM interventions among outpatients with chronic illnesses. DATA SOURCES: MEDLINE, Cochrane Library, and International Pharmaceutical Abstracts through January 9, 2014. STUDY SELECTION: Two reviewers selected studies with comparators and eligible outcomes of ambulatory adults. DATA EXTRACTION AND SYNTHESIS: Dual review of titles, abstracts, full-text, extractions, risk of bias, and strength of evidence grading. We conducted meta-analyses using random-effects models. MAIN OUTCOMES AND MEASURES: Medication-related problems, morbidity, mortality, quality of life, health care use, costs, and harms. RESULTS: Forty-four studies met the inclusion criteria. The evidence was insufficient to determine the effect of MTM interventions on most evaluated outcomes (eg, drug therapy problems, adverse drug events, disease-specific morbidity, disease-specific or all-cause mortality, and harms). The interventions improved a few measures of medication-related problems and health care use and costs (low strength of evidence) when compared with usual care. Specifically, MTM interventions improved medication appropriateness (4.9 vs 0.9 points on the medication appropriateness index, P < .001), adherence (approximately 4.6%), and percentage of patients achieving a threshold adherence level (odds ratios [ORs] ranged from 0.99 to 5.98) and reduced medication dosing (mean difference, -2.2 doses; 95% CI, -3.738 to -0.662). Medication therapy management interventions reduced health plan expenditures on medication costs, although the studies reported wide CIs. For patients with diabetes mellitus or heart failure, MTM interventions lowered the odds of hospitalization (diabetes: OR, 0.91 to 0.93 based on type of insurance; adjusted hazard rate for heart failure: 0.55; 95% CI, 0.39 to 0.77) and hospitalization costs (mean differences ranged from -$363.45 to -$398.98). The interventions conferred no benefit for patient satisfaction and most measures of health-related quality of life (low strength). CONCLUSIONS AND RELEVANCE: We graded the evidence as insufficient for most outcomes because of inconsistency and imprecision that stem in part from underlying heterogeneity in populations and interventions. Medication therapy management interventions may reduce the frequency of some medication-related problems, including nonadherence, and lower some health care use and costs, but the evidence is insufficient with respect to improvement in health outcomes.

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

BACKGROUND: Nearly 25% of patients hospitalized with heart failure (HF) are readmitted within 30 days. PURPOSE: To assess the efficacy, comparative effectiveness, and harms of transitional care interventions to reduce readmission and mortality rates for adults hospitalized with HF. DATA SOURCES: MEDLINE, Cochrane Library, CINAHL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (1 January 1990 to late October 2013). STUDY SELECTION: Two reviewers independently selected randomized, controlled trials published in English reporting a readmission or mortality rate within 6 months of an index hospitalization. DATA EXTRACTION: One reviewer extracted data, and another checked accuracy. Two reviewers assessed risk of bias and graded strength of evidence (SOE). DATA SYNTHESIS: Forty-seven trials were included. Most enrolled adults with moderate to severe HF and a mean age of 70 years. Few trials reported 30-day readmission rates. At 30 days, a high-intensity home-visiting program reduced all-cause readmission and the composite end point (all-cause readmission or death; low SOE). Over 3 to 6 months, home-visiting programs and multidisciplinary heart failure (MDS-HF) clinic interventions reduced all-cause readmission (high SOE). Home-visiting programs reduced HF-specific readmission and the composite end point (moderate SOE). Structured telephone support (STS) interventions reduced HF-specific readmission (high SOE) but not all-cause readmissions (moderate SOE). Home-visiting programs, MDS-HF clinics, and STS interventions produced a mortality benefit. Neither telemonitoring nor primarily educational interventions reduced readmission or mortality rates. LIMITATIONS: Few trials reported 30-day readmission rates. Usual care was heterogeneous and sometimes not adequately described. CONCLUSION: Home-visiting programs and MDS-HF clinics reduced all-cause readmission and mortality; STS reduced HF-specific readmission and mortality. These interventions should receive the greatest consideration by systems or providers seeking to implement transitional care interventions for persons with HF. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

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.

A comparative effectiveness review of parenting and trauma-focused interventions for children exposed to maltreatment.

OBJECTIVE: To systematically review the comparative effectiveness evidence for interventions to ameliorate the negative sequelae of maltreatment exposure in children ages birth to 14 years. METHODS: We assessed the research on pharmacological and psychosocial interventions (parent-mediated approaches or trauma-focused treatments) reporting mental and behavioral health, caregiver-child relationship, and developmental and/or school functioning outcomes. We conducted focused searches of MEDLINE (through PubMed), Social Sciences Citation Index, PsycINFO, and the Cochrane Library (1990-2012). Reviewer pairs independently evaluated the studies for eligibility using predetermined inclusion/exclusion criteria, evaluated studies for risk of bias, extracted data, and graded the strength of evidence (SOE) for each comparison and each outcome based on predetermined criteria. RESULTS: Based on our review of 6282 unduplicated citations, we found 17 trials eligible for inclusion. Although several interventions show promising comparative benefit for child well-being outcomes, the SOE for all but one of these interventions was low. The results highlight numerous substantive and methodological gaps to address in the future research. CONCLUSIONS: It is too early to make strong treatment recommendations, as comparative research remains relatively nascent in the child maltreatment arena. These gaps reflect, in large part, the Herculean demands on researchers involved in conducting high-quality clinical studies with this highly vulnerable population. The National Child Traumatic Stress Network and the Developmental-Behavioral Pediatrics Research Network (DBPNet) are two potentially powerful platforms to conduct large rigorous trials needed to move the field forward. More broadly, a paradigm shift among researchers and funders alike is needed to galvanize the commitment and resources necessary for conducting collaborative clinical trials with this highly vulnerable population.

Interventions to improve adherence to self-administered medications for chronic diseases in the United States: a systematic review.

BACKGROUND: Suboptimum medication adherence is common in the United States and leads to serious negative health consequences but may respond to intervention. PURPOSE: To assess the comparative effectiveness of patient, provider, systems, and policy interventions that aim to improve medication adherence for chronic health conditions in the United States. DATA SOURCES: Eligible peer-reviewed publications from MEDLINE and the Cochrane Library indexed through 4 June 2012 and additional studies from reference lists and technical experts. STUDY SELECTION: Randomized, controlled trials of patient, provider, or systems interventions to improve adherence to long-term medications and nonrandomized studies of policy interventions to improve medication adherence. DATA EXTRACTION: Two investigators independently selected, extracted data from, and rated the risk of bias of relevant studies. DATA SYNTHESIS: The evidence was synthesized separately for each clinical condition; within each condition, the type of intervention was synthesized. Two reviewers graded the strength of evidence by using established criteria. From 4124 eligible abstracts, 62 trials of patient-, provider-, or systems-level interventions evaluated 18 types of interventions; another 4 observational studies and 1 trial of policy interventions evaluated the effect of reduced medication copayments or improved prescription drug coverage. Clinical conditions amenable to multiple approaches to improving adherence include hypertension, heart failure, depression, and asthma. Interventions that improve adherence across multiple clinical conditions include policy interventions to reduce copayments or improve prescription drug coverage, systems interventions to offer case management, and patient-level educational interventions with behavioral support. LIMITATIONS: Studies were limited to adults with chronic conditions (excluding HIV, AIDS, severe mental illness, and substance abuse) in the United States. Clinical and methodological heterogeneity hindered quantitative data pooling. CONCLUSION: Reduced out-of-pocket expenses, case management, and patient education with behavioral support all improved medication adherence for more than 1 condition. Evidence is limited on whether these approaches are broadly applicable or affect longterm medication adherence and health outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Closing the quality gap: revisiting the state of the science (vol. 4: medication adherence interventions: comparative effectiveness).

OBJECTIVES: To assess the effectiveness of patient, provider, and systems interventions (Key Question [KQ] 1) or policy interventions (KQ 2) in improving medication adherence for an array of chronic health conditions. For interventions that are effective in improving adherence, we then assessed their effectiveness in improving health, health care utilization, and adverse events. DATA SOURCES: MEDLINE®, the Cochrane Library. Additional studies were identified from reference lists and technical experts. REVIEW METHODS: Two people independently selected, extracted data from, and rated the risk of bias of relevant trials and systematic reviews. We synthesized the evidence for effectiveness separately for each clinical condition, and within each condition, by type of intervention. We also evaluated the prevalence of intervention components across clinical conditions and the effectiveness of interventions for a range of vulnerable populations. Two reviewers graded the strength of evidence using established criteria. RESULTS: We found a total of 62 eligible studies (58 trials and 4 observational studies) from our review of 3,979 abstracts. These studies included patients with diabetes, hyperlipidemia, hypertension, heart failure, myocardial infarction, asthma, depression, glaucoma, multiple sclerosis, musculoskeletal diseases, and multiple chronic conditions. Fifty-seven trials of patient, provider, or systems interventions (KQ 1) evaluated 20 different types of interventions; 4 observational studies and one trial of policy interventions (KQ 2) evaluated the effect of reduced out-of-pocket expenses or improved prescription drug coverage. We found the most consistent evidence of improvement in medication adherence for interventions to reduce out-of-pocket expenses or improve prescription drug coverage, case management, and educational interventions across clinical conditions. Within clinical conditions, we found the strongest support for self-management of medications for short-term improvement in adherence for asthma patients; collaborative care or case management programs for short-term improvement of adherence and to improve symptoms for patients taking depression medications; and pharmacist-led approaches for hypertensive patients to improve systolic blood pressure. CONCLUSIONS: Diverse interventions offer promising approaches to improving medication adherence for chronic conditions, particularly for the short term. Evidence on whether these approaches have broad applicability for clinical conditions and populations is limited, as is evidence regarding long-term medication adherence or health outcomes.