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Editor's Note: This article is a reprint of a previously published article. For citation purposes, please use the original publication details: Harris RP, Helfand M, Woolf SH, et al. Current methods of the U.S. Preventive Services Task Force: a review of the process. Am J Prev Med. 2001;20(3S):21-35. The U.S. Preventive Services Task Force (USPSTF/Task Force) represents one of several efforts to take a more evidence-based approach to the development of clinical practice guidelines. As methods have matured for assembling and reviewing evidence and for translating evidence into guidelines, so too have the methods of the USPSTF. This paper summarizes the current methods of the third USPSTF, supported by the Agency for Healthcare Research and Quality (AHRQ) and two of the AHRQ Evidence-based Practice Centers (EPCs). The Task Force limits the topics it reviews to those conditions that cause a large burden of suffering to society and that also have available a potentially effective preventive service. It focuses its reviews on the questions and evidence most critical to making a recommendation. It uses analytic frameworks to specify the linkages and key questions connecting the preventive service with health outcomes. These linkages, together with explicit inclusion criteria, guide the literature searches for admissible evidence. Once assembled, admissible evidence is reviewed at three strata: (1) the individual study, (2) the body of evidence concerning a single linkage in the analytic framework, and (3) the body of evidence concerning the entire preventive service. For each stratum, the Task Force uses explicit criteria as general guidelines to assign one of three grades of evidence: good, fair, or poor. Good or fair quality evidence for the entire preventive service must include studies of sufficient design and quality to provide an unbroken chain of evidence-supported linkages, generalizable to the general primary care population, that connect the preventive service with health outcomes. Poor evidence contains a formidable break in the evidence chain such that the connection between the preventive service and health outcomes is uncertain. For services supported by overall good or fair evidence, the Task Force uses outcomes tables to help categorize the magnitude of benefits, harms, and net benefit from implementation of the preventive service into one of four categories: substantial, moderate, small, or zero/negative. The Task Force uses its assessment of the evidence and magnitude of net benefit to make a recommendation, coded as a letter: from A (strongly recommended) to D (recommend against). It gives an I recommendation in situations in which the evidence is insufficient to determine net benefit. The third Task Force and the EPCs will continue to examine a variety of methodologic issues and document work group progress in future communications.

Health services research studies how social factors, financing systems, organizational structures and processes, technology, and personal behaviors affect access to health care, the costs and quality of health care, and the health and well-being of individuals and populations. HSR, a boundary-crossing field, engages a very wide set of clinical and academic disciplines, investigates a broad array of questions relating to health care delivery and management, financing, clinical practice, personal health care decision-making, and health policy, and employs virtually all quantitative and qualitative methods found in the social sciences, economics, outcomes measurement, management and administration, epidemiology and statistics, law, and policy analysis. It has one major professional organization, Academy Health, and is supported in the US in large measure by the federal Agency for Healthcare Research and Quality, certain other federal agencies, and philanthropic organizations; numerous journals exclusively or predominantly publish on HSR-related topics. Keywords: access; costs; economics; health services research; health care; policy; quality; technology

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.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.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.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.

Psychological and pharmacological interventions for binge-eating disorder have previously demonstrated efficacy (compared with placebo or waitlist control); thus, we aimed to expand that literature with a review of comparative effectiveness. We searched MEDLINE,® EMBASE,® Cochrane Library, Academic OneFile, CINAHL® for binge-eating disorder treatment articles and selected studies using predetermined inclusion and exclusion criteria. Data were sufficient for network meta-analysis comparing two pharmacological interventions; psychological interventions were analysed qualitatively. In all, 28 treatment comparisons were included in this review: one pharmacological comparison (second-generation antidepressants versus lisdexamfetamine) and 26 psychological comparisons. Only three statistically significant differences emerged: lisdexamfetamine was better at increasing binge abstinence than second-generation antidepressants; therapist-led cognitive behavioural therapy was better at reducing binge-eating frequency than behavioural weight loss, but behavioural weight loss was better at reducing weight. The majority of other treatment comparisons revealed few significant differences between groups. Thus, patients and clinicians can choose from several effective treatment options. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

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.

BACKGROUND Studies have explored the risk for and impact of respiratory syncytial virus (RSV) infection requiring hospitalization among healthy preterm infants born at 29-35 weeks of gestational age not given RSV immunoprophylaxis. We performed a systematic review and qualitative synthesis of these studies. METHODS Two experienced reviewers used prespecified inclusion/exclusion criteria to screen titles/abstracts and full-text studies using MEDLINE, Embase, BIOSIS and Cochrane Library (January 1, 1985, to November 6, 2014). We abstracted data on risk factors for RSV hospitalization, incidence and short- and long-term outcomes of RSV hospitalization. Using standard procedures, we assessed study risk of bias and graded strength of evidence (SOE). RESULTS We identified 4754 records and reviewed 27. Important risk factors for RSV hospitalization included young age during the RSV season, having school-age siblings and day-care attendance, with odds ratios >2.5 in at least one study (high SOE). Incidence rates for RSV hospitalizations ranged from 2.3% to 10% (low SOE). Length of hospital stays ranged from 3.8 to 6.1 days (low SOE). Recurrent wheezing rates ranged from 20.7% to 42.8% 1 to 2 years after RSV hospitalization (low SOE). CONCLUSIONS Young chronological age and some environmental risk factors are important clinical indicators of an increased risk of RSV hospitalization in healthy preterm infants 32 to 35 weeks of gestational age. SOE was low for estimates of incidence of RSV hospitalizations, in-hospital resource use and recurrent wheezing in this population. Studies were inconsistent in study characteristics, including weeks of gestational age, age during RSV season and control for confounding factors.

Objective To assess efficacy, comparative effectiveness, and harms of psychological and pharmacological treatments for adults with posttraumatic stress disorder (PTSD) and to update the original 2013 review. Data sources MEDLINE®, CINAHL®, Cochrane Library, Cochrane Clinical Trials Registry, PILOTS (Published International Literature on Traumatic Stress), PsycINFO®, and reference lists of published literature (May 2012–September 2017). Review methods Two investigators independently selected, extracted data from, and rated risk of bias of relevant studies. We conducted meta-analyses or network meta-analyses using random-effects models when we had evidence from three or more studies with low heterogeneity. We graded strength of evidence (SOE) following established Agency for Healthcare Research and Quality guidance. Results We included 193 randomized controlled trials (207 articles) for this review. Several psychological treatments were associated with the reduction of PTSD symptoms and loss of PTSD diagnosis compared with inactive comparators; high SOE supports efficacy of cognitive behavioral therapy (CBT)-exposure and CBT-mixed treatments, and moderate SOE supports efficacy of cognitive processing therapy (CPT), cognitive therapy (CT), eye movement desensitization and reprocessing (EMDR), and narrative exposure therapy (NET). When directly comparing two treatments of interest, moderate SOE favors CBT-exposure over relaxation therapy. Several pharmacological treatments reduced PTSD symptoms; moderate SOE supports the efficacy of fluoxetine, paroxetine, and venlafaxine compared with placebo. Our network meta-analysis (33 trials; N=4,817) of Clinician-Administered PTSD Scale (CAPS)-measured PTSD symptoms showed no differences in effectiveness between medications with at least moderate SOE of efficacy (fluoxetine, paroxetine, and venlafaxine) (low SOE for no difference). Studies provided insufficient strength of evidence for serious adverse events associated with any treatments of interest. The majority of psychological studies reported no information about adverse events. Among pharmacological treatments with evidence of efficacy (moderate SOE), we found increased risk of nausea with venlafaxine compared with placebo (moderate SOE). Our review found insufficient strength of evidence for the comparative effectiveness of any psychological versus pharmacological treatment and for differences in the efficacy or comparative effectiveness of treatments by patient characteristics (e.g., co-occurring conditions) or type, number, severity, or chronicity of trauma exposure(s). We did not find evidence for many of our outcomes of interest or interventions of interest, including the newer treatments added since our prior review. Conclusions Several psychological and pharmacological treatments have moderate to high SOE of efficacy for treating adults with PTSD. Future research is needed on the comparative effectiveness of treatments (including different comparisons of psychological and pharmacological treatments), differences in treatment benefits by trauma type or other patient characteristics, and adverse events associated with treatments.

Objectives The objective of our study was to use a diverse sample of medical interventions to assess empirically whether first trials rendered substantially different treatment effect estimates than reliable, high-quality bodies of evidence. Study Design and Setting We used a meta-epidemiologic study design using 100 randomly selected bodies of evidence from Cochrane reports that had been graded as high quality of evidence. To determine the concordance of effect estimates between first and subsequent trials, we applied both quantitative and qualitative approaches. For quantitative assessment, we used Lin's concordance correlation and calculated z-scores; to determine the magnitude of differences of treatment effects, we calculated standardized mean differences (SMDs) and ratios of relative risks. We determined qualitative concordance based on a two-tiered approach incorporating changes in statistical significance and magnitude of effect. Results First trials both overestimated and underestimated the true treatment effects in no discernible pattern. Nevertheless, depending on the definition of concordance, effect estimates of first trials were concordant with pooled subsequent studies in at least 33% but up to 50% of comparisons. The pooled magnitude of change as bodies of evidence advanced from single trials to high-quality bodies of evidence was 0.16 SMD [95% confidence interval (CI): 0.12, 0.21]. In 80% of comparisons, the difference in effect estimates was smaller than 0.5 SMDs. In first trials with large treatment effects (>0.5 SMD), however, estimates of effect substantially changed as new evidence accrued (mean change 0.68 SMD; 95% CI: 0.50, 0.86). Conclusion Results of first trials often change, but the magnitude of change, on average, is small. Exceptions are first trials that present large treatment effects, which often dissipate as new evidence accrues.

Objectives To revise 2010 guidance on grading the strength of evidence (SOE) of the effectiveness of drugs, devices, and other preventive and therapeutic interventions in systematic reviews produced by the Evidence-based Practice Center (EPC) program, established by the US Agency for Healthcare Research and Quality (AHRQ). Study Design and Setting A cross-EPC working group reviewed authoritative systems for grading SOE [primarily the approach from the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group] and conducted extensive discussions with GRADE and other experts. Results Updated guidance continues to be conceptually similar to GRADE. Reviewers are to evaluate SOE separately for each major treatment comparison for each major outcome. We added reporting bias as a required domain and retained study limitations (risk of bias), consistency, directness, and precision (and three optional domains). Additional guidance covers scoring consistency, precision, and reporting bias, grading bodies of evidence with randomized controlled trials and observational studies, evaluating single study bodies of evidence, using studies with high risk of bias, and presenting findings with greater clarity and transparency. SOE is graded high, moderate, low, or insufficient, reflecting reviewers' confidence in the findings for a specific treatment comparison and outcome. Conclusion No single approach for grading SOE suits all reviews, but a more consistent and transparent approach to reporting summary information will make reviews more useful to the broad range of audiences that AHRQ's work aims to reach. EPC working groups will consider ongoing challenges and modify guidance as needed, on issues such as combining trials and observational studies in bodies of evidence, weighting domains, and combining qualitative and quantitative syntheses.

BACKGROUND AND OBJECTIVES:No recommendation exists for or against routine use of brief, formal screening instruments in primary care to detect speech and language delay in children through 5 years of age. This review aimed to update the evidence on screening and treating children for speech and language since the 2006 US Preventive Services Task Force systematic review.METHODS:Medline, the Cochrane Library, PsycInfo, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and reference lists. We included studies reporting diagnostic accuracy of screening tools and randomized controlled trials reporting benefits and harms of treatment of speech and language. Two independent reviewers extracted data, checked accuracy, and assigned quality ratings using predefined criteria.RESULTS:We found no evidence for the impact of screening on speech and language outcomes. In 23 studies evaluating the accuracy of screening tools, sensitivity ranged between 50% and 94%, and specificity ranged between 45% and 96%. Twelve treatment studies improved various outcomes in language, articulation, and stuttering; little evidence emerged for interventions improving other outcomes or for adverse effects of treatment. Risk factors associated with speech and language delay were male gender, family history, and low parental education. A limitation of this review is the lack of well-designed, well-conducted studies addressing whether screening for speech and language delay or disorders improves outcomes.CONCLUSIONS:Several screening tools can accurately identify children for diagnostic evaluations and interventions, but evidence is inadequate regarding applicability in primary care settings. Some treatments for young children identified with speech and language delays and disorders may be effective.

Cancer survivors have unique physical, psychological, social, and spiritual health needs. These can include symptoms and side effects associated with cancer and cancer treatment, such as pain, cognitive dysfunction, insomnia, and elevated anxiety and depression. This research brief summarizes a landscape review done for the Patient Centered Outcomes Research Institute (PCORI) to develop a clear, comprehensive understanding of the state of research as of the mid-2000s. We conducted a targeted search strategy to identify projects funded by federal and commercial sources and the American Cancer Society (ACS) in addition to identifying funding opportunities released by the National Institutes of Health (NIH). We conducted additional review to identify studies focused on symptom and side-effect measures and five priority topic areas (selected by PCORI prior to the review) in the following five databases (from January 2005- through September 2015) with an inclusion criteria in an adapted PICOTS framework (populations, interventions, comparators, outcomes, time frames, and settings). We identified 692 unduplicated studies (1/2005 to 9/2015) and retained 189 studies about cancer symptom and side-effect management. Of these studies, NIH funded 40% and the ACS 33%. Academic institutions, health care systems, other government agencies, and private foundations or industry supported the remainder. We identified critical gaps in the knowledge base pertaining to populations, interventions, comparators (when those are relevant for comparative effectiveness reviews), and outcomes. We also discovered gaps in cross-cutting topics, particularly for patient decision-making studies, patient self-management of cancer symptoms and side effects, and coordinated care.

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).Systematic review and meta-analysis.Outpatient clinics.Adults, aged 18 years and older, with MDD receiving an initial treatment attempt with SGA.Any CAM or exercise intervention compared with an SGA.Treatment response, remission, change in depression rating, adverse events, treatment discontinuation, and treatment discontinuation due to adverse events.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.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.

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 study's 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.

In 2011, the Institute of Medicine (IOM) (now the National Academy of Medicine) published standards for trustworthy guidelines and recommended that the National Guideline Clearinghouse (NGC) of the Agency for Healthcare Research and Quality clearly indicate the extent to which guidelines adhere to these standards. To accomplish this, the authors developed and tested the NGC Extent of Adherence to Trustworthy Standards (NEATS) instrument. The standards were operationalized as an instrument containing 15 items that cover disclosure of the funding source; disclosure and management of conflicts of interest; multidisciplinary input; incorporation of patient perspectives; rigorous systematic review; recommendations accompanied by rationale, assessment of benefits and harms, clear linkage to the evidence, and assessment of strength of evidence and strength of recommendation; clear articulation of recommendations; external review by diverse stakeholders; and plans for updating. After multiple rounds of feedback from experts on clinical practice guideline development, the external validity and interrater reliability of the instrument were evaluated. For each item, 80% to 100% of survey respondents judged it to be a good measure of the IOM standards. All external stakeholders stated that NEATS was suitable for its intended goal. Interrater reliability for the final NEATS instrument had a weighted κ of 0.73. The NEATS instrument is a focused tool that provides a concise evaluation of a guideline's adherence to the IOM standards for trustworthy guidelines. It has good external validity among guideline developers and good interrater reliability across trained reviewers.

Objectives: In response to the need for an evidence-based review of factors within long-term care settings that affect the quality of care, this review compared characteristics of nursing homes and other residential long-term care settings for people with dementia and their informal family caregivers with respect to health and psychosocial outcomes. Design Databases were searched for literature published between 1990 and March 2012 that met review criteria, including that at least 80% of the subject population had dementia. Results Fourteen articles meeting review criteria that were of at least fair quality were found: four prospective cohort studies, nine randomized controlled trials (RCTs), and one nonrandomized controlled trial. Overall, low or insufficient strength of evidence was found regarding the effect of most organizational characteristics, structures, and processes of care on health and psychosocial outcomes for people with dementia and no evidence for informal caregivers. Findings of moderate strength of evidence indicate that pleasant sensory stimulation reduces agitation for people with dementia. Also, although the strength of evidence is low, protocols for individualized care and to improve function result in better outcomes for these individuals. Finally, outcomes do not differ between nursing homes and residential care or assisted living settings for people with dementia except when medical care is indicated. Conclusion: Given the paucity of high-quality studies in this area, additional research is needed to develop a sufficient evidence base to support consumer selection, practice, and policy regarding the best settings and characteristics of settings for residential long-term care of people with dementia.

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.

Objectives This study aims to summarise the evidence on more than 140 pharmacological and non-pharmacological treatment options for major depressive disorder (MDD) and to evaluate the confidence that patients and clinicians can have in the underlying science about their effects. Design This is a review of systematic reviews. Data sources This study used MEDLINE, Embase, Cochrane Library, PsycINFO and Epistemonikos from 2011 up to February 2017 for systematic reviews of randomised controlled trials in adult patients with acute-phase MDD. Methods We dually reviewed abstracts and full-text articles, rated the risk of bias of eligible systematic reviews and graded the strength of evidence. Results Nineteen systematic reviews provided data on 28 comparisons of interest. For general efficacy, only second-generation antidepressants were supported with high strength evidence, presenting small beneficial treatment effects (standardised mean difference: −0.35; 95% CI −0.31 to −0.38), and a statistically significantly higher rate of discontinuation because of adverse events than patients on placebo (relative risk (RR) 1.88; 95% CI 1.0 to 3.28). Only cognitive behavioural therapy is supported by reliable evidence (moderate strength of evidence) to produce responses to treatment similar to those of second-generation antidepressants (45.5% vs 44.2%; RR 1.10; 95% CI 0.93 to 1.30). All remaining comparisons of non-pharmacological treatments with second-generation antidepressants either led to inconclusive results or had substantial methodological shortcomings (low or insufficient strength of evidence). Conclusions In contrast to pharmacological treatments, the majority of non-pharmacological interventions for treating patients with MDD are not evidence based. For patients with strong preferences against pharmacological treatments, clinicians should focus on therapies that have been compared directly with antidepressants. Trial registration number International Prospective Register of Systematic Reviews (PROSPERO) registration number: 42016035580.

Psychological and pharmacological interventions for binge-eating disorder have previously demonstrated efficacy (compared with placebo or waitlist control); thus, we aimed to expand that literature with a review of comparative effectiveness. We searched MEDLINE,® EMBASE,® Cochrane Library, Academic OneFile, CINAHL® for binge-eating disorder treatment articles and selected studies using predetermined inclusion and exclusion criteria. Data were sufficient for network meta-analysis comparing two pharmacological interventions; psychological interventions were analysed qualitatively. In all, 28 treatment comparisons were included in this review: one pharmacological comparison (second-generation antidepressants versus lisdexamfetamine) and 26 psychological comparisons. Only three statistically significant differences emerged: lisdexamfetamine was better at increasing binge abstinence than second-generation antidepressants; therapist-led cognitive behavioural therapy was better at reducing binge-eating frequency than behavioural weight loss, but behavioural weight loss was better at reducing weight. The majority of other treatment comparisons revealed few significant differences between groups. Thus, patients and clinicians can choose from several effective treatment options. Copyright © 2017 John WileySons, Ltd and Eating Disorders Association.

Aims: To evaluate the impact of systematic reviews on research funded by the Agency for Healthcare Research and Quality (AHRQ) through Evidence-based Practice Centers (EPCs), and to identify barriers to and facilitators for the effects of these documents on future research. Methods & materials: Two AHRQ systematic reviews were selected as case studies to evaluate their impact on future research. Key citations generated by these reports were identified through ISI Web of Science and PubMed Central and traced forward to identify effects on subsequent studies through citation analysis from updated systematic reviews on the topics. Requests for applications and program announcements from the NIH Guide for Grants and Contracts website were reviewed and dissemination data were obtained from AHRQ. Finally, interviews were conducted with 13 key informants to help identify short-, medium- and long-term impacts of the EPC reviews. Results: The measurable impact of the two EPC reviews is demonstrably greater on short-term outcomes (greater awareness of the issues) than on medium-term (e.g., the generation of new knowledge) or long-term outcomes (e.g., changes in patient practice or health outcomes). Factors such as the topic and the timing of the report relative to the development of the field may explain the impact of these two AHRQ reports. The degree to which the new research can be directly attributed to the AHRQ reviews remains unclear. Key informants discussed several benefits stemming from the EPC reports, including providing a foundation for the research community on which to build, heightening awareness of the gaps in knowledge, increasing the quality of research and sparking new directions of research. However, the degree to which these reports were influential hinged on several factors including marketing efforts, the very nature of the reports and other influences external to the EPC domain. Conclusions: The findings outlined in this article illustrate the importance of numerous factors influencing future research: the breadth, specificity and readiness of the topic for more research, ongoing developments in the field, availability of funding and active engagement of champions. AHRQ and the EPCs may be able to improve the likelihood of impact by creating more targeted products, planning for and expanding dissemination activities, improving the readability and other attributes of the reports themselves, and actively involving funders early on and throughout the process of creating and publishing the reviews.

Background Patients with major depressive disorder (MDD) often suffer from accompanying symptoms that influence the choice of pharmacotherapy with second-generation antidepressants (SGAs). We conducted a systematic review to determine the comparative effectiveness of citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, desvenlafaxine, duloxetine, venlafaxine, bupropion, mirtazapine, nefazodone, and trazodone, for accompanying anxiety, insomnia, and pain in patients with MDD. Methods We conducted searches in multiple databases including MEDLINE®, Embase, the Cochrane Library, International Pharmaceutical Abstracts, and PsycINFO, from 1980 through August 2011 and reviewed reference lists of pertinent articles. We dually reviewed abstracts, full-text articles, and abstracted data. We included randomized, head-to-head trials of SGAs of at least 6 weeks’ duration. We grouped SGAs into three classes for the analysis: selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors, and others. We graded the strength of the evidence as high, moderate, low, or very low based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group (GRADE) approach. Results We located 19 head-to-head trials in total: 11 on anxiety, six on insomnia, and four on pain. For the majority of comparisons, the strength of the evidence was moderate or low: evidence is weakened by inconsistency and imprecision. For treating anxiety, insomnia, and pain moderate evidence suggests that the SSRIs do not differ. Conclusions Evidence guiding the selection of an SGA based on accompanying symptoms of depression is limited. Very few trials were designed and adequately powered to answer questions about accompanying symptoms; analyses were generally of subgroups in larger MDD trials.

Objective. To examine the effects of a community-based intervention on decisions about prostate-specific antigen (PSA) screening using multiple measures of informed decision making (IDM). Data Sources/Study Setting. Nonequivalent control group time series design collecting primary data in late 2004 and 2005. Study Design. We developed a multimodal intervention designed to convey the medical uncertainty about the benefits of PSA screening and early treatment and the limited predictive ability of both the PSA test and pathological specimens collected from prostate biopsy. We examined (1) patients' recognition that there is a decision to be made about PSA screening, (2) prostate cancer knowledge levels, (3) their preferred and actual levels of participation in decision making about screening at three points in time, and (4) screening decision. Data Collection. Baseline data collection occurred in community-based organizations. These organizations served as recruiting sources and as sites for the intervention. We collected follow-up data by mail with telephone reminders. Principal Findings. Our intervention was associated with greater recognition of the PSA test as a decision to be made, levels of knowledge, both preferred and actual levels of involvement in decision making, but did not have an impact on the screening decision. Conclusions. Community-based interventions can influence key measures of IDM about PSA screening.

Child maltreatment, also referred to as child abuse and neglect, can result in lifelong negative consequences.To update the evidence on interventions provided in or referable from primary care to prevent child maltreatment for the US Preventive Services Task Force.PubMed, Cochrane Library, EMBASE, and trial registries through December 18, 2017; references; experts; literature surveillance through July 17, 2018.English-language fair- and good-quality randomized clinical trials that (1) included children with no known exposure to maltreatment and no signs or symptoms of current or past maltreatment, (2) evaluated interventions feasible in a primary care setting or that could result from a referral from primary care, and (3) reported abuse or neglect outcomes or proxies for abuse or neglect (eg, injury with a specificity for abuse, visits to the emergency department, hospitalization).Two reviewers independently assessed titles/abstracts, full-text articles, and study quality; a third resolved conflicts when needed. When at least 3 similar trials were available, random-effects meta-analyses were conducted.Direct measures (including reports to child protective services and removal of the child from the home) or proxy measures of abuse or neglect; behavioral, emotional, mental, or physical well-being; and harms.Twenty-two trials (33 publications) were included (N = 11 132). No significant association was found between interventions and reports to child protective services within 1 year of intervention completion (10.6% vs 11.9%; pooled odds ratio [OR], 0.94 [95% CI, 0.72-1.23]; 10 trials [n = 2444]) or removal of the child from the home within 1 to 3 years of follow-up (3.5% vs 3.7%; pooled OR, 1.09 [95% CI, 0.16-7.28]; 4 trials [n = 609]). No statistically significant associations were observed between interventions and outcomes for emergency department visits in the short term (2 years), hospitalizations, child development, school performance, and prevention of death. Nonsignificant results from single trials led to a conclusion of insufficient evidence for injuries, failure to thrive, failure to immunize, school attendance, and other measures of abuse or neglect. Inconsistent results led to a conclusion of insufficient evidence for long-term (≥2 years) outcomes for reports to child protective services (ORs range from 0.48 to 1.13; 3 trials [n = 1690]), emergency department visits (1 of 2 trials reported significant differences) and internalizing and externalizing behavior symptoms (3 of 6 trials reported reductions in behavior difficulties). No eligible trials on harms of interventions were identified.Interventions provided in or referable from primary care did not consistently prevent child maltreatment. No evidence on harms is available.

Background:The Agency for Healthcare Research and Quality, in expanding its efforts to advance methods for comparative effectiveness research (CER), convened a second invitational symposium in June 2009 through its Developing Evidence to Inform Decisions About Effectiveness (DEcIDE) network. A disti

A systematic review and meta-analysis was conducted to evaluate the comparative efficacy and tolerability of second-generation antidepressants in social anxiety disorder. Studies were identified by searching MEDLINE®, Embase, The Cochrane Library, PsychLit, and the International Pharmaceutical Abstracts from January 1980 through October 2006. Comparative evidence was summarized and indirect comparisons were made using network meta-analysis. Only three head-to-head trials were identified; comparative trials found only minimal differences in efficacy between escitalopram and paroxetine, and no statistically significant differences in efficacy between extended-release venlafaxine and paroxetine. Pooled evidence from 15 placebo-controlled trials suggests that escitalopram (relative benefit 1.3; 95% CI 1.2 to 1.5), paroxetine (relative benefit 1.9; 95% CI 1.5 to 2.3), sertraline (relative benefit 1.8; 95% CI 1.5 to 2.2), and venlafaxine (relative benefit 1.7; 95% CI 1.5 to 1.9) all produce significantly more responders than placebo; evidence favored fluvoxamine over placebo but was not significant (relative benefit 1.5; 95% CI 0.9 to 2.4). Network meta-analysis did not reveal differences in efficacy among drugs. Overall, fair evidence supports the efficacy of escitalopram, fluvoxamine, paroxetine, sertraline, and venlafaxine in social anxiety disorder. The drugs do not differ in efficacy, although their adverse event profiles do.

Background: Evidence indicates that only minor differences in efficacy exist among second-generation antidepressants for the treatment of major depressive disorder (MDD). However, a comprehensive assessment of both benefits and harms is crucial to evaluate the net benefit. Objective: To review systematically the comparative harms of second-generation antidepressants for the treatment of MDD in adults by including both experimental and observational evidence. Data sources: We searched MEDLINE®, EMBASE, PsychLit, The Cochrane Library and the International Pharmaceutical Abstracts from 1980 to April 2007. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database to identify unpublished research. Study selection: Eligible study designs were trials and observational studies comparing one drug of interest with another. Data extraction: Two persons independently reviewed abstracts and full-text articles. One investigator extracted relevant data. A senior reviewer checked data for completeness and accuracy. Data synthesis: We included 104 experimental and observational studies. If data were sufficient, we conducted meta-analyses of randomized controlled trials on the relative risk of specific adverse events. Findings indicate that the spectrum of adverse events is similar. The frequency of specific adverse events, however, differed across drugs. Venlafaxine was associated with a significantly higher rate of nausea and vomiting than selective serotonin reuptake inhibitors. Compared with other drugs, paroxetine frequently led to more sexual adverse effects and bupropion to fewer such effects; mirtazapine and paroxetine was associated with more weight gain and sertraline with a higher rate of diarrhoea. Overall, however, these differences did not lead to different discontinuation rates. The evidence is insufficient to draw conclusions about rare but severe adverse events. Conclusions: Adverse event profiles are similar among second-generation antidepressants. However, different frequencies of specific adverse events might be clinically relevant and influence the choice of a treatment.

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.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.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.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.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.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.High dropout rates, dosing inequalities, small sample sizes, and poor assessment of adverse events limit confidence in the evidence.Given their similar efficacy, CBT and antidepressants are both viable choices for initial treatment of MDD.Agency for Healthcare Research and Quality.

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.

Background The best treatment options for binge-eating disorder are unclear. Purpose To summarize evidence about the benefits and harms of psychological and pharmacologic therapies for adults with binge-eating disorder. Data sources English-language publications in EMBASE, the Cochrane Library, Academic OneFile, CINAHL, and ClinicalTrials.gov through 18 November 2015, and in MEDLINE through 12 May 2016. Study selection 9 waitlist-controlled psychological trials and 25 placebo-controlled trials that evaluated pharmacologic (n = 19) or combination (n = 6) treatment. All were randomized trials with low or medium risk of bias. Data extraction 2 reviewers independently extracted trial data, assessed risk of bias, and graded strength of evidence. Data synthesis Therapist-led cognitive behavioral therapy, lisdexamfetamine, and second-generation antidepressants (SGAs) decreased binge-eating frequency and increased binge-eating abstinence (relative risk, 4.95 [95% CI, 3.06 to 8.00], 2.61 [CI, 2.04 to 3.33], and 1.67 [CI, 1.24 to 2.26], respectively). Lisdexamfetamine (mean difference [MD], -6.50 [CI, -8.82 to -4.18]) and SGAs (MD, -3.84 [CI, -6.55 to -1.13]) reduced binge-eating-related obsessions and compulsions, and SGAs reduced symptoms of depression (MD, -1.97 [CI, -3.67 to -0.28]). Headache, gastrointestinal upset, sleep disturbance, and sympathetic nervous system arousal occurred more frequently with lisdexamfetamine than placebo (relative risk range, 1.63 to 4.28). Other forms of cognitive behavioral therapy and topiramate also increased abstinence and reduced binge-eating frequency and related psychopathology. Topiramate reduced weight and increased sympathetic nervous system arousal, and lisdexamfetamine reduced weight and appetite. Limitations Most study participants were overweight or obese white women aged 20 to 40 years. Many treatments were examined only in single studies. Outcomes were measured inconsistently across trials and rarely assessed beyond end of treatment. Conclusion Cognitive behavioral therapy, lisdexamfetamine, SGAs, and topiramate reduced binge eating and related psychopathology, and lisdexamfetamine and topiramate reduced weight in adults with binge-eating disorder. Primary funding source Agency for Healthcare Research and Quality.

Background: Interest in new methods for comparative effectiveness, drug and patient safety, and related studies is burgeoning. The advent of Medicare Part D for outpatient prescription drugs has drawn significant attention to the need for efficient ways to monitor the potential benefits and harms of pharmaceuticals. These trends prompted the Effective Health Care program at the Agency for Healthcare Research and Quality and its DEcIDE (Developing Evidence to Inform Decisions about Effectiveness) network to examine innovative approaches for such investigations through an invitational symposium in June 2006. Results: Conference papers covered numerous points about ways to structure both interventional and database-oriented studies, particularly those concerned with adverse drug events, to avoid bias in those studies, and to apply advanced statistical tools to exploit the information from these studies to their fullest. Of particular importance are: (1) using new types of experimental designs, including cluster randomization, delayed designs, pragmatic trials, and practice-based investigations that incorporate the natural variation of data from routine clinical practice; (2) finding efficient ways to use different types of databases-eg, Department of Veterans Affairs files, Centers for Disease Control and Prevention surveillance files, Medicaid claims data, and state hospital data-for examining initiation, persistence, and adherence, and the benefits and adverse events of pharmaceutical use; and (3) inventing or refining ways to decrease the threats to validity of analyses relying on administrative or other observational data, particularly through propensity scoring, inverse probability weighting, risk adjustment, and direct or indirect methods for synthesizing comparative effectiveness information.

Biologics are an important therapeutic option for treating patients with juvenile idiopathic arthritis (JIA). In adults, they are associated with rare but severe adverse events such as serious infections and malignancies. We reviewed systematically the evidence on the efficacy and safety of biologics for the treatment of JIA. We searched electronic databases up to August 2006. We limited evidence to prospective studies for efficacy but included retrospective observational evidence for safety. Outcomes of interest were clinical response, radiographic progression, quality of life, and adverse events. One randomized controlled trial (RCT) and 11 uncontrolled prospective studies provided data on efficacy; three additional studies assessed safety. The only RCT and six uncontrolled trials support the general efficacy of etanercept for the treatment of JIA. Internal and external validity of these studies are limited. The evidence on other biologic agents such as adalimumab, abatacept, anakinra, infliximab, rituximab, and tocilizumab is sparse or entirely missing. Because of the lack of sound long-term safety data, evidence is insufficient to draw firm conclusions about the balance of risks and benefits of any biologic agent for the treatment of JIA. Clinicians have to be aware of the lack of evidence supporting a long-term net benefit when considering biologics for patients with JIA.

The RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center systematically reviewed evidence on efficacy of treatment for bulimia nervosa (BN), harms associated with treatments, factors associated with treatment efficacy, and differential outcome by sociodemographic characteristics.We searched six major databases published from 1980 to September 2005 in all languages against a priori inclusion/exclusion criteria; we focused on eating, psychiatric or psychological, and biomarker outcomes.Forty-seven studies of medication only, behavioral interventions only, and medication plus behavioral interventions for adults or adolescents met our inclusion criteria. Fluoxetine (60 mg/day) decreases the core symptoms of binge eating and purging and associated psychological features in the short term. Cognitive behavioral therapy reduces core behavioral and psychological features in the short and long term.Evidence for medication or behavioral treatment for BN is strong, for self-help is weak; for harms related to medication is strong but either weak or nonexistent for other interventions; and evidence for differential outcome by sociodemographic factors is nonexistent. Attention to sample size, standardization of outcome measures, attrition, and reporting of abstinence from target behaviors are required. Longer follow-up intervals, innovative treatments, and attention to sociodemographic factors would enhance the literature.

Patient functioning is an important outcome in Alzheimer's disease, but treatment-related improvements in patient function are difficult to quantify because a number of different scales are used in its measurement.To evaluate systematically the evidence relating to patient functioning as an outcome measure in the drug treatment of Alzheimer's disease. Data were obtained by searching MEDLINE, EMBASE, The Cochrane Library and the International Pharmaceutical Abstracts from 1980 through to December 2005 for studies assessing functional outcomes with donepezil, galantamine, rivastigmine and memantine in Alzheimer's disease. Reference lists were searched manually and pharmaceutical manufacturers were invited to submit dossiers. Trained reviewers abstracted data and assessed the internal validity (quality) of trials using predefined criteria. Standardised effect sizes (i.e. Cohen's standardised mean difference [d]) for various functional outcome scales and pooled mean incidence and 95% CIs for adverse events were calculated and summarised qualitatively and quantitatively. Meta regression was used to explore potential heterogeneity.Overall, the standardised effect size for functional outcome measures was small (d = 0.1-0.4) among included studies. However, effect sizes consistently favoured drug treatment over placebo. For all drugs, pooled standardised effect sizes were consistent in both short (24 weeks; d = 0.25; 95% CI 0.13, 0.37) and long trials (or=24 weeks; d = 0.29; 95% CI 0.22, 0.36). The pooled effect size was not significantly affected by parameters such as disease severity, age, gender and drug dose. Adverse events were generally limited to gastrointestinal problems, weight loss and dizziness, all of which were reported in20% of patients on average.Standardised estimates of effect size across diverse functional outcome measures for drug treatment in patients with Alzheimer's disease were small and the data reflect only a modest trend favouring active treatment over placebo. However, given the current lack of other effective treatments for Alzheimer's disease, this trend supports the clinical benefits of these treatments with regard to this important health outcome.

Objective: The Research Triangle Institute-University of North Carolina Evidence Based Practice Center (RTI-EPC) systematically reviewed evidence on efficacy of treatment for binge eating disorder (BED), harms associated with treatments, factors associated with treatment efficacy, and differential outcome by sociodemographic characteristics. Method: We searched six major databases for studies on the treatment of BED published from 1980 to September, 2005, in all languages against a priori inclusion/exclusion criteria and focused on eating, psychiatric or psychological, or biomarker outcomes. Results: Twenty-six studies, including medication-only, medication plus behavioral intervention, and behavioral intervention only designs, met inclusion criteria. The strength of the evidence for medication and behavioral interventions was moderate, for self-help and other interventions was weak, for treatment-related harms was strong, for factors associated with efficacy of treatment was weak, and for differential outcome by sociodemographic factors was nonexistent. Individual or group CBT reduces binge eating and improves abstinence rates for up to 4 months after treatment but does not lead to weight loss. Medications may play a role in treating BED patients. Conclusion: The literature regarding treatment efficacy for BED is variable. Future directions include the identification of optimal interventions that are associated with both sustained abstinence from binge eating and permanent weight loss.

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 January1990 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/.

Objective To determine the predictive validity of the U.S. Evidence-based Practice Center (EPC) approach to GRADE (Grading of Recommendations Assessment, Development and Evaluation). Study Design and Setting Based on Cochrane reports with outcomes graded as high quality of evidence (QOE), we prepared 160 documents which represented different levels of QOE. Professional systematic reviewers dually graded the QOE. For each document, we determined whether estimates were concordant with high QOE estimates of the Cochrane reports. We compared the observed proportion of concordant estimates with the expected proportion from an international survey. To determine the predictive validity, we used the Hosmer-Lemeshow test to assess calibration and the C (concordance) index to assess discrimination. Results The predictive validity of the EPC approach to GRADE was limited. Estimates graded as high QOE were less likely, estimates graded as low or insufficient QOE more likely to remain stable than expected. The EPC approach to GRADE could not reliably predict the likelihood that individual bodies of evidence remain stable as new evidence becomes available. C-indices ranged between 0.56 (95% CI, 0.47 to 0.66) and 0.58 (95% CI, 0.50 to 0.67) indicating a low discriminatory ability. Conclusion The limited predictive validity of the EPC approach to GRADE seems to reflect a mismatch between expected and observed changes in treatment effects as bodies of evidence advance from insufficient to high QOE.

OBJECTIVE:We systematically review evidence on the prevalence and incidence of perinatal depression and compare these rates with those of depression in women at nonchildbearing times.DATA SOURCES:We searched MEDLINE, CINAHL, PsycINFO, and Sociofile for English-language articles published from 1980 t

Background: Chronic periodontitis affects many adults in the United States, some severely enough to threaten tooth loss. Of particular clinical importance is whether scaling and root planing (SRP) accompanied by a local adjunctive therapeutic agent improves outcomes over time compared to SRP alone. The adjunctive therapeutic agents investigated include: tetracycline, minocycline, metronidazole, a group of other antibiotics, chlorhexidine, and a group of antimicrobials. Primary outcomes considered are reductions in probing depth (PD) and gains in clinical attachment level (CAL). Methods: RTI-UNC Evidence-Based Practice Center staff searched MEDLINE (1966 through December 2002) and EMBASE (through February 2002) to identify clinical trials published in English that 1) involved adults with chronic periodontitis but no serious comorbidities; 2) tested one or more chemical antimicrobial agents as an adjunct to SRP alone or with a placebo; 3) had a concurrent control group that received the same SRP as the trea...

To determine whether a positive financial return on investment for quality-enhancing interventions is more likely for particular health conditions, in specific organizational settings, or with the use of particular interventions.Electronic search of MEDLINE.Search keywords included: business case, cost-effectiveness, cost-benefit, return on investment, costs, cost savings, quality, quality improvement, and program evaluation.Only 15 of 1968 articles identified contained sufficient information on both the costs of implementing quality-enhancing interventions and the resultant changes in costs of care or revenues to permit the calculation of a return on investment.Scant attention is currently paid in the quality-of-care literature to the cost of implementing quality-enhancing interventions. To understand which quality-enhancing interventions are likely to produce positive returns on investments, data collection and analysis must include tracking the investment and operating costs of implementing the intervention as well as the changes in revenues and costs that result from the intervention.

To perform a systematic review of interventions designed to improve health outcomes for persons with low literacy skills.We searched MEDLINE, Cumulative Index to Nursing and Allied Health (CINAHL), Educational Resources Information Center (ERIC), Public Affairs Information Service (PAIS), Industrial and Labor Relations Review (ILLR), PsycInfo, and Ageline from 1980 to 2003.We included controlled and uncontrolled trials that measured literacy and examined the effect of interventions for people with low literacy on health outcomes, including health knowledge, health behaviors, use of health care resources, intermediate markers of disease status, and measures of morbidity or mortality. Two abstractors reviewed each study for inclusion. Disagreements were resolved by consensus among the research team.One reviewer abstracted data from each article into an evidence table; the second reviewer checked each entry. Disagreements about information in evidence tables were resolved by team consensus. Both data extractors independently completed an 11-item quality scale for each article; scores were averaged to give a final measure of article quality.We identified 20 articles examining interventions designed to improve health among people with low literacy. The most common outcome studied was health knowledge; fewer studies examined health behaviors, intermediate markers, or measures of disease prevalence or severity. The effectiveness of interventions appeared mixed. Limitations in research quality and heterogeneity in outcome measures make drawing firm conclusions about effective strategies difficult. Only 5 articles examined the interaction between literacy level and the effect of the intervention; they also found mixed results.Several interventions have been developed to improve health for people with low literacy. Limitations in study design, interventions tested, and outcomes assessed make drawing conclusions about effectiveness difficult. Further research is required to understand better the types of interventions that are most effective and efficient for overcoming literacy-related barriers to good health.

Context Almost 20% of children aged 2 to 5 years have untreated dental caries. Physician interventions to prevent and manage dental caries in preschool children could help address this common problem. Objective To review the evidence for effectiveness of five possible physician interventions— (1) screening and risk assessment, (2) referral, (3) provision of dietary supplemental fluoride, (4) application of fluoride varnish, and (5) counseling—for the prevention of dental caries for the U.S. Preventive Services Task Force. Data sources Articles from 1966 to 2001 addressing the effectiveness of primary care clinicians' interventions to prevent or manage dental caries were identified in MEDLINE. The evidence for effectiveness of supplemental fluorides, fluoride varnish, and counseling for caries prevention performed by dental personnel was also examined through existing and new systematic reviews. Data synthesis For most key questions related to the five interventions, the evidence for primary care clinician effectiveness was rated as poor owing to the scarcity of studies. Ten surveys of physicians' knowledge and behavior about fluoride supplementation provided fair evidence, suggesting that supplementation decisions were often made without consideration of other fluoride exposures. Reviews of the dental literature identified fair evidence supporting the effectiveness of both fluoride supplements and varnish, although information describing effectiveness and adverse outcomes of supplementation with the most recent dosage schedule is not available. Conclusions Evidence for the effectiveness of traditionally recommended primary care clinician interventions (screening, referral, counseling) to prevent dental caries in preschool children is lacking. There is fair evidence for the effectiveness of two fluoride-based interventions (fluoride supplementation and varnish) applicable in primary care practice. However, there is also fair evidence indicating that physicians' consideration of fluoride exposure is incomplete, thus increasing the risk for fluorosis among those prescribed supplements.

Objectives. To summarize an extensive review of systems for grading the quality of research articles and rating the strength of bodies of evidence, and to highlight for health professionals and decision-makers concerned with quality measurement and improvement the available ‘best practices’ tools by which these steps can be accomplished. Design. Drawing on an extensive review of checklists, questionnaires, and other tools in the Weld of evidence-based practice, this paper discusses clinical, management, and policy rationales for rating strength of evidence in a quality improvement context, and documents best practices methods for these tasks. Results. After review of 121 systems for grading the quality of articles, 19 systems, mostly study design speciWc, met a priori scientiWc standards for grading systematic reviews, randomized controlled trials, observational studies, and diagnostic tests; eight systems (of 40 reviewed) met similar standards for rating the overall strength of evidence. All can be used as is or adapted for particular types of evidence reports or systematic reviews. Conclusions. Formally grading study quality and rating overall strength of evidence, using sound instruments and procedures, can produce reasonable levels of conWdence about the science base for parts of quality improvement programs. With such information, health care professionals and administrators concerned with quality improvement can understand better the level of science (versus only clinical consensus or opinion) that supports practice guidelines, review criteria, and assessments that feed into quality assurance and improvement programs. New systems are appearing and research is needed to conWrm the conceptual and practical underpinnings of these grading and rating systems, but the need for those developing systematic reviews, practice guidelines, and quality or audit criteria to understand and undertake these steps is becoming increasingly clear.

Objective To systematically review the evidence for screening for gestational diabetes mellitus (GDM). Data sources We established eligibility criteria for relevant studies. We systematically searched MEDLINE and the Cochrane Collaboration Library for studies meeting eligibility criteria. We supplemented this search with further studies identified from reference lists of reviews. Methods of study selection Two reviewers examined each article for eligibility. A single reviewer abstracted relevant data from the included articles; a second reviewer checked the abstractions. We graded the quality of the articles according to criteria developed by the U.S. Preventive Services Task Force. Tabulation, integration, and results No well-conducted, randomized, controlled trial provides direct evidence for the health benefits of screening for GDM. The evidence is unclear regarding the optimal screening and reference diagnostic test for GDM. The impact of hyperglycemia on adverse maternal and neonatal health outcomes is probably continuous. Although insulin therapy decreases the incidence of fetal macrosomia for those women with more severe degrees of hyperglycemia, the magnitude of any effect on maternal and neonatal health outcomes is not clear. The evidence is insufficient to determine the magnitude of health benefit for any treatment among the large number of women with GDM at milder degrees of hyperglycemia. We found limited evidence regarding the potential adverse effects of screening for GDM. Conclusion Because of the lack of high-quality evidence concerning critical issues, we are unable to determine the extent to which screening has an important impact on maternal and neonatal health outcomes. A randomized, controlled trial of screening is necessary to answer the many remaining questions.

Objective The purpose of this study was to examine the effectiveness of counseling to promote a healthy diet among patients in primary care settings. Design and data sources We conducted a MEDLINE search from 1966 to December 2001. Study selection We included randomized controlled trials of at least 3 months’ duration with measures of dietary behavior that were conducted in patient populations similar to those found in primary care practices. We excluded studies that reported only biochemical or anthropomorphic endpoints, had dropout rates greater than 50%, or enrolled patients based on the presence of a chronic disease. Data extraction One author extracted relevant data from each included article into evidence tables. Using definitions developed by the research team, two authors independently rated each study in terms of its effect size, the intensity of its intervention, the patient risk level, and the use of well-proven counseling techniques. Data synthesis We identified 21 trials for use in this review. Dietary counseling produces modest changes in self-reported consumption of saturated fat, fruits and vegetables, and possibly dietary fiber. More-intensive interventions were more likely to produce important changes than brief interventions, but they may be more difficult to apply to typical primary care patients. Interventions using interactive health communications, including computer-generated telephone or mail messages, can also produce moderate dietary changes. Conclusions Moderate- or high-intensity counseling interventions, including use of interactive health communication tools, can reduce consumption of saturated fat and increase intake of fruit and vegetable. Brief counseling of unselected patients by primary care providers appears to produce small changes in dietary behavior, but its effect on health outcomes is unclear.

OBJECTIVE: The purpose of this study was to evaluate the evidence regarding antibiotics for the treatment of preterm labor. STUDY DESIGN: Through dual review, we abstracted study design and masking, definitions of preterm labor and pregnancy outcome, patient inclusion/exclusion characteristics, patient demographic characteristics, drug and cointerventions, and numerous birth, maternal, and neonatal outcome measures. We graded the quality of the individual articles and the strength of the evidence for antibiotic benefit. RESULTS: We abstracted data from 14 randomized trials and 1 observational study. Of these studies, 13 trials met the requirements for a meta-analysis. The meta-analysis demonstrated a mixed outcome pattern with small improvements in pregnancy prolongation, estimated gestational age at birth, and birth weight. Data were insufficient to show a beneficial effect on neonatal morbidity or mortality rates. CONCLUSION: Treatment of preterm labor with antibiotic therapy can prolong gestation. The benefits of antibiotics are small, and there is considerable uncertainty about the optimal agent, route, dosage, and duration of therapy. (Am J Obstet Gynecol 2002;186:587-92.)

Quality measurement has achieved a powerful momentum across the spectrum of healthcare, driven primarily by the search for strategies to contain rapidly rising healthcare costs without sacrificing quality of care. Because pharmaceutical care is involved in almost all elements of healthcare, it is subject to the general impact of quality measurement on the healthcare system as well as quality measurements of pharmaceutical care. The assumption that measuring quality improves the processes and outcomes of care lies behind the drive for quality measurement, but this assumption remains largely untested. Whether the assumption is true depends upon the attributes of measures (importance, perspective, reliability, validity and responsiveness), the quality of the data used, and how and by whom the measures are collected, interpreted and used. Focusing attention on aspects of care that get measured may ‘crowd out’ attention on equally important, but unmeasured elements and may not contribute to allocative efficiency. Successfully turning quality measurement into quality improvement in pharmaceutical care will require two essential elements: continued research to develop, refine and update measures of quality, and education in how to use them.