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Comprehensive systematic reviews require many hours of manual review by researchers. This study retrospectively investigates the use of GPT-3.5 Turbo to screen titles and abstracts as a second reviewer or to prescreen citations for human review. The authors describe the process of prompt development as well as the performance of GPT-3.5 Turbo in terms of citations missed and the added number of citations for reconciliation for 5 different already completed reviews. Background: Systematic reviews are performed manually despite the exponential growth of scientific literature. Objective: To investigate the sensitivity and specificity of GPT-3.5 Turbo, from OpenAI, as a single reviewer, for title and abstract screening in systematic reviews. Design: Diagnostic test accuracy study. Setting: Unannotated bibliographic databases from 5 systematic reviews representing 22 665 citations. Participants: None. Measurements: A generic prompt framework to instruct GPT to perform title and abstract screening was designed. The output of the model was compared with decisions from authors under 2 rules. The first rule balanced sensitivity and specificity, for example, to act as a second reviewer. The second rule optimized sensitivity, for example, to reduce the number of citations to be manually screened. Results: Under the balanced rule, sensitivities ranged from 81.1% to 96.5% and specificities ranged from 25.8% to 80.4%. Across all reviews, GPT identified 7 of 708 citations (1%) missed by humans that should have been included after full-text screening at the cost of 10 279 of 22 665 false-positive recommendations (45.3%) that would require reconciliation during the screening process. Under the sensitive rule, sensitivities ranged from 94.6% to 99.8% and specificities ranged from 2.2% to 46.6%. Limiting manual screening to citations not ruled out by GPT could reduce the number of citations to screen from 127 of 6334 (2%) to 1851 of 4077 (45.4%), at the cost of missing from 0 to 1 of 26 citations (3.8%) at the full-text level. Limitations: Time needed to fine-tune prompt. Retrospective nature of the study, convenient sample of 5 systematic reviews, and GPT performance sensitive to prompt development and time. Conclusion: The GPT-3.5 Turbo model may be used as a second reviewer for title and abstract screening, at the cost of additional work to reconcile added false positives. It also showed potential to reduce the number of citations before screening by humans, at the cost of missing some citations at the full-text level. Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Data extraction is a crucial, yet labor‐intensive and error‐prone part of evidence synthesis. To date, efforts to harness machine learning for enhancing efficiency of the data extraction process have fallen short of achieving sufficient accuracy and usability. With the release of large language models (LLMs), new possibilities have emerged to increase efficiency and accuracy of data extraction for evidence synthesis. The objective of this proof‐of‐concept study was to assess the performance of an LLM (Claude 2) in extracting data elements from published studies, compared with human data extraction as employed in systematic reviews. Our analysis utilized a convenience sample of 10 English‐language, open‐access publications of randomized controlled trials included in a single systematic review. We selected 16 distinct types of data, posing varying degrees of difficulty (160 data elements across 10 studies). We used the browser version of Claude 2 to upload the portable document format of each publication and then prompted the model for each data element. Across 160 data elements, Claude 2 demonstrated an overall accuracy of 96.3% with a high test–retest reliability (replication 1: 96.9%; replication 2: 95.0% accuracy). Overall, Claude 2 made 6 errors on 160 data items. The most common errors (n = 4) were missed data items. Importantly, Claude 2's ease of use was high; it required no technical expertise or labeled training data for effective operation (i.e., zero‐shot learning). Based on findings of our proof‐of‐concept study, leveraging LLMs has the potential to substantially enhance the efficiency and accuracy of data extraction for evidence syntheses. [ABSTRACT FROM AUTHOR]

Primary care patients and clinicians may prefer alternative options to second-generation antidepressants for major depression. This systematic review and network meta-analysis summarizes studies on the effectiveness of pharmacologic, nonpharmacologic, and alternative interventions for initial and second-line treatment of major depression. Background: Primary care patients and clinicians may prefer alternative options to second-generation antidepressants for major depressive disorder (MDD). Purpose: To compare the benefits and harms of nonpharmacologic treatments with second-generation antidepressants as first-step interventions for acute MDD, and to compare second-step treatment strategies for patients who did not achieve remission after an initial attempt with antidepressants. Data Sources: English-language studies from several electronic databases from 1 January 1990 to 8 August 2022, trial registries, gray literature databases, and reference lists to identify unpublished research. Study Selection: 2 investigators independently selected randomized trials of at least 6 weeks' duration. Data Extraction: Reviewers abstracted data about study design and conduct, participants, interventions, and outcomes. They dually rated the risk of bias of studies and the certainty of evidence for outcomes of interest. Data Synthesis: 65 randomized trials met the inclusion criteria; eligible data from nonrandomized studies were not found. Meta-analyses and network meta-analyses indicated similar benefits of most nonpharmacologic treatments and antidepressants as first-step treatments. Antidepressants had higher risks for discontinuation because of adverse events than most other treatments. For second-step therapies, different switching and augmentation strategies provided similar symptomatic relief. The certainty of evidence for most comparisons is low; findings should be interpreted cautiously. Limitations: Many studies had methodological limitations or dosing inequalities; publication bias might have affected some comparisons. In some cases, conclusions could not be drawn because of insufficient evidence. Conclusion: Although benefits seem to be similar among first- and second-step MDD treatments, the certainty of evidence is low for most comparisons. Clinicians and patients should focus on options with the most reliable evidence and take adverse event profiles and patient preferences into consideration. Primary Funding Source: American College of Physicians. (PROSPERO: CRD42020204703) [ABSTRACT FROM AUTHOR]

Importance: It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers.Objective: To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions.Data Sources: PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries from January 1, 2016, through October 12, 2021; surveillance through July 2022.Study Selection: English-language randomized clinical trials and prospective cohort studies of fair or good quality.Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available.Main Outcomes and Measures: Morbidity and mortality related to chronic conditions; health-related quality of life.Results: Twenty trials (N = 39 145) and 3 cohort studies (N = 1 155 410) were included. Participants using estrogen only compared with placebo had significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]) per 10 000 persons. Risks per 10 000 persons were statistically significantly increased for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). Participants using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 persons, for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). Risks, per 10 000 persons, were significantly increased for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia (179 vs 91 cases; 88 more [95% CI, 15-212]) over 4.0 years; and urinary incontinence (1707 vs 1145 cases; 562 more [95% CI, 412-726]) over 1 year.Conclusions and Relevance: Use of hormone therapy in postmenopausal persons for the primary prevention of chronic conditions was associated with some benefits but also with an increased risk of harms. [ABSTRACT FROM AUTHOR]

Background: Utilisation of crowdsourcing within evidence synthesis has increased over the last decade. Crowdsourcing platform Cochrane Crowd has engaged a global community of 22,000 people from 170 countries. The COVID‐19 pandemic presented an opportunity to engage the community and keep up with the exponential output of COVID‐19 research. Aims: To test whether a crowd could accurately assess study eligibility for reviews under time constraints. Outcome measures: time taken to complete each task, time to produce required training modules, crowd sensitivity, specificity and crowd consensus. Methods: We created four crowd tasks, corresponding to four Cochrane COVID‐19 Rapid Reviews. The search results of each were uploaded and an interactive training module was developed for each task. Contributors who had participated in another COVID‐19 task were invited to participate. Each task was live for 48‐h. The final inclusion and exclusion decisions made by the core author team were used as the reference standard. Results: Across all four reviews 14,299 records were screened by 101 crowd contributors. The crowd completed each screening task within 48‐h for three reviews and in 52 h for one. Sensitivity ranged from 94% to 100%. Four studies, out of a total of 109, were incorrectly rejected by the crowd. However, their absence ultimately would not have altered the conclusions of the reviews. Crowd consensus ranged from 71% to 92% across the four reviews. Conclusion: Crowdsourcing can play a valuable role in study identification and offers willing contributors the opportunity to help identify COVID‐19 research for rapid evidence syntheses. [ABSTRACT FROM AUTHOR]

Background: Borderline personality disorder (BPD) is a debilitating psychiatric disorder that affects 0.4–3.9% of the population in Western countries. Currently, no medications have been approved by regulatory agencies for the treatment of BPD. Nevertheless, up to 96% of patients with BPD receive at least one psychotropic medication. Objectives: The objective of this systematic review was to assess the general efficacy and the comparative effectiveness of different pharmacological treatments for BPD patients. Methods: We conducted systematic literature searches limited to English language in MEDLINE, EMBASE, the Cochrane Library, and PsycINFO up to April 6, 2021, and searched reference lists of pertinent articles and reviews. Inclusion criteria were (i) patients 13 years or older with a diagnosis of BPD, (ii) treatment with anticonvulsive medications, antidepressants, antipsychotic medications, benzodiazepines, melatonin, opioid agonists or antagonists, or sedative or hypnotic medications for at least 8 weeks, (iii) comparison with placebo or an eligible medication, (iv) assessment of health-relevant outcomes, (v) randomized or non-randomized trials or controlled observational studies. Two investigators independently screened abstracts and full-text articles and graded the certainty of evidence based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. For meta-analyses, we used restricted maximum likelihood random effects models to estimate pooled effects. Results: Of 12,062 unique records, we included 21 randomized controlled trials (RCTs) with data on 1768 participants. Nineteen RCTs compared pharmacotherapies with placebo; two RCTs assessed active treatments head-to-head. Out of 87 medications in use in clinical practice, we found studies on just nine. Overall, the evidence indicates that the efficacy of pharmacotherapies for the treatment of BPD is limited. Second-generation antipsychotics, anticonvulsants, and antidepressants were not able to consistently reduce the severity of BPD. Low-certainty evidence indicates that anticonvulsants can improve specific symptoms associated with BPD such as anger, aggression, and affective lability but the evidence is mostly limited to single studies. Second-generation antipsychotics had little effect on the severity of specific BPD symptoms, but they improved general psychiatric symptoms in patients with BPD. Conclusions: Despite the common use of pharmacotherapies for patients with BPD, the available evidence does not support the efficacy of pharmacotherapies alone to reduce the severity of BPD. Registration: PROSPERO registration number, CRD42020194098. [ABSTRACT FROM AUTHOR]

Background: Dyspnea is a common and often debilitating symptom with a complex diagnostic work-up.Purpose: To evaluate the benefits, harms, and diagnostic test accuracy of point-of-care ultrasonography (POCUS) in patients with acute dyspnea. (PROSPERO: CRD42019126419).Data Sources: Searches of multiple electronic databases without language limitations (January 2004 to August 2020) and reference lists of pertinent articles and reviews.Study Selection: Five randomized controlled trials (RCTs) and 44 prospective cohort-type studies in patients with acute dyspnea evaluated POCUS as a diagnostic tool to determine the underlying cause of dyspnea. Two investigators independently screened the literature for inclusion.Data Extraction: Data abstraction by a single investigator was confirmed by a second investigator; 2 investigators independently rated risk of bias and determined certainty of evidence.Data Synthesis: Point-of-care ultrasonography, when added to a standard diagnostic pathway, led to statistically significantly more correct diagnoses in patients with dyspnea than the standard diagnostic pathway alone. In-hospital mortality and length of hospital stay did not differ significantly between patients who did or did not receive POCUS in addition to standard diagnostic tests. Finally, POCUS consistently improved the sensitivities of standard diagnostic pathways to detect congestive heart failure, pneumonia, pulmonary embolism, pleural effusion, or pneumothorax; specificities increased in most but not all studies.Limitations: Most studies assessed diagnostic test accuracy, which has limited utility for clinical decision making. Studies rarely reported on the proportion of indeterminate sonography results, and no evidence is available on adverse health outcomes of false-positive or false-negative POCUS results.Conclusion: Point-of-care ultrasonography can improve the correctness of diagnosis in patients with acute dyspnea.Primary Funding Source: American College of Physicians. [ABSTRACT FROM AUTHOR]

Accurate data extraction is a key component of evidence synthesis and critical to valid results. The advent of publicly available large language models (LLMs) has generated interest in these tools for evidence synthesis and created uncertainty about the choice of LLM. We compare the performance of two widely available LLMs (Claude 2 and GPT‐4) for extracting pre‐specified data elements from 10 published articles included in a previously completed systematic review. We use prompts and full study PDFs to compare the outputs from the browser versions of Claude 2 and GPT‐4. GPT‐4 required use of a third‐party plugin to upload and parse PDFs. Accuracy was high for Claude 2 (96.3%). The accuracy of GPT‐4 with the plug‐in was lower (68.8%); however, most of the errors were due to the plug‐in. Both LLMs correctly recognized when prespecified data elements were missing from the source PDF and generated correct information for data elements that were not reported explicitly in the articles. A secondary analysis demonstrated that, when provided selected text from the PDFs, Claude 2 and GPT‐4 accurately extracted 98.7% and 100% of the data elements, respectively. Limitations include the narrow scope of the study PDFs used, that prompt development was completed using only Claude 2, and that we cannot guarantee the open‐source articles were not used to train the LLMs. This study highlights the potential for LLMs to revolutionize data extraction but underscores the importance of accurate PDF parsing. For now, it remains essential for a human investigator to validate LLM extractions. [ABSTRACT FROM AUTHOR]

Importance: Childhood hypertension can result in adverse outcomes during adulthood; identifying and treating primary and secondary childhood hypertension may reduce such risks.Objective: To update the evidence on screening and treatment of hypertension in childhood and adolescence for the US Preventive Services Task Force.Data Sources: PubMed, Cochrane Library, International Pharmaceutical Abstracts, EMBASE, and trial registries through September 3, 2019; bibliographies from retrieved articles, experts, and surveillance of the literature through October 6, 2020.Study Selection: Fair- or good-quality English-language studies evaluating diagnostic accuracy of blood pressure screening; cohort studies assessing the association of hypertension in childhood and adolescence with blood pressure or other intermediate outcomes in adulthood; randomized clinical trials (RCTs) or meta-analyses of pharmacological and lifestyle interventions.Data Extraction and Synthesis: Two reviewers independently assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; the evidence was synthesized qualitatively.Main Outcomes and Measures: Sensitivity, specificity, and measures of association between childhood and adulthood blood pressure; reduction of childhood blood pressure; adverse effects of treatments.Results: Forty-two studies from 43 publications were included (N>12 400). No studies evaluated the benefits or harms of screening and the effect of treating childhood hypertension on outcomes in adulthood. One study reported a sensitivity of 0.82 and a specificity of 0.70 for 2 office-based blood pressure measurements. Twenty observational studies suggested a significant association between childhood hypertension and abnormal blood pressure in adulthood (odds ratios, 1.1-4.5; risk ratios, 1.45-3.60; hazard ratios, 2.8-3.2). Thirteen placebo-controlled RCTs and 1 meta-analysis assessed reductions in systolic (SBP) and diastolic blood pressure from pharmacological treatments. Pooled reductions of SBP were -4.38 mm Hg (95% CI, -7.27 to -2.16) for angiotensin-converting enzyme inhibitors and -3.07 mm Hg (95% CI, -4.99 to -1.44) for angiotensin receptor blockers. Candesartan reduced SBP by -6.56 mm Hg (P < .001; n = 240). β-Blockers, calcium channel blockers, and mineralocorticoid receptor antagonists did not achieve significant reductions over 2 to 4 weeks. SBP was significantly reduced by exercise over 8 months (-4.9 mm Hg, P ≤ .05; n = 69), by dietary approaches to stop hypertension over 3 months (-2.2 mm Hg, P < .01; n = 57), and by a combination of drug treatment and lifestyle interventions over 6 months (-7.6 mm Hg; P < .001; n = 95). Low-salt diet did not achieve reductions of blood pressure.Conclusions and Relevance: Observational studies indicate an association between hypertension in childhood and hypertension in adulthood. However, the evidence is inconclusive whether the diagnostic accuracy of blood pressure measurements is adequate for screening asymptomatic children and adolescents in primary care. [ABSTRACT FROM AUTHOR]

Importance: Postmenopausal status coincides with increased risks for chronic conditions such as heart disease, osteoporosis, cognitive impairment, or some types of cancers. Previously, hormone therapy was used for the primary prevention of these chronic conditions.Objective: To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions.Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries from June 1, 2011, through August 1, 2016. Surveillance for new evidence in targeted publications was conducted through July 1, 2017.Study Selection: English-language randomized clinical trials reporting health outcomes.Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available.Main Outcomes and Measures: Beneficial or harmful changes in risks for various chronic conditions.Results: Eighteen trials (n = 40 058; range, 142-16 608; mean age, 53-79 years) were included. Women using estrogen-only therapy compared with placebo had significantly lower risks, per 10 000 person-years, for diabetes (-19 cases [95% CI, -34 to -3]) and fractures (-53 cases [95% CI, -69 to -39]). Risks were statistically significantly increased, per 10 000 person-years, for gallbladder disease (30 more cases [95% CI, 16 to 48]), stroke (11 more cases [95% CI, 2 to 23]), venous thromboembolism (11 more cases [95% CI, 3 to 22]), and urinary incontinence (1261 more cases [95% CI, 880 to 1689]). Women using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 person-years, for colorectal cancer (-6 cases [95% CI, -9 to -1]), diabetes (-14 cases [95% CI, -24 to -3), and fractures (-44 cases [95% CI, -71 to -13). Risks, per 10 000 person-years, were significantly increased for invasive breast cancer (9 more cases [95% CI, 1 to 19]), probable dementia (22 more cases [95% CI, 4 to 53]), gallbladder disease (21 more cases [95% CI, 10 to 34]), stroke (9 more cases [95% CI, 2 to 19]), urinary incontinence (876 more cases [95% CI, 606 to 1168]), and venous thromboembolism (21 more cases [95% CI, 12 to 33]).Conclusions and Relevance: Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms. The available evidence regarding benefits and harms of early initiation of hormone therapy is inconclusive. [ABSTRACT FROM AUTHOR]

Background: Summary of findings tables in systematic reviews are highly informative but require epidemiological training to be interpreted correctly. The usage of fishbone diagrams as graphical displays could offer researchers an effective approach to simplify content for readers with limited epidemiological training. In this paper we demonstrate how fishbone diagrams can be applied to systematic reviews and present the results of an initial user testing.Methods: Findings from two systematic reviews were graphically depicted in the form of the fishbone diagram. To test the utility of fishbone diagrams compared with summary of findings tables, we developed and pilot-tested an online survey using Qualtrics. Respondents were randomized to the fishbone diagram or a summary of findings table presenting the same body of evidence. They answered questions in both open-ended and closed-answer formats; all responses were anonymous. Measures of interest focused on first and second impressions, the ability to find and interpret critical information, as well as user experience with both displays. We asked respondents about the perceived utility of fishbone diagrams compared to summary of findings tables. We analyzed quantitative data by conducting t-tests and comparing descriptive statistics.Results: Based on real world systematic reviews, we provide two different fishbone diagrams to show how they might be used to display complex information in a clear and succinct manner. User testing on 77 students with basic epidemiological training revealed that participants preferred summary of findings tables over fishbone diagrams. Significantly more participants liked the summary of findings table than the fishbone diagram (71.8% vs. 44.8%; p < .01); significantly more participants found the fishbone diagram confusing (63.2% vs. 35.9%, p < .05) or indicated that it was difficult to find information (65.8% vs. 45%; p < .01). However, more than half of the participants in both groups were unable to find critical information and answer three respective questions correctly (52.6% in the fishbone group; 51.3% in the summary of findings group).Conclusions: Fishbone diagrams are compact visualizations that, theoretically, may prove useful for summarizing the findings of systematic reviews. Initial user testing, however, did not support the utility of such graphical displays. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An important aspect of risk-of-bias assessment is that risk of bias can vary by outcome. This explains why we rated outcomes from some ancillary studies of the WHI as low risk of bias, as Anderson notes. Comment & Response B In Reply b Regarding our systematic review on hormone therapy for the primary prevention of chronic conditions in postmenopausal persons,[1] Dr Anderson and Dr Chlebowski and Mr Aragaki express concern about our assessment of the methodological quality of the WHI, which we rated as fair quality or moderate risk of bias.[[2]] Bias, in general terms, is a systematic error in study design, conduct, or analysis that can overestimate or underestimate the true intervention effect.[4] However, quantifying bias and assessing the extent of the impact of bias on study results are usually impossible. [Extracted from the article]

We conducted this systematic review for the American Psychiatric Association (APA) to support the development of clinical practice guidelines on BPD. Finally, Pereira Ribeiro and colleagues make the important point that minimal clinically important differences (MCID) of individual scales would have been a valuable addition to our systematic review. Following advice from experts of the APA (the publisher of the Diagnostic and Statistical Manual [DSM]), we excluded studies that enrolled participants based on criteria of the DSM-III. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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/. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine whether producers or users of systematic reviews using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach or a close variation give the same meanings to terms intended to convey uncertainty about treatment effects when interpreting grades for the quality or strength of evidence. Study Design and Setting: Following exploratory interviews with stakeholders and user testing, we conducted an international Webbased survey among producers and users of systematic reviews. For each quality grade (high, moderate, low, very low/insufficient), we asked participants to assign a minimum likelihood that treatment effects will not change substantially as new studies emerge. Using multivariate analysis of covariance, we tested whether the estimated likelihoods differed between producers and users. Results: In all, 244 participants completed the survey. The associated minimum likelihoods that treatment effects will not change substantially for high, moderate, and low grades of quality of evidence (QOE) were 86% [95% confidence interval (CI): 85%, 87%], 61% (95% CI: 59%, 63%), and 34% (95% CI: 32%, 36%), respectively (very low was preset at 0%). Likelihoods for each grade were similar between producers and users of systematic reviews (P O 0.05 for all comparisons). Conclusion: GRADE is, in general, a suitable method to convey uncertainties for systematic review producers to users. The wide ranges of likelihoods associated with GRADE terms suggest that current definitions of levels of QOE that rely exclusively on qualitative certainty expressions should be augmented by numerical predictions once such data are available. [ABSTRACT FROM AUTHOR]

Background: Sexual dysfunction (SD) is prevalent in patients with major depressive disorder (MDD) and is also associated with second-generation antidepressants (SGADs) that are commonly used to treat the condition. Evidence indicates under-reporting of SD in efficacy studies. SD associated with antidepressant treatment is a serious side effect that may lead to early termination of treatment and worsening of quality of life. Objectives: Our objective was to systematically assess the harms of SD associated with SGADs in adult patients with MDD by drug type. Methods: We retrieved English-language abstracts from PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to October 2012 as well as from reference lists of pertinent review articles and grey literature searches. Two independent reviewers identified randomized controlled trials (RCTs) of at least 6 weeks' duration and observational studies with at least 1,000 participants. Study Selection: Reviewers abstracted data on study design, conduct, participants, interventions, outcomes and method of SD ascertainment, and rated risk of bias. A senior reviewer checked and confirmed extracted data and risk-of-bias ratings. Analyses: Random effects network meta-analysis using Bayesian methods for data from head-to-head trials and placebo-controlled comparisons; descriptive analyses calculating weighted mean rates from individual trials and observational studies. Results/Synthesis: Data from 63 studies of low and moderate risk of bias (58 RCTs, five observational studies) with more than 26,000 patients treated with SGADs were included. Based on network meta-analyses of 66 pairwise comparisons from 37 RCTs, most comparisons showed a similar risk of SD among included SGADs. However, credible intervals were wide and included differences that would be considered clinically relevant. We observed three main patterns: bupropion had a statistically significantly lower risk of SD than some other SGADs, and both escitalopram and paroxetine showed a statistically significantly higher risk of SD than some other SGADs. We found reporting of harms related to SD inconsistent and insufficient in some trials. Limitations: Most trials were conducted in highly selected populations. Search was restricted to English-language only. Conclusion and Implications: Because of the indirect nature of the comparisons, the often wide credible intervals, and the high variation in magnitude of outcome, we rated the overall strength of evidence with respect to our findings as low. The current degree of evidence does not allow a precise estimate of comparative risk of SD associated with a specific antidepressant. In the absence of such evidence, clinicians need to be aware of SD as a common adverse event and should discuss patients' preferences before initiating antidepressant therapy. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

Background Screening with mammography has the ability to detect breast cancer at an early stage but misses some cancers. Supporters of adjunct ultrasonography to the screening regimen argue that it might be a safe and inexpensive approach to reduce the false-negative rates of screening. Critics are concerned that adjunct ultrasonography will also increase the rate of false-positive findings and can lead to unnecessary biopsies and treatments in women at average risk. Aims The purpose of this review was to systematically assess the comparative benefits and harms of mammography with adjunct breast ultrasonography and mammography only in breast cancer screening. Methods We searched multiple electronic databases and the Cochrane Breast Cancer Group's Specialised Register (from 1995 to February 2012). To detect ongoing or unpublished studies, we searched trial registries and multiple sources of grey literature. Two researchers independently reviewed all abstracts and full-text articles against pre-defined eligibility criteria. We dually rated the risk of bias of studies and the strength of evidence based on established guidance. Results We did not detect any controlled studies that provide evidence for (or against) the use of adjunct ultrasonography for screening in women at average risk for breast cancer. Extrapolations of results from women at elevated risk for breast cancer indicate that the false-positive rates in women at average risk who were recalled because of positive ultrasonographies will exceed 98%. In women with dense or very dense breast tissue, the evidence regarding the use of adjunct ultrasonography is not conclusive. Conclusions No methodologically sound evidence is available justifying the routine use of ultrasonography as an adjunct screening tool in women at average risk for breast cancer. Implications for practice Clinicians should not use ultrasonography as a screening tool for breast cancer screening on a routine basis. The use should be limited to women with dense breasts for whom the accuracy of mammography is low, or for diagnostic purposes. [ABSTRACT FROM AUTHOR]

Background: Second-generation antidepressants dominate the management of major depressive disorder (MDD), but evidence on the comparative benefits and harms of these agents is contradictory. Purpose: To compare the benefits and harms of second-generation antidepressants for treating MDD in adults. Data Sources: English-language studies from PubMed, Embase, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to August 2011 and reference lists of pertinent review articles and gray literature. Study Selection: 2 independent reviewers identified randomized trials of at least 6 weeks' duration to evaluate efficacy and observational studies with at least 1000 participants to assess harm. Data Extraction: Reviewers abstracted data about study design and conduct, participants, and interventions and outcomes and rated study quality. A senior reviewer checked and confirmed extracted data and quality ratings. Data Synthesis: Meta-analyses and mixed-treatment comparisons of response to treatment and weighted mean differences were conducted on specific scales to rate depression. On the basis of 234 studies, no clinically relevant differences in efficacy or effectiveness were detected for the treatment of acute, continuation, and maintenance phases of MDD. No differences in efficacy were seen in patients with accompanying symptoms or in subgroups based on age, sex, ethnicity, or comorbid conditions. Individual drugs differed in onset of action, adverse events, and some measures of healthrelated quality of life. Limitations: Most trials were conducted in highly selected populations. Publication bias might affect the estimates of some comparisons. Mixed-treatment comparisons cannot conclusively exclude differences in efficacy. Evidence within subgroups was limited. Conclusion: Current evidence does not warrant recommending a particular second-generation antidepressant on the basis of differences in efficacy. Differences in onset of action and adverse events may be considered when choosing a medication. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This article is to establish recommendations for conducting quantitative synthesis, or meta-analysis, using study-level data in comparative effectiveness reviews (CERs) for the Evidence-based Practice Center (EPC) program of the Agency for Healthcare Research and Quality. Study Design and Setting: We focused on recurrent issues in the EPC program and the recommendations were developed using group discussion and consensus based on current knowledge in the literature. Results: We first discussed considerations for deciding whether to combine studies, followed by discussions on indirect comparison and incorporation of indirect evidence. Then, we described our recommendations on choosing effect measures and statistical models, giving special attention to combining studies with rare events; and on testing and exploring heterogeneity. Finally, we briefly presented recommendations on combining studies of mixed design and on sensitivity analysis. Conclusion: Quantitative synthesis should be conducted in a transparent and consistent way. Inclusion of multiple alternative interventions in CERs increases the complexity of quantitative synthesis, whereas the basic issues in quantitative synthesis remain crucial considerations in quantitative synthesis for a CER. We will cover more issues in future versions and update and improve recommendations with the accumulation of new research to advance the goal for transparency and consistency. [Copyright &y& Elsevier]

Being male or female is an important determinant of risks for certain diseases, patterns of illness and life expectancy. Although differences in risks for and prognoses of several diseases have been well documented, sex-based differences in responses to pharmaceutical treatments and accompanying risks of adverse events are less clear. The objective of this umbrella review was to determine whether clinically relevant differences in efficacy and safety of commonly prescribed medications exist between men and women. We retrieved all available systematic reviews of the Oregon Drug Effectiveness Review Project published before January 2010. Two persons independently reviewed each report to identify relevant studies. We dually abstracted data from the original publications into standardized forms. We synthesized the available evidence for each drug class and rated its quality applying the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Findings, based on 59 studies and data of more than 250,000 patients suggested that for the majority of drugs no substantial differences in efficacy and safety exist between men and women. Some clinically important exceptions, however, were apparent: women experienced substantially lower response rates with newer antiemetics than men (45% vs. 58%; relative risk 1.49, 95% confidence interval 1.35–1.64); men had higher rates of sexual dysfunction than women while on paroxetine for major depressive disorder; women discontinued lovastatin more frequently than men because of adverse events. Overall, for the majority of drugs sex does not appear to be a factor that has to be taken into consideration when choosing a drug treatment. The available body of evidence, however, was limited in quality and quantity, confining the range and certainty of our conclusions. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The objective of this study was to determine the effect of industry bias in a systematically reviewed body of evidence of head-to-head trials. Study Design and Setting: We limited our analysis to published head-to-head randomized controlled trials of selective serotonin reuptake inhibitors (SSRIs) identified in a comparative effectiveness review. Two reviewers independently determined the status of funding for each trial. We classified drugs into one of two groups: (1) drugs associated with the funding source and (2) drugs not associated with the funding source. To determine the effect of any underlying industry bias, we conducted relative-benefit meta-analyses comparing the response rates of drugs when associated with the funding source with response rates of the same drugs when not associated with the funding source. Results: Thirteen out of 20 studies (65%) numerically favored drugs associated with the funding source over drugs used as controls. The pooled response rates of SSRIs, when associated with the funding source, are significantly greater than those of the same SSRIs when not associated with the sponsor (relative benefit=1.07; 95% confidence interval=1.02–1.11). The difference, however, is likely to be not of clinical importance. Conclusions: The effect of industry bias in comparative effectiveness reviews might play a lesser role than in systematic reviews of placebo-controlled trials. [Copyright &y& Elsevier]

Background: Second-generation antidepressants dominate the management of major depressive disorder, dysthymia, and subsyndromal depression. Evidence on the comparative benefits and harms is still accruing. Purpose: To compare the benefits and harms of second-generation antidepressants (bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine) for the treatment of depressive disorders in adults. Data Sources: MEDLINE, EMBASE, PsychLit, Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts from 1980 to April 2007, limited to English-language articles. Reference lists of pertinent review articles were manually searched and the Center for Drug Evaluation and Research database was explored to identify unpublished research. Study Selection: Abstracts and full-text articles were independently reviewed by 2 persons. Six previous good- or fair-quality systematic reviews or meta-analyses were included, as were 155 good- or fair-quality double-blind, placebo-controlled, or head-to-head randomized, controlled trials of at least 6 weeks' duration. For harms, 35 observational studies with at least 100 participants and follow- up of at least 12 weeks were also included. Data Extraction: Using a standard protocol, investigators abstracted data on study design and quality-related details, funding, settings, patients, and outcomes. Data Synthesis: If data were sufficient, meta-analyses of head-tohead trials were conducted to determine the relative benefit of response to treatment and the weighted mean differences on specific depression rating scales. If sufficient evidence was not available, adjusted indirect comparisons were conducted by using meta-regressions and network meta-analyses. Secondgeneration antidepressants did not substantially differ in efficacy or effectiveness for the treatment of major depressive disorder on the basis of 203 studies; however, the incidence of specific adverse events and the onset of action differed. The evidence is insufficient to draw conclusions about the comparative efficacy, effectiveness, or harms of these agents for the treatment of dysthymia and subsyndromal depression. Limitation: Adjusted indirect comparisons have methodological limitations and cannot conclusively rule out differences in efficacy. Conclusion: Current evidence does not warrant the choice of one second-generation antidepressant over another on the basis of differences in efficacy and effectiveness. Other differences with respect to onset of action and adverse events may be relevant for the choice of a medication. [ABSTRACT FROM AUTHOR]

Background: The comparative effectiveness of rheumatoid arthritis therapies is uncertain. Purpose: To compare the benefits and harms of disease-modifying antirheumatic drugs (DMARDs) for adults with rheumatoid arthritis. Data Sources: Records limited to the English language and studies of adults were identified by using MEDLINE, EMBASE, The Cochrane Library, and International Pharmaceutical Abstracts from 1980 to September 2007. Study Selection: Two persons independently selected relevant head-to-head trials and prospective cohort studies with at least 100 participants and 12-week follow-up and relevant good- or fair-quality meta-analyses that compared benefits or harms of 11 drug therapies. For harms, they included retrospective cohort studies. Data Extraction: Information on study design, interventions, outcomes,and quality were extracted according to a standard protocol. Data Synthesis: Head-to-head trials (n = 23), mostly examining synthetic DMARDs, showed no clinically important differences in efficacy among synthetic DMARDs (limited to methotrexate, leflunomide, and sulfasalazine) or among anti-tumor necrosis factor drugs (adalimumab, etanercept, and infliximab). Monotherapy with anti-tumor necrosis factor drugs resulted in better radiographic outcomes than did methotrexate but no important differences in clinical outcomes (for example, 20%, 50%, or 70% improvement according to American College of Rheumatology response criteria). Various combinations of biological DMARDs plus methotrexate improved clinical response rates and functional outcomes more than monotherapy with either methotrexate or biological DMARDs. In patients whose monotherapy failed, combination therapy with synthetic DMARDs improved response rates. Numbers and types of short-term adverse events were similar for biological and synthetic DMARDs. The evidence was insufficient to draw conclusions about differences for rare but serious adverse events for biological DMARDs. Limitation: Most studies were short-term efficacy trials conducted in selected populations with few comorbid conditions. Conclusion: Limited available comparative evidence does not support one monotherapy over another for adults with rheumatoid arthritis. Although combination therapy is more effective for patients whose monotherapy fails, the evidence is insufficient to draw firm conclusions about whether one combination or treatment strategy is better than another or is the best treatment for early rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Objective: 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. Results: 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 (≥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 in <20% of patients on average. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To propose and test a simple instrument based on seven criteria of study design to distinguish effectiveness (pragmatic) from efficacy (explanatory) trials. Study Design: Currently no validated definition of effectiveness studies exists. We asked the directors of 12 Evidence-based Practice Centers to select six studies each: four that they considered to be examples of effectiveness trials and two considered efficacy studies. We then applied our proposed criteria to test the construct validity using the selected studies as if they had been identified by a gold standard. Results: Based on the rationale to identify effectiveness studies reliably with minimal false positives (i.e., a high specificity), a cutoff of six criteria produced the most desirable balance between sensitivity and specificity. This setting produced a specificity of 0.83 and a sensitivity of 0.72. Conclusion: When applied in a standardized manner, our proposed criteria can provide a valid and simple tool to distinguish effectiveness from efficacy studies. The applicability of systematic reviews can improve when analysts place more emphasis on the generalizability of included studies. In addition, clinicians can also use our criteria to determine the external validity of individual studies, given an appropriate population of interest. [Copyright &y& Elsevier]

The article aims to investigate the efficacy, effectiveness and safety of inhaled corticosteroids with respect to health outcomes in patients with chronic obstructive pulmonary disease (COPD). The findings revealed that 13 double-blinded randomized controlled trials determined the efficacy of an inhaled corticosteroid compared with placebo while 11 additional studies confirmed the safety of inhaled corticosteroid treatment in patients with asthma or COPD.

Background: Reviews have compared the efficacy and tolerability of newer second-generation antidepressants with those of placebo or older treatments, but comparative evidence for use of second-generation antidepressants to treat major depressive disorder has not been evaluated. Purpose: To systematically evaluate comparative data on the efficacy, effectiveness, and tolerability of commonly prescribed second-generation anti depressants (selective seroton in reuptake inhibitors, bupropion, duloxetine, mirtazapine, and venlafaxine) in the treatment of major depressive disorder. Data Sources: MEDLINE, EMBASE, and PsychLit; the Cochrane Library; and the International Pharmaceutical Abstracts were searched from January 1980 through February 2005 for reviews; randomized, controlled trials; meta-analyses; and observational studies. Study Selection: The authors reviewed 46 head-to-head randomized, controlled trials comparing one second-generation antidepressant with another. Twenty-four observational studies and placebo-controlled trials were also included for assessment of safety and tolerability. Data Extraction: Two researchers independently reviewed titles and abstracts. Trained reviewers abstracted data from each study and assigned an initial quality rating. A second reviewer verified the data extraction and quality rating. Data Synthesis: According to fair to good evidence, the second-generation antidepressants that were compared had only minimal differences in efficacy, and 88% of comparative efficacy studies reported no statistically significant difference in any outcome measure at the end of the study. One effectiveness trial rated good and 2 effectiveness trials rated fair reported no statistically significant differences in primary outcome measures for compared drugs. Meta-analyses showed a modest but statistically significant additional treatment effect for sertraline and venlafaxine compared with fluoxetine. About 96% of comparative trials were sponsored by or had at least 1 author affiliated with a pharmaceutical company; the remaining trials did not report funding sources. Adverse event profiles differed among drugs; however, the degree and quality of adverse event assessment varied and only 13% of trials used a standardized scale to assess adverse events. Limitations: Quantitative analyses could not be done for many drug comparisons because the quantity and quality of the evidence were inadequate. Most published evidence was from trials sponsored by pharmaceutical companies, and publication bias may have occurred. Conclusions: Overall, second-generation antidepressants probably do not differ substantially for treatment of major depressive disorder. Choosing the agent that is most appropriate for a given patient is difficult. [ABSTRACT FROM AUTHOR]

Background Peripheral intravenous catheters (PIVCs) contribute substantially to the global burden of infections. This systematic review assessed 24 infection prevention and control (IPC) interventions to prevent PIVC-associated infections and other complications. Methods We searched Ovid MEDLINE, Embase, Cochrane Library, WHO Global Index Medicus, CINAHL, and reference lists for controlled studies from 1 January 1980–16 March 2023. We dually selected studies, assessed risk of bias, extracted data, and rated the certainty of evidence (COE). For outcomes with 3 or more trials, we conducted Bayesian random-effects meta-analyses. Results 105 studies met our prespecified eligibility criteria, addressing 16 of the 24 research questions; no studies were identified for 8 research questions. Based on findings of low to high COE, wearing gloves reduced the risk of overall adverse events related to insertion compared with no gloves (1 non-randomized controlled trial [non-RCT]; adjusted risk ratio [RR],.52; 95% CI,.33–.85), and catheter removal based on defined schedules potentially resulted in a lower phlebitis/thrombophlebitis incidence (10 RCTs; RR, 0.74, 95% credible interval,.49–1.01) compared with clinically indicated removal in adults. In neonates, chlorhexidine reduced the phlebitis score compared with non–chlorhexidine-containing disinfection (1 RCT; 0.14 vs 0.68; P =.003). No statistically significant differences were found for other measures. Conclusions Despite their frequent use and concern about PIVC-associated complications, this review underscores the urgent need for more high-quality studies on effective IPC methods regarding safe PIVC management. In the absence of valid evidence, adherence to standard precaution measures and documentation remain the most important principles to curb PIVC complications. Clinical Trials Registration The protocol was registered in the Open Science Framework (https://osf.io/exdb4). [ABSTRACT FROM AUTHOR]

Summary: Importance: The effectiveness of anti‐obesity medications for children and adolescents is unclear. Objective: To update the evidence on the benefits and harms of anti‐obesity medication. Data Sources: Cochrane CENTRAL, MEDLINE, ClinicalTrials.gov and WHO ICTRP (1/1/16–17/3/23). Study Selection: Randomized controlled trials ≥6 months in people <19 years living with obesity. Data Extraction and Synthesis: Screening, data extraction and quality assessment conducted in duplicate, independently. Main Outcomes and Measures: Body mass index (BMI): 95th percentile BMI, adverse events and quality of life. Results: Thirty‐five trials (N = 4331), follow‐up: 6–24 months; age: 8.8–16.3 years; BMI: 26.2–41.7 kg/m2. Moderate certainty evidence demonstrated a −1.71 (95% confidence interval [CI]: −2.27 to −1.14)‐unit BMI reduction, ranging from −0.8 to −5.9 units between individual drugs with semaglutide producing the largest reduction of −5.88 kg/m2 (95% CI: −6.99 to −4.77, N = 201). Drug type explained ~44% of heterogeneity. Low certainty evidence demonstrated reduction in 95th percentile BMI: −11.88 percentage points (95% CI: −18.43 to −5.30, N = 668). Serious adverse events and study discontinuation due to adverse events did not differ between medications and comparators, but medication dose adjustments were higher compared to comparator (10.6% vs 1.7%; RR = 3.74 [95% CI: 1.51 to 9.26], I2 = 15%), regardless of approval status. There was a trend towards improved quality of life. Evidence gaps exist for children, psychosocial outcomes, comorbidities and weight loss maintenance. Conclusions and Relevance: Anti‐obesity medications in addition to behaviour change improve BMI but may require dose adjustment, with 1 in 100 adolescents experiencing a serious adverse event. [ABSTRACT FROM AUTHOR]

Objective: Borderline personality disorder (BPD) is the most common personality disorder, affecting 1.8% of the general population, 10% of psychiatric outpatients, and 15%–25% of psychiatric inpatients. Practice guidelines recommend psychotherapies as first-line treatments. However, psychotherapies commonly used for the treatment of BPD are numerous, and little is known about the comparative effectiveness of each individual psychotherapy versus treatment as usual (TAU) or other psychotherapies. To systematically assess the comparative effectiveness of commonly used psychotherapies versus TAU or versus other psychotherapies for BPD treatment. Method: We conducted systematic literature searches in MEDLINE, EMBASE, the Cochrane Library, and APA PsycINFO up to July 14, 2022, and searched reference lists of pertinent articles and reviews. Inclusion criteria were (a) patients 13 years or older with a diagnosis of BPD, (b) treatment with commonly used psychotherapies, (c) comparison with TAU or another psychotherapy, (d) assessment of relevant BPD-related health outcomes, and (e) randomized or nonrandomized trials or controlled observational studies. Two investigators independently screened abstracts and full-text articles and graded the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: We found 25 psychotherapy studies meeting inclusion criteria with data on 2,545 participants. Seventeen studies compared nine psychotherapies with TAU and nine studies compared eight psychotherapies with another psychotherapy for the treatment of BPD. Overall, both TAU and included psychotherapies were effective in treating the severity and symptoms of BPD. Moderate certainty of evidence suggests that systems training for emotional predictability and problem solving is more effective than TAU for the treatment of BPD; low certainty of evidence suggests that dialectical behavior therapy, schema therapy, transference-focused psychotherapy, acceptance and commitment therapy, manual-assisted cognitive therapy, and cognitive behavioral therapy are more effective than TAU for treating BPD. We were unable to draw conclusions from head-to-head comparisons of psychotherapies, which were limited to single studies with very low to low certainty of evidence. Conclusions: All commonly used psychotherapies improve BPD severity, symptoms, and functioning. Our assessment found no strong evidence suggesting that any one psychotherapy is more beneficial than another. What is the public health significance of this article?: For clinicians, this work can be used to inform practice guidelines on psychotherapies to treat BPD. For funders, policymakers, and researchers, this work identifies research gaps and opportunities for future research in the area. [ABSTRACT FROM AUTHOR]

Background: Web applications that employ natural language processing technologies to support systematic reviewers during abstract screening have become more common. The goal of our project was to conduct a case study to explore a screening approach that temporarily replaces a human screener with a semi-automated screening tool. Methods: We evaluated the accuracy of the approach using DistillerAI as a semi-automated screening tool. A published comparative effectiveness review served as the reference standard. Five teams of professional systematic reviewers screened the same 2472 abstracts in parallel. Each team trained DistillerAI with 300 randomly selected abstracts that the team screened dually. For all remaining abstracts, DistillerAI replaced one human screener and provided predictions about the relevance of records. A single reviewer also screened all remaining abstracts. A second human screener resolved conflicts between the single reviewer and DistillerAI. We compared the decisions of the machine-assisted approach, single-reviewer screening, and screening with DistillerAI alone against the reference standard. Results: The combined sensitivity of the machine-assisted screening approach across the five screening teams was 78% (95% confidence interval [CI], 66 to 90%), and the combined specificity was 95% (95% CI, 92 to 97%). By comparison, the sensitivity of single-reviewer screening was similar (78%; 95% CI, 66 to 89%); however, the sensitivity of DistillerAI alone was substantially worse (14%; 95% CI, 0 to 31%) than that of the machine-assisted screening approach. Specificities for single-reviewer screening and DistillerAI were 94% (95% CI, 91 to 97%) and 98% (95% CI, 97 to 100%), respectively. Machine-assisted screening and single-reviewer screening had similar areas under the curve (0.87 and 0.86, respectively); by contrast, the area under the curve for DistillerAI alone was just slightly better than chance (0.56). The interrater agreement between human screeners and DistillerAI with a prevalence-adjusted kappa was 0.85 (95% CI, 0.84 to 0.86%). Conclusions: The accuracy of DistillerAI is not yet adequate to replace a human screener temporarily during abstract screening for systematic reviews. Rapid reviews, which do not require detecting the totality of the relevant evidence, may find semi-automation tools to have greater utility than traditional systematic reviews. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 ). [ABSTRACT FROM AUTHOR]

There is concern that preprint articles will lead to an increase in the amount of scientifically invalid work available. The objectives of this study were to determine the proportion of prevention preprints published within 12 months, the consistency of the effect estimates and conclusions between preprint and published articles, and the reasons for the nonpublication of preprints. Of the 329 prevention preprints that met our eligibility criteria, almost half (48.9%) were published in a peer-reviewed journal within 12 months of being posted. While 16.8% published preprints showed some change in the magnitude of the primary outcome effect estimate, 4.4% were classified as having a major change. The style or wording of the conclusion changed in 42.2%, the content in 3.1%. Preprints on chemoprevention, with a cross-sectional design, and with public and noncommercial funding had the highest probabilities of publication. The main reasons for the nonpublication of preprints were journal rejection or lack of time. The reliability of preprint articles for evidence-based decision-making is questionable. Less than half of the preprint articles on prevention research are published in a peer-reviewed journal within 12 months, and significant changes in effect sizes and/or conclusions are still possible during the peer-review process. [ABSTRACT FROM AUTHOR]

This update of a living, rapid review assesses the benefits and harms of 22 medications for treating the Omicron variant of COVID-19 in the outpatient setting. This systematic review summarizes the evidence published from 26 November 2021 to 2 March 2023. Background: Clinicians and patients want to know the benefits and harms of outpatient treatment options for the Omicron variant of SARS-CoV-2. Purpose: To assess the benefits and harms of 22 different COVID-19 treatments. Data Sources: The Epistemonikos COVID-19 L·OVE platform, the iSearch COVID-19 portfolio, and the World Health Organization (WHO) COVID-19 Research Database from 26 November 2021 to 2 March 2023. Study Selection: Two reviewers independently screened abstracts and full texts against a priori–defined criteria. Data Extraction: One reviewer extracted the data and assessed the risk of bias and certainty of evidence (COE). A second reviewer verified the data abstraction and assessments. Data Synthesis: Two randomized controlled trials and 6 retrospective cohort studies were included. Nirmatrelvir–ritonavir was associated with a reduction in hospitalization due to COVID-19 (for example, 0.7% vs. 1.2%; moderate COE) and all-cause mortality (for example, <0.1% vs. 0.2%; moderate COE). Molnupiravir led to a higher recovery rate (31.8% vs. 22.6%; moderate COE) and reduced time to recovery (9 vs. 15 median days; moderate COE) but had no effect on all-cause mortality (0.02% vs. 0.04%; moderate COE) and the incidence of serious adverse events (0.4% vs. 0.3%; moderate COE). Ivermectin had no effect on time to recovery (moderate COE) and resulted in no difference in adverse events compared with placebo (low COE). Sotrovimab resulted in no difference in all-cause mortality compared with no treatment (low COE). No eligible studies for all other treatments of interest were identified. Limitation: Evidence for nirmatrelvir–ritonavir and sotrovimab is based on nonrandomized studies only. Conclusion: Nirmatrelvir–ritonavir and molnupiravir probably improve outcomes for outpatients with mild to moderate COVID-19. Primary Funding Source: American College of Physicians. (PROSPERO: CRD42023406456) [ABSTRACT FROM AUTHOR]

A response from the authors of the article "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" that was published in the 2016 issue is presented.

Several letters to the editor and a response from the author of the article "Salt in Health and Disease—A Delicate Balance, " by T. A. Kotchen and colleagues in the 2013 issue are presented.

The article focuses on the study by A. Cipriani and colleagues which rated second-generation antidepressants sertraline and escitalopram as having the most favorable balance between benefit and harm in patients with major depressive disorder (MDD) published in "The Lancet." The authors are said to formulate their results using a statistical technique called multiple treatment meta-analysis. It cites the authors' use of attrition rates in their study, which is said to be an inadequate measure of treatment tolerability.

Developers of clinical practice guidelines need to take patient values and preferences into consideration when weighing benefits and harms of treatment options for depressive disorders. This rapid review summarizes studies on patient values and preferences for initial or second-line treatment of major depression. Background: Developers of clinical practice guidelines need to take patient values and preferences into consideration when weighing benefits and harms of treatment options for depressive disorder. Purpose: To assess patient values and preferences regarding pharmacologic and nonpharmacologic treatments of depressive disorder. Data Sources: MEDLINE (Ovid) and PsycINFO (EBSCO) were searched for eligible studies published from 1 January 2014 to 30 November 2022. Study Selection: Pairs of reviewers independently screened 30% of search results. The remaining 70% of the abstracts were screened by single reviewers; excluded abstracts were checked by a second reviewer. Pairs of reviewers independently screened full texts. Data Extraction: One reviewer extracted data and assessed the certainty of evidence, and a second reviewer checked for completeness and accuracy. Two reviewers independently assessed risk of bias. Data Synthesis: The review included 11 studies: 4 randomized controlled trials, 5 cross-sectional studies, and 2 qualitative studies. In 1 randomized controlled trial, participants reported at the start of therapy that they expected supportive-expressive psychotherapy and antidepressants to yield similar improvements. A cross-sectional study reported that non-Hispanic White participants and men generally preferred antidepressants over talk therapy, whereas Hispanic and non-Hispanic Black participants and women generally did not have a preference. Another cross-sectional study reported that the most important nonserious adverse events for patients treated with antidepressants were insomnia, anxiety, fatigue, weight gain, agitation, and sexual dysfunction. For other comparisons and outcomes, no conclusions could be drawn because of the insufficient certainty of evidence. Limitations: The main limitation of this review is the low or insufficient certainty of evidence for most outcomes. No evidence was available on second-step depression treatment or differences in values and preferences based on gender, race/ethnicity, age, and depression severity. Conclusion: Low-certainty evidence suggests that there may be some differences in preferences for talk therapy or pharmacologic treatment of depressive disorders based on gender or race/ethnicity. In addition, low-certainty evidence suggests that insomnia, anxiety, fatigue, weight gain, agitation, and sexual dysfunction may be the most important nonserious adverse events for patients treated with antidepressants. Evidence is lacking or insufficient to draw any further conclusions about patients' weighing or valuation of the benefits and harms of depression treatments. Primary Funding Source: American College of Physicians. (PROSPERO: CRD42020212442) [ABSTRACT FROM AUTHOR]

Major depressive disorder is the most prevalent, disabling form of depression and has a large economic effect. This rapid review summarizes the evidence on cost-effectiveness of pharmacologic and nonpharmacologic interventions as first- and second-step treatments in patients with major depression. Background: Major depressive disorder (MDD) is the most prevalent, disabling form of depression, with a high economic effect. Purpose: To assess evidence on cost-effectiveness of pharmacologic and nonpharmacologic interventions as first- and second-step treatments in patients with MDD. Data Sources: Multiple electronic databases limited to English language were searched (1 January 2015 to 29 November 2022). Study Selection: Two investigators independently screened the literature. Seven economic modeling studies fulfilled the eligibility criteria. Data Extraction: Data abstraction by a single investigator was confirmed by a second; 2 investigators independently rated risk of bias. One investigator determined certainty of evidence, and another checked for plausibility. Data Synthesis: Seven modeling studies met the eligibility criteria. In a U.S. setting over a 5-year time horizon, cognitive behavioral therapy (CBT) was cost-effective compared with second-generation antidepressants (SGAs) as a first-step treatment from the societal and health care sector perspectives. However, the certainty of evidence is low, and the findings should be interpreted cautiously. For second-step treatment, only switch strategies between SGAs were assessed. The evidence is insufficient to draw any conclusions. Limitations: Methodologically heterogeneous studies, which compared only CBT and some SGAs, were included. No evidence on other psychotherapies or complementary and alternative treatments as first-step treatment or augmentation strategies as second-step treatment was available. Conclusion: Although CBT may be cost-effective compared with SGAs as a first-step treatment at a 5-year time horizon from the societal and health care sector perspectives, the certainty of evidence is low, and the findings need to be interpreted cautiously. For other comparisons, the evidence was entirely missing or insufficient to draw conclusions. Primary Funding Source: American College of Physicians. [ABSTRACT FROM AUTHOR]

Background: Policymakers and healthcare stakeholders are increasingly seeking evidence to inform the policymaking process, and often use existing or commissioned systematic reviews to inform decisions. However, the methodologies that make systematic reviews authoritative take time, typically 1 to 2 years to complete. Outside the traditional SR timeline, "rapid reviews" have emerged as an efficient tool to get evidence to decision-makers more quickly. However, the use of rapid reviews does present challenges. To date, there has been limited published empirical information about this approach to compiling evidence. Thus, it remains a poorly understood and ill-defined set of diverse methodologies with various labels. In recent years, the need to further explore rapid review methods, characteristics, and their use has been recognized by a growing network of healthcare researchers, policymakers, and organizations, several with ties to Cochrane, which is recognized as representing an international gold standard for high-quality, systematic reviews. Purpose: In this commentary, we introduce the newly established Cochrane Rapid Reviews Methods Group developed to play a leading role in guiding the production of rapid reviews given they are increasingly employed as a research synthesis tool to support timely evidence-informed decision-making. We discuss how the group was formed and outline the group's structure and remit. We also discuss the need to establish a more robust evidence base for rapid reviews in the published literature, and the importance of promoting registration of rapid review protocols in an effort to promote efficiency and transparency in research. Conclusion: As with standard systematic reviews, the core principles of evidence-based synthesis should apply to rapid reviews in order to minimize bias to the extent possible. The Cochrane Rapid Reviews Methods Group will serve to establish a network of rapid review stakeholders and provide a forum for discussion and training. By facilitating exchange, the group will strive to conduct research to advance the methods of rapid reviews. [ABSTRACT FROM AUTHOR]

Background: Clinicians and patients want to know the benefits and harms of outpatient treatment options for SARS-CoV-2 infection.Purpose: To assess the benefits and harms of 12 different COVID-19 treatments in the outpatient setting.Data Sources: Epistemonikos COVID-19 L·OVE Platform, searched on 4 April 2022.Study Selection: Two reviewers independently screened abstracts and full texts against a priori-defined criteria. Randomized controlled trials (RCTs) that compared COVID-19 treatments in adult outpatients with confirmed SARS-CoV-2 infection were included.Data Extraction: One reviewer extracted data and assessed risk of bias and certainty of evidence (COE). A second reviewer verified data abstraction and assessments.Data Synthesis: The 26 included studies collected data before the emergence of the Omicron variant. Nirmatrelvir-ritonavir and casirivimab-imdevimab probably reduced hospitalizations (1% vs. 6% [1 RCT] and 1% vs. 4% [1 RCT], respectively; moderate COE). Nirmatrelvir-ritonavir probably reduced all-cause mortality (0% vs. 1% [1 RCT]; moderate COE), and regdanvimab probably improved recovery (87% vs. 72% [1 RCT]; moderate COE). Casirivimab-imdevimab reduced time to recovery by a median difference of 4 days (10 vs. 14 median days [1 RCT]; high COE). Molnupiravir may reduce all-cause mortality, sotrovimab may reduce hospitalization, and remdesivir may improve recovery (low COE). Lopinavir-ritonavir and azithromycin may have increased harms, and hydroxychloroquine may result in lower recovery rates (low COE). Other treatments had insufficient evidence or no statistical difference in efficacy and safety versus placebo.Limitation: Many outcomes had few events and small samples.Conclusion: Some antiviral medications and monoclonal antibodies may improve outcomes for outpatients with mild to moderate COVID-19. However, the generalizability of the findings to the currently dominant Omicron variant is limited.Primary Funding Source: American College of Physicians. (PROSPERO: CRD42022323440). [ABSTRACT FROM AUTHOR]