Search

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]

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]

Paracoccidioidomycosis is a systemic mycosis that is endemic in geographical regions of Central and South America. Cases that occur in nonendemic regions of the world are imported through migration and travel. Due to the limited number of cases in Europe, most physicians are not familiar with paracoccidioidomycosis and its close clinical and histopathological resemblance to other infectious and noninfectious disease. To increase awareness of this insidious mycosis, we conducted a systematic review to summarize the evidence on cases diagnosed and reported in Europe. We searched PubMed and Embase to identify cases of paracoccidioidomycosis diagnosed in European countries. In addition, we used Scopus for citation tracking and manually screened bibliographies of relevant articles. We conducted dual abstract and full-text screening of references yielded by our searches. To identify publications published prior to 1985, we used the previously published review by Ajello et al. Overall, we identified 83 cases of paracoccidioidomycosis diagnosed in 11 European countries, published in 68 articles. Age of patients ranged from 24 to 77 years; the majority were male. Time from leaving the endemic region and first occurrence of symptoms considerably varied. Our review illustrates the challenges of considering systemic mycosis in the differential diagnosis of people returning or immigrating to Europe from endemic areas. Travel history is important for diagnostic-workup, though it might be difficult to obtain due to possible long latency period of the disease. [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]

The European Union member states received about 385,000 asylum applications from children and adolescents below 18 years in 2015, and 398,000 in 2016. The latest political crises and war have led to an upsurge in refugee movements into European countries, giving rise to a re-evaluation of the epidemiology of psychiatric disorders and mental health problems among young refugees and asylum seekers. We systematically searched five electronic databases and reference lists of pertinent review articles. We then screened the results of forward citation tracking of key articles for relevant studies in the field for the period from January 1990 to October 2017. We dually reviewed citations and assessed risk of bias. We reported the results narratively, as meta-analyses were impeded due to high heterogeneity. We included 47 studies covered in 53 articles. Overall, the point prevalence of the investigated psychiatric disorders and mental health problems varied widely among studies (presenting interquartile ranges): for posttraumatic stress disorder between 19.0 and 52.7%, for depression between 10.3 and 32.8%, for anxiety disorders between 8.7 and 31.6%, and for emotional and behavioural problems between 19.8 and 35.0%. The highly heterogeneous evidence base could be improved by international, methodologically comparable studies with sufficiently large sample sizes drawn randomly among specific refugee populations. The prevalence estimates suggest, nevertheless, that specialized mental health care services for the most vulnerable refugee and asylum-seeking populations are needed. Registration: The systematic review protocol was registered in PROSPERO on October 19th, 2017 with the number: CRD42017080039 and is available from: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=80039 [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]

Background: Decisionmakers and guideline developers demand rapid syntheses of the evidence when time sensitive evidence-informed decisions are required. A potential trade-off of such rapid reviews is that their results can have less reliability than results of systematic reviews that can lead to an increased risk of making incorrect decisions or recommendations. We sought to determine how much incremental uncertainty about the correctness of an answer guideline developers and health policy decisionmakers are willing to accept in exchange for a rapid evidence-synthesis.Methods: Employing a purposive sample, we conducted an international web-based, anonymous survey of decisionmakers and guideline developers. Based on a clinical treatment, a public health, and a clinical prevention scenario, participants indicated the maximum risk of getting an incorrect answer from a rapid review that they would be willing to accept. We carefully reviewed data and performed descriptive statistical analyses.Results: In total, 325 (58.5%) of 556 participants completed our survey and were eligible for analysis. The median acceptable incremental risk for getting an incorrect answer from a rapid review across all three scenarios was 10.0% (interquartile range [IQR] 5.0-15.0). Acceptable risks were similar for the clinical treatment (n = 313, median 10.0% [IQR 5.0-15.0]) and the public health scenarios (n = 320, median 10.0% [IQR 5.0-15.0]) and lower for the clinical prevention scenario (n = 312, median 6.5% [IQR 5.0-10.5]).Conclusions: Findings suggest that decisionmakers are willing to accept some trade-off in validity in exchange for a rapid review. Nevertheless, they expect the validity of rapid reviews to come close to that of systematic reviews. [ABSTRACT FROM AUTHOR]

Background: Systematic reviews offer the most reliable and valid support for health policy decision-making, patient information, and guideline development. However, they are labor intensive and frequently take longer than 1 year to complete. Consequently, they often do not meet the needs of those who need to make decisions quickly. Rapid reviews have therefore become a pragmatic alternative to systematic reviews. They are knowledge syntheses that abbreviate certain methodological aspects of systematic reviews to produce information more quickly. Methodological shortcuts often take place in literature identification. A potential drawback is less reliable results. To date, the impact of abbreviated searches on estimates of treatment effects and subsequent conclusions has not been analyzed systematically across multiple bodies of evidence. We aim to answer the research question: Do bodies of evidence that are based on abbreviated literature searches lead to different conclusions about benefits and harms of interventions compared with bodies of evidence that are based on comprehensive, systematic literature searches? Methods: We will use a non-inferiority and meta-epidemiologic design. The primary outcome is the proportion of discordant conclusions based on different search approaches. Drawing of a pool of Cochrane reports published between 2012 and 2016, we will randomly select 60 reports. Eligible reports are those that present a summary-of-findings table, draw a clear conclusion, present data for meta-analyses, and document the search strategy clearly. We will conduct several abbreviated searches to detect whether included studies in these Cochrane reviews could be detected. If searches could not detect all studies, we will revise the original summary-of-findings table and ask review authors whether the missed evidence would change conclusions of their report. We will determine the proportion of discordant conclusions for each abbreviated search approach. We will consider an abbreviated search as non-inferior if the lower limit of the 95% confidence interval of the proportion of discordant conclusions is below the non-inferiority margin, which is determined based on results of a survey for clinical and public health scenarios. Discussion: This will be the first study to assess whether the reduced sensitivity of abbreviated searches has an impact on conclusions across multiple bodies of evidence, not only on effect estimates. [ABSTRACT FROM AUTHOR]

Background: Most European and North American clinical practice guidelines recommend screening for asymptomatic bacteriuria (ASB) as a routine pregnancy test. Antibiotic treatment of ASB in pregnant women is supposed to reduce maternal upper urinary tract infections (upper UTIs) and preterm labour. However, most studies supporting the treatment of ASB were conducted in the 1950s to 1980s. Because of subsequent changes in treatment options for ASB and UTI, the applicability of findings from these studies has come into question. Our systematic review had three objectives: firstly, to assess the patient-relevant benefits and harms of screening for ASB versus no screening; secondly, to compare the benefits and harms of different screening strategies; and thirdly, in case no reliable evidence on the overarching screening question was identified, to determine the benefits and harms of treatment of ASB. Methods: We systematically searched several bibliographic databases, trial registries, and other sources (up to 02/2016) for randomised controlled trials (RCTs) and prospective non-randomised trials. Two authors independently reviewed abstracts and full-text articles and assessed the risk of bias of the studies included. As meta-analyses were not possible, we summarised the results qualitatively. Results: We did not identify any eligible studies that investigated the benefits and harms of screening for ASB versus no screening or that compared different screening strategies. We identified four RCTs comparing antibiotics with no treatment or placebo in 454 pregnant women with ASB. The results of 2 studies published in the 1960s showed a statistically significant reduction in rates of pyelonephritis (odds ratio [OR] = 0.21, 95 % confidence interval [CI] 0.07-0.59) and lower UTI (OR = 0.10, 95 % CI 0.03-0.35) in women treated with antibiotics. By contrast, event rates reported by a recent study were not statistically significantly different, neither regarding pyelonephritis (0 % vs. 2.2 %; OR = 0.37, CI 0.01-9.25, p = 0.515) nor regarding lower UTI during pregnancy (10 % vs. 18 %; Peto odds ratio [POR] = 0.53, CI 0.16-1.79, p = 0.357). Data were insufficient to determine the risk of harms. As three of the four studies were conducted several decades ago and have serious methodological shortcomings, the applicability of their findings to current health care settings is likely to be low. The recent high-quality RCT was stopped early due to a very low number of primary outcome events, a composite of preterm delivery and pyelonephritis. Therefore, the results did not show a benefit of treating ASB. Conclusions: To date, no reliable evidence supports routine screening for ASB in pregnant women. [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]

Objective: To summarize the best available evidence regarding the short- and long-term health effects of cow's milk intake in healthy, full-term infants up to 3 years of age.Design: We conducted a systematic review and meta-analysis.Setting: We searched MEDLINE (via PubMed), EMBASE and the Cochrane Library between 1960 and July 2013 and manually reviewed reference lists of pertinent articles. Two researchers independently reviewed abstracts and full-text articles and extracted relevant data.Subjects: We included (randomized/non-randomized) controlled trials and observational studies.Results: We included data from twenty-three studies (one randomized controlled trial, four non-randomized controlled trials, eight case-control studies and ten cohort studies) for the evidence synthesis. Pooled results of four studies revealed a higher risk of Fe-deficiency anaemia for infants consuming cow's milk compared with those consuming follow-on formula (relative risk=3·76; 95 % CI 2·73, 5·19). For type 1 diabetes mellitus, six out of seven case-control studies did not show a difference in the risk of developing this disease based on the age of introduction of cow's milk. We did not find negative associations for other health effects.Conclusions: Cow's milk consumption in infancy is associated with an increased risk of developing Fe-deficiency anaemia. Limiting cow's milk consumption may be important to ensure an adequate Fe intake for infants and toddlers. High-quality patient information for caregivers is needed on how infants' Fe requirements can be met. [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]

Background: Non-communicable diseases (NCDs) are the largest cause of premature death worldwide. Socioeconomic inequalities contribute to a disparity in the burden of NCDs among disadvantaged and advantaged populations in low (LIC), middle (MIC), and high income countries (HIC). We conducted an overview of systematic reviews to systematically and objectively assess the available evidence on socioeconomic inequalities in relation to morbidity and mortality of NCDs and their risk factors.Methods: We searched PubMed, The Cochrane Library, EMBASE, SCOPUS, Global Health, and Business Source Complete for relevant systematic reviews published between 2003 and December 2013. Two authors independently screened abstracts and full-text publications and determined the risk of bias of the included systematic reviews.Results: We screened 3302 abstracts, 173 full-text publications and ultimately included 22 systematic reviews. Most reviews had major methodological shortcomings; however, our synthesis showed that having low socioeconomic status (SES) and/or living in low and middle income countries (LMIC) increased the risk of developing cardiovascular diseases (CVD), lung and gastric cancer, type 2 diabetes, and chronic obstructive pulmonary disease (COPD). Furthermore, low SES increased the risk of mortality from lung cancer, COPD, and reduced breast cancer survival in HIC. Reviews included here indicated that lower SES is a risk factor for obesity in HIC, but this association varied by SES measure. Early case fatalities of stroke were lower and survival of retinoblastoma was higher in MIC compared to LIC.Conclusions: The current evidence supports an association between socioeconomic inequalities and NCDs and risk factors for NCDs. However, this evidence is incomplete and limited by the fairly low methodological quality of the systematic reviews, including shortcomings in the study selection and quality assessment process. [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: Major depressive disorder (MDD) has detrimental effects on an individual's personal life, leads to increased risk of comorbidities, and places an enormous economic burden on society. Several 'second-generation' antidepressants are available as both immediate-release (IR) and extended-release formulations. The advantage of extended-release formulations may be the potentially improved adherence and a lower risk of adverse events. Objective: We conducted a systematic review to assess the comparative efficacy, risk of harms, and patients' adherence of IR and extended-release antidepressants for the treatment of MDD. Data Source: English-language abstracts were retrieved 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. Eligibility Criteria: We included head-to-head randomized controlled trials (RCTs) of at least 6 weeks' duration that compared an IR formulation with an extended-release formulation of the same antidepressant in adult patients with MDD. We also included placebo-controlled trials to conduct a network meta-analysis. To assess harms and adherence, in addition to RCTs, we searched for observational studies with ≥1,000 participants and a follow-up of ≥12 weeks. Study Appraisal and Synthesis Methods: We dually reviewed abstracts and full texts and assessed quality ratings. Lacking head-to-head evidence for many comparisons of interest, we conducted network meta-analyses using Bayesian methods. Our outcome measure of choice was response on the Hamilton Depression Rating Scale. Results: We located seven head-to-head trials and 94 placebo- and active-controlled trials for network meta-analysis. Overall, our analyses indicate that IR and extended-release formulations do not differ substantially with respect to efficacy and risk of harms. The evidence is mixed with respect to differences in adherence, indicating lower adherence for IR formulations. Limitations: The lack of head-to-head comparisons for many drugs compromises our conclusions. Network meta-analyses have methodological limitations that need to be taken into consideration when interpreting findings. Conclusion: Available evidence currently shows no clear differences between the two formulations and therefore we cannot recommend a first choice. However, if adherence or compliance with one medication is an issue, then clinicians and patients should consider the alternative medication. If adherence or costs are a problem with one formulation, consideration of the other formulation to provide an adequate treatment trial is reasonable. [ABSTRACT FROM AUTHOR]

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]

Zusammenfassung: Evidenzbasierte Medizin (EbM) fordert, dass bei klinischen Entscheidungen das weltweit beste verfügbare Wissen berücksichtigt wird, um eine optimale Behandlung der Patienten zu garantieren. Aufgrund der rasanten Entwicklung der medizinischen Forschung mit mehr als 3 Millionen publizierten Artikeln pro Jahr ist es jedoch unmöglich, auf dem aktuellen Stand der Wissenschaft zu bleiben. Systematische Übersichtsarbeiten fassen Resultate einer Vielzahl von Studien zusammen, bewerten die methodische Qualität und die Aussagekraft für die medizinische Praxis. Dieser Artikel fasst Konzepte der EbM sowie methodische Aspekte von systematischen Übersichtsarbeiten und Meta-Analysen zusammen und bietet Lesern eine Anleitung, wie Resultate systematischer Übersichtsarbeiten kritisch gelesen und bewertet werden können. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To minimise retrieval bias, manual literature searches are a key part of the search process of any systematic review. Considering the need to have accurate information, valid results of the manual literature search are essential to ensure scientific standards; likewise efficient approaches that minimise the amount of personnel time required to conduct a manual literature search are of great interest. Objective: The objective of this project was to determine the validity and efficiency of a new manual search method that utilises thescopus™ database. Methods: We used the traditional manual search approach as the gold standard to determine the validity and efficiency of the proposedscopus method. Outcome measures included completeness of article detection and personnel time involved. Using both methods independently, we compared the results based on accuracy of the results, validity and time spent conducting the search, efficiency. Results: Regarding accuracy, thescopus method identified the same studies as the traditional approach indicating its validity. In terms of efficiency, usingscopus led to a time saving of 62.5% compared with the traditional approach (3 h versus 8 h). Conclusions: Thescopus method can significantly improve the efficiency of manual searches and thus of systematic reviews. [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: Uncertainty about the applicability of controlled trial findings is an increasing concern for clinicians and policy decision makers. This study aimed to determine whether information reported in studies included in systematic reviews was adequate enough to assess their applicability. Methods: We used the databases of four recently conducted systematic reviews on the comparative efficacy and safety of second-generation antidepressants, inhaled corticosteroids, Alzheimer's drugs, and targeted immune modulators. We developed and pilot-tested a questionnaire to assess the adequacy of reporting with respect to seven previously validated criteria of study design that distinguish explanatory from pragmatic studies. For each of the 137 included studies, two reviewers independently assessed the adequacy of reporting. Results: Overall, only 12 percent of the included studies provided sufficient information to reliably distinguish explanatory from pragmatic studies. The areas with the greatest lack of reporting were the setting of the study, methods of adverse event assessment, and sample size considerations to determine a minimally important difference from a patient perspective. Conclusions: Substantial shortcomings in reporting exist in aspects of study design important to determine whether a study is applicable to specific populations of interest. [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]

Abstract: Background: The Z0011-study, a landmark randomised controlled trial (RCT) challenged the benefits of complete axillary lymph node dissection (ALND) compared with sentinel lymph node dissection only (SLND) in breast cancer patients with positive sentinel nodes. The study, however, has been criticised for lack of power and low applicability. The aim of this review was to systematically assess the evidence on the comparative benefits and harms of ALND versus SLND for sentinel node positive breast cancer patients. Methods: We systematically searched PubMed, Embase, the Cochrane Library, and reference lists of pertinent review articles from January 2006 to August 2011. We dually reviewed the literature and rated the risk of bias of each study. For effectiveness, we included RCTs and observational studies of at least 1year follow-up. In addition, we considered studies conducted in sentinel node-negative women to assess the risk of harms. If data were sufficient, we conducted random effects meta-analysis of outcomes of interest. Results: Meta-analysis of three studies with 50,120 patients indicated similar 5-year survival and regional recurrence rates between patients treated with ALND or SLND, although prognostic tumour characteristics varied among the 3 study-populations. Results from 6 studies on more than 11,500 patients reported a higher risk for harms for ALND than SLND. Long-term evidence on pertinent health outcomes is missing. Conclusion: The available evidence indicates that for some women with early invasive breast cancer SLND appears to be a justifiable alternative to ALND. Surgeons need to discuss advantages and disadvantages of both approaches with their patients. [Copyright &y& Elsevier]

Abstract: Objective: To describe a systematic approach for identifying, reporting, and synthesizing information to allow consistent and transparent consideration of the applicability of the evidence in a systematic review according to the Population, Intervention, Comparator, Outcome, Setting domains. Study Design and Setting: Comparative effectiveness reviews need to consider whether available evidence is applicable to specific clinical or policy questions to be useful to decision makers. Authors reviewed the literature and developed guidance for the Effective Health Care program. Results: Because applicability depends on the specific questions and needs of the users, it is difficult to devise a valid uniform scale for rating the overall applicability of individual studies or body of evidence. We recommend consulting stakeholders to identify the factors most relevant to applicability for their decisions. Applicability should be considered separately for benefits and harms. Observational studies can help determine whether trial populations and interventions are representative of “real world” practice. Reviewers should describe differences between available evidence and the ideally applicable evidence for the question being asked and offer a qualitative judgment about the importance and potential effect of those differences. Conclusion: Careful consideration of applicability may improve the usefulness of systematic reviews in informing practice and policy. [Copyright &y& Elsevier]

Background: Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Levomilnacipran, vilazodone and vortioxetine are the latest therapeutic options approved for the treatment of MDD. This systematic review aims to compare the benefits and harms of vilazodone, levomilnacipran, and vortioxetine with one another and other second-generation antidepressants.Methods: We searched electronic databases up to September 2017 and reviewed reference lists and pharmaceutical dossiers to detect published and unpublished studies. Two reviewers independently screened abstracts and full text articles, and rated the risk of bias of included studies. Randomized controlled trials (RCTs) and controlled observational studies including adult outpatients with MDD were eligible for inclusion. We conducted network meta-analyses on response to treatment using frequentist multivariate meta-analyses models. Placebo- and active-controlled trials were eligible for network meta-analyses.Results: Twenty-four studies met our inclusion criteria. Direct comparisons were limited to vilazodone versus citalopram, and vortioxetine versus duloxetine, paroxetine, or venlafaxine XR (extended release). Results of head-to-head trials and network meta-analyses, overall, indicated similar efficacy among levomilnacipran, vilazodone, or vortioxetine and other second-generation antidepressants. Although rates of overall adverse events and discontinuation due to adverse events were similar, RCTs reported several differences in specific adverse events. For most outcomes the strength of evidence was low.Limitations: Limitations are the focus of literature searches on studies published in English, possible reporting biases, and general methodological limitations of network meta-analyses.Conclusions: Overall, the available evidence does not indicate greater benefits or fewer harms of levomilnacipran, vilazodone, and vortioxetine compared with other second-generation antidepressants. [ABSTRACT FROM AUTHOR]

Objectives: Pooled-studies publications (PSPs) present statistical analyses of multiple randomized controlled trials without a systematic literature search or critical appraisal. We explored the characteristics of PSPs and their potential impact on a systematic review (SR). Study Design and Setting: We systematically evaluated PSPs excluded from an SR of second-generation antidepressants. We analyzed their basic characteristics, risk of bias, and the effect of new data on review conclusions. Results: We identified 57 PSPs containing a median of five trials (range, 2-11) and 1,233 patients (range, 117 2,919). Ninety-six percent of PSPs were industry funded, and 49% of PSPs contained unpublished data. The median number of citations for PSPs was 29 (range, 0-549). Only 7% planned pooling a priori, and 19% combined trials with identical protocols. Fifty-nine percent of PSPs eligible e for general efficacy provided no new data. For some subgroups and accompanying symptoms (e.g., anxiety, insomnia, melancholia, fatigue, sex, and race), more than 30% of PSPs presented entirely new data or data that could alter the strength of the evidence available in the SR. Conclusion: In this case study, PSPs provided new information on subgroups and secondary outcomes; however, guidance for reviewers and development of a system to assess their susceptibility to bias are required. [ABSTRACT FROM AUTHOR]