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Importance: Combining antidepressants is frequently done in the treatment of acute depression, but studies have yielded conflicting results.Objective: To conduct a systematic review and meta-analysis assessing efficacy and tolerability of combination therapy. Combinations using presynaptic α2-autoreceptor antagonists or bupropion were investigated separately.Data Sources: MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were systematically searched from each database inception through January 2020.Study Selection: Randomized clinical trials (RCTs) comparing combinations of antidepressants with antidepressant monotherapy in adult patients with acute depression were included.Data Extraction and Synthesis: Following guidelines from Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and recommendations from the Cochrane Handbook, 2 reviewers independently performed a literature search, study selection, data extraction, and evaluation of risk of bias. Data were pooled in random-effects analyses.Main Outcomes and Measures: Primary outcome was efficacy measured as standardized mean difference (SMD); secondary outcomes were response, remission, change from baseline in rating scale scores, number of dropouts, and number of dropouts due to adverse events.Results: Thirty-nine RCTs including 6751 patients were eligible. Combination treatment was statistically significantly associated with superior treatment outcomes relative to monotherapy (SMD = 0.31; 95% CI, 0.19-0.44). Combining a reuptake inhibitor with an antagonist of presynaptic α2-autoreceptors was superior to other combinations (SMD = 0.37; 95% CI, 0.19-0.55). Bupropion combinations were not superior to monotherapy (SMD = 0.10; 95% CI, -0.07 to 0.27). Numbers of dropouts and dropouts due to adverse events did not differ between treatments. Studies were heterogeneous, and there was indication of publication bias (Egger test result was positive; P = .007, df = 36), but results remained robust across prespecified secondary outcomes and sensitivity and subgroup analyses, including analyses restricted to studies with low risk of bias.Conclusions and Relevance: In this meta-analysis of RCTs comparing combinations of antidepressants with antidepressant monotherapy, combining antidepressants was associated with superior treatment outcomes but not with more patients dropping out of treatment. Combinations using an antagonist of presynaptic α2-autoreceptors may be preferable and may be applied as a first-line treatment in severe cases of depression and for patients considered nonresponders. [ABSTRACT FROM AUTHOR]

Updating systematic reviews is often a time‐consuming process that involves a lot of human effort and is therefore not conducted as often as it should be. The aim of our research project was to explore the potential of machine learning methods to reduce human workload. Furthermore, we evaluated the performance of deep learning methods in comparison to more established machine learning methods. We used three available reviews of diagnostic test studies as the data set. In order to identify relevant publications, we used typical text pre‐processing methods. The reference standard for the evaluation was the human‐consensus based on binary classification (inclusion, exclusion). For the evaluation of the models, various scenarios were generated using a grid of combinations of data preprocessing steps. Moreover, we evaluated each machine learning approach with an approach‐specific predefined grid of tuning parameters using the Brier score metric. The best performance was obtained with an ensemble method for two of the reviews, and by a deep learning approach for the other review. Yet, the final performance of approaches strongly depends on data preparation. Overall, machine learning methods provided reasonable classification. It seems possible to reduce human workload in updating systematic reviews by using machine learning methods. Yet, as the influence of data preprocessing on the final performance seems to be at least as important as choosing the specific machine learning approach, users should not blindly expect a good performance by solely using approaches from a popular class, such as deep learning. [ABSTRACT FROM AUTHOR]

Introduction: Achieving tuberculosis (TB) elimination in low TB incidence countries requires identification and treatment of individuals at risk for latent TB infection (LTBI). Persons travelling to high TB incidence countries are potentially at risk for TB exposure. This systematic review and meta-analysis estimates incident LTBI and active TB among individuals travelling from low to higher TB incidence countries.Methods: Five electronic databases were searched from inception to 18 February 2020. We identified incident LTBI and active TB among individuals travelling from low (<10 cases/100 000 population) to intermediate (10-100/100 000) or high (>100/100 000) TB incidence countries. We conducted a meta-analysis and meta-regression using a random effects model of log-transformed proportions (cumulative incidence). Subgroup analyses investigated the impact of travel duration, travel purpose and TB incidence in the destination country.Results: Our search identified 799 studies, 120 underwent full-text review, and 10 studies were included. These studies included 1 154 673 travellers observed between 1994 and 2013, comprising 443 health care workers (HCW), 1 068 636 military personnel and 85 594 general travellers/volunteers. We did not identify any studies that estimated incidence of LTBI or active TB among people travelling to visit friends and relatives (VFRs). The overall cumulative incidence of LTBI was 2.3%, with considerable heterogeneity. Among individuals travelling for a mean/median of up to 6 months, HCWs had the highest cumulative incidence of LTBI (4.3%), whereas the risk was lower for military (2.5%) and general travellers/volunteers (1.6%). Meta-regression did not identify a difference in incident LTBI based on travel duration and TB incidence in the destination country. Five studies reported cases of active TB, with an overall pooled estimate of 120.7 cases per 100 000 travellers.Conclusions: We found that travelling HCWs were at highest risk of developing LTBI. Individual risk activities and travel purpose were most associated with risk of TB infection acquired during travel. [ABSTRACT FROM AUTHOR]

Background Herpes simplex virus type 1 (HSV-1) epidemiology in Asia was characterized by assessing seroprevalence levels and extent to which HSV-1 is isolated from clinically diagnosed genital ulcer disease (GUD) and genital herpes. Methods HSV-1 reports in Asia were systematically reviewed and synthesized, following PRISMA guidelines. Random-effects meta-analyses estimated pooled mean seroprevalence and proportion of HSV-1 detection in GUD and genital herpes. Random-effects meta-regressions identified predictors of seroprevalence and sources of between-study heterogeneity. Results Forty-nine relevant publications were identified. Fifty-four overall seroprevalence measures (182 stratified measures), and 8 and 24 proportions of HSV-1 detection in GUD and in genital herpes, respectively, were extracted. The pooled mean seroprevalence was 50.0% (n = 26; 95% confidence interval [CI], 41.3%–58.7%) for children and 76.5% (n = 151; 73.3%–79.6%) for adults. By age group, the pooled mean was lowest at 55.5% (n = 37; 95% CI, 47.5%–63.4%) in individuals aged <20 years, followed by 67.9% (n = 48; 62.4%–73.3%) in those aged 20–39 and 87.5% (n = 44; 83.4%–91.1%) in those aged ≥40 years. In meta-regression, age was the major predictor of seroprevalence. The mean proportion of HSV-1 detection was 5.6% (n = 8; 95% CI, 0.8%–13.6%) in GUD and 18.8% (n = 24; 12.0%–26.7%) in genital herpes. Conclusions HSV-1 epidemiology is transitioning in Asia. HSV-1 is probably playing a significant role as a sexually transmitted infection, explaining one-fifth of genital herpes cases. There is a need for expanded seroprevalence monitoring and GUD/genital herpes etiological surveillance. [ABSTRACT FROM AUTHOR]

Network meta-analysis has evolved into a core method for evidence synthesis in health care. In network meta-analysis, 3 or more treatments for a given medical condition are compared, based on a number of clinical studies, usually randomized controlled trials. Often, many different endpoints are investigated, related to different aspects of the patient's outcome, such as efficacy, safety, acceptability, or costs of a treatment. Different outcomes may lead to different rankings of the treatments. We use the existing theory of partially ordered sets and show how the relations between the treatments in a network meta-analysis can be illustrated by Hasse diagrams, that is, directed graphs showing the partial order relations, and by structured scatter plots and biplots. [ABSTRACT FROM AUTHOR]

Systematic reviewers conducting pairwise meta-analyses sometimes encounter multi-arm studies. To include these studies, and to avoid a unit-of-analysis error, often two or more arms are combined or the control arm is split. In this tutorial, we present 5 different approaches that can be used. Particularly, we present a novel approach (method 4) that to the best of our knowledge has not been presented before. We demonstrate their application on 3 selected data sets, discuss their scope of application and their advantages and limitations, and give recommendations. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatitis C virus (HCV) infection is a significant global health issue that leads to 350,000 preventable deaths annually due to associated cirrhosis and hepatocellular carcinoma (HCC). Immigrants and refugees (migrants) originating from intermediate/high HCV endemic countries are likely at increased risk for HCV infection due to HCV exposure in their countries of origin. The aim of this study was to estimate the HCV seroprevalence of the migrant population living in low HCV prevalence countries. Methods: Four electronic databases were searched from database inception until June 17, 2014 for studies reporting the prevalence of HCV antibodies among migrants. Seroprevalence estimates were pooled with a random-effect model and were stratified by age group, region of origin and migration status and a meta-regression was modeled to explore heterogeneity. Results: Data from 50 studies representing 38,635 migrants from all world regions were included. The overall anti-HCV prevalence (representing previous and current infections) was 1.9% (95% CI, 1.4–2.7%, I2 96.1). Older age and region of origin, particularly Sub-Saharan Africa, Asia, and Eastern Europe were the strongest predictors of HCV seroprevalence. The estimated HCV seroprevalence of migrants from these regions was >2% and is higher than that reported for most host populations. Conclusion: Adult migrants originating from Asia, Sub-Saharan Africa and Eastern Europe are at increased risk for HCV and may benefit from targeted HCV screening. [ABSTRACT FROM AUTHOR]

Background: This review of cancer outcomes is based on key literature searches of the medical databases and meta-analysis of short-term benefits of laparoscopy in rectal cancer treatment. Methods: We carried out a systematic review of randomized clinical trials (RCTs) and prospective non-randomized controlled trials (non-RCTs) published between January 2000 and September 2013 listed in the MEDLINE and EMBASE databases (PROSPERO Registration number: CRD42013005076). The primary endpoint was clearance of the circumferential resection margin. Meta-analysis was performed using a fixed-effect model, and sensitivity analysis by a random-effect model; subgroup analysis was performed on subsets of patients with extraperitoneal cancer of the rectum. Relative risk (RR) and mean difference (MD) were used as outcome measures. Results: Twenty-seven studies (10,861 patients) met the inclusion criteria; eight were RCTs (2,659 patients). The RCTs reported involvement of the circumferential margin in 7.9 % of patients who underwent laparoscopic and in 6.9 % of those undergoing open surgery; the overall RR was 1.00 (95 % confidence interval 0.73-1.35) with no heterogeneity. Subgroup analysis of patients with extraperitoneal cancer showed equivalent involvement of the circumferential margin in the two treatment groups. Although significantly more lymph nodes were retrieved in the surgical specimen after open surgery, the MD of −0.56 was of marginal clinical significance. The sensitivity and subgroup analyses revealed no other significant differences between laparoscopic and open surgery in the rate of R0 resections, distal margin clearance, mesorectal fascia integrity, or local recurrence at 5 years. Conclusions: Based on the evidence from RCTs and non-RCTs, the short-term benefit and oncological adequacy of laparoscopic rectal resection appear to be equivalent to open surgery, with some evidence potentially pointing to comparable long-term outcomes and oncological adequacy in selected patients with primary resectable rectal cancer. [ABSTRACT FROM AUTHOR]

Background: The synthesis of published research in systematic reviews is essential when providing evidence to inform clinical and health policy decision-making. However, the validity of systematic reviews is threatened if journal publications represent a biased selection of all studies that have been conducted (dissemination bias). To investigate the extent of dissemination bias we conducted a systematic review that determined the proportion of studies published as peer-reviewed journal articles and investigated factors associated with full publication in cohorts of studies (i) approved by research ethics committees (RECs) or (ii) included in trial registries. Methods and Findings: Four bibliographic databases were searched for methodological research projects (MRPs) without limitations for publication year, language or study location. The searches were supplemented by handsearching the references of included MRPs. We estimated the proportion of studies published using prediction intervals (PI) and a random effects meta-analysis. Pooled odds ratios (OR) were used to express associations between study characteristics and journal publication. Seventeen MRPs (23 publications) evaluated cohorts of studies approved by RECs; the proportion of published studies had a PI between 22% and 72% and the weighted pooled proportion when combining estimates would be 46.2% (95% CI 40.2%–52.4%, I2 = 94.4%). Twenty-two MRPs (22 publications) evaluated cohorts of studies included in trial registries; the PI of the proportion published ranged from 13% to 90% and the weighted pooled proportion would be 54.2% (95% CI 42.0%–65.9%, I2 = 98.9%). REC-approved studies with statistically significant results (compared with those without statistically significant results) were more likely to be published (pooled OR 2.8; 95% CI 2.2–3.5). Phase-III trials were also more likely to be published than phase II trials (pooled OR 2.0; 95% CI 1.6–2.5). The probability of publication within two years after study completion ranged from 7% to 30%. Conclusions: A substantial part of the studies approved by RECs or included in trial registries remains unpublished. Due to the large heterogeneity a prediction of the publication probability for a future study is very uncertain. Non-publication of research is not a random process, e.g., it is associated with the direction of study findings. Our findings suggest that the dissemination of research findings is biased. [ABSTRACT FROM AUTHOR]

Background: Tricyclic antidepressants (TCA) continue to be an important group of drugs, but it is unclear whether a dose-response relationship is supported by high-level evidence.Methods: Systematic review in the Cochrane Collaboration's Central Register of Controlled Trials (CENTRAL) of studies randomizing patients to at least two doses of one TCA, complemented by searches in Medline, Embase, and PsycInfo. In multilevel regression, we calculated the standardized mean difference (SMD) in antidepressant efficacy per mg TCA dose increase, and we analyzed drop-outs due to adverse events. Finally, we computed random effects meta-analyses of all dose comparisons investigated in a minimum of two studies.Results: Out of 5365 studies screened, we included 15 randomized trials on 24 comparisons of 14 different dose contrasts. We found a statistically non-significant positive effect of increasing the dose: 0.34 SMD with 100 mg/d dose increase ([-0.03; 0.70] p = 0.073). While several comparisons showed no clear signal of a dose gradient, 300 mg of imipramine/desipramine is statistically significantly superior to 150 mg (SMD: 0.80 [0.28; 1.33], p = 0.003, I2: 0%). Drop-outs increased with higher doses, albeit not statistically significantly: Odds ratio (OR) of 1.44 with 100 mg dose increase [0.54; 3.86]. Overall, risk of bias was high.Limitations: Limited number of studies with mainly high risk of bias.Conclusions: So far, data on a dose-response relationship in TCAs from direct dose comparisons are inconclusive. Clinically, escalation to high doses may be justified if side effects are bearable. [ABSTRACT FROM AUTHOR]

CONTEXT: Migraine is a common neurologic disorder in children and adolescents. However, a comparison of multiple nonpharmacological treatments is lacking. OBJECTIVE: To examine whether nonpharmacological treatments are more effective than waiting list and whether there are differences between interventions regarding efficacy. DATA SOURCES: Systematic review and network meta-analysis of studies in Medline, Cochrane, Embase, and PsycINFO published through August 5, 2019. STUDY SELECTION: Randomized controlled trials of nonpharmacological treatments in children and adolescents diagnosed with episodic migraine. DATA EXTRACTION: Effect sizes, calculated as standardized mean differences (SMDs) for the primary outcome efficacy, were assessed in a random-effects model. RESULTS: Twelve studies (N = 576) were included. When interventions were classified into groups on the basis of similarity of treatment components, self-administered treatments, biofeedback, relaxation, psychological treatments, and psychological placebos were significantly more effective than waiting list with effect sizes ranging between SMD = 1.14 (95% confidence interval, 0.09 to 2.19) for long-term psychological placebos to SMD = 1.44 (95% confidence interval, 0.26 to 2.62) for short-term self-administered treatments. However, when all interventions were examined individually (ie, 1 node per intervention), none were significantly more effective compared with waiting list, mainly because of lack of statistical power. LIMITATIONS: Because of our focus on pediatric migraine, only a small number of studies could be included. CONCLUSIONS: Our findings reveal that components of nonpharmacological interventions are effective in treating pediatric migraine. Some effects have to be interpreted carefully because they are based on small studies. Future researchers should identify factors associated with individual responses in large, multicentered studies. [ABSTRACT FROM AUTHOR]