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Background and aim This network meta-analysis (NMA) compares the effects of different types of olive oil (OO) on cardiovascular risk factors. Methods and results Literature search was conducted on three electronic databases (Medline, Web of Science, and Cochrane Central). Inclusion criteria: Randomized controlled trials (RCTs) (≥3 weeks duration of intervention) comparing at least two of the following types of OO: refined OO (ROO), mixed OO (MOO), low phenolic (extra) virgin OO (LP(E)VOO), and high phenolic (extra) virgin OO (HP(E)VOO). Random-effects NMA was performed for seven outcomes; and surface under the cumulative ranking curve (SUCRA) was estimated, using an analytical approach (P-score). Thirteen RCTs (16 reports) with 611 mainly healthy participants (mean age: 26–70 years) were identified. No differences for total cholesterol, HDL-cholesterol, triacylglycerols, and diastolic blood pressure were observed comparing ROO, MOO, LP(E)VOO and HP(E)VOO. HP(E)VOO slightly reduce LDL-cholesterol (LDL-C) compared to LP(E)VOO (mean difference [MD]: −0.14 mmol/L, 95%–CI: −0.28, −0.01). Both, HP(E)VOO and LP(E)VOO reduces SBP compared to ROO (range of MD: −2.99 to −2.87 mmHg), and HP(E)VOO may improve oxidized LDL-cholesterol (oxLDL-C) compared to ROO (standardized MD: −0.68, 95%–CI: −1.31, −0.04). In secondary analyses, EVOO may reduce oxLDL-C compared to ROO, and a dose-response relationship between higher intakes of phenolic compounds from OO and lower SBP and oxLDL-C values was detected. HP(E)VOO was ranked as best treatment for LDL-C (P-score: 0.83), oxLDL-C (0.88), and SBP (0.75). Conclusions HP(E)VOO may improve some cardiovascular risk factors, however, public health implications are limited by overall low or moderate certainty of evidence.

Traditional pairwise meta-analysis (PMA) is a very useful method that pools evidence from one study design type if appropriate; its widespread use in nutrition research is an important phenomenon. Recently, a promising method for more advanced evidence-synthesis, called network meta-analysis (NMA), was introduced. NMA is an extension of PMA that enables simultaneous comparison of multiple interventions. NMA combines direct evidence (i.e., trials comparing 2 interventions directly) and indirect evidence (i.e., from a connected route via ≥1 comparators, e.g. placebo) in a network of studies. NMAs have the potential to advance knowledge in the field of nutrition as they provide insights that cannot be obtained by individual 2-arm randomized controlled trials or PMA. Thus, in this perspective paper, we aim to summarize the current (methodologic) status of published NMAs in nutrition research and emphasize advances and strengths in comparison with traditional PMA through specific examples, and highlight potential pitfalls and limitations. NMA is an emerging methodology in the field of nutrition research. A PubMed search identified only 23 nutrition research-related NMAs published since the inception of journals up to January 8, 2019 (61% of them published since 2017), compared with >5000 published PMAs. Moreover, we aim to highlight the scientific concepts and standards through the use of the following NMA example: “Which type of oils/solid fats offers the greatest impact on blood lipids?” In this regard, we discuss intervention definitions, transitivity/similarity, statistical methods, description and visualization of results, inconsistency, ranking, dissemination bias, assessing the certainty of evidence by Grading of Recommendations Assessment, Development and Evaluation, and reporting guidelines. We expect that rigorously conducted NMAs based on high-quality systematic reviews will become the new evidence synthesis benchmark in nutrition research. However, caution is warranted because abuse and misinterpretations of PMA and NMA findings could hamper the scientific field and possibly decision-making regarding public policy.

The authors thank Theshani De Silva, Shazia Siddiqui,and Krystle Amog for helping format the manuscript.

Summary This review aimed to assess the impact of behavioural therapy for insomnia administered alone (BT-I) or in combination with cognitive techniques (cognitive-behavioural therapy for insomnia, CBT-I) on depressive and fatigue symptoms using network meta-analysis. PubMed, Scopus and Web of Science were searched from 1986 to May 2015. Studies were included if they incorporated sleep restriction, a core technique of BT-I treatment, and an adult insomnia sample, a control group and a standardised measure of depressive and/or fatigue symptoms. Face-to-face, group, self-help and internet therapies were all considered. Forty-seven studies were included in the meta-analysis. Eleven classes of treatment or control conditions were identified in the network. Cohen's d at 95% confidence interval (CI) was calculated to assess the effect sizes of each treatment class as compared with placebo. Results showed significant effects for individual face-to-face CBT-I on depressive ( d = 0.34, 95% CI: 0.06–0.63) but not on fatigue symptoms, with high heterogeneity between studies. The source of heterogeneity was not identified even after including sex, age, comorbidity and risk of bias in sensitivity analyses. Findings highlight the need to reduce variability between study methodologies and suggest potential effects of individual face-to-face CBT-I on daytime symptoms.

Introduction Lesions of uncertain malignant potential (B3) represent a heterogeneous group with an overall risk for malignancy of 9.85–35.1% after total resection. Positive predictive values (PPV) for malignancy vary depending on B3 subtype. The aim of this study was to evaluate the PPV for malignancy in B3 lesions and to determine the clinical significance of atypia-dependent sub-classification (a = without epithelial atypia; b = with epithelial atypia) of B3 into B3a and B3b and papillary lesions (PL) in PLa and PLb. Methods 219 patients with histopathologically proven B3 lesions on core needle/vacuum-assisted biopsy who subsequently underwent diagnostic excision biopsy were included in this study. PPVs for malignancy were reported for B3 in general and all B3 sub-categories. Logistic regression analysis identified associations between B3-subgroups and outcome after excision biopsy as well as the impact of clinical and diagnostic findings on excision diagnosis. Results The overall PPV rate was 10.0% (22/219). Excision histology exhibited a higher malignancy rate in PLb (2/7; PPV: 28.6%) than in PLa (6/127; PPV: 4.7%) (p = 0.057) and in B3b (12/50; PPV: 24.0%) compared to B3a category (8/165; PPV: 4.8%) (p Discussion These findings support the necessity of B3 lesion sub-classification into B3a and B3b and of PL into PLa and PLb when considering epithelial atypia. The determination of atypia status represents a relevant factor in risk-stratification for clinical management of B3 lesions. Should future studies using the sub-classification of PL confirm these results, observation may be a safe option for the clinical management of patients with asymptomatic PLa lesions.

Objectives We aimed to evaluate the underlying assumptions of a network meta-analysis investigating which depression treatment works best in primary care and to highlight challenges and pitfalls of interpretation under consideration of these assumptions. Study Design and Setting We reviewed 100 randomized trials investigating pharmacologic and psychological treatments for primary care patients with depression. Network meta-analysis was carried out within a frequentist framework using response to treatment as outcome measure. Transitivity was assessed by epidemiologic judgment based on theoretical and empirical investigation of the distribution of trial characteristics across comparisons. Homogeneity and consistency were investigated by decomposing the Q statistic. Results There were important clinical and statistically significant differences between “pure” drug trials comparing pharmacologic substances with each other or placebo (63 trials) and trials including a psychological treatment arm (37 trials). Overall network meta-analysis produced results well comparable with separate meta-analyses of drug trials and psychological trials. Although the homogeneity and consistency assumptions were mostly met, we considered the transitivity assumption unjustifiable. Conclusion An exchange of experience between reviewers and, if possible, some guidance on how reviewers addressing important clinical questions can proceed in situations where important assumptions for valid network meta-analysis are not met would be desirable.

Insomnia disorder, defined by nocturnal and daytime symptoms, is highly prevalent worldwide and is associated with the onset of mental illness. Although daytime symptoms are often the reason insomnia patients seek help, it is not clear whether recommended treatment is effective on daytime symptoms. We aimed to investigate the efficacy of cognitive and behavior therapies for insomnia (CBT–I) on all daytime symptoms explored in the literature using both direct and indirect data. 86 studies (15,578 participants) met inclusion criteria. Results showed significant effects of CBT-I administered face-to-face individually, in group and different self-help settings on depressive symptoms, anxiety, daytime sleepiness, fatigue, quality of life, daytime and social functioning and mental state, with Cohen's d's ranging from −0.52 and 0.81. Our results suggest that CBT-I is effective in the treatment of daytime symptoms, albeit with predominantly small to moderate effects compared to far stronger effects on the core symptoms of insomnia. Effects may be biased for depressive and anxiety symptoms, since many included studies excluded patients with severe levels of these complaints. Further, small to moderate effects may reflect that CBT–I, by improving nighttime symptoms, has a positive effect on daytime symptoms, but it does not target the daytime symptoms directly. Future studies may benefit from adding therapeutic techniques that address daytime symptoms more directly.

Numerous studies have analyzed predation risk on bird nests along forest edges, but results are inconsistent and contributing factors not well understood. Few of these studies have been carried out in tropical regions, where predator communities and responses to edges may be different. In the face of ongoing forest fragmentation, understanding factors driving predation patterns along tropical forest edges are most likely crucial. We present a formal meta-analysis on tropical forest edge effects in nest predation, advancing the method applied by Batary and Baldi (2004) . We performed a meta-analysis of 20 tropical nest predation studies including data on more than 5000 artificial nests. We tested for edge effects on nest predation probability in relation to distance from a forest edge and assessed effects of forest cover, matrix type, geographic location and nest parameters. Further, we analyzed our data together with 13 nest predation studies from temperate forests ( Batary and Baldi, 2004 ) in a combined meta-analysis, summing up to evidence from almost 9000 nests. Our meta-analysis of the tropical nest predation studies did not provide evidence of a forest edge effect on nest predation probability, while the result of the combined meta-analysis suggested a higher nest predation probability along forest edges. However, heterogeneity was extreme in both analyses (I2 = 85% and 90.1%), indicating that each study, with its unique characteristics, may result in varying nest predation patterns. Landscape context, here: forest cover, appeared to modulate nest predation risk in relation to edge distance. Conservation managers should be aware that a standard formula for conservation actions might be of little help, since edge effects seem to vary with study site settings and landscape context. We further point out that standardized reporting guidelines for primary research might help to interpret high variation in field data.

Objective Capture–recapture methods were proposed to evaluate the comprehensiveness of systematic literature searches. We investigate the statistical feasibility of capture–recapture techniques with model selection for estimating the number of missing references in literature searches using two systematic reviews in gastroenterology and hematology. Study Design and Setting First, we compared manually selected Poisson regression models that differ with respect to included interactions. Secondly, we performed selection via componentwise boosting, which provides automatic variable selection. The proposed boosting technique is a regularized, stepwise procedure allowing to distinguish between mandatory and optional variables. Results from all models were compared based on Akaike’s Information Criterion and the Bayesian Information Criterion. Results For the first example, the best manually selected model suggested a number of 82 missing articles (95% CI: 52–128), whereas the boosting technique provided 127 (95% CI: 86–186) missing articles. For the second example, 140 (95% CI: 116–168) missing articles were estimated for the manually selected and 188 (95% CI: 159–223) for the automatically selected model. Conclusion Capture–recapture analysis requires the selection of an appropriate model. Because of problems of variable selection and overfitting, manual model selection yielded large estimates, varying markedly, with broad confidence intervals. By contrast, boosting was robust against overfitting and automatically created an appropriate model for inference.

Objective Meta-analysis yields a biased result if published studies represent a biased selection of the evidence. Copas proposed a selection model to assess the sensitivity of meta-analysis conclusions to possible selection bias. An alternative proposal is the trim-and-fill method. This article reports an empirical comparison of the two methods. Study Design and Setting We took 157 meta-analyses with binary outcomes, analyzed each one using both methods, then performed an automated comparison of the results. We compared the treatment estimates, standard errors, associated P -values, and number of missing studies estimated by both methods. Results Both methods give similar point estimates, but standard errors and P -values are systematically larger for the trim-and-fill method. Furthermore, P -values from the trim-and-fill method are typically larger than those from the usual random effects model when no selection bias is detected. By contrast, P -values from the Copas selection model and the usual random effects model are similar in this setting. The trim-and-fill method reports more missing studies than the Copas selection model, unless selection bias is detected when the position is reversed. Conclusions The assumption that the most extreme studies are missing leads to excessively conservative inference in practice for the trim-and-fill method. The Copas selection model appears to be the preferable approach.

Publication bias in meta-analysis occurs if the probability of publication depends on the estimated treatment effect and the precision/size of a study. In this article we describe the funnel plot as a graphical method to evaluate the presence of publication bias. Furthermore, tests of publication bias based on funnel plots are explained, and methods are presented that estimate treatment effects adjusted for publication bias. The article closes with a critical discussion of the various statistical methods.

Background: Moxifloxacin triple therapy (MTT) has shown promising results in first-line and rescue therapy of H. pylori infection. Aims: To systematically review the efficacy and tolerability of MTT for first-line and rescue treatment of H. pylori infection, and to compare MTT with standard triple therapy (STT) and with bismuth quadruple therapy (BQT), respectively. Methods: By searching PubMed and the Cochrane Central Registry of Controlled Trials, randomized controlled trials (RCT) and other studies reporting eradication rates of MTT were identified. Metaanalyses of RCT comparing first-line MTT with STT and RCT comparing rescue MTT with BQT were performed and pooled intention-to-treat eradication rates and risk ratios (RR) with 95% confidence intervals were calculated. Results: We identified 16 studies (2481 patients) including three RCT comparing MTT with STT and five RCT comparing MTT with BQT. Pooled estimates revealed similar efficacy (RR 1.06; 0.91-1.23) and similar tolerability (RR 0.61; 0.25-1.48) of first-line MTT and STT. Rescue MTT was superior over BQT in terms of efficacy (RR 1.20; 1.07-1.36) and tolerability (RR 0.41; 0.25-0.67). Considering all MTT arms, the ITT eradication rate was 79% (72-86%) in first-line therapy and 77% (72-82%) in rescue therapy. The adverse event rate of MTT was 18.5% in first-line therapy and 18.7% in rescue therapy. Conclusions: Moxifloxacin triple therapy is superior to bismuth quadruple therapy for rescue treatment of H. pylori infection, but does not appear to offer an advantage over standard triple therapy in firstline treatment.