Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders

2021 ◽  
Author(s):  
Abdullah Al Maruf ◽  
Ethan A. Poweleit ◽  
Lisa C. Brown ◽  
Jeffrey R. Strawn ◽  
Chad A. Bousman

Abstract Objectives  Partial response to pharmacotherapy is common in major depressive disorder (MDD) and many patients require alternative pharmacotherapy or augmentation, including adjunctive L-methylfolate. Given that L-methylfolate augmentation is rarely included in major clinical practice guidelines, we sought to systematically review evidence for L-methylfolate augmentation in adults with MDD and to examine its efficacy meta-analytically. Methods  We systematically searched PubMed for articles up to December 31, 2020, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Included studies were published in peer-reviewed, English-language journals and examined L-methylfolate adjunctive therapy in depressive disorders or its effect on antidepressant response. A fixed- and random-effects meta-analysis and risk of bias assessment using the Cochrane Risk of Bias Tool were conducted. Results  Qualitative assessment of nine articles (N=6,707 patients) suggests that adjunctive L-methylfolate improved antidepressant response. In the meta-analysis of categorical Hamilton Rating Scale for Depression-17 response, (three studies, N=483) adjunctive L-methylfolate was associated with a small effect versus antidepressant monotherapy (relative risk: 1.25, 95% confidence interval [CI]=1.08 to 1.46, p=0.004). A meta-analysis of four studies (N=507) using a continuous measure of depressive symptoms showed a similar effect of adjunctive L-methylfolate (standardized mean difference=− 0.38, 95% CI=− 0.59 to−0.17, p=0.0003). Conclusion  Adjunctive L-methylfolate may have modest efficacy in antidepressant-treated adults with MDD.

2021 ◽  
Vol 8 (1) ◽  
pp. e000739
Author(s):  
Paul Middleton ◽  
Catherine Hsu ◽  
Mark P Lythgoe

BackgroundCOVID-19 continues to pose a significant healthcare challenge throughout the world. Comorbidities including diabetes and hypertension are associated with a significantly higher mortality risk. However, the effect of cirrhosis on COVID-19 outcomes has yet to be systematically assessed.ObjectivesTo assess the reported clinical outcomes of patients with cirrhosis who develop COVID-19 infection.Design/MethodPubMed and EMBASE databases were searched for studies included up to 3 February 2021. All English language primary research articles that reported clinical outcomes in patients with cirrhosis and COVID-19 were included. The study was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The risk of bias was assessed using the Quality In Prognostic Score (QUIPS) risk-of-bias assessment instrument for prognostic factor studies template. Meta-analysis was performed using Cochrane RevMan V.5.4 software using a random effects model.Results63 studies were identified reporting clinical outcomes in patients with cirrhosis and concomitant COVID-19. Meta-analysis of cohort studies which report a non-cirrhotic comparator yielded a pooled mortality OR of 2.48 (95% CI: 2.02 to 3.04). Analysis of a subgroup of studies reporting OR for mortality in hospitalised patients adjusted for significant confounders found a pooled adjusted OR 1.81 (CI: 1.36 to 2.42).ConclusionCirrhosis is associated with an increased risk of all-cause mortality in COVID-19 infection compared to non-cirrhotic patients. Patients with cirrhosis should be considered for targeted public health interventions to prevent COVID-19 infection, such as shielding and prioritisation of vaccination.


Medicina ◽  
2019 ◽  
Vol 56 (1) ◽  
pp. 6
Author(s):  
Carole A. Paley ◽  
Mark I. Johnson

Background and Objectives: It is estimated that 28 million people in the UK live with chronic pain. A biopsychosocial approach to chronic pain is recommended which combines pharmacological interventions with behavioural and non-pharmacological treatments. Acupuncture represents one of a number of non-pharmacological interventions for pain. In the current climate of difficult commissioning decisions and constantly changing national guidance, the quest for strong supporting evidence has never been more important. Although hundreds of systematic reviews (SRs) and meta-analyses have been conducted, most have been inconclusive, and this has created uncertainty in clinical policy and practice. There is a need to bring all the evidence together for different pain conditions. The aim of this review is to synthesise SRs of RCTs evaluating the clinical efficacy of acupuncture to alleviate chronic pain and to consider the quality and adequacy of the evidence, including RCT design. Materials and Methods: Electronic databases were searched for English language SRs and meta-analyses on acupuncture for chronic pain. The SRs were scrutinised for methodology, risk of bias and judgement of efficacy. Results: A total of 177 reviews of acupuncture from 1989 to 2019 met our eligibility criteria. The majority of SRs found that RCTs of acupuncture had methodological shortcomings, including inadequate statistical power with a high risk of bias. Heterogeneity between RCTs was such that meta-analysis was often inappropriate. Conclusions: The large quantity of RCTs on acupuncture for chronic pain contained within systematic reviews provide evidence that is conflicting and inconclusive, due in part to recurring methodological shortcomings of RCTs. We suggest that an enriched enrolment with randomised withdrawal design may overcome some of these methodological shortcomings. It is essential that the quality of evidence is improved so that healthcare providers and commissioners can make informed choices on the interventions which can legitimately be provided to patients living with chronic pain.


Author(s):  
Beatrice Heim ◽  
Florian Krismer ◽  
Klaus Seppi

AbstractDifferential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology. Quantitative MR planimetric measurements were reported to discriminate between progressive supranuclear palsy (PSP) and non-PSP-parkinsonism. Several studies have used midbrain to pons ratio (M/P) and the Magnetic Resonance Parkinsonism Index (MRPI) in distinguishing PSP patients from those with Parkinson's disease. The current meta-analysis aimed to compare the performance of these measures in discriminating PSP from multiple system atrophy (MSA). A systematic MEDLINE review identified 59 out of 2984 studies allowing a calculation of sensitivity and specificity using the MRPI or M/P. Meta-analyses of results were carried out using random effects modelling. To assess study quality and risk of bias, the QUADAS-2 tool was used. Eight studies were suitable for analysis. The meta‐analysis showed a pooled sensitivity and specificity for the MRPI of PSP versus MSA of 79.2% (95% CI 72.7–84.4%) and 91.2% (95% CI 79.5–96.5%), and 84.1% (95% CI 77.2–89.2%) and 89.2% (95% CI 81.8–93.8%), respectively, for the M/P. The QUADAS-2 toolbox revealed a high risk of bias regarding the methodological quality of patient selection and index test, as all patients were seen in a specialized outpatient department without avoiding case control design and no predefined threshold was given regarding MRPI or M/P cut-offs. Planimetric brainstem measurements, in special the MRPI and M/P, yield high diagnostic accuracy for the discrimination of PSP from MSA. However, there is an urgent need for well-designed, prospective validation studies to ameliorate the concerns regarding the risk of bias.


2021 ◽  
Vol 5 (1) ◽  
pp. e001129
Author(s):  
Bill Stevenson ◽  
Wubshet Tesfaye ◽  
Julia Christenson ◽  
Cynthia Mathew ◽  
Solomon Abrha ◽  
...  

BackgroundHead lice infestation is a major public health problem around the globe. Its treatment is challenging due to product failures resulting from rapidly emerging resistance to existing treatments, incorrect treatment applications and misdiagnosis. Various head lice treatments with different mechanism of action have been developed and explored over the years, with limited report on systematic assessments of their efficacy and safety. This work aims to present a robust evidence summarising the interventions used in head lice.MethodThis is a systematic review and network meta-analysis which will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement for network meta-analyses. Selected databases, including PubMed, Embase, MEDLINE, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials will be systematically searched for randomised controlled trials exploring head lice treatments. Searches will be limited to trials published in English from database inception till 2021. Grey literature will be identified through Open Grey, AHRQ, Grey Literature Report, Grey Matters, ClinicalTrials.gov, WHO International Clinical Trials Registry and International Standard Randomised Controlled Trials Number registry. Additional studies will be sought from reference lists of included studies. Study screening, selection, data extraction and assessment of methodological quality will be undertaken by two independent reviewers, with disagreements resolved via a third reviewer. The primary outcome measure is the relative risk of cure at 7 and 14 days postinitial treatment. Secondary outcome measures may include adverse drug events, ovicidal activity, treatment compliance and acceptability, and reinfestation. Information from direct and indirect evidence will be used to generate the effect sizes (relative risk) to compare the efficacy and safety of individual head lice treatments against a common comparator (placebo and/or permethrin). Risk of bias assessment will be undertaken by two independent reviewers using the Cochrane Risk of Bias tool and the certainty of evidence assessed using the Grading of Recommendations, Assessment, Development and Evaluations guideline for network meta-analysis. All quantitative analyses will be conducted using STATA V.16.DiscussionThe evidence generated from this systematic review and meta-analysis is intended for use in evidence-driven treatment of head lice infestations and will be instrumental in informing health professionals, public health practitioners and policy-makers.PROSPERO registration numberCRD42017073375.


2021 ◽  
pp. 146531252110272
Author(s):  
Despina Koletsi ◽  
Anna Iliadi ◽  
Theodore Eliades

Objective: To evaluate all available evidence on the prediction of rotational tooth movements with aligners. Data sources: Seven databases of published and unpublished literature were searched up to 4 August 2020 for eligible studies. Data selection: Studies were deemed eligible if they included evaluation of rotational tooth movement with any type of aligner, through the comparison of software-based and actually achieved data after patient treatment. Data extraction and data synthesis: Data extraction was done independently and in duplicate and risk of bias assessment was performed with the use of the QUADAS-2 tool. Random effects meta-analyses with effect sizes and their 95% confidence intervals (CIs) were performed and the quality of the evidence was assessed through GRADE. Results: Seven articles were included in the qualitative synthesis, of which three contributed to meta-analyses. Overall results revealed a non-accurate prediction of the outcome for the software-based data, irrespective of the use of attachments or interproximal enamel reduction (IPR). Maxillary canines demonstrated the lowest percentage accuracy for rotational tooth movement (three studies: effect size = 47.9%; 95% CI = 27.2–69.5; P < 0.001), although high levels of heterogeneity were identified (I2: 86.9%; P < 0.001). Contrary, mandibular incisors presented the highest percentage accuracy for predicted rotational movement (two studies: effect size = 70.7%; 95% CI = 58.9–82.5; P < 0.001; I2: 0.0%; P = 0.48). Risk of bias was unclear to low overall, while quality of the evidence ranged from low to moderate. Conclusion: Allowing for all identified caveats, prediction of rotational tooth movements with aligner treatment does not appear accurate, especially for canines. Careful selection of patients and malocclusions for aligner treatment decisions remain challenging.


2021 ◽  
Vol 10 (13) ◽  
pp. 2760
Author(s):  
María León-López ◽  
Daniel Cabanillas-Balsera ◽  
Victoria Areal-Quecuty ◽  
Jenifer Martín-González ◽  
María C. Jiménez-Sánchez ◽  
...  

Aim. To conduct a systematic review and meta-analysis according to the following PICO question: in extracted human permanent teeth, does preflaring, compared with unflared canals, influence the accuracy of WL determination with EAL? Material and Methods. A systematic review was conducted according to the PRISMA checklist, using the following databases: PubMed, Science Direct, Scopus, and Web of Science. Studies related to WL determination using EAL both in preflared and unflared root canals of extracted human teeth were included. The outcome of interest was the accuracy of the electronic WL determination. A quality assessment of the included studies was performed, determining the risk of bias. The meta-analyses were calculated with the 5.4 RevMan software using the inverse variance method with random effects. PROSPERO registration: CRD42021243412. Results. Ten experimental studies fulfilled the inclusion criteria, and most of them found that preflaring increases the accuracy of the EALs in WL determination. The calculated OR was 1.98 (95% CI = 1.65–2.37; p < 0.00001; I2 = 10%), indicating that the determination of WL by EALs is almost twice as accurate in preflared canals. The accuracy of Root ZX in WL determination increases more than three times (OR = 3.25; p < 0.00001). Preflaring with Protaper files significantly increases the accuracy of EALs (OR = 1.76; p < 0.00001). The total risk of bias of the included studies was low. No obvious publication bias was observed. Conclusions. The results indicate a significant increase in the accuracy of WL determination with EAL after preflaring, doubling the percentage of exact measurements. Preflaring should be recommended as an important step during mechanical enlargement of the root canal, not only because it improves the access of the files to the canal, but also because it allows one to obtain more accurate electronic determinations of WL.


2012 ◽  
Vol 9 (5) ◽  
pp. 610-620 ◽  
Author(s):  
Thomas A Trikalinos ◽  
Ingram Olkin

Background Many comparative studies report results at multiple time points. Such data are correlated because they pertain to the same patients, but are typically meta-analyzed as separate quantitative syntheses at each time point, ignoring the correlations between time points. Purpose To develop a meta-analytic approach that estimates treatment effects at successive time points and takes account of the stochastic dependencies of those effects. Methods We present both fixed and random effects methods for multivariate meta-analysis of effect sizes reported at multiple time points. We provide formulas for calculating the covariance (and correlations) of the effect sizes at successive time points for four common metrics (log odds ratio, log risk ratio, risk difference, and arcsine difference) based on data reported in the primary studies. We work through an example of a meta-analysis of 17 randomized trials of radiotherapy and chemotherapy versus radiotherapy alone for the postoperative treatment of patients with malignant gliomas, where in each trial survival is assessed at 6, 12, 18, and 24 months post randomization. We also provide software code for the main analyses described in the article. Results We discuss the estimation of fixed and random effects models and explore five options for the structure of the covariance matrix of the random effects. In the example, we compare separate (univariate) meta-analyses at each of the four time points with joint analyses across all four time points using the proposed methods. Although results of univariate and multivariate analyses are generally similar in the example, there are small differences in the magnitude of the effect sizes and the corresponding standard errors. We also discuss conditional multivariate analyses where one compares treatment effects at later time points given observed data at earlier time points. Limitations Simulation and empirical studies are needed to clarify the gains of multivariate analyses compared with separate meta-analyses under a variety of conditions. Conclusions Data reported at multiple time points are multivariate in nature and are efficiently analyzed using multivariate methods. The latter are an attractive alternative or complement to performing separate meta-analyses.


2021 ◽  
Vol 67 (1) ◽  
pp. 27-34
Author(s):  
Fernanda Cardoso ◽  
Jéssica Breder ◽  
Priscila Apolinário ◽  
Henrique Oliveia ◽  
Maria Saidel ◽  
...  

BACKGROUND: Plantago major is a medicinal plant that has been used for centuries to treat various health conditions including wounds. PURPOSE: To investigate the effectiveness of the topical use of P major in healing skin wounds in animal models. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted. Seven (7) electronic databases (Virtual Health Library, Public/Publisher MEDLINE, Scopus, Web of Science, Embase, Cumulative Index of Nursing and Allied Health Literature, and CAB Direct) were searched for controlled studies published in English from January 2006 to March 2020. The Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies tools guided the evaluation of the studies and determined their quality. The Systematic Review Center for Laboratory Animal Experimentation was used to assess the risk of bias. RESULTS: Of the 176 publications identified, 4 met the inclusion criteria. Studies included 20 to 100 animals and varying concentrations of P major. There were no reports of losses during research. Wound healing was assessed between 17 and 21 days following wounding. The best response in terms of wound contraction rate occurred with 10%, 20%, and 50% concentrations when compared with control groups. One (1) study did not have an animal ethics committee review. All studies had a high risk of bias and a lack of methodological rigor. CONCLUSION: The results of this review did not find evidence about the in vivo effectiveness of P major for wound healing. More rigorous preclinical studies with adequate sample sizes are required to identify the best concentrations and formulations as well as increase understanding about the mechanisms of action of P major in wound healing.


Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 1
Author(s):  
Hye Won Lee ◽  
Lin Ang ◽  
Jung Tae Kim ◽  
Myeong Soo Lee

Background and Objectives: This review aimed to provide an updated review of evidence regarding the effects of aromatherapy in relieving symptoms of burn injuries, focusing on pain and physiological distress. Materials and Methods: Fifteen databases (including five English databases, four Korean medical databases, and four Iranian databases) and trial registries were searched for studies published between their dates of inception and July 2021. Two review authors individually performed study selection, data extraction, and risk of bias assessment, and any discrepancies were solved by a third review author. Results: Eight RCTs met our inclusion criteria and were analyzed in this updated systematic review. Our meta-analyses revealed that inhaled aromatherapy plus routine care showed beneficial effects in relieving pain after dressing, as compared to placebo plus routine care (p < 0.00001) and routine care alone (p = 0.02). Additionally, inhaled aromatherapy plus routine care (p < 0.00001) and aromatherapy massage plus routine care (p < 0.0001) also showed superior effects in calming anxiety, as compared to routine care alone. None of the included studies reported on AEs. Overall, the risk of bias across the studies was concerning. Conclusions: This updated review and synthesis of the studies had brought a more detailed understanding of the potential application of aromatherapy for easing the pain and anxiety of burn patients.


Methodology ◽  
2020 ◽  
Vol 16 (4) ◽  
pp. 278-298
Author(s):  
Gabriel Nudelman ◽  
Kathleen Otto

It is important to evaluate risk of bias of the primary studies included in systematic reviews and meta-analyses. Since tools pertinent to surveys are scarce, the goal of the current research was to develop a measure to address this need. In Study 1, an initial list of 10 relevant topics was compiled from previous measures. In Study 2, the list was refined into an eight-item risk-of-bias measure via discussion and a pilot study. In Study 3, experienced researchers used the measure to asses 70 studies, demonstrating high interrater agreement (weighted Kappa = .82). Inexperienced raters also utilized the measure to code 26 different studies included in a prior meta-analysis, which resulted in adequate interrater agreement (weighted Kappa = .64) and excellent convergent validity (r = .66). Thus, the new measure, designed to be accessible and flexible, can increase standardization of risk-of-bias evaluations and contribute to the interpretation of systematic reviews and meta-analytic findings.


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