scholarly journals Reporting methodological issues of the mendelian randomization studies in health and medical research: a systematic review

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Shabab Noor Islam ◽  
Tanvir Ahammed ◽  
Aniqua Anjum ◽  
Olayan Albalawi ◽  
Md. Jamal Uddin

Abstract Background Mendelian randomization (MR) studies using Genetic risk scores (GRS) as an instrumental variable (IV) have increasingly been used to control for unmeasured confounding in observational healthcare databases. However, proper reporting of methodological issues is sparse in these studies. We aimed to review published papers related to MR studies and identify reporting problems. Methods We conducted a systematic review using the clinical articles published between 2009 and 2019. We searched PubMed, Scopus, and Embase databases. We retrieved information from every MR study, including the tests performed to evaluate assumptions and the modelling approach used for estimation. Using our inclusion/exclusion criteria, finally, we identified 97 studies to conduct the review according to the PRISMA statement. Results Only 66 (68%) of the studies empirically verified the first assumption (Relevance assumption), and 40 (41.2%) studies reported the appropriate tests (e.g., R2, F-test) to investigate the association. A total of 35.1% clearly stated and discussed theoretical justifications for the second and third assumptions. 30.9% of the studies used a two-stage least square, and 11.3% used the Wald estimator method for estimating IV. Also, 44.3% of the studies conducted a sensitivity analysis to illuminate the robustness of estimates for violations of the untestable assumptions. Conclusions We found that incompleteness of the justification of the assumptions for the instrumental variable in MR studies was a common problem in our selected studies. This may misdirect the findings of the studies.

Author(s):  
Inge A. T. van de Luitgaarden ◽  
Sabine van Oort ◽  
Emma J. Bouman ◽  
Linda J. Schoonmade ◽  
Ilse C. Schrieks ◽  
...  

AbstractThe causal effects of alcohol-in-moderation on cardiometabolic health are continuously debated. Mendelian randomization (MR) is an established method to address causal questions in observational studies. We performed a systematic review of the current evidence from MR studies on the association between alcohol consumption and cardiometabolic diseases, all-cause mortality and cardiovascular risk factors. We performed a systematic search of the literature, including search terms on type of design and exposure. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. We additionally looked at exploration of non-linearity. We reported the direction of the studied associations. Our search yielded 24 studies that were eligible for inclusion. A full instrumental variable analysis was performed in 17 studies (71%) and 13 out of 24 studies (54%) validated all three key assumptions. Five studies (21%) assessed potential non-linearity. In general, null associations were reported for genetically predicted alcohol consumption with the primary outcomes cardiovascular disease (67%) and diabetes (75%), while the only study on all-cause mortality reported a detrimental association. Considering the heterogeneity in methodological quality of the included MR studies, it is not yet possible to draw conclusions on the causal role of moderate alcohol consumption on cardiometabolic health. As MR is a rapidly evolving field, we expect that future MR studies, especially with recent developments regarding instrument selection and non-linearity methodology, will further substantiate this discussion.


2019 ◽  
Author(s):  
James Donald ◽  
Emma L Bradshaw ◽  
Richard Ryan ◽  
Geetanjali Basarkod ◽  
Joseph Ciarrochi ◽  
...  

Mindfulness has been shown to have varied associations with different forms of motivation, leading to a lack of clarity as to how and when it may foster healthy motivational states. Grounded in self-determination theory, the present study proposes a theoretical model for how mindfulness supports different forms of human motivation, and then tests this via meta-analysis. A systematic review identified 89 relevant studies (N = 25,176), comprised of 104 independent datasets and 200 effect sizes. We used a three-level modelling approach to meta-analyze these data. Across both correlational and intervention studies, we found consistent support for mindfulness predicting more autonomous forms of motivation; and among correlational studies, less controlled motivation and amotivation. We conducted moderation analyses to probe heterogeneity in the effects, including bias within studies. We conclude by highlighting substantive and methodological issues that need to be addressed in future research in this area.


2018 ◽  
Vol 12 (02) ◽  
pp. 317-326 ◽  
Author(s):  
Natália Gomes de Oliveira ◽  
Pollyana Rodrigues de Souza Araújo ◽  
Marina Torreão da Silveira ◽  
Ana Paula Veras Sobral ◽  
Marianne de Vasconcelos Carvalho

ABSTRACTThe objective of this systematic review was to evaluate the biocompatibility and interaction of bioceramic materials with animal and human mesenchymal cells in vitro and in vivo and to compare them with mineral trioxide aggregate (MTA). Two independent researchers conducted PubMed/Medline, Web of Science, and Scopus searches to identify studies published in English, without restrictions on year of publication using the following keywords: “root canal sealer,” “root repair material,” “cytotoxicity,” and “bioceramics.” The articles were selected following the PRISMA statement. A total of 1486 titles were identified in the initial search. However, only 18 studies met the inclusion and exclusion criteria. The results showed that bioceramic materials have biological properties similar to those of MTA, including low cytotoxicity as well as promoting cell proliferation and adhesion, low expression of inflammatory cytokines, and reduced pulp inflammation. This systematic review therefore suggests that the choice of repair bioceramic materials or MTA based on biocompatibility should be the professional's decision.


Author(s):  
John R. Thompson ◽  
Cosetta Minelli ◽  
Fabiola Del Greco M

AbstractMendelian randomization (MR) is a technique that seeks to establish causation between an exposure and an outcome using observational data. It is an instrumental variable analysis in which genetic variants are used as the instruments. Many consortia have meta-analysed genome-wide associations between variants and specific traits and made their results publicly available. Using such data, it is possible to derive genetic risk scores for one trait and to deduce the association of that same risk score with a second trait. The properties of this approach are investigated by simulation and by evaluating the potentially causal effect of birth weight on adult glucose level. In such analyses, it is important to decide whether one is interested in the risk score based on a set of estimated regression coefficients or the score based on the true underlying coefficients. MR is primarily concerned with the latter. Methods designed for the former question will under-estimate the variance if used for MR. This variance can be corrected but it needs to be done with care to avoid introducing bias. MR based on public data sources is useful and easy to perform, but care must be taken to avoid false precision or bias.


2019 ◽  
Author(s):  
Frank D Mann ◽  
Andrey A Shabalin ◽  
Anna R Docherty ◽  
Robert F Krueger

AbstractBackgroundWhen a randomized experimental study is not possible, Mendelian randomization studies use genetic variants or polygenic scores as instrumental variables to control for gene-environment correlation while estimating the association between an exposure and outcome. Polygenic scores have become increasingly potent predictors of their respective phenotypes, satisfying the relevance criteria of an instrumental variable. Evidence for pleiotropy, however, casts doubt on whether the exclusion criteria of an instrumental variable is likely to hold for polygenic scores of complex phenotypes, and a number of methods have been developed to adjust for pleiotropy in Mendelian randomization studies.MethodUsing multiple polygenic scores and path analysis we implement an extension of genetic instrumental variable regression, genetic path analysis, and use it to test whether educational attainment is associated with two health-related outcomes in adulthood, body mass index and smoking initiation, while estimating and controlling for both gene-environment correlations and pleiotropy.ResultsGenetic path analysis provides compelling evidence for a complex set of gene-environment transactions that undergird the relations between educational attainment and health-related outcomes in adulthood. Importantly, results are consistent with education having a protective effect on body mass index and smoking initiation, even after controlling for gene-environment correlations and pleiotropy.ConclusionsThe proposed method is capable of addressing the exclusion criteria for a sound instrumental variable and, consequently, has the potential to help advance Mendelian randomization studies of complex phenotypes.


2020 ◽  
Vol 01 ◽  
Author(s):  
Carla Pires ◽  
Ana Fernandes

Background: Natural products are commonly used for treating health problems. These products may be associated with adverse events, which are defined as "noxious and unintended response to a medicinal product" by the European Medicine Agency. Objectives: To identify studies describing at least one adverse event (or with potential to promote an adverse event) related to the use of natural products, as well as to describe the involved product(s) and adverse event(s). Methods: A pre-systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Keywords: "natural product(s)" and ["adverse drug reaction(s)" or "adverse effect(s)"]. Screened databases: PubMed, SciELO, DOAJ and Google Scholar. Inclusion criteria: papers describing at least one adverse event associated with the use of natural products and published between 2017 and 2019. Exclusion criteria: Repeated studies, reviews and papers written in other languages than English, Portuguese, French or Spanish. Results: 104 studies were identified (20 PubMed; 0 SciELO; 2 DOAJ; 82 Google Scholar), but only 10 were selected (4 PubMed and 6 Google Scholar): 1 in-vitro study; 2 non-clinical studies, 1 study reporting in-vitro and clinical data and 5 studies were cases reports. Globally, 997 reports of adverse drug reactions with natural products were identified, mainly non-severe cases. Conclusion: Since a limited number of studies was found, we conclude that adverse events due to natural products may be underreported, or natural products may have a good safety profile. This review contributes for assuring the safety of natural products consumers, by evaluating the knowledge/information on the potential adverse events and interactions of these products.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Marie-Camille Patoz ◽  
Diego Hidalgo-Mazzei ◽  
Bruno Pereira ◽  
Olivier Blanc ◽  
Ingrid de Chazeron ◽  
...  

Abstract Background Despite an increasing number of available mental health apps in the bipolar disorder field, these tools remain scarcely implemented in everyday practice and are quickly discontinued by patients after downloading. The aim of this study is to explore adherence characteristics of bipolar disorder patients to dedicated smartphone interventions in research studies. Methods A systematic review following PRISMA guidelines was conducted. Three databases (EMBASE, PsychInfo and MEDLINE) were searched using the following keywords: "bipolar disorder" or "mood disorder" or “bipolar” combined with “digital” or “mobile” or “phone” or “smartphone” or “mHealth” or “ehealth” or "mobile health" or “app” or “mobile-health”. Results Thirteen articles remained in the review after exclusion criteria were applied. Of the 118 eligible studies, 39 did not provide adherence characteristics. Among the selected papers, study length, sample size and definition of measures of adherence were strongly heterogeneous. Activity rates ranged from 58 to 91.6%. Conclusion The adherence of bipolar patients to apps is understudied. Standardised measures of adherence should be defined and systematically evaluated in future studies dedicated to these tools.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Nassr Nama ◽  
Mirna Hennawy ◽  
Nick Barrowman ◽  
Katie O’Hearn ◽  
Margaret Sampson ◽  
...  

Abstract Background Accepted systematic review (SR) methodology requires citation screening by two reviewers to maximise retrieval of eligible studies. We hypothesized that records could be excluded by a single reviewer without loss of sensitivity in two conditions; the record was ineligible for multiple reasons, or the record was ineligible for one or more specific reasons that could be reliably assessed. Methods Twenty-four SRs performed at CHEO, a pediatric health care and research centre in Ottawa, Canada, were divided into derivation and validation sets. Exclusion criteria during abstract screening were sorted into 11 specific categories, with loss in sensitivity determined by individual category and by number of exclusion criteria endorsed. Five single reviewer algorithms that combined individual categories and multiple exclusion criteria were then tested on the derivation and validation sets, with success defined a priori as less than 5% loss of sensitivity. Results The 24 SRs included 930 eligible and 27390 ineligible citations. The reviews were mostly focused on pediatrics (70.8%, N=17/24), but covered various specialties. Using a single reviewer to exclude any citation led to an average loss of sensitivity of 8.6% (95%CI, 6.0–12.1%). Excluding citations with ≥2 exclusion criteria led to 1.2% average loss of sensitivity (95%CI, 0.5–3.1%). Five specific exclusion criteria performed with perfect sensitivity: conference abstract, ineligible age group, case report/series, not human research, and review article. In the derivation set, the five algorithms achieved a loss of sensitivity ranging from 0.0 to 1.9% and work-saved ranging from 14.8 to 39.1%. In the validation set, the loss of sensitivity for all 5 algorithms remained below 2.6%, with work-saved between 10.5% and 48.2%. Conclusions Findings suggest that targeted application of single-reviewer screening, considering both type and number of exclusion criteria, could retain sensitivity and significantly decrease workload. Further research is required to investigate the potential for combining this approach with crowdsourcing or machine learning methodologies.


2021 ◽  
Vol 9 (1) ◽  
pp. 1911766
Author(s):  
Martin Owusu Ansah ◽  
Rosemary Boateng Coffie ◽  
Samuel Awuni Azinga ◽  
Michael Nimo

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