scholarly journals Strength of functional signature correlates with effect size in autism

2016 ◽  
Author(s):  
Sara Ballouz ◽  
Jesse Gillis
Keyword(s):  
Study Design ◽  
Effect Size ◽  
Statistical Power ◽  
Fragile X ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Protein Interaction Data ◽  
Functional Convergence ◽  
Study Designs ◽  
The Impact

AbstractBackgroundDisagreements over genetic signatures associated with disease have been particularly prominent in the field of psychiatric genetics, creating a sharp divide between disease burdens attributed to common and rare variation, with study designs independently targeting each. Meta-analysis within each of these study designs is routine, whether using raw data or summary statistics, but combining results across study designs is atypical. However, tests of functional convergence are used across all study designs, where candidate gene sets are assessed for overlaps with previously known properties. This suggests one possible avenue for combining not study data, but the functional conclusions that they reach.MethodIn this work, we test for functional convergence in autism spectrum disorder (ASD) across different study types, and specifically whether the degree to which a gene is implicated in autism is correlated with the degree to which it drives functional convergence. Because different study designs are distinguishable by their differences in effect size, this also provides a unified means of incorporating the impact of study design into the analysis of convergence.ResultsWe detected remarkably significant positive trends in aggregate (p < 2.2e-16) with 14 individually significant properties (FDR<0.01), many in areas researchers have targeted based on different reasoning, such as the fragile X mental retardation protein (FMRP) interactor enrichment (FDR 0.003). We are also able to detect novel technical effects and we see that network enrichment from protein-protein interaction data is heavily confounded with study design, arising readily in control data.ConclusionsWe see a convergent functional signal for a subset of known and novel functions in ASD from all sources of genetic variation. Meta-analytic approaches explicitly accounting for different study designs can be adapted to other diseases to discover novel functional associations and increase statistical power.

Exploring power in response inhibition tasks using the bootstrap: The impact of number of participants, number of trials, effect magnitude, and study design

2019 ◽  
Author(s):  
Curtis David Von Gunten ◽  
Bruce D Bartholow
Keyword(s):  
Study Design ◽  
Effect Size ◽  
Statistical Power ◽  
Bootstrap Sampling ◽  
Reliable Measure ◽  
Internal Reliability ◽  
The Impact ◽  
Power Analyses ◽  
Effect Magnitude

A primary psychometric concern with laboratory-based inhibition tasks has been their reliability. However, a reliable measure may not be necessary or sufficient for reliably detecting effects (statistical power). The current study used a bootstrap sampling approach to systematically examine how the number of participants, the number of trials, the magnitude of an effect, and study design (between- vs. within-subject) jointly contribute to power in five commonly used inhibition tasks. The results demonstrate the shortcomings of relying solely on measurement reliability when determining the number of trials to use in an inhibition task: high internal reliability can be accompanied with low power and low reliability can be accompanied with high power. For instance, adding additional trials once sufficient reliability has been reached can result in large gains in power. The dissociation between reliability and power was particularly apparent in between-subject designs where the number of participants contributed greatly to power but little to reliability, and where the number of trials contributed greatly to reliability but only modestly (depending on the task) to power. For between-subject designs, the probability of detecting small-to-medium-sized effects with 150 participants (total) was generally less than 55%. However, effect size was positively associated with number of trials. Thus, researchers have some control over effect size and this needs to be considered when conducting power analyses using analytic methods that take such effect sizes as an argument. Results are discussed in the context of recent claims regarding the role of inhibition tasks in experimental and individual difference designs.

scholarly journals The impact of selection criteria and study design on reported survival outcomes in extracorporeal oxygenation cardiopulmonary resuscitation (ECPR): a systematic review and meta-analysis

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Sameer Karve ◽  
Dominique Lahood ◽  
Arne Diehl ◽  
Aidan Burrell ◽  
David H. Tian ◽  
...  
Keyword(s):  
Systematic Review ◽  
Study Design ◽  
Prospective Studies ◽  
Selection Criteria ◽  
Meta Analysis ◽  
Inclusion Criteria ◽  
Newcastle Ottawa Scale ◽  
Study Designs ◽  
Based Medicine ◽  
The Impact

Abstract Background The use of extracorporeal membrane oxygenation (ECMO) during cardiac arrest (ECPR) has increased exponentially. However, reported outcomes vary considerably due to differing study designs and selection criteria. This review assessed the impact of pre-defined selection criteria on ECPR survival. Methods Systematic review applying PRISMA guidelines. We searched Medline, Embase, and Evidence-Based Medicine Reviews for RCTs and observational studies published from January 2000 to June 2021. Adult patients (> 12 years) receiving ECPR were included. Two investigators reviewed and extracted data on study design, number and type of inclusion criteria. Study quality was assessed using the Newcastle–Ottawa Scale (NOS). Outcomes included overall and neurologically favourable survival. Meta-analysis and meta-regression were performed. Results 67 studies were included: 14 prospective and 53 retrospective. No RCTs were identified at time of search. The number of inclusion criteria to select ECPR patients (p = 0.292) and study design (p = 0.962) was not associated with higher favourable neurological survival. However, amongst prospective studies, increased number of inclusion criteria was associated with improved outcomes in both OHCA and IHCA cohorts. (β = 0.12, p = 0.026) and arrest to ECMO flow time was predictive of survival. (β = -0.023, p < 0.001). Conclusions Prospective studies showed number of selection criteria and, in particular, arrest to ECMO time were associated with significant improved survival. Well-designed prospective studies assessing the relative importance of criteria as well as larger efficacy studies are required to ensure appropriate application of what is a costly intervention.

scholarly journals Conceptualising natural and quasi experiments in public health

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Frank de Vocht ◽  
Srinivasa Vittal Katikireddi ◽  
Cheryl McQuire ◽  
Kate Tilling ◽  
Matthew Hickman ◽  
...  
Keyword(s):  
Public Health ◽  
Study Design ◽  
Grey Literature ◽  
Public Health Research ◽  
Natural Experiments ◽  
Target Trial ◽  
Design Elements ◽  
Randomized Controlled ◽  
Study Designs ◽  
The Impact

Abstract Background Natural or quasi experiments are appealing for public health research because they enable the evaluation of events or interventions that are difficult or impossible to manipulate experimentally, such as many policy and health system reforms. However, there remains ambiguity in the literature about their definition and how they differ from randomized controlled experiments and from other observational designs. We conceptualise natural experiments in the context of public health evaluations and align the study design to the Target Trial Framework. Methods A literature search was conducted, and key methodological papers were used to develop this work. Peer-reviewed papers were supplemented by grey literature. Results Natural experiment studies (NES) combine features of experiments and non-experiments. They differ from planned experiments, such as randomized controlled trials, in that exposure allocation is not controlled by researchers. They differ from other observational designs in that they evaluate the impact of events or process that leads to differences in exposure. As a result they are, in theory, less susceptible to bias than other observational study designs. Importantly, causal inference relies heavily on the assumption that exposure allocation can be considered ‘as-if randomized’. The target trial framework provides a systematic basis for evaluating this assumption and the other design elements that underpin the causal claims that can be made from NES. Conclusions NES should be considered a type of study design rather than a set of tools for analyses of non-randomized interventions. Alignment of NES to the Target Trial framework will clarify the strength of evidence underpinning claims about the effectiveness of public health interventions.

Preemptive interventions for infants and toddlers with a high likelihood for autism: A systematic review and meta-analysis

Autism ◽  
2021 ◽  
pp. 136236132110504
Author(s):  
Lauren H Hampton ◽  
Elizabeth M Rodriguez
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Child Outcomes ◽  
Developmental Outcomes ◽  
Autism Spectrum ◽  
Early Interventions ◽  
Infants And Toddlers ◽  
High Likelihood ◽  
Parent Implementation ◽  
The Impact

Understanding the impact of preemptive interventions on development for those with a high likelihood for autism is a critical step in building a transdiagnostic model of optimized intervention. The purpose of this systematic review and meta-analysis is to examine the impact of preemptive autism interventions on parent outcomes and child developmental outcomes. A total of 345 unique records were assessed for eligibility yielding 13 unique studies with 715 total infant/toddlers with a high likelihood for autism. There was a significant association between the early interventions on parent implementation of intervention strategies immediately following the intervention. However, there was no significant association between the early interventions and child developmental outcomes. The studies reporting moderator and/or mediator analyses suggest a meaningful association between parent implementation and long-term child social communication outcomes. Taken together, these findings suggest that parent-mediated interventions are associated with improved parent use of strategies, and although these results do not translate into immediate or short-term child developmental outcomes, there is evidence that parents with the greatest implementation facilitate later improved communication outcomes for their children. There is an urgent need to develop a nuanced intervention approach during a time of ever-changing concern about child development. Lay abstract Interventions to address core symptoms for young children on the autism spectrum have a strong and growing evidence base. Adapting and delivering evidence-based interventions to infants and toddlers with a high likelihood for autism is a logical next step. This systematic review and meta-analysis summarize the association between infant and toddler interventions and developmental and family outcomes. Results indicate that these early interventions are effective for improving parent implementation of core strategies, yet the effects do not readily translate to child outcomes. However, key studies demonstrate conditional results that indicate that parent implementation is associated with child outcome. Implications for research and practice toward building adaptive interventions that respond to parent implementation and changing child characteristics are discussed.

Evaluating the effectiveness of interventions to reducing screen time in children: meta-analysis of randomized controlled trials

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Duygu Akçay ◽  
Nuray Barış
Keyword(s):  
Effect Size ◽  
Subgroup Analysis ◽  
Screen Time ◽  
Meta Analysis ◽  
Intervention Group ◽  
Evidence Base ◽  
Control Group ◽  
Content Type ◽  
Mean Differences ◽  
The Impact

Purpose The purpose of this paper is to evaluate the impact of interventions focused on reducing screen time in children. Design/methodology/approach Studies that aim to investigate the effects of interventions aimed at reducing the time spent in front of the screen (i.e. screen time). A Random-effects model was used to calculate the pooled standard mean differences. The outcome was to evaluate the screen time in children in the 0–18 age range. A subgroup analysis was performed to reveal the extent to which the overall effect size varied by subgroups (participant age, duration of intervention and follow). Findings For the outcome, the meta-analysis included 21 studies, and the standard difference in mean change in screen time in the intervention group compared with the control group was −0.16 (95% confidence interval [CI], −0.21 to −0.12) (p < 0.001). The effect size was found to be higher in long-term (=7 months) interventions and follow-ups (p < 0.05). Originality/value Subgroup analysis showed that a significant effect of screen time reduction was observed in studies in which the duration of intervention and follow-up was =7 months. As the evidence base grows, future researchers can contribute to these findings by conducting a more comprehensive analysis of effect modifiers and optimizing interventions to reduce screen time.

scholarly journals Sleep in youth with autism spectrum disorders: systematic review and meta-analysis of subjective and objective studies

2018 ◽  
Vol 21 (4) ◽  
pp. 146-154 ◽  
Author(s):  
Amparo Díaz-Román ◽  
Junhua Zhang ◽  
Richard Delorme ◽  
Anita Beggiato ◽  
Samuele Cortese
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorders ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Newcastle Ottawa Scale ◽  
Spectrum Disorders ◽  
Sleep Alterations ◽  
The Impact ◽  
Ottawa Scale

BackgroundSleep problems are common and impairing in individuals with autism spectrum disorders (ASD). Evidence synthesis including both subjective (ie, measured with questionnaires) and objective (ie, quantified with neurophysiological tools) sleep alterations in youth with ASD is currently lacking.ObjectiveWe conducted a systematic review and meta-analysis of subjective and objective studies sleep studies in youth with ASD.MethodsWe searched the following electronic databases with no language, date or type of document restriction up to 23 May 2018: PubMed, PsycInfo, Embase+Embase Classic, Ovid Medline and Web of Knowledge. Random-effects models were used. Heterogeneity was assessed with Cochran’s Q and I2 statistics. Publication (small studies) bias was assessed with final plots and the Egger’s test. Study quality was evaluated with the Newcastle Ottawa Scale. Analyses were conducted using Review Manager and Comprehensive Meta-Analysis.FindingsFrom a pool of 3359 non-duplicate potentially relevant references, 47 datasets were included in the meta-analyses. Subjective and objective sleep outcome measures were extracted from 37 and 15 studies, respectively. Only five studies were based on comorbidity free, medication-naïve participants. Compared with typically developing controls, youth with ASD significantly differed in 10/14 subjective parameters and in 7/14 objective sleep parameters. The average quality score in the Newcastle-Ottawa Scale was 5.9/9.Discussion and clinical implicationsA number of subjective and, to a less extent, objective sleep alterations might characterise youth with ASD, but future studies should assess the impact of pharmacological treatment and psychiatric comorbidities.

scholarly journals Reliability of Computerized Neurocognitive Tests for Concussion Assessment: A Meta-Analysis

2017 ◽  
Vol 52 (9) ◽  
pp. 826-833 ◽  
Author(s):  
James L. Farnsworth ◽  
Lucas Dargo ◽  
Brian G. Ragan ◽  
Minsoo Kang
Keyword(s):  
Correlation Coefficient ◽  
Intraclass Correlation Coefficient ◽  
Effect Size ◽  
Sampling Error ◽  
Meta Analysis ◽  
Intraclass Correlation ◽  
Cognitive Testing ◽  
Test Duration ◽  
Neurocognitive Tests ◽  
The Impact

Objective:  Although widely used, computerized neurocognitive tests (CNTs) have been criticized because of low reliability and poor sensitivity. A systematic review was published summarizing the reliability of Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) scores; however, this was limited to a single CNT. Expansion of the previous review to include additional CNTs and a meta-analysis is needed. Therefore, our purpose was to analyze reliability data for CNTs using meta-analysis and examine moderating factors that may influence reliability. Data Sources:  A systematic literature search (key terms: reliability, computerized neurocognitive test, concussion) of electronic databases (MEDLINE, PubMed, Google Scholar, and SPORTDiscus) was conducted to identify relevant studies. Study Selection:  Studies were included if they met all of the following criteria: used a test-retest design, involved at least 1 CNT, provided sufficient statistical data to allow for effect-size calculation, and were published in English. Data Extraction:  Two independent reviewers investigated each article to assess inclusion criteria. Eighteen studies involving 2674 participants were retained. Intraclass correlation coefficients were extracted to calculate effect sizes and determine overall reliability. The Fisher Z transformation adjusted for sampling error associated with averaging correlations. Moderator analyses were conducted to evaluate the effects of the length of the test-retest interval, intraclass correlation coefficient model selection, participant demographics, and study design on reliability. Heterogeneity was evaluated using the Cochran Q statistic. Data Synthesis:  The proportion of acceptable outcomes was greatest for the Axon Sports CogState Test (75%) and lowest for the ImPACT (25%). Moderator analyses indicated that the type of intraclass correlation coefficient model used significantly influenced effect-size estimates, accounting for 17% of the variation in reliability. Conclusions:  The Axon Sports CogState Test, which has a higher proportion of acceptable outcomes and shorter test duration relative to other CNTs, may be a reliable option; however, future studies are needed to compare the diagnostic accuracy of these instruments.

scholarly journals Efectos de la intervención en conciencia morfológica sobre la lectura, escritura y comprensión: Meta-análisis

2015 ◽  
Vol 32 (1) ◽  
pp. 60 ◽  
Author(s):  
Mercedes I. Rueda-Sánchez ◽  
Patricia López-Bastida
Keyword(s):  
Effect Size ◽  
Selection Criteria ◽  
Meta Analysis ◽  
Reading Difficulties ◽  
Morphological Awareness ◽  
Awareness Training ◽  
Moderating Variables ◽  
Reading Vocabulary ◽  
Morphological Awareness Training ◽  
The Impact

The aim is to check, through a meta-analysis, the impact of morphological awareness training on writing, reading, comprehension and vocabulary of grade schooler. 31 studies were included in the meta-analysis; they were obtained from 19 articles that meet the selection criteria. Morphological awareness instruction has a high-medium and significant effect size in studied variables of literacy. On writing, <em>g</em>=0.491, <em>SE</em>=0.078, <em>IQ</em>=0339-0643, <em>p</em>=.000, reading, <em>g</em>=0.473, <em>SE</em>=0.096, <em>IQ</em>=0284-0662, <em>p</em>=.000, comprehension, <em>g</em>=0.468, <em>SE</em>=0.123, <em>IQ</em>=0227-0708, <em>p</em>= .000 and finally vocabulary, <em>g</em>=0.501, <em>SE</em>=0.152, <em>IQ</em>=0203-0798, <em>p</em>= .001. The test of Heterogeneity <em>Q</em> is only significant on writing so other moderating variables were explored but no differences between groups were found. It shows morphological awareness training improves reading, vocabulary and comprehension of grade schooler with and without reading difficulties. Nevertheless, the results on writing are more heterogeneous.

scholarly journals Estimating the statistical performance of different approaches to meta-analysis of data from animal studies in identifying the impact of aspects of study design

2018 ◽  
Author(s):  
Qianying Wang ◽  
Jing Liao ◽  
Kaitlyn Hair ◽  
Alexandra Bannach-Brown ◽  
Zsanett Bahor ◽  
...  
Keyword(s):  
Effect Size ◽  
False Positive ◽  
Latent Variable ◽  
Statistical Power ◽  
Animal Studies ◽  
Meta Analysis ◽  
False Positive Rate ◽  
Mean Difference ◽  
Positive Rate ◽  
Meta Regression

AbstractBackgroundMeta-analysis is increasingly used to summarise the findings identified in systematic reviews of animal studies modelling human disease. Such reviews typically identify a large number of individually small studies, testing efficacy under a variety of conditions. This leads to substantial heterogeneity, and identifying potential sources of this heterogeneity is an important function of such analyses. However, the statistical performance of different approaches (normalised compared with standardised mean difference estimates of effect size; stratified meta-analysis compared with meta-regression) is not known.MethodsUsing data from 3116 experiments in focal cerebral ischaemia to construct a linear model predicting observed improvement in outcome contingent on 25 independent variables. We used stochastic simulation to attribute these variables to simulated studies according to their prevalence. To ascertain the ability to detect an effect of a given variable we introduced in addition this “variable of interest” of given prevalence and effect. To establish any impact of a latent variable on the apparent influence of the variable of interest we also introduced a “latent confounding variable” with given prevalence and effect, and allowed the prevalence of the variable of interest to be different in the presence and absence of the latent variable.ResultsGenerally, the normalised mean difference (NMD) approach had higher statistical power than the standardised mean difference (SMD) approach. Even when the effect size and the number of studies contributing to the meta-analysis was small, there was good statistical power to detect the overall effect, with a low false positive rate. For detecting an effect of the variable of interest, stratified meta-analysis was associated with a substantial false positive rate with NMD estimates of effect size, while using an SMD estimate of effect size had very low statistical power. Univariate and multivariable meta-regression performed substantially better, with low false positive rate for both NMD and SMD approaches; power was higher for NMD than for SMD. The presence or absence of a latent confounding variables only introduced an apparent effect of the variable of interest when there was substantial asymmetry in the prevalence of the variable of interest in the presence or absence of the confounding variable.ConclusionsIn meta-analysis of data from animal studies, NMD estimates of effect size should be used in preference to SMD estimates, and meta-regression should, where possible, be chosen over stratified meta-analysis. The power to detect the influence of the variable of interest depends on the effect of the variable of interest and its prevalence, but unless effects are very large adequate power is only achieved once at least 100 experiments are included in the meta-analysis.

Abstract WMP37: Methodological Quality and Meta-Analysis of Animal Studies of Mesenchymal Stromal Cells for Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Kate Xie* ◽  
Quynh Vu* ◽  
Mark Eckert ◽  
Weian Zhao ◽  
Steven C Cramer
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Effect Size ◽  
Stromal Cells ◽  
Methodological Quality ◽  
Meta Analysis ◽  
Quality Score ◽  
Behavioral Effects ◽  
Behavioral Measure ◽  
Routes Of Administration ◽  
The Impact

INTRODUCTION: Mesenchymal stromal cells (MSC) are multipotent cells that support numerous restorative processes after stroke. The ease of isolation and immunoprivileged status of MSC have stimulated numerous preclinical stroke studies. We performed a meta-analysis to estimate study quality, size of behavioral effects, and the impact of variables such as timing of MSC administration in relation to stroke onset. METHODS: Studies of MSC and stroke were identified through PubMed and Web of Science. Studies of hemorrhage, not in English, or using modified MSC were excluded. A Quality Score was determined for each study, estimating methodological quality using 10 criteria derived from STAIR guidelines, with higher Quality Scores reflecting greater compliance with issues such as randomization and outcome blinding. Outcome data extracted for MSC and control arms were used to derive estimates of effect size using Cohen’s d. RESULTS: A total of 46 studies met criteria, with 39 studying rats, 6 mice, and 1 primates. There were 61 treatment groups, as some studies had >1 independent MSC treatment arms; MSC were introduced intravenously in 41, intracerebrally in 15, and intraarterially in 6. MSC source was rat in 24, human in 16, and mouse in 6. Time of MSC administration ranged from 5 weeks pre- to 1 month post-stroke. MSC dose ranged from 1x10^4 to 3.25x10^7. The median Quality Score was 6 (IQR 5-7). Quality Score was not related to time of MSC administration relative to stroke or to behavioral effect size. Median effect size was 2.05 for the Modified Neurological Severity Scale (n=23), 1.88 for Adhesive Removal Test (n=19), and 2.70 for the Rotarod Test (n=14). Effect sizes were substantial across all routes of administration and differed only for the mNSS (p<0.04), favoring the IC route. Effect size did not vary with time of MSC administration relative to stroke for any behavioral measure. CONCLUSIONS: The quality of preclinical MSC stroke studies has generally been good. MSC consistently provide very large behavioral benefits, across scales and routes of administration. The magnitude of behavioral effects was not related to the Quality Score or to the time of MSC administration relative to stroke. These findings support translation of MSC to human trials.

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