scholarly journals Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis

2017 ◽  
Author(s):  
Fernando Pires Hartwig ◽  
Neil Martin Davies ◽  
Bernardo Lessa Horta ◽  
Tarunveer S. Ahluwalia ◽  
Hans Bisgaard ◽  
...  
Keyword(s):  
De Novo ◽  
Meta Analysis ◽  
Secondary Analysis ◽  
Breastfeeding Duration ◽  
Large Individual ◽  
Environment Interaction ◽  
Primary Analysis ◽  
Interaction Coefficients ◽  
Individual Level ◽  
Z Scores

AbstractBackgroundAccumulating evidence suggests that breastfeeding benefits the children’s intelligence. Long-chain polyunsaturated fatty acids (LC-PUFAs) present in breast milk may explain part of this association. Under a nutritional adequacy hypothesis, an interaction between breastfeeding and genetic variants associated with endogenous LC-PUFAs synthesis might be expected. However, the literature on this topic is controversial.Methods and FindingsWe investigated this Gene×Environment interaction in a de novo meta-analysis involving >12,000 individuals in the primary analysis, and >45,000 individuals in a secondary analysis using relaxed inclusion criteria. Our primary analysis used ever breastfeeding, FADS2 polymorphisms rs174575 and rs1535 coded assuming a recessive effect of the G allele, and intelligence quotient (IQ) in Z scores. Using random effects meta-analysis, ever breastfeeding was associated with 0.17 (95% CI: 0.03; 0.32) higher Z scores in IQ, or about 2.1 points. There was no strong evidence of interaction, with pooled covariate-adjusted interaction coefficients (i.e., difference between genetic groups of the difference in IQZ scores comparing ever with never breastfed individuals) of 0.12 (95% CI: −0.19; 0.43) and 0.06 (95% CI: −0.16; 0.27) for the rs174575 and rs1535 variants, respectively. Secondary analyses corroborated these results. In studies with >5.85 and <5.85 months of breastfeeding duration, pooled estimates for the rs174575 variant were 0.50 (95% CI: −0.06; 1.06) and 0.14 (95% CI: −0.10; 0.38), respectively, and 0.27 (95% CI: −0.28; 0.82) and −0.01 (95% CI: −0.19; 0.16) for the rs1535 variant. However, between-group comparisons were underpowered.ConclusionsOur findings do not support an interaction between ever breastfeeding and FADS2 polymorphisms. However, our subgroup analysis raises the possibility that breastfeeding supplies LC-PUFAs requirements for cognitive development (if such threshold exists) if it lasts for some (currently unknown) time. Future studies in large individual-level datasets would allow properly powered subgroup analyses and would improve our understanding on the role of breastfeeding duration in the breastfeeding×FADS2 interaction.

scholarly journals Modulation of corticomotor excitability in response to distal focal cooling

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e6163 ◽  
Author(s):  
Yekta Ansari ◽  
Anthony Remaud ◽  
François Tremblay
Keyword(s):  
Skin Temperature ◽  
Motor Evoked Potentials ◽  
Secondary Analysis ◽  
Initial Study ◽  
Primary Analysis ◽  
Single Digit ◽  
Corticomotor Excitability ◽  
Individual Level ◽  
Cooling Phase ◽  
The Individual

Background Thermal stimulation has been proposed as a modality to facilitate motor recovery in neurological populations, such as stroke. Recently (Ansari, Remaud & Tremblay, 2018), we showed that application of cold or warm stimuli distally to a single digit produced a variable and short lasting modulation in corticomotor excitability. Here, our goal was to extend these observations to determine whether an increase in stimulation area could elicit more consistent modulation. Methods Participants (n = 22) consisted of a subset who participated in our initial study. Participants were asked to come for a second testing session where the thermal protocol was repeated but with extending the stimulation area from single-digit (SD) to multi-digits (MD, four fingers, no thumb). As in the first session, skin temperature and motor evoked potentials (MEPs) elicited with transcranial magnetic stimulation were measured at baseline (BL, neutral gel pack at 22 °C), at 1 min during the cooling application (pre-cooled 10 °C gel pack) and 5 and 10 min post-cooling (PC5 and PC10). The analysis combined the data obtained previously with single-SD cooling (Ansari, Remaud & Tremblay, 2018) with those obtained here for MD cooling. Results At BL, participants exhibited comparable measures of resting corticomotor excitability between testing sessions. MD cooling induced similar reductions in skin temperature as those recorded with SD cooling with a peak decline at C1 of respectively, −11.0 and −10.3 °C. For MEPs, the primary analysis revealed no main effect attributable to the stimulation area. A secondary analysis of individual responses to MD cooling revealed that half of the participants exhibited delayed MEP facilitation (11/22), while the other half showed delayed inhibition (10/22); which was sustained in the post-cooling phase. More importantly, a correlation between variations in MEP amplitude recorded during the SD cooling session with those recorded in the second session with MD cooling, revealed a very good degree of correspondence between the two at the individual level. Conclusion These results indicate that increasing the cooling area in the distal hand, while still eliciting variable responses, did produce more sustained modulation in MEP amplitude in the post-cooling phase. Our results also highlight that responses to cooling in terms of either depression or facilitation of corticomotor excitability tend to be fairly consistent in a given individual with repeated applications.

Validation of new ICD-10-based patient safety indicators for identification of in-hospital complications in surgical patients: a study of diagnostic accuracy

2019 ◽  
Vol 29 (3) ◽  
pp. 209-216 ◽  
Author(s):  
Daniel I McIsaac ◽  
Gavin M Hamilton ◽  
Karim Abdulla ◽  
Luke T Lavallée ◽  
Husien Moloo ◽  
...  
Keyword(s):  
Patient Safety ◽  
Secondary Analysis ◽  
Data Systems ◽  
Reference Standard ◽  
Likelihood Ratios ◽  
Primary Analysis ◽  
Predictive Values ◽  
Individual Level ◽  
Patient Safety Indicators ◽  
Icd 10

ObjectiveAdministrative data systems are used to identify hospital-based patient safety events; few studies evaluate their accuracy. We assessed the accuracy of a new set of patient safety indicators (PSIs; designed to identify in hospital complications).Study designProspectively defined analysis of registry data (1 April 2010–29 February 2016) in a Canadian hospital network. Assignment of complications was by two methods independently. The National Surgical Quality Improvement Programme (NSQIP) database was the clinical reference standard (primary outcome=any in-hospital NSQIP complication); PSI clusters were assigned using International Classification of Disease (ICD-10) codes in the discharge abstract. Our primary analysis assessed the accuracy of any PSI condition compared with any complication in the NSQIP; secondary analysis evaluated accuracy of complication-specific PSIs.PatientsAll inpatient surgical cases captured in NSQIP data.AnalysisWe assessed the accuracy of PSIs (with NSQIP as reference standard) using positive and negative predictive values (PPV/NPV), as well as positive and negative likelihood ratios (±LR).ResultsWe identified 12 898 linked episodes of care. Complications were identified by PSIs and NSQIP in 2415 (18.7%) and 2885 (22.4%) episodes, respectively. The presence of any PSI code had a PPV of 0.55 (95% CI 0.53 to 0.57) and NPV of 0.93 (95% CI 0.92 to 0.93); +LR 6.41 (95% CI 6.01 to 6.84) and −LR 0.40 (95% CI 0.37 to 0.42). Subgroup analyses (by surgery type and urgency) showed similar performance. Complication-specific PSIs had high NPVs (95% CI 0.92 to 0.99), but low to moderate PPVs (0.13–0.61).ConclusionValidation of the ICD-10 PSI system suggests applicability as a first screening step, integrated with data from other sources, to produce an adverse event detection pathway that informs learning healthcare systems. However, accuracy was insufficient to directly identify or rule out individual-level complications.

Terbinafine is More Effective Than Itraconazole in Treating Toenail Onychomycosis: Results from a Meta-analysis of Randomized Controlled Trials

2003 ◽  
Vol 7 (4) ◽  
pp. 306-311 ◽  
Author(s):  
H. Alexander Krob ◽  
Alan B. Fleischer ◽  
Ralph D'Agostino ◽  
Steven R. Feldman
Keyword(s):  
Odds Ratio ◽  
Fixed Effects ◽  
English Language ◽  
Meta Analysis ◽  
Secondary Analysis ◽  
Fixed Effects Model ◽  
Primary Analysis ◽  
Medline Search ◽  
Mycologic Cure ◽  
The Difference

Background: Toenail onychomycosis is a challenge for clinicians to treat, and this challenge is compounded by conflicting information in the medical literature concerning the efficacy of the two principal agents used in its treatment: Terbinafine and itraconazole. Objective: The purpose of this meta-analysis is to compare the efficacy of terbinafine with that of itraconazole in the treatment of toenail onychomycosis caused by dermatophytes. Methods: A Medline search was performed for all English language publications from 1966 to June 1999 on the use of terbinafine and itraconazole in the treatment of toenail onychomycosis. Included were randomized studies in which subjects received no less than 3 months (or cycles) and no more than 4 months (or cycles) of either terbinafine or itraconazole. Data were abstracted and statistical analyses (random effects model, fixed effects model, and Peto's method) were applied. Results: Thirteen studies were included from the original literature review of 1636 total referenced reports; four studies did not fulfill our inclusion or exclusion criteria. The primary analysis of six studies directly comparing terbinafine to itraconazole resulted in an odds ratio ranging from 1.8 (95% CI = 1.8, 2.8) to 2.9 (1.9, 4.1). The secondary analysis of three studies comparing either itraconazole or terbinafine to placebo estimated an odds ratio of 1.1–1.7. The former shows that terbinafine is 80%–190% more likely to result in mycologic cure than is itraconazole; the latter demonstrates a 10%–70% greater likelihood. The difference between the relative efficacies of terbinafine and itraconazole was highly statistically significant ( p < 0.0001). Conclusion: Meta-analysis of the published worldwide literature finds that terbinafine is significantly more effective than itraconazole at achieving mycologic cure of toenail onychomycosis.

scholarly journals 262. A Systematic Review and Meta-Analysis of the Impact of Delayed Appropriate Antibiotic Therapy on Mortality in Patients with Gram-Positive Bacteremia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S130-S130
Author(s):  
Steve Liu ◽  
Paochee Moua ◽  
Selam Monjor ◽  
Evan J Zasowski
Keyword(s):  
Systematic Review ◽  
Antibiotic Resistance ◽  
Antibiotic Therapy ◽  
Meta Analysis ◽  
Secondary Analysis ◽  
Primary Analysis ◽  
Gram Positive ◽  
Random Effects Models ◽  
Search Results ◽  
The Impact

Abstract Background Antibiotic resistance is common and frequently leads to unintentional delays in appropriate antibiotic therapy. The detrimental impact of delayed therapy is well-accepted, but the majority of evidence focuses on gram-negative infections. A review and synthesis of the evidence evaluating the impact of delayed appropriate antibiotic therapy in serious gram-positive infections does not exist. Such data would define the scope of the problem in this important patient population where antibiotic resistance is common. The objective of this systematic review and meta-analysis was to assess the impact of delayed appropriate antibiotic therapy on mortality in patients with gram-positive bacteremia. Methods Pubmed and Embase were searched from inception to March 30, 2020 to identify clinical studies of patients with bacteremia due to staphylococci, enterococci, or streptococci that reported the association between delayed appropriate antibiotic therapy and mortality. Three independent reviewers screened search results. Study quality was assessed via Newcastle-Ottawa Assessment Scale. Meta-analyses evaluating association between delayed therapy and mortality were conducted via random effects models in Review Manager 5.3. The primary analysis included unadjusted effect estimates from studies reporting unadjusted data. Secondary analysis included adjusted effect estimates from studies adjusting for confounding. Results Of 3684 search results, 16 cohort studies encompassing 4173 bacteremias were included. Ten studies involved S. aureus, 5 enterococci, and 2 S. pneumoniae. One-third (33.7%) of the 3659 patients in the primary analysis received delayed appropriate antibiotic therapy. The primary meta-analysis of 15 studies reporting unadjusted data showed a statistically significant association between delayed therapy and mortality (figure 1). Results from secondary analysis using adjusted point estimates from 9 studies were similar (figure 2). Figure 1. Forrest plot of meta-analysis of unadjusted association between delayed therapy and mortality Figure 2. Forrest plot of meta-analysis of covariate adjusted association between delayed therapy and mortality Conclusion Delayed appropriate therapy was common and associated with increased mortality in patients with gram-positive bacteremia. These findings underscore the need for continued antimicrobial stewardship efforts to ensure expeditious appropriate antibiotic therapy for patients with gram-positive bacteremia. Disclosures All Authors: No reported disclosures

scholarly journals Re-use of trial data in the first 10 years of the data-sharing policy of the Annals of Internal Medicine: a survey of published studies

2020 ◽  
Author(s):  
Claude Pellen ◽  
Laura Caquelin ◽  
Alexia Jouvance-Le Bail ◽  
Jeanne Gaba ◽  
Mathilde Vérin ◽  
...  
Keyword(s):  
Internal Medicine ◽  
Data Sharing ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Secondary Analysis ◽  
Primary Analysis ◽  
Share Data ◽  
Recherche Médicale ◽  
Secondary Outcomes ◽  
The Impact

ABSTRACTBackgroundThe Annals of Internal Medicine (AIM) has adopted a policy encouraging data-sharing since 2007.ObjectiveTo explore the impact of the AIM data-sharing policy for randomized controlled trials (RCTs) in terms of output from data-sharing (i.e. publications re-using the data).DesignRetrospective study.SettingAIM.ParticipantsRCTs published in the AIM between 2007 and 2017 were retrieved on PubMed. Publications where the data had been re-used were identified on Web of Science. Searches were performed by two independent reviewers.InterventionsIntention to share data (or not) expressed in a data-sharing statement.MeasurementsThe primary outcome was any published re-use of the data (i.e. re-analysis, secondary analysis, or meta-analysis of individual participant data [MIPD]), where the first, last and corresponding authors were not among the authors of the RCT. Components of the primary outcome and analyses without any author restriction were secondary outcomes. Analyses used Cox (primary analysis) models adjusting for RCT characteristics.Results185 RCTs were identified. 106 (57%) mentioned willingness to share data and 79 (43%) did not. 208 secondary analyses, 67 MIPD and no re-analyses were identified. No significant association was found between intent to share and re-use where the first, last and corresponding authors were not among the authors of the primary RCT (adjusted hazard ratio = 1.04 [0.47-2.30]). Secondary outcomes also showed no association between intent to share and re-use.LimitationsPossibility of residual confounding and limited power.ConclusionOver ten years, RCTs published in AIM expressing an intention to share data were not associated with more extensive re-use of the data.Registrationhttps://osf.io/8pj5e/Funding SourceGrants from the Fondation pour la Recherche Médicale, Région Bretagne, and French National Research Agency.

scholarly journals The clinical effectiveness and cost-effectiveness of heated humidified high-flow nasal cannula compared with usual care for preterm infants: systematic review and economic evaluation

2016 ◽  
Vol 20 (30) ◽  
pp. 1-68 ◽  
Author(s):  
Nigel Fleeman ◽  
James Mahon ◽  
Vickie Bates ◽  
Rumona Dickson ◽  
Yenal Dundar ◽  
...  
Keyword(s):  
Economic Evaluation ◽  
Usual Care ◽  
Preterm Infants ◽  
Meta Analysis ◽  
Secondary Analysis ◽  
Clinical Effectiveness ◽  
High Flow ◽  
High Flow Nasal Cannula ◽  
Primary Analysis ◽  
The Cost

BackgroundRespiratory problems are one of the most common causes of morbidity in preterm infants and may be treated with several modalities for respiratory support such as nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive-pressure ventilation. The heated humidified high-flow nasal cannula (HHHFNC) is gaining popularity in clinical practice.ObjectivesTo address the clinical effectiveness of HHHFNC compared with usual care for preterm infants we systematically reviewed the evidence of HHHFNC with usual care following ventilation (the primary analysis) and with no prior ventilation (the secondary analysis). The primary outcome was treatment failure defined as the need for reintubation (primary analysis) or intubation (secondary analysis). We also aimed to assess the cost-effectiveness of HHHFNC compared with usual care if evidence permitted.Data sourcesThe following databases were searched: MEDLINE (2000 to 12 January 2015), EMBASE (2000 to 12 January 2015), The Cochrane Library (issue 1, 2015), ISI Web of Science (2000 to 12 January 2015), PubMed (1 March 2014 to 12 January 2015) and seven trial and research registers. Bibliographies of retrieved citations were also examined.Review methodsTwo reviewers independently screened all titles and abstracts to identify potentially relevant studies for inclusion in the review. Full-text copies were assessed independently. Data were extracted and assessed for risk of bias. Summary statistics were extracted for each outcome and, when possible, data were pooled. A meta-analysis was only conducted for the primary analysis, using fixed-effects models. An economic evaluation was planned.ResultsClinical evidence was derived from seven randomised controlled trials (RCTs): four RCTs for the primary analysis and three RCTs for the secondary analysis. Meta-analysis found that only for nasal trauma leading to a change of treatment was there a statistically significant difference, favouring HHHFNC over NCPAP [risk ratio (RR) 0.21, 95% confidence interval (CI) 0.10 to 0.42]. For the following outcomes, there were no statistically significant differences between arms: treatment failure (reintubation < 7 days; RR 0.76, 95% CI 0.54 to 1.09), bronchopulmonary dysplasia (RR 0.92, 95% CI 0.72 to 1.17), death (RR 0.56, 95% CI 0.22 to 1.44), pneumothorax (RR 0.33, 95% CI 0.03 to 3.12), intraventricular haemorrhage (grade ≥ 3; RR 0.41, 95% CI 0.15 to 1.15), necrotising enterocolitis (RR 0.41, 95% CI 0.15 to 1.14), apnoea (RR 1.08, 95% CI 0.74 to 1.57) and acidosis (RR 1.16, 95% CI 0.38 to 3.58). With no evidence to support the superiority of HHHFNC over NCPAP, a cost-minimisation analysis was undertaken, the results suggesting HHHFNC to be less costly than NCPAP. However, this finding is sensitive to the lifespan of equipment and the cost differential of consumables.LimitationsThere is a lack of published RCTs of relatively large-sized populations comparing HHHFNC with usual care; this is particularly true for preterm infants who had received no prior ventilation.ConclusionsThere is a lack of convincing evidence suggesting that HHHFNC is superior or inferior to usual care, in particular NCPAP. There is also uncertainty regarding whether or not HHHFNC can be considered cost-effective. Further evidence comparing HHHFNC with usual care is required.Study registrationThis review is registered as PROSPERO CRD42015015978.FundingThe National Institute for Health Research Health Technology Assessment programme.

scholarly journals Duration of Breastfeeding and Risk of SIDS: An Individual Participant Data Meta-analysis

2018 ◽  
pp. 127-136
Author(s):  
John M.D. Thompson ◽  
Kawai Tanabe ◽  
Rachel Y. Moon ◽  
Edwin A. Mitchell ◽  
Cliona McGarvey ◽  
...  
Keyword(s):  
Exclusive Breastfeeding ◽  
Data Extraction ◽  
Meta Analysis ◽  
Case Control ◽  
Breastfeeding Duration ◽  
Sudden Infant ◽  
Case Control Studies ◽  
Individual Level ◽  
Individual Participant ◽  
Duration Of Breastfeeding

CONTEXT Sudden infant death syndrome (SIDS) is a leading cause of postneonatal infant mortality. Our previous meta-analyses showed that any breastfeeding is protective against SIDS with exclusive breastfeeding conferring a stronger effect. The duration of breastfeeding required to confer a protective effect is unknown. OBJECTIVE To assess the associations between breastfeeding duration and SIDS. DATA SOURCES Individual-level data from 8 case-control studies. STUDY SELECTION Case-control SIDS studies with breastfeeding data. DATA EXTRACTION Breastfeeding variables, demographic factors, and other potential confounders were identified. Individual-study and pooled analyses were performed. RESULTS A total of 2267 SIDS cases and 6837 control infants were included. In multivariable pooled analysis, breastfeeding for &lt;2 months was not protective (adjusted odds ratio [aOR]: 0.91, 95% confidence interval [CI]: 0.68–1.22). Any breastfeeding ≥2 months was protective, with greater protection seen with increased duration (2–4 months: aOR: 0.60, 95% CI: 0.44– 0.82; 4–6 months: aOR: 0.40, 95% CI: 0.26–0.63; and &gt;6 months: aOR: 0.36, 95% CI: 0.22– 0.61). Although exclusive breastfeeding for &lt;2 months was not protective (aOR: 0.82, 95% CI: 0.59–1.14), longer periods were protective (2–4 months: aOR: 0.61, 95% CI: 0.42–0.87; 4–6 months: aOR: 0.46, 95% CI: 0.29–0.74). LIMITATIONS The variables collected in each study varied slightly, limiting our ability to include all studies in the analysis and control for all confounders. CONCLUSIONS Breastfeeding duration of at least 2 months was associated with half the risk of SIDS. Breastfeeding does not need to be exclusive to confer this protection.

scholarly journals Leveraging both individual-level genetic data and GWAS summary statistics increases polygenic prediction

2020 ◽  
Author(s):  
Clara Albiñana ◽  
Jakob Grove ◽  
John J. McGrath ◽  
Esben Agerbo ◽  
Naomi R. Wray ◽  
...  
Keyword(s):  
Association Studies ◽  
Meta Analysis ◽  
Training Sample ◽  
Risk Scores ◽  
Large Individual ◽  
Genome Wide Association Studies ◽  
Summary Statistics ◽  
Uk Biobank ◽  
Individual Level ◽  
Level Data

AbstractThe accuracy of polygenic risk scores (PRSs) to predict complex diseases increases with the training sample size. PRSs are generally derived based on summary statistics from large meta-analyses of multiple genome-wide association studies (GWAS). However, it is now common for researchers to have access to large individual-level data as well, such as the UK biobank data. To the best of our knowledge, it has not yet been explored how to best combine both types of data (summary statistics and individual-level data) to optimize polygenic prediction. The most widely used approach to combine data is the meta-analysis of GWAS summary statistics (Meta-GWAS), but we show that it does not always provide the most accurate PRS. Through simulations and using twelve real case-control and quantitative traits from both iPSYCH and UK Biobank along with external GWAS summary statistics, we compare Meta-GWAS with two alternative data-combining approaches, stacked clumping and thresholding (SCT) and Meta-PRS. We find that, when large individual-level data is available, the linear combination of PRSs (Meta-PRS) is both a simple alternative to Meta-GWAS and often more accurate.

Hierarchical Modelling of Facial Perceptions: A Secondary Analysis of Aggressiveness Ratings

2020 ◽  
Author(s):  
Mark Christopher Adkins ◽  
Nataly Beribisky ◽  
Stephan Bonfield ◽  
Linda Farmus
Keyword(s):  
Factor Analysis ◽  
Mixed Model ◽  
Structural Information ◽  
Secondary Analysis ◽  
Specific Factor ◽  
Primary Analysis ◽  
Model Framework ◽  
Psychological Science ◽  
Individual Traits ◽  
Confirmatory Factor

The Psychological Science Accelerator’s (PSA) primary project tested for latent structure using exploratory factor analysis and confirmatory factor analysis but we decided to diverge from this approach and model individual traits separately. Our interest mainly was in examining the interplay between “stimulus ethnicity” and “stimulus sex” to discover how differing levels of these criterion differ across region, country, lab etc. While the necessary and prerequisite hierarchical structural information about each trait could certainly be found within the primary project’s dataset, we did not assume that any specific factor structure from the PSA’s primary analysis would necessarily hold, therefore we based our decision to model the data from each trait separately using a mixed model framework.

Sign in / Sign up

Export Citation Format

Share Document