Combined Effect Estimates Research Articles

Mastering meta-analysis in Microsoft Excel with MetaXL add-in: A comprehensive tutorial and guide to meta-analysis.

Meta-analysis, a powerful technique for combining effect estimates from multiple studies, enhances statistical power and precision. However, its adoption can be hindered by challenges in statistical interpretation and the complexity of specialized software. MetaXL, a freely available Microsoft Excel add-in, aims to mitigate these barriers by providing comprehensive support and facilitating seamless integration of meta-analytical results into research publications. This tutorial illustrates the practical application of MetaXL for synthesizing meta-analytical evidence, with a focus on common effect sizes and their presentation. This paper reintroduce MetaXL's functions and provide concise explanations of common effect sizes employed in meta-analysis. The tutorial delves into fundamental concepts such as the selection of appropriate effect sizes for pooling and the choice of meta-analytical models. Eight illustrative examples are presented, incorporating diverse effect sizes and data formats, including scenarios involving incidence rate ratios, weighted and standardized mean differences, hazard ratios, and prevalence. Additionally, key concepts in network meta-analysis are discussed, along with their implementation in MetaXL. MetaXL provides convenient access to data formatting templates tailored to various data types and effect sizes encountered in included studies. This tutorial offers researchers, particularly those with limited resources, detailed explanations and insights into commonly used methodologies for pooling effect sizes. Furthermore, it introduces the new Excel functions that comes with the MetaXL add-in. Accurate population of this function and adherence to the correct format are essential to ensure error-free analyzes.

Social network-based approaches to HIV testing: a systematic review and meta-analysis.

Social network-based testing approaches (SNAs) encourage individuals ("test promoters") to motivate sexual partners and/or those in their social networks to test for HIV. We conducted a systematic review to examine the effectiveness, acceptability and cost-effectiveness of SNA. We searched five databases from January 2010 to May 2023, and included studies that compared SNA with non-SNA. We used random-effects meta-analysis to combine effect estimates. Certainty was assessed using the GRADE approach. We identified 47 studies. SNA may increase uptake of HIV testing compared to non-SNA (RR 2.04, 95% CI: 1.06-3.95, Low certainty). The proportion of first-time testers was probably higher among partners or social contacts of test promoters using SNA compared to non-SNA (RR 1.49, 95% CI: 1.22-1.81, Moderate certainty). The proportion of people who tested positive for HIV may be higher among partners or social contacts of test promoters using SNA compared to non-SNA (RR 1.84, 95% CI: 1.01-3.35, Low certainty). There were no reports of any adverse events or harms associated with SNA. Based on six cost-effectiveness studies, SNA was generally cheaper per person tested and per person diagnosed compared to non-SNA. Based on 23 qualitative studies, SNA is likely to be acceptable to a variety of populations. Our review collated evidence for SNA to HIV testing covering the key populations and the general population who may benefit from HIV testing. We summarized evidence for the effectiveness, acceptability and cost-effectiveness of different models of SNA. While we did not identify an ideal model of SNA that could be immediately scaled up, for each setting and population targeted, we recommend various implementation considerations as our meta-analysis showed the effectiveness might differ due to factors which include the testing modality (i.e. use of HIV self-testing), type of test promoters, long or short duration of recruitment and use of financial incentives. Social network-based approaches may enhance HIV testing uptake, increase the proportion of first-time testers and those testing positive for HIV. Heterogeneity among studies highlights the need for context-specific adaptations, but the overall positive impact of SNA on HIV testing outcomes could support its integration into existing HIV testing services.

Comparison for the diagnostic performance of early diagnostic methods for biliary atresia: a systematic review and network meta-analysis.

Biliary atresia (BA), a progressive condition affecting canalicular-bile duct function/anatomy, requires prompt surgical intervention for favorable outcomes. Therefore, we conducted a network meta-analysis of common diagnostic methods to assess their performance and provide evidence-based support for clinical decision-making. We reviewed literature in PubMed, EMBASE, and Cochrane for BA diagnostics. The search included gamma-glutamyl transferase (GGT), direct/combined bilirubin, matrix metalloproteinase 7 (MMP-7), ultrasonic triangular cord sign (TCS), hepatic scintigraphy (HS), and percutaneous cholangiocholangiography/percutaneous transhepatic cholecysto-cholangiography (PCC/PTCC). QUADAS-2 assessed study quality. Heterogeneity and threshold effect were evaluated using I2 and Spearman's correlation. We combined effect estimates, constructed SROC models, and conducted a network meta-analysis based on the ANOVA model, along with meta-regression and subgroup analysis, to obtain precise diagnostic performance assessments for BA. A total of 40 studies were included in our analysis. GGT demonstrated high diagnostic accuracy for BA with a sensitivity of 81.5% (95% CI 0.792-0.836) and specificity of 72.1% (95% CI 0.693-0.748). Direct bilirubin/conjugated bilirubin showed a sensitivity of 87.6% (95% CI 0.833-0.911) but lower specificity of 59.4% (95% CI 0.549-0.638). MMP-7 exhibited a total sensitivity of 91.5% (95% CI 0.893-0.934) and a specificity of 84.3% (95% CI 0.820-0.863). TCS exhibited a sensitivity of 58.1% (95% CI 0.549-0.613) and high specificity of 92.9% (95% CI 0.911-0.944). HS had a high sensitivity of 98.4% (95% CI 0.968-0.994) and moderate specificity of 79.0% (95% CI 0.762-0.816). PCC/PTCC exhibited excellent diagnostic performance with a sensitivity of 100% (95% CI 0.900-1.000) and specificity of 87.0% (95% CI 0.767-0.939). Based on the ANOVA model, the network meta-analysis revealed that MMP-7 ranked second overall, with PCC/PTCC ranking first, both exhibiting superior diagnostic accuracy compared to other techniques. Our analysis showed no significant bias in most methodologies, but MMP-7 and hepatobiliary scintigraphy exhibited biases, with p values of 0.023 and 0.002, respectively. MMP-7 and ultrasound-guided PCC/PTCC show diagnostic potential in the early diagnosis of BA, but their clinical application is restricted due to practical limitations. Currently, the cutoff value of MMP-7 is unclear, and further evidence-based medical research is needed to firmly establish its diagnostic value. Until more evidence is available, MMP-7 is not suitable for widespread diagnostic use. Therefore, considering cost and operational simplicity, liver function tests combined with ultrasound remain the most clinically valuable non-invasive diagnostic methods for BA.

Exploring individual responses to welfare issues in growing-finishing pig feeding behaviour

The feeding behaviour of individual growing-finishing pigs can be continuously monitored using sensors such as electronic feeding stations (EFSs), and this could be further used to monitor pig welfare. To make accurate conclusions about individual pig welfare, however, it is important to know whether deviations in feeding behaviour in response to welfare issues are shown only on average or by each individual pig. Therefore, this study aimed (1) to quantify the individual variation in feeding behaviour changes in response to a range of welfare issues, and (2) to explain this individual variation by quantifying the responses to welfare issues for specific subgroups of pigs. We monitored four rounds of 110 growing-finishing pigs each (3–4 months per round). We collected feeding behaviour data using IVOG® EFSs and identified health issues and heat stress using climate sensors and twice-weekly health observations. For each pig, a generalised additive model was fitted, which modelled feeding behaviour through time and estimated the effect of each welfare issue that the pig had suffered from. The range of these effect estimates was compared between pigs to study the individual variation in responses. Subsequently, pigs were repeatedly grouped using physical and feeding characteristics, and, with meta–subset analysis, it was determined for each group whether a deviation in response to the welfare issue (i.e. their combined effect estimates) was present. We found that the range in effect estimates was very large, approaching normal distributions for most combinations of welfare issues and feeding variables. This indicates that most pigs did not show feeding behaviour deviations during the welfare issue, while those that did could show both increases and reductions. One exception was heat stress, for which almost all pigs showed reductions in their feed intake, feeding duration and feeding frequency. When looking at subgroups of pigs, it was seen that especially for lameness and tail damage pigs with certain physical characteristics or feeding strategies did consistently deviate on some feeding components during welfare issues (e.g. only relatively heavier pigs reduced their feeding frequency during lameness). In conclusion, while detection of individual pigs suffering from heat stress using feeding variables should be feasible, detection of (mild) health issues would be difficult due to pigs responding differently, if at all, to a given health issue. For some pigs with specific physical or behavioural characteristics, nevertheless, detection of some health issues, such as lameness or tail damage, may be possible.

Obesity and thyroid cancer: unraveling the connection through a systematic review and meta-analysis of cohort studies.

The relationship between adiposity indicators and thyroid cancer (TC) risk has garnered increasing attention due to the rising prevalence of obesity and its potential impact on cancer incidence. We conducted a comprehensive meta-analysis to investigate this association across various effect measures. Until July 2022, a comprehensive search of databases was conducted to identify cohort studies that assessed the association between adiposity and the development of TC. Meta-analysis was performed using random effects models. Subgroup analyses were conducted to explore heterogeneity. Publication bias was assessed using Begg's tests. A systematic literature search identified 27 eligible studies reporting odds ratios (OR), relative risks (RR), or hazard ratios (HR) as effect measures. Pooling the studies irrespective of the effect measure, a significant positive association between adiposity indicators and TC risk was observed, yielding an effect estimate of 1.16 (95% CI 1.12-1.21). The combined effect estimate for OR/RR studies was 1.10 (95%CI 1.04-1.17), while HR studies yielded an effect estimate of 1.20 (95%CI 1.13-1.26). Subgroup analyses revealed associations across different age groups, obesity indices, and regions, with some variations based on effect measure. Meta-regression identified follow-up duration as a confounding factor only in HR studies. The synthesis of 27 studies with diverse designs and populations underscores a robust positive association between adiposity and TC risk, providing compelling evidence for the potential role of increased adiposity in TC development. The online version contains supplementary material available at 10.1007/s40200-024-01425-3.

Risk of Long-Term Ischemic Stroke in Patients With Traumatic Brain Injury and Incident Hypertension.

Traumatic brain injury (TBI) is independently associated with hypertension and ischemic stroke. The goal of this study was to determine the interplay between TBI and incident hypertension in the occurrence of post-TBI stroke. This prospective study used a hospital-based registry to identify patients without pre-existing comorbidities. TBI patients (n = 3664) were frequency matched on age, sex, and race to non-TBI patients (n = 1848). Follow-up started 6 months post-TBI or study entry and extended up to 10 years. To examine hypertension's role in post-TBI stroke, we used logistic regression models to calculate the effect estimates for stroke in four exposure categories that included TBI or hypertension in isolation and in combination. Second, we calculated the conditional direct effect (CDE) of TBI in models that considered hypertension as intermediary. Third, we examined whether TBI effect was modified by antihypertensive medication use. The 10-year cumulative incidence of stroke was higher in the TBI group (4.7%) than the non-TBI group (1.3%; p < 0.001). TBI patients who developed hypertension had the highest risk of stroke (odds ratio [OR] = 4.83, 95% confidence interval [CI] = 2.53-9.23, p < 0.001). The combined effect estimates were less than additive, suggesting an overlapping biological pathway. The total effect of TBI (OR = 3.16, 95% CI = 1.94-5.16, p < 0.001) was higher than the CDE that accounted for hypertension (OR = 2.45, 95% CI = 0.93-6.47, p = 0.06). Antihypertensives attenuated the TBI effect, suggesting that the TBI effect on stroke is partially mediated through hypertension. TBI is an independent risk factor for long-term stroke, and the underlying biological pathway may partly operate through TBI-precipitated hypertension. These findings suggest that screening for hypertension may mitigate stroke risk in TBI.

Association between oxidative stress and chronic orofacial pain and potential druggable targets: Evidence from a Mendelian randomization study.

Oxidative stress indicators affect chronic orofacial pain (COFP), but how to reduce these effects is uncertain. 11 oxidative stress biomarkers were collected as exposures, while four forms of COFP were chosen as outcomes for Mendelian randomization (MR) study. The effect estimates between oxidative stress and COFP were calculated using inverse variance-weighted MR (IVW-MR). Then, functional mapping and annotation (FUMA) was utilized in order to carry out SNP-based functional enrichment analyses. In addition, the IVW-MR method was applied to combine effect estimates when using genetic variants associated with oxidative stress biomarkers as an instrument for exploring potential druggable targets. The results indicated that oxidative stress biomarkers (causal OR of uric acid (UA), 0.998 for myofascial pain, 95% CI 0.996-1.000, p < .05; and OR of glutathione transferase (GST), 1.002 for dentoalveolar pain, 95% CI 1.000-1.003, p < .05) were significantly linked with the probability of COFP. Functional analysis also demonstrated that UA and myofascial pain genes were prominent in nitrogen and uracil metabolism, while GST and dentoalveolar pain genes were enriched in glutathione metabolism. Also, the study provided evidence that solute carrier family 2 member 9 (SLC2A9) and glutathione S-transferase alpha 2 (GSTA2) cause discomfort in the myofascial pain (OR = 1.003, 95% CI 1.000-1.006; p < .05) and dentoalveolar region (OR = 1.001, 95% CI 1.000-1.002; p < .05), respectively. In conclusion, this MR study indicates that genetically predicted myofascial pain was significantly associated with decreased UA and dentoalveolar pain was significantly associated with increased GST level. SLC2A9 inhibitor and GSTA2 inhibitor were novel chronic orofacial pain therapies and biomarkers, but clinical trials are called to examine if these oxidative biomarkers have the protective effect against orofacial pain, and further research are needed to explore the underlying mechanisms.

Ambient temperature and preterm birth: A case-crossover study.

To investigate the association between ambient temperature and preterm birth (PTB) and to estimate the population attributable fraction (PAF) of PTBs due to low and high temperatures. Time-stratified case-crossover design. Japan (46 prefectures, excluding Okinawa), 2011-2020. 214 050 PTBs registered in the Japan Perinatal Registry Network database among 1 908 168 singleton live births. A quasi-Poisson regression model with a distributed lag nonlinear model was employed to assess the associations between daily mean temperature and PTBs for a lag of 0-27 days in each prefecture. A random effects meta-analysis was conducted by combining effect estimates from the 46 prefectures to estimate pooled relative risks (RRs). The PAFs of the PTBs due to below or above the mean of the 46 median temperatures (16.0°C) were calculated. Preterm singleton live births. The association between daily mean temperature and PTB risk exhibited a U-shaped curve. The adjusted RRs were 1.15 (95% confidence interval [CI] 1.05-1.25) at the mean of the 1st percentiles (0.8°C) and 1.08 (95% CI 1.00-1.17) at the mean of the 99th percentiles (30.2°C) of 46 prefectures, with 16.0°C as the reference temperature. Approximately 2.3% (95% CI 0.6-4.0) of PTBs were attributable to low temperatures. Both low and possibly high temperatures were associated with an increased risk of PTBs. These findings may help to inform preventive measures for pregnant women.

Efficacy of platelet-rich plasma (PRP) in benign vocal fold lesions: a systematic review and meta-analysis.

To evaluate the efficacy of platelet-rich plasma (PRP) in benign vocal fold lesions. MEDLINE, Cochrane Central, Web of Science, and Scopus databases were searched in April 2023 for relevant clinical trials. Inclusion criteria were clinical trials evaluating the efficacy of PRP in benign vocal fold lesions. We conducted a comparative double-arm analysis using the pooled mean difference (MD) and 95% confidence interval (CI). Outcomes of interest included the vocal handicap index (VHI), the Jitter and Shimmer percentages, and the noise-to-harmonic ratio (NHR). Six studies matched the inclusion criteria. The pooled analysis shows that PRP was associated with significantly lower VHI scores compared with the control (MD = - 5.06, p < 0.01). Regarding the Jitter percentage, the PRP group was not superior to the control group at 2 and 4 weeks. However, the results revealed that PRP significantly reduced the Jitter percentage at 3 months (MD = - 0.61, p = 0.0008). The overall analysis favored the PRP arm significantly (p < 0.001). As for the Shimmer percentage, the combined effect estimate favored the PRP group (MD = - 1.22, p = 0.002). Subgroup analysis according to the time did not reveal any significant differences between studies at 2 weeks, 4 weeks, and 3 months. The analysis of the NHR outcome revealed a significant difference between both groups (MD = -1.09, p = 0.01). However, at 4 weeks, the treatment group had a significantly lower NHR % compared to the control group (MD = - 0.61, p = 0.02). There was no significant difference at 3 months (MD = - 2.14, p = 0.14). Platelet-rich plasma is effective in reducing VHI scores, Jitter and Shimmer percentages, and NHR values. This effect is more evident after follow-up, especially 3 months.

Effect of Malaria on Blood Levels of Vitamin E: A Systematic Review and Meta-Analysis.

Vitamin E has an antioxidant property and is associated with protection against malaria. The current study used systematic review and meta-analysis approaches examining the variance in blood levels of vitamin E in malaria patients as compared with uninfected individuals. The protocol for the systematic review was registered with PROSPERO (CRD4202341481). Searches for pertinent studies were carried out on Embase, MEDLINE, Ovid, PubMed, Scopus, ProQuest, and Google Scholar. The combined effect estimate (Cohen's d) of the difference in vitamin E levels in malaria patients as compared with uninfected individuals was estimated using the random effects model. The searches yielded 2009 records, and 23 studies were included in the systematic review. The majority of the studies (80%) found that vitamin E levels were significantly lower in malaria patients than those who were not infected. Overall, the results revealed a significant reduction in blood levels of vitamin E in malaria patients when compared with uninfected individuals (p < 0.01, Cohen's d: -2.74, 95% CI: -3.72-(-1.76), I2: 98.69%, 21 studies). There was a significant reduction in blood levels of vitamin E in patients suffering from severe malaria, in comparison with those experiencing less severe forms of the disease (p < 0.01, Cohen's d: -0.56, 95% CI: -0.85-(-0.26), I2: 0%, 2 studies), but no variation in blood levels of vitamin E among patients suffering from either P. falciparum or P. vivax malaria (p = 0.13, Cohen's d: -1.15, 95% CI: -2.62-0.33, I2: 93.22%, 3 studies). In summary, the present study strongly suggests that vitamin E levels are significantly reduced in malaria patients, with a more pronounced decrease observed in cases of severe malaria. However, the type of malaria parasite, specifically P. falciparum or P. vivax, did not appear to influence the levels of vitamin E. This study highlights the potential role of vitamin E in the pathogenesis of malaria and suggests that improved vitamin E status might be beneficial for improving disease outcomes.

Better-constrained climate sensitivity when accounting for dataset dependency on pattern effect estimates

Abstract. The best estimate of equilibrium climate sensitivity (ECS) constrained based on the instrumental record of historical warming becomes coherent with other lines of evidence when the dependence of radiative feedback on the pattern of surface temperature change (pattern effect) is incorporated. Pattern effect strength is usually estimated with atmosphere-only model simulations forced with observed historical sea-surface temperature (SST) and sea-ice change and constant pre-industrial forcing. However, recent studies indicate that pattern effect estimates depend on the choice of SST boundary condition dataset, due to differences in the measurement sources and the techniques used to merge and construct them. Here, we systematically explore this dataset dependency by applying seven different observed SST datasets to the MPI-ESM1.2-LR model covering 1871–2017. We find that the pattern effect ranges from -0.01±0.09 to 0.42±0.10 W m−2 K−1 (standard error), whereby the commonly used Atmospheric Model Intercomparison Project II (AMIPII) dataset produces by far the largest estimate. When accounting for the generally weaker pattern effect in MPI-ESM1.2-LR compared to other models, as well as dataset dependency and intermodel spread, we obtain a combined pattern effect estimate of 0.37 W m−2 K−1 [−0.14 to 0.88 W m−2 K−1] (5th–95th percentiles) and a resulting instrumental record ECS estimate of 3.2 K [1.8 to 11.0 K], which as a result of the weaker pattern effect is slightly lower and better constrained than in previous studies.

Risk factors for early-onset colorectal cancer: systematic review and meta-analysis.

The incidence of early-onset colorectal cancer (EOCRC), which means colorectal cancer diagnosed in patients under 50 years, has been increasing around the world. However, the etiology remains unclear. This study aims to identify risk factors for EOCRC. This systematic review was conducted in PubMed, Embase, Scopus, and Cochrane Library databases from inception to November 25, 2022. We examined risk factors for EOCRC, including demographic factors, chronic conditions, and lifestyle behaviors or environmental factors. Random-effects/fixed-effects meta-analysis was adopted to combine effect estimates from published data. Study quality was evaluated with the Newcastle-Ottawa Scale (NOS). Statistical analysis was performed Revman5.3. Studies not suitable for the meta-analysis were analyzed by a systematic review. A total of 36 studies were identified for this review, and 30 studies were included in the meta-analysis. Significant risk factors for EOCRC included male (OR=1.20; 95% CI, 1.08-1.33), Caucasian (OR=1.44; 95% CI, 1.15-1.80), a family history of CRC (OR=5.90; 95% CI, 3.67-9.48), inflammatory bowel disease (OR=4.43; 95% CI, 4.05-4.84), obesity (OR=1.52; 95%CI, 1.20-1.91), overweight (OR=1.18; 95% CI, 1.12-1.25), triglycerides (OR=1.12; 95% CI, 1, 08-1.18), hypertension (OR=1.16; 95% CI, 1.12-1.21), metabolic syndrome (OR=1.29; 95% CI, 1.15-1.45), smoking (OR=1.44; 95% CI, 1.10-1.88), alcohol consumption (OR=1.41; 95% CI, 1.22-1.62), a sedentary lifestyle (OR=1.24; 95% CI, 1.05-1.46), red meat (OR=1.10; 95% CI, 1.04-1.16), processed meat (OR=1.53; 95% CI, 1.13-2.06), Western dietary patterns (OR=1.43; 95% CI, 1.18-1.73) and sugar-sweetened beverages (OR=1.55; 95% CI, 1.23-1.95). However, no statistical differences were found for hyperlipidemia and hyperglycemia. Vitamin D may be a protective factor (OR=0.72; 95% CI, 0.56-0.92). There was considerable heterogeneity among studies (I2>60%). The study provides an overview of the etiology and risk factors of EOCRC. Current evidence can provide baseline data for risk prediction models specific to EOCRC and risk-tailored screening strategies.

Menopause is associated with increased prevalence of nonalcoholic fatty liver disease: a systematic review and meta-analysis.

Data are inconsistent on whether menopause is a risk for nonalcoholic fatty liver disease (NAFLD). Using systematic review and meta-analysis, we aimed to collect all available data to determine the association between menopause and NAFLD. Potentially eligible studies were identified from EMBASE, MEDLINE, and Web of Science databases from inception to December 2021 using a search strategy that was composed of the terms for "NAFLD" and "menopause." Eligible study must contain two groups of participants: one group of postmenopausal women and another group of premenopausal women. Then, the study must report the association between menopause and prevalent NAFLD. We extracted such data from each study and calculated pooled odds ratio (OR) by combining effect estimates of each study using a random-effects model. Funnel plot was used to assess for the presence of publication bias. A total of 587 articles were identified. After two rounds of independent review by two investigators, 12 cross-sectional studies fulfilled the eligibility criteria. The meta-analysis of 12 studies revealed the significant association between menopause and NAFLD with a pooled OR of 2.37 (95% CI, 1.99-2.82; I2 = 73%). The association remained significant in a sensitivity meta-analysis of six studies that reported the association with adjustment for age and metabolic factors with a pooled OR of 2.19 (95% CI, 1.73-2.78; I2 = 74%). The funnel plot was fairly symmetric and was not suggestive of publication bias. The meta-analysis reveals that menopausal status was associated with approximately 2.4 times higher odds of NAFLD.

Non-contrast computed tomography-based factors in predicting ESWL success: A systematic review and meta-analysis.

We assessed the efficacy of some predictive factors that can be measured with non-contrast computed tomography and may affect ESWL success with a systematic review and meta-analysis. All data sources were broadly investigated up to April 2022. Data were extracted from the relevant studies and analyzed with RevMan software. In a random effects model, standard mean difference (SMD) and risk ratio (RR) values were given with 95% confidence intervals. In total, pooled analysis included 7148 patients in 43 studies. The combined effect estimate showed significant differences between the ESWL success and ESWL failure groups in terms of Hounsfield unit (HU), Hounsfield density (HD), skin to stone distance (SSD), ureteral wall thickness (UWT), stone volume, stone area, abdominal fat parameters, diameter of proximal ureter, and hydronephrosis. However, perinephric stranding and renal cortical thickness were not found to be statistically significant between the study groups. HU, HD, SSD, UWT, stone volume, stone area, abdominal fat parameters, diameter of proximal ureter and hydronephrosis are effective factors for prediction of ESWL success. It is important to decide on treatment before the procedure for stones with appropriate diameter for ESWL.

Shared genetic architecture of hernias: A genome-wide association study with multivariable meta-analysis of multiple hernia phenotypes.

Abdominal hernias are common and characterised by the abnormal protrusion of a viscus through the wall of the abdominal cavity. The global incidence is 18.5 million annually and there are limited non-surgical treatments. To improve understanding of common hernia aetiopathology, we performed a six-stage genome-wide association study (GWAS) of 62,637 UK Biobank participants with either single or multiple hernia phenotypes including inguinal, femoral, umbilical and hiatus hernia. Additionally, we performed multivariable meta-analysis with metaUSAT, to allow integration of summary data across traits to generate combined effect estimates. On individual hernia analysis, we identified 3404 variants across 38 genome-wide significant (p < 5×10-8) loci of which 11 are previously unreported. Robust evidence for five shared susceptibility loci was discovered: ZC3H11B, EFEMP1, MHC region, WT1 and CALD1. Combined hernia phenotype analyses with additional multivariable meta-analysis of summary statistics in metaUSAT revealed 28 independent (seven previously unreported) shared susceptibility loci. These clustered in functional categories related to connective tissue and elastic fibre homeostasis. Weighted genetic risk scores also correlated with disease severity suggesting a phenotypic-genotypic severity correlation, an important finding to inform future personalised therapeutic approaches to hernia.

S1258 Menopausal Status and Risk of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Introduction: Previous studies reported that nonalcoholic fatty liver disease (NAFLD) tended to be associated with menopausal status, although the strength of evidence is limited given the inconsistent results across the studies and limited number of participants included in some studies. This meta-analysis aims to pool data from all previous studies and determine whether menopausal status is a risk factor for NAFLD. Methods: Potentially eligible studies were identified from Embase, Medline, and Web of Sciences databases from inception to December 2021 using search strategy that comprised of terms for “nonalcoholic fatty liver disease” and “menopause”. Eligible study must consist of cases with NAFLD and controls without NAFLD. Then the study must explore history of menopausal status in each group and report effect estimates and 95% Confidence Interval (95% CI) of the association between presence NAFLD and menopausal status. We extracted such data from each study and calculated pooled odds ratio (OR) by combining effect estimates of each study using random-effects model. Funnel plot was used to assess for the presence of publication bias. Results: A total of 587 articles were identified. After two rounds of independent review by two investigators, 12 studies fulfilled the eligibility criteria and were included into the meta-analysis. The meta-analysis of 12 studies consisting of 160,306 participants revealed the significant association between menopausal status and presence of NAFLD with the pooled OR of 2.37 (95%CI 1.99 – 2.82, I2 73%, Figure A). The association remained significant in a subgroup meta-analysis of 6 studies that reported the association with adjustment for age and metabolic factors with the pooled OR of 2.19 (95%CI 1.73 – 2.78, I2 74%, Figure B). The funnel plot for was fairly symmetric and was not suggestive of publication bias. Conclusion: The meta-analysis revealed that menopausal status was associated with approximately 2.4 increased likelihood of NAFLD. The association remained significant in a subgroup meta-analysis of studies with adjustment for age and metabolic factors, suggesting that menopausal status could be an independent risk factor for NAFLD.Figure 1.: A) Forest plot of the meta-analysis of the association between nonalcoholic fatty liver disease and menopausal status, B) Forest plot after adjusted for age and metabolic factors

A meta-analysis approach for evaluating the effectiveness of complex multisite programs.

The National Institutes of Health (NIH) created the Building Infrastructure Leading to Diversity (BUILD) initiative to incentivize undergraduate institutions to create innovative approaches to increasing diversity in biomedical research, with the ultimate goal of diversifying the NIH-funded research enterprise. Initiatives such as BUILD involve designing and implementing programs at multiple sites that share common objectives. Evaluation of initiatives like this often includes statistical analyses that combine data across sites to estimate the program's impact on particular outcomes. Meta-analysis is a statistical technique for combining effect estimates from different studies to obtain a single overall effect estimate and to estimate heterogeneity across studies. However, it has not been commonly applied to evaluate the impact of a program across multiple different sites. In this chapter, we use the BUILD Scholar program-one component of the broader initiative-to demonstrate the application of meta-analysis to combine effect estimates from different sites of a multisite initiative. We analyze three student outcomes using a typical "single-stage" modeling approach and a meta-analysis approach. We show how a meta-analysis approach can provide more nuanced information about program impacts on student outcomes and thus can help support a robust evaluation.

Maternal occupational exposure to chemicals and child cognitive function.

Limited data exist regarding child neurodevelopment in relation to maternal occupational exposure to endocrine-disrupting chemicals (EDCs). We included 1058 mother-child pairs from the INfancia y Medio Ambiente (INMA) project (2003-2008). Using a job-exposure matrix, exposure probability scores for ten EDC groups were assigned to each mother based on her longest held job during pregnancy. At the child's 5-year visit, the McCarthy Scales of Children's Abilities was administered, yielding the general cognitive index and scales for specific cognitive domains. We analyzed region-specific associations between EDC exposures and each outcome separately using adjusted linear regression and combined region-specific effect estimates using random-effects meta-analyses. Approximately 24% of women were exposed to at least one EDC group, but exposure to most individual EDC groups was low (<5%). Maternal organic solvent exposure was associated with lower quantitative scores among children (-5.8 points, 95% confidence interval: -11.0, -0.5). Though statistically non-significant, exposures to polycyclic aromatic hydrocarbons, phthalates, alkylphenolic compounds, and miscellaneous chemicals were associated with poorer offspring performance for most or all cognitive domains. This study found limited evidence for a role of maternal occupational EDC exposures on child cognition. Further research is needed to better characterize exposures among pregnant workers. Using data from a prospective birth cohort, we help fill an important research gap regarding the potential consequences of work-related exposure to endocrine-disrupting chemicals (EDCs) among pregnant women on child neurodevelopment. We expand on existing literature-largely limited to pesticide and organic solvent exposures-by using a job-exposure matrix to estimate exposure to several EDC groups. We found limited evidence of an association between maternal occupational EDC exposure and children's overall cognition. We did observe specific associations between exposure to organic solvents and lower quantitative reasoning scores.

A systematic review and meta-analysis of the association between uric acid levels and chronic kidney disease

The function of uric acid (UA) in the genesis and evolution of chronic kidney disease (CKD) has motivated numerous studies, but the results remain inconclusive. We sought to conduct a systematic review and meta-analysis of cohort studies aiming to analyze the association of UA levels with the incidence and progression of CKD. Pubmed/Medline, Lilacs/Bireme and Web of Science were searched to identify eligible studies, following the PRISMA protocol. Data were presented for CKD incidence and progression separately. For the meta-analysis, studies with data stratified by subgroups according to serum UA levels were selected. The inverse variance-weighted random effects model was used to generate a combined effect estimate. Meta-regressions were performed to identify the causes of heterogeneity. The Newcastle–Ottawa Scale was used to assess the risk of bias. The publication bias was tested by funnel plot and Egger’s test. Eighteen CKD incidence studies (n = 398,663) and six CKD progression studies (n = 13,575) were included. An inverse relationship was observed between UA levels and protection from CKD incidence and progression. Lower UA levels were protective for the risk of CKD incidence (RR 0.65 [95% CI 0.56–0.75]) and progression (RR 0.55 [95% CI 0.44–0.68]). UA seems to be implicated both in the genesis of CKD and its evolution.

Efficacy of hyoscine in pain management during hysteroscopy: a systematic review and meta-analysis

We conducted a systematic review and meta-analysis of relevant clinical trials from full-text, scientific journal archives to assess the efficacy of hyoscine for the management of pain during in-office hysteroscopy (OH) procedures. Cochrane CENTRAL, ClinicalTrials.Gov, MEDLINE, PubMed, SCOPUS and the Web of Science were searched for all clinical trials that matched our search criteria. A full assessment of bias was made using the Cochrane Group tool-set. The following outcomes were included: visual analogue scale (VAS) score for postoperative pain, postoperative need for analgesia, and procedure time. In the case of homogeneous data, the analysis was performed using a fixed effects system, and the random effects system was used with heterogeneous data. Inclusion criteria included only randomized clinical trials, and interventions that included patients receiving hyoscine-N-Butyl Bromide during OH, regardless of dose or mode of administration, and compared this with placebo. Three clinical trials were included. The actual mean difference (MD) of the VAS pain score showed no significant difference between hyoscine or placebo [MD: -0.28 (-1.08, 0.52), (p=0.49)]. For postoperative analgesia, the overall MD showed no significant difference between hyoscine or placebo [MD: 0.43 (0.16, 1.14), (p=0.09)]. For procedure time, the combined effect estimate failed to show any significant difference between hyoscine and placebo [MD: -0.66 (-2.77, 1.44) (p=0.54)]. Contrary to previously published data, our meta-analysis using the latest available RCTs fails to show hyoscine as being effective in reducing pain or the need for other forms of anesthesia in OH.