BMC Medicine最新文献

{"title":"Dissecting shared genetic architecture between depression and body mass index.","authors":"Hengyu Zhang, Rui Zheng, Binhe Yu, Yuefeng Yu, Xiaomin Luo, Shujuan Yin, Yingjun Zheng, Jie Shi, Sizhi Ai","doi":"10.1186/s12916-024-03681-9","DOIUrl":"10.1186/s12916-024-03681-9","url":null,"abstract":"<p><strong>Background: </strong>A growing body of evidence supports the comorbidity between depression (DEP) and obesity, yet the genetic mechanisms underlying this association remain unclear. Our study explored the shared genetic architecture and causal associations of DEP with BMI.</p><p><strong>Methods: </strong>We investigated the multigene overlap and genetic correlation between DEP (N > 1.3 million) and BMI (N = 806,834) based on genome-wide association studies (GWAS) and using the bivariate causal mixture model and linkage disequilibrium score regression (LDSC). The causal association was explored by bi-directional Mendelian randomization (MR). Common risk loci were identified through cross-trait meta-analyses. Stratified LDSC and multi-marker gene annotation analyses were applied to investigate single-nucleotide polymorphisms enrichment across tissue types, cell types, and functional categories. Finally, we explored shared functional genes by Summary Data-Based Mendelian Randomization (SMR) and further detected differential expression genes (DEG) in brain tissues of individuals with depression and obesity.</p><p><strong>Results: </strong>We found a positive genetic correlation between DEP and BMI (r_{g =} 0.19, P = 4.07 × 10^-26), which was more evident in local genomic regions. Cross-trait meta-analyses identified 16 shared genetic loci, 5 of which were newly identified, and they had influence on both diseases in the same direction. MR analysis showed a bidirectional causal association between DEP and BMI, with comparable effect sizes estimated in both directions. Combined with gene expression information, we found that genetic correlations between DEP and BMI were enriched in 6 brain regions, predominantly in the nucleus accumbens and anterior cingulate cortex. Moreover, 6 specific cell types and 23 functional genes were found to have an impact on both DEP and BMI across the brain regions. Of which, NEGR1 was identified as the most significant functional gene and associated with DEP and BMI at the genome-wide significance level (P < 5 × 10^-8). Compared with healthy controls, the expression levels of NEGR1 gene were significant lower in brain tissues of individuals with depression and obesity.</p><p><strong>Conclusions: </strong>Our study reveals shared genetic basis underpinnings between DEP and BMI, including genetic correlations and common genes. These insights offer novel opportunities and avenues for future research into their comorbidities.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"22 1","pages":"455"},"PeriodicalIF":7.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic architectures of the human hippocampus and those involved in neuropsychiatric traits.","authors":"Caibo Ning, Meng Jin, Yimin Cai, Linyun Fan, Kexin Hu, Zequn Lu, Ming Zhang, Can Chen, Yanmin Li, Naifan Hu, Donghui Zhang, Yizhuo Liu, Shuoni Chen, Yuan Jiang, Chunyi He, Zhuo Wang, Zilong Cao, Hanting Li, Gaoyuan Li, Qianying Ma, Hui Geng, Wen Tian, Heng Zhang, Xiaojun Yang, Chaoqun Huang, Yongchang Wei, Bin Li, Ying Zhu, Xiangpan Li, Xiaoping Miao, Jianbo Tian","doi":"10.1186/s12916-024-03682-8","DOIUrl":"10.1186/s12916-024-03682-8","url":null,"abstract":"<p><strong>Background: </strong>The hippocampus, with its complex subfields, is linked to numerous neuropsychiatric traits. While most research has focused on its global structure or a few specific subfields, a comprehensive analysis of hippocampal substructures and their genetic correlations across a wide range of neuropsychiatric traits remains underexplored. Given the hippocampus's high heritability, considering hippocampal and subfield volumes (HASV) as endophenotypes for neuropsychiatric conditions is essential.</p><p><strong>Methods: </strong>We analyzed MRI-derived volumetric data of hippocampal and subfield structures from 41,525 UK Biobank participants. Genome-wide association studies (GWAS) on 24 HASV traits were conducted, followed by genetic correlation, overlap, and Mendelian randomization (MR) analyses with 10 common neuropsychiatric traits. Polygenic risk scores (PRS) based on HASV traits were also evaluated for predicting these traits.</p><p><strong>Results: </strong>Our analysis identified 352 independent genetic variants surpassing a significance threshold of 2.1 × 10^-9 within the 24 HASV traits, located across 93 chromosomal regions. Notably, the regions 12q14.3, 17q21.31, 12q24.22, 6q21, 9q33.1, 6q25.1, and 2q24.2 were found to influence multiple HASVs. Gene set analysis revealed enrichment of neural differentiation and signaling pathways, as well as protein binding and degradation. Of 240 HASV-neuropsychiatric trait pairs, 75 demonstrated significant genetic correlations (P < 0.05/240), revealing 433 pleiotropic loci. Particularly, genes like ACBD4, ARHGAP27, KANSL1, MAPT, ARL17A, and ARL17B were involved in over 50 HASV-neuropsychiatric pairs. Leveraging Mendelian randomization analysis, we further confirmed that atrophy in the left hippocampus, right hippocampus, right hippocampal body, and right CA1-3 region were associated with an increased risk of developing Parkinson's disease (PD). Furthermore, PRS for all four HASVs were significantly linked to a higher risk of Parkinson's disease (PD), with the highest hazard ratio (HR) of 1.30 (95% CI 1.18-1.43, P = 6.15 × 10⁻⁸) for right hippocampal volume.</p><p><strong>Conclusions: </strong>These findings highlight the extensive distribution of pleiotropic genetic determinants between HASVs and neuropsychiatric traits. Moreover, they suggest a significant potential for effectively managing and intervening in these diseases during their early stages.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"22 1","pages":"456"},"PeriodicalIF":7.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome-derived metabolites in early to mid-pregnancy and risk of gestational diabetes: a metabolome-wide association study.","authors":"Sita Manasa Susarla, Oliver Fiehn, Ines Thiele, Amanda L Ngo, Dinesh K Barupal, Rana F Chehab, Assiamira Ferrara, Yeyi Zhu","doi":"10.1186/s12916-024-03606-6","DOIUrl":"10.1186/s12916-024-03606-6","url":null,"abstract":"<p><strong>Background: </strong>Pre-diagnostic disturbances in the microbiome-derived metabolome have been associated with an increased risk of diabetes in non-pregnant populations. However, the roles of microbiome-derived metabolites, the end-products of microbial metabolism, in gestational diabetes (GDM) remain understudied. We examined the prospective association of microbiome-derived metabolites in early to mid-pregnancy with GDM risk in a diverse population.</p><p><strong>Methods: </strong>We conducted a prospective discovery and validation study, including a case-control sample of 91 GDM and 180 non-GDM individuals within the multi-racial/ethnic The Pregnancy Environment and Lifestyle Study (PETALS) as the discovery set, a random sample from the PETALS (42 GDM, 372 non-GDM) as validation set 1, and a case-control sample (35 GDM, 70 non-GDM) from the Gestational Weight Gain and Optimal Wellness randomized controlled trial as validation set 2. We measured untargeted fasting serum metabolomics at gestational weeks (GW) 10-13 and 16-19 by gas chromatography/time-of-flight mass spectrometry (TOF-MS), liquid chromatography (LC)/quadrupole TOF-MS, and hydrophilic interaction LC/quadrupole TOF-MS. GDM was diagnosed using the 3-h, 100-g oral glucose tolerance test according to the Carpenter-Coustan criteria around GW 24-28.</p><p><strong>Results: </strong>Among 1362 annotated compounds, we identified 140 of gut microbiome metabolism origin. Multivariate enrichment analysis illustrated that carbocyclic acids and branched-chain amino acid clusters at GW 10-13 and the unsaturated fatty acids cluster at GW 16-19 were positively associated with GDM risk (FDR < 0.05). At GW 10-13, the prediction model that combined conventional risk factors and LASSO-selected microbiome-derived metabolites significantly outperformed the model with only conventional risk factors including fasting glucose (discovery AUC: 0.884 vs. 0.691; validation 1: 0.945 vs. 0.731; validation 2: 0.987 vs. 0.717; all P < 0.01). At GW 16-19, similar results were observed (discovery AUC: 0.802 vs. 0.691, P < 0.01; validation 1: 0.826 vs. 0.780; P = 0.10).</p><p><strong>Conclusions: </strong>Dysbiosis in microbiome-derived metabolites is present early in pregnancy among individuals progressing to GDM.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"22 1","pages":"449"},"PeriodicalIF":7.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential impact of rotavirus vaccine introduction in India's Universal Immunisation Programme on private sector vaccine utilisation: an interrupted time series analysis.","authors":"Habib Hasan Farooqui, Anup Karan, Aashna Mehta, Giridhara Rathnaiah Babu, Onno C P van Schayck","doi":"10.1186/s12916-024-03664-w","DOIUrl":"10.1186/s12916-024-03664-w","url":null,"abstract":"<p><strong>Background: </strong>Despite free immunisation services through the Universal Immunisation Programme (UIP), around 14% of Indian households seek immunisation in the private sector. We examined the potential impact of rotavirus vaccine (RVV) introduction in the Universal Immunisation Programme (UIP) on private-sector rotavirus vaccine utilisation.</p><p><strong>Methods: </strong>We analysed nationally representative private-sector vaccine sales data. The intervention under consideration is RVV introduction in the UIP in selected Indian states. The outcome is the 'monthly RVV sales volume'-a proxy for vaccine utilisation. We performed a Poisson regression interrupted time series analysis to detect the pre-intervention trend, post-intervention level change and trend change relative to the pre-intervention for monthly rotavirus vaccine utilisation.</p><p><strong>Results: </strong>Poisson segmented regression analysis showed that immediately after RVV introduction in the UIP private-sector RVV sales showed a decline in Rajasthan by 37.4% (Incidence Risk Ratio (IRR): 0.626; 95% CI: 0.504-0.779), in Tamil Nadu by 26% (IRR: 0.740; 95% CI: 0.513-1.068), in Uttar Pradesh-East by 72.2% (IRR: 0.278; 95% CI: 0.178-0.436) and in Kerala by 3% (IRR: 0.970; 95% CI: 0.651-1.447). Rajasthan, Tamil Nadu and Kerala had sustained reduction in the postintervention trend relative to the preintervention trend by 20.1% (IRR: 0.799; 95% CI: 0.763-0.836), 6.4% (IRR: 0.936; 95% CI: 0.906-0.967) and 3.3% (IRR: 0.967; 95% CI: 0.926-0.960) per month, respectively. However, in Haryana and UP-west, in the first-month post-UIP introduction, the private-sector RVV sales increased by 101% and 3.8%, respectively which was followed by a sustained decrease of 14.2% (IRR: 0.858; 95% CI: 0.688-1.070) and 5.8% (IRR: 0.942; 95% CI: 0.926-0.960) per month, respectively. In terms of long-term impact, the private sector RVV sales post-UIP introduction decreased at a monthly rate of 4.4% (IRR: 0.956, 95% CI: 0.939-0.974) in Rajasthan but increased by 5.5% (IRR: 1.055; 95% CI: 1.040-1.070) in UP-east, 0.3% (IRR: 1.003, 95% CI: 0.976-1.031)) in Kerala and 0.2% (IRR: 1.002, 95% CI: 0.993-1.011) in Tamil Nadu whereas Haryana and UP-west had a reduction in RVV utilisation by 2.8% (IRR: 0.972; 95% CI: 0.955-0.990) and 1% (IRR: 0.990; 95% CI: 0.982-0.998), respectively.</p><p><strong>Conclusions: </strong>The study provides evidence that access to RVV through UIP leads to a reduction in private-sector RVV utilisation. We recommend strengthening UIP to expand the basket of new vaccines.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"22 1","pages":"453"},"PeriodicalIF":7.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse pregnancy outcomes and multiple cancers risk in both mother and offspring: an umbrella review of systematic reviews with meta-analyses of observational studies.","authors":"Na Liu, Rui-Han Bao, Yu-Jiao Chang, Fang-Hua Liu, Lang Wu, Jia-Yi Wang, Zi-Ping Niu, Shuai Ma, Yi-Xuan Men, Ke-Xin Liu, Dong-Hui Huang, Qian Xiao, Song Gao, Yue-Yang Zhao, Jian-Hua Fu, Qi-Jun Wu, Ting-Ting Gong","doi":"10.1186/s12916-024-03680-w","DOIUrl":"10.1186/s12916-024-03680-w","url":null,"abstract":"<p><strong>Background: </strong>Adverse pregnancy outcomes have reached epidemic proportions in recent years with serious health ramifications, especially for diverse cancers risk. Therefore, we carried out an umbrella review to systematically evaluate the validity and strength of the data and the extent of potential biases of the established association between adverse pregnancy outcomes and cancers risk in both mother and offspring.</p><p><strong>Methods: </strong>PubMed, Embase, and Web of Science databases were searched from inception until 18 January 2024. Meta-analyses of observational studies investigating the relationship between adverse pregnancy outcomes and multiple cancers risk in both mother and offspring were included. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. The protocol for this umbrella review was prospectively registered in PROSPERO (CRD42023470544).</p><p><strong>Results: </strong>The search identified 129 meta-analyses of observational studies and 42 types of cancer. Moderate certainty of evidence, exhibiting statistical significance, has been observed linking per kilogram increase in birth weight to a heightened risk of breast cancer (OR = 1.07, 95% CI = 1.02-1.12), prostate cancer (OR = 1.02, 95% CI = 1.00-1.05), leukemia (OR = 1.18, 95% CI = 1.13-1.23), and acute lymphoblastic leukemia in offspring (OR = 1.18, 95% CI = 1.12-1.23); rubella infection during pregnancy to an increased risk of leukemia in offspring (OR = 2.79, 95% CI = 1.16-6.71); and a linear dose-response association between an increase in the proportion of optimal birth weight and an elevated risk of acute lymphoblastic leukemia in offspring (OR = 1.16, 95% CI = 1.09-1.24), respectively.</p><p><strong>Conclusions: </strong>Although some adverse pregnancy outcomes have clinically promising associations with risk of several cancers in both mother and offspring, it is essential to conduct additional research to solidify the evidence, evaluate causality, and ascertain clinical utility.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"22 1","pages":"454"},"PeriodicalIF":7.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of suicide in patients with atrial fibrillation receiving different oral anticoagulants: a nationwide analysis using target trial emulation framework.","authors":"Brian Meng-Hsun Li, Avery Shuei-He Yang, Michael Chun-Yuan Cheng, Huei-Kai Huang, Edward Chia-Cheng Lai","doi":"10.1186/s12916-024-03645-z","DOIUrl":"10.1186/s12916-024-03645-z","url":null,"abstract":"<p><strong>Background: </strong>The suicide risk in patients with atrial fibrillation receiving novel oral anticoagulants or warfarin has not been evaluated in real-world practice. Moreover, reducing vitamin K levels may increase the suicide risk, underscoring the importance of selecting appropriate oral anticoagulants to prevent unintended outcomes. Therefore, we aimed to evaluate the association between different types of oral anticoagulants and the risk of attempted and completed suicide among patients with atrial fibrillation.</p><p><strong>Methods: </strong>This nationwide study retrieved data from Taiwan's National Health Insurance Research Database from 2012 to 2020. This study included patients with atrial fibrillation aged 20 years and older who newly received oral anticoagulant treatment, and who had no contraindications for NOACs and no history of suicide-related events. The main outcomes were suicide-related outcomes, including attempted suicide and completed suicide. This study employed the target trial emulation framework to improve the causal inference for the observed association.  RESULTS: A total of 103,768 (71.74%) patients taking NOACs and 40,877 (28.26%) patients taking warfarin were included in this study. Compared to those receiving warfarin, patients receiving NOACs were associated with a lower risk of suicide-related outcomes (HR, 0.82; 95% CIs, 0.69-0.96).</p><p><strong>Conclusions: </strong>The findings of this cohort study suggested that patients receiving NOACs were associated with a lower risk of suicidal attempts but similar risk of complete suicide, compared to those receiving warfarin. Considering the risk of suicide, NOACs could be the preferred anticoagulants for patients with atrial fibrillation.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"22 1","pages":"451"},"PeriodicalIF":7.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of probiotic and vitamin D co-supplementation on clinical symptoms, mental health, and inflammation in adult patients with migraine headache: a randomized, triple-blinded, placebo-controlled trial.","authors":"Shahnaz Amani Tirani, Fariborz Khorvash, Parvane Saneei, Zahra Moradmand, Gholamreza Askari","doi":"10.1186/s12916-024-03684-6","DOIUrl":"10.1186/s12916-024-03684-6","url":null,"abstract":"<p><strong>Background: </strong>Migraine headache is a major public health problem. Routine medications for migraine treatment are not useful in treating all patients and may have some side effects. The present study aimed to investigate the effect of vitamin D and probiotic co-supplementation on clinical characteristics of migraine, daily functioning, mental health outcomes, and serum levels of high-sensitivity C-reactive protein (hs-CRP).</p><p><strong>Methods: </strong>In this randomized, triple-blinded, placebo-controlled trial, patients aged 18 to 55 years diagnosed with migraine based on the International Classification of Headache Disorders-3 (ICHD-3) were randomized to either vitamin D (50,000 IU every 2 weeks) plus probiotic (4.5 × 10¹¹ CFU per day) or placebo for 12 weeks. The Headache Impact Test (HIT-6) and Depression, Anxiety, and Stress Scale (DASS) questionnaires were administered to patients at baseline and after 12 weeks. In addition, the frequency, duration, and severity of migraine headaches per month were assessed using a self-administered 30-day headache diary at baseline and the end of the intervention. Anthropometric indices, blood pressure, and serum levels of 25-hydroxy vitamin D and hs-CRP were also examined at first and the end of the study.</p><p><strong>Results: </strong>Seventy-two migraine patients with a mean age of 37.46 <math><mo>±</mo></math> 8.32 years were included in this trial. Probiotic and vitamin D co-supplementation compared to placebo resulted in a significant increase in serum levels of vitamin D (+ 12.86 <math><mo>±</mo></math> 1.64 vs. + 1.12 <math><mo>±</mo></math> 0.80 ng/mL, P < 0.001). The between-group analysis in the adjusted model showed a significantly greater reduction in migraine headache frequency (- 3.17 <math><mo>±</mo></math> 0.84 vs. - 1.25 <math><mo>±</mo></math> 0.34; P = 0.031) and severity (- 1.55 <math><mo>±</mo></math> 0.35 vs. + 0.67 <math><mo>±</mo></math> 0.29; P = 0.017) in the probiotic and vitamin D group than the placebo group. No significant difference was found between the two arms of the intervention regarding the change in headache duration, hs-CRP, scores of DASS, and HIT-6 questionnaires (P > 0.05).</p><p><strong>Conclusions: </strong>This trial showed that probiotic and vitamin D co-supplementation for 12 weeks has beneficial effects on migraine headache characteristics. Further research is needed to confirm this finding.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"22 1","pages":"457"},"PeriodicalIF":7.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harm effects in non-registered versus registered randomized controlled trials of medications: a retrospective cohort study of clinical trials.","authors":"Chang Xu, Shiqi Fan, Luis Furuya-Kanamori, Sheyu Li, Lifeng Lin, Haitao Chu, Su Golder, Yoon Loke, Sunita Vohra","doi":"10.1186/s12916-024-03621-7","DOIUrl":"10.1186/s12916-024-03621-7","url":null,"abstract":"<p><strong>Background: </strong>Trial registration aims to address potential bias from selective or non-reporting of findings, and therefore has a vital role in promoting transparency and accountability of clinical research. In this study, we aim to investigate the influence of trial registration on estimated harm effects in randomized controlled trials of medication interventions.</p><p><strong>Methods: </strong>We searched PubMed for systematic reviews and meta-analyses of randomized trials on medication harms indexed between January 1, 2015, and January 1, 2020. To be included in the analyses, eligible meta-analyses should have at least five randomized trials with distinct registration statuses (i.e., prospectively registered, retrospectively registered, and non-registered) and 2 by 2 table data for adverse events for each trial. To control for potential confounding, trials in each meta-analysis were analyzed within confounder-harmonized groups (e.g., dosage) identified using the Directed Acyclic Graph method. The harm estimates arising from the trials with different registration statuses were compared within the confounder-harmonized groups using hierarchical linear regression. Results are shown as ratio of odds ratio (OR) and 95% confidence interval (CI).</p><p><strong>Results: </strong>The dataset consists of 629 meta-analyses of harms with 10,069 trials. Of these trials, 74.3% were registered, and 23.9% were not registered, and for those registered, 70.6% were prospectively registered, while 26.3% were retrospectively registered. In comparison to prospectively registered trials, both non-registered trials (ratio of OR = 0.82, 95%CI 0.68 to 0.98, P = 0.03) and retrospectively registered trials (ratio of OR = 0.75, 95%CI 0.66 to 0.86, P < 0.01) had lower OR for harms based on 69 and 126 confounders-harmonized groups. The OR of harms did not differ between retrospectively registered and non-registered trials (ratio of OR = 1.02, 95%CI 0.85 to 1.23, P = 0.83) based on 76 confounders-harmonized groups.</p><p><strong>Conclusions: </strong>Medication-related harms may be understated in non-registered trials, and there was no obvious evidence that retrospective registration had a demonstrable benefit in reducing such selective or absent reporting. Prospective registration is highly recommended for future trials.</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"22 1","pages":"450"},"PeriodicalIF":7.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Representation of multimorbidity and frailty in the development and validation of kidney failure prognostic prediction models: a systematic review.","authors":"Heather Walker, Scott Day, Christopher H Grant, Catrin Jones, Robert Ker, Michael K Sullivan, Bhautesh Dinesh Jani, Katie Gallacher, Patrick B Mark","doi":"10.1186/s12916-024-03649-9","DOIUrl":"10.1186/s12916-024-03649-9","url":null,"abstract":"<p><strong>Background: </strong>Prognostic models that identify individuals with chronic kidney disease (CKD) at greatest risk of developing kidney failure help clinicians to make decisions and deliver precision medicine. It is recognised that people with CKD usually have multiple long-term health conditions (multimorbidity) and often experience frailty. We undertook a systematic review to evaluate the representation and consideration of multimorbidity and frailty within CKD cohorts used to develop and/or validate prognostic models assessing the risk of kidney failure.</p><p><strong>Methods: </strong>We identified studies that described derivation, validation or update of kidney failure prognostic models in MEDLINE, CINAHL Plus and the Cochrane Library-CENTRAL. The primary outcome was representation of multimorbidity or frailty. The secondary outcome was predictive accuracy of identified models in relation to presence of multimorbidity or frailty.</p><p><strong>Results: </strong>Ninety-seven studies reporting 121 different kidney failure prognostic models were identified. Two studies reported prevalence of multimorbidity and a single study reported prevalence of frailty. The rates of specific comorbidities were reported in a greater proportion of studies: 67.0% reported baseline data on diabetes, 54.6% reported hypertension and 39.2% reported cardiovascular disease. No studies included frailty in model development, and only one study considered multimorbidity as a predictor variable. No studies assessed model performance in populations in relation to multimorbidity. A single study assessed associations between frailty and the risks of kidney failure and death.</p><p><strong>Conclusions: </strong>There is a paucity of kidney failure risk prediction models that consider the impact of multimorbidity and/or frailty, resulting in a lack of clear evidence-based practice for multimorbid or frail individuals. These knowledge gaps should be explored to help clinicians know whether these models can be used for CKD patients who experience multimorbidity and/or frailty.</p><p><strong>Systematic review registration: </strong>This review has been registered on PROSPERO (CRD42022347295).</p>","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"22 1","pages":"452"},"PeriodicalIF":7.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Gut microbiome in endometriosis: a cohort study on 1000 individuals.","authors":"Inmaculada Pérez-Prieto, Eva Vargas, Eduardo Salas-Espejo, Kreete Lüll, Analuce Canha-Gouveia, Laura Antequera Pérez, Juan Fontes, Andres Salumets, Reidar Andreson, Oliver Aasmets, Katrine Whiteson, Elin Org, Signe Altmäe","doi":"10.1186/s12916-024-03692-6","DOIUrl":"10.1186/s12916-024-03692-6","url":null,"abstract":"","PeriodicalId":9188,"journal":{"name":"BMC Medicine","volume":"22 1","pages":"448"},"PeriodicalIF":7.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}