Pub Date : 2024-07-29DOI: 10.1101/2024.07.28.24311129
Jiayi Huang, Khaloud O. Alzahrani, Ge Zhou, Shahad A. Alsalman, Ayidh Almansour, M. Alhadlaq, Shaykhah Alhussain, Abdullah A. Alajlan, Saleh I. Al-Akeel, Malfi S Al Rashidy, Abdulrahman Alzauhair, Fahad M. Alreshoodi, Amani T. Alsufyani, Nourah M Alotaibi, Afnan Althubaiti, Elaf A. Alshdokhi, Ashwaq S. Alhamed, Manal Almusa, Talah M Almadi, Nouf Almutairi, Lenah E. Mukhtar, Abdulmohsen L. Alharbi, M. Banzhaf, Mathew Milner, Mohammad AlArawi, Sulaiman M. Alajel, D. Moradigaravand
Background: Salmonella enterica serovar Minnesota (S. Minnesota) is an emerging serovar of non-typhoidal Salmonella, known to persist in the food chain and distribution systems, potentially leading to outbreaks of Salmonella infections in human settings. Understanding the population genomics and dynamics of this pathogen is key to designing preventative measures and containing its spread within the poultry production chain. Methods: In this study, we conducted a large-scale study on S. Minnesota outbreak by fully characterizing population diversity and dynamics of a systematic collection from the poultry production chain in the Kingdom of Saudi Arabia (KSA). We sequenced 260 S. Minnesota strains from the western, eastern, and central regions of the country. We analyzed sequencing data to decipher the population diversity and dynamics of multidrug resistant strains and characterize the genetic basis of resistance and virulence. A hybrid long- and short-read sequencing approach was employed to analyze the population diversity of plasmids carrying antimicrobial resistance and virulence factors. Results: Our results indicate the rise of four clones (Bayesian Analysis of Population Structure; BAPS groups) in Saudi Arabia, three of which were mixed with global strains. The clones emerged over the past five to ten years and exhibited circulation between countries. The transmission analysis shows evidence of the spread of strains across cities, between countries, and mixing of strains from different suppliers, on epidemiological time scales. The emerging clones also harbored a higher resistance and virulence level than ancestral clones, owing to the acquisition of multiple plasmids, most importantly the IncC plasmid. The IncC plasmid was a mosaic plasmid, which carried antimicrobial resistance islands with blaCMY-2, ESBL blaCTX-M, aminoglycoside, and tetracycline resistance genes, as well as a hyperpathogenicity island with yersiniabactin genes. The plasmidome analysis revealed a high level of dynamics in the IncC plasmid structures with various configurations of resistance genes. Conclusion: Taken together, our results demonstrate a dynamic population and the emergence of multidrug-resistant clones in S. Minnesota. The results also highlight the role of plasmid acquisition and genomic variations in driving the concurrent evolution of pathogenicity and resistance in S. Minnesota.
{"title":"Large-scale Genomic Survey of Non-typhoidal Salmonella enterica serovar Minnesota Strains in Chicken Products Reveals the Emergence of Multidrug Resistant Clones","authors":"Jiayi Huang, Khaloud O. Alzahrani, Ge Zhou, Shahad A. Alsalman, Ayidh Almansour, M. Alhadlaq, Shaykhah Alhussain, Abdullah A. Alajlan, Saleh I. Al-Akeel, Malfi S Al Rashidy, Abdulrahman Alzauhair, Fahad M. Alreshoodi, Amani T. Alsufyani, Nourah M Alotaibi, Afnan Althubaiti, Elaf A. Alshdokhi, Ashwaq S. Alhamed, Manal Almusa, Talah M Almadi, Nouf Almutairi, Lenah E. Mukhtar, Abdulmohsen L. Alharbi, M. Banzhaf, Mathew Milner, Mohammad AlArawi, Sulaiman M. Alajel, D. Moradigaravand","doi":"10.1101/2024.07.28.24311129","DOIUrl":"https://doi.org/10.1101/2024.07.28.24311129","url":null,"abstract":"Background: Salmonella enterica serovar Minnesota (S. Minnesota) is an emerging serovar of non-typhoidal Salmonella, known to persist in the food chain and distribution systems, potentially leading to outbreaks of Salmonella infections in human settings. Understanding the population genomics and dynamics of this pathogen is key to designing preventative measures and containing its spread within the poultry production chain. Methods: In this study, we conducted a large-scale study on S. Minnesota outbreak by fully characterizing population diversity and dynamics of a systematic collection from the poultry production chain in the Kingdom of Saudi Arabia (KSA). We sequenced 260 S. Minnesota strains from the western, eastern, and central regions of the country. We analyzed sequencing data to decipher the population diversity and dynamics of multidrug resistant strains and characterize the genetic basis of resistance and virulence. A hybrid long- and short-read sequencing approach was employed to analyze the population diversity of plasmids carrying antimicrobial resistance and virulence factors. Results: Our results indicate the rise of four clones (Bayesian Analysis of Population Structure; BAPS groups) in Saudi Arabia, three of which were mixed with global strains. The clones emerged over the past five to ten years and exhibited circulation between countries. The transmission analysis shows evidence of the spread of strains across cities, between countries, and mixing of strains from different suppliers, on epidemiological time scales. The emerging clones also harbored a higher resistance and virulence level than ancestral clones, owing to the acquisition of multiple plasmids, most importantly the IncC plasmid. The IncC plasmid was a mosaic plasmid, which carried antimicrobial resistance islands with blaCMY-2, ESBL blaCTX-M, aminoglycoside, and tetracycline resistance genes, as well as a hyperpathogenicity island with yersiniabactin genes. The plasmidome analysis revealed a high level of dynamics in the IncC plasmid structures with various configurations of resistance genes. Conclusion: Taken together, our results demonstrate a dynamic population and the emergence of multidrug-resistant clones in S. Minnesota. The results also highlight the role of plasmid acquisition and genomic variations in driving the concurrent evolution of pathogenicity and resistance in S. Minnesota.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1101/2024.07.27.24310809
Jamil S. Samaan, S. Md, N. Bs, A. Ba, Y. Ms, MSc Rajsavi Anand Md, F. S. Md, J. Ms, S. Ms, Ahmad Safavi-Naini, Bara El Kurdi Md, A. Md, MS Rabindra Watson Md, S. Md, M. J. G. Md, Mph Brennan M.R. Spiegel Md, N. P. T. Mshs
Background: Large language models (LLMs) have shown promise in answering medical licensing examination-style questions. However, there is limited research on the performance of multimodal LLMs on subspecialty medical examinations. Our study benchmarks the performance of multimodal LLMs enhanced by model prompting strategies on gastroenterology subspecialty examination-style questions and examines how these prompting strategies incrementally improve overall performance. Methods: We used the 2022 American College of Gastroenterology (ACG) self-assessment examination (N=300). This test is typically completed by gastroenterology fellows and established gastroenterologists preparing for the gastroenterology subspecialty board examination. We employed a sequential implementation of model prompting strategies: prompt engineering, Retrieval-Augmented Generation (RAG), five-shot learning, and an LLM-powered answer validation revision model (AVRM). GPT-4 and Gemini Pro were tested. Results: Implementing all prompting strategies improved the overall score of GPT-4 from 60.3% to 80.7% and Gemini Pro from 48.0% to 54.3%. GPT-4's score surpassed the 70% passing threshold and 75% average human test-taker scores unlike Gemini Pro. Stratification of questions by difficulty showed the accuracy of both LLMs mirrored that of human examinees, demonstrating higher accuracy as human test-taker accuracy increased. The addition of the AVRM to prompt, RAG, and 5-shot increased GPT-4's accuracy by 4.4%. The incremental addition of model prompting strategies improved accuracy for both non-image (57.2% to 80.4%) and image-based (63.0% to 80.9%) questions for GPT-4, but not Gemini Pro. Conclusions: Our results underscore the value of model prompting strategies in improving LLM performance on subspecialty-level licensing exam questions. We also present a novel implementation of an LLM-powered reviewer model in the context of subspecialty medicine which further improved model performance when combined with other prompting strategies. Our findings highlight the potential future role of multimodal LLMs, particularly with the implementation of multiple model prompting strategies, as clinical decision support systems in subspecialty care for healthcare providers. Keywords: ChatGPT, Gemini pro, gastroenterology, RAG, prompt engineering, medical specialty examination.
{"title":"Multimodal Large Language Model Passes Specialty Board Examination and Surpasses Human Test-Taker Scores: A Comparative Analysis Examining the Stepwise Impact of Model Prompting Strategies on Performance","authors":"Jamil S. Samaan, S. Md, N. Bs, A. Ba, Y. Ms, MSc Rajsavi Anand Md, F. S. Md, J. Ms, S. Ms, Ahmad Safavi-Naini, Bara El Kurdi Md, A. Md, MS Rabindra Watson Md, S. Md, M. J. G. Md, Mph Brennan M.R. Spiegel Md, N. P. T. Mshs","doi":"10.1101/2024.07.27.24310809","DOIUrl":"https://doi.org/10.1101/2024.07.27.24310809","url":null,"abstract":"Background: Large language models (LLMs) have shown promise in answering medical licensing examination-style questions. However, there is limited research on the performance of multimodal LLMs on subspecialty medical examinations. Our study benchmarks the performance of multimodal LLMs enhanced by model prompting strategies on gastroenterology subspecialty examination-style questions and examines how these prompting strategies incrementally improve overall performance. Methods: We used the 2022 American College of Gastroenterology (ACG) self-assessment examination (N=300). This test is typically completed by gastroenterology fellows and established gastroenterologists preparing for the gastroenterology subspecialty board examination. We employed a sequential implementation of model prompting strategies: prompt engineering, Retrieval-Augmented Generation (RAG), five-shot learning, and an LLM-powered answer validation revision model (AVRM). GPT-4 and Gemini Pro were tested. Results: Implementing all prompting strategies improved the overall score of GPT-4 from 60.3% to 80.7% and Gemini Pro from 48.0% to 54.3%. GPT-4's score surpassed the 70% passing threshold and 75% average human test-taker scores unlike Gemini Pro. Stratification of questions by difficulty showed the accuracy of both LLMs mirrored that of human examinees, demonstrating higher accuracy as human test-taker accuracy increased. The addition of the AVRM to prompt, RAG, and 5-shot increased GPT-4's accuracy by 4.4%. The incremental addition of model prompting strategies improved accuracy for both non-image (57.2% to 80.4%) and image-based (63.0% to 80.9%) questions for GPT-4, but not Gemini Pro. Conclusions: Our results underscore the value of model prompting strategies in improving LLM performance on subspecialty-level licensing exam questions. We also present a novel implementation of an LLM-powered reviewer model in the context of subspecialty medicine which further improved model performance when combined with other prompting strategies. Our findings highlight the potential future role of multimodal LLMs, particularly with the implementation of multiple model prompting strategies, as clinical decision support systems in subspecialty care for healthcare providers. Keywords: ChatGPT, Gemini pro, gastroenterology, RAG, prompt engineering, medical specialty examination.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Over two billion people worldwide are infected with the protozoan Toxoplasma gondii, which influences human behavior and cognition. Standard diagnosis methods involve costly medical tests, which prevents widespread testing and hinders the study of the infection's effects. We propose and validate an inexpensive and easy-to deploy diagnostic method for latent Toxoplasmosis infections using response times and finite-mixture models. A clinical study showed that the method is sensitive and accurate. A large, representative UK study showed that the infection's consequences are relevant and pervasive, both economically (decrease in yearly income and employment) and behaviorally (increase in risky behaviors, stress, and depression).
{"title":"Two Billion Infected: An Inexpensive Method to Measure Latent Toxoplasmosis and its Economic Consequences","authors":"Anja Achtziger, ‡. CarlosAl´os-Ferrer, §. MicheleGaragnani","doi":"10.1101/2024.07.27.24311112","DOIUrl":"https://doi.org/10.1101/2024.07.27.24311112","url":null,"abstract":"Over two billion people worldwide are infected with the protozoan Toxoplasma gondii, which influences human behavior and cognition. Standard diagnosis methods involve costly medical tests, which prevents widespread testing and hinders the study of the infection's effects. We propose and validate an inexpensive and easy-to deploy diagnostic method for latent Toxoplasmosis infections using response times and finite-mixture models. A clinical study showed that the method is sensitive and accurate. A large, representative UK study showed that the infection's consequences are relevant and pervasive, both economically (decrease in yearly income and employment) and behaviorally (increase in risky behaviors, stress, and depression).","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1101/2024.07.26.24311087
M. P. McGowan, C. Xing, A. Khera, C.-Y. Huang, Y. Shao, M. Xing, E. Brandt, D. MacDougall, C. D. Ahmed, K. Wilemon, Z. Ahmad
Background Individuals with familial hypercholesterolemia (FH) require intensive lipid-lowering therapy, starting with high-intensity statins and adding ezetimibe and PCSK9 inhibitors (PCSK9i) as needed to reach target LDL-C levels. There are limited data on disparities in the use of these therapies among individuals with FH in the US. Methods: We queried a large US healthcare claims repository consisting of 324 million individuals, focusing on prescriptions for high-intensity statins, ezetimibe, and PCSK9i in two patient groups: those diagnosed with FH (ICD-10 E.78.01) and those not diagnosed with FH but identified as having probable FH (PFH) via the FIND-FH(R) machine learning algorithm. We used multivariable regression models to examine correlations with demographic/socioeconomic variables. Results In the FH cohort (n = 85,457), 45.9% were female, 79.4% identified as White, 12.2% Black, and 8.4% as Hispanic. In the PFH cohort (n = 287,580), 42.2% were female, 78.2% White, 13.7% as Black, and 8.1% as Hispanic. Males were more likely to be prescribed high-intensity statins than females: odds ratio (OR) [95% confidence interval (CI)] = 2.05 [1.97, 2.13] and 1.60 [1.56,1.63] in the FH and the PFH cohorts, respectively. In both cohorts, White individuals were more likely to get ezetimibe, PCSK9i, or combination therapy compared to Black individuals (ORs: 1.12-1.40). Higher income was associated with increased odds of receiving these treatments (OR: 1.17-1.59 for incomes >$50,000). Higher education was linked to a higher likelihood of combination therapy (ORs [95% CI] = 1.49 [1.33, 1.68] and 1.18 [1.10, 1.27] in the FH and PFH cohorts, respectively). Conclusions: Real-world data indicate that more aggressive lipid-lowering therapy (ezetimibe and PCSK9i) is more often prescribed to White individuals, individuals with higher income, or those with advanced education, highlighting the need to improve equity in cardiovascular risk reduction for all individuals with FH.
{"title":"Using Healthcare Claims Data to Identify Health Disparities for Individuals with Diagnosed and Undiagnosed Familial Hypercholesterolemia","authors":"M. P. McGowan, C. Xing, A. Khera, C.-Y. Huang, Y. Shao, M. Xing, E. Brandt, D. MacDougall, C. D. Ahmed, K. Wilemon, Z. Ahmad","doi":"10.1101/2024.07.26.24311087","DOIUrl":"https://doi.org/10.1101/2024.07.26.24311087","url":null,"abstract":"Background Individuals with familial hypercholesterolemia (FH) require intensive lipid-lowering therapy, starting with high-intensity statins and adding ezetimibe and PCSK9 inhibitors (PCSK9i) as needed to reach target LDL-C levels. There are limited data on disparities in the use of these therapies among individuals with FH in the US. Methods: We queried a large US healthcare claims repository consisting of 324 million individuals, focusing on prescriptions for high-intensity statins, ezetimibe, and PCSK9i in two patient groups: those diagnosed with FH (ICD-10 E.78.01) and those not diagnosed with FH but identified as having probable FH (PFH) via the FIND-FH(R) machine learning algorithm. We used multivariable regression models to examine correlations with demographic/socioeconomic variables. Results In the FH cohort (n = 85,457), 45.9% were female, 79.4% identified as White, 12.2% Black, and 8.4% as Hispanic. In the PFH cohort (n = 287,580), 42.2% were female, 78.2% White, 13.7% as Black, and 8.1% as Hispanic. Males were more likely to be prescribed high-intensity statins than females: odds ratio (OR) [95% confidence interval (CI)] = 2.05 [1.97, 2.13] and 1.60 [1.56,1.63] in the FH and the PFH cohorts, respectively. In both cohorts, White individuals were more likely to get ezetimibe, PCSK9i, or combination therapy compared to Black individuals (ORs: 1.12-1.40). Higher income was associated with increased odds of receiving these treatments (OR: 1.17-1.59 for incomes >$50,000). Higher education was linked to a higher likelihood of combination therapy (ORs [95% CI] = 1.49 [1.33, 1.68] and 1.18 [1.10, 1.27] in the FH and PFH cohorts, respectively). Conclusions: Real-world data indicate that more aggressive lipid-lowering therapy (ezetimibe and PCSK9i) is more often prescribed to White individuals, individuals with higher income, or those with advanced education, highlighting the need to improve equity in cardiovascular risk reduction for all individuals with FH.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1101/2024.07.29.24311160
U. Tripathi, Y. Stern, I. Dagan, R. Nayak, E. Romanovsky, S. Stern
Inflammatory Bowel Disease (IBD), which includes Crohn's disease (CD) and Ulcerative Colitis (UC), is a complex and multifactorial condition marked by chronic inflammation of the gastrointestinal tract. This study leverages data from genome-wide association studies (GWAS) and gene expression data from the Genotype-Tissue Expression (GTEx) project to investigate the genetic and expression profiles of IBD and its subtypes. We examined 207 studies related to IBD, 71 specific to CD, and 66 focused on UC, identifying both shared and unique genetic factors among these conditions. GWAS meta-analysis revealed the top IBD associated genes that include IL23R, NOD2, ATG16L1, HLA-DRB9, and more. Pathway enrichment analyses identified consistently enriched pathways such as the NF-kappa B signaling pathway, JAK-STAT signaling pathway, and cytokine-cytokine receptor interaction, all of which play critical roles in immune responses and inflammation. Gene Ontology (GO) term analysis highlighted processes like cytokine production, cell activation, and leukocyte activation, reinforcing their involvement in the pathogenesis of IBD. Gene expression analysis showed that genes associated with IBD are expressed not only in the gastrointestinal tract but also in various regions of the brain, suggesting potential links between IBD and neurological functions. Our study further explored the genetic overlap between IBD and several neurological disorders, including schizophrenia, depression, autism spectrum disorder, and attention-deficit/hyperactivity disorder, uncovering a shared genetic architecture. These findings emphasize the systemic nature of IBD and its potential neurological implications, paving the way for targeted therapeutic strategies that address both gastrointestinal and neurological aspects of the disease.
{"title":"Genetic Overlap Between Inflammatory Bowel Disease and Neurological Disorders: Insights from GWAS and Gene Expression Analysis","authors":"U. Tripathi, Y. Stern, I. Dagan, R. Nayak, E. Romanovsky, S. Stern","doi":"10.1101/2024.07.29.24311160","DOIUrl":"https://doi.org/10.1101/2024.07.29.24311160","url":null,"abstract":"Inflammatory Bowel Disease (IBD), which includes Crohn's disease (CD) and Ulcerative Colitis (UC), is a complex and multifactorial condition marked by chronic inflammation of the gastrointestinal tract. This study leverages data from genome-wide association studies (GWAS) and gene expression data from the Genotype-Tissue Expression (GTEx) project to investigate the genetic and expression profiles of IBD and its subtypes. We examined 207 studies related to IBD, 71 specific to CD, and 66 focused on UC, identifying both shared and unique genetic factors among these conditions. GWAS meta-analysis revealed the top IBD associated genes that include IL23R, NOD2, ATG16L1, HLA-DRB9, and more. Pathway enrichment analyses identified consistently enriched pathways such as the NF-kappa B signaling pathway, JAK-STAT signaling pathway, and cytokine-cytokine receptor interaction, all of which play critical roles in immune responses and inflammation. Gene Ontology (GO) term analysis highlighted processes like cytokine production, cell activation, and leukocyte activation, reinforcing their involvement in the pathogenesis of IBD. Gene expression analysis showed that genes associated with IBD are expressed not only in the gastrointestinal tract but also in various regions of the brain, suggesting potential links between IBD and neurological functions. Our study further explored the genetic overlap between IBD and several neurological disorders, including schizophrenia, depression, autism spectrum disorder, and attention-deficit/hyperactivity disorder, uncovering a shared genetic architecture. These findings emphasize the systemic nature of IBD and its potential neurological implications, paving the way for targeted therapeutic strategies that address both gastrointestinal and neurological aspects of the disease.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1101/2024.07.28.24311148
T. Zhai
Metformin may affect patients with multi-comorbid bipolar disorder through the integrated stress response, but their relationship remains unclear This study aimed to explore the relationship between metformin use and early (30-day) readmission in bipolar disorder patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. Adult patients with a documented diagnosis of bipolar disorder were screened. Multivariable logistic regression and propensity score matching were used to investigate any association. Data on 1688 patients were included. The crude early (30-day) readmission was significantly higher in patients with metformin use (17/114 vs. 132/1574 p = 0.033). In the extended multivariable logistic models, the hazard ratio (HR) of metformin use was consistently significant in all models (HR range 1.87~2.99, p < 0.05 for all). After propensity score matching, the early (30-day) readmission remained significantly higher in the metformin use group (|t|>1.64). Although residual confounding cannot be excluded, metformin use is associated with higher readmission.
二甲双胍可能会通过综合应激反应影响多合并双相情感障碍患者，但两者之间的关系仍不清楚。本研究旨在探讨使用二甲双胍与双相情感障碍患者早期（30 天）再入院之间的关系。数据提取自重症监护医学信息市场（Medical Information Mart for Intensive Care IV）数据库。研究筛选了确诊为躁狂症的成人患者。采用多变量逻辑回归和倾向得分匹配法研究两者之间的关联。共纳入了 1688 名患者的数据。使用二甲双胍的患者早期（30 天）再入院的粗略率明显较高（17/114 对 132/1574 p = 0.033）。在扩展的多变量逻辑模型中，使用二甲双胍的危险比（HR）在所有模型中都具有显著性（HR 范围为 1.87~2.99，P < 0.05）。经过倾向评分匹配后，使用二甲双胍组的早期（30 天）再入院率仍然显著较高（|t|>1.64）。虽然不能排除残余混杂因素，但二甲双胍的使用与较高的再入院率有关。
{"title":"Metformin Use and Thirty-Day Readmission Among Patients with Bipolar Disorders: A Propensity Score-matching Analysis","authors":"T. Zhai","doi":"10.1101/2024.07.28.24311148","DOIUrl":"https://doi.org/10.1101/2024.07.28.24311148","url":null,"abstract":"Metformin may affect patients with multi-comorbid bipolar disorder through the integrated stress response, but their relationship remains unclear This study aimed to explore the relationship between metformin use and early (30-day) readmission in bipolar disorder patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. Adult patients with a documented diagnosis of bipolar disorder were screened. Multivariable logistic regression and propensity score matching were used to investigate any association. Data on 1688 patients were included. The crude early (30-day) readmission was significantly higher in patients with metformin use (17/114 vs. 132/1574 p = 0.033). In the extended multivariable logistic models, the hazard ratio (HR) of metformin use was consistently significant in all models (HR range 1.87~2.99, p < 0.05 for all). After propensity score matching, the early (30-day) readmission remained significantly higher in the metformin use group (|t|>1.64). Although residual confounding cannot be excluded, metformin use is associated with higher readmission.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-27DOI: 10.1101/2024.07.25.24311012
Yamuna Thapa, Bimala Bhatta
Background: Human Papilloma virus (HPV) associated cervical cancer is the fourth most common cancer in women worldwide and it is the leading cause of death among women in Nepal. The screening seeking behavior encompasses a woman's decision to engage in medical evaluations essential for the early detection and prophylaxis of cervical cancer. Even though there is a proven importance of cervical cancer screening, the incidence and mortality rate in Nepal is high. Therefore, we aimed to assess the cervical cancer screening seeking behavior and its associated factors among female community health volunteers (FCHVs) of Surkhet district, Nepal. Methods: A community based cross-sectional study was carried out in the municipalities and rural municipalities of Surkhet district. A pre-tested structured interview was conducted among 148 FCHVs from 30-49 years. Results: This study showed that 90 (60.8%) of FCHVs have cervical cancer screening seeking behavior. Age (AOR: 7.2, 95% CI: 3.01-17.3) and marital status (AOR: 9.2, 95% CI: 2.6-166.2) of FCHVs were significant factors for cervical cancer seeking behavior. Conclusion: These findings highlight the importance of demographic factors in promoting screening participation among FCHVs. Enhancing cervical cancer screening rates among FCHVs requires multifaceted approaches that address both individual perceptions and barriers. Interventions should focus on increasing accessibility, improving education and awareness programs, and providing tailored support to different demographic groups.
{"title":"Cervical Cancer Screening Seeking Behavior among Female Community Health Volunteers of Surkhet District, Nepal","authors":"Yamuna Thapa, Bimala Bhatta","doi":"10.1101/2024.07.25.24311012","DOIUrl":"https://doi.org/10.1101/2024.07.25.24311012","url":null,"abstract":"Background: Human Papilloma virus (HPV) associated cervical cancer is the fourth most common cancer in women worldwide and it is the leading cause of death among women in Nepal. The screening seeking behavior encompasses a woman's decision to engage in medical evaluations essential for the early detection and prophylaxis of cervical cancer. Even though there is a proven importance of cervical cancer screening, the incidence and mortality rate in Nepal is high. Therefore, we aimed to assess the cervical cancer screening seeking behavior and its associated factors among female community health volunteers (FCHVs) of Surkhet district, Nepal. Methods: A community based cross-sectional study was carried out in the municipalities and rural municipalities of Surkhet district. A pre-tested structured interview was conducted among 148 FCHVs from 30-49 years. Results: This study showed that 90 (60.8%) of FCHVs have cervical cancer screening seeking behavior. Age (AOR: 7.2, 95% CI: 3.01-17.3) and marital status (AOR: 9.2, 95% CI: 2.6-166.2) of FCHVs were significant factors for cervical cancer seeking behavior. Conclusion: These findings highlight the importance of demographic factors in promoting screening participation among FCHVs. Enhancing cervical cancer screening rates among FCHVs requires multifaceted approaches that address both individual perceptions and barriers. Interventions should focus on increasing accessibility, improving education and awareness programs, and providing tailored support to different demographic groups.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141798930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-27DOI: 10.1101/2024.07.27.24310936
Y. Du, P. A. Benny, R. J. Schlueter, A. Gurary, A. Lum-Jones, C. B. Lassiter, F. M. AlAkwaa, M. Tiirikainen, D. Towner, W. S. Ward, L. X. Garmire
Maternal obesity is a health concern that may predispose newborns to a high risk of medical problems later in life. To understand the transgenerational effect of maternal obesity, we conducted a multi-omics study, using DNA methylation and gene expression in the CD34+/CD38-/Lin- umbilical cord blood hematopoietic stem cells (uHSCs) and metabolomics of the cord blood, all from a multi-ethnic cohort (n=72) from Kapiolani Medical Center for Women and Children in Honolulu, Hawaii (collected between 2016 and 2018). Differential methylation (DM) analysis unveiled a global hypermethylation pattern in the maternal pre-pregnancy obese group (BH adjusted p<0.05), after adjusting for major clinical confounders. Comprehensive functional analysis showed hypermethylation in promoters of genes involved in cell cycle, protein synthesis, immune signaling, and lipid metabolism. Utilizing Shannon entropy on uHSCs methylation, we discerned notably higher quiescence of uHSCs impacted by maternal obesity. Additionally, the integration of multi-omics data-including methylation, gene expression, and metabolomics-provided further evidence of dysfunctions in adipogenesis, erythropoietin production, cell differentiation, and DNA repair, aligning with the findings at the epigenetic level. This study reveals the significant correlation between pre-pregnancy maternal obesity and multi-omics level molecular changes in the uHSCs of offspring, particularly in DNA methylation.
{"title":"Multi-omics Analysis of Umbilical Cord Hematopoietic Stem Cells from a Multi-ethnic Cohort of Hawaii Reveals the Transgenerational Effect of Maternal Pre-Pregnancy Obesity","authors":"Y. Du, P. A. Benny, R. J. Schlueter, A. Gurary, A. Lum-Jones, C. B. Lassiter, F. M. AlAkwaa, M. Tiirikainen, D. Towner, W. S. Ward, L. X. Garmire","doi":"10.1101/2024.07.27.24310936","DOIUrl":"https://doi.org/10.1101/2024.07.27.24310936","url":null,"abstract":"Maternal obesity is a health concern that may predispose newborns to a high risk of medical problems later in life. To understand the transgenerational effect of maternal obesity, we conducted a multi-omics study, using DNA methylation and gene expression in the CD34+/CD38-/Lin- umbilical cord blood hematopoietic stem cells (uHSCs) and metabolomics of the cord blood, all from a multi-ethnic cohort (n=72) from Kapiolani Medical Center for Women and Children in Honolulu, Hawaii (collected between 2016 and 2018). Differential methylation (DM) analysis unveiled a global hypermethylation pattern in the maternal pre-pregnancy obese group (BH adjusted p<0.05), after adjusting for major clinical confounders. Comprehensive functional analysis showed hypermethylation in promoters of genes involved in cell cycle, protein synthesis, immune signaling, and lipid metabolism. Utilizing Shannon entropy on uHSCs methylation, we discerned notably higher quiescence of uHSCs impacted by maternal obesity. Additionally, the integration of multi-omics data-including methylation, gene expression, and metabolomics-provided further evidence of dysfunctions in adipogenesis, erythropoietin production, cell differentiation, and DNA repair, aligning with the findings at the epigenetic level. This study reveals the significant correlation between pre-pregnancy maternal obesity and multi-omics level molecular changes in the uHSCs of offspring, particularly in DNA methylation.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-26DOI: 10.1101/2024.07.25.24310975
T. Vanbaelen, A. Rotsaert, I. De Baetselier, T. Platteau, B. Hensen, T. Reyniers, C. Kenyon
Objectives We aimed to assess the awareness, willingness to use, and actual use of doxycycline post-exposure prophylaxis (doxyPEP) among men who have sex with men (MSM) and transgender women (TGW) in Belgium. Additionally, we aimed to identify factors associated with doxyPEP use and concerns regarding antimicrobial resistance (AMR). Methods Cross-sectional online survey among MSM and TGW in Belgium in April 2024. Participants were recruited through sexual networking applications and social media of community-based organizations. Numerical variables were compared with Wilcoxon rank-sum test and categorical variables with chi-square or Fisher s exact tests. Factors associated with doxyPEP use were assessed using logistic regression. Willingness to use doxyPEP and concerns about side-effects/AMR were assessed before and after presenting a brief paragraph on the potential effects of doxyPEP on AMR. Results A total of 875 individuals initiated the survey. Almost all identified as men (860/875, 98.3%) with a median age of 40 years (IQR 32-48). Among all respondents, 40.4% (n=352/875) had heard of doxyPEP and 9.4% (n=82/875) had used it, among whom the majority used it within the last six months (70/81, 86.4%). In multivariable logistic regression, doxyPEP use was associated with having had [≥]1 STI in the past 12 months and engagement in chemsex. About 80% of the participants initially reported being willing to use doxyPEP, and about 50% reported being concerned about side effects. After reading about the potential effects of doxyPEP on AMR, willingness to use doxyPEP decreased to 60% and concerns of side-effects including AMR increased to around 70%. Conclusions Approximately one in ten MSM and TGW in Belgium reported using doxyPEP, with those at highest STI risk reporting higher usage. Importantly, concerns about AMR and side effect influenced willingness to use doxyPEP. If doxyPEP is introduced, informing patients about doxyPEP benefits and risks is crucial to enable informed decision-making.
{"title":"Doxycycline post-exposure prophylaxis among men who have sex with men and transgender women in Belgium: awareness, use, and antimicrobial resistance concerns in a cross-sectional online survey","authors":"T. Vanbaelen, A. Rotsaert, I. De Baetselier, T. Platteau, B. Hensen, T. Reyniers, C. Kenyon","doi":"10.1101/2024.07.25.24310975","DOIUrl":"https://doi.org/10.1101/2024.07.25.24310975","url":null,"abstract":"Objectives We aimed to assess the awareness, willingness to use, and actual use of doxycycline post-exposure prophylaxis (doxyPEP) among men who have sex with men (MSM) and transgender women (TGW) in Belgium. Additionally, we aimed to identify factors associated with doxyPEP use and concerns regarding antimicrobial resistance (AMR). Methods Cross-sectional online survey among MSM and TGW in Belgium in April 2024. Participants were recruited through sexual networking applications and social media of community-based organizations. Numerical variables were compared with Wilcoxon rank-sum test and categorical variables with chi-square or Fisher s exact tests. Factors associated with doxyPEP use were assessed using logistic regression. Willingness to use doxyPEP and concerns about side-effects/AMR were assessed before and after presenting a brief paragraph on the potential effects of doxyPEP on AMR. Results A total of 875 individuals initiated the survey. Almost all identified as men (860/875, 98.3%) with a median age of 40 years (IQR 32-48). Among all respondents, 40.4% (n=352/875) had heard of doxyPEP and 9.4% (n=82/875) had used it, among whom the majority used it within the last six months (70/81, 86.4%). In multivariable logistic regression, doxyPEP use was associated with having had [≥]1 STI in the past 12 months and engagement in chemsex. About 80% of the participants initially reported being willing to use doxyPEP, and about 50% reported being concerned about side effects. After reading about the potential effects of doxyPEP on AMR, willingness to use doxyPEP decreased to 60% and concerns of side-effects including AMR increased to around 70%. Conclusions Approximately one in ten MSM and TGW in Belgium reported using doxyPEP, with those at highest STI risk reporting higher usage. Importantly, concerns about AMR and side effect influenced willingness to use doxyPEP. If doxyPEP is introduced, informing patients about doxyPEP benefits and risks is crucial to enable informed decision-making.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141798848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-21DOI: 10.1101/2024.07.19.24310268
D. Schoenaker, O. Gafari, E. Taylor, J. Hall, C. Barker, B. Jones, N. A. Alwan, D. Watson, C. Jacob, M. Barker, K. M. Godfrey, E. Reason, F. Forder, J. Stephenson
Introduction: There is growing scientific and policy recognition that optimising health before a potential pregnancy (preconception health) improves reproductive outcomes and the lifelong health of future children. However, public awareness on this topic is low. We conducted a public consultation to develop language recommendations and identify and prioritise approaches to inform research and improve public awareness of preconception health. Methods: A public consultation was undertaken with people of any gender aged 18-50 years living in the UK who were not currently expecting a child. Public contributors were recruited through patient and public involvement, community and support groups, an existing cohort study, and an LGBTQ+ charity. An initial round of online group discussions (February/March 2021) explored public contributors knowledge of preconception health, their recommendations for appropriate language, and ideas about public health approaches. In a subsequent discussion round (May 2021), language recommendations were refined, and suggested approaches prioritised. Discussions were summarised based on notes taken by two researchers. Results: 54 people joined the initial discussion round (66% women, 21% men, 13% non-binary or transgender; 55% aged 18-30 years, 30% 31-40 years, 15% 41-50 years). Of these, 36 people (67%) participated in the subsequent round. Very few had heard the term preconception health, understood what it means, or why and for whom it is important. They recommended avoiding unfamiliar terms without further explanation (e.g. preconception health, medical terms), using language that is positive, encouraging and gender-sensitive where possible, and using messages that are specific, non-judgmental and realistic. The phrases health and wellbeing during the childbearing years, health and wellbeing before pregnancy and parenthood and planning for parenthood resonated with most public contributors. School-based education, social media campaigns and the National Health Service emerged as priority approaches/settings for raising awareness. Conclusion: This public consultation produced recommendations from a diverse group of people of reproductive age in the UK to improve language and prioritise approaches that increase public understanding of preconception health in ways that are relevant and appropriate to them. This should begin in schools and will require adaptation of curricula, alongside co-development of public awareness campaigns and guidance for healthcare professionals.
{"title":"What does preconception health mean to people? A public consultation on awareness and use of language","authors":"D. Schoenaker, O. Gafari, E. Taylor, J. Hall, C. Barker, B. Jones, N. A. Alwan, D. Watson, C. Jacob, M. Barker, K. M. Godfrey, E. Reason, F. Forder, J. Stephenson","doi":"10.1101/2024.07.19.24310268","DOIUrl":"https://doi.org/10.1101/2024.07.19.24310268","url":null,"abstract":"Introduction: There is growing scientific and policy recognition that optimising health before a potential pregnancy (preconception health) improves reproductive outcomes and the lifelong health of future children. However, public awareness on this topic is low. We conducted a public consultation to develop language recommendations and identify and prioritise approaches to inform research and improve public awareness of preconception health. Methods: A public consultation was undertaken with people of any gender aged 18-50 years living in the UK who were not currently expecting a child. Public contributors were recruited through patient and public involvement, community and support groups, an existing cohort study, and an LGBTQ+ charity. An initial round of online group discussions (February/March 2021) explored public contributors knowledge of preconception health, their recommendations for appropriate language, and ideas about public health approaches. In a subsequent discussion round (May 2021), language recommendations were refined, and suggested approaches prioritised. Discussions were summarised based on notes taken by two researchers. Results: 54 people joined the initial discussion round (66% women, 21% men, 13% non-binary or transgender; 55% aged 18-30 years, 30% 31-40 years, 15% 41-50 years). Of these, 36 people (67%) participated in the subsequent round. Very few had heard the term preconception health, understood what it means, or why and for whom it is important. They recommended avoiding unfamiliar terms without further explanation (e.g. preconception health, medical terms), using language that is positive, encouraging and gender-sensitive where possible, and using messages that are specific, non-judgmental and realistic. The phrases health and wellbeing during the childbearing years, health and wellbeing before pregnancy and parenthood and planning for parenthood resonated with most public contributors. School-based education, social media campaigns and the National Health Service emerged as priority approaches/settings for raising awareness. Conclusion: This public consultation produced recommendations from a diverse group of people of reproductive age in the UK to improve language and prioritise approaches that increase public understanding of preconception health in ways that are relevant and appropriate to them. This should begin in schools and will require adaptation of curricula, alongside co-development of public awareness campaigns and guidance for healthcare professionals.","PeriodicalId":506788,"journal":{"name":"medRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141818640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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