Pub Date : 2024-07-29DOI: 10.1101/2024.07.26.24311042
O. Serri, A. Meunier, P. E. Bouet, H. El Hachem, B. Liu, P. May-Panloup
Purpose: Infertility is associated with different factors, highly intricated but sometimes ill-defined. Despite the significant recent technological and therapeutic advancements, the success rates of assisted reproductive technologies (ART) remain relatively low. In this context several women have recourse to complementary practices (CP), in the hope of improving success rates and lowering the associated strain. These methods, are quite heterogenous, and are yet to be comprehensively analyzed in the literature. The objective of our study was to evaluate, in women consulting at our fertility center, the current interest in these CP and more specifically, the role of Traditional Chinese Medicine (TCM) and associated Mind Body Intervention (MBI). Methods: A prospective monocentric survey study at the fertility center of the Angers University Hospital between January and May 2022. Results: 150 questionnaires were analyzed. Approximately 50% of women have recourse to CP, in the hope of improving the success rates of ART and reducing the associated stress and fatigue. The main CP used were the ones based on body manipulation, TCM and MBI. The lack of use was mainly linked to a lack of knowledge of these methods, and the vast majority of women would like to receive additional information about CP from the physicians at the center. Conclusion: Our study shows a significant interest in CP in reproductive medicine. In view of the benefits of some of these practices, at least on the quality of life of patients, information on their value should be made available to all couples undergoing ART.
目的：不孕不育与不同的因素有关，这些因素错综复杂，但有时并不明确。尽管最近在技术和治疗方面取得了重大进展，但辅助生殖技术（ART）的成功率仍然相对较低。在这种情况下，一些妇女求助于辅助方法（CP），希望提高成功率并减轻相关压力。这些方法种类繁多，尚未在文献中进行全面分析。我们的研究目的是评估在我们不孕不育中心就诊的妇女目前对这些辅助治疗方法的兴趣，更具体地说，是对传统中医（TCM）和相关的身心干预（MBI）的作用的兴趣。研究方法2022年1月至5月期间在昂热大学医院不孕不育中心进行的前瞻性单中心调查研究。结果：分析了150份问卷：对150份问卷进行了分析。约50%的妇女求助于CP，希望提高抗逆转录病毒疗法的成功率，并减轻相关的压力和疲劳。使用的主要 CP 是基于体操、中医和 MBI 的 CP。不使用的主要原因是对这些方法缺乏了解，绝大多数妇女希望从中心的医生那里获得更多有关 CP 的信息。结论我们的研究表明，人们对生殖医学中的 CP 非常感兴趣。鉴于其中一些方法的益处，至少是对患者生活质量的益处，应向所有接受人工生殖技术的夫妇提供有关这些方法价值的信息。
{"title":"THE USE OF COMPLEMENTARY PRACTICES BY PATIENTS UNDERGOING MEDICALLY ASSISTED REPRODUCTION: The place of Chinese medicine and related practices.","authors":"O. Serri, A. Meunier, P. E. Bouet, H. El Hachem, B. Liu, P. May-Panloup","doi":"10.1101/2024.07.26.24311042","DOIUrl":"https://doi.org/10.1101/2024.07.26.24311042","url":null,"abstract":"Purpose: Infertility is associated with different factors, highly intricated but sometimes ill-defined. Despite the significant recent technological and therapeutic advancements, the success rates of assisted reproductive technologies (ART) remain relatively low. In this context several women have recourse to complementary practices (CP), in the hope of improving success rates and lowering the associated strain. These methods, are quite heterogenous, and are yet to be comprehensively analyzed in the literature. The objective of our study was to evaluate, in women consulting at our fertility center, the current interest in these CP and more specifically, the role of Traditional Chinese Medicine (TCM) and associated Mind Body Intervention (MBI). Methods: A prospective monocentric survey study at the fertility center of the Angers University Hospital between January and May 2022. Results: 150 questionnaires were analyzed. Approximately 50% of women have recourse to CP, in the hope of improving the success rates of ART and reducing the associated stress and fatigue. The main CP used were the ones based on body manipulation, TCM and MBI. The lack of use was mainly linked to a lack of knowledge of these methods, and the vast majority of women would like to receive additional information about CP from the physicians at the center. Conclusion: Our study shows a significant interest in CP in reproductive medicine. In view of the benefits of some of these practices, at least on the quality of life of patients, information on their value should be made available to all couples undergoing ART.","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":"141796714","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: 10.1101/2024.07.26.24311058
P. M. Patricia J. Rodriguez, BA Vincent Zhang, PhD Samuel Gratzl, PhD Duy Do, MS Brianna Goodwin Cartwright, DrPH Mph Cph Charlotte Baker, M. M. Ty J. Gluckman, MD PhD Nicholas Stucky, MD PhD Ezekiel J. Emanuel
Importance: Adherence to GLP-1 RA is important for efficacy. Discontinuation and reinitiation patterns for patients with and without type 2 diabetes (T2D) are not well-understood. Objective: To describe rates and factors associated with discontinuation and reinitiation of GLP-1 RA, for patients with and without T2D. Design: In this retrospective cohort study, adults with overweight or obesity initiated on GLP-1 RA between January 2018 and December 2023 were identified using electronic health record (EHR) data from a collective of 30 US healthcare systems. Patients were followed for up to 2 years to assess discontinuation and for 2 additional years to assess reinitiation. Setting: Clinical and prescribing data from EHRs linked to dispensing information Participants: Adults newly initiated on GLP-1 RA between 2018 and 2023, with a baseline BMI [≥]27 and an available weight measurement within 60 days before initiation, and regular care in the year before initiation. Exposure/Covariates: Patients were stratified by presence of T2D at baseline. Associations with socio-demographics, health factors, weight changes, and gastrointestinal (GI) adverse events (AE) were modeled. Main Outcomes and Measures: Proportion of patients discontinuing and reinitiating GLP-1 RA were estimated from Kaplan-Meier models. Associations between covariates and discontinuation and reinitiation outcomes were modeled using time-varying Cox proportional hazards models. All analyses were conducted for patients with and without T2D. Results: Among 96,544 adults initiating GLP-1 RA, the mean (SD) age was 55.1 (13.3) years, 65.2% were female, 73.7% were white, and 61.3% had T2D. Individual income exceeded $50,000 for 49.7% of patients with and 57.2% of patients without T2D. One-year discontinuation was significantly higher for patients without T2D (65.1%), compared to those with T2D (45.8%). Higher weight loss, absence of GI AE, and higher income (T2D only) were significantly associated with higher discontinuation. Of 28,142 (49.6%) who discontinued one-year reinitiation was lower for those without T2D (34.7%), compared to those with T2D (51.0%). Weight re-gain was significantly associated with increased reinitiation. Conclusions and Relevance: Most patients with overweight or obesity discontinue GLP-1 RA within 1 year, but those without T2D discontinue at higher rates and reinitiate at lower rates. Inequities in access and adherence to effective treatments have the potential exacerbate disparities in obesity.
{"title":"Discontinuation and Reinitiation of GLP-1 Receptor Agonists Among US Adults with Overweight or Obesity","authors":"P. M. Patricia J. Rodriguez, BA Vincent Zhang, PhD Samuel Gratzl, PhD Duy Do, MS Brianna Goodwin Cartwright, DrPH Mph Cph Charlotte Baker, M. M. Ty J. Gluckman, MD PhD Nicholas Stucky, MD PhD Ezekiel J. Emanuel","doi":"10.1101/2024.07.26.24311058","DOIUrl":"https://doi.org/10.1101/2024.07.26.24311058","url":null,"abstract":"Importance: Adherence to GLP-1 RA is important for efficacy. Discontinuation and reinitiation patterns for patients with and without type 2 diabetes (T2D) are not well-understood. Objective: To describe rates and factors associated with discontinuation and reinitiation of GLP-1 RA, for patients with and without T2D. Design: In this retrospective cohort study, adults with overweight or obesity initiated on GLP-1 RA between January 2018 and December 2023 were identified using electronic health record (EHR) data from a collective of 30 US healthcare systems. Patients were followed for up to 2 years to assess discontinuation and for 2 additional years to assess reinitiation. Setting: Clinical and prescribing data from EHRs linked to dispensing information Participants: Adults newly initiated on GLP-1 RA between 2018 and 2023, with a baseline BMI [≥]27 and an available weight measurement within 60 days before initiation, and regular care in the year before initiation. Exposure/Covariates: Patients were stratified by presence of T2D at baseline. Associations with socio-demographics, health factors, weight changes, and gastrointestinal (GI) adverse events (AE) were modeled. Main Outcomes and Measures: Proportion of patients discontinuing and reinitiating GLP-1 RA were estimated from Kaplan-Meier models. Associations between covariates and discontinuation and reinitiation outcomes were modeled using time-varying Cox proportional hazards models. All analyses were conducted for patients with and without T2D. Results: Among 96,544 adults initiating GLP-1 RA, the mean (SD) age was 55.1 (13.3) years, 65.2% were female, 73.7% were white, and 61.3% had T2D. Individual income exceeded $50,000 for 49.7% of patients with and 57.2% of patients without T2D. One-year discontinuation was significantly higher for patients without T2D (65.1%), compared to those with T2D (45.8%). Higher weight loss, absence of GI AE, and higher income (T2D only) were significantly associated with higher discontinuation. Of 28,142 (49.6%) who discontinued one-year reinitiation was lower for those without T2D (34.7%), compared to those with T2D (51.0%). Weight re-gain was significantly associated with increased reinitiation. Conclusions and Relevance: Most patients with overweight or obesity discontinue GLP-1 RA within 1 year, but those without T2D discontinue at higher rates and reinitiate at lower rates. Inequities in access and adherence to effective treatments have the potential exacerbate disparities in obesity.","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":"141796410","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: 10.1101/2024.07.25.24311007
M.-M. Aynaud, L. Caldwell, K. Al-Zahrani, S. Barutcu, K. Chan, A. Obersterescu, A. Ogunjimi, M. jin, K.-R. Zakoor, S. Patel, R. padilla, M. Jen, P. Mae, N. Dewsi, F. Yonathan, L. Zhang, A. Ayson-Fortunato, A. Aquino, P. Krzyzanowski, J. T. Simpson, J. Bartlett, I. Lungu, S. Poutanen, B. Wouters, M. Gekas, J. Rini, L. Pelletier, T. Mazzulli, J. L. Wrana
Highly mutable pathogens generate viral diversity that impacts virulence, transmissibility, treatment, and thwarts acquired immunity. We previously described C19-SPAR-Seq, a high-throughput, next-generation sequencing platform to detect SARS-CoV-2 that we deployed to systematically profile variant dynamics of SARS-CoV-2 for over 3 years in a large, North American urban environment (Toronto, Canada). Sequencing of the ACE2 receptor binding motif and polybasic furin cleavage site of Spike in over 70,000 patients revealed that population sweeps of canonical variants of concern (VOCs) occurred in repeating wavelets. Furthermore, we found that subvariants and putative quasi-species with alterations characteristic of future VOCs and/or predicted to be functionally important arose frequently, but always extinguished. Systematic screening of functionally relevant domains in pathogens could thus provide a powerful tool for monitoring spread and mutational trajectories, particularly those with zoonotic potential.
{"title":"Systematic surveillance of SARS-CoV-2 reveals dynamics of variant mutagenesis and transmission in a large urban population","authors":"M.-M. Aynaud, L. Caldwell, K. Al-Zahrani, S. Barutcu, K. Chan, A. Obersterescu, A. Ogunjimi, M. jin, K.-R. Zakoor, S. Patel, R. padilla, M. Jen, P. Mae, N. Dewsi, F. Yonathan, L. Zhang, A. Ayson-Fortunato, A. Aquino, P. Krzyzanowski, J. T. Simpson, J. Bartlett, I. Lungu, S. Poutanen, B. Wouters, M. Gekas, J. Rini, L. Pelletier, T. Mazzulli, J. L. Wrana","doi":"10.1101/2024.07.25.24311007","DOIUrl":"https://doi.org/10.1101/2024.07.25.24311007","url":null,"abstract":"Highly mutable pathogens generate viral diversity that impacts virulence, transmissibility, treatment, and thwarts acquired immunity. We previously described C19-SPAR-Seq, a high-throughput, next-generation sequencing platform to detect SARS-CoV-2 that we deployed to systematically profile variant dynamics of SARS-CoV-2 for over 3 years in a large, North American urban environment (Toronto, Canada). Sequencing of the ACE2 receptor binding motif and polybasic furin cleavage site of Spike in over 70,000 patients revealed that population sweeps of canonical variants of concern (VOCs) occurred in repeating wavelets. Furthermore, we found that subvariants and putative quasi-species with alterations characteristic of future VOCs and/or predicted to be functionally important arose frequently, but always extinguished. Systematic screening of functionally relevant domains in pathogens could thus provide a powerful tool for monitoring spread and mutational trajectories, particularly those with zoonotic potential.","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":"141796430","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: 10.1101/2024.07.27.24310872
Anna Mammel, Ging-Yuek Robin, Ali Mousavi, Kelsey Hallett, Ian R MacKenzie, Veronica Hirsch-Reinshagen, Donald Biehl, Pradip Gill, Mary Encarnacion, Hans Frykman
INTRODUCTION: We evaluated the diagnostic performance of two commercial plasma p-tau217 immunoassays compared to CSF testing and neuropathology. METHODS: 170 plasma samples from University of British Columbia Hospital Clinic for Alzheimer's (AD) and Related Disorders were analyzed for p-tau217 using Fujirebio and ALZpath assays. Decision points were determined using CSF testing and autopsy findings as the standard. RESULTS: Fujirebio and ALZpath p-tau217 had similar overall analytical and clinical performance, with distinct decision points for each assay. Based on autopsy finding, both p-tau217 assays identified individuals with AD from other neurodegenerative diseases (ALZpath AUC = 0.94, Fujirebio AUC= 0.90). The ALZpath assay detected AD pathology at milder disease stages compared to the Fujirebio assay. DISCUSSION: Our study reinforces the clinical utility of plasma p-tau217 as an AD biomarker. Differences in test performance and clinical decision points suggest an assay specific diagnostic approach is required for plasma p-tau217 in clinical practice.
{"title":"Alzheimer's Disease clinical decision points for two plasma p-tau217 laboratory developed tests in neuropathology confirmed samples","authors":"Anna Mammel, Ging-Yuek Robin, Ali Mousavi, Kelsey Hallett, Ian R MacKenzie, Veronica Hirsch-Reinshagen, Donald Biehl, Pradip Gill, Mary Encarnacion, Hans Frykman","doi":"10.1101/2024.07.27.24310872","DOIUrl":"https://doi.org/10.1101/2024.07.27.24310872","url":null,"abstract":"INTRODUCTION: We evaluated the diagnostic performance of two commercial plasma p-tau217 immunoassays compared to CSF testing and neuropathology. METHODS: 170 plasma samples from University of British Columbia Hospital Clinic for Alzheimer's (AD) and Related Disorders were analyzed for p-tau217 using Fujirebio and ALZpath assays. Decision points were determined using CSF testing and autopsy findings as the standard. RESULTS: Fujirebio and ALZpath p-tau217 had similar overall analytical and clinical performance, with distinct decision points for each assay. Based on autopsy finding, both p-tau217 assays identified individuals with AD from other neurodegenerative diseases (ALZpath AUC = 0.94, Fujirebio AUC= 0.90). The ALZpath assay detected AD pathology at milder disease stages compared to the Fujirebio assay. DISCUSSION: Our study reinforces the clinical utility of plasma p-tau217 as an AD biomarker. Differences in test performance and clinical decision points suggest an assay specific diagnostic approach is required for plasma p-tau217 in clinical practice.","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":"141796517","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: 10.1101/2024.07.28.24311115
H. Chemaitelly, H. Ayoub, P. Coyle, P. Tang, M. R. Hasan, H. Yassine, A. Althani, Z. Al-Kanaani, E. Al-Kuwari, A. Jeremijenko, A. Kaleeckal, A. Latif, R. Shaik, H. Abdul-Rahim, G. Nasrallah, M. G. Al-Kuwari, H. Al-Romaihi, M. Al-Thani, A. Al-Khal, R. Bertollini, A. A. Butt, L. Abu-Raddad
Background: This study investigated the presence of the healthy vaccinee bias in two COVID-19 vaccine effectiveness studies, involving primary series and booster vaccinations, as well as its temporal patterns and variability across different subpopulations, by examining the association between COVID-19 vaccination and non-COVID-19 mortality in Qatar. Methods: Two matched, retrospective cohort studies assessed the incidence of non-COVID-19 death in national cohorts of individuals with a primary series vaccination versus no vaccination (two-dose analysis), and individuals with three-dose (booster) vaccination versus primary series vaccination (three-dose analysis), from January 5, 2021, to April 9, 2024. Results: The adjusted hazard ratio (aHR) for non-COVID-19 death was 0.76 (95% CI: 0.64-0.90) in the two-dose analysis and 0.85 (95% CI: 0.67-1.07) in the three-dose analysis. In the first six months of follow-up in the two-dose analysis, the aHR was 0.35 (95% CI: 0.27-0.46); however, the combined analysis of all subsequent periods showed an aHR of 1.52 (95% CI: 1.19-1.94). In the first six months of follow-up in the three-dose analysis, the aHR was 0.31 (95% CI: 0.20-0.50); however, the combined analysis of all subsequent periods showed an aHR of 1.37 (95% CI: 1.02-1.85). The overall effectiveness of the primary series and third-dose vaccinations against severe, critical, or fatal COVID-19 was 95.9% (95% CI: 94.0-97.1) and 34.1% (95% CI: -46.4-76.7), respectively. Subgroup analyses showed that the healthy vaccinee bias is pronounced among those aged 50 years and older and among those more clinically vulnerable to severe COVID-19. Conclusion: A strong healthy vaccinee bias was observed in the first six months following vaccination. This bias may have stemmed from a lower likelihood of vaccination among seriously ill, end-of-life individuals, and less mobile elderly populations. Despite this bias, vaccination provided strong protection against severe COVID-19.
{"title":"Assessing Healthy Vaccinee Bias in COVID-19 Vaccine Effectiveness Studies: A National Cohort Study in Qatar","authors":"H. Chemaitelly, H. Ayoub, P. Coyle, P. Tang, M. R. Hasan, H. Yassine, A. Althani, Z. Al-Kanaani, E. Al-Kuwari, A. Jeremijenko, A. Kaleeckal, A. Latif, R. Shaik, H. Abdul-Rahim, G. Nasrallah, M. G. Al-Kuwari, H. Al-Romaihi, M. Al-Thani, A. Al-Khal, R. Bertollini, A. A. Butt, L. Abu-Raddad","doi":"10.1101/2024.07.28.24311115","DOIUrl":"https://doi.org/10.1101/2024.07.28.24311115","url":null,"abstract":"Background: This study investigated the presence of the healthy vaccinee bias in two COVID-19 vaccine effectiveness studies, involving primary series and booster vaccinations, as well as its temporal patterns and variability across different subpopulations, by examining the association between COVID-19 vaccination and non-COVID-19 mortality in Qatar. Methods: Two matched, retrospective cohort studies assessed the incidence of non-COVID-19 death in national cohorts of individuals with a primary series vaccination versus no vaccination (two-dose analysis), and individuals with three-dose (booster) vaccination versus primary series vaccination (three-dose analysis), from January 5, 2021, to April 9, 2024. Results: The adjusted hazard ratio (aHR) for non-COVID-19 death was 0.76 (95% CI: 0.64-0.90) in the two-dose analysis and 0.85 (95% CI: 0.67-1.07) in the three-dose analysis. In the first six months of follow-up in the two-dose analysis, the aHR was 0.35 (95% CI: 0.27-0.46); however, the combined analysis of all subsequent periods showed an aHR of 1.52 (95% CI: 1.19-1.94). In the first six months of follow-up in the three-dose analysis, the aHR was 0.31 (95% CI: 0.20-0.50); however, the combined analysis of all subsequent periods showed an aHR of 1.37 (95% CI: 1.02-1.85). The overall effectiveness of the primary series and third-dose vaccinations against severe, critical, or fatal COVID-19 was 95.9% (95% CI: 94.0-97.1) and 34.1% (95% CI: -46.4-76.7), respectively. Subgroup analyses showed that the healthy vaccinee bias is pronounced among those aged 50 years and older and among those more clinically vulnerable to severe COVID-19. Conclusion: A strong healthy vaccinee bias was observed in the first six months following vaccination. This bias may have stemmed from a lower likelihood of vaccination among seriously ill, end-of-life individuals, and less mobile elderly populations. Despite this bias, vaccination provided strong protection against severe COVID-19.","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":"141796541","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: 10.1101/2024.07.26.24311075
Musa Yilanli, Ian McKay, Daniel I. Jackson BSc, Emre Sezgin
Importance: In mental healthcare, the potential of Large Language Models (LLMs) to enhance psychoeducation is a burgeoning field. This study explored the potential of ChatGPT as an individualized psychoeducational support tool specifically for psychosis education. Objective: The study aims to evaluate psychosis-related questions to provide accurate, clear, and clinically relevant individualized information for patients and caregivers. Design: This cross-sectional study uses a qualitative analysis design. The researchers specifically employed a question-answering system (GPT-4 via ChatGPT) to generate responses to common questions about psychosis. Experts in the field then evaluated these responses to assess their quality for use in a clinical setting. Primary Outcome: Researchers presented ChatGPT with 20 common questions frequently asked by patients' caregivers and relatives. Two experts in psychosis then assessed the quality of the responses using six criteria: accuracy (1-3), clarity (1-3), inclusivity (1-3), completeness (0-1), clinical utility (1-5) and an overall score (1-4). Results: The evaluation yielded positive results overall. Responses were rated as accurate (M:SD= 2.89:0.22) and clear (mean score of 2.93:0.18). There was potential for improvement in terms of inclusivity (mean score of 2.30:0.41), suggesting a need to incorporate more diverse perspectives. Completeness received high ratings (mean score of 0.93:0.18), indicating responses addressed all aspects of the questions. Most importantly, the responses were deemed clinically useful (mean score of 4.35:0.52). Conclusions: In summary, this study underscores the significant promise of ChatGPT as a psychoeducational tool for patients with psychosis, their relatives, and their caregivers. The experts' findings affirm that the information delivered by ChatGPT is not only accurate and clinically relevant but also conveyed conversationally, enhancing its accessibility and usability. The initial performance of ChatGPT as a psychoeducational tool in the context of psychosis education is undeniably positive.
{"title":"Large Language Models for Individualized Psychoeducational Tools for Psychosis: A cross-sectional study","authors":"Musa Yilanli, Ian McKay, Daniel I. Jackson BSc, Emre Sezgin","doi":"10.1101/2024.07.26.24311075","DOIUrl":"https://doi.org/10.1101/2024.07.26.24311075","url":null,"abstract":"Importance: In mental healthcare, the potential of Large Language Models (LLMs) to enhance psychoeducation is a burgeoning field. This study explored the potential of ChatGPT as an individualized psychoeducational support tool specifically for psychosis education. Objective: The study aims to evaluate psychosis-related questions to provide accurate, clear, and clinically relevant individualized information for patients and caregivers. Design: This cross-sectional study uses a qualitative analysis design. The researchers specifically employed a question-answering system (GPT-4 via ChatGPT) to generate responses to common questions about psychosis. Experts in the field then evaluated these responses to assess their quality for use in a clinical setting. Primary Outcome: Researchers presented ChatGPT with 20 common questions frequently asked by patients' caregivers and relatives. Two experts in psychosis then assessed the quality of the responses using six criteria: accuracy (1-3), clarity (1-3), inclusivity (1-3), completeness (0-1), clinical utility (1-5) and an overall score (1-4). Results: The evaluation yielded positive results overall. Responses were rated as accurate (M:SD= 2.89:0.22) and clear (mean score of 2.93:0.18). There was potential for improvement in terms of inclusivity (mean score of 2.30:0.41), suggesting a need to incorporate more diverse perspectives. Completeness received high ratings (mean score of 0.93:0.18), indicating responses addressed all aspects of the questions. Most importantly, the responses were deemed clinically useful (mean score of 4.35:0.52). Conclusions: In summary, this study underscores the significant promise of ChatGPT as a psychoeducational tool for patients with psychosis, their relatives, and their caregivers. The experts' findings affirm that the information delivered by ChatGPT is not only accurate and clinically relevant but also conveyed conversationally, enhancing its accessibility and usability. The initial performance of ChatGPT as a psychoeducational tool in the context of psychosis education is undeniably positive.","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":"141796548","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: 10.1101/2024.07.28.24311142
A. Zulli, E. Chan, A. Boehm
Wastewater-based epidemiology, which seeks to assess disease occurrence in communities through measurements of infectious disease biomarkers in wastewater, may represent a valuable tool for understanding occurrence of hepatitis A infections in communities. In this study, we measured concentrations of Hepatovirus A (HAV) RNA, in samples from 191 wastewater treatment plants spanning 40 US states and the District of Columbia from September 2023 to June 2024 and compared the measurements with traditional measures of disease occurrence. Nationally, 13.76% of the 21,602 wastewater samples were positive for HAV RNA, and both concentrations and positivity rates were associated with NNDSS hepatitis A case data nationally (Kendall rank correlation coefficient = 0.20, concentrations; and 0.33, positivity rate; both p<0.05). We further demonstrated that higher rates of wastewater HAV detection were positively associated with socioeconomic indicators of vulnerability including homelessness and drug overdose deaths (both p<0.0001). Areas with above average levels of homelessness were 48% more likely to have HAV wastewater detections, while areas with above average levels of drug overdose deaths were 14% more likely to have HAV wastewater detections. Using more granular case data, we present a case study in the state of Maine that reinforces these results and suggests a potential lead time for wastewater over clinical case detection and exposure events. The ability to detect HAV RNA in wastewater before clinical cases emerge could allow public health officials to implement targeted interventions like vaccination campaigns.
{"title":"Detection of Hepatovirus A (HAV) in wastewater indicates widespread national distribution and association with socioeconomic indicators of vulnerability","authors":"A. Zulli, E. Chan, A. Boehm","doi":"10.1101/2024.07.28.24311142","DOIUrl":"https://doi.org/10.1101/2024.07.28.24311142","url":null,"abstract":"Wastewater-based epidemiology, which seeks to assess disease occurrence in communities through measurements of infectious disease biomarkers in wastewater, may represent a valuable tool for understanding occurrence of hepatitis A infections in communities. In this study, we measured concentrations of Hepatovirus A (HAV) RNA, in samples from 191 wastewater treatment plants spanning 40 US states and the District of Columbia from September 2023 to June 2024 and compared the measurements with traditional measures of disease occurrence. Nationally, 13.76% of the 21,602 wastewater samples were positive for HAV RNA, and both concentrations and positivity rates were associated with NNDSS hepatitis A case data nationally (Kendall rank correlation coefficient = 0.20, concentrations; and 0.33, positivity rate; both p<0.05). We further demonstrated that higher rates of wastewater HAV detection were positively associated with socioeconomic indicators of vulnerability including homelessness and drug overdose deaths (both p<0.0001). Areas with above average levels of homelessness were 48% more likely to have HAV wastewater detections, while areas with above average levels of drug overdose deaths were 14% more likely to have HAV wastewater detections. Using more granular case data, we present a case study in the state of Maine that reinforces these results and suggests a potential lead time for wastewater over clinical case detection and exposure events. The ability to detect HAV RNA in wastewater before clinical cases emerge could allow public health officials to implement targeted interventions like vaccination campaigns.","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":"141796388","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: 10.1101/2024.07.26.24310655
X. Liu, Z.-Q. Liu, B. Wan, X. Zhang, L. Liu, J. Xiao, Y. Meng, S. Wang, C. Weng, Y. Gao
Understanding the alterations in brain function across different episodes of bipolar disorder (BD), including manic (BipM), depressive (BipD), and remission states (rBD), poses a significant challenge. In our cross-sectional study, we collected resting-state functional magnetic resonance imaging data from 117 BD patients (BipM: 38, BipD: 42, rBD: 37) and 35 healthy controls. Our aim was to delineate functional connections associated with episode dynamics, delineate common and specific patterns, validate them as biomarkers, and elucidate their biological underpinnings. Initially, we identified a common altered pattern within the sub-regions of the ventral-attention network, alongside specific patterns observed in the default mode network for BipM, the prefrontal network for BipD, and the limbic network for rBD. Using large-sample data from the Human Connectome Project, we further identified that these connectivity patterns exhibit relatively high reliability and heritability. Also, these distinct patterns accurately characterized the diverse episodes of BD and effectively predicted the cor responding clinical symptoms linked with each episode type. Importantly, using out of sample data to decode possible neurobiological mechanisms underlying these patterns, we found that regions of particular interest were enriched in multiple receptors, including MOR, NMDA, and H3 for specific alterations, and A4B2, 5HTT, and 5HT1a for common alterations. Moreover, both episode-specific and common patterns demonstrated a high enrichment for cell types such as L5ET, Micro/PVM,oligodendrites and Chandelier. Our study offers novel insights concerning episode dynamics in BD, paving the way for personalized medicine approaches tailored to address the various episodes.
{"title":"Episode-specific and common intrinsic functional network patterns in bipolar","authors":"X. Liu, Z.-Q. Liu, B. Wan, X. Zhang, L. Liu, J. Xiao, Y. Meng, S. Wang, C. Weng, Y. Gao","doi":"10.1101/2024.07.26.24310655","DOIUrl":"https://doi.org/10.1101/2024.07.26.24310655","url":null,"abstract":"Understanding the alterations in brain function across different episodes of bipolar disorder (BD), including manic (BipM), depressive (BipD), and remission states (rBD), poses a significant challenge. In our cross-sectional study, we collected resting-state functional magnetic resonance imaging data from 117 BD patients (BipM: 38, BipD: 42, rBD: 37) and 35 healthy controls. Our aim was to delineate functional connections associated with episode dynamics, delineate common and specific patterns, validate them as biomarkers, and elucidate their biological underpinnings. Initially, we identified a common altered pattern within the sub-regions of the ventral-attention network, alongside specific patterns observed in the default mode network for BipM, the prefrontal network for BipD, and the limbic network for rBD. Using large-sample data from the Human Connectome Project, we further identified that these connectivity patterns exhibit relatively high reliability and heritability. Also, these distinct patterns accurately characterized the diverse episodes of BD and effectively predicted the cor responding clinical symptoms linked with each episode type. Importantly, using out of sample data to decode possible neurobiological mechanisms underlying these patterns, we found that regions of particular interest were enriched in multiple receptors, including MOR, NMDA, and H3 for specific alterations, and A4B2, 5HTT, and 5HT1a for common alterations. Moreover, both episode-specific and common patterns demonstrated a high enrichment for cell types such as L5ET, Micro/PVM,oligodendrites and Chandelier. Our study offers novel insights concerning episode dynamics in BD, paving the way for personalized medicine approaches tailored to address the various episodes.","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":"141796515","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: 10.1101/2024.07.28.24311101
A. Rose, Jennifer Maxwell, E. Rousselle, M. Riaud, Islam E. Elkholi, Chantel L. Mukonoweshuro, M. Biondini, Erica Cianfarano, I. Soria-Bretones, Chantal Tobin, Meghan Mcguire, Ian King, Tong Zhang, T. J. Pugh, Z. Kamil, Frances A. Shepherd, Natasha B. Leighl, A. A. Razak, A. Hansen, Sam Saibil, Philippe L. Bedard, Peter M. Siegel, Lillian L. Siu, D. Cescon, A. Spreafico, Dr. Soria Bretones, RocheGenentech, AstraZenecaMedimmune, Abbvie Amgen Symphogen Emd Bayer, Serono, Daiichi Sankyo, M. Gilead, Medicenna Lilly, Takara
Class 2 and 3 non-V600E BRAF mutations are oncogenic drivers in many cancer types. Currently, there are no established targeted therapies with proven efficacy for cancers with non-V600E BRAF mutations. We developed the investigator-initiated, Phase II BEAVER clinical trial (NCT03839342) to evaluate the efficacy of BRAF and MEK inhibitors in patients with non-V600E BRAF mutations. The best objective response rate was 14% (3/21). By analyzing genomic data from patient tumors, circulating tumor DNA (ctDNA), patient-derived xenograft (PDX) models generated from enrolled patients, and Class 2 & 3 BRAF mutant cell lines, we discovered MAPK-dependent and independent mechanisms of resistance to BRAF/MEK inhibition. These mechanisms included the acquisition of new mutations in NRAS, MAP2K1, RAF1, and RB in ctDNA at the time of disease progression. CDK4/6 and SHP2 were identified as mediators of intrinsic resistance to BRAF/MEK inhibition in Class 2 & 3 BRAF mutant tumors. Therapeutic strategies combining CDK4/6 or SHP2 inhibitors with BRAF/MEK inhibitors were more effective than BRAF/MEK inhibitors alone in these cancers.
{"title":"CDK4/6 and SHP2 mediate BRAF/MEK inhibitor resistance in Class 2 and 3 BRAF mutant cancers","authors":"A. Rose, Jennifer Maxwell, E. Rousselle, M. Riaud, Islam E. Elkholi, Chantel L. Mukonoweshuro, M. Biondini, Erica Cianfarano, I. Soria-Bretones, Chantal Tobin, Meghan Mcguire, Ian King, Tong Zhang, T. J. Pugh, Z. Kamil, Frances A. Shepherd, Natasha B. Leighl, A. A. Razak, A. Hansen, Sam Saibil, Philippe L. Bedard, Peter M. Siegel, Lillian L. Siu, D. Cescon, A. Spreafico, Dr. Soria Bretones, RocheGenentech, AstraZenecaMedimmune, Abbvie Amgen Symphogen Emd Bayer, Serono, Daiichi Sankyo, M. Gilead, Medicenna Lilly, Takara","doi":"10.1101/2024.07.28.24311101","DOIUrl":"https://doi.org/10.1101/2024.07.28.24311101","url":null,"abstract":"Class 2 and 3 non-V600E BRAF mutations are oncogenic drivers in many cancer types. Currently, there are no established targeted therapies with proven efficacy for cancers with non-V600E BRAF mutations. We developed the investigator-initiated, Phase II BEAVER clinical trial (NCT03839342) to evaluate the efficacy of BRAF and MEK inhibitors in patients with non-V600E BRAF mutations. The best objective response rate was 14% (3/21). By analyzing genomic data from patient tumors, circulating tumor DNA (ctDNA), patient-derived xenograft (PDX) models generated from enrolled patients, and Class 2 & 3 BRAF mutant cell lines, we discovered MAPK-dependent and independent mechanisms of resistance to BRAF/MEK inhibition. These mechanisms included the acquisition of new mutations in NRAS, MAP2K1, RAF1, and RB in ctDNA at the time of disease progression. CDK4/6 and SHP2 were identified as mediators of intrinsic resistance to BRAF/MEK inhibition in Class 2 & 3 BRAF mutant tumors. Therapeutic strategies combining CDK4/6 or SHP2 inhibitors with BRAF/MEK inhibitors were more effective than BRAF/MEK inhibitors alone in these cancers.","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":"141796520","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: 10.1101/2024.07.27.24311102
R. Allen, J. Wellens-Mensah, O. Leavy, S. Bourke, W. Henderson, H. Smith, E. Johnson, D. Marks, Y. Myat, C. Rafique, G. Parcesepe, T. Hernandez-Beeftink, B. Guillen-Guio, E. Cheng, C. Chan, G. Clark, S. Dickson, A. Pearson, M. Embley, P. Lynch, G. Boyd, B. Gooptu, Y. Ji, C. McSharry, L. Wain, M. Spears
Introduction Hypersensitivity pneumonitis (HP), a common interstitial lung disease (ILD), comprises two distinct but related forms, acute and fibrotic (fHP). HP is classically described as a disease triggered by antigen exposure. However, a wide range of triggers are described and in ~50% of cases no cause is identified, rendering observational studies challenging. The British Pigeon Fanciers Genetics of ILD (BPF-GILD) study aims to address this by studying a population with a clear history of exposure to a common trigger. Methods Participants were recruited from 2019 to 2023 at large UK Pigeon Fancier meetings. Each participant performed spirometry, completed a standardised questionnaire with a doctor, and provided blood samples. We present our baseline data in this manuscript. Results 417 subjects were recruited from four shows. The median age of the cohort was 63 years, 95% were male and 94% self-reported white ethnicity. The median number of pigeons kept was 80 [range 4-800], with fanciers spending 14 hours per week [1-100] in their lofts. 52% of participants had occupational dust exposures. 49% of the cohort reported at least one respiratory symptom related to loft exposure. 14% had a history of ILD and these individuals had more loft-related respiratory symptoms, poorer lung function, and appeared more likely to wear a mask with their pigeons than those without (74% vs 57%). 41% of participants had positive responses to questions employed to detect occult connective tissue disease in ILD clinics. Discussion Our well characterised cohort of pigeon fanciers commonly experience acute HP symptoms and are likely to be at increased risk of fHP. Subsequent work using stored samples will enable us to determine genetic risk factors and pathways relevant to the development of fHP.
{"title":"BPF-GILD study: an observational cohort study of UK pigeon fanciers","authors":"R. Allen, J. Wellens-Mensah, O. Leavy, S. Bourke, W. Henderson, H. Smith, E. Johnson, D. Marks, Y. Myat, C. Rafique, G. Parcesepe, T. Hernandez-Beeftink, B. Guillen-Guio, E. Cheng, C. Chan, G. Clark, S. Dickson, A. Pearson, M. Embley, P. Lynch, G. Boyd, B. Gooptu, Y. Ji, C. McSharry, L. Wain, M. Spears","doi":"10.1101/2024.07.27.24311102","DOIUrl":"https://doi.org/10.1101/2024.07.27.24311102","url":null,"abstract":"Introduction Hypersensitivity pneumonitis (HP), a common interstitial lung disease (ILD), comprises two distinct but related forms, acute and fibrotic (fHP). HP is classically described as a disease triggered by antigen exposure. However, a wide range of triggers are described and in ~50% of cases no cause is identified, rendering observational studies challenging. The British Pigeon Fanciers Genetics of ILD (BPF-GILD) study aims to address this by studying a population with a clear history of exposure to a common trigger. Methods Participants were recruited from 2019 to 2023 at large UK Pigeon Fancier meetings. Each participant performed spirometry, completed a standardised questionnaire with a doctor, and provided blood samples. We present our baseline data in this manuscript. Results 417 subjects were recruited from four shows. The median age of the cohort was 63 years, 95% were male and 94% self-reported white ethnicity. The median number of pigeons kept was 80 [range 4-800], with fanciers spending 14 hours per week [1-100] in their lofts. 52% of participants had occupational dust exposures. 49% of the cohort reported at least one respiratory symptom related to loft exposure. 14% had a history of ILD and these individuals had more loft-related respiratory symptoms, poorer lung function, and appeared more likely to wear a mask with their pigeons than those without (74% vs 57%). 41% of participants had positive responses to questions employed to detect occult connective tissue disease in ILD clinics. Discussion Our well characterised cohort of pigeon fanciers commonly experience acute HP symptoms and are likely to be at increased risk of fHP. Subsequent work using stored samples will enable us to determine genetic risk factors and pathways relevant to the development of fHP.","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":"141796705","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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