medRxiv : the preprint server for health sciences最新文献

{"title":"Frequency dynamics predict viral fitness, antigenic relationships and epidemic growth.","authors":"Marlin D Figgins, Trevor Bedford","doi":"10.1101/2024.12.02.24318334","DOIUrl":"10.1101/2024.12.02.24318334","url":null,"abstract":"<p><p>During the COVID-19 pandemic, SARS-CoV-2 variants drove large waves of infections, fueled by increased transmissibility and immune escape. Current models focus on changes in variant frequencies without linking them to underlying transmission mechanisms of intrinsic transmissibility and immune escape. We introduce a framework connecting variant dynamics to these mechanisms, showing how host population immunity interacts with viral transmissibility and immune escape to determine relative variant fitness. We advance a selective pressure metric that provides an early signal of epidemic growth using genetic data alone, crucial with current underreporting of cases. Additionally, we show that a latent immunity space model approximates immunological distances, offering insights into population susceptibility and immune evasion. These insights refine real-time forecasting and lay the groundwork for research into the interplay between viral genetics, immunity, and epidemic growth.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Directed exploration is reduced by an aversive interoceptive state induction in healthy individuals but not in those with affective disorders.","authors":"Ning Li, Claire A Lavalley, Ko-Ping Chou, Anne E Chuning, Samuel Taylor, Carter M Goldman, Taylor Torres, Rowan Hodson, Robert C Wilson, Jennifer L Stewart, Sahib S Khalsa, Martin P Paulus, Ryan Smith","doi":"10.1101/2024.06.19.24309110","DOIUrl":"10.1101/2024.06.19.24309110","url":null,"abstract":"<p><p>Elevated anxiety and uncertainty avoidance are known to exacerbate maladaptive choice in individuals with affective disorders. However, the differential roles of state vs. trait anxiety remain unclear, and underlying computational mechanisms have not been thoroughly characterized. In the present study, we investigated how a somatic (interoceptive) state anxiety induction influences learning and decision-making under uncertainty in individuals with clinically significant levels of trait anxiety. A sample of 58 healthy comparisons (HCs) and 61 individuals with affective disorders displaying elevated anxiety symptoms (iADs; i.e., anxiety and/or depression) completed a previously validated explore-exploit decision task, with and without an added breathing resistance manipulation designed to induce state anxiety. Computational modeling revealed a significant group-by-condition interaction, such that information-seeking (i.e., directed exploration) in HCs was reduced by the anxiety induction (Cohen's <i>d</i> =.47, <i>p</i> =.013), while no change was observed in iADs. The iADs also showed slower learning rates than HCs across conditions (Cohen's <i>d</i> =.52, <i>p</i> =.003), suggesting more persistent uncertainty. These findings highlight a complex interplay between trait anxiety and state anxiety. Specifically, state anxiety may attenuate reflection on uncertainty in healthy individuals, while familiarity with anxious states in those with high trait anxiety may create an insensitivity to this effect.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Playbook for Pragmatic Trial Operations to Monitor and Evaluate Ambient Artificial Intelligence in Clinical Practice.","authors":"Majid Afshar, Felice Resnik, Mary Ryan Baumann, Josie Hintzke, Anne Gravel Sullivan, Tina Shah, Anthony Stordalen, Michael Oberst, Jason Dambach, Leigh Ann Mrotek, Mariah Quinn, Kirsten Abramson, Peter Kleinschmidt, Tom Brazelton, Heidi Twedt, David Kunstman, John Long, Brian Patterson, Frank Liao, Stacy Rasmussen, Elizabeth Burnside, Cherodeep Goswami, Joel Gordon","doi":"10.1101/2024.12.27.24319685","DOIUrl":"https://doi.org/10.1101/2024.12.27.24319685","url":null,"abstract":"<p><strong>Background: </strong>Ambient artificial intelligence offers promise for improving documentation efficiency and reducing provider burden through clinical note generation. However, challenges persist in workflow integration, compliance, and widespread adoption. This study leveraged a Learning Health System (LHS) framework to align research and operations using a hybrid effectiveness-implementation protocol, embedded as pragmatic trial operations within the electronic health record (EHR).</p><p><strong>Methods: </strong>An alpha phase was conducted to pilot technical integration, refine workflows, and determine sample size in planning for a beta phase designed as a pragmatic randomized controlled trial with the Stanford Professional Fulfillment Index (PFI) as primary outcome. During alpha, bi-directional governance was established between IS operations and LHS team with multidisciplinary workgroups for analytics, technical, documentation, and user experience. Ambient AI was embedded into the EHR using Fast Healthcare Interoperability Resources (FHIR), with real-time data dashboards tracking utilization and documentation accuracy for operations and research. Performance metrics were monitored serially using a difference-in-differences (DiD) analysis to detect drift caused by software workflow changes.</p><p><strong>Results: </strong>The alpha phase, designed as Type 1 Hybrid, informed a 24-week beta phase stepped-wedge trial with 90% power to detect changes in PFI. Across the alpha phase, the weighted median of average provider Ambient AI utilization was 65.4% following Plan-Do-Study-Act cycles addressing organizational feasibility and task-dependent adoption. During initial implementation, a workflow issue caused discrepancies between ICD-10 diagnosis entries and note content, reducing accuracy from 79% to 35% (p < 0.01). After implementing a new note template and provider training, accuracy returned to pre-intervention levels. DiD did not detect significant drifts in work outside of work or time in notes two weeks before and after the new note template. Beta phase enrollment achieved its targeted 66 providers across eight specialties, initiating on schedule.</p><p><strong>Conclusions and relevance: </strong>We provide a novel playbook for integrating Generative AI platforms in healthcare, combining pragmatic trial operations, human-centered design, and real-time monitoring to advance evidence-based implementation.</p><p><strong>Clinicaltrialsgov id: </strong>NCT06517082.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-scale genetic characterization of Parkinson's disease in the African and African admixed populations.","authors":"Fulya Akçimen, Kimberly Paquette, Peter Wild Crea, Paula Saffie-Awad, Charles Achoru, Funmilola Taiwo, Simon Ozomma, Gerald Onwuegbuzie, Marzieh Khani, Spencer Grant, Lukman Owolabi, Chiamaka Okereke, Olajumoke Oshinaike, Emmanuel Iwuozo, Paul Suhwan Lee, Shyngle Oyakhire, Nosakhare Osemwegie, Kensuke Daida, Sani Abubakar, Adedunni Olusanya, Mariam Isayan, Rami Traurig, Adebimpe Ogunmodede, Sarah Samuel, Mary B Makarious, Fadimatu Sa'ad, Rashidat Olanigan, Kristin Levine, Ewere Marie Ogbimi, Dan Vitale, Francis Odiase, Mathew J Koretsky, Francis Ojini, Olanike Odeniyi, Zih-Hua Fang, Nkechi Obianozie, Deborah A Hall, Ernest Nwazor, Tao Xie, Francisca Nwaokorie, Mahesh Padmanaban, Paul Nwani, Ejaz A Shamim, Alero Nnama, David Standaert, Morenikeji Komolafe, Marissa Dean, Godwin Osaigbovo, Elizabeth Disbrow, Ismaila Ishola, Ashley Rawls, Frank Imarhiagbe, Shivika Chandra, Cyril Erameh, Vanessa Hinson, Naomi Louie, Ahmed Idowu, J Solle, Scott A Norris, Abdullahi Ibrahim, Camilla Kilbane, Gauthaman Sukumar, Lisa M Shulman, Daniel Ezuduemoih, Julia Staisch, Sarah Breaux, Clifton Dalgard, Erin R Foster, Abiodun Bello, Andrew Ameri, Raquel Real, Erica Ikwenu, Huw R Morris, Roosevelt Anyanwu, Erin Furr Stimming, Kimberley Billingsley, Wemimo Alaofin, Pilar Alvarez Jerez, Osigwe Agabi, Dena G Hernandez, Rufus Akinyemi, Sampath Arepalli, Laksh Malik, Raymond Owolabi, Yakub Nyandaiti, Hampton L Leonard, Kolawole Wahab, Kathryn Step, Oladunni Abiodun, Carlos F Hernandez, Fatima Abdulai, Hirotaka Iwaki, Soraya Bardien, Christine Klein, John Hardy, Henry Houlden, Kamalini Ghosh Galvelis, Mike A Nalls, Nabila Dahodwala, Whitley Aamodt, Emily Hill, Alberto Espay, Stewart Factor, Chantale Branson, Cornelis Blauwendraat, Andrew B Singleton, Oluwadamilola Ojo, Lana M Chahine, Njideka Okubadejo, Sara Bandres-Ciga","doi":"10.1101/2025.01.14.25320205","DOIUrl":"https://doi.org/10.1101/2025.01.14.25320205","url":null,"abstract":"<p><p>Elucidating the genetic contributions to Parkinson's disease (PD) etiology across diverse ancestries is a critical priority for the development of targeted therapies in a global context. We conducted the largest sequencing characterization of potentially disease-causing, protein-altering and splicing mutations in 710 cases and 11,827 controls from genetically predicted African or African admixed ancestries. We explored copy number variants (CNVs) and runs of homozygosity (ROHs) in prioritized early onset and familial cases. Our study identified rare <i>GBA1</i> coding variants to be the most frequent mutations among PD patients, with a frequency of 4% in our case cohort. Out of the 18 <i>GBA1</i> variants identified, ten were previously classified as pathogenic or likely pathogenic, four were novel, and four were reported as of uncertain clinical significance. The most common known disease-associated <i>GBA1</i> variants in the Ashkenazi Jewish and European populations, p.Asn409Ser, p.Leu483Pro, p.Thr408Met, and p.Glu365Lys, were not identified among the screened PD cases of African and African admixed ancestry. Similarly, the European and Asian <i>LRRK2</i> disease-causing mutational spectrum, including <i>LRRK2</i> p.Gly2019Ser and p.Gly2385Arg genetic risk factors, did not appear to play a major role in PD etiology among West African-ancestry populations. However, we found three heterozygous novel missense <i>LRRK2</i> variants of uncertain significance overrepresented in cases, two of which - p.Glu268Ala and p.Arg1538Cys - had a higher prevalence in the African ancestry population reference datasets. Structural variant analyses revealed the presence of <i>PRKN</i> CNVs with a frequency of 0.7% in African and African admixed cases, with 66% of CNVs detected being compound heterozygous or homozygous in early-onset cases, providing further insights into the genetic underpinnings in early-onset juvenile PD in these populations. Novel genetic variation overrepresented in cases versus controls among screened genes warrants further replication and functional prioritization to unravel their pathogenic potential. Here, we created the most comprehensive genetic catalog of both known and novel coding and splicing variants potentially linked to PD etiology in an underserved population. Our study has the potential to guide the development of targeted therapies in the emerging era of precision medicine. By expanding genetics research to involve underrepresented populations, we hope that future PD treatments are not only effective but also inclusive, addressing the needs of diverse ancestral groups.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of the maternal and fetal proteome on birth weight: a Mendelian randomization analysis.","authors":"Nancy McBride, Alba Fernández-Sanlés, Marwa Al Arab, Tom A Bond, Jie Zheng, Maria C Magnus, Elizabeth C Corfield, Gemma L Clayton, Liang-Dar Hwang, Robin N Beaumont, David M Evans, Rachel M Freathy, Tom R Gaunt, Deborah A Lawlor, Maria Carolina Borges","doi":"10.1101/2023.10.20.23297135","DOIUrl":"10.1101/2023.10.20.23297135","url":null,"abstract":"<p><strong>Background: </strong>Fetal growth is an important indicator of survival, regulated by maternal and fetal genetic and environmental factors. However, little is known about the underlying molecular mechanisms. Proteins play a major role in a wide range of biological processes and could provide key insights into maternal and fetal molecular mechanisms regulating fetal growth.</p><p><strong>Method: </strong>We used intergenerational two-sample Mendelian randomization to explore the effects of 1,139 maternal and fetal genetically-instrumented plasma proteins on birth weight. We used genome-wide association summary data from the Early Growth Genetics (EGG) consortium (n=406,063 with maternal and/or fetal genotype), with independent replication in the Norwegian Mother, Father and Child Cohort Study (MoBa; n=74,932 mothers and n=62,108 offspring). Maternal and fetal data were adjusted for the correlation between fetal and maternal genotype, to distinguish their independent genetic effects.</p><p><strong>Results: </strong>We found that higher genetically-predicted maternal levels of NEC1 increased birth weight (mean-difference: 12g (95% CI [6g, 18g]) per 1 standard deviation protein level) as did PRS57 (20g [10g, 31g]) and ULK3 (140g [81g, 199g]). Higher maternal levels of Galectin_4 decreased birth weight (-206g [-299g, -113g]). In contrast, in the offspring, higher genetically-predicted offspring levels of NEC1 decreased birth weight (-10g [-16g, -5g]), alongside sLeptin_R (-8g [-12g, -4g]), and UBS3B (-78g [-116g, -41g]). Higher fetal levels of Galectin_4 increased birth weight (174g [89g, 258g]). We replicated these results in MoBa, and found supportive evidence for shared causal variants from genetic colocalization analyses and protein-protein network associations.</p><p><strong>Conclusions: </strong>We find strong evidence for causal effects, sometimes in opposing directions, of maternal and fetal genetically-instrumented proteins on birth weight. These provide new insights into maternal and fetal molecular mechanisms regulating fetal growth, involving glucose metabolism, energy balance, and vascular function that could be used to identify new intervention targets to reduce the risk of fetal growth disorders, and their associated adverse maternal and fetal outcomes.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10615012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71416465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matching Heterogeneous Cohorts by Projected Principal Components Reveals Two Novel Alzheimer's Disease-Associated Genes in the Hispanic Population.","authors":"Julian Daniel Sunday Willett, Kristina Mullin, Rudolph E Tanzi, Dmitry Prokopenko","doi":"10.1101/2025.01.18.25320774","DOIUrl":"10.1101/2025.01.18.25320774","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common form of dementia in elderly, affecting 6.9 million individuals in the United States. Some studies have suggested the prevalence of AD is greater in individuals who self-identify as Hispanic. Focused results are relevant for personalized and equitable clinical interventions. Ethnicity as a stratifying tool in genetic studies is often accompanied by genomic inflation due to heterogeneity. In this study, we report GWAS and meta-analyses conducted among NIAGADS subjects who self-identified as Hispanic and All of Us (AoU) sub-cohorts matched to that cohort, using projected genetically-derived principal components, with and without age and sex. In Hispanic NIAGADS subjects, we identified a common variant in <i>PIEZO2</i> that was protective for AD with a p-value just beyond genome-wide significance (p = 5.4 * 10^-8). Meta-analyses with genetically-matched AoU participants yielded three (two novel) genome-wide significant AD-associated loci based on rare lead variants: rs374043832 (<i>RGS6/PSEN1</i>), rs192423465 (<i>ASPSCR1</i>), and rs935208076 (<i>GDAP2</i>), which were also nominally significant in AoU sub-cohorts. We also show how genomic inflation can be mitigated in heterogeneous populations while increasing sample size and result generalizability.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating distinct and common fMRI-complexity patterns in pre-adolescent children with Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, and Obsessive-Compulsive Disorder diagnoses.","authors":"Ru Zhang, Steven Cen, Dilmini Wijesinghe, Leon Aksman, Stuart B Murray, Christina J Duval, Danny J J Wang, Kay Jann","doi":"10.1101/2025.01.17.25320748","DOIUrl":"10.1101/2025.01.17.25320748","url":null,"abstract":"<p><strong>Importance: </strong>The pathophysiology of ADHD is complicated by high rates of psychiatric comorbidities, thus delineating unique versus shared functional brain perturbations is critical in elucidating illness pathophysiology.</p><p><strong>Objective: </strong>To investigate resting-state fMRI (rsfMRI)-complexity alterations among children with ADHD, oppositional defiant disorder (ODD), and obsessive-compulsive disorder (OCD), respectively, and comorbid ADHD, ODD, and OCD, within the cool and hot executive function (EF) networks.</p><p><strong>Design: </strong>We leveraged baseline data (wave 0) from the Adolescent Brain and Cognitive Development (ABCD) Study.</p><p><strong>Setting: </strong>The data was collected between September 2016 and September 2019 from 21 sites in the USA.</p><p><strong>Participants: </strong>Children who singularly met all DSM-5 behavioral criteria for ADHD (<i>N</i> = 61), ODD (<i>N</i> = 38), and OCD (<i>N</i> = 48), respectively, were extracted, alongside children with comorbid ADHD, ODD, OCD, and/or other psychiatric diagnoses (<i>N</i> = 833). A control sample of age-, sex-, and developmentally-matched children was also extracted (<i>N</i> = 269).</p><p><strong>Main outcomes and measures: </strong>Voxel-wise sample entropy (SampEn) was computed using the LOFT Complexity Toolbox. Mean SampEn within all regions of the EF networks was calculated for each participant and hierarchical models with Generalized Estimating Equations compared SampEn of comorbid-free and comorbid ADHD, ODD, and OCD within the EF networks.</p><p><strong>Results: </strong>SampEn was reduced in comorbid-free ADHD and ODD in overlapping regions of both EF networks, including the bilateral superior frontal gyrus, anterior/posterior cingulate gyrus, and bilateral caudate (Wald statistic = 5.682 to 10.798, <i>p</i> < 0.05 & BH corrected), with ADHD additionally affected in the right inferior/middle frontal gyrus and bilateral frontal orbital cortex (Wald statistic = 7.231 to 9.420, <i>p</i> < 0.05 & BH corrected). Among comorbid presentations, the additional presence of ADHD symptomatology was associated with significantly lower SampEn in every region of interest (<i>z</i> = -3.973 to -2.235, <i>p</i> < 0.05 & BH corrected).</p><p><strong>Conclusions and relevance: </strong>ADHD and ODD shared common impairments underlying the EF networks in the comorbid-free presentations, with ADHD showing more widespread complexity reduction. When ADHD co-occurred with other psychiatric disorders, the reduction in SampEn extended beyond the regions affected in comorbid-free ADHD, indicating that comorbidities amplify neural complexity deficits.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protocol and Statistical Analysis Plan for the Randomized Trial of Sedative Choice for Intubation (RSI).","authors":"Stephanie C DeMasi, Brant Imhoff, Ariel A Lewis, Kevin P Seitz, Brian E Driver, Kevin W Gibbs, Adit A Ginde, Stacy A Trent, Derek W Russell, Amelia L Muhs, Matthew E Prekker, John P Gaillard, Daniel Resnick-Ault, L Jane Stewart, Micah R Whitson, Graham W W Van Schaik, Aaron E Robinson, Jessica A Palakshappa, Neil R Aggarwal, Jason C Brainard, David J Douin, Carolynn Lyle, Sheetal Gandotra, Aaron J Lacy, Kristen C Sherlin, Greta K Carlson, J Maycee Cain, Brianne Redman, Carrie Higgins, Cori Withers, Logan L Beach, Barbara Gould, Jasmine McIntosh, Bradley D Lloyd, Tiffany L Israel, Li Wang, Todd W Rice, Wesley H Self, Jin H Han, Jonathan D Casey, Matthew W Semler","doi":"10.1101/2025.01.18.25320768","DOIUrl":"https://doi.org/10.1101/2025.01.18.25320768","url":null,"abstract":"<p><strong>Background: </strong>Emergency tracheal intubation is a common and high-risk procedure. Ketamine and etomidate are sedative medicines commonly used to induce anesthesia for emergency tracheal intubation, but whether the induction medication used affects patient outcomes is uncertain.</p><p><strong>Research question: </strong>Does the use of ketamine for induction of anesthesia decrease the incidence of death among adults undergoing emergency tracheal intubation, compared to the use of etomidate?</p><p><strong>Study design and methods: </strong>The Randomized trial of Sedative choice for Intubation (RSI) is a pragmatic, multicenter, unblinded, parallel-group, randomized trial being conducted in 14 sites (6 emergency departments and 8 intensive care units) in the United States. The trial compares ketamine vs etomidate for induction of anesthesia among 2,364 critically ill adults undergoing emergency tracheal intubation. The primary outcome is all-cause, 28-day in-hospital mortality. The secondary outcome is the incidence of cardiovascular collapse during intubation, a composite of hypotension, receipt of vasopressors, and cardiac arrest. Enrollment began on April 6, 2022, and is expected to conclude in 2025.</p><p><strong>Interpretation: </strong>The RSI trial will provide important data on the effects of ketamine vs etomidate on death and other outcomes for critically ill adults undergoing emergency tracheal intubation. Specifying the protocol and statistical analysis plan before the conclusion of enrollment increases the rigor, reproducibility, and interpretability of the trial.</p><p><strong>Trial registry: </strong>ClinicalTrials.gov ; No.: NCT05277896 ; URL: www.clinicaltrials.gov.</p><p><strong>Take-home points: </strong><b>Study Question:</b> Does use of ketamine for induction of anesthesia during emergency tracheal intubation decrease the incidence of death, compared with use of etomidate?<b>Results:</b> This manuscript describes the protocol and statistical analysis plan for the Randomized trial of Sedative choice for Intubation (RSI) comparing ketamine vs etomidate for induction of anesthesia for emergency tracheal intubation.<b>Interpretation:</b> Prespecifying the full statistical analysis plan before completion of enrollment increases rigor, reproducibility, and transparency of the trial results.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Household Air Pollution Exposures Over Pregnancy and Maternal Blood Pressure Trajectories through 8 Years Postpartum: Evidence from the Ghana Randomized Air Pollution and Health Study (GRAPHS).","authors":"Seyram Kaali, Michelle Li, Mohamed Nuhu Mujtaba, Elena Colicino, Sule Awuni, Blair Wylie, Musah Osei, Kholiswa Tsotetsi, Tawfiq Yussif, Steve Chillrud, Darby Jack, Kwaku Poku Asante, Alison Lee","doi":"10.1101/2025.01.17.25320752","DOIUrl":"10.1101/2025.01.17.25320752","url":null,"abstract":"<p><strong>Background: </strong>Household air pollution is a major contributor to cardiovascular disease burden in women in Sub-Saharan Africa. However, little is known about exposures during pregnancy or the effect of clean cooking interventions on postpartum blood pressure trajectories.</p><p><strong>Methods: </strong>The Ghana Randomized Air Pollution and Health Study (GRAPHS) randomized 1414 non-smoking women in the first and second trimesters to liquefied petroleum gas (LPG) or improved biomass stoves - vs control (traditional three-stone open fire). Personal exposure to carbon monoxide was measured at four prenatal timepoints and three times over the first postpartum year. Participants were prospectively followed with annual resting BP measurements at 2, 4, 5, 6, 7, and 8 years postpartum. We employed linear mixed effects models to determine effect of GRAPHS interventions on postpartum BP, and to examine associations between prenatal and postnatal CO and postpartum BP.</p><p><strong>Results: </strong>LPG intervention was associated with 3.54mmHg (95% CI -5.55, -1.53) lower change in systolic BP from enrolment through 8 years postpartum, and 2.27mmHg (95% CI -3.61, -0.93) lower change in diastolic BP from enrolment through 8 years postpartum, as compared to control. In exposure-response analysis, average prenatal CO was positively associated with change in systolic BP from enrolment (β=0.71mmHg, 95% CI 0.08, 1.30, per doubling of CO).</p><p><strong>Conclusions: </strong>LPG cookstove intervention initiated in early pregnancy and maintained through the first postpartum year was associated with lower systolic and diastolic BP trajectories through 8 years postpartum. These findings support the need to integrate clean cooking solutions into existing antenatal care packages.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-life infectious disease exposure, the 'hygiene hypothesis', and lifespan: evidence from hookworm.","authors":"Ralph Lawton","doi":"10.1101/2024.12.09.24318730","DOIUrl":"10.1101/2024.12.09.24318730","url":null,"abstract":"<p><p>Exposure to infectious disease in early life may have long-term ramifications for health and mortality. However, the ``hygiene hypothesis'' suggests reduced pathogen exposure may not be uniformly beneficial. This study leverages quasi-experimental variation from the Rockefeller Sanitary Commission's de-worming campaign in the early 20th century, combined with pre-campaign hookworm prevalence, to rigorously examine the impacts of childhood hookworm exposure on adult lifespan and morbidity. Pre-intervention surveys find widespread hookworm exposure among children in the American South, but minimal prevalence among adults, enabling separation of in-utero and childhood exposure. I show de-worming before age five leads to 2.5 additional months of life in a sample of adult mortality. Further, decreasing hookworm exposure is related to declines in biomarkers for inflammation and skin-tested allergies, in contrast with the predictions of the ``hygiene hypothesis''. Placebo tests using health outcomes that should not be affected by de-worming do not show similar patterns. Childhood de-worming leads to improvements in morbidity and mortality decades later.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}