medRxiv : the preprint server for health sciences最新文献

{"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}

{"title":"Recipient Cells Are the Source of Hematologic Malignancies After Graft Failure and Mixed Chimerism in Adults with SCD.","authors":"Mohamed A E Ali, Emily M Limerick, Matthew M Hsieh, Kalpana Upadhyaya, Xin Xu, Oswald Phang, Jean Pierre Kambala Mukendi, Katherine R Calvo, Maria Lopez-Ocasio, Pradeep Dagur, Courtney D Fitzhugh","doi":"10.1101/2025.01.17.25320670","DOIUrl":"10.1101/2025.01.17.25320670","url":null,"abstract":"<p><p>Non-myeloablative hematopoietic cell transplantation (HCT) is a curative option for individuals with sickle cell disease (SCD). Our traditional goal with this approach has been to achieve a state of mixed donor/recipient chimerism. Recently, we reported an increased risk of hematologic malignancies (HMs) in adults with SCD following graft failure or mixed chimerism. To evaluate the origin of HMs, we performed chimerism analyses of 5 patients with SCD who developed HMs after non-myeloablative HCT. DNA was extracted from sorted peripheral blood or bone marrow cells representing mature cell lineages or leukemic blasts and subjected to chimerism analysis by PCR amplification of polymorphic short tandem repeats. Unlike mature cell lineages in patients with mixed chimerism, which still showed a donor-derived fraction of cells, leukemic blast cells were found to be 99-100% recipient-derived in all patients. Non-myeloablative conditioning allows for the survival of patients' cells that might harbor pre-leukemic clones that possess the capacity to evolve under genotoxic or environmental stress into malignancies; therefore, we have modified our HCT protocols with the goal of full donor chimerism to mitigate the risk of HM development.</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/PMC11759619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049292","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":"Computable Phenotypes for Respiratory Viral Infections in the <i>All of Us</i> Research Program.","authors":"Bennett J Waxse, Fausto Andres Bustos Carrillo, Tam C Tran, Huan Mo, Emily E Ricotta, Joshua C Denny","doi":"10.1101/2025.01.17.25320744","DOIUrl":"10.1101/2025.01.17.25320744","url":null,"abstract":"<p><p>Electronic health records (EHRs) contain rich temporal data about infectious diseases, but an optimal approach to identify infections remains undefined. Using the <i>All of Us</i> Research Program, we developed computable phenotypes for respiratory viruses by integrating billing codes, prescriptions, and laboratory results within 90-day episodes. Phenotypes computed from 265,222 participants yielded cohorts ranging from 238 (adenovirus) to 28,729 (SARS-CoV-2) cases. Virus-specific billing codes showed varied sensitivity (8-67%) and high positive predictive value (90-97%), except for influenza virus and SARS-CoV-2 where lower PPV (69-70%) improved with increasing billing codes. Identified infections exhibited expected seasonal patterns and virus proportions when compared with CDC data. This integrated approach identified episodic disease more effectively than individual components alone and demonstrated utility in identifying severe infections. The method enables large-scale studies of host genetics, health disparities, and clinical outcomes across episodic diseases.</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/PMC11759596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049053","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":"Physical therapists' perceptions of telerehabilitation for patients with musculoskeletal conditions in a post-pandemic world.","authors":"Kevin McLaughlin, Kate I Minick, Julie M Fritz, Nicole Tannahill, Anne Spar, Marissa Feinsilver, Matthew Weber, Erika Opoku, Jeff Adams, Richard L Skolasky","doi":"10.1101/2025.01.17.25320739","DOIUrl":"10.1101/2025.01.17.25320739","url":null,"abstract":"<p><strong>Objective: </strong>To examine physical therapists' experience providing telerehabilitation and their perceptions of telerehabilitation for patients with musculoskeletal conditions.</p><p><strong>Methods: </strong>Survey of members of the Academy of Orthopaedic Physical Therapy.</p><p><strong>Results: </strong>We received 208 completed responses to our survey invitation. Most physical therapists responding to our survey reported using little to no telerehabilitation prior to the pandemic but increased use during the pandemic, followed by decreased use of telerehabilitation after the pandemic. Respondents reported using telerehabilitation slightly more after the pandemic than beforehand. Physical therapists reported that they believed they could deliver effective care using telerehabilitation but that it was not as effective as in-clinic care and they would prefer to use telerehabilitation as part of a hybrid care model versus using only telerehabilitation. Physical therapists suggested that certain patients were more likely than others to benefit from telerehabilitation and identified specific factors (e.g., patient preference, self-efficacy, postoperative status) that influenced whom they would consider to be most appropriate for telerehabilitation. \"Patient issues with technology\" was identified as the most common barrier to telerehabilitation use. Most physical therapists reported that they planned to use telerehabilitation in the future and agreed that telerehabilitation plays an important role in expanding access to physical therapy in the United States.</p><p><strong>Conclusions: </strong>Physical therapists believed that telerehabilitation continues to play an important role in a post-pandemic world. Although physical therapists reported that they considered telerehabilitation to be an effective method for delivering care, they did not consider it to be a replacement for in-clinic care and believed that certain patients are more likely than others to benefit from this approach.</p><p><strong>Impact statement: </strong>Physical therapists consider telerehabilitation to be a viable care option for patients with musculoskeletal pain.</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/PMC11759599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049271","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":"Prediction-powered Inference for Clinical Trials.","authors":"Pierre-Emmanuel Poulet, Maylis Tran, Sophie Tezenas du Montcel, Bruno Dubois, Stanley Durrleman, Bruno Jedynak","doi":"10.1101/2025.01.15.25320578","DOIUrl":"https://doi.org/10.1101/2025.01.15.25320578","url":null,"abstract":"<p><p>Prediction-powered inference (PPI) [1] and its subsequent development called PPI++ [2] provide a novel approach to standard statistical estimation leveraging machine learning systems to enhance unlabeled data with predictions. We use this paradigm in clinical trials. The predictions are provided by disease progression models, providing prognostic scores for all the participants as a function of baseline covariates. The proposed method would empower clinical trials by providing untreated digital twins of the treated patients while remaining statistically valid. The potential implications of this new estimator of the treatment effect in a two-arm randomized clinical trial (RCT) are manifold. First, it leads to an overall reduction of the sample size required to reach the same power as a standard RCT. Secondly, it advocates for an imbalance of controls and treated patients, requiring fewer controls to achieve the same power. Finally, this technique directly transfers any disease prediction model trained on large cohorts to practical and scientifically valid use. In this paper, we demonstrate the theoretical properties of this estimator and illustrate them through simulations. We show that it is asymptotically unbiased for the Average Treatment Effect and derive an explicit formula for its variance. An application to an Alzheimer's disease clinical trial showcases the potential to reduce the sample size.</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/PMC11759613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049277","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":"Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia.","authors":"Noreen Bukhari-Parlakturk, Patrick J Mulcahey, Michael W Lutz, Rabia Ghazi, Ziping Huang, Moritz Dannhauer, Pichet Termsarasab, Burton Scott, Zeynep B Simsek, Skylar Groves, Mikaela Lipp, Michael Fei, Tiffany K Tran, Eleanor Wood, Lysianne Beynel, Chris Petty, James T Voyvodic, Lawrence G Appelbaum, Hussein R Al-Khalidi, Simon W Davis, Andrew M Michael, Angel V Peterchev, Nicole Calakos","doi":"10.1101/2024.09.30.24314652","DOIUrl":"https://doi.org/10.1101/2024.09.30.24314652","url":null,"abstract":"<p><strong>Background: </strong>Writer's cramp (WC) dystonia is an involuntary movement disorder with distributed abnormalities in the brain's motor network. Prior studies established the potential for repetitive transcranial magnetic stimulation (rTMS) to either premotor cortex (PMC) or primary somatosensory cortex (PSC) to modify symptoms. However, clinical effects have been modest with limited understanding of the neural mechanisms hindering therapeutic advancement of this promising approach.</p><p><strong>Objective: </strong>This study aimed to understand the motor network effects of rTMS in WC that correspond with behavioral efficacy. We hypothesized that behavioral efficacy is associated with modulation of cortical and subcortical regions of the motor network.</p><p><strong>Methods: </strong>In a double-blind, cross-over design, twelve WC participants underwent rTMS in one of three conditions (Sham-TMS, 10 Hz PSC-rTMS, 10 Hz PMC-rTMS) while engaged in a writing task to activate dystonic movements and measure writing fluency. Brain connectivity was evaluated using task-based fMRI after each TMS session.</p><p><strong>Results: </strong>10 Hz rTMS to PSC, but not PMC, significantly improved writing dysfluency. PSC-TMS also significantly weakened cortico-basal ganglia, cortico-cerebellum, and intra-cerebellum functional connectivity (FC), and strengthened striatal FC relative to Sham. Changes in PSC and SPC BOLD activity were associated with reduced dysfluent writing behavior.</p><p><strong>Conclusions: </strong>10 Hz rTMS to PSC improved writing dysfluency by redistributing motor network connectivity and strengthening somatosensory-parietal connectivity. A key signature for effective stimulation at PSC and improvement in writing dysfluency may be strengthening of intra-cortical connectivity between primary somatosensory and superior parietal cortices. These findings offer mechanistic hypotheses to advance the therapeutic application of TMS for dystonia.</p><p><strong>Highlights: </strong>10 Hz repetitive TMS to somatosensory cortex reduces writing dysfluency in dystoniaIncreased somatosensory cortex activity correlates with reduced writing dysfluencyIn dystonia + sham-TMS, writing dysfluency correlates with cerebellar connectivity.10 Hz rTMS to somatosensory cortex induces reorganization of the motor network.</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/PMC11759594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049223","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 Secondary Analysis Suggests That Repetitive Transcranial Magnetic Stimulation Applied to the Left Dorsolateral Prefrontal Cortex Reduces Cue-Induced-Craving in Treatment Seeking Participants with Cannabis Use Disorder.","authors":"Brendan L Wong, Bohye Kim, Manpreet K Singh, Jane P Kim, Aimee L McRae-Clark, Gregory L Sahlem","doi":"10.1101/2025.01.16.25320690","DOIUrl":"10.1101/2025.01.16.25320690","url":null,"abstract":"<p><strong>Background: </strong>Studies across multiple addictions have suggested that repetitive transcranial magnetic stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (L-DLPFC) reduces cue-induced-craving (CIC), however there are no studies in treatment seeking participants with cannabis use disorder (CUD). In this secondary analysis of a previously completed trial, we explore whether a multi-session course of rTMS reduces CIC in CUD.</p><p><strong>Methods: </strong>Seventy-one participants with ≥moderate CUD (age=30.2±9.9;37.5% female) were randomized to twenty sessions of active or sham rTMS applied to the left DLPFC (20-sessions, Beam-F3; 10Hz) in a two-site, double-blind, sham-controlled, phase-2 trial where they also received motivational enhancement therapy. Participants rated their craving for cannabis via the short-form of the marijuana craving questionnaire (MCQ-SF) before and after a neutral and cannabis-cue presentation. Participants underwent assessment before (immediate-pre), after (immediate-post), and two-, and four- weeks following the course of rTMS.</p><p><strong>Results: </strong>The MCQ-SF scores increased following the presentation of cannabis cues relative to neutral cues at the immediate-pre timepoint in both treatment groups (<i>p</i><0.0001). Following study treatment, the percent increase in MCQ-SF following cues diverged between the active and sham groups with significantly reduced CIC in the active group at the two-week post time-point (5.8±7.1% sham group, 0.91±4.1% active group; <i>p</i>=0.02). Between-group effect sizes (Cohen's d) were 0.24, 0.89, and 0.67 at the immediate-post, 2-week, and 4-week follow-up periods respectively.</p><p><strong>Conclusions: </strong>L-DLPFC applied rTMS may reduce CIC in treatment seeking participants with CUD.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049127","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":"Immune-sensitization to <i>Mycobacterium tuberculosis</i> Among Young Children With and Without Tuberculosis.","authors":"Jesús Gutierrez, LaShaunda L Malone, Mitchka Mohammadi, John Mukisa, Michael Atuhairwe, Simon Peter G Mwesigwa, Salome Athieno, Sharon Buwule, Faith Ameda, Sophie Kiyingi, Ezekiel Mupere, Catherine M Stein, Christina L Lancioni","doi":"10.1101/2025.01.16.25320625","DOIUrl":"https://doi.org/10.1101/2025.01.16.25320625","url":null,"abstract":"<p><strong>Background: </strong>Identification of young children with <i>Mycobacterium tuberculosis</i> ( <i>Mtb</i> )-infection is critical to curb Tuberculosis (TB)-related pediatric morbidity and mortality. The optimal test to identify young children with evidence of <i>Mtb</i> -infection remains controversial.</p><p><strong>Methods: </strong>Using a TB household contact (HHC) study design among 130 Ugandan children less than 5 years with established <i>Mtb</i> -exposure, we compared the usefulness of the tuberculin skin test (TST) and QuantiFERON Gold Plus (QFT-Plus) to identify children with evidence for <i>Mtb</i> -sensitization. We conducted univariate analysis to compare findings between children with and without TB disease, and performed a logistic regression model to estimate the odds of TB. We performed a sensitivity analysis by stratifying results by age (< 2 years vs. 2-5 years). Finally, we compared results of the QFT-Plus TB tube 1 and TB tube 2 to establish concordance.</p><p><strong>Results: </strong>A 5 mm TST threshold identified the most children with evidence of <i>Mtb</i> -sensitization; this result was most pronounced in children with TB. Moreover, the odds of TB were 2 times higher [aOR: 2.09 (CI: 1.02 - 4.37)] among children with a positive TST. The QFT-Plus' TB tube 1 and TB tube 2 results were highly correlated.</p><p><strong>Conclusions: </strong>TST identified more TB-exposed young children with evidence of <i>Mtb-</i> immune-sensitization, when compared to QFT-Plus. These findings are highly relevant for children who are TB HHCs in endemic settings, and most at risk for TB following an exposure. We recommend that TST testing continue to be performed to assess for <i>Mtb</i> -sensitization in young children.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048500","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}