tbuckley/cabot-search huggingface dataset:
Brain Waves Appear to Wash Out Waste During Sleep
Authors: Samantha Anderer
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Pain Exposure and Brain Connectivity in Preterm Infants
Authors: Thiviya Selvanathan, Steven Ufkes, Ting Guo, Vann Chau, Helen M. Branson, George M. Ibrahim, Linh G. Ly, Edmond N. Kelly, Ruth E. Grunau, Steven P. Miller
Journal: JAMA Network Open (2024)

Importance Early-life exposure to painful procedures has been associated with altered brain maturation and neurodevelopmental outcomes in preterm infants, although sex-specific differences are largely unknown. Objective To examine sex-specific associations among early-life pain exposure, alterations in neonatal structural connectivity, and 18-month neurodevelopment in preterm infants. Design, Setting, and Participants This prospective cohort study recruited 193 very preterm infants from April 1, 2015, to April 1, 2019, across 2 tertiary neonatal intensive care units in Toronto, Canada. Structural connectivity data were available for 150 infants; neurodevelopmental outcomes were available for 123 infants. Data were analyzed from January 1, 2022, to December 31, 2023. Exposure Pain was quantified in the initial weeks after birth as the total number of invasive procedures. Main Outcome and Measure Infants underwent early-life and/or term-equivalent-age magnetic resonance imaging with diffusion tensor imaging to quantify structural connectivity using graph theory measures and regional connection strength. Eighteen-month neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition. Stratifying by sex, generalized estimating equations were used to assess whether pain exposure modified the maturation of structural connectivity using an interaction term (early-life pain exposure × postmenstrual age [PMA] at scan). Generalized estimating equations were used to assess associations between structural connectivity and neurodevelopmental outcomes, adjusting for extreme prematurity and maternal education. Results A total of 150 infants (80 [53%] male; median [IQR] gestational age at birth, 27.1 [25.4-29.0] weeks) with structural connectivity data were analyzed. Sex-specific associations were found between early-life pain and neonatal brain connectivity in female infants only, with greater early-life pain exposure associated with slower maturation in global efficiency (pain × PMA at scan interaction P = .002) and local efficiency (pain × PMA at scan interaction P = .005). In the full cohort, greater pain exposure was associated with lower global efficiency (coefficient, −0.46; 95% CI, −0.78, to −0.15; P = .004) and local efficiency (coefficient, −0.57; 95% CI, −1.04 to −0.10; P = .02) and regional connection strength. Local efficiency (coefficient, 0.003; 95% CI, 0.001-0.004; P = .005) and regional connection strength in the striatum were associated with cognitive outcomes. Conclusions and Relevance In this cohort study of very preterm infants, greater exposure to early-life pain was associated with altered maturation of neonatal structural connectivity, particularly in female infants. Alterations in structural connectivity were associated with neurodevelopmental outcomes, with potential regional specificities.
Bringing Pediatric Chronic Critical Illness Into Acute Focus
Authors: Robert J. Graham
Journal: JAMA Network Open (2024)

Katherine E. Nelson, MD, PhD; Jingqin Zhu, MSc; Joanna Thomson, MD, MPH; Sanjay Mahant, MD, MSc; Kimberley Widger, PhD; Chris Feudtner, MD, PhD, MPH; Eyal Cohen, MD, MSc; Eleanor Pullenayegum, PhD; James A. Feinstein, MD, MPH
Recurrent Intensive Care Episodes and Mortality Among Children With Severe Neurologic Impairment
Authors: Katherine E. Nelson, Jingqin Zhu, Joanna Thomson, Sanjay Mahant, Kimberley Widger, Chris Feudtner, Eyal Cohen, Eleanor Pullenayegum, James A. Feinstein
Journal: JAMA Network Open (2024)

Importance Children requiring care in a pediatric intensive care unit (PICU) are known to have increased risk of subsequent mortality. Children with severe neurologic impairment (SNI)—who carry neurologic or genetic diagnoses with functional impairments and medical complexity—are frequently admitted to PICUs. Although recurrent PICU critical illness episodes (PICU-CIEs) are assumed to indicate a poor prognosis, the association between recurrent PICU-CIEs and mortality in this patient population is poorly understood. Objective To assess the association between number of recent PICU-CIEs and survival among children with severe neurologic impairment. Design, Setting, and Participants This population-based retrospective cohort study used health administrative data from April 1, 2002, to March 31, 2020, on 4774 children born between 2002 and 2019 with an SNI diagnosis code in an Ontario, Canada, hospital record before 16 years of age and a first PICU-CIE from 2002 to 2019. Data were analyzed from November 2021 to June 2023. Exposure Pediatric intensive care unit critical illness episodes (excluding brief postoperative PICU admissions). Main Outcome and Measures One-year survival conditioned on the number and severity (length of stay &amp;amp;gt;15 days or use of invasive mechanical ventilation) of PICU-CIEs in the preceding year. Results In Ontario, 4774 children with SNI (mean [SD] age, 2.1 [3.6] months; 2636 [55.2%] &amp;amp;lt;1 year of age; 2613 boys [54.7%]) were discharged alive between 2002 and 2019 after their first PICU-CIE. Ten-year survival after the initial episode was 81% (95% CI, 79%-82%) for children younger than 1 year of age and 84% (95% CI, 82%-86%) for children 1 year of age or older; the age-stratified curves converged by 15 years after the initial episode at 79% survival (95% CI, 78%-81% for children &amp;amp;lt;1 year and 95% CI, 75%-84% for children ≥1 year). Adjusted for age category and demographic factors, the presence of nonneurologic complex chronic conditions (adjusted hazard ratio [AHR], 1.70 [95% CI, 1.43-2.02]) and medical technology assistance (AHR, 2.32 [95% CI, 1.92-2.81]) were associated with increased mortality. Conditional 1-year mortality was less than 20% regardless of number or severity of recent PICU-CIEs. Among children with high-risk PICU-CIEs, 1-year conditional survival decreased from 90% (95% CI, 89%-91%) after the first PICU-CIE to 81% (95% CI, 77%-86%) after the fourth PICU-CIE. Conclusions and Relevance This cohort study of children with SNI demonstrated a modest dose-dependent association between PICU-CIEs and short-term mortality. These data did not support the conventional wisdom that recurrent PICU admissions are associated with subsequent high mortality risk.
Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
Authors: Nicolas Anselmino, Estefania Labanca, Peter D.A. Shepherd, Jiabin Dong, Jun Yang, Xiaofei Song, Subhiksha Nandakumar, Ritika Kundra, Cindy Lee, Nikolaus Schultz, Jianhua Zhang, John C. Araujo, Ana M. Aparicio, Sumit K. Subudhi, Paul G. Corn, Louis L. Pisters, John F. Ward, John W. Davis, Elba S. Vazquez, Geraldine Gueron, Christopher J. Logothetis, Andrew Futreal, Patricia Troncoso, Yu Chen, Nora M. Navone
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer models. This initiative builds on the rich MD Anderson (MDA) prostate cancer (PCa) patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal prostate cancer. Experimental Design: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids. The cohort includes models derived from different morphologic groups, disease states, and involved organ sites (including circulating tumor cells), as well as paired samples representing heterogeneity or stages before and after therapy. Results: The cohort recapitulates clinically reported alterations in prostate cancer genes, providing a data resource for clinical and molecular interrogation of suitable experimental models. Paired samples displayed conserved molecular alteration profiles, suggesting the relevance of other regulatory mechanisms (e.g., epigenomic) influenced by the microenvironment and/or treatment. Transcriptomically, models were grouped on the basis of morphologic classification. DNA damage response–associated mechanisms emerged as differentially regulated between adenocarcinoma and neuroendocrine prostate cancer in a cross-interrogation of PDX/patient datasets. Conclusions: We addressed the gap in clinically relevant prostate cancer models through comprehensive molecular characterization of MDA PCa PDXs, providing a discovery platform that integrates with patient data and benchmarked to therapeutically relevant consensus clinical groupings. This unique resource supports robust hypothesis generation and testing from basic, translational, and clinical perspectives.
Neovaginal Human Papilloma Virus–Related Squamous Cell Carcinoma in a Transgender Woman
Authors: Susan M. Lang, Ravali A. Reddy, Malte Renz
Journal: JAMA Network Open (2024)

This case series discusses a human papilloma virus (HPV)–related neovaginal squamous cell carcinoma in a transgender woman and the need for formal gynecologic screening recommendations.
Cannabis Use Linked to Elevated Myocardial Infarction and Stroke Risk
Authors: Samantha Anderer
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Josephine K. Dermawan, Sarah Chiang, Samuel Singer, Bhumika Jadeja, Martee L. Hensley, William D. Tap, Sujana Movva, Robert G. Maki, Cristina R. Antonescu
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Leiomyosarcomas (LMS) are clinically and molecularly heterogeneous tumors. Despite recent large-scale genomic studies, current LMS risk stratification is not informed by molecular alterations. We propose a clinically applicable genomic risk stratification model. Experimental Design: We performed comprehensive genomic profiling in a cohort of 195 soft tissue LMS (STLMS), 151 primary at presentation, and a control group of 238 uterine LMS (ULMS), 177 primary at presentation, with at least 1-year follow-up. Results: In STLMS, French Federation of Cancer Centers (FNCLCC) grade but not tumor size predicted progression-free survival (PFS) or disease-specific survival (DSS). In contrast, in ULMS, tumor size, mitotic rate, and necrosis were associated with inferior PFS and DSS. In STLMS, a 3-tier genomic risk stratification performed well for DSS: high risk: co-occurrence of RB1 mutation and chr12q deletion (del12q)/ATRX mutation; intermediate risk: presence of RB1 mutation, ATRX mutation, or del12q; low risk: lack of any of these three alterations. The ability of RB1 and ATRX alterations to stratify STLMS was validated in an external AACR GENIE cohort. In ULMS, a 3-tier genomic risk stratification was significant for both PFS and DSS: high risk: concurrent TP53 mutation and chr20q amplification/ATRX mutations; intermediate risk: presence of TP53 mutation, ATRX mutation, or amp20q; low risk: lack of any of these three alterations. Longitudinal sequencing showed that most molecular alterations were early clonal events that persisted during disease progression. Conclusions: Compared with traditional clinicopathologic models, genomic risk stratification demonstrates superior prediction of clinical outcome in STLMS and is comparable in ULMS.
Rintatolimod in Advanced Pancreatic Cancer Enhances Antitumor Immunity through Dendritic Cell–Mediated T-Cell Responses
Authors: Casper W.F. van Eijck, Hassana el Haddaoui, Songul Kucukcelebi, Disha Vadgama, Amine Fellah, Dana A.M. Mustafa, Joachim G.J.V. Aerts, Casper H.J. van Eijck, Marcella Willemsen
Journal: Clinical Cancer Research (2024)

Amid the need for new approaches to improve survival in pancreatic ductal adenocarcinoma (PDAC), immune-based therapies have garnered interest. Rintatolimod, a Toll-like receptor 3 (TLR-3) agonist, is a potential candidate due to its dual impact on restraining PDAC cell functions and boosting the antitumor immune response. This study investigates the effect of TLR-3 activation through rintatolimod on the peripheral immune landscape of patients with advanced PDAC.
Recognition of Genetic Conditions After Learning With Images Created Using Generative Artificial Intelligence
Authors: Rebekah L. Waikel, Amna A. Othman, Tanviben Patel, Suzanna Ledgister Hanchard, Ping Hu, Cedrik Tekendo-Ngongang, Dat Duong, Benjamin D. Solomon
Journal: JAMA Network Open (2024)

Importance The lack of standardized genetics training in pediatrics residencies, along with a shortage of medical geneticists, necessitates innovative educational approaches. Objective To compare pediatric resident recognition of Kabuki syndrome (KS) and Noonan syndrome (NS) after 1 of 4 educational interventions, including generative artificial intelligence (AI) methods. Design, Setting, and Participants This comparative effectiveness study used generative AI to create images of children with KS and NS. From October 1, 2022, to February 28, 2023, US pediatric residents were provided images through a web-based survey to assess whether these images helped them recognize genetic conditions. Interventions Participants categorized 20 images after exposure to 1 of 4 educational interventions (text-only descriptions, real images, and 2 types of images created by generative AI). Main Outcomes and Measures Associations between educational interventions with accuracy and self-reported confidence. Results Of 2515 contacted pediatric residents, 106 and 102 completed the KS and NS surveys, respectively. For KS, the sensitivity of text description was 48.5% (128 of 264), which was not significantly different from random guessing (odds ratio [OR], 0.94; 95% CI, 0.69-1.29; P = .71). Sensitivity was thus compared for real images vs random guessing (60.3% [188 of 312]; OR, 1.52; 95% CI, 1.15-2.00; P = .003) and 2 types of generative AI images vs random guessing (57.0% [212 of 372]; OR, 1.32; 95% CI, 1.04-1.69; P = .02 and 59.6% [193 of 324]; OR, 1.47; 95% CI, 1.12-1.94; P = .006) (denominators differ according to survey responses). The sensitivity of the NS text-only description was 65.3% (196 of 300). Compared with text-only, the sensitivity of the real images was 74.3% (205 of 276; OR, 1.53; 95% CI, 1.08-2.18; P = .02), and the sensitivity of the 2 types of images created by generative AI was 68.0% (204 of 300; OR, 1.13; 95% CI, 0.77-1.66; P = .54) and 71.0% (247 of 328; OR, 1.30; 95% CI, 0.92-1.83; P = .14). For specificity, no intervention was statistically different from text only. After the interventions, the number of participants who reported being unsure about important diagnostic facial features decreased from 56 (52.8%) to 5 (7.6%) for KS ( P &amp;amp;lt; .001) and 25 (24.5%) to 4 (4.7%) for NS ( P &amp;amp;lt; .001). There was a significant association between confidence level and sensitivity for real and generated images. Conclusions and Relevance In this study, real and generated images helped participants recognize KS and NS; real images appeared most helpful. Generated images were noninferior to real images and could serve an adjunctive role, particularly for rare conditions.
Assessing robustness to worst case publication bias using a simple subset meta-analysis
Authors: Maya B Mathur
Journal: BMJ (2024)

This article discusses a simple method, known as a meta-analysis of non-affirmative studies, to assess how robust a meta-analysis is to publication bias that favors affirmative studies (studies with significant P values and point estimates in the desired direction) over non-affirmative studies (studies with non-significant P values or point estimates in the undesired direction). This method is a standard meta-analysis that includes only non-affirmative studies. The resulting meta-analytical estimate corrects for worst case publication bias, a hypothetical scenario in which affirmative studies are almost infinitely more likely to be published than non-affirmative studies. If this estimate remains in the same direction as the uncorrected estimate and is of clinically meaningful size, this suggests that the meta-analysis conclusions would not be overturned by any amount of publication bias favoring affirmative studies. Meta-analysis of non-affirmative studies complements an uncorrected meta-analysis and other publication bias analyses by accommodating small meta-analyses, non-normal effects, heterogeneous effects across studies, and additional forms of selective reporting (in particular, P-hacking).
Sobering assessment of Scotland’s NHS
Authors: Gerry McCartney, Neil Craig
Journal: BMJ (2024)

Audit Scotland's latest report on the Scottish NHS is sobering reading. 1 It highlights costs rising due to inflation, higher utility costs, and pay and prescribing pressures; demand for services rising faster than activity post-pandemic; and operational challenges impacting on patient safety and experience.It concludes that, without reform, the future financial sustainability of NHS services is in doubt.It calls for investment in prevention to address the causes of ill-health, and the development of a clear national strategy for health and social care.Without this, according to Audit Scotland, long-term planning will be more difficult for NHS Boards. 1
Clinicians Who Practice Primarily in Nursing Homes and the Quality of End-of-Life Care Among Residents
Authors: Arnab K. Ghosh, Mark Aaron Unruh, Hyunkyung Yun, Hye-Young Jung
Journal: JAMA Network Open (2024)

Importance Clinician specialization in the care of nursing home (NH) residents or patients in skilled nursing facilities (SNFs) has become increasingly common. It is not known whether clinicians focused on NH care, often referred to as SNFists (ie, physicians, nurse practitioners, and physician assistants concentrating their practice in the NH or SNF setting), are associated with a reduced likelihood of burdensome transitions in the last 90 days of life for residents, which are a marker of poor-quality end-of-life (EOL) care. Objective To quantify the association between receipt of care from an SNFist and quality of EOL care for NH residents. Design, Setting, and Participants This cohort study analyzed Medicare fee-for-service claims for a nationally representative 20% sample of beneficiaries to examine burdensome transitions among NH decedents at the EOL from January 1, 2013, through December 31, 2019. Statistical analyses were conducted from December 2022 to June 2023. Exposure Receipt of care from an SNFist, defined as physicians and advanced practitioners who provided 80% or more of their evaluation and management visits in NHs annually. Main Outcomes and Measures This study used augmented inverse probability weighting in analyses of Medicare fee-for-service claims for a nationally representative 20% sample of beneficiaries. Main outcomes included 4 measures of burdensome transitions: (1) hospital transfer in the last 3 days of life; (2) lack of continuity in NHs after hospitalization in the last 90 days of life; (3) multiple hospitalizations in the last 90 days of life for any reason or any hospitalization for pneumonia, urinary tract infection, dehydration, or sepsis; and (4) any hospitalization in the last 90 days of life for an ambulatory care–sensitive condition. Results Of the 2 091 954 NH decedents studied (mean [SD] age, 85.4 [8.5] years; 1 470 724 women [70.3%]), 953 722 (45.6%) received care from SNFists and 1 138 232 (54.4%) received care from non-SNFists; 422 575 of all decedents (20.2%) experienced a burdensome transition at the EOL. Receipt of care by an SNFist was associated with a reduced risk of (1) hospital transfer in the last 3 days of life (−1.6% [95% CI, −2.5% to −0.8%]), (2) lack of continuity in NHs after hospitalization (−4.8% [95% CI, −6.7% to −3.0%]), and (3) decedents experiencing multiple hospitalizations for any reason or any hospitalization for pneumonia, urinary tract infection, dehydration, or sepsis (−5.8% [95% CI, −10.1% to −1.7%]). There was not a statistically significant association with the risk of hospitalization for an ambulatory care–sensitive condition in the last 90 days of life (0.0% [95% CI, −14.7% to 131.7%]). Conclusions and Relevance This study suggests that SNFists may be an important resource to improve the quality of EOL care for NH residents.