tbuckley/cabot-search huggingface dataset:
Caring for Hospitalized Adults With Opioid Use Disorder in the Era of Fentanyl
Authors: Honora Englander, Ashish P. Thakrar, Sarah M. Bagley, Theresa Rolley, Kathryn Dong, Elaine Hyshka
Journal: JAMA Internal Medicine (2024)

Importance The rise of fentanyl and other high-potency synthetic opioids across US and Canada has been associated with increasing hospitalizations and unprecedented overdose deaths. Hospitalization is a critical touchpoint to engage patients and offer life-saving opioid use disorder (OUD) care when admitted for OUD or other medical conditions. Observations Clinical best practices include managing acute withdrawal and pain, initiating medication for OUD, integrating harm reduction principles and practices, addressing in-hospital substance use, and supporting hospital-to-community care transitions. Fentanyl complicates hospital OUD care. Fentanyl’s high potency intensifies pain, withdrawal, and cravings and increases the risk for overdose and other harms. Fentanyl’s unique pharmacology has rendered traditional techniques for managing opioid withdrawal and initiating buprenorphine and methadone inadequate for some patients, necessitating novel strategies. Further, co-use of opioids with stimulants drugs is common, and the opioid supply is unpredictable and can be contaminated with benzodiazepines, xylazine, and other substances. To address these challenges, clinicians are increasingly relying on emerging practices, such as low-dose buprenorphine initiation with opioid continuation, rapid methadone titration, and the use of alternative opioid agonists. Hospitals must also reconsider conventional approaches to in-hospital substance use and expand clinicians’ understanding and embrace of harm reduction, which is a philosophy and set of practical strategies that supports people who use drugs to be safer and healthier without judgment, coercion, or discrimination. Hospital-to-community care transitions should ensure uninterrupted access to OUD care after discharge, which requires special consideration and coordination. Finally, improving hospital-based addiction care requires dedicated infrastructure and expertise. Preparing hospitals across the US and Canada to deliver OUD best practices requires investments in clinical champions, staff education, leadership commitment, community partnerships, quality metrics, and financing. Conclusions and Relevance The findings of this review indicate that fentanyl creates increased urgency and new challenges for hospital OUD care. Hospital clinicians and systems have a central role in addressing the current drug crisis.
Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer
Authors: Wendy Y. Chen, Karla V. Ballman, Ann H. Partridge, Olwen M. Hahn, Frederick M. Briccetti, William J. Irvin, Banu Symington, Kala Visvanathan, Paula R. Pohlmann, Thomas H. Openshaw, Anna Weiss, Eric P. Winer, Lisa A. Carey, Michelle D. Holmes
Journal: JAMA (2024)

Importance Observational studies of survivors of breast cancer and prospective trials of aspirin for cardiovascular disease suggest improved breast cancer survival among aspirin users, but prospective studies of aspirin to prevent breast cancer recurrence are lacking. Objective To determine whether aspirin decreases the risk of invasive cancer events among survivors of breast cancer. Design, Setting, and Participants A011502, a phase 3, randomized, placebo-controlled, double-blind trial conducted in the United States and Canada with 3020 participants who had high-risk nonmetastatic breast cancer, enrolled participants from 534 sites from January 6, 2017, through December 4, 2020, with follow-up to March 4, 2023. Interventions Participants were randomized (stratified for hormone receptor status [positive vs negative], body mass index [≤30 vs &amp;amp;gt;30], stage II vs III, and time since diagnosis [&amp;amp;lt;18 vs ≥18 months]) to receive 300 mg of aspirin (n = 1510) or placebo once daily (n = 1510) for 5 years. Main Outcomes and Measures The primary outcome was invasive disease–free survival. Overall survival was a key secondary outcome. Results A total of 3020 participants were randomized when the data and safety monitoring committee recommended suspending the study at the first interim analysis because the hazard ratio had crossed the prespecified futility bound. By median follow-up of 33.8 months (range, 0.1-72.6 months), 253 invasive disease–free survival events were observed (141 in the aspirin group and 112 in the placebo group), yielding a hazard ratio of 1.27 (95% CI, 0.99-1.63; P = .06). All invasive disease–free survival events, including death, invasive progression (both distant and locoregional), and new primary events, were numerically higher in the aspirin group, although the differences were not statistically significant. There was no difference in overall survival (hazard ratio, 1.19; 95% CI, 0.82-1.72). Rates of grades 3 and 4 adverse events were similar in both groups. Conclusion and Relevance Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. Despite its promise and wide availability, aspirin should not be recommended as an adjuvant breast cancer treatment. Trial Registration ClinicalTrials.gov Identifier: NCT02927249
Vascular disease persistence in giant cell arteritis: are stromal cells neglected?
Authors: Maira Karabayas, Hafeez E Ibrahim, Anke J Roelofs, Gary Reynolds, Dana Kidder, Cosimo De Bari
Journal: Annals of the Rheumatic Diseases (2024)

Giant cell arteritis (GCA), the most common systemic vasculitis, is characterised by aberrant interactions between infiltrating and resident cells of the vessel wall. Ageing and breach of tolerance are prerequisites for GCA development, resulting in dendritic and T-cell dysfunction. Inflammatory cytokines polarise T-cells, activate resident macrophages and synergistically enhance vascular inflammation, providing a loop of autoreactivity. These events originate in the adventitia, commonly regarded as the biological epicentre of the vessel wall, with additional recruitment of cells that infiltrate and migrate towards the intima. Thus, GCA-vessels exhibit infiltrates across the vascular layers, with various cytokines and growth factors amplifying the pathogenic process. These events activate ineffective repair mechanisms, where dysfunctional vascular smooth muscle cells and fibroblasts phenotypically shift along their lineage and colonise the intima. While high-dose glucocorticoids broadly suppress these inflammatory events, they cause well known deleterious effects. Despite the emerging targeted therapeutics, disease relapse remains common, affecting >50% of patients. This may reflect a discrepancy between systemic and local mediators of inflammation. Indeed, temporal arteries and aortas of GCA-patients can show immune-mediated abnormalities, despite the treatment induced clinical remission. The mechanisms of persistence of vascular disease in GCA remain elusive. Studies in other chronic inflammatory diseases point to the fibroblasts (and their lineage cells including myofibroblasts) as possible orchestrators or even effectors of disease chronicity through interactions with immune cells. Here, we critically review the contribution of immune and stromal cells to GCA pathogenesis and analyse the molecular mechanisms by which these would underpin the persistence of vascular disease.
EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer. Part II—2024 Update: Treatment of Relapsing and Metastatic Prostate Cancer
Authors: Derya Tilki, Roderick C.N. van den Bergh, Erik Briers, Thomas Van den Broeck, Oliver Brunckhorst, Julie Darraugh, Daniel Eberli, Gert De Meerleer, Maria De Santis, Andrea Farolfi, Giorgio Gandaglia, Silke Gillessen, Nikolaos Grivas, Ann M. Henry, Michael Lardas, Geert J.L.H. van Leenders, Matthew Liew, Estefania Linares Espinos, Jan Oldenburg, Inge M. van Oort, Daniela E. Oprea-Lager, Guillaume Ploussard, Matthew J. Roberts, Olivier Rouvière, Ivo G. Schoots, Natasha Schouten, Emma J. Smith, Johan Stranne, Thomas Wiegel, Peter-Paul M. Willemse, Philip Cornford
Journal: European Urology (2024)
A measles and rubella vaccine microneedle patch in The Gambia: a phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial
Authors: Ikechukwu Adigweme, Mohammed Yisa, Michael Ooko, Edem Akpalu, Andrew Bruce, Simon Donkor, Lamin B Jarju, Baba Danso, Anthony Mendy, David Jeffries, Anne Segonds-Pichon, Abdoulie Njie, Stephen Crooke, Elina El-Badry, Hilary Johnstone, Michael Royals, James L Goodson, Mark R Prausnitz, Devin V McAllister, Paul A Rota, Sebastien Henry, Ed Clarke
Journal: The Lancet (2024)

Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children.
Characterizing Important Dietary Exposure Sources of Perfluoroalkyl Acids in Inuit Youth and Adults in Nunavik Using a Feature Selection Tool
Authors: Amira Aker, Vy Nguyen, Pierre Ayotte, Sylvie Ricard, Mélanie Lemire
Journal: Environmental Health Perspectives (2024)

Previous studies have identified the consumption of country foods (hunted/harvested foods from the land) as the primary exposure source of perfluoroalkyl acids (PFAA) in Arctic communities. However, identifying the specific foods associated with PFAA exposures is complicated due to correlation between country foods that are commonly consumed together.
Higher Adalimumab Concentration Is Associated With Complete Fistula Healing in Patients With Perianal Fistulizing Crohn’s Disease
Authors: Konstantinos Papamichael, Andrea Centritto, Lucas Guillo, Jessica Hier, Zachary Sherman, Dorsaf Zoghlami, Sivan Harnik, Lieven Mulders, Nikolaos Kamperidis, Sylvia Sidky, Alexandra Bruss, Tina Deyhim, Mark A. Samaan, Andres J. Yarur, Byron P. Vaughn, Naila Arebi, Krisztina B. Gecse, Bella Ungar, Xavier Roblin, Stephane Paul, Robert Battat, Waqqas Afif, Laurent Peyrin-Biroulet, Peter M. Irving, Adam S. Cheifetz
Journal: Clinical Gastroenterology and Hepatology (2024)
A Hazard-Based Framework for Identifying Safer Alternatives to Classes of Chemicals: A Case Study on Phthalates in Consumer Products
Authors: Marissa N. Smith, Sascha Stump, Saskia K. van Bergen, Holly G. Davies, Elinor Fanning, Rae Eaton, Craig C. Manahan, Amber Sergent, Ken Zarker
Journal: Environmental Health Perspectives (2024)

Humans are exposed to hazardous chemicals found in consumer products. In 2019, the Pollution Prevention for Healthy People and Puget Sound Act was passed in Washington State. This law is meant to reduce hazardous chemicals in consumer products and protect human health and the environment. The law directs the Washington State Department of Ecology to assess chemicals and chemical classes found in products, determine whether there are safer alternatives, and make regulatory determinations.
A Modular Trial of Androgen Signaling Inhibitor Combinations Testing a Risk-Adapted Strategy in Patients with Metastatic Castration–Resistant Prostate Cancer
Authors: Ana M. Aparicio, Rebecca S.S. Tidwell, Shalini S. Yadav, Jiun-Sheng Chen, Miao Zhang, Jingjing Liu, Shuai Guo, Patrick G. Pilié, Yao Yu, Xingzhi Song, Haswanth Vundavilli, Sonali Jindal, Keyi Zhu, Paul V. Viscuse, Justin M. Lebenthal, Andrew W. Hahn, Rama Soundararajan, Paul G. Corn, Amado Zurita-Saavedra, Sumit K. Subudhi, Jianhua Zhang, Wenyi Wang, Chad Huff, Patricia Troncoso, James P. Allison, Padmanee Sharma, Christopher J. Logothetis
Journal: Clinical Cancer Research (2024)

Abstract Purpose: To determine the efficacy and safety of risk-adapted combinations of androgen signaling inhibitors and inform disease classifiers for metastatic castration–resistant prostate cancers. Patients and Methods: In a modular, randomized phase II trial, 192 men were treated with 8 weeks of abiraterone acetate, prednisone, and apalutamide (AAPA; module 1) and then allocated to modules 2 or 3 based on satisfactory (≥50% PSA decline from baseline and &amp;lt;5 circulating tumor cell/7.5 mL) versus unsatisfactory status. Men in the former were randomly assigned to continue AAPA alone (module 2A) or with ipilimumab (module 2B). Men in the latter group had carboplatin + cabazitaxel added to AAPA (module 3). Optional baseline biopsies were subjected to correlative studies. Results: Median overall survival (from allocation) was 46.4 [95% confidence interval (CI), 39.2–68.2], 41.4 (95% CI, 33.3–49.9), and 18.7 (95% CI, 14.3–26.3) months in modules 2A (n = 64), 2B (n = 64), and 3 (n = 59), respectively. Toxicities were within expectations. Of 192 eligible patients, 154 (80.2%) underwent pretreatment metastatic biopsies. The aggressive-variant prostate cancer molecular profile (defects in ≥2 of p53, RB1, and PTEN) was associated with unsatisfactory status. Exploratory analyses suggested that secreted phosphoprotein 1–positive and insulin-like growth factor–binding protein 2–positive macrophages, druggable myeloid cell markers, and germline pathogenic mutations were enriched in the unsatisfactory group. Conclusions: Adding ipilimumab to AAPA did not improve outcomes in men with androgen-responsive metastatic castration–resistant prostate cancer. Despite the addition of carboplatin + cabazitaxel, men in the unsatisfactory group had shortened survivals. Adaptive designs can enrich for biologically and clinically relevant disease subgroups to contribute to the development of marker-informed, risk-adapted therapy strategies in men with prostate cancer.
The Benefits and Risks of Receiving Investigational Solid Tumor Drugs in Randomized Trials
Authors: Renata Iskander, Hannah Moyer, Dean Fergusson, Sean McGrath, Andrea Benedetti, Jonathan Kimmelman
Journal: Annals of Internal Medicine (2024)

Many patients participate in cancer trials to access new therapies. The extent to which new treatments produce clinical benefit for trial participants is unclear. To estimate the progression-free survival (PFS) and overall survival (OS) advantage of assignment to experimental groups in randomized trials for 6 solid tumors. ClinicalTrials.gov was searched for trials of investigational drugs with results posted between 2017 and 2021. Investigational drugs were defined as those not yet having full approval from the U.S. Food and Drug Administration for the study indication. Trials were included if they were randomized and tested drugs or biologics. Data extraction was completed by 2 independent reviewers. Data were pooled using a random-effects model. The sample included 128 trials comprising 141 comparisons of a new drug and a comparator. These comparisons included 47 050 patients. The pooled hazard ratio for PFS was 0.80 (95% CI, 0.75 to 0.85), indicating statistically significant benefit for patients in experimental groups. This corresponded to a median PFS advantage of 1.25 months (CI, 0.80 to 1.68 months). The pooled hazard ratio for OS was 0.92 (CI, 0.88 to 0.95), corresponding to a survival gain of 1.18 months (CI, 0.72 to 1.71 months). The absolute risk for a serious adverse event for comparator group patients was 29.56% (CI, 26.64% to 32.65%), with an increase in risk of 7.40% (CI, 5.66% to 9.14%) for patients in experimental groups. Trials in this sample were heterogeneous. Comparator group interventions were assumed to reflect standard of care. Assignment to experimental groups produces statistically significant survival gains. However, the absolute survival gain is small, and toxicity is statistically significantly greater. The findings of this review provide reassuring evidence that patients are not meaningfully disadvantaged by assignment to comparator groups. Canadian Institutes of Health Research.
The Effect of Open-Label Semaglutide on Metabolic Dysfunction–Associated Steatotic Liver Disease in People With HIV
Authors: Jordan E. Lake, Douglas W. Kitch, Amy Kantor, Raja Muthupillai, Karin L. Klingman, Christina Vernon, Pablo F. Belaunzaran-Zamudio, Carl J. Fichtenbaum, Sonya Heath, Hugo Perazzo, Kathleen Corey, Todd T. Brown, Alan Landay, Fred Sattler, Kristine M. Erlandson
Journal: Annals of Internal Medicine (2024)
Tissue-specific features of innate lymphoid cells in antiviral defense
Authors: Sytse J Piersma
Journal: Cellular and Molecular Immunology (2024)

Innate lymphocytes (ILCs) rapidly respond to and protect against invading pathogens and cancer. ILCs include natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer (LTi) cells and include type I, type II, and type III immune cells. While NK cells have been well recognized for their role in antiviral immunity, other ILC subtypes are emerging as players in antiviral defense. Each ILC subset has specialized functions that uniquely impact the antiviral immunity and health of the host depending on the tissue microenvironment. This review focuses on the specialized functions of each ILC subtype and their roles in antiviral immune responses across tissues. Several viruses within infection-prone tissues will be highlighted to provide an overview of the extent of the ILC immunity within tissues and emphasize common versus virus-specific responses.
Best practices for the dissemination and implementation of neuromuscular training injury prevention warm-ups in youth team sport: a systematic review
Authors: Destiny Lutz, Carla van den Berg, Anu M Räisänen, Isla J Shill, Jemma Kim, Kenzie Vaandering, Alix Hayden, Kati Pasanen, Kathryn J Schneider, Carolyn A Emery, Oluwatoyosi B A Owoeye
Journal: British Journal of Sports Medicine (2024)

Objective To evaluate best practices for neuromuscular training (NMT) injury prevention warm-up programme dissemination and implementation (D&amp;I) in youth team sports, including characteristics, contextual predictors and D&amp;I strategy effectiveness. Design Systematic review. Data sources Seven databases were searched. Eligibility The literature search followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria: participation in a team sport, ≥70% youth participants (&lt;19 years), D&amp;I outcomes with/without NMT-related D&amp;I strategies. The risk of bias was assessed using the Downs &amp; Black checklist. Results Of 8334 identified papers, 68 were included. Sport participants included boys, girls and coaches. Top sports were soccer, basketball and rugby. Study designs included randomised controlled trials (RCTs) (29.4%), cross-sectional (23.5%) and quasi-experimental studies (13.2%). The median Downs &amp; Black score was 14/33. Injury prevention effectiveness (vs efficacy) was rarely (8.3%) prioritised across the RCTs evaluating NMT programmes. Two RCTs (2.9%) used Type 2/3 hybrid approaches to investigate D&amp;I strategies. 19 studies (31.6%) used D&amp;I frameworks/models. Top barriers were time restrictions, lack of buy-in/support and limited benefit awareness. Top facilitators were comprehensive workshops and resource accessibility. Common D&amp;I strategies included Workshops with supplementary Resources (WR; n=24) and Workshops with Resources plus in-season Personnel support (WRP; n=14). WR (70%) and WRP (64%) were similar in potential D&amp;I effect. WR and WRP had similar injury reduction (36–72%) with higher adherence showing greater effectiveness. Conclusions Workshops including supplementary resources supported the success of NMT programme implementation, however, few studies examined effectiveness. High-quality D&amp;I studies are needed to optimise the translation of NMT programmes into routine practice in youth sport.
Catalytic Nanoparticles in Biomedical Applications: Exploiting Advanced Nanozymes for Therapeutics and Diagnostics
Authors: Divinah Manoharan, Liu‐Chun Wang, Ying‐Chi Chen, Wei‐Peng Li, Chen‐Sheng Yeh
Journal: Advanced Healthcare Materials (2024)

Catalytic nanoparticles (CNPs) as heterogeneous catalyst reveals superior activity due to their physio-chemical features, such as high surface-to-volume ratio and unique optical, electric, and magnetic properties. The CNPs, based on their physio-chemical nature, can either increase the reactive oxygen species (ROS) level for tumor and antibacterial therapy or eliminate the ROS for cytoprotection, anti-inflammation, and anti-aging. In addition, the catalytic activity of nanozymes can specifically trigger a specific reaction accompanied by the optical feature change, presenting the feasibility of biosensor and bioimaging applications. Undoubtedly, CNPs play a pivotal role in pushing the evolution of technologies in medical and clinical fields, and advanced strategies and nanomaterials rely on the input of chemical experts to develop. Herein, a systematic and comprehensive review of the challenges and recent development of CNPs for biomedical applications is presented from the viewpoint of advanced nanomaterial with unique catalytic activity and additional functions. Furthermore, the biosafety issue of applying biodegradable and non-biodegradable nanozymes and future perspectives are critically discussed to guide a promising direction in developing span-new nanozymes and more intelligent strategies for overcoming the current clinical limitations.
Sepsis-trained macrophages promote antitumoral tissue-resident T cells
Authors: Alexis Broquet, Victor Gourain, Thomas Goronflot, Virginie Le Mabecque, Debajyoti Sinha, Mitra Ashayeripanah, Cédric Jacqueline, Pierre Martin, Marion Davieau, Lea Boutin, Cecile Poulain, Florian P Martin, Cynthia Fourgeux, Melanie Petrier, Manon Cannevet, Thomas Leclercq, Maeva Guillonneau, Tanguy Chaumette, Thomas Laurent, Christelle Harly, Emmanuel Scotet, Laurent Legentil, Vincent Ferrières, Stephanie Corgnac, Fathia Mami-Chouaib, Jean Francois Mosnier, Nicolas Mauduit, Hamish E G McWilliam, Jose A Villadangos, Pierre Antoine Gourraud, Karim Asehnoune, Jeremie Poschmann, Antoine Roquilly
Journal: Nature Immunology (2024)
Influence of COVID-19 on trust in routine immunization, health information sources and pandemic preparedness in 23 countries in 2023
Authors: Jeffrey V Lazarus, Trenton M White, Katarzyna Wyka, Scott C Ratzan, Kenneth Rabin, Heidi J Larson, Federico Martinon-Torres, Ernest Kuchar, Salim S Abdool Karim, Tamara Giles-Vernick, Selina Müller, Carolina Batista, Nellie Myburgh, Beate Kampmann, Ayman El-Mohandes
Journal: Nature Medicine (2024)

Abstract It is unclear how great a challenge pandemic and vaccine fatigue present to public health. We assessed perspectives on coronavirus disease 2019 (COVID-19) and routine immunization as well as trust in pandemic information sources and future pandemic preparedness in a survey of 23,000 adults in 23 countries in October 2023. The participants reported a lower intent to get a COVID-19 booster vaccine in 2023 (71.6%), compared with 2022 (87.9%). A total of 60.8% expressed being more willing to get vaccinated for diseases other than COVID-19 as a result of their experience during the pandemic, while 23.1% reported being less willing. Trust in 11 selected sources of vaccine information each averaged less than 7 on a 10-point scale with one’s own doctor or nurse and the World Health Organization, averaging a 6.9 and 6.5, respectively. Our findings emphasize that vaccine hesitancy and trust challenges remain for public health practitioners, underscoring the need for targeted, culturally sensitive health communication strategies.