tbuckley/cabot-search huggingface dataset:
Cannabis or Cannabinoids for the Management of Chronic Noncancer Pain: Best Practice Advice From the American College of Physicians
Authors: Devan Kansagara, Kevin P. Hill, Jennifer Yost, Linda L. Humphrey, Beth Shaw, Adam J. Obley, Ray Haeme, Elie A. Akl, Amir Qaseem, Linda L. Humphrey, Adam J. Obley, Andrew S. Dunn, Andrew S. Dunn, Ray Haeme, Christopher D. Jackson, Christopher D. Jackson, Janet A. Jokela, Janet A. Jokela, Devan Kansagara, Rachael A. Lee, Rachael A. Lee, Katherine Mackey, Katherine Mackey, Sameer D. Saini, Sameer D. Saini, Mark P. Tschanz, Mark P. Tschanz, Timothy J. Wilt, Timothy J. Wilt, Itziar Etxeandia-Ikobaltzeta, Itziar Etxeandia-Ikobaltzeta, Amir Qaseem, Tatyana Shamliyan, Tatyana Shamliyan, Chelsea Vigna, Chelsea Vigna, Jennifer Yost
Journal: Annals of Internal Medicine (2025)

The American College of Physicians' Population Health and Medical Science Committee (PHMSC) developed this best practice advice to inform clinicians about what is currently known about the benefits and harms of cannabis or cannabinoids in the management of chronic noncancer pain and to provide advice for clinicians counseling patients seeking this therapy. The PHMSC considers areas where evidence is uncertain or emerging or practice does not follow the evidence to provide clinical advice based on a review and assessment of scientific work, including systematic reviews and individual studies. Sources of evidence included a living systematic review on cannabis and cannabinoid treatments for chronic noncancer pain and a series of living systematic reviews and primary studies. Clinicians should counsel patients about the benefits and harms of cannabis or cannabinoids when patients are considering whether to start or continue to use cannabis or cannabinoids to manage their chronic noncancer pain. Clinicians should counsel the following subgroups of patients that the harms of cannabis or cannabinoid use for chronic noncancer pain are likely to outweigh the benefits: young adult and adolescent patients, patients with current or past substance use disorder, patients with serious mental illness, and frail patients and those at risk for falling. Clinicians should advise against starting or continuing to use cannabis or cannabinoids to manage chronic noncancer pain in patients who are pregnant or breastfeeding or actively trying to conceive. Clinicians should advise patients against the use of inhaled cannabis to manage chronic noncancer pain.
Comparison of Initial Artificial Intelligence (AI) and Final Physician Recommendations in AI-Assisted Virtual Urgent Care Visits
Authors: Dan Zeltzer, Zehavi Kugler, Lior Hayat, Tamar Brufman, Ran Ilan Ber, Keren Leibovich, Tom Beer, Ilan Frank, Ran Shaul, Caroline Goldzweig, Joshua Pevnick
Journal: Annals of Internal Medicine (2025)

Whether artificial intelligence (AI) assistance is associated with quality of care is uncertain. To compare initial AI recommendations with final recommendations of physicians who had access to the AI recommendations and may or may not have viewed them. Retrospective cohort study. Cedars-Sinai Connect, an AI-assisted virtual urgent care clinic with intake questions via structured chat. When confidence is sufficient, AI presents diagnosis and management recommendations (prescriptions, laboratory tests, and referrals). 461 physician-managed visits with AI recommendations of sufficient confidence and complete medical records for adults with respiratory, urinary, vaginal, eye, or dental symptoms from 12 June to 14 July 2024. Concordance of diagnosis and management recommendations of initial AI recommendations and final physician recommendations. Physician adjudicators scored all nonconcordant and a sample of concordant recommendations as optimal, reasonable, inadequate, or potentially harmful. Initial AI and final physician recommendations were concordant for 262 visits (56.8%). Among the 461 weighted visits, AI recommendations were more frequently rated as optimal (77.1% [95% CI, 72.7% to 80.9%]) compared with treating physician decisions (67.1% [CI, 62.9% to 71.1%]). Quality scores were equal in 67.9% (CI, 64.8% to 70.9%) of cases, better for AI in 20.8% (CI, 17.8% to 24.0%), and better for treating physicians in 11.3% (CI, 9.0% to 14.2%), respectively. Single-center retrospective study. Adjudicators were not blinded to the source of recommendations. It is unknown whether physicians viewed AI recommendations. When AI and physician recommendations differed, AI recommendations were more often rated better quality. Findings suggest that AI performed better in identifying critical red flags and supporting guideline-adherent care, whereas physicians were better at adapting recommendations to changing information during consultations. Thus, AI may have a role in assisting physician decision making in virtual urgent care. K Health.
Comparison of Dose Escalation Versus Switching to Tirzepatide Among People With Type 2 Diabetes Inadequately Controlled on Lower Doses of Dulaglutide
Authors: Liana K. Billings, Linsey Winne, Palash Sharma, Elisa Gomez-Valderas, K. Karthik Chivukula, Anita Y. M. Kwan
Journal: Annals of Internal Medicine (2025)

Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for the treatment of adults with type 2 diabetes or obesity, showed clinically meaningful reductions in hemoglobin A1c (HbA1c) and body weight in the SURPASS phase 3 clinical trial program. To compare efficacy and safety of escalation of dulaglutide dose versus switching to tirzepatide in inadequately controlled type 2 diabetes. Multicenter, randomized, open-label, phase 4 trial (SURPASS-SWITCH [A Phase 4, Randomized, Open-Label, Active-Controlled Study to Investigate the Efficacy and Safety of Switching from Weekly Dulaglutide to Weekly Tirzepatide in Adults with Type 2 Diabetes], ClinicalTrials.gov: NCT05564039). 38 sites across 5 countries. Adults with HbA1c 7.0% or greater to 9.5% or less, stable body weight, body mass index of 25 kg/m2 or greater, receiving a stable dose of dulaglutide (0.75 or 1.5 mg) for at least 6 months and 0 to 3 oral antihyperglycemic medications for at least 3 months. Escalation of dulaglutide to 4.5 mg or maximum tolerated dose (MTD) or switching to tirzepatide. The primary end point was change from baseline in HbA1c at week 40. The key secondary end point was change from baseline in weight at week 40. A total of 282 adults were randomly assigned to tirzepatide (n = 139) or dulaglutide (n = 143). Change from baseline in HbA1c at week 40 was -1.44% (SE, 0.07) with tirzepatide, 15 mg or MTD, and -0.67% (SE, 0.08) with dulaglutide, 4.5 mg or MTD (estimated treatment difference, -0.77% [95% CI, -0.98% to -0.56%; P < 0.001]). Change from baseline in weight at week 40 was -10.5 kg (SE, 0.5) with tirzepatide and -3.6 kg (SE, 0.5) with dulaglutide (estimated treatment difference, -6.9 kg [CI, -8.3 to -5.5 kg; P < 0.001]). Serious adverse events were reported by 10 (7.2%) tirzepatide and 10 (7.0%) dulaglutide participants. The most common treatment-emergent adverse events were nausea and diarrhea. Open-label design. In SURPASS-SWITCH, switching treatment to tirzepatide provided additional HbA1c reduction and weight loss compared with escalating treatment with dulaglutide. Eli Lilly and Company.
Evidence for antimicrobial stewardship and reduced antimicrobial resistance in the Mid-West of Ireland, 2012 to 2023: findings from a One Health study
Authors: James Powell, Santosh Sharma, Alan Johnson, Siobhan Barrett, Caroline Garvan, Nuala H O’Connell, Colum P Dunne
Journal: Eurosurveillance (2025)

Background Escherichia coli , a pathogen commonly infecting humans and bovines, is a prime sentinel indicator and predictor for antimicrobial resistance (AMR). Tracking epidemiological trends of AMR is essential to address this global One Health threat. Aim To perform a comprehensive retrospective epidemiological analysis of AMR trends in E. coli isolated from human urine and blood and bovine specimens, and compare with antimicrobial consumption or sales data for humans. Methods All E. coli isolates with susceptibility results from human urine (n = 122,419), blood (n = 2,373) and bovine specimens (n = 585) from 2012–23 in the Mid-West of Ireland were analysed. The resistance trends of nine commonly used antimicrobials were compared with their consumption by humans or sales in community and hospital settings. Results Over the 12-year period, resistance against common antimicrobials was lowest among the bovine isolates (range: 2–44%). Human urine isolates showed lower resistance (5–59%) than bloodstream isolates (12–69%). There was a downward trend in resistance to all antimicrobials between 2012 and 2023 in the human isolates (p &lt; 0.001), except for piperacillin/tazobactam where resistance increased, in each case correlating with antimicrobial usage. Bovine isolates demonstrated reduced resistance to co-amoxiclav (p = 0.001), with no trend observed for other antimicrobials. Conclusion Our data showed reduced resistance to many antimicrobials for E. coli from human and bovine populations in our region. Increased use of ‘preferred’ antimicrobials in humans and reduced use of those ‘to be avoided’ was observed. The findings indicate the emerging effectiveness of AMR strategies and highlight the value of One Health AMR.
Emergence of Salmonella enterica carrying blaOXA-181 carbapenemase gene, Italy, 2021 to 2024
Authors: Luca Bolzoni, Erika Scaltriti, Chiara Bracchi, Sara Angelone, Ilaria Menozzi, Roberta Taddei, Patricia Alba, Virginia Carfora, Elena Lavinia Diaconu, Marina Morganti, Alessandra Dodi, Melissa Berni, Laura Manni, Massimiliano Vinci, Martina Tambassi, Laura Mazzera, Irene Venturelli, Simone Ambretti, Antonio Battisti, Stefano Pongolini
Journal: Eurosurveillance (2025)

Between 2021 and 2024, we detected carbapenemase gene bla OXA-181 in 16 of 11,398 Salmonella enterica (SE) isolates: 10 SE 1,4,[5],12:i:-, three Bovismorbificans, two London and one Rissen from pigs, humans, pork meat and wild roe deer. The gene was first detected in pig isolates, later in humans, suggesting zoonotic transmission. Phylogenetic analysis indicated that horizontal transfer, mainly through plasmids, contributed to the spread. These findings highlight a possible emerging public health threat and the importance of One Health surveillance.
Identifying hotspots and risk factors for tick-borne encephalitis virus emergence at its range margins to guide interventions, Great Britain
Authors: Richard MJ Hassall, Maya Holding, Jolyon M Medlock, Festus A Asaaga, Sophie O Vanwambeke, Roger Hewson, Bethan V Purse
Journal: Eurosurveillance (2025)

Background Tick-borne encephalitis virus (TBEV) is expanding its range in Europe, with increasing human cases reported. Since the first detection of TBEV in ticks in the United Kingdom in 2019, one possible, two probable and two confirmed autochthonous cases in humans have been reported. Aim We aimed to understand the environmental and ecological factors limiting TBEV foci at their range edge and predict suitable areas for TBEV establishment across Great Britain (GB) by modelling patterns of exposure to TBEV in deer. Methods We developed spatial risk models for TBEV by integrating data between 2018 and 2021 on antibodies against tick-borne flavivirus in fallow, muntjac, red and roe deer with data on potential risk factors, including climate, land use, forest connectivity and distributions of bank voles and yellow-necked mice. We overlayed modelled suitability for TBEV exposure across GB with estimations on number of visitors to predict areas of high human exposure risk. Results Models for fallow, muntjac and roe deer performed well in independent validation (Boyce index &gt; 0.92). Probable exposure to TBEV was more likely to occur in sites with a greater percentage cover of coniferous woodland, with multiple deer species, higher winter temperatures and rates of spring warming. Conclusion The resulting TBEV suitability maps can be used by public health bodies in GB to tailor surveillance and identify probable high-risk areas for human exposure to guide awareness raising and vaccination policy. Combining animal surveillance and iterative spatial risk modelling can enhance preparedness in areas of tick-borne disease emergence.
Fulminant infective endocarditis with toxin-negative Corynebacterium diphtheriae in people with substance use experiencing homelessness, England, 2024 to 2025
Authors: Tara Patel, Tasnim Anwar, Eleni Mavrogiorgou, Natasa Utjesanovic, Anna Aryee, David J Litt, Joshua C. D’Aeth, Christopher Primus, Satya Das, Nikolaos Karogiannis, Karthik Paranthaman, Gayatri Amirthalingam, Rebecca Cordery
Journal: Eurosurveillance (2025)

Between July 2024 and January 2025, five male patients in their early 20s to early 50s were confirmed with infective endocarditis associated with non-toxigenic Corynebacterium diphtheriae in England. Three were known to have experienced homelessness. All five used non-intravenous recreational drugs. Disease progression was rapid, four patients required surgical intervention, one died. Whole-genome sequencing and multilocus sequence type (MLST) analysis identified four individuals as ST559. Clinicians and substance use services have been alerted and enhanced surveillance implemented. A prevalence study is planned.
Use of integrated genomic surveillance by local public health authorities: Recommendations based on a mixed-methods study of current adoption, applications and success factors, Germany, 2023
Authors: Anna Bludau, Alexander Jack, Nicole Fischer, Johannes Dreesman, Christian Drosten, Richard Egelkamp, Lutz Ehlkes, Fabian Feil, Adam Grundhoff, Hajo Grundmann, Pascal Kreuzer, Masyar Monazahian, Inga Overesch, Daniel Schmitt, Markus Tröger, Alexandra von Reiswitz, Jonas Weber, Alexander Dilthey, Claudia Hornberg, Sandra Reuter, Simone Scheithauer
Journal: Eurosurveillance (2025)

Background Integrated genomic surveillance (IGS), i.e. the integrated analysis of pathogen whole genome sequencing and classical epidemiological data, can contribute substantially to the disease surveillance and infection prevention activities of local public health authorities (LPHAs). Aim Our aim was to characterise how LPHAs use IGS, and factors required or important for their implementation, in the context of the German public health system. Methods We employed a mixed-methods design combining a quantitative survey of 60 LPHAs in three German states with five qualitative case studies based on LPHAs in four German localities and one state-level public health authority. Results Approximately half of LPHAs reported adoption of IGS; applications included outbreak analysis (n = 25), targeting and evaluation of infection control measures (n = 25 and n = 18, respectively) and characterisation of pathogen transmission chains (n = 25). Factors identified as required or important for the implementation of IGS in LPHAs included fast sample-to-result turnaround times, organisational data interpretation capabilities and clearly defined surveillance sampling strategies. Based on the case studies in which the adoption of IGS was successful, we formulate recommendations for implementing IGS at the level of LPHAs, including establishment of dedicated IGS analysis teams within LPHAs, use of user-friendly digital solutions (e.g. browser-based dashboards) for data exchange and analysis, and implementation of IGS in collaboration with local academic institutions. Conclusion Our analysis paves the way for increasing the implementation of IGS by LPHAs in Germany and other countries with similarly structured public health systems.
The Present and Future of Genetic Sequencing as Applied to Diagnosis and Management in Rheumatology
Authors: Jason Liebowitz, Hila Milo Rasouly, Kelsie Bogyo, Lynn Petukhova, Elana J Bernstein, Daniella M Schwartz, Peter C Grayson, David Beck, Yiming Luo
Journal: Arthritis & Rheumatology (2025)
Piezo1 in PASMCs: Critical for Hypoxia-Induced Pulmonary Hypertension Development
Authors: Fenja Knoepp, Shariq Abid, Amal Houssaini, Larissa Lipskaia, Mira Yasemin Gökyildirim, Emmanuelle Born, Elisabeth Marcos, Malika Arhatte, Edyta Glogowska, Nora Vienney, Andreas Günther, Simone Kraut, Ingrid Breitenborn-Mueller, Karin Quanz, Dagmar Fenner-Nau, Geneviève Derumeaux, Norbert Weissmann, Eric Honoré, Serge Adnot
Journal: Circulation Research (2025)

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening and progressive yet incurable disease. The hallmarks of PH comprise (1) sustained contraction and (2) excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs). A major stimulus to which PASMCs are exposed during PH development is altered mechanical stress, originating from increased blood pressure, changes in blood flow velocity, and a progressive stiffening of pulmonary arteries. Mechanosensitive ion channels, including Piezo1, perceive such mechanical stimuli and translate them into a variety of cellular responses, including contractility or proliferation. Thus, the objective of the present study was to elucidate the specific role of Piezo1 in PASMCs for PH development and progression. METHODS: The cell-type specific function of Piezo1 in PH was assessed in (1) PASMCs and lung tissues from patients with PH and (2) 2 mouse strains characterized by smooth muscle cell–specific, conditional Piezo1 knockout. Taking advantage of these strains, the smooth muscle cell–specific role of Piezo1 in PH development and progression was assessed in isolated, perfused, and ventilated mouse lungs, wire myography, and proliferation assays. Finally, in vivo function of smooth muscle cell–specific Piezo1 knockout was evaluated upon induction of chronic hypoxia–induced PH in these mice with insights into pulmonary vascular cell senescence. RESULTS: Compared with healthy controls, PASMCs from patients with PH featured an elevated Piezo1 expression and increased proliferative phenotype. Smooth muscle cell–specific Piezo1 deletion, as confirmed via quantitative real-time polymerase chain reaction and patch clamp recordings, prevented the hypoxia-induced increase in PASMC proliferation in mice. Moreover, Piezo1 knockout reduced hypoxic pulmonary vasoconstriction in isolated, perfused, and ventilated mouse lungs, endothelial-denuded pulmonary arteries, and hemodynamic measurements in vivo. Consequently, Piezo1-deficient mice were considerably protected against chronic hypoxia–induced PH development with ameliorated right heart hypertrophy and improved hemodynamic function. In addition, distal pulmonary capillaries were preserved in the Piezo1-knockout mice, associated with a lower number of senescent endothelial cells. CONCLUSIONS: This study provides evidence that Piezo1 expressed in PASMCs is critically involved in the pathogenesis of PH by controlling pulmonary vascular tone, arterial remodeling, and associated lung capillary rarefaction due to endothelial cell senescence.
Antibiotics for common infections in primary care before, during and after the COVID-19 pandemic: cohort study of extent of prescribing based on risks of infection-related hospital admissions
Authors: Ali Fahmi, Ya-Ting Yang, Xiaomin Zhong, Alexander Pate, Anita Sharma, Simon Watts, Darren M Ashcroft, Ben Goldacre, Brian MacKenna, Jon Massey, Amir Mehrkar, Seb Bacon, Brian McMillan, Paul Dark, Kieran Hand, Victoria Palin, Tjeerd Pieter van Staa
Journal: Journal of the Royal Society of Medicine (2025)

Objectives Antibiotics are effective in treating bacterial infections, but they carry the risks of antimicrobial resistance and effectiveness loss. This study aimed to assess whether antibiotics for common infections are prescribed in a risk-based manner and how this changed during the COVID-19 pandemic. Design Cohort study of common infections and antibiotic prescribing. Setting With the approval of NHS England, we accessed pseudonymised patient-level electronic health records of primary care data from The Phoenix Partnership through OpenSAFELY. Participants We included adults registered at general practices in England with a record of common infection, including lower respiratory tract infection (LRTI), upper respiratory tract infections (URTI) and lower urinary tract infection (UTI), from January 2019 to March 2023. Patients with a record of COVID-19 were excluded. Main outcome measures Patient-specific risks of infection-related hospital admission were estimated for each infection using risk prediction scores for patients who were not prescribed an antibiotic. The infection cohorts were then grouped into risk deciles, and probabilities of being prescribed an antibiotic were assessed. Results We found 15,719,750 diagnoses of common infections. Of them, 450,215 (2.86%) were hospitalised in the 30 days after the diagnosis and 10,429,060 (66.34%) were prescribed an antibiotic. There were substantial differences in observed rates of hospital admissions between the lowest and highest risk deciles (25-fold difference in URTI). The probability of being prescribed an antibiotic for LRTI or UTI was unrelated to hospital admission risk, and that for URTI was weakly related to hospital admission risk. During the COVID-19 pandemic, the level of risk-based antibiotic prescribing reduced. Conclusions There is a need to better target antibiotics in primary care to patients with worse prognosis and strengthen treatment guidelines in personalisation of prescribing.
Intranasal NAP (Davunetide): Neuroprotection and circadian rhythmicity
Authors: Artur Galushkin, Illana Gozes
Journal: Advanced Drug Delivery Reviews (2025)

In this review we examine the neuroprotective potential of NAP (davunetide), a small peptide derived from Activity-Dependent Neuroprotective Protein (ADNP), in the context of neurodevelopmental and neurodegenerative disorders. ADNP, a protein essential for brain development and function, is associated with tauopathy-related diseases, such as Alzheimer's Disease (AD), and circadian rhythm regulation. NAP enhances microtubule stability and prevents tauopathy. In preclinical studies, NAP shows promise in improving cognitive performance and correcting behavioral deficits in different models. Clinical studies on NAP (davunetide) administered via intranasal delivery have demonstrated its safety, favorable bioavailability, and potential efficacy in improving cognitive function, making it a viable therapeutic option. In the pure tauopathy, progressive supranuclear palsy, NAP (davunetide) significantly slowed disease progression in women in a phase II-III clinical trial. Additionally, the complex interactions between ADNP, associated pathways, and circadian regulation and the extensive NAP compensation upon ADNP deficiency attest to further clinical development. Thus, NAP is an example of a reductionist approach in drug delivery, replacing/enhancing the critical large ADNP-related pathways including dysregulated microtubules and tauopathy with a small brain bioavailable investigational drug, davunetide.