tbuckley/cabot-search huggingface dataset:
Electrocardiogram Intricacies in a Patient With Prostate Cancer—The Heart of the Matter
Authors: Cuizhen Yuan, Linfeng Peng, Dandan Yang
Journal: JAMA Internal Medicine (2024)

This case report describes the electrocardiagram findings of a patient in their 60s with chest tightness and dyspnea, left ventricular systolic impairment, and elevated troponin I levels.
Large Language Model Influence on Diagnostic Reasoning
Authors: Ethan Goh, Robert Gallo, Jason Hom, Eric Strong, Yingjie Weng, Hannah Kerman, Joséphine A. Cool, Zahir Kanjee, Andrew S. Parsons, Neera Ahuja, Eric Horvitz, Daniel Yang, Arnold Milstein, Andrew P. J. Olson, Adam Rodman, Jonathan H. Chen
Journal: JAMA Network Open (2024)

Importance Large language models (LLMs) have shown promise in their performance on both multiple-choice and open-ended medical reasoning examinations, but it remains unknown whether the use of such tools improves physician diagnostic reasoning. Objective To assess the effect of an LLM on physicians’ diagnostic reasoning compared with conventional resources. Design, Setting, and Participants A single-blind randomized clinical trial was conducted from November 29 to December 29, 2023. Using remote video conferencing and in-person participation across multiple academic medical institutions, physicians with training in family medicine, internal medicine, or emergency medicine were recruited. Intervention Participants were randomized to either access the LLM in addition to conventional diagnostic resources or conventional resources only, stratified by career stage. Participants were allocated 60 minutes to review up to 6 clinical vignettes. Main Outcomes and Measures The primary outcome was performance on a standardized rubric of diagnostic performance based on differential diagnosis accuracy, appropriateness of supporting and opposing factors, and next diagnostic evaluation steps, validated and graded via blinded expert consensus. Secondary outcomes included time spent per case (in seconds) and final diagnosis accuracy. All analyses followed the intention-to-treat principle. A secondary exploratory analysis evaluated the standalone performance of the LLM by comparing the primary outcomes between the LLM alone group and the conventional resource group. Results Fifty physicians (26 attendings, 24 residents; median years in practice, 3 [IQR, 2-8]) participated virtually as well as at 1 in-person site. The median diagnostic reasoning score per case was 76% (IQR, 66%-87%) for the LLM group and 74% (IQR, 63%-84%) for the conventional resources-only group, with an adjusted difference of 2 percentage points (95% CI, −4 to 8 percentage points; P = .60). The median time spent per case for the LLM group was 519 (IQR, 371-668) seconds, compared with 565 (IQR, 456-788) seconds for the conventional resources group, with a time difference of −82 (95% CI, −195 to 31; P = .20) seconds. The LLM alone scored 16 percentage points (95% CI, 2-30 percentage points; P = .03) higher than the conventional resources group. Conclusions and Relevance In this trial, the availability of an LLM to physicians as a diagnostic aid did not significantly improve clinical reasoning compared with conventional resources. The LLM alone demonstrated higher performance than both physician groups, indicating the need for technology and workforce development to realize the potential of physician-artificial intelligence collaboration in clinical practice. Trial Registration ClinicalTrials.gov Identifier: NCT06157944
Job Lock and Parents of Children With Cystic Fibrosis
Authors: Lenore S. Azaroff, Steffie Woolhandler, Danny McCormick, David U. Himmelstein, David Bor, Samuel Dickman, Adam Gaffney
Journal: JAMA Pediatrics (2024)

This cross-sectional study examined whether parental job lock and other financial and employment factors are associated with access to care for children with cystic fibrosis.
Prenatal Cannabis Exposure and Executive Function and Aggressive Behavior at Age 5 Years
Authors: Sarah A. Keim, Peter Fried, Keith Owen Yeates, Kelly M. Boone, Daphne M. Vrantsidis, Abigail Dean, Aaron W. Murnan, Joseph Rausch, Mark A. Klebanoff
Journal: JAMA Pediatrics (2024)

Importance Cannabis use during pregnancy is increasingly common in the US and may affect the development and behavior of preschool-aged children. Objective To prospectively investigate the association of prenatal cannabis exposure with executive function and aggressive behavior at age 5 years. Design, Setting, Participants This cohort study was conducted from 2016 through 2020. Data analysis was conducted from 2022 through 2024. Patients aged 16 through 50 years who were able to communicate in English and intended to deliver at the Ohio State University Wexner Medical Center were enrolled in a pregnancy research repository. Participants (n = 355) who gave consent for future contact and whose child(ren) was presumed to be alive were invited to participate again at child age 5 years (children born May 25, 2010, through February 7, 2016) and 250 children participated (70%). Exposure Cannabis exposure was measured prospectively by urine toxicology, maternal self-report, and obstetric record abstraction. Main Outcomes and Measures Executive function and aggressive behavior, measured via multimodal assessment by staff masked to exposure status. Outcomes were chosen a priori. Results Of 250 children, 80 were exposed to cannabis (32%). Use of tobacco, other drugs, and alcohol during pregnancy was common (22% to 39% each). Most families were living in poverty. There were 155 children who were Black/African American, non-Hispanic (62%); 11 were Hispanic (4%); 34 indicated more than one race or another race, non-Hispanic (14%); and 50 were White, non-Hispanic (20%). Age-corrected standard scores for children’s attention and inhibitory control (National Institutes of Health Toolbox) were about 0.4 SDs lower for those exposed to cannabis compared with unexposed (β = −6.1 points; 95% CI, −10.8 to −1.4), following propensity score weighting and adjustment for confounders. Exposed children also exhibited poorer task-based planning ability and more observed aggression. Caregiver ratings of executive function and behavior and laboratory assessments of other aspects of executive functioning showed no differences by exposure status. Conclusions and Relevance Results from this contemporary US cohort where prenatal cannabis exposure was common and indicated that exposed children exhibited some differences in aspects of executive function and behavior relevant to long-term academic success and adaptive functioning. These results may be considered in refining clinical recommendations regarding cannabis use during pregnancy.
Error in Methods
Journal: JAMA Network Open (2024)

Error in MethodsIn the Original Investigation titled "Absolute and Functional Iron Deficiency in the US, 2017-2020," 1 published September 24, 2024, there was an error in the definition of functional iron deficiency in the Methods.The threshold should have been transferrin saturation less than 20%, not less than 30%.This article has been corrected.
Protecting Podocytes in Glomerular Diseases Beyond Glucocorticoids
Authors: Rachel Njeim, Alessia Fornoni
Journal: Journal of the American Society of Nephrology (2024)

Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida; and Peggy and Harold Katz Family Drug Discovery Center, University of Miami Miller School of Medicine, Miami, Florida Correspondence: Prof. Alessia Fornoni, email: [email protected] See related article, "A Small Molecule agonist of Krüppel-Like Factor 15 in Proteinuric Kidney Disease," on pages XXX–XXX.
Mechanisms Underlying Acute Cognitive Impairment following Carbon Dioxide Inhalation in a Randomized Crossover Trial
Authors: Frederic T. Lu, Disha Gupta, Nancy Fiedler, Usha Satish, Kathleen G. Black, Alicia Legard, Adriana De Resende, Changjiang Guo, Andrew J. Gow, Howard M. Kipen
Journal: Environmental Health Perspectives (2024)
Critical care admissions and outcomes in pregnant and postpartum women: a systematic review
Authors: Swagata Tripathy, Neha Singh, Aparajita Panda, Subhasish Nayak, Nivedita Jayanti Bodra, Suma Rabab Ahmad, Madhusmita Parida, Monalisa Sarkar, Soumya Sarkar
Journal: Intensive Care Medicine (2024)
Phase III Evaluation of Treatment Combinations in Three-Arm Trials
Authors: Edward L. Korn, Carmen J. Allegra, Boris Freidlin
Journal: Journal of Clinical Oncology (2024)

Phase III trials that randomly assign patients to a control treatment (C), an experimental treatment (A), or a combination treatment (AB) should be designed with the goal to recommend the best treatment: AB (if it is better than A and C), A (if it is better than C, and AB is not better than A), or C (if neither AB nor A is better than C). However, this goal can be challenging to achieve with statistical confidence. We performed a survey of cancer trials published in five journals from January 2018 to May 2024 to assess the trial designs being used in this setting and found that three quarters of them did not have a provision for a formal comparison of the AB treatment arm with the A treatment arm, a possible shortcoming. A limited simulation evaluates two analysis strategies that incorporate an AB versus A comparison and is used to formulate some recommendations for designing these types of trials.
Projected Impact and Cost-Effectiveness of Novel Molecular Blood-Based or Stool-Based Screening Tests for Colorectal Cancer
Authors: Uri Ladabaum, Ajitha Mannalithara, Robert E. Schoen, Jason A. Dominitz, David Lieberman
Journal: Annals of Internal Medicine (2024)

Cell-free DNA blood tests (cf-bDNA) and next-generation stool tests could change colorectal cancer (CRC) screening.
Risk for Financial Precarity From Hospitalization: Implications for Targeting Financial Assistance in Medicare
Authors: Paula Chatterjee, Eliza Macneal, Syama R. Patel, Eric T. Roberts
Journal: Annals of Internal Medicine (2024)

High out-of-pocket costs in Medicare may leave many beneficiaries in financial precarity. Beneficiaries with modest incomes are often ineligible for Medicaid (which covers most out-of-pocket Medicare costs) and may have insufficient resources to pay an unexpected health care bill. This has prompted calls to improve financial protections, but the target population remains uncharacterized.
Comparative Effectiveness and Safety of Atorvastatin Versus Rosuvastatin
Authors: Shiyu Zhou, Ruixuan Chen, Jiao Liu, Zhixin Guo, Licong Su, Yanqin Li, Xiaodong Zhang, Fan Luo, Qi Gao, Yuxin Lin, Mingzhen Pang, Lisha Cao, Xin Xu, Sheng Nie
Journal: Annals of Internal Medicine (2024)

Rosuvastatin and atorvastatin are the most widely prescribed moderate- to high-intensity statins. However, evidence on their efficacy and safety during actual use is limited.
2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline for the Management of Headache
Authors: Jason J. Sico, Natasha M. Antonovich, Jennifer Ballard-Hernandez, Andrew C. Buelt, Amy S. Grinberg, Franz J. Macedo, Ian W. Pace, James Reston, James Sall, Friedhelm Sandbrink, Karen M. Skop, Thomas R. Stark, Rebecca Vogsland, Lisa Wayman, Aven W. Ford
Journal: Annals of Internal Medicine (2024)

Headache medicine and therapeutics evidence have been rapidly expanding and evolving since the 2020 U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) clinical practice guideline (CPG) for the management of headache. Therefore, the CPG was revised in 2023, earlier than the standard 5-year cycle. This article reviews the 2023 CPG recommendations relevant to primary care clinicians for treatment and prevention of migraine and tension-type headache (TTH).
The association between drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a case-control study
Authors: Mikolaj Swiderski, Yana Vinogradova, Roger D Knaggs, Karen Harman, Rowan H Harwood, Vibhore Prasad, Monica S M Persson, Grazziela Figueredo, Carron Layfield, Sonia Gran
Journal: British Journal of Dermatology (2024)

Abstract Background Bullous pemphigoid (BP) is an autoimmune skin disease that affects mainly older people. Numerous drugs have been previously associated with BP based on case series and small hospital-based studies. More reliable and precise estimates of associations between a broad selection of drugs/vaccines and BP will enable greater awareness of potential increased risk of BP following certain medicines and help identify clinical, histological and genomic characteristics of drug-induced BP for different types of culprit drugs. Greater awareness could lead to earlier recognition or suspicion of BP and referral to a dermatologist for diagnosis. Earlier diagnosis may lead to less aggressive treatment and improved well-being. Objectives To determine the association between drugs/vaccines commonly prescribed to older people and BP risk. Methods We conducted a population-based nested case-control study between 1998-2021 using electronic primary care records from the Clinical Practice Research Datalink. We matched BP cases with up to 5 controls. Exposures were drugs/vaccines commonly prescribed to older people. We used multivariable conditional logistic regression adjusting for multiple drug use. For antibiotics, we considered prescriptions may be prescribed for undiagnosed symptoms of BP which resemble skin infection (protopathic bias) in a sensitivity analysis. Results Antibiotics were the therapeutic group associated with the highest risk of BP (OR: 4.60; 95%CI 4.40-4.80). However, after adjusting for protopathic bias, the OR reduced to 2.08 (95%CI 1.99-2.17). After adjusting for protopathic bias, of all antibiotic classes and subclasses, penicillins and penicillinase-resistant penicillins had the strongest associations with BP risk (OR: 3.44; 95%CI 3.29-3.60; sensitivity analysis OR; 1.74; 1.66-1.84 and OR: 7.56; 95%CI 7.15-8.00; sensitivity analysis OR: 2.64; 95%CI 2.45-2.85, respectively). Other drugs strongly associated with increased risk were gliptins (OR: 2.77; 95% CI 2.37-3.23), and second-generation antipsychotics (OR: 2.58; 95%CI 2.20-3.03). Conclusions Healthcare professionals need to be aware of BP risk in older people particularly when prescribing penicillinase-resistant penicillins, gliptins, and second-generation antipsychotic drugs to recognise and manage BP early. Due to the low prevalence of disease, we do not suggest avoidance of drugs/vaccines to prevent BP. Further research should consider recency, dosage, and duration of antibiotic treatments.
Longitudinal validity of the Hyperhidrosis Quality of Life Index (HidroQoL©) in a phase IIIb clinical trial population with hyperhidrosis: responsiveness and meaningful change
Authors: Theresa Donhauser, Michaela Gabes, Clarissa Masur, Paul Kamudoni, Sam Salek, Christoph Abels, Christian Apfelbacher
Journal: British Journal of Dermatology (2024)

Abstract Background The Hyperhidrosis Quality of Life Index (HidroQoL ©) is a well-developed patient-reported outcome measure assessing the quality of life (QoL) impacts in hyperhidrosis, which has proven very good measurement properties, such as structural validity and internal consistency. Objectives We aimed to investigate responsiveness over time and estimate values for meaningful within-person change (MWPC) towards symptom improvement for different measurement time points (4 and 12 weeks), extending the existing validity evidence in patients with primary axillary hyperhidrosis. Methods Data (from a phase IIIb clinical trial) was collected at baseline, week 4, week 8, week 12, week 28, week 52, and week 72. For the assessment of responsiveness, HidroQoL change scores were correlated with corresponding change scores of the Hyperhidrosis Disease Severity Scale (HDSS), the Dermatology Life Quality Index (DLQI), and the gravimetric sweat production based on a-priori formulated hypotheses. Furthermore, it was tested whether the different HDSS change score groups differed significantly from each other over time and whether the HidroQoL was sensitive towards these group differences over time. This was extended by the calculation of matched-pair tests and effect sizes to test significance for each change group separately. For the estimation of MWPC thresholds towards symptom improvement, different anchor-based and integrated approaches were used. Results In total, the sample was composed of 357 patients with primary axillary hyperhidrosis. For the assessment of responsiveness, 5 out of 14 a-priori hypotheses regarding the correlation of the change scores could be confirmed, whereas the rejected hypotheses only marginally differed from the expected values. Furthermore, regarding responsiveness, the HidroQoL showed sensitivity towards symptom improvement at each measurement time point. Effect sizes were large as expected (d ≥ 0.806). MWPC thresholds towards symptom improvement were proposed for two measurement time points: 5 (week 4) and 6 (week 12). Increasing MWPC values over time were observed. Conclusion This study extends the evidence for the longitudinal validity of the HidroQoL up to 72 weeks and proposed MWPC thresholds for different time intervals (4 and 12 weeks) after baseline, aiding interpretability. Results concur with findings from previous validation studies.
Further evidence for strong non-neutrality of yeast synonymous mutations
Authors: Xukang Shen, Siliang Song, Chuan Li, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2024)

Abstract Although synonymous mutations are commonly assumed neutral or nearly so, recent years have seen reports of fitness effects of synonymous mutations detected under laboratory conditions. In a previous study, we used genome editing to construct thousands of yeast mutants each carrying a synonymous or nonsynonymous mutation in one of 21 genes and discovered that most synonymous and most nonsynonymous mutations are deleterious. A concern was raised that this observation could be caused by the fitness effects of potential CRISPR/Cas9 off-target edits and/or secondary mutations, and an experiment that would be refractory to such effects was proposed. Using genome sequencing, we here show that no CRISPR/Cas9 off-target editing occurred, although some mutants did carry secondary mutations. Analysis of mutants with negligible effects from secondary mutations and new data collected from the proposed experiment confirms the original conclusion. These findings, along with other reports of fitness effects of synonymous mutations from both case and systematic studies, necessitate a paradigm shift from assuming (near) neutrality of synonymous mutations.
Long-term survival with donor CD19 CAR-T cell treatment for relapsed patients after allogeneic hematopietic stem cell transplantation
Authors: Cheng Zhang, Xiaoqi Wang, Hai Yi, Yi Wang, Zhiling Yan, Jian Zhou, Ting Yang, Aibin Liang, Zhen Wang, Yingying Ma, Qin Wen, Lei Gao, Li Gao, Peiyan Kong, Xu Tan, Erlie Jiang, Xi Zhang
Journal: Journal of Hematology & Oncology (2024)

Chimeric Antigen Receptor T (CAR-T) cell therapy has significantly advanced in treating B-cell acute lymphoblastic leukemia (B-ALL) and has shown efficacy in managing relapsed B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor-derived CAR-T cell offer both high efficacy and rapid response. Although promising results exist, current research lacks definitive evidence of long-term survival benefits for patients treated with donor-derived CAR-T therapy. We report the long-term survival of 32 patients with post-transplant relapsed B-ALL treated with donor-derived CD19 CAR-T cell, achieving either complete Remission (CR) or CR with incomplete peripheral blood recovery (CRi). The median follow-up was 42 months, with 2-year overall survival (OS) and event-free survival (EFS) rates of 56.25% and 50.0%, respectively. The 5-year OS and EFS rates were 53.13% and 46.88%, with no new long-term adverse events observed. These findings demonstrate good long-term safety, supporting donor-derived CAR-T cell as a recommended treatment option for relapsed B-ALL patients post-transplantation. Trial registration: https://www.chictr.org.cn/showproj.html?proj=14315 . Registration number: ChiCTR-OOC-16008447.
Development and validation of the post-CAR prognostic index for large B-cell lymphoma patients after CAR-T progression in third or later line treatment
Authors: Gloria Iacoboni, Víctor Navarro, Pierre Sesques, Kai Rejeski, Mariana Bastos-Oreiro, Fabio Serpenti, Ana Africa Martin Lopez, Josu Iraola-Truchuelo, Javier Delgado, Ariadna Perez, Manuel Guerreiro, Ana Carolina Caballero, Nuria Martinez-Cibrian, Hugo Luzardo Henriquez, Jose Maria Sanchez Pina, Juan-Manuel Sancho, Hervé Ghesquieres, Alberto Mussetti, Lucia Lopez Corral, Rafael Hernani, Juan Luis Reguera, Anna Sureda, Francesc Bosch, Alejandro Martin Garcia-Sancho, Mi Kwon, Marion Subklewe, Andrea Kuhnl, Emmanuel Bachy, Pere Barba, Guillermo Villacampa, Pau Abrisqueta
Journal: Journal of Hematology & Oncology (2024)

Chimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. After CAR-T failure, survival outcomes are heterogeneous and a prognostic model in this patient population is lacking. A training cohort of 216 patients with progressive disease (PD) after CAR-T from 12 Spanish centers was used to develop the Post-CAR Prognostic Index (PC-PI); primary endpoint was overall survival (OS) from CAR-T progression. Validation was performed in an external cohort from three different European centers (n = 204). The prognostic score incorporated five variables, assessed at time of PD to CAR-T: ECOG (> 0), hemoglobin (< 10 g/dL), LDH (≥ 2xULN), number of extranodal sites (> 1) and time from CAR-T to PD (< 4 months). Patients were classified in four risk groups with distinct OS (p-value < 0.05 in all comparisons). In the validation cohort, median OS in the low (31%), intermediate-low (26%), intermediate-high (17%) and high risk (26%) were 15.7, 7.1, 1.8 and 1.0 months, respectively (p < 0.05 in all comparisons). Results were consistent following adjustment for subsequent treatment. In the external cohort, the PC-PI showed a C-statistic of 0.79 (95%CI 0.76–0.82), outperforming IPI and R-IPI. In conclusion, the PC-PI score is a novel tool for OS prediction and could facilitate risk-adapted management of LBCL patients relapsing after CAR T-cells. Additionally, these results will help stratification and interpretation of trials and real-world data incorporating CART-exposed patients. The Post-CAR Prognostic Index (PC-PI) is a tool to inform on overall survival after CAR T-cell progression in large B-cell lymphoma patients. The PC-PI can help risk-stratification and interpretation of trials and real-world data of regimens incorporating CART-exposed patients.