tbuckley/cabot-search huggingface dataset:
Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations
Authors: Niall J. Lennon, Leah C. Kottyan, Christopher Kachulis, Noura S. Abul-Husn, Josh Arias, Gillian Belbin, Jennifer E. Below, Sonja I. Berndt, Wendy K. Chung, James J. Cimino, Ellen Wright Clayton, John J. Connolly, David R. Crosslin, Ozan Dikilitas, Digna R. Velez Edwards, QiPing Feng, Marissa Fisher, Robert R. Freimuth, Tian Ge, Sonja Berndt, Joel Hirschhorn, Ruth Loos, Joseph T. Glessner, Adam S. Gordon, Candace Patterson, Hakon Hakonarson, Maegan Harden, Margaret Harr, Joel N. Hirschhorn, Clive Hoggart, Li Hsu, Marguerite R. Irvin, Gail P. Jarvik, Elizabeth W. Karlson, Atlas Khan, Amit Khera, Krzysztof Kiryluk, Iftikhar Kullo, Katie Larkin, Nita Limdi, Jodell E. Linder, Ruth J. F. Loos, Yuan Luo, Edyta Malolepsza, Teri A. Manolio, Lisa J. Martin, Li McCarthy, Elizabeth M. McNally, James B. Meigs, Tesfaye B. Mersha, Jonathan D. Mosley, Anjene Musick, Bahram Namjou, Nihal Pai, Lorenzo L. Pesce, Ulrike Peters, Josh F. Peterson, Cynthia A. Prows, Megan J. Puckelwartz, Heidi L. Rehm, Dan M. Roden, Elisabeth A. Rosenthal, Robb Rowley, Konrad Teodor Sawicki, Daniel J. Schaid, Roelof A. J. Smit, Johanna L. Smith, Jordan W. Smoller, Minta Thomas, Hemant Tiwari, Diana M. Toledo, Nataraja Sarma Vaitinadin, David Veenstra, Theresa L. Walunas, Zhe Wang, Wei-Qi Wei, Chunhua Weng, Georgia L. Wiesner, Xianyong Yin, Eimear E. Kenny
Journal: Nature Medicine (2024)

Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented in the clinic, including reduced predictive performance of PRSs in diverse populations, and the interpretation and communication of genetic results to both providers and patients. To address these challenges, the National Human Genome Research Institute-funded Electronic Medical Records and Genomics (eMERGE) Network has developed a framework and pipeline for return of a PRS-based genome-informed risk assessment to 25,000 diverse adults and children as part of a clinical study. From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer. Standardized metrics were considered in the selection process, with additional consideration given to strength of evidence in African and Hispanic populations. We then developed a pipeline for clinical PRS implementation (score transfer to a clinical laboratory, validation and verification of score performance), and used genetic ancestry to calibrate PRS mean and variance, utilizing genetically diverse data from 13,475 participants of the All of Us Research Program cohort to train and test model parameters. Finally, we created a framework for regulatory compliance and developed a PRS clinical report for return to providers and for inclusion in an additional genome-informed risk assessment. The initial experience from eMERGE can inform the approach needed to implement PRS-based testing in diverse clinical settings.
A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk
Authors: Marc Ferrell, Zeneng Wang, James T. Anderson, Xinmin S. Li, Marco Witkowski, Joseph A. DiDonato, James R. Hilser, Jaana A. Hartiala, Arash Haghikia, Tomas Cajka, Oliver Fiehn, Naseer Sangwan, Ilja Demuth, Maximilian König, Elisabeth Steinhagen-Thiessen, Ulf Landmesser, W. H. Wilson Tang, Hooman Allayee, Stanley L. Hazen
Journal: Nature Medicine (2024)
Passive Smoking–Induced Mutagenesis as a Promoter of Lung Carcinogenesis
Authors: Akifumi Mochizuki, Kouya Shiraishi, Takayuki Honda, Ryoko Inaba Higashiyama, Kuniko Sunami, Maiko Matsuda, Yoko Shimada, Yasunari Miyazaki, Yukihiro Yoshida, Shun-Ichi Watanabe, Yasushi Yatabe, Ryuji Hamamoto, Takashi Kohno
Journal: Journal of Thoracic Oncology (2024)
Transgender Patient Preferences When Discussing Gender in Health Care Settings
Authors: Vern Harner, Megan Moore, Boi Casillas, Jess Chrivoli, Amaranta Lopez Olivares, Erin Harrop
Journal: JAMA Network Open (2024)

Importance Transgender (trans) patients report frequent discriminatory and harmful experiences in health care settings; gender-affirming, competent health care improves trans individuals’ health and well-being. Objective To identify factors influencing trans patients’ decision-making regarding sharing gender-related information with providers (clinicians, health care organizations, health care systems) and trans patient preferences for gender-related questions, as well as the subsequent impact on health care experiences. Design, Setting, and Participants A qualitative, interpretivist phenomenological study was conducted via telephone or video (using Zoom) in English and Spanish from August 10 to September 11, 2020. Participants were recruited via trans-specific social media groups and email listservs. Interviews were transcribed verbatim and analyzed from October 2020 to January 2022 using thematic analysis by a majority trans research team. Main Outcomes and Measures Semistructured interviews explored patient health care experiences and preferences. Results Participants included 27 trans and/or nonbinary adults (mean [SD] age, 30.9 [10.4] years; range, 21-69 years) from 13 US states. Four themes were identified: (1) impact of provider behaviors, (2) engaging in relational risk assessment, (3) receiving affirming vs medically competent care, and (4) “how are you going to fit [me] into your system?” The first theme reflected the impact of provider actions, including level of flexibility in care and interpersonal interactions, ability to explain medical relevance of gender-related questions, and preparedness to work with trans patients. Second, respondents weighed a variety of implicit or explicit safety cues when deciding whether and how to share information with providers. Third, participants spoke at length about affirming and medically competent care, noting that they have had to prioritize one over the other. Last, participants reported their needs often being at odds with health care system norms and standards of care. Conclusion and Relevance In this qualitative study of trans patient preferences when discussing gender-related information with providers, it was found that equitable, gender-affirming, and competent health care requires flexibility and responsiveness to patient preferences. It requires provider humility and engagement, as well as institutional policies that support competent and gender-affirming spaces. Future research could identify additional roles that providers, administrators, and systems can play in ensuring competent care for trans patients.
Sequence of Epinephrine and Advanced Airway Placement After Out-of-Hospital Cardiac Arrest
Authors: Masashi Okubo, Sho Komukai, Junichi Izawa, Kosuke Kiyohara, Tasuku Matsuyama, Taku Iwami, Tetsuhisa Kitamura
Journal: JAMA Network Open (2024)

Importance While epinephrine and advanced airway management (AAM) (supraglottic airway insertion and endotracheal intubation) are commonly used for out-of-hospital cardiac arrest (OHCA), the optimal sequence of these interventions remains unclear. Objective To evaluate the association of the sequence of epinephrine administration and AAM with patient outcomes after OHCA. Design, Setting, and Participants This cohort study analyzed the nationwide, population-based OHCA registry in Japan and included adults (aged ≥18 years) with OHCA for whom emergency medical services personnel administered epinephrine and/or placed an advanced airway between January 1, 2014, and December 31, 2019. The data analysis was performed between October 1, 2022, and May 12, 2023. Exposure The sequence of intravenous epinephrine administration and AAM. Main Outcomes and Measures The primary outcome was 1-month survival. Secondary outcomes were 1-month survival with favorable functional status and prehospital return of spontaneous circulation. To control imbalances in measured patient demographics, cardiac arrest characteristics, and bystander and prehospital interventions, propensity scores and inverse probability of treatment weighting (IPTW) were performed for shockable and nonshockable initial rhythm subcohorts. Results Of 259 237 eligible patients (median [IQR] age, 79 [69-86] years), 152 289 (58.7%) were male. A total of 21 592 patients (8.3%) had an initial shockable rhythm, and 237 645 (91.7%) had an initial nonshockable rhythm. Using IPTW, all covariates between the epinephrine-first and AAM-first groups were well balanced, with all standardized mean differences less than 0.100. After IPTW, the epinephrine-first group had a higher likelihood of 1-month survival for both shockable (odds ratio [OR], 1.19; 95% CI, 1.09-1.30) and nonshockable (OR, 1.28; 95% CI, 1.19-1.37) rhythms compared with the AAM-first group. For the secondary outcomes, the epinephrine-first group experienced an increased likelihood of favorable functional status and prehospital return of spontaneous circulation for both shockable and nonshockable rhythms compared with the AAM-first group. Conclusions and Relevance These findings suggest that for patients with OHCA, administration of epinephrine before placement of an advanced airway may be the optimal treatment sequence for improved patient outcomes.
Opioid Use After First Opioid Prescription in Children With Sickle Cell Disease
Authors: Angela B. Snyder, Mei Zhou, Brandon K. Attell, Lindsey L. Cohen, Sierra Carter, Fiona Bock, Carlton Dampier
Journal: JAMA Pediatrics (2024)

This cohort study assesses the level of opioid use, number of vaso-occlusive crises, and days’ supply of opioids among opioid-naive pediatric patients.
Ethics and Terminology for Opting In and Out
Authors: Alain Braillon
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Trends in Integration Between Physician Organizations and Pharmacies for Self-Administered Drugs
Authors: Pragya Kakani, David M. Cutler, Meredith B. Rosenthal, Nancy L. Keating
Journal: JAMA Network Open (2024)

Importance Increasing integration across medical services may have important implications for health care quality and spending. One major but poorly understood dimension of integration is between physician organizations and pharmacies for self-administered drugs or in-house pharmacies. Objective To describe trends in the use of in-house pharmacies, associated physician organization characteristics, and associated drug prices. Design, Setting, and Participants A cross-sectional study was conducted from calendar years 2011 to 2019. Participants included 20% of beneficiaries enrolled in fee-for-service Medicare Parts A, B, and D. Data analysis was performed from September 15, 2020, to December 20, 2023. Exposures Prescriptions filled by in-house pharmacies. Main Outcomes and Measures The share of Medicare Part D spending filled by in-house pharmacies by drug class, costliness, and specialty was evaluated. Growth in the number of physician organizations and physicians in organizations with in-house pharmacies was measured in 5 specialties: medical oncology, urology, infectious disease, gastroenterology, and rheumatology. Characteristics of physician organizations with in-house pharmacies and drug prices at in-house vs other pharmacies are described. Results Among 8 020 652 patients (median age, 72 [IQR, 66-81] years; 4 570 114 [57.0%] women), there was substantial growth in the share of Medicare Part D spending on high-cost drugs filled at in-house pharmacies from 2011 to 2019, including oral anticancer treatments (from 10% to 34%), antivirals (from 12% to 20%), and immunosuppressants (from 2% to 9%). By 2019, 63% of medical oncologists, 20% of urologists, 29% of infectious disease specialists, 21% of gastroenterologists, and 22% of rheumatologists were in organizations with specialty-relevant in-house pharmacies. Larger organizations had a greater likelihood of having an in-house pharmacy (0.75 percentage point increase [95% CI, 0.56-0.94] per each additional physician), as did organizations owning hospitals enrolled in the 340B Drug Discount Program (10.91 percentage point increased likelihood [95% CI, 6.33-15.48]). Point-of-sale prices for high-cost drugs were 1.76% [95% CI, 1.66%-1.87%] lower at in-house vs other pharmacies. Conclusions and Relevance In this cross-sectional study of physician organization–operated pharmacies, in-house pharmacies were increasingly used from 2011 to 2019, especially for high-cost drugs, potentially associated with organizations’ financial incentives. In-house pharmacies offered high-cost drugs at lower prices, in contrast to findings of integration in other contexts, but their growth highlights a need to understand implications for patient care.
Promising Efforts to Define a Novel Approach to Neuroprotection for Acute Ischemic Stroke
Authors: Craig S. Anderson, Lili Song
Journal: JAMA Neurology (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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
Late morbidity and mortality after autologous blood or marrow transplantation for lymphoma in children, adolescents and young adults—a BMTSS report
Authors: Anna Sällfors Holmqvist, Qingrui Meng, Chen Dai, Lindsey Hageman, Wendy Landier, Jessica Wu, Liton F. Francisco, Elizabeth Schlichting Ross, Nora Balas, Alysia Bosworth, Hok Sreng Te, Ravi Bhatia, Joseph Rosenthal, F. Lennie Wong, Daniel Weisdorf, Saro H. Armenian, Smita Bhatia
Journal: Leukemia (2024)

We determined the risk of late morbidity and mortality after autologous blood or marrow transplantation (BMT) for lymphoma performed before age 40. The cohort included autologous BMT recipients who had survived ≥2 years after transplantation (N = 583 [HL = 59.9%; NHL = 40.1%]) and a comparison cohort (N = 1070). Participants self-reported sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life threatening] or 5 [fatal]) was assigned to the conditions using CTCAE v5.0. Logistic regression estimated the odds of grade 3-4 conditions in survivors vs. comparison subjects. Proportional subdistribution hazards models identified predictors of grade 3-5 conditions among BMT recipients. Median age at BMT was 30.0 years (range: 2.0-40.0) and median follow-up was 9.8 years (2.0-32.1). Survivors were at a 3-fold higher adjusted odds for grade 3-4 conditions (95% CI = 2.3-4.1) vs. comparison subjects. Factors associated with grade 3-5 conditions among BMT recipients included age at BMT (>30 years: adjusted hazard ratio [aHR] = 2.31; 95% CI = 1.27-4.19; reference: ≤21 years), pre-BMT radiation (aHR = 1.52; 95% CI = 1.13-2.03; reference: non-irradiated), and year of BMT (≥2000: aHR = 0.54; 95% CI = 0.34-0.85; reference: <1990). The 25 years cumulative incidence of relapse-related and non-relapse-related mortality was 18.2% and 25.9%, respectively. The high risk for late morbidity and mortality after autologous BMT for lymphoma performed at age <40 calls for long-term anticipatory risk-based follow-up.
Post-transplant cyclophosphamide versus anti-thymocyte globulin after reduced intensity peripheral blood allogeneic cell transplantation in recipients of matched sibling or 10/10 HLA matched unrelated donors: final analysis of a randomized, open-label, multicenter, phase 2 trial
Authors: Eolia Brissot, Myriam Labopin, Helene Labussière, Gaelle Fossard, Patrice Chevallier, Thierry Guillaume, Ibrahim Yakoub-Agha, Micha Srour, Claude-Eric Bulabois, Anne Huynh, Sylvain Chantepie, Anne-Lise Menard, Marie-Therese Rubio, Patrice Ceballos, Rémy Dulery, Sabine Furst, Florent Malard, Didier Blaise, Mohamad Mohty
Journal: Blood Cancer Journal (2024)

Abstract The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is not established after reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) from fully matched donors. This was a randomized, open-label, multicenter, phase 2 trial. All patients received a RIC regimen with fludarabine, intravenous busulfan for 2 days (Flu-Bu2), and a peripheral blood stem cell (PBSC) graft from a matched related or 10/10 HLA-matched unrelated donor. Patients were randomly assigned to receive anti-thymocyte globulin (ATG) 5 mg/kg plus standard GVHD prophylaxis or PTCy 50 mg/kg/d at days +3 and +4 plus standard GVHD prophylaxis. The primary endpoint was the composite endpoint of GVHD- and relapse-free survival (GRFS) at 12 months after HSCT. Eighty-nine patients were randomly assigned to receive either PTCy or control prophylaxis with ATG. At 12 months, disease-free survival was 65.9% in the PTCy group and 67.6% in the ATG group ( P = 0.99). Cumulative incidence of relapse, non-relapse mortality, and overall survival were also comparable in the two groups. GRFS at 12 months was 54.5% in the PTCy group versus 43.2% in the ATG group ( P = 0.27). The median time to neutrophil and platelet count recovery was significantly longer in the PTCy group compared to the ATG group. Except for day +30, where EORTC QLQ-C30 scores were significantly lower in the PTCy compared to the ATG group, the evolution with time was not different between the two groups. Although the primary objective was not met, PTCy is effective for GVHD prophylaxis in patients receiving Flu-Bu2 conditioning with a PBSC graft from a fully matched donor and was well tolerated in term of adverse events and quality of life. This trial was registered at clinicaltrials.gov: NCT02876679.
Effect of Intravenous Zoledronic Acid on Total Knee Replacement in Patients With Symptomatic Knee Osteoarthritis and Without Severe Joint Space Narrowing: A Prespecified Secondary Analysis of a <scp>Two‐Year</scp>, Multicenter, <scp>Double‐Blind</scp>, <scp>Placebo‐Controlled</scp> Clinical Trial
Authors: Guoqi Cai, Laura L. Laslett, Michael Thompson, Flavia Cicuttini, Catherine Hill, Anita E. Wluka, Lyn March, Yuanyuan Wang, Petr Otahal, James D. Stoney, Benny Antony, Kathy Buttigieg, Tania Winzenberg, Graeme Jones, Dawn Aitken
Journal: Arthritis & Rheumatology (2024)

Objective To determine the effect of zoledronic acid (ZA) on the risk of total knee replacement (TKR) in patients with symptomatic knee osteoarthritis and without severe joint space narrowing (JSN). Methods We included 222 participants (mean age 62 years, 52% female) from the two‐year Zoledronic Acid for Osteoarthritis Knee Pain trial (113 received 5 mg of ZA annually and 109 received placebo) conducted between November 2013 and October 2017. Primary TKR were identified until February 22, 2022. The effect of ZA on TKR risk was evaluated using Cox proportional hazard regression models. Because the treatment effect failed the proportional hazards assumption, a time‐varying coefficients analysis for treatment was conducted by splitting the study into two periods (ie, within and after two years of randomization). Results Over a mean follow‐up of seven years, 39% and 30% of participants had any TKR in the ZA and placebo groups, and 28% and 18% had TKR in the study knee, respectively. Use of ZA was associated with a higher risk of TKR in any knee (hazard ratio [HR] 4.2, 95% confidence interval [CI] 1.2–14.7) and showed a trend in the study knee (HR 6.8, 95%CI 0.9–53.9) during the trial. In the posttrial period, the risk of TKR was similar in the ZA and the placebo groups for any knee (HR 1.2, 95%CI 0.5–1.8) and the study knee (HR 1.4, 95%CI 0.5–2.2). Conclusion These results suggest that ZA is not protective against TKR in patients with symptomatic knee osteoarthritis and without severe JSN. image
PRX1-positive mesenchymal stem cells drive molar morphogenesis
Authors: Xiaoqiao Xu, Xuyan Gong, Lei Zhang, Han Zhang, Yao Sun
Journal: International Journal of Oral Science (2024)

Mammalian teeth, developing inseparable from epithelial-mesenchymal interaction, come in many shapes and the key factors governing tooth morphology deserve to be answered. By merging single-cell RNA sequencing analysis with lineage tracing models, we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1+ cells within M1. These PRX1+ cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation. Deeper into the mechanisms, we have discovered that Wnt5a, bestowed by mesenchymal PRX1+ cells, stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway. The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1. Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs. These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.
Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort
Authors: Ioannis Parodis, Julius Lindblom, Guillermo Barturen, Rafaela Ortega-Castro, Ricard Cervera, Jacques-Olivier Pers, Fernanda Genre, Falk Hiepe, Maria Gerosa, László Kovács, Ellen De Langhe, Silvia Piantoni, Georg Stummvoll, Carlos Vasconcelos, Barbara Vigone, Torsten Witte, Marta E Alarcón-Riquelme, Lorenzo Beretta
Journal: Annals of the Rheumatic Diseases (2024)

To unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE).