tbuckley/cabot-search huggingface dataset:
Clinical Characteristics and Survival Outcomes of Metastatic Invasive Lobular and Ductal Carcinoma
Authors: Akshara S. Raghavendra, Roland Bassett, Senthil Damodaran, Carlos H. Barcenas, Jason A. Mouabbi, Rachel Layman, Debu Tripathy
Journal: JAMA Network Open (2025)

Importance Comparing the clinical and molecular features of metastatic invasive lobular carcinoma (mILC) and metastatic invasive ductal carcinoma (mIDC) is essential to enhance understanding of breast cancer biology and improve personalized treatment approaches. Objective To compare mILC and mIDC in terms of survival outcomes and to investigate the association of clinicopathologic characteristics with those outcomes. Design, Setting, and Participants This cohort study included adult patients at the University of Texas MD Anderson Cancer Center with their first metastatic diagnosis occurring between January 1997 and December 2020. Patient records were obtained from an institutional database. The study follow-up concluded in July 2023, and data were analyzed from July to December 2024. Exposure Diagnosis of mIDC and mILC. Main Outcomes and Measures Progression-free survival (PFS), overall survival (OS), and disease-free interval (DFI) were estimated using the Kaplan-Meier method. Survival distributions were compared using the log-rank test. Multivariable Cox proportional hazards regression was used to assess the association of metastasis onset, estrogen receptor (ER) expression level, and tumor grade with OS and PFS. Results The analysis included a total of 9714 patients (9628 women [99%]), 8535 with mIDC and 1179 with mILC. The median age at metastasis was 53.3 years (range, 17.6-62.0 years). Generally, patients with mILC were older and had lower nuclear grade tumors and fewer metastasis sites than patients with mIDC. Patients with mILC had longer PFS (median, 0.65 years; 95% CI, 0.58-0.74) than patients with mIDC (median, 0.46 years; 95% CI, 0.45-0.48) (hazard ratio [HR], 0.78; 95% CI, 0.73-0.84; P &amp;amp;lt; .001). For OS, patients with mILC had longer OS (median, 3.06 years; 95% CI, 2.87-3.29) than patients with mIDC (median, 2.60 years; 95% CI, 2.52-2.67 years) (HR, 0.91; 95% CI, 0.84-0.98; P = .01). Overall, patients with mILC had longer DFI than patients with mIDC (HR, 0.69; 95% CI, 0.64-0.75; P &amp;amp;lt; .001). At initial diagnosis, patients with mILC were less likely to present with visceral metastasis (522 patients [44.3%]) than patients with mIDC (4909 patients [57.5%]). A higher proportion of patients with mILC (931 patients [79.0%]) than patients with mIDC (5431 patients [63.6%]) had bone-only metastasis. Conclusions and Relevance In this cohort study, patients with mILC had longer OS and PFS than those with mIDC. Metastasis onset, ER positivity, and tumor grade were associated with survival outcomes, and distinct metastatic patterns of mIDC and mILC were also associated with survival for mIDC and mILC, which may help guide more personalized treatment strategies for each subtype.
Cerebrospinal Fluid Biomarkers for Alzheimer Disease Among Patients With Dementia
Authors: Tobias Borgh Skillbäck, Linus Jönsson, Ingmar Skoog, Kaj Blennow, Maria Eriksdotter, Henrik Zetterberg, Silke Kern
Journal: JAMA Neurology (2025)

Importance The defining pathological features of Alzheimer disease (AD) may also be contributing factors in other dementias. Objective To examine the prevalence of β-amyloid (Aβ) and tau pathophysiological changes as indicated by cerebrospinal fluid biomarkers, as well as their association with clinical disease progression, across a broad range of dementias. Design, Setting, and Participants In this cross-sectional study with a duration of 12 years (October 5, 2010, to August 31, 2022), clinical data from the Swedish registry for cognitive disorders and dementia (SveDem) were merged with clinical routine biomarker measurements of the core cerebrospinal fluid biomarkers of AD: Aβ1-42, total tau (t-tau), and phosphorylated tau 181 (p-tau181). Participants were individuals with a dementia diagnosis who had a complete set of cerebrospinal fluid Aβ1-42, t-tau, and p-tau measurements registered less than 3 years after the date of diagnosis. Data were analyzed from April to November 2023. Exposures Age, sex, and dementia diagnosis. Main Outcomes and Measures Biomarker profiles in relation to diagnosis and cognitive status as indicated by Mini-Mental State Examination (MMSE) scores. Results Among 15 004 individuals with a dementia diagnosis in the SveDem database, 13 882 were included in this study (7328 females [53%], 6554 males [47%]; median [IQR] age, 74 [68-79] years). Apart from the AD groups (early-onset AD, 1150 [68%]; late-onset AD, 3392 [65%]; mixed AD and vascular dementia, 1038 [52%]), the dementia not otherwise specified group had the most patients (443 [25%]) with a clear AD-like biomarker profile, while Parkinson disease dementia and the frontotemporal dementia groups had the smallest shares (15 [9%] and 51 [8%], respectively). MMSE score was associated with cerebrospinal fluid Aβ1-42 in late-onset AD, vascular dementia, frontotemporal dementia, and dementia not otherwise specified; with t-tau in late-onset AD, early-onset AD, and dementia not otherwise specified; and with p-tau181 in early-onset AD. Conclusions and Relevance Aβ-related pathology is a defining feature of AD, and most patients clinically diagnosed with AD have biomarker evidence of this process, but the same is found in other dementias, although less commonly. Cerebrospinal fluid biomarker concentrations of AD-like pathology were associated with cognitive function but mainly in patients with an AD-related diagnosis (early- and late-onset AD).
Low-Intensity Social Care and Child Acute Health Care Utilization
Authors: Stacy Tessler Lindau, Jennifer A. Makelarski, Victoria A. Winslow, Emily M. Abramsohn, Veera Anand, Deborah L. Burnet, Charles M. Fuller, Mellissa Grana, Doriane C. Miller, Eva S. Ren, Elaine Waxman, Kristen E. Wroblewski
Journal: JAMA Pediatrics (2025)

Importance Social care could be sustained with savings resulting from reduced acute health care utilization. Objective To evaluate the impact of CommunityRx, a low-intensity, high-scale social care assistance intervention. Design, Setting, and Participants This double-blind randomized clinical trial took place from November 2020 through August 2023 at an urban children’s hospital with 12-month follow-up. Inclusion criteria were primary caregiver of a child younger than 18 years who was hospitalized in general, intensive care, or transplant units, living in 1 of 42 zip codes, and consenting to text messages. Caregivers of healthy newborns and children with expected hospitalization less than 24 hours or longer than 30 days were excluded. Interventions Participants were randomized to usual care (n = 320) or usual care plus CommunityRx (n = 320). Essential intervention components included education about common social conditions, personalized information about local resources, and ongoing navigator support with automated, proactive text messages (3 months) and ongoing availability for participant-initiated requests (12 months). Main Outcomes and Measures Preplanned analyses focused on food insecure (FI) subgroup outcomes (n = 223): self-efficacy for finding resources at 12 months (primary), caregiver-reported child health, and number of child emergency department (ED) and hospital admissions over 12 months. Regression models were fit with treatment group and baseline outcome characteristics. Odds ratios (ORs) or incidence rate ratios (IRRs) and 95% CIs were calculated. Post hoc analysis examined outcomes among the food secure (FS) subgroup (n = 414). Results Preplanned analyses included 223 FI participants and most identified as female (180 [95%]) and had household income less than $50 000 per year (197 [91%]). Self-efficacy at 12 months was similar among treatment groups (OR, 0.59; 95% CI, 0.25-1.39, P = .23). At 3 months, when automated navigator texts ended, 53 intervention group participants (69%) and 39 controls (45%) rated their child’s health as excellent or very good (OR, 2.67; 95% CI, 1.14-6.24). During 12 months postdischarge, 54 FI children (41%) had 1 or more ED visits (median, 0; range, 0-32; intervention, 30%; control, 52%; IRR, 0.40; 95% CI, 0.21-0.76) and 32 had 1 or more hospitalizations (24%) (median, 0; range, 0-5; intervention, 15%; control, 34%; IRR, 0.48; 95% CI, 0.21-1.06). The intervention did not impact outcomes among FS caregivers. Conclusions and Relevance A low-intensity, high-scale social care assistance intervention beginning with pediatric hospitalization may be sustainable by reducing acute health care utilization, but did not increase caregiver self-efficacy for finding resources. Trial Registration ClinicalTrials.gov Identifier: NCT04171999
Long-Term Spending of Accountable Care Organizations in the Medicare Shared Savings Program
Authors: Amelia M. Bond, Yasin Civelek, William L. Schpero, Lawrence P. Casalino, Manyao Zhang, Reekarl Pierre, Dhruv Khullar
Journal: JAMA (2025)

Evidence from initial cohorts of accountable care organizations (ACOs) participating in the Medicare Shared Savings Program (MSSP) found modest reductions in health care spending. Little is known about whether these effects have changed over time. To determine long-term changes in spending for MSSP ACO participants. Using 2010 to 2019 traditional Medicare data, difference-in-differences analyses were performed to compare spending changes for patients attributed to ACOs relative to changes for patients at non-ACO organizations. Outcomes included total Medicare spending and spending by category. Three- and 6-year effects and estimated differential changes overall and by ACO characteristics were calculated, including size (small defined as <10 000 patients), rurality, and whether an ACO included a hospital (hospital-associated ACO) or not (physician-group ACO). Attribution to a medical group or clinic in an ACO during the first 2 years of ACO tenure. Total annual per-patient Medicare spending. The sample included 41 973 272 Medicare patient-years. Baseline characteristics for 2 719 406 ACO patients and 5 523 652 control patients were similar (average age, 72 years; 58% female; and 82% to 84% White) prior to ACO formation in 2010 and 2011, and unadjusted annual per-patient spending was slightly lower in the ACO group vs control group ($12 147 vs $12 318; difference, -$171 [95% CI, -$223 to -$118]) in the 2 years prior to ACO formation. ACO formation was associated with a mean differential reduction of $142 (95% CI, -$193 to -$92) in annual per-patient spending over 3 years and $294 (95% CI, -$347 to -$241) over 6 years. Spending reductions associated with ACO formation increased over time: compared with control patients, ACO patients experienced a mean reduction of $234 (95% CI, -$298 to -$171) in year 3 and $584 (95% CI, -$680 to -$489) in year 6. Physician-group and small ACOs generated larger spending reductions. Spending changes resulted in $4.1 billion to $8.1 billion in savings to Medicare between 2012 and 2019. During the MSSP's first decade, ACOs generated meaningful reductions in spending, with larger effects over time.
Development of Common Data Elements for Organ Transplantation
Authors: Lisa M. McElroy, Ursula Rogers, Liz Nichols, Nrupen A. Bhavsar, Tyler Schappe, Jessica Harding, Alexandra T. Strauss, Elisa J. Gordon, Katie Ross-Driscoll, Rhiannon Deirhoi-Reed, Norine W. Chan, Jackie B. Henson, Yue Harn Ng, Dave J. Taber, Adam J. Milam, Jesse D. Schold, Juan Carlos Caicedo, Andrew B. Adams, Rachel E. Patzer, Samuel I. Berchuck, Roland Matsouaka, Jennifer Gagnon, Allan D. Kirk
Journal: JAMA Network Open (2025)

This cohort study examines the validity of an electronic health record data model for organ transplantation.
SGLT2 Inhibitors and Risk for Hyperkalemia Among Individuals Receiving RAAS Inhibitors
Authors: Sara Wing, Joel G. Ray, Kevin Yau, Nivethika Jeyakumar, Sheikh Abdullah, Bin Luo, David Z. I. Cherney, Ziv Harel, Gregory L. Hundemer, Thomas A. Mavrakanas, Amber O. Molnar, Ayodele Odutayo, Jeffrey Perl, Ann Young, David Charytan, Matthew Weir, Ron Wald
Journal: JAMA Internal Medicine (2025)

Importance Hyperkalemia is a common complication of taking a renin-angiotensin-aldosterone system inhibitor (RAASi). Post hoc analyses of large randomized clinical trials suggested that the addition of sodium-glucose cotransporter 2 inhibitors (SGLT2i) may attenuate this risk. It is unknown if this observation extends to daily clinical practice. Objective To evaluate the association between SGLT2i initiation and hyperkalemia in individuals receiving RAASi with a background of diabetes, heart failure, or chronic kidney disease. Design, Setting, and Participants This population-based retrospective cohort study was conducted in Ontario, Canada, from July 1, 2015, to June 30, 2021. The cohort comprised adults 66 years and older who were prescribed a RAASi and had a history of diabetes or heart failure, an estimated glomerular filtration rate of less than 45 mL/min/1.73 m 2 , and/or a urine albumin to creatinine ratio of greater than 30 mg/mmol. The data were analyzed between March 28, 2023, and March 22, 2024. Exposure The study exposure was a new prescription of an SGLT2i compared to noninitiation of an SGLT2i. Inverse probability of treatment weighting by a propensity score for the receipt of SGLT2i was used to achieve balance of baseline covariates in both exposure groups. Main Outcomes and Measures The primary study outcome was hyperkalemia, defined as a serum potassium of greater than 5.5 mEq/L or an administrative code for an inpatient or outpatient encounter with hyperkalemia within 1 year of the index date. Results A total of 20 063 individuals who initiated an SGLT2i (mean [SD] age, 76.9 [6.6] years; 12 020 [59.9%] male) were compared to a pseudopopulation of 19 781 nonusers (mean [SD] age, 76.8 [7.0] years; 11 731 [59.3%] male). In the overall cohort, 95% had diabetes, 17% had heart failure, and 32% had stage 3 to 5 chronic kidney disease. SGLT2i initiation was associated with a lower risk of hyperkalemia (hazard ratio, 0.89 [95% CI, 0.82-0.96]). SGLT2i users had a significantly lower rate of RAASi discontinuation compared to nonusers (36% vs 45%; P &amp;amp;lt; .001). Conclusions and Relevance This cohort study demonstrated that, among individuals with diabetes, heart failure, or chronic kidney disease who were receiving a RAASi, SGLT2i initiation was associated with a lower risk of hyperkalemia and RAASi discontinuation.
Emergency Department Visits for Medication-Related Events With vs Without Pharmacist Intervention
Authors: Maxime Villiet, Marion Laureau, Damien Perier, Véronique Pinzani, Isabelle Giraud, Laura Lohan, Xavier Bobbia, Grégoire Mercier, Audrey Jaussent, Valérie Macioce, Mustapha Sebbane, Marie Faucanié, Cyril Breuker
Journal: JAMA Internal Medicine (2025)

Medication-related events (MREs) are a frequent cause of emergency department (ED) visits and patient harm. To assess the efficacy of a pharmacist-led transition of care program in reducing ED visits related to the same MRE at 6 months compared with usual care. This prospective, open-label, parallel-group randomized clinical trial was conducted from November 2018 to July 2021 at the ED of Montpellier University Hospital, Montpellier, France, with a 6-month follow-up period. Adult patients with an MRE detected at ED admission were included. MREs included adverse drug events with or without misuse and medication nonadherence with unfavorable clinical evolution. End points were assessed blindly from the randomization arm. Data were analyzed from January 2022 to March 2024. Participants were randomized to a pharmacist-led transition of care program or usual care. Usual care included the ED pharmacist carrying out a medication history. In the transition of care group, ED pharmacists additionally made a postdischarge telephone call to the general practitioner (GP) and community pharmacist, along with a letter, notifying them about MRE type, suspected medication, and management recommendations. The primary outcome was the proportion of patients with an ED visit for the same MRE at 6 months (same symptom and medication involved). Secondary outcomes included proportions of all-cause and MRE-related ED visits, hospitalizations, deaths, and medical office visits. Among 330 patients analyzed, 187 (56.7%) were female, the median (IQR) age was 71 (50-83) years, and the median (IQR) home medications count was 6 (3-10). A total of 167 patients were randomized to the transition of care group and 163 to the control group. At 6 months, fewer participants in the transition of care group had ED visits related to the same MRE (5 [3.0%] vs 36 [22.1%]; risk difference [RD], -19.1 percentage points; 95% CI, -26.0 to -12.2; P < .001), all-cause ED visits (35 [21.0%] vs 57 [35.0%]; RD, -14.0 percentage points; 95% CI, -23.6 to -4.4), hospitalization related to the same MRE (3 [1.8%] vs 29 [17.8%]; RD, -16.0 percentage points; 95% CI, -22.2 to -9.8), and more GP office visits (88 of 158 [55.7%] vs 26 of 146 [17.8%]; RD, 37.9 percentage points; 95% CI, 28.0 to 47.8) and specialist office visits (67 of 158 [42.4%] vs 35 of 146 [24.0%]; RD, 18.4 percentage points; 95% CI, 8.1 to 28.8) related to the same MRE. All-cause hospitalization and death were similar between groups. In this randomized clinical trial, a pharmacist-led transitional care intervention in the ED among patients with MRE significantly reduced ED visits and hospitalizations for the same MRE. If replicated in subsequent trials, this strategy offers a novel approach for reducing drug-related harms. ClinicalTrials.gov Identifier: NCT03725046.
Donor History of Drug Use and Graft Survival in Pediatric Heart Transplant Recipients
Authors: Paul Esteso, Kimberlee Gauvreau, Caitlin Milligan, Linda Vo, Francis Fynn-Thompson, Elizabeth D. Blume, Tajinder P. Singh
Journal: JAMA Network Open (2025)

Importance Older children awaiting a heart transplant (HT) sometimes receive a heart offer from a donor with a history of drug use (HDU). The effect of using such donor hearts on posttransplant survival in pediatric recipients is unclear. Objective To assess the association of using hearts from donors with HDU on posttransplant graft survival in pediatric HT recipients. Design, Setting, and Participants For this retrospective cohort study, all pediatric HT recipients (aged &amp;amp;lt;18 years) in the Organ Procurement and Transplantation Network database during January 1, 2000, to December 31, 2020, were identified. Among the recipients who received a heart from a donor with HDU, nearly all donors were aged 11 years or older. A propensity score (PS) model was developed to assess the probability of receiving a heart from a donor with HDU using baseline recipient and donor variables, limiting the study cohort to donors aged 11 years or older. Data were analyzed from October 2023 to November 2024. Exposure HT using a heart from a donor with HDU (exposure group) vs from a donor without HDU (control group). Main Outcomes and Measures The main outcome was graft loss (death or retransplant) assessed at 90 days after transplant and long term among 90-day survivors. Kaplan-Meier survival curves and a Cox proportional hazards regression model that accounted for matching of exposure and control groups were used to compare risk of graft loss. Results This study included 2730 pediatric HT recipients. Their median age at HT was 14 years (IQR, 11-16 years), and most (1642 [60.1%]) were male. Overall, the exposure group comprised 822 children who received a heart from a donor with HDU; of these, 765 (93.1%) were PS matched to the control group. There was no difference in risk of graft loss within 90 days (hazard ratio [HR], 0.93 [95% CI, 0.55-1.57]; P = .78) or at long-term follow-up (HR, 1.04 [95% CI, 0.87-1.25]; P = .68) between PS-matched groups. Risk of graft loss within 90 days was not significantly different in children who received a heart from a donor with a history of cocaine use (157 pairs) vs children in the control group (HR, 0.55 [95% CI, 0.19-1.54]; P = .25); however, the risk of long-term graft loss among 90-day survivors was significantly higher (HR, 2.03 [95% CI, 1.35-3.06]; P = .001). Conclusions and Relevance In this cohort study of pediatric HT recipients, there was no association of 90-day graft survival with donor HDU; however, donor history of cocaine use was associated with a higher risk of long-term graft loss. These findings may be important when considering a donor with HDU for pediatric HT candidates.
Barriers and Opportunities for Cancer Clinical Trials in Low- and Middle-Income Countries
Authors: Linsey Eldridge, Nina R. Goodman, Amina Chtourou, Annette Galassi, Cecilia Monge, Mishka Kohli Cira, Paul C. Pearlman, Patrick J. Loehrer, Satish Gopal, Ophira Ginsburg
Journal: JAMA Network Open (2025)

Importance Clinical trials represent the gold standard to test the safety and efficacy of new or updated approaches to treatments that will inform quality cancer care. However, cancer trials enroll few patients in low- and middle-income countries (LMICs), are often led by investigators from high-income countries, and do not adequately reflect global disease burden or population diversity. Objective To identify key challenges and strategies to advance contextually relevant, quality cancer trials in LMICs. Design, Setting, and Participants The survey used in this survey study was available in English, Arabic, French, Portuguese, and Spanish and was conducted by the US National Cancer Institute from October 18 to December 22, 2023. Clinicians with experience in cancer therapeutic clinical trials in LMICs were eligible. The survey covered their professional background and views on challenges and strategies for improving clinical trial opportunities in LMICs. Analysis was performed from April 2 to August 26, 2024. Main Outcomes and Measures Respondents were asked to rate 34 challenges by impact on their ability to conduct cancer trials using a 4-point Likert scale and 8 strategies by importance using a 5-point Likert scale. Descriptive statistics summarized participants’ backgrounds, challenges, and priorities. Results Of 453 respondents who began the survey, a total of 223 (49%) were eligible for inclusion, and 131 of those (59%) completed the survey in full. Among the 133 respondents who provided gender data, 81 (61%) were male. In all, 107 of 130 respondents (82%) were affiliated with LMIC institutions, 65 of 223 (29%) were medical oncologists, and 52 of 133 (39%) were midcareer. Financial challenges were rated as the most impactful, with 133 of 170 respondents (78%) rating difficulty obtaining funding for investigator-initiated trials as having a large impact on ability to carry out a trial. Human capacity issues followed, with 105 of 192 respondents (55%) rating lack of dedicated research time as having a large impact. Increasing opportunities for funding and improving human capacity were reported as key strategies to advance capacity to conduct clinical trials in LMICs. Conclusions and Relevance This survey study of clinicians with clinical trial experience in LMICs suggests that adequate funding and a well-trained research workforce are 2 predominant challenges to advancing cancer therapeutic clinical trials in LMICs. Understanding these obstacles can inform efforts to support cancer clinical trials that better reflect worldwide needs and diversity by prioritizing and sustaining research led by LMIC investigators.