Racial equity in urine drug screening policies in labor and delivery

IMPORTANCE: Black pregnant patients are significantly more likely than their White counterparts to undergo peripartum urine drug screening (UDS) and subsequent reporting to child protective services (CPS). OBJECTIVE: To evaluate the association of removing isolated cannabis use and limited prenatal care as order indications, combined with clinician-facing clinical decision support, with racial parity in peripartum UDS and CPS reporting. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study assessed 9396 pregnant patients at a single tertiary care center in a Midwestern US urban metropolitan region who delivered before (June 1, 2021, to September 31, 2022) and after (October 1, 2022, to January 31, 2024) the intervention. EXPOSURE: Updated UDS indications combined with clinical decision support. MAIN OUTCOMES AND MEASURES: Primary outcomes included UDS and CPS report rate by race before vs after the intervention. The secondary outcome was the rate of nonprescribed, noncannabis substance-positive UDS. Neonatal outcomes were included as balancing measures. RESULTS: Of 9396 female patients (median [IQR] age, 29 [24-33] years; 4305 [45.8%] Black, 4277 [45.5%] White, and 814 [8.7%] other race) included in the analysis, 4639 and 4757 delivered in the preintervention and postintervention periods, respectively. There was a small but statistically significant decrease in the number of Black patients before vs after the intervention (2210 [47.6%] vs 2095 [44.0%], P = .005); there were no significant differences in other race groups, median age, or multiparity. Before the intervention, 513 (23.2%) and 228 (11.1%) Black and White patients, respectively, had UDS (P \u3c .001) compared with 95 (4.5%) and 79 (3.6%) Black and White patients, respectively, after the intervention (P = .40). Before the intervention, an association between Black race and CPS report was observed (249 [11.3%] Black and 119 [5.8%] White patients, P \u3c .001); there was no association between race and CPS report after the intervention (87 [4.2%] Black and 78 [3.5%] White patients, P = .67). There was no association between the intervention and the percentage of UDS results that were positive for nonprescribed, noncannabis substances (107 [2.5%] preintervention vs 88 [2.0%] postintervention; P = .14). There was no significant association between the intervention and any measured neonatal outcomes. CONCLUSIONS AND RELEVANCE: In this quality improvement study, removal of isolated cannabis use and limited prenatal care as UDS indications, coupled with clinical decision support, was associated with improved racial equity in UDS testing and CPS reporting. The intervention was not associated with a significant change in UDS positivity for nonprescribed, noncannabis substances. These findings suggest that this intervention improved equity in UDS practices without decreasing identification of clinically relevant substance use

Social media as a platform for cancer care decision-making among women: Internet survey-based study on trust, engagement, and preferences

BACKGROUND: Decision aids improve patient and clinician decision-making but are underused and often restricted to clinical settings. OBJECTIVE: Given limited studies analyzing the feasibility of disseminating decision aids through social media, this study aimed to evaluate the acceptability, trust, and engagement of women with social media as a tool to deliver online decision aids for cancer treatment. METHODS: To prepare for potential dissemination of a breast cancer decision aid via social media, a cross-sectional survey in February 2023 was conducted via Prime Panels, an online market research platform, of women aged 35-75 years in the United States. Demographics, health, cancer information-seeking behaviors, social media use, trust in social media for health information, as well as the likelihood of viewing cancer-related health information and clicking on decision aids through social media, were assessed. Statistical analyses included descriptive statistics, correlations, and multivariable ordinal regression. RESULTS: Of 607 respondents, 397 (65.4%) had searched for cancer information, with 185 (46.6%) using the internet as their primary source. Facebook (Meta) was the most popular platform (511/607, 84.2%). Trust in social media for health information was higher among Black (14/72, 19.4%) and Asian respondents (7/27, 25.9%) than among White respondents (49/480, 10.2%; P=.003). Younger respondents aged 35-39 years (17/82, 20.7%) showed higher trust than those aged 70-79 years (12/70, 17.1%; P\u3c.001). Trust in social media for health information was linked to a higher likelihood of viewing cancer information and accessing a decision aid online (P\u3c.001). Participants who rated social media as Trustworthy (n=73) were more likely to view cancer information (61/73, 83.6%) and click on decision aids (61/73, 83.6%) than those who found it Untrustworthy (n=277; view: 133/277, 48.0%; click: 125/277, 45.1%). Engagement with social media positively correlated with viewing online cancer information (Spearman ρ=0.20, P\u3c.001) and willingness to use decision aids (ρ=0.21, P\u3c.001). Multivariable ordinal regression analyses confirmed that perception of social media\u27s trustworthiness is a significant predictor of engagement with decision aids (untrustworthy vs trustworthy β=-1.826, P\u3c.001; neutral vs trustworthy β=-0.926, P=.007) and of viewing cancer information (untrustworthy vs trustworthy β=-1.680, P\u3c.001, neutral vs trustworthy β=-0.581, P=.098), while age and employment status were not significant predictors. CONCLUSIONS: This exploratory study suggests that social media platforms may increase access to health information and decision aids. No significant differences were observed between demographic variables and the use or trust in social media for health information. However, trust in social media emerged as a mediating factor between demographics and engagement with cancer information online. Before disseminating decision aids on social media, groups should identify existing trust and engagement patterns with different platforms within their target demographic

Two-hit mouse model of heart failure with preserved ejection fraction combining diet-induced obesity and renin-mediated hypertension

Heart failure with preserved ejection fraction (HFpEF) is increasingly common but its pathogenesis is poorly understood. The ability to assess genetic and pharmacologic interventions is hampered by the lack of robust preclinical mouse models of HFpEF. We developed a novel two-hit model, which combines obesity and insulin resistance with chronic pressure overload to recapitulate clinical features of HFpEF. C57Bl6/NJ mice fed a high-fat diet (HFD) for \u3e 10 weeks were administered an AAV8-driven vector resulting in constitutive overexpression of mouse Renin1d. HFD-Renin (aka HFpEF ) mice demonstrated obesity and insulin resistance, moderate left ventricular hypertrophy, preserved systolic function, and diastolic dysfunction indicated by echocardiographic measurements; increased left atrial mass; elevated natriuretic peptides; and exercise intolerance. Transcriptomic and metabolomic profiling of HFD-Renin myocardium demonstrated upregulation of pro-fibrotic pathways and downregulation of metabolic pathways, in particular branched chain amino acid catabolism, similar to human HFpEF. Treatment with empagliflozin, an effective but incompletely understood HFpEF therapy, improved multiple endpoints. The HFD-Renin mouse model recapitulates key features of human HFpEF and will enable studies dissecting the contribution of individual pathogenic drivers to this complex syndrome. Additional preclinical HFpEF models allow for orthogonal studies to increase validity in assessment of interventions

Germline predisposition in multiple myeloma

We present a study of rare germline predisposition variants in 954 unrelated individuals with multiple myeloma (MM) and 82 MM families. Using a candidate gene approach, we identified such variants across all age groups in 9.1% of sporadic and 18% of familial cases. Implicated genes included genes suggested in other MM risk studies as potential risk genes

The foundational capabilities of large language models in predicting postoperative risks using clinical notes

Clinical notes recorded during a patient\u27s perioperative journey holds immense informational value. Advances in large language models (LLMs) offer opportunities for bridging this gap. Using 84,875 preoperative notes and its associated surgical cases from 2018 to 2021, we examine the performance of LLMs in predicting six postoperative risks using various fine-tuning strategies. Pretrained LLMs outperformed traditional word embeddings by an absolute AUROC of 38.3% and AUPRC of 33.2%. Self-supervised fine-tuning further improved performance by 3.2% and 1.5%. Incorporating labels into training further increased AUROC by 1.8% and AUPRC by 2%. The highest performance was achieved with a unified foundation model, with improvements of 3.6% for AUROC and 2.6% for AUPRC compared to self-supervision, highlighting the foundational capabilities of LLMs in predicting postoperative risks, which could be potentially beneficial when deployed for perioperative care

Mechanisms of uropathogenic E. coli mucosal association in the gastrointestinal tract

Urinary tract infections (UTIs) are highly recurrent and frequently caused by Uropathogeni

Virologic effects of broadly neutralizing antibodies VRC01LS and VRC07-523LS on chronic HIV-1 infection

BACKGROUNDHIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs) have emerged as promising interventions with the potential to effectively treat and prevent HIV-1 infections. We conducted a phase I clinical trial evaluating the potent CD4-binding site-specific (CD4bs-specific) bNAbs VRC01LS and VRC07-523LS in people with HIV-1 (PWH) not receiving antiretroviral therapy (ART).METHODSParticipants received a single intravenous 40 mg/kg dose of either VRC01LS (n = 7) or VRC07-523LS (n = 9) and did not initiate ART for a minimum of 14 days. The primary study objective was to evaluate safety and tolerability; the secondary study objectives were to evaluate pharmacokinetics (PK) and the impact of administered bNAbs on viral loads (VL) and CD4+ T cell counts in the absence of ART.RESULTSThis trial enrolled 16 PWH aged 20 to 57 years. Both bNAbs were safe and well tolerated. Mild local reactogenicity was only reported in participants who received VRC07-523LS, while both bNAbs were associated with mild systemic symptoms. Maximum serum concentrations (Cmax) following VRC01LS or VRC07-523LS were 1,566 ± 316 and 1,295 ± 376 μg/mL, respectively. VRC07-523LS administration significantly decreased VL in 8 out of 9 participants, with an average decline of 1.7 ± 0.8 log10 copies/mL within 14 days after administration. In contrast, VRC01LS administration resulted in a smaller average decline (0.8 ± 0.8 log10 copies/mL), and 3 out of 7 participants showedno change in VL. Postinfusion maximum decline in VL correlated with post hoc baseline in vitro viral susceptibility results for both bNAbs.CONCLUSIONThe results of this trial support inclusion of potent CD4bs-specific bNAbs, such as VRC07-523LS, into next-generation treatment regimens for HIV-1.TRIAL REGISTRATIONClinicalTrials.gov NCT02840474.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID)/NIH (grants UM1 AI068634, UM1 AI068636, UM1 AI106701, UM1AI069424, UM1AI069501, UM1AI69415, UM1AI069534, UM1AI69494); the Intramural Research Program of the NIAID/NIH; National Center for Advancing Translational Sciences/NIH (grants UM1TR004548, UL1TR001881, and UL1TR001878); and the National Cancer Institute/NIH (contract 75N91019D00024)

RAG suppresses group 2 innate lymphoid cells

Antigen specificity is the central trait distinguishing adaptive from innate immune function. Assembly of antigen-specific T cell and B cell receptors occurs through V(D)J recombination mediated by the Recombinase Activating Gene endonucleases RAG1 and RAG2 (collectively called RAG). In the absence of RAG, mature T and B cells do not develop and thus RAG is critically associated with adaptive immune function. In addition to adaptive T helper 2 (Th2) cells, group 2 innate lymphoid cells (ILC2s) contribute to type 2 immune responses by producing cytokines like Interleukin-5 (IL-5) and IL-13. Although it has been reported that RAG expression modulates the function of innate natural killer (NK) cells, whether other innate immune cells such as ILC2s are affected by RAG remains unclear. We find that in RAG-deficient mice, ILC2 populations expand and produce increased IL-5 and IL-13 at steady state and contribute to increased inflammation in atopic dermatitis (AD)-like disease. Furthermore, we show that RAG modulates ILC2 function in a cell-intrinsic manner independent of the absence or presence of adaptive T and B lymphocytes. Lastly, employing multiomic single cell analyses of RAG1 lineage-traced cells, we identify key transcriptional and epigenomic ILC2 functional programs that are suppressed by a history of RAG expression. Collectively, our data reveal a novel role for RAG in modulating innate type 2 immunity through suppression of ILC2s