Citations

ABSTRACT: Background Type 2 diabetes (T2D) is common among patients undergoing coronary artery bypass grafting (CABG), but optimal post‐CABG glucose‐lowering therapy remains uncertain. Methods We conducted a retrospective cohort study using the OptumLabs Data Warehouse of adults with T2D undergoing isolated CABG from 2012–2024. Follow‐up began 30 days after discharge. Glucose‐lowering therapy was modeled as a time‐varying exposure with patients contributing no‐observed‐therapy person‐time until the first qualifying post‐discharge fill. Pairwise comparisons used stabilized inverse probability of treatment weighting. The primary outcome was all‐cause mortality; secondary outcomes were heart failure hospitalization, stroke, and repeat coronary revascularization. Results Among 19,237 patients, 24.9% had no observed post‐discharge therapy, 42.8% received metformin, 22.9% received insulin, and 9.4% received GLP‐1RA/SGLT2i therapy. All active therapies were associated with lower mortality compared with no observed therapy, including GLP‐1RA/SGLT2i (HR 0.71, 95% CI 0.58–0.87), metformin (HR 0.60, 95% CI 0.55–0.66), and insulin (HR 0.75, 95% CI 0.67–0.84). Among active therapies, metformin was associated with lower mortality than insulin (HR, 0.61 [0.54–0.70]); GLP‐1RA/SGLT2i comparisons with metformin and insulin were less precise. Metformin was also associated with lower cumulative incidence of heart failure hospitalization than no observed therapy and insulin, and lower stroke incidence than insulin. Conclusions Observed glucose‐lowering therapy initiation after CABG was associated with lower mortality compared with no observed therapy across all active treatment groups. These findings highlight a potential care gap and suggest that proper initiation of diabetes therapy after CABG represents an important opportunity to improve long‐term outcomes following surgical revascularization.

Introduction The World Health Organization (WHO) endorses male circumcision as an effective human immunodeficiency virus (HIV) prevention intervention in settings where the expected impact is greatest, including Sub-Saharan Africa. Data on cost implications of early infant male circumcision (EIMC) are limited. The ShangRing (SR) is a WHO pre-qualified device for circumcision. We sought to perform a comprehensive cost assessment alongside a randomized controlled trial (RCT) of the SR versus the standard of care Mogen clamp (MoC) for EIMC to enable future scale-up towards a cost-effective HIV prevention strategy. Methods We collected resource utilization and economic data as part of an RCT of infants aged 0–60 days old undergoing EIMC in Kenya, Tanzania, and Uganda. Cost data for both the SR and MoC included baseline facility costs, direct costs, and indirect costs. The Decision Makers Program Planning Tool v1.0 was used to perform a direct cost comparison of these two devices. The Goals model was used to compare the costs of EIMC in 2023 using the present value of money to circumcise an adolescent male 15 years from now. Results A total of 1,378 infant males underwent circumcision, 689 via SR and 689 via MoC. The overall cost of a single EIMC in Kenya, Tanzania, and Uganda were 61.30 United States Dollars ($), $47.14, and $64.59 respectively for the SR, and $56.38, $50.43, and $58.57 respectively for the MoC. In Kenya, EIMC would be less expensive based on nominal present costs in 2023 compared to waiting for adolescent circumcision at age 15 years in 2038. This finding is reversed in Tanzania and Uganda. Conclusions The overall cost of EIMC via SR versus MoC is comparable in an RCT. With scale-up utilizing lower level personnel, the cost of SR may be further reduced. The SR is an attractive alternative for future EIMC initiatives in Sub-Saharan Africa to further reduce HIV burden.

Abstract Background Women remain underrepresented in alcohol use disorder (AUD) research despite sex- and gender-specific health disparities and barriers to treatment. Community-engaged approaches can identify opportunities for patient-centered comparative effectiveness research (CER) that reflect women’s lived experiences. The WomenWise project used community engaged, bi-directional, partnered learning sessions (PLS) to qualitatively explore women’s perspectives on alcohol misuse, treatment barriers, and priorities for future CER. Methods In 2025, we conducted five 90-minute PLSs via Zoom with attendees who were aged ≥ 18 years, self-identified as a woman, reported lived experience of alcohol misuse, were a family member/caregiver of a woman with AUD, and were affiliated with a WomenWise partner organization or a healthcare provider treating AUD. Moderated PLSs focused on bi-directional knowledge exchange and sharing of experiences. Audio transcripts, Zoom chat content, and one asynchronous online discussion thread were analyzed using reflexive thematic analysis. Suggested future CER topics generated during sessions were presented to the WomenWise community advisory board (CAB), which ranked priority topics by vote. Results In total, 51 attendees shared their experiences. The major themes centered on a sense of shame and stigma unique to women, with many attendees mentioning gendered norms, “mom culture,” “quiet drinking,” and caregiver role strain. Barriers to treatment included structural challenges, poor healthcare provider communication, the need for trauma-informed care, and concerns about privacy particularly in rural areas. Six future CER topics emerged, of which the CAB selected three priorities: (1) harm reduction/moderation versus abstinence-only approaches, (2) trauma-focused care versus standard AUD treatment, and (3) care access and engagement strategies. Conclusions These bidirectional, co-learning sessions identified patient-centered, community-informed priorities for future AUD research in women. The findings highlight the importance of addressing stigma, trauma, structural barriers, and provider communication when designing future women-centered treatment studies and care models.

Background: Pulse pressure variation (PPV) is widely used to guide fluid responsiveness in mechanically ventilated patients, but its accuracy in the prone position remains uncertain. Prone positioning alters respiratory mechanics and venous return, potentially diminishing the respiratory variation in stroke volume that PPV is designed to detect. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of PPV for predicting fluid responsiveness during prone spine surgery. Methods: We searched MEDLINE, Embase, Scopus, and Cochrane through July 2025 for prospective studies evaluating PPV in adults undergoing prone spine surgery. Two reviewers independently screened studies, extracted data, assessed risk of bias using QUADAS-2, and pooled diagnostic performance using a bivariate random-effects model. The protocol was registered with PROSPERO (CRD420251106134). Results: Of 599 records, 34 underwent full-text review, and 10 studies (433 patients) were included. PPV thresholds ranged from 7% to 15%. Most studies were at low risk of bias except for the index test because thresholds were determined post hoc. For predicting fluid responsiveness, PPV had a pooled sensitivity of 68% (95% CI: 61%-75%) and specificity of 76% (95% CI: 65%-84%), with a summary area under the receiver operating characteristic curve of 0.72 (95% CI: 0.64-0.80). Conclusions: PPV showed only moderate diagnostic performance for predicting fluid responsiveness during prone spine surgery. Its performance may have been influenced by threshold variability, heterogeneous reference standards, fluid-challenge protocols, ventilation strategies, and positioning systems. PPV should therefore be interpreted alongside complementary dynamic assessments rather than in isolation, particularly during lung-protective ventilation.

ABSTRACT Purpose This study assesses the association between colorectal cancer (CRC) screening and a validated, housing-based measure of individual-level socioeconomic status (SES, called HOUSES hereafter) within rural communities and determines whether HOUSES-integrated geospatial analysis can be used to tailor interventions. Methods We used CRC screening data from a subset of Mayo Clinic Midwest patients living in cities without ready access to routine care in the Mayo Clinic Health System in 2019 to represent rural communities. At the individual level, we assessed the association between CRC screening rates and the HOUSES index, adjusting for age, sex, race/ethnicity, comorbidity, distance from home address to clinic, and area deprivation index, using a multilevel mixed-effects logistic regression model. Additionally, we conducted geospatial analysis to examine the correlation between hotspots of 1) lower CRC screening rates and 2) lower SES of the subject population (HOUSES quartile 1). Findings Among 34,489 individuals (median age 64.0 years, 52.4% female), those with the lowest SES (HOUSES Q1) had 37% lower odds of being CRC screening adherent than those with the highest SES (HOUSES Q4) (adj. OR [95% CI]: 0.63 [0.58-0.69]). In the 14 identified HOUSES Q1 hotspots, there was a significant correlation in counts of HOUSES Q1 and low CRC screening (correlation coefficient=0.81). Conclusion Lower SES was significantly associated with lower CRC screening among rural populations. HOUSES-enabled geospatial analysis identified geographic hotspots with lower CRC screening rates for targeted interventions to address disparities in CRC screening in rural communities. HOUSES may be a useful digital tool for cancer preventive care and research.

Abstract. Introduction: Preterm birth drives adverse perinatal maternal and infant health outcomes through heterogeneous symptoms, severity, and etiologies. Delivery prior to reaching 37 weeks of gestation may result from medically indicated intervention for pregnancy complications or spontaneously in the absence of prior symptoms. Placental tissue collected following preterm birth exhibits differential DNA methylation compared to full-term placentas and may indicate pregnancy health during gestation. Placental DNA currently has limited utility for assessing health of ongoing pregnancy, as sampling placental tissue during gestation increases the risk of infection and miscarriage. Risks associated with placental sampling during pregnancy limit the use of DNA methylation in clinical preterm birth prediction. Assessing preterm birth risk during gestation requires non-invasive methods for characterizing placental DNA methylation. Results: We quantified genome-wide DNA methylation patterns of hypermethylated cell-free DNA in pregnant (n = 99) and non-pregnant (n = 93) plasma using cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq). In each sample, we assessed DNA methylation status in 300-bp genomic windows, examining both sequencing read counts and calculated absolute molar DNA amount. Known hypermethylated placental regions, including RASSF1, STAT5A, and ERG promoters showed significantly increased odds of detection in pregnant samples, suggesting enrichment of cell-free placental DNA. Of the 536,444 300-bp windows examined, 173,071 (32%) showed significant enrichment in pregnant plasma. Linear modeling identified 107,505 differentially methylated regions (DMRs) associated with pregnancies later diagnosed with intrauterine growth restriction (IUGR) (n = 22). Alu elements showed increased representation in these DMRs than expected, while other repetitive elements exhibited underrepresentation. Discussion: These results demonstrate cfMeDIP-seq's ability to enrich for cell-free placental DNA and characterize cell-free DNA methylation signatures of pregnancies complicated by IUGR. Enrichment of cell-free placental DNA enables non-invasive profiling of placental DNA methylation from maternal plasma. Detectable epigenetic signatures in maternal plasma may identify pregnancies at elevated risk for preterm birth before clinical symptoms appear. Our findings further highlight the potential of cell-free placental DNA for monitoring pregnancy health.

Importance Patients undergoing cardiac surgery with cardiopulmonary bypass often require platelet transfusions for bleeding. Platelets are routinely stored at room temperature (20-24 °C) for up to 5 to 7 days; however, cold storage (1-6 °C) may allow for increased storage duration without loss of hemostatic function. Objective To determine the maximum cold-storage duration, up to 21 days, for which cold-stored platelets (CSPs) are noninferior or superior in hemostatic efficacy to room-temperature platelets (RTPs) when transfused in actively bleeding patients undergoing cardiac surgery with cardiopulmonary bypass. Design, Setting, and Participants A phase 3, multicenter, randomized, partially blinded, adaptive, noninferiority, storage duration–ranging trial conducted in pediatric and adult patients undergoing cardiac surgery with planned cardiopulmonary bypass at 27 sites in the US and Australia from December 2021 to March 2025. Statistical analysis was conducted from September 9 to October 3, 2025. Intervention Patients were randomized 2:1 to receive CSPs with a maximum of 21 days of storage vs RTPs with a maximum of 7 days of storage. Main Outcomes and Measures The primary outcome was a hemostatic efficacy score with values ranging from 1 to 5 and higher values indicating greater bleeding. The noninferiority margin was 1 point. The success criterion was met if at least 1 cold-storage duration of 7 days or more had a posterior probability of noninferiority of at least 97.5%. The secondary outcome was 24-hour chest tube output. Results Of the 1000 patients who underwent platelet transfusion, 989 were included in the primary analysis (650 CSPs and 339 RTPs). The cohort had a mean (SD) age of 42.1 (30.1) years and 67.8% were male. CSPs were noninferior to RTPs for the primary outcome, with a probability of greater than 99.9% for all cold-storage durations. Pooled across storage durations, CSPs had a mean difference from RTPs of 0.09 (95% credible interval, −0.06 to 0.23). Median (IQR) chest tube output at 24 hours (8.9 mL/kg [5.2-15.4] for CSPs vs 8.4 mL/kg [5.5-15.9] for RTPs; difference in medians, 0.4 [95% CI, −1.0 to 1.5]) was not statistically different between study groups. In a post hoc analysis, as all storage durations were noninferior, considering the CSPs as a single group, the hemostatic efficacy score was similar between both groups: mean (SD) of 3.08 (1.15) CSPs vs 2.99 (1.10) RTPs. There were no differences in venous or arterial thrombotic events, transfusion-associated adverse events, acute respiratory distress syndrome, kidney failure, septic shock, and mortality between the study groups, except for increased reexploration rates in the CSP group. Conclusions and Relevance For patients undergoing cardiac surgery, CSPs stored up to 21 days are noninferior to RTPs for the control of active surgical bleeding. Use of CSPs may allow for increased availability of platelets by reducing wastage and shortages and may allow for incorporation of platelets into inventory at locations where platelets cannot be maintained due to the 5- to 7-day shelf life of RTPs. Trial Registration ClinicalTrials.gov Identifier: NCT04834414

Abstract Aim To confirm or refute recent pilot studies showing unexpectedly high rates of undetected heart failure (HF) in cardiology patients. Methods We assessed the prevalence, characteristics, and outcome of undetected HF in a large prospective cohort study of patients referred for non-invasive coronary artery disease (CAD) work-up with cardiac positron emission tomography computed tomography. HF presence and phenotype were centrally adjudicated by an independent cardiologist according to clinical practice guidelines requiring three mandatory criteria: symptoms, elevated natriuretic peptides, and structural/functional cardiac abnormalities. The endpoint was a composite of cardiovascular death and acute HF (AHF) hospitalization through 2-year of follow-up. Results Among 1738 eligible patients (median age 67 years, 30% women), 138 patients (7.9%) had known HF, and 534 of 1600 patients (33.4%) without known HF had adjudicated undetected HF, resulting in a ratio of undetected HF to known HF of 3.9 (95%CI, 3.2–4.7)-to-1 and a number needed to screen to detect one patient with undetected HF of 3.0 (95%CI, 2.9-3.1). In undetected HF, left ventricular ejection fraction (LVEF) was preserved in 72.3%, mildly reduced in 16%, and reduced in 11.7%. Older age, known CAD, atrial fibrillation, previous pacemaker implantation, and ECG abnormalities were associated with a higher likelihood for undetected HF. Undetected HF was associated with an increased cumulative incidence of the composite endpoint (adjusted subdistribution hazard ratio 7.37 [95%CI, 3.87-14.06], p<0.001, versus no HF). Conclusion One-out-of three patients referred for CAD work-up had undetected HF, which was associated with cardiovascular death and AHF hospitalization.

ABSTRACT Objectives To investigate pharmacological treatment patterns in individuals with bipolar disorder (BD) with and without comorbid substance use disorder (SUD) and anxiety disorder (AX), we leveraged the Global Bipolar Cohort to analyze cross‐regional practices across North America, Europe, and the Pacific. Methods Fourteen cohorts contributed aggregate data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities. Proportional meta‐analyses using generalized linear mixed models were conducted to examine prescription trends and identify clinical differences. Results The sample ( N = 11,521) was 60% female and 84% Caucasian. Participants were categorized into four mutually exclusive groups based on comorbidity status: those with comorbid AX only, comorbid SUD only, both AX and SUD, or neither. The AX+SUD subgroup showed higher rates of attention‐deficit/hyperactivity disorder (ADHD), post‐traumatic stress disorder (PTSD), rapid cycling, obesity, and unemployment, reflecting a more severe clinical profile. Regional variations were notable: North American cohorts reported higher prevalence of AX and SUD than European and Pacific cohorts. Antidepressants use for AX were more common in Europe and the Pacific, while North American prescribing patterns were more variable. Benzodiazepine use was high among individuals with SUD across all regions. Lithium and first‐generation antipsychotic prescriptions varied, with higher rates observed in Europe. Conclusions Findings underscore the heterogeneity of BD and the influence of comorbid AX and SUD on illness burden and treatment. Regional prescribing variations underscore the need for context‐specific guidelines. Gaps in data on medication‐assisted treatment for SUD point to areas for future research. These insights can support more individualized and effective care for complex BD presentations.