Citations

Objectives: Sexual minority women (SMW) have worse mental and physical health outcomes compared with heterosexual women. Limited research has explored menopause in SMW. This study compared menopause symptoms in cisgender SMW and heterosexual women. Methods: This cross-sectional analysis examined questionnaires from women 40-65 years, seen at women’s health clinics in Arizona, Florida, and Minnesota between December 2016 and February 2023. Menopause symptoms were evaluated using the Menopause Rating Scale (MRS). An MRS score ≥ 12 indicates moderate or greater symptoms. Multivariable logistic regression was used to compare scores between cisgender SMW and heterosexual women, adjusting for factors that may impact menopause symptoms. Results: Data from 2,273 women were included, with 69 SMW. The mean age was 53.2 (SD: 6.1), body mass index 25.7 kg/m 2 , and a majority were White (91.9%). The median MRS score among all participants was 15 (interquartile range=10, 20); 67.3% reported MRS scores ≥ 12. The likelihood of being on hormone therapy or selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors was comparable between groups. In both univariate (OR: 0.85, 95% CI: 0.52-1.40) and multivariable (OR: 0.83, 95% CI: 0.47-1.48) analyses, no significant associations between sexual orientation and MRS ≥ 12 were found. Conclusions: Menopause symptoms and likelihood of treatment were similar for cisgender SMW and heterosexual women presenting to tertiary care centers. Limited diversity in the cohort and the small number of SMW reduce the generalizability of the results. The lack of adverse social determinants of health may have contributed to the findings, but additional research in larger cohorts is needed.

Background Frontotemporal dementia is an umbrella term that encompasses several clinical syndromes with impaired behavioral, language, and motor functions. These syndromes show considerable overlap in clinical features and imaging patterns. Therefore, there is a need to investigate the syndromic heterogeneity in FTD using unbiased data-driven approaches. Methods We used data-driven clustering analysis of structural magnetic resonance imaging (MRI) data on 400 patients with clinical FTD diagnoses [behavioral variant of frontotemporal dementia (bvFTD), semantic variant of primary progressive aphasia (svPPA), right temporal variant of frontotemporal dementia (rtvFTD), apraxia of speech with agrammatic aphasia (AOS-PAA), primary progressive apraxia of speech (PPAOS), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and primary progressive aphasia who did not fit into the other diagnostic categories (PPA-other)]. MR images were w-scored relative to cognitively unimpaired individuals, and principal component analysis was performed. A clustering ensemble approach, including hierarchical algorithms, was applied to the MR-based principal components, and imaging and clinical characteristics of the clusters were investigated. Various numbers of clusters ( K = 2, 3, or 4) were evaluated. Results The K = 3 solution offered the most clinically meaningful separation of FTD syndromes. The first cluster captured mostly frontal MRI abnormalities related to the speech, language and behavioral clinical dimensions, including patients with AOS-PAA, PPAOS, PPA-other, and bvFTD. The second cluster captured mostly temporal abnormalities and included mainly patients with svPPA and rtvFTD, but also bvFTD, AOS-PAA, and PPA-other. The third cluster captured cortical and subcortical atrophy, particularly in the midbrain, and included atypical Parkinsonian syndromes, with all PSP and CBS patients captured in this cluster, as well as most PPAOS patients. Considerable overlap of clinical syndromes was noted across these clusters, whereby patients with AOS-PAA, svPPA, PPA-other, and bvFTD were captured in more than one cluster. Discussion Our findings highlight heterogeneity in FTD, which mainly exists along three axes: speech, language and behavioral deficits reflecting frontal atrophy, language deficits reflecting temporal atrophy, and motor and motor speech deficits reflecting mostly midbrain and subcortical atrophy, with cortical involvement.

ABSTRACT Purpose To validate a custom smartphone application for at‐home visual acuity (VA) measurement in children. Methods A total of 452 children aged 3–17.5 years participated. Certified examiners measured in‐office test–retest VA (logMAR) using gold‐standard Amblyopia Treatment Study HOTV (3‐to‐6‐year‐olds, younger cohort) or electronic Early Treatment of Diabetic Retinopathy Study (7‐to‐17.5‐year‐olds, older cohort) protocols at 3–4.5 m and app‐based VA at 1.5 m. Caregivers measured at‐home app‐based VA at 1.5 m. Results Comparing at‐home app‐based with gold‐standard VA, in eyes 20/40 or better, 95% (143/151) and 93% (91/98) of the younger and older cohorts were within 2 lines, respectively (mean differences: younger = −0.03, older = −0.04; 95% limits‐of‐agreement half‐width (LOA): younger = ±0.26, older = ±0.22). In eyes 20/50 or worse, 66% (42/64) and 75% (76/101) of the younger and older cohorts were within 2 lines, respectively (mean differences: younger = 0.11, older = 0.13, LOA: younger = ±0.50, older = ±0.51). Comparing in‐office app‐based VA with gold‐standard VA, in eyes 20/40 or better, 98% (160/164) and 94% (99/105) of the younger and older cohorts were within 2 lines, respectively (mean differences: younger = −0.03, older = −0.03; LOA: younger = ±0.22; older = ±0.24). In eyes 20/50 or worse, 85% (60/71) and 91% (101/111) of the younger and older cohorts were within 2 lines, respectively (mean differences: younger = 0.04; older = 0.04; LOA: younger = ±0.39; older = ±0.24). For gold‐standard test–retest, in eyes 20/40 or better, 99% (163/164) and 99% (104/105) of the younger and older cohorts had retest within 2 lines, respectively (mean differences: younger = 0.00; older = 0.01; LOA: younger = ±0.17; older = ±0.11). For 20/50 or worse, 92% (66/72) and 100% (111/111) in the younger and older cohorts were within 2 lines, respectively (mean differences: younger = 0.01; older = 0.02; LOA: younger = ±0.35; older = ±0.15). Conclusions Our app demonstrated good concordance with the gold standard at home and in the office for eyes with VA of 20/40 or better. However, concordance decreased considerably for eyes with VA 20/50 or worse, particularly at home.

Introduction: Diabetes, a modifiable risk factor for dementia, is thought to impart increased risk of dementia through cerebral small vessel disease. While the importance of diabetes in midlife is well-documented, the influence of different glycemic levels, duration of diabetes, and Alzheimer’s disease genetic risk (apolipoprotein [ APOE ] ε4 genotype) in late-life on dementia risk remains uncertain. This could have implications for individualized prevention strategies. In this study, we investigated whether a higher glycemic level and longer duration of diabetes in late-life is associated with a higher risk of dementia, and whether associations vary by APOE ε4 genotype. Methods: We performed a prospective cohort analysis with the Atherosclerosis Risk in Communities Study using up to 11 years of follow-up (baseline, 2011-2013). We defined diabetes as glycated hemoglobin A1c (HbA 1c ) ≥6.5%, self-reported physician diagnosis, or use of any diabetes medication. Among those with diabetes, we categorized participants as having a lower glycemic level (HbA 1c <7%) or higher level (HbA 1c ≥7%), and duration as short (<5 years) or long (≥5 years). We estimated hazard ratios (HR) for incident dementia by HbA 1c levels and by diabetes duration in separate multivariable-adjusted Cox regression models. We tested for statistical multiplicative interaction on the relative risk of dementia by fitting interaction terms between diabetes measures and APOE ε4 genotype in separate regression models. Results: In 5030 participants without dementia (mean age, 75.4 years; 58.6% female; 21% Black; 28% with diabetes), there were 1167 (23.2%) incident dementia cases over a median follow-up of 9.0 years. Compared to no diabetes, a lower glycemic level and higher level were both associated with elevated dementia risk ( P -trend <.0001; Table). A higher glycemic level was associated with an elevated risk of dementia relative to a lower level (HR=1.47 [95% CI: 1.22-1.77]; Table). Compared to no diabetes, both shorter duration and longer duration were associated with an increase in dementia risk ( P -trend <.0001; Table). Longer duration was associated with an increased risk of dementia relative to shorter duration (HR=1.57 [95% CI: 1.24-1.98]; Table). Associations for glycemic level and diabetes duration did not significantly differ by APOE ε4 genotype (all P >.05). Conclusions: Diabetes management in older adults that includes lower glycemic goals may help reduce dementia risk.

Background: Given the faster onset and shorter duration of action of ultra-rapid insulin lispro-aabc (URLi, Lyumjev™ insulin), compared with insulin lispro (a rapid-acting insulin [RAI]), the present study investigated the safety and glycemic outcomes of MiniMed™ 780G advanced hybrid closed-loop (AHCL) use with URLi in youths and adults with T1D. Methods: This 19-site, single-arm, clinical trial enrolled children and adolescents (aged 7–17 years) and adults (aged 18–80 years) with T1D who underwent a run-in period (∼2 weeks) using open loop or automated basal only with an RAI (aspart or lispro), followed by a 3-month study period using URLi with AHCL (AHCL + URLi). End-of-study glycemic metrics and A1c were compared to predefined thresholds and to data from baseline/run-in. Use of recommended optimal settings (ROS, 100 mg/dL glucose target with an active insulin time [AIT] of 2 h) was also assessed. Results: In an intention-to-treat population ( N = 101 pediatric and N = 110 adult participants), percentage of time in range (%TIR) during the last ∼6 weeks of the study period was significantly greater than the predefined thresholds for both the pediatric and adult participants. A1c was unchanged in the pediatric cohort but significantly reduced in the adult cohort (from 7.4 ± 0.9% to 6.9 ± 0.6% [ P < 0.001]). Compared with run-in, study period %TIR and percentage of time in tight target range (%TITR) were significantly increased (pediatric mean %TIRΔ [17.4%] and %TITRΔ [16.0%], respectively, and adult mean %TIRΔ [10.6%] and %TITRΔ [11.6%], respectively; P < 0.001 for all). Additionally, % time above range for both groups was significantly reduced. Use of ROS allowed more participants to achieve recommended glycemic targets. There were no severe hypoglycemia or diabetic ketoacidosis events. Most caregivers agreed that mealtime versus premeal URLi delivery simplified pediatric meal management. Conclusions: Similar to previous studies investigating automated URLi delivery, URLi use in the MiniMed™ 780G system was safe, and glycemic outcomes were favorable for pediatric and adult participants.

Abstract Background : Traumatic encephalopathy syndrome (TES) is a clinical research construct used to identify individuals at risk for chronic traumatic encephalopathy (CTE) following exposure to repetitive head impacts (RHI). Adjudication of TES relies on clinical features such as progressive cognitive impairment and neurobehavioral dysregulation. Blood-based biomarkers and structural neuroimaging abnormalities have been associated with TES but are not part of the criteria. This study evaluated whether TES identification was associated with the combined contribution of cognitive performance, blood biomarkers, and structural neuroimaging measures across two well-characterized cohorts. Methods : Participants included 158 professional fighters from the Professional Athletes Brain Health Study and 149 former American football players from The DIAGNOSE CTE Research Project. Three indices were constructed representing complementary domains: a cognitive index reflecting cohort-specific cognitive features, a blood biomarker index including plasma neurofilament light chain, glial fibrillary acidic protein, total tau, tau phosphorylated at amino acid 231, and APOE -ε4 carrier status, and an imaging index comprising volumetric MRI measures of subcortical structures, ventricles, and corpus callosum subregions. Grouped weighted quantile sum regression models were estimated within each cohort to evaluate associations between these indices and TES while adjusting for age, race, competition status, and RHI exposure. Results : Multidomain models demonstrated improved model performance compared with single-domain models in both cohorts (PABHS: AUC=0.91, PPV=0.80; DIAGNOSE CTE: AUC=0.84, PPV=0.85). Biomarker and imaging indices contributed additional information across cohorts, although imaging contributions were more prominent in fighters whereas blood biomarker associations were stronger in football players. Conclusion : TES in RHI-exposed athletes was associated with a convergent clinicobiological profile observed across two independent cohorts with distinct exposure patterns. These findings support multidomain analytic frameworks for evaluating correlated biological signals in RHI-exposed populations and may inform future studies of TES and CTE.

Abstract Purpose We evaluated healthcare resource utilization (HCRU) and costs in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Methods Patients with newly diagnosed EGPA (2017–2021), ≥12 months’ pre-diagnosis health plan enrollment, and ≥1 inpatient or ≥2 outpatient claims with an EGPA diagnosis were included. Follow-up was from EGPA diagnosis until disenrollment or database end. HCRU and health insurer payment costs during follow-up were compared with those for matched cohorts of general insured patients without EGPA (comparison A) and without EGPA but with severe uncontrolled asthma (SUA; comparison B). Results In comparison A, all-cause HCRU was higher in the EGPA cohort (n = 213) versus matched patients (n = 779) for all clinical encounters/pharmacy claim types; annualized, mean total all-cause costs were 16-fold higher ($117,563/patient) versus matched patients ($7,520/patient). In comparison B, all-cause HCRU was higher for the EGPA cohort (n = 182) versus the matched SUA cohort (n = 640) for all clinical encounters/pharmacy claim types, with 5-fold higher mean total all-cause costs ($118,127/patient vs $22,286/patient). In both EGPA cohorts, HCRU and associated costs increased between the baseline and follow-up periods. Conclusions These findings highlight the need for more effective treatments to reduce the clinical and economic burden of EGPA.