Faculty Bibliography

BACKGROUND/UNASSIGNED:This study investigates the association between intra-operative balance and 2-year outcomes within subgroups defined by demographics and pre-operative joint balance. Our hypothesis is that patient demographics and the pre-operative state of the joint will impact patient sensitivity to post-operative balance and laxity and subsequent impact on outcome. METHODS/UNASSIGNED:A retrospective analysis of prospectively captured data across 5 sites with 5 surgeons was performed. All cases completed pre-operative demographics surveys, 2-year post-operative Knee Injury and Osteoarthritis Outcome Score (KOOS) and had a robot assisted total knee arthroplasty with an integrated digital joint balancing tool. Differences in associations between intra-operative final joint balance and 2-year KOOS pain outcomes in demographic and pre-operative balance subgroups were characterized. Associations informed clinically relevant thresholds to optimize TKA treatment for subgroups. RESULTS/UNASSIGNED:A total of 276 patients completed 2-year KOOS scores. Subgroups were defined from Sex, Age, BMI and pre-operative extension laxity. Men prefer a tight tolerance medially in extension and mid-flexion while females prefer a tight lateral flexion gap. Patients <70 years show a strong preference for equal rectangular gaps in extension, mid-flexion, and flexion, while older patients do not show a preference. Patients with BMI ≤30 demonstrate a preference for rectangular gaps, while patients with higher BMI do not. Finally, patients with looser pre-operative extension laxity (>3 mm) preferred a TKA with increased extension laxity compared to patients with minimal preoperative laxity. CONCLUSION/UNASSIGNED:Intraoperative differences in knee balance can influence patient outcome scores among different demographic groups at two years postoperatively. This suggests further research is warranted to determine how ligament balance and laxity may be optimized based on individual patient factors.

The COVID-19 pandemic profoundly impacted global health, with disproportionate consequences for healthcare workers (HCWs). Religious beliefs and practices may improve psychological resilience by fostering community, providing purpose and giving meaning to hardships. Yet, how religiosity impacts HCWs during a time of crisis is unclear. We therefore performed a cross-sectional study to investigate how religiosity contributes to resilience among HCWs who were routinely exposed to high levels of stress during the pandemic, through a physiological measure (the Auditory Sustained Attention Test; ASAT) and psychological self-reports. Forty-two HCWs were recruited from COVID-19 units and 44 HCWs from general internal medicine units during June and July 2022. COVID-19 HCWs showed significantly elevated emotional and attentional dysregulation with the ASAT, as measured by acoustic startle and prepulse inhibition, that was undetectable with self-reports. Furthermore, after dividing the HCWs into a 'high' and 'low' religiosity group, those in the 'low' group showed higher emotional and attentional dysregulation with the ASAT. Findings suggest that the ASAT has greater sensitivity at detecting emotional and attentional dysregulations than self-reports. Moderate or high religiosity may lead to better performance on the ASAT which could suggest greater resilience to mental health problems in the face of a crisis.

Background and ObjectivesWhile hearing loss is a known risk factor for dementia, the impact of incident hearing loss on subsequent dementia risk remains underexplored. This study examined the association between newly reported hearing loss and dementia risk in U.S. adults, focusing on critical intervention periods for dementia prevention.Research Design and MethodsParticipants from the Health and Retirement Study who reported no hearing loss or hearing aid use in 2010 or 2012 were included. Incident hearing loss and dementia were assessed via self-report and proxy report. Pooled logistic regression models with inverse probability weighting estimated the cumulative incidence of dementia at 2, 4, 6, and 8 years after baseline. Risk ratios (RR) with 95% confidence intervals were calculated from 200 bootstrap samples. Subgroup analyses were conducted by age, sex, and cardiovascular disease (CVD) status.ResultsAmong 13,599 participants, 1125 (8.3%) reported incident hearing loss. Dementia incidence was higher among those with hearing loss (6.6%) compared to those without (4.9%). Starting at 4 years, incident hearing loss was associated with a higher dementia risk, persisting at 8 years (RR = 1.34; 95% CI: 1.05, 1.59). This association was significant among individuals aged 50-64 years and those with CVD.Discussion and ImplicationsIncident hearing loss is associated with a heightened dementia risk, particularly in midlife and among individuals with CVD. Future research should investigate the effectiveness of timely interventions aimed at preventing dementia in individuals with hearing loss.

This study aimed to assess factors impacting obstetric triage time to disposition. The primary and secondary hypotheses were that high-risk patients and patients evaluated during periods with less staffing would experience prolonged length of stay (LOS), respectively.This single-site, retrospective cohort study analyzed 9,704 obstetric triage visits of 6,182 patients between January 1, 2022, to February 28, 2023. Inclusion criteria included patients 18 years or older with one or more evaluations. Exclusion criteria included scheduled admissions, unknown chief complaints, triage time under 10 minutes, and patients under 18 years old. A total of 6,612 visits representing 4,390 patients were included. The visits were stratified by disposition: admission versus nonadmission (transfer or discharge). Descriptive statistics analyze continuous variables. Frequencies and percentages were calculated for categorical variables. SAS was used for chi-square or Fisher's exact test for categorical variables and the two-sample t-test or Mann-Whitney test for continuous data. Statistical significance was p-value < 0.05.Of 6,612 visits, 3,475 admissions, and 3,137 nonadmissions occurred. The most common chief complaints were contractions (42%), amniotic fluid index evaluation (18%), and preeclampsia evaluation (8%). Admitted compared with nonadmitted patients had shorter LOS (64 minutes vs. 185 minutes, p < 0.001). Admitted compared with nonadmitted patients had shorter LOS by chief complaint, gestational age, high-risk maternal-fetal medicine status, time of day, and day of the week (all p < 0.001).Nonadmitted, maternal-fetal medicine and preterm patients evaluated during daytime and weekdays had significantly longer LOS. Vulnerable populations and target times for triage workflow improvement were identified. · Patient and unit factors influenced LOS.. · Nonadmitted patients had triple the LOS.. · High-risk patients had longer LOS.. · Daytime and weekday visits had longer LOS..

INTRODUCTION/BACKGROUND:Atopic dermatitis (AD) is a chronic, relapsing disease that can start at any age and has a significant negative impact on quality of life, including a significant itch burden. Here we report the proportion of patients in a real-world study achieving a complete/almost complete resolution of itch, as measured by the Peak Pruritus Numeric Rating Scale (PP-NRS) and improvement in overall disease severity score (ODS), in patients aged ≥ 12 years with moderate-to-severe AD up to 3 years after commencing dupilumab treatment. METHODS:PROSE is an ongoing, prospective, observational, multicenter registry in the USA and Canada, collecting real-world data from patients aged ≥ 12 years with moderate-to-severe AD who initiated dupilumab in accordance with country-specific prescribing information. Assessments include patient-reported PP-NRS (range 0-10) and clinician-measured ODS score (range 0-4). RESULTS:A total of 857 patients were enrolled, of whom 42% were male and 6.4% were adolescents aged ≥ 12 to < 18 years. The mean [standard deviation (SD)] age was 40.1 (17.9) years, and the duration of AD was 17.4 (16.2) years. The subsequent mean (SD) duration of dupilumab treatment was 23.1 (13.7) months. The proportion of patients achieving complete/almost complete itch resolution (PP-NRS score of 0 or 1) improved consistently over time, from 2.7% (17/622) of patients at baseline to 56.3% (58/103) at 3 years. Additionally, by year 3, 65.1% (54/83) of patients had an ODS score of no/minimal disease (score of 0 or 1), versus 2.2% (19/852) at baseline. CONCLUSIONS:In this real-world setting of the PROSE registry, adult and adolescent patients with moderate-to-severe AD followed up for up to 3 years after the initiation of dupilumab treatment experienced sustained and substantial improvement in pruritus and ODS, using the stringent endpoints of PP-NRS 0 or 1 and ODS 0 or 1. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT03428646.

BACKGROUND:The prognostic impact of cohesin mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is controversial. METHODS:In patients with AML and MDS who underwent next-generation sequencing at the authors' center during 2017-2023, the authors assessed the landscape of cohesin mutations and the impact of co-occurring mutations on overall survival (OS) and compared outcomes between patients with cohesin mutations and those with wild-type (WT) cohesin genes. RESULTS:The study included 83 patients, 36 with cohesin mutations (STAG2, n = 28; SMC1A, n = 7; SMC3, n = 3; co-expression of cohesin mutations, n = 2) and 47 with WT cohesin genes. Of the 36 patients with cohesin mutations, 17 (47%) had AML (six de novo and 11 secondary), and 19 (53%) had MDS. Patients who had STAG2 mutations had better median OS than patients who had only SMC1A and SMC3 mutations (26 vs. 10 months; p = .043). SRSF2 mutation was the most frequent co-occurring mutation (n = 12; 33%) and was associated with worse median OS than WT SRSF2 (13 vs. 43 months; p = .016). Seven patients (19%) with cohesin mutations underwent hematopoietic transplantation; their median OS was 70 months. Compared with the WT cohesin group, patients who had cohesin mutations were more likely to have adverse-risk AML (82% vs. 53%). The median OS was similar among patients with adverse-risk AML in the cohesin-mutation and WT cohesin groups (10 vs. 14 months, respectively; p = .9). CONCLUSIONS:The current study provides insight into the prognostic impact of cohesin mutations and co-occurring mutations in patients with myeloid malignancies.

Idursulfase is the first-line and only available enzyme replacement therapy (ERT) for Mucopolysaccharidosis type II (MPS II), or Hunter Syndrome. Deficiency in the lysosomal enzyme iduronate-2-sulfatase leads to progressive skeletal deformities, neurologic deterioration, airway obstruction, and cardiomyopathy. In severe cases, these deformities can lead to death during teenage years (Stapleton et al. 2017). Continuous treatment with ERT is essential to prevent irreversible changes. However, 16 out of 108 (15%) patients had hypersensitivity reactions to idursulfase during clinical trials. Hypersensitivity reactions have also been reported several years into treatment (Elaprase 2018). Therefore, it is critical to evaluate for hypersensitivity reactions and desensitize patients to idursulfase. We report a fourteen-year-old male who was evaluated using a nonirritating skin test concentration and underwent a novel desensitization protocol for Lysosomal Storage Disease ERT.

This observational cohort study examined the association between Alzheimer's disease and related dementias (ADRD) and hospital and skilled nursing facility (SNF) utilization among community-dwelling older adults aged 65 and older. Using four waves of longitudinal survey data from the 2016-2022 Health and Retirement Study conducted by the University of Michigan and multivariate, individual-level regressions, we found that the cognitive impairment but no dementia (CIND) and ADRD groups exhibited similar patterns in hospitalizations, hospital visits, and total hospital days compared to the normal cognition group. However, CIND was significantly associated with increased odds of SNF stays (odds ratio [OR], 1.22) and a higher number of SNF visits (incidence rate ratio [IRR], 1.45) than the normal cognition group. Higher odds of any SNF stay (OR, 1.26) and number of SNF visits (IRR, 1.45) were also observed for ADRD compared to normal cognition. These findings suggest that CIND or ADRD was not associated with hospital use but was significantly associated with increased SNF use.

OBJECTIVE:To examine the associations between patient out-of-pocket (OOP) costs and nonadherence to glucagon-like peptide 1 receptor agonists (GLP-1a), and the consequent impact on adverse outcomes, including hospitalizations and emergency department (ED) visits. RESEARCH DESIGN AND METHODS/METHODS:This retrospective cohort study used MarketScan Commercial data (2016-2021). The cohort included nonpregnant adults aged 18-64 years with type 2 diabetes who initiated GLP-1a therapy. Participants were continuously enrolled in the same private insurance plan for 6 months before the prescription date and 1 year thereafter. Exposures included average first 30-day OOP costs for GLP-1a, categorized into quartiles (lowest [Q1] to highest [Q4]). Primary outcomes were the annual proportion of days covered (PDC) for GLP-1a and nonadherence, defined as PDC <0.8. Secondary outcomes included diabetes-related and all-cause hospitalizations and ED visits 1 year post-GLP-1a initiation. RESULTS:Among 61,907 adults who initiated GLP-1a, higher 30-day OOP costs were associated with decreased adherence. Patients in the highest OOP cost quartile (Q4: $80-$3,375) had significantly higher odds of nonadherence (odds ratio [OR]1.25; 95% CI 1.19-1.31) compared with those in Q1 ($0-$21). Nonadherence was linked to increased incidence rates of diabetes-related hospitalizations or ED visits (incidence rate ratio [IRR] 1.86; 95% CI 1.43-2.42), cumulative length of hospitalization (IRR 1.56; 95% CI 1.41-1.72), all-cause ED visits (IRR 1.38; 95% CI 1.32-1.45), and increased ED-related costs ($69.81, 95% CI $53.54-$86.08). CONCLUSIONS:Higher OOP costs for GLP-1a were associated with reduced adherence and increased rates of adverse outcomes among type 2 diabetes patients.