Faculty Bibliography

OBJECTIVE:The objective of this study is to examine real-world dose titration patterns of semaglutide for weight management (Wegovy, Novo Nordisk A/S) in US adults and identify characteristics associated with early discontinuation. METHODS:We identified 15,811 commercially insured adults who started semaglutide for weight management (administrated through single-dose prefilled pens) between June 2021 and December 2023. We depicted dose-titration patterns over 5 months and identified factors associated with discontinuation using multivariable Cox regression. Sensitivity analyses examined patterns after supply shortage resolution (after October 2023). RESULTS:Most semaglutide users deviated from the recommended monthly dose-escalation schedule within the first 5 months. By the fifth month, nearly one-half (46%) had discontinued the treatment, with similar rates (48%) among those initiating after supply stabilization. Discontinuation was strongly associated with copayment amount, with rates increased from 41% in the lowest quintile ($1-$54 per month) to 51% in the highest quintile ($161-$1460 per month). Higher discontinuation rates were also associated with lower household income and education level. CONCLUSIONS:The deviations from the recommended dose-escalation schedule and high discontinuation rate among real-world semaglutide users indicate important challenges in the delivery of evidence-based care. Policy interventions that reduce financial barriers to the persistence of semaglutide are needed.

IMPORTANCE/OBJECTIVE:Patients with poor glycaemic control have a high risk for major cardiovascular events. Improving glycaemic monitoring in patients with diabetes can improve morbidity and mortality. OBJECTIVE:To assess the effectiveness of a patient portal message in prompting patients with poorly controlled diabetes without a recent glycated haemoglobin (HbA1c) result to have their HbA1c repeated. DESIGN/METHODS:A pragmatic, randomised clinical trial. SETTING/METHODS:A large academic health system consisting of over 350 ambulatory practices. PARTICIPANTS/METHODS:Patients who had an HbA1c greater than 10% who had not had a repeat HbA1c in the prior 6 months. EXPOSURES/METHODS:A single electronic health record (EHR)-based patient portal message to prompt patients to have a repeat HbA1c test versus usual care. MAIN OUTCOMES/RESULTS:The primary outcome was a follow-up HbA1c test result within 90 days of randomisation. RESULTS:The study included 2573 patients with a mean (SD) HbA1c of 11.2%. Among 1317 patients in the intervention group, 24.2% had follow-up HbA1c tests completed within 90 days, versus 21.1% of 1256 patients in the control group (p=0.07). Patients in the intervention group were more likely to log into the patient portal within 60 days as compared with the control group (61.2% vs 52.3%, p<0.001). CONCLUSIONS:Among patients with poorly controlled diabetes and no recent HbA1c result, a brief patient portal message did not significantly increase follow-up testing but did increase patient engagement with the patient portal. Automated patient messages could be considered as a part of multipronged efforts to involve patients in their diabetes care.

Objectives Improve concordance between patient end-of-life preferences and code status orders by incorporating data from a state registry with Clinical Decision Support (CDS) within the electronic health record (EHR) to preserve patient autonomy and ensure that patients receive care that aligns with their wishes. Methods Leveraging a Health Information exchange (HIE) interface between the New York State Medical Orders for Life-Sustaining Treatment (eMOLST) registry and the EHR of our academic health system, we developed a bundled CDS intervention that displays eMOLST information at the time of code status ordering and provides an in-line alert when providers enter a resuscitation order discordant with wishes documented in the eMOLST registry. To evaluate this intervention, we performed a segmented regression analysis of an interrupted times series to compare percentage of discordant orders before and after implementation among all hospitalizations for which an eMOLST was available. Results We identified a total of 3648 visits that had an eMOLST filed prior to inpatient admission and a code status order placed during admission. There was a statistically significant decrease of discordant resuscitation orders of -5.95% after the intervention went live, with a relative risk reduction of 25%, [95% CI: -9.95%, -1.94%, p=0.009] in the pre- and post-intervention period. Logistic regression model after adjusting for co-variates showed an average marginal effect of -5.12% after the intervention [CI =-9.75%, -0.50%, p=0.03]. Conclusions Our intervention resulted in a decrease in discordant resuscitation orders. This study demonstrates that accessibility to eMOLST data within the provider workflow supported by CDS can reduce discrepancies between patient end-of-life wishes and hospital code status orders.

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.

IMPORTANCE/UNASSIGNED:It remains unclear whether children and adolescents with SARS-CoV-2 infection are at heightened risk for long-term kidney complications. OBJECTIVE/UNASSIGNED:To investigate whether SARS-CoV-2 infection is associated with an increased risk of postacute kidney outcomes among pediatric patients, including those with preexisting kidney disease or acute kidney injury (AKI). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective cohort study used data from 19 health institutions in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) initiative from March 1, 2020, to May 1, 2023 (follow-up ≤2 years completed December 1, 2024; index date cutoff, December 1, 2022). Participants included children and adolescents (aged <21 years) with at least 1 baseline visit (24 months to 7 days before the index date) and at least 1 follow-up visit (28 to 179 days after the index date). EXPOSURES/UNASSIGNED:SARS-CoV-2 infection, determined by positive laboratory test results (polymerase chain reaction, antigen, or serologic) or relevant clinical diagnoses. A comparison group included children with documented negative test results and no history of SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Outcomes included new-onset chronic kidney disease (CKD) stage 2 or higher or CKD stage 3 or higher among those without preexisting CKD; composite kidney events (≥50% decline in estimated glomerular filtration rate [eGFR], eGFR ≤15 mL/min/1.73 m2, dialysis, transplant, or end-stage kidney disease diagnosis), and at least 30%, 40%, or 50% eGFR decline among those with preexisting CKD or acute-phase AKI. Hazard ratios (HRs) were estimated using Cox proportional hazards regression models with propensity score stratification. RESULTS/UNASSIGNED:Among 1 900 146 pediatric patients (487 378 with and 1 412 768 without COVID-19), 969 937 (51.0%) were male, the mean (SD) age was 8.2 (6.2) years, and a range of comorbidities was represented. SARS-CoV-2 infection was associated with higher risk of new-onset CKD stage 2 or higher (HR, 1.17; 95% CI, 1.12-1.22) and CKD stage 3 or higher (HR, 1.35; 95% CI, 1.13-1.62). In those with preexisting CKD, COVID-19 was associated with an increased risk of composite kidney events (HR, 1.15; 95% CI, 1.04-1.27) at 28 to 179 days. Children with acute-phase AKI had elevated HRs (1.29; 95% CI, 1.21-1.38) at 90 to 179 days for composite outcomes. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this large US cohort study of children and adolescents, SARS-CoV-2 infection was associated with a higher risk of adverse postacute kidney outcomes, particularly among those with preexisting CKD or AKI, suggesting the need for vigilant long-term monitoring.

Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients' clinical histories to then identify groups of patients with similar presentations. The results indicate that cardiorespiratory presentations are most common (present in 54% of patients) followed by subphenotypes marked (in decreasing order of frequency) by musculoskeletal pain, neuropsychiatric conditions, gastrointestinal symptoms, headache, and fatigue.

BACKGROUND:Medication non-adherence, which is common in chronic diseases such as heart failure, is often estimated using proportion of days covered (PDC). PDC is typically calculated using medication fill information from pharmacy or insurance claims data, which lack information on when medications are prescribed. Many electronic health records (EHRs) have prescription and pharmacy fill data available, enabling enhanced PDC assessment that can be utilized in routine clinical care. OBJECTIVE:To describe our approach to calculating PDC using linked EHR-pharmacy data and to compare to PDC calculated using pharmacy-only data for patients with heart failure. METHODS:We performed a retrospective cohort study of adult patients with heart failure who were prescribed guideline-directed medical therapy (GDMT) and seen in a large health system. Using linked EHR-pharmacy data, we estimated medication adherence by PDC as the percent of days in which a patient possessed GDMT based on medication pharmacy fills over the number of days the prescription order was active. We also calculated PDC using pharmacy-only data, calculated as medications possessed over days with continued medication fills. We compared these two approaches for days observed and PDC using a paired t-test. RESULTS:Among 33,212 patients with heart failure who were prescribed GDMT, 2226 (6.7%) never filled their medications, making them unavailable in the assessment of PDC using pharmacy-only data (n = 30,995). Linked EHR-pharmacy data had slightly longer days observed for PDC assessment (164.7 vs. 163.4 days; p < 0.001) and lower PDC (78.5 vs. 90.6, p < 0.001) as compared to assessment using pharmacy-only data. CONCLUSIONS:Linked EHR-pharmacy data can be used to identify patients who never fill their prescriptions. Estimating adherence using linked EHR-pharmacy data resulted in a lower mean PDC as compared to estimates using pharmacy-only data.

BACKGROUND:Cardiometabolic comorbidities such as obesity, diabetes, and hypertension are highly prevalent in heart failure (HF). We aimed to examine the association between severity of cardiometabolic comorbidities and hospitalization in patients with HF. METHODS: RESULTS: CONCLUSIONS:Greater cardiometabolic comorbidity burden was associated with increased risk of all-cause hospitalization in HF. This reinforces the role for targeting severely uncontrolled cardiometabolic comorbidities to reduce morbidity in HF.

PURPOSE/UNASSIGNED:We aimed to determine whether implementation of clinical decision support (CDS) tool integrated into the electronic health record of a multisite academic medical center increased the proportion of patients with AUA "high-risk" microscopic hematuria (MH) who receive guideline concordant evaluations. MATERIALS AND METHODS/UNASSIGNED:We conducted a two-arm cluster randomized quality improvement project in which 202 ambulatory sites from a large health system were randomized to either have their physicians receive at time of test results an automated CDS alert for patients with "high-risk" MH with associated recommendations for imaging and cystoscopy (intervention) or usual care (control). Primary outcome was met if a patient underwent both imaging and cystoscopy within 180 days from MH result. Secondary outcomes assessed individual completion of imaging, cystoscopy, or placement of imaging orders. RESULTS/UNASSIGNED:= .09). CONCLUSIONS/UNASSIGNED:Implementing an electronic health record-integrated CDS tool to promote evaluation of patients with high-risk MH did not lead to improvements in patient completion of a full guideline-concordant evaluation. The development of an algorithm to trigger a CDS alert was demonstrated to be feasible and effective. Further multilevel assessment of barriers to evaluation is necessary to continue to improve the approach to evaluating high-risk patients with MH.