Mortality, Hospitalization, and Cardiac Interventions in Patients With Atrial Fibrillation Aged <65 Years.

BACKGROUND: The risk factor (RF) burden, clinical course, and long-term outcome among patients with atrial fibrillation (AF) aged <65 years is unclear. METHODS: Adult (n=67 221; mean age, 72.4±12.3 years; and 45% women) patients with AF evaluated at the University of Pittsburgh Medical Center between January 2010 and December 2019 were studied. Hospital system-wide electronic health records and administrative data were utilized to ascertain RFs, comorbidities, and subsequent hospitalization and cardiac interventions. The association of AF with all-cause mortality among those aged <65 years was analyzed using an internal contemporary cohort of patients without AF (n=918 073). RESULTS: Nearly one-quarter (n=17 335) of the cohort was aged <65 years (32% women) with considerable cardiovascular RFs (current smoker, 16%; mean body mass index, 33.0±8.3; hypertension, 55%; diabetes, 21%; heart failure, 20%; coronary artery disease, 19%; and prior ischemic stroke, 6%) and comorbidity burden (chronic obstructive pulmonary disease, 11%; obstructive sleep apnea, 18%; and chronic kidney disease, 1.3%). Over mean follow-up of >5 years, 2084 (6.7%, <50 years; 13%, 50-65 years) patients died. The proportion of patients with >1 hospitalization for myocardial infarction, heart failure, and stroke was 1.3%, 4.8%, and 1.1% for those aged <50 years and 2.2%, 7.4%, and 1.1% for the 50- to 65-year subgroup, respectively. Multiple cardiac and noncardiac RFs were associated with increased mortality in younger patients with AF with heart failure and hypertension demonstrating significant age-related interaction (P=0.007 and P=0.013, respectively). Patients with AF aged <65 years experienced significantly worse survival compared with comorbidity-adjusted patients without AF (men aged <50 years and hazard ratio, 1.5 [95% CI, 1.24-1.79]; 50-65 years and hazard ratio, 1.3 [95% CI, 1.26-1.43]; women aged <50 years and hazard ratio, 2.4 [95% CI, 1.82-3.16]; 50-65 years and hazard ratio, 1.7 [95% CI, 1.6-1.92]). CONCLUSIONS: Patients with AF aged <65 years have significant comorbidity burden and considerable long-term mortality. They are also at a significantly increased risk of hospitalization for heart failure, stroke, and myocardial infarction. These patients warrant an aggressive focus on RF and comorbidity evaluation and management.

Statin utilization and cardiovascular outcomes in a real-world primary prevention cohort of older adults.

Background: Statins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years). Objective: Investigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network. Methods: We included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and 'moderate or high' intensity statins with a follow up period of ∼7 years. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Data was adjusted for competing risk using Elixhauser Comorbidity Index. Results: Compared with those on moderate or high intensity statins, high-risk older patients not on any statin had a significantly increased risk of MI [HR 1.51 (1.17-1.95); p<0.01], stroke [HR 1.47 (1.14-1.90); p<0.01] and all-cause mortality [HR 1.37 (1.19-1.58); p<0.001] in models adjusted for Elixhauser Comorbidity Index. When comparing the no statin group versus the moderate or high intensity statin group in the intermediate risk cohort, although a trend for increased risk was seen, it did not meet statistical significance thresholds for MI, stroke or all-cause mortality. Conclusion: Lack of statin use was associated with increased cardiovascular events and mortality in high-risk older adults. Given the benefits appreciated, statin use may need to be strongly considered for primary ASCVD prevention among high-risk older adults. Future studies will assess the risk-benefit ratio of statin intervention in older adults.

Is LDL cholesterol associated with long-term mortality among primary prevention adults? A retrospective cohort study from a large healthcare system.

OBJECTIVES: Among primary prevention-type adults not on lipid-lowering therapy, conflicting results exist on the relationship between low-density lipoprotein cholesterol (LDL-C) and long-term mortality. We evaluated this relationship in a real-world evidence population of adults. DESIGN: Retrospective cohort study. SETTING: Electronic medical record data for adults, from 4 January 2000 through 31 December 2022, were extracted from the University of Pittsburgh Medical Center healthcare system. PARTICIPANTS: Adults without diabetes aged 50-89 years not on statin therapy at baseline or within 1 year and classified as primary prevention-type patients. To mitigate potential reverse causation, patients who died within 1 year or had baseline total cholesterol (T-C) ≤120 mg/dL or LDL-C <30 mg/dL were excluded. MAIN EXPOSURE MEASURE: Baseline LDL-C categories of 30-79, 80-99, 100-129, 130-159, 160-189 or ≥190 mg/dL. MAIN OUTCOME MEASURE: All-cause mortality with follow-up starting 365 days after baseline cholesterol measurement. RESULTS: 177 860 patients with a mean (SD) age of 61.1 (8.8) years and mean (SD) LDL-C of 119 (31) mg/dL were evaluated over a mean of 6.1 years of follow-up. A U-shaped relationship was observed between the six LDL-C categories and mortality with crude 10-year mortality rates of 19.8%, 14.7%, 11.7%, 10.7%, 10.1% and 14.0%, respectively. Adjusted mortality HRs as compared with the referent group of LDL-C 80-99 mg/dL were: 30-79 mg/dL (HR 1.23, 95% CI 1.17 to 1.30), 100-129 mg/dL (0.87, 0.83-0.91), 130-159 mg/dL (0.88, 0.84-0.93), 160-189 mg/dL (0.91, 0.84-0.98) and ≥190 mg/dL (1.19, 1.06-1.34), respectively. Unlike LDL-C, both T-C/HDL cholesterol (high-density lipoprotein cholesterol) and triglycerides/HDL cholesterol ratios were independently associated with long-term mortality. CONCLUSIONS: Among primary prevention-type patients aged 50-89 years without diabetes and not on statin therapy, the lowest risk for long-term mortality appears to exist in the wide LDL-C range of 100-189 mg/dL, which is much higher than current recommendations. For counselling these patients, minimal consideration should be given to LDL-C concentration.

Blood Serum Stimulates the Virulence Potential of Mucorales through Enhancement in Mitochondrial Oxidative Metabolism and Rhizoferrin Production.

This study analyzed the role of blood serum in enhancing the mitochondrial metabolism and virulence of Mucorales through rhizoferrin secretion. We observed that the spores of clinically relevant Mucorales produced in the presence of serum exhibited higher virulence in a heterologous infection model of Galleria mellonella. Cell-free supernatants of the culture broth obtained from spores produced in serum showed increased toxicity against Caenorhabditis elegans, which was linked with the enhanced secretion of rhizoferrin. Spores from Mucoralean species produced or germinated in serum showed increased respiration rates and reactive oxygen species levels. The addition of non-lethal concentrations of potassium cyanide and N-acetylcysteine during the aerobic or anaerobic growth of Mucorales decreased the toxicity of the cell-free supernatants of the culture broth, suggesting that mitochondrial metabolism is important for serum-induced virulence. In support of this hypothesis, a mutant strain of Mucor lusitanicus that lacks fermentation and solely relies on oxidative metabolism exhibited virulence levels comparable to those of the wild-type strain under serum-induced conditions. Contrary to the lower virulence observed, even in the serum, the ADP-ribosylation factor-like 2 deletion strain exhibited decreased mitochondrial activity. Moreover, spores produced in the serum of M. lusitanicus and Rhizopus arrhizus that grew in the presence of a mitophagy inducer showed low virulence. These results suggest that serum-induced mitochondrial activity increases rhizoferrin levels, making Mucorales more virulent.

REMAP Periop: a randomised, embedded, multifactorial adaptive platform trial protocol for perioperative medicine to determine the optimal enhanced recovery pathway components in complex abdominal surgery patients within a US healthcare system.

INTRODUCTION: Implementation of enhanced recovery pathways (ERPs) has resulted in improved patient-centred outcomes and decreased costs. However, there is a lack of high-level evidence for many ERP elements. We have designed a randomised, embedded, multifactorial, adaptive platform perioperative medicine (REMAP Periop) trial to evaluate the effectiveness of several perioperative therapies for patients undergoing complex abdominal surgery as part of an ERP. This trial will begin with two domains: postoperative nausea/vomiting (PONV) prophylaxis and regional/neuraxial analgesia. Patients enrolled in the trial will be randomised to arms within both domains, with the possibility of adding additional domains in the future. METHODS AND ANALYSIS: In the PONV domain, patients are randomised to optimal versus supraoptimal prophylactic regimens. In the regional/neuraxial domain, patients are randomised to one of five different single-injection techniques/combination of techniques. The primary study endpoint is hospital-free days at 30 days, with additional domain-specific secondary endpoints of PONV incidence and postoperative opioid consumption. The efficacy of an intervention arm within a given domain will be evaluated at regular interim analyses using Bayesian statistical analysis. At the beginning of the trial, participants will have an equal probability of being allocated to any given intervention within a domain (ie, simple 1:1 randomisation), with response adaptive randomisation guiding changes to allocation ratios after interim analyses when applicable based on prespecified statistical triggers. Triggers met at interim analysis may also result in intervention dropping. ETHICS AND DISSEMINATION: The core protocol and domain-specific appendices were approved by the University of Pittsburgh Institutional Review Board. A waiver of informed consent was obtained for this trial. Trial results will be announced to the public and healthcare providers once prespecified statistical triggers of interest are reached as described in the core protocol, and the most favourable interventions will then be implemented as a standardised institutional protocol. TRIAL REGISTRATION NUMBER: NCT04606264.

Impact of Guideline-Directed Statin Intervention for Primary Prevention in Patients With Diabetes.

OBJECTIVE: We examined guideline-directed statin intensity (GDSI) use and atherosclerotic cardiovascular disease (ASCVD) outcomes in patients with diabetes across a contemporary health care system. RESEARCH DESIGN AND METHODS: Patients without preexisting ASCVD were categorized by diabetes status and 10-year ASCVD risk (borderline [5-7.4%], intermediate [7.5-19.9%], high [≥20%]). Mean ±SD time to start of or change to GDSI was calculated. Incident ASCVD and all-cause mortality association, stratified by ASCVD risk, was calculated using Cox regression. RESULTS: Among 282,298 patients, 28,807 (10.2%) had diabetes and 253,491 (89.8%) did not. Only two-thirds of intermediate- and high-risk patients with diabetes were receiving GDSI therapy at 5-year follow-up. In fully adjusted models, patients with diabetes not taking a statin (vs. GDSI) had a significantly higher risk of stroke and mortality in the intermediate- and high-risk groups (hazard ratio for mortality 1.81 [95% CI 1.58-2.07] vs. 1.41 [1.26-1.57]; P for interaction < 0.01). CONCLUSIONS: Significant gaps remain in GDSI use for high-risk patients with diabetes, conferring an increased risk of ASCVD outcomes and all-cause mortality.

Implementing a Discharge Follow-up Phone Call Program Reduces Readmission Rates in an Integrated Health System.

ABSTRACT: In this study, we sought to determine the effect of implementing a large-scale discharge follow-up phone call program on hospital readmission rates. Previous work has shown that patients with unaddressed concerns during discharge have significantly higher rates of care complications and hospital readmissions. This study is an observational quality improvement project completed from April 17, 2020 to January 31, 2022 at 22 hospitals in a large, integrated academic health system. A nurse-led scripted discharge follow-up phone call program was implemented to contact all patients discharged from inpatient care within 72 hours of discharge. Readmission rates were tracked before and after project implementation. Over a 21-month span, 137,515 phone calls were placed, and 57.92% of patients were successfully contacted within 7 days of discharge. The 7-day readmission rate for contacted patients was 2.91% compared with 4.73% for noncontacted patients. The 30-day readmission rate for contacted patients was 11.00% compared with 12.17% for noncontacted patients. We have found that discharge follow-up phone calls targeting patients decreases risk of readmission, which improves overall patient outcomes.

Challenges in posterior uveitis-tips and tricks for the retina specialist.

PURPOSE: Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic. The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases. Inflammation can be confined to the eye or may be a part of systemic disease. A useful outline is therefore proposed to aid in the correct diagnosis of these challenging entities. The situation is further complicated by the fact that many neoplastic conditions resemble features of posterior uveitis; they are known as "masqueraders of uveitis". Here, we summarize different posterior uveitides that present with rare findings, along with masqueraders that can be difficult to distinguish. These conditions pose a diagnostic dilemma resulting in delay in treatment because of diagnostic uncertainty. METHODS: An extensive literature search was performed on the MEDLINE/PUBMED, EBSCO and Cochrane CENTRAL databases from January 1985 to January 2022 for original studies and reviews of predetermined diagnoses that include posterior uveitic entities, panuveitis and masquerade syndromes. RESULTS: We described conditions that can present as mimickers of posterior uveitis (i.e., immune check-points inhibitors and Vogt-Koyanagi-Harada-like uveitis; leukemia and lymphoma associated posterior uveitis), inflammatory conditions that present as mimickers of retinal diseases (i.e., Purtscher-like retinopathy as a presentation of systemic lupus erythematosus; central serous chorioretinopathy masquerading inflammatory exudative retinal detachment), and uveitic conditions with rare and diagnostically challenging etiologies (i.e., paradoxical inflammatory effects of anti-TNF-α; post vaccination uveitis; ocular inflammation after intravitreal injection of antiangiogenic drugs). CONCLUSION: This review of unique posterior uveitis cases highlights the overlapping features of posterior uveitis (paradoxical inflammatory effects of anti -TNF α and uveitis; Purtscher-like retinopathy as a presentation of systemic lupus erythematosus, …) and the nature of retinal conditions (ischemic ocular syndrome, or central retinal vein occlusion, amyloidosis, inherited conditions like retinitis pigmentosa, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), etc.…) that may mimic them is represented. Careful review of past uveitis history, current medications and recent vaccinations, detailed examination of signs of past or present inflammation, eventually genetic testing and/ or multimodal retinal imaging (like fluorescein angiography, EDI-OCT, OCT-angiography for lupus Purtscher-like retinopathy evaluation, or ICG for central serous retinopathy, or retinal amyloid angiopathy) may aid in correct diagnosis.

Implementing a Serious Illness Risk Prediction Model: Impact on Goals of Care Documentation.

CONTEXT: Goals of care conversations can promote high value care for patients with serious illness, yet documented discussions infrequently occur in hospital settings. OBJECTIVES: We sought to develop a quality improvement initiative to improve goals of care documentation for hospitalized patients. METHODS: Implementation occurred at an academic medical center in Pittsburgh, Pennsylvania. Intervention included integration of a 90-day mortality prediction model grouping patients into low, intermediate, and high risk; a centralized goals of care note; and automated notifications and targeted palliative consults. We compared documented goals of care discussions by risk score before and after implementation. RESULTS: Of the 12,571 patients hospitalized preimplementation and 10,761 postimplementation, 1% were designated high risk and 11% intermediate risk of mortality. Postimplementation, goals of care documentation increased for high (17.6%-70.8%, P< 0.0001) and intermediate risk patients (9.6%-28.0%, P < 0.0001). For intermediate risk patients, the percentage of goals of care documentation performed by palliative medicine specialists increased from pre- to postimplementation (52.3%-71.2%, P = 0.0002). For high-risk patients, the percentage of goals of care documentation completed by the primary service increased from pre-to postimplementation (36.8%-47.1%, P = 0.5898, with documentation performed by palliative medicine specialists slightly decreasing from pre- to postimplementation (63.2%-52.9%, P = 0.5898). CONCLUSIONS: Implementation of a goals of care initiative using a mortality prediction model significantly increased goals of care documentation especially among high-risk patients. Further study to assess strategies to increase goals of care documentation for intermediate risk patients is needed especially by nonspecialty palliative care.

Development and Validation of a Machine Learning Model to Identify Patients Before Surgery at High Risk for Postoperative Adverse Events.

Importance: Identifying patients at high risk of adverse outcomes prior to surgery may allow for interventions associated with improved postoperative outcomes; however, few tools exist for automated prediction. Objective: To evaluate the accuracy of an automated machine-learning model in the identification of patients at high risk of adverse outcomes from surgery using only data in the electronic health record. Design, Setting, and Participants: This prognostic study was conducted among 1 477 561 patients undergoing surgery at 20 community and tertiary care hospitals in the University of Pittsburgh Medical Center (UPMC) health network. The study included 3 phases: (1) building and validating a model on a retrospective population, (2) testing model accuracy on a retrospective population, and (3) validating the model prospectively in clinical care. A gradient-boosted decision tree machine learning method was used for developing a preoperative surgical risk prediction tool. The Shapley additive explanations method was used for model interpretability and further validation. Accuracy was compared between the UPMC model and National Surgical Quality Improvement Program (NSQIP) surgical risk calculator for predicting mortality. Data were analyzed from September through December 2021. Exposure: Undergoing any type of surgical procedure. Main Outcomes and Measures: Postoperative mortality and major adverse cardiac and cerebrovascular events (MACCEs) at 30 days were evaluated. Results: Among 1 477 561 patients included in model development (806 148 females [54.5%; mean [SD] age, 56.8 [17.9] years), 1 016 966 patient encounters were used for training and 254 242 separate encounters were used for testing the model. After deployment in clinical use, another 206 353 patients were prospectively evaluated; an additional 902 patients were selected for comparing the accuracy of the UPMC model and NSQIP tool for predicting mortality. The area under the receiver operating characteristic curve (AUROC) for mortality was 0.972 (95% CI, 0.971-0.973) for the training set and 0.946 (95% CI, 0.943-0.948) for the test set. The AUROC for MACCE and mortality was 0.923 (95% CI, 0.922-0.924) on the training and 0.899 (95% CI, 0.896-0.902) on the test set. In prospective evaluation, the AUROC for mortality was 0.956 (95% CI, 0.953-0.959), sensitivity was 2148 of 2517 patients (85.3%), specificity was 186 286 of 203 836 patients (91.4%), and negative predictive value was 186 286 of 186 655 patients (99.8%). The model outperformed the NSQIP tool as measured by AUROC (0.945 [95% CI, 0.914-0.977] vs 0.897 [95% CI, 0.854-0.941], for a difference of 0.048), specificity (0.87 [95% CI, 0.83-0.89] vs 0.68 [95% CI, 0.65-0.69]), and accuracy (0.85 [95% CI, 0.82-0.87] vs 0.69 [95% CI, 0.66, 0.72]). Conclusions and Relevance: This study found that an automated machine learning model was accurate in identifying patients undergoing surgery who were at high risk of adverse outcomes using only preoperative variables within the electronic health record, with superior performance compared with the NSQIP calculator. These findings suggest that using this model to identify patients at increased risk of adverse outcomes prior to surgery may allow for individualized perioperative care, which may be associated with improved outcomes.

Herpes zoster ophthalmicus: frequency and risk factors for developing uncommon ocular manifestations.

OBJECTIVE: To determine the frequency of herpes zoster ophthalmicus (HZO) and assess risk factors for developing uncommon ocular manifestations of laboratory-verified HZO. DESIGN: Retrospective cohort study. METHODS: The frequency of HZO out of all herpes zoster cases was calculated using International Classification of Diseases codes for patients seen at the University of Pittsburgh Medical Center from January 1, 2004 to October 31, 2021. We also collected demographic and clinical data of patients with HZO identified by polymerase chain reaction (PCR) detection of varicella zoster virus from January 1, 2011 to December 31, 2020. RESULTS: The frequency of HZO from 2004 to 2021 in all ages was 4.2% and ranged from 2.7% to 6.7% annually, with a consistent increase of 2.9% from 2012 to 2021. After the live zoster vaccine became available in 2008, the frequency of HZO decreased by 5.1% from 2008 to 2012 in patients aged 60 and older. Among 50 cases of PCR-verified HZO, 62% represented clinically-common ocular manifestations, mostly comprised of 13 cases of keratitis and 10 cases of anterior uveitis. Fifteen cases of acute retinal necrosis (ARN) represented the majority of uncommon HZO manifestations (38%), which were significantly more likely to occur in immunosuppressed patients (unadjusted odds ratio 4.55, 95% confidence interval 1.29-13.83). CONCLUSIONS: The overall frequency of HZO from 2004 to 2021 was 4.2% and has increased annually since 2012. Uncommon ocular manifestations of PCR-verified HZO, mostly comprised of ARN, were more likely to occur in immunosuppressed patients.

Evolving Real-World Effectiveness of Monoclonal Antibodies for Treatment of COVID-19 : A Cohort Study.

BACKGROUND: Treatment guidelines and U.S. Food and Drug Administration emergency use authorizations (EUAs) of monoclonal antibodies (mAbs) for treatment of high-risk outpatients with mild to moderate COVID-19 changed frequently as different SARS-CoV-2 variants emerged. OBJECTIVE: To evaluate whether early outpatient treatment with mAbs, overall and by mAb product, presumed SARS-CoV-2 variant, and immunocompromised status, is associated with reduced risk for hospitalization or death at 28 days. DESIGN: Hypothetical pragmatic randomized trial from observational data comparing mAb-treated patients with a propensity score-matched, nontreated control group. SETTING: Large U.S. health care system. PARTICIPANTS: High-risk outpatients eligible for mAb treatment under any EUA with a positive SARS-CoV-2 test result from 8 December 2020 to 31 August 2022. INTERVENTION: Single-dose intravenous mAb treatment with bamlanivimab, bamlanivimab-etesevimab, sotrovimab, bebtelovimab, or intravenous or subcutaneous casirivimab-imdevimab administered within 2 days of a positive SARS-CoV-2 test result. MEASUREMENTS: The primary outcome was hospitalization or death at 28 days among treated patients versus a nontreated control group (no treatment or treatment ≥3 days after SARS-CoV-2 test date). RESULTS: The risk for hospitalization or death at 28 days was 4.6% in 2571 treated patients and 7.6% in 5135 nontreated control patients (risk ratio [RR], 0.61 [95% CI, 0.50 to 0.74]). In sensitivity analyses, the corresponding RRs for 1- and 3-day treatment grace periods were 0.59 and 0.49, respectively. In subgroup analyses, those receiving mAbs when the Alpha and Delta variants were presumed to be predominant had estimated RRs of 0.55 and 0.53, respectively, compared with 0.71 for the Omicron variant period. Relative risk estimates for individual mAb products all suggested lower risk for hospitalization or death. Among immunocompromised patients, the RR was 0.45 (CI, 0.28 to 0.71). LIMITATIONS: Observational study design, SARS-CoV-2 variant presumed by date rather than genotyping, no data on symptom severity, and partial data on vaccination status. CONCLUSION: Early mAb treatment among outpatients with COVID-19 is associated with lower risk for hospitalization or death for various mAb products and SARS-CoV-2 variants. PRIMARY FUNDING SOURCE: None.

Changes in body weight and glycemic control in association with COVID-19 Shutdown among 23,000 adults with type 2 diabetes.

AIMS: To examine the association between COVID-19 Shutdown and within-subjects changes in body weight, body mass index (BMI), and glycemic parameters using electronic health record (EHR) data from 23,000 adults with type 2 diabetes (T2DM). METHODS: Patients with T2DM with outpatient visit data on body weight, BMI, hemoglobin A1c (HbA1c), and blood glucose (≥ 2 measures before and after 3/16/2020) recorded in the EHR at the University of Pittsburgh Medical Center were included. A within-subjects analysis compared average and clinically significant changes in weight, BMI, HbA1c, and blood glucose during the year POST-Shutdown (Time 2-3) compared to the same interval during the PRE-Shutdown year (Time 0-1) using paired samples t-tests and the McNemar-Bowker test. RESULTS: We studied 23,697 adults with T2DM (51% female; 89% White; mean age = 66 ± 13 years; mean BMI = 34 ± 7 kg/m2; mean HbA1c = 7 ± 2% [53 ± 21.9 mmol/mol]). Weight and BMI decreased during both the PRE- and POST-Shutdown intervals, but the changes were statistically smaller during the year POST-Shutdown relative to PRE (0.32 kg and 0.11 units, p < 0.0001). HbA1c showed statistically greater improvements during the POST-Shutdown interval compared to PRE (- 0.18% [-2 mmol/mol], p < 0.0001), but changes in glucose did not differ for the two intervals. CONCLUSIONS: Despite widespread discussion of weight gain in association with the COVID-19 Shutdown, study data showed no evidence of adverse effects of Shutdown on body weight, BMI, HbA1C, or blood glucose in a large sample of adults with T2DM. This information may help to inform future public health decision-making.

A Retrospective Analysis of Clinical Utilization Between Patients Who Used Telemedicine and Office Visits in Outpatient Physical Medicine and Rehabilitation Clinics During the COVID-19 Pandemic.

OBJECTIVE: To describe the demographic characteristics of patients who used telemedicine and office visits in physical medicine and rehabilitation during the COVID-19 pandemic and to quantify differences in clinical utilization between groups. Clinical utilization was defined as emergency department, urgent care, and hospital visits. DESIGN: This was a retrospective cohort study of 1096 patients who used telemedicine and 1171 patients who used office visits from April to June 2020 in the outpatient physical medicine and rehabilitation clinics at University of Pittsburgh Medical Center for musculoskeletal-related complaints. RESULTS: The telemedicine groups contained proportionally more people of color and higher comorbidities than the office visit groups. Patients who were seen in the telemedicine groups were more likely to be prescribed opioids than the office visit group. There were no differences in clinical utilizations between the telemedicine and office visit groups. CONCLUSIONS: The higher use of telemedicine in patients of color suggests a need for studying long-term outcomes to evaluate differences in care standards. There is an urgent need to understand how telemedicine affects opioid prescribing practices. Lastly, future studies are needed to understand why there were no differences in clinical utilization between the telemedicine and office visit groups.

Evaluation of Bebtelovimab for Treatment of Covid-19 During the SARS-CoV-2 Omicron Variant Era.

Background: Monoclonal antibody (mAb) treatment is associated with decreased risk of hospitalization and death in high-risk outpatients with mild to moderate coronavirus disease 2019 (COVID-19) caused by early severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Bebtelovimab exhibits in vitro activity against the Omicron variant and its sublineages; however, clinical data are lacking. Methods: A retrospective cohort study was conducted comparing bebtelovimab-treated patients with propensity score-adjusted and matched nontreated control groups. Participants included high-risk outpatients eligible for bebtelovimab treatment under Emergency Use Authorization with a positive SARS-CoV-2 test from March 30 to May 28, 2022. Treated patients received single-dose intravenous treatment with bebtelovimab. The primary outcome was hospitalization or death over 28 days. Results: Before matching/statistical adjustment, mAb-treated patients were, on average, 10 years older than nontreated patients (61.6 vs 51.3 years) and had higher prevalence of obstructive sleep apnea, hypertension, chronic kidney disease, cancer, organ or cell transplant, and immunocompromised status (standardized mean differences ≥0.20). The adjusted odds ratio (OR) of hospitalization or death comparing 1006 treated with 2023 nontreated patients was 0.50 (95% CI, 0.31-0.80). Among 930 treated and 930 propensity score-matched nontreated patients, the incidence of hospitalization or death was 3.1% vs 5.5%, respectively (conditional OR, 0.53; 95% CI, 0.32-0.86). The lower odds ratio of hospitalization or death associated with bebtelovimab treatment was most evident in older patients, those with immunocompromised status, and fully vaccinated patients. Conclusions: Monoclonal antibody treatment with bebtelovimab among COVID-19 outpatients is associated with lower odds of hospitalization or death, particularly among immunocompromised and older patients.

Healthcare Use in the Year Following Bronchiolitis Hospitalization.

OBJECTIVES: Healthcare utilization after bronchiolitis hospitalization is incompletely understood. We aimed to characterize readmissions and outpatient visits within 1 year after hospital discharge. METHODS: Retrospective multicenter observational cohort study of children under 24-months old admitted with bronchiolitis between January 1, 2010 and December 12, 2019 to the Pediatric Health Information Systems database. A single-center nested subset using linked electronic health records allowed analysis of outpatient visits. RESULTS: There were 308 306 admissions for bronchiolitis among 271 115 patients across 47 hospitals between 2010-2019. The percent of patients readmitted within 30 days after discharge was 6.0% (16 167 of 271 115), and 17.8% (48 332 of 271 115) of patients were readmitted within 1 year. 22.9% (16 919 of 74 001) of patients admitted to an ICU and 26.8% (7865 of 29 378) of patients undergoing mechanical ventilation were readmitted within 1 year. There were 1438 patients with outpatient healthcare data available. There were a median (interquartile range) of 9 (6-13) outpatient visits per patient within 1 year after discharge. Outpatient healthcare use increased for 4 months following bronchiolitis hospitalization compared with previously reported age-matched controls. Higher income, white race, commercial insurance, complex chronic conditions, ICU admission, and mechanical ventilation were associated with higher outpatient utilization. Higher quartiles of outpatient use were associated with readmission for bronchiolitis and all-cause readmissions. CONCLUSIONS: Readmissions in the year after bronchiolitis hospitalization are common, and outpatient healthcare use is increased for 4 months following discharge. Prospective study is needed to track long-term outcomes of infants with bronchiolitis.

A learning health system approach to the COVID-19 pandemic: System-wide changes in clinical practice and 30-day mortality among hospitalized patients.

Introduction: Rapid, continuous implementation of credible scientific findings and regulatory approvals is often slow in large, diverse health systems. The coronavirus disease 2019 (COVID-19) pandemic created a new threat to this common "slow to learn and adapt" model in healthcare. We describe how the University of Pittsburgh Medical Center (UPMC) committed to a rapid learning health system (LHS) model to respond to the COVID-19 pandemic. Methods: A treatment cohort study was conducted among 11 429 hospitalized patients (pediatric/adult) from 22 hospitals (PA, NY) with a primary diagnosis of COVID-19 infection (March 19, 2020 - June 6, 2021). Sociodemographic and clinical data were captured from UPMC electronic medical record (EMR) systems. Patients were grouped into four time-defined patient "waves" based on nadir of daily hospital admissions, with wave 3 (September 20, 2020 - March 10, 2021) split at its zenith due to high volume with steep acceleration and deceleration. Outcomes included changes in clinical practice (eg, use of corticosteroids, antivirals, and other therapies) in relation to timing of internal system analyses, scientific publications, and regulatory approvals, along with 30-day rate of mortality over time. Results: The mean (SD) daily number of admissions across hospitals was 26 (29) with a maximum 7-day moving average of 107 patients. System-wide implementation of the use of dexamethasone, remdesivir, and tocilizumab occurred within days of release of corresponding seminal publications and regulatory actions. After adjustment for differences in patient clinical profiles over time, each month of hospital admission was associated with an estimated 5% lower odds of 30-day mortality (adjusted odds ratio [OR] = 0.95, 95% confidence interval: 0.93-0.97, P < .001). Conclusions: In our large LHS, near real-time changes in clinical management of COVID-19 patients happened promptly as scientific publications and regulatory approvals occurred throughout the pandemic. Alongside these changes, patients with COVID-19 experienced lower adjusted 30-day mortality following hospital admission over time.

Predictive model for severe COVID-19 using SARS-CoV-2 whole-genome sequencing and electronic health record data, March 2020-May 2021.

OBJECTIVE: We used SARS-CoV-2 whole-genome sequencing (WGS) and electronic health record (EHR) data to investigate the associations between viral genomes and clinical characteristics and severe outcomes among hospitalized COVID-19 patients. METHODS: We conducted a case-control study of severe COVID-19 infection among patients hospitalized at a large academic referral hospital between March 2020 and May 2021. SARS-CoV-2 WGS was performed, and demographic and clinical characteristics were obtained from the EHR. Severe COVID-19 (case patients) was defined as having one or more of the following: requirement for supplemental oxygen, mechanical ventilation, or death during hospital admission. Controls were hospitalized patients diagnosed with COVID-19 who did not meet the criteria for severe infection. We constructed predictive models incorporating clinical and demographic variables as well as WGS data including lineage, clade, and SARS-CoV-2 SNP/GWAS data for severe COVID-19 using multiple logistic regression. RESULTS: Of 1,802 hospitalized SARS-CoV-2-positive patients, we performed WGS on samples collected from 590 patients, of whom 396 were case patients and 194 were controls. Age (p = 0.001), BMI (p = 0.032), test positive time period (p = 0.001), Charlson comorbidity index (p = 0.001), history of chronic heart failure (p = 0.003), atrial fibrillation (p = 0.002), or diabetes (p = 0.007) were significantly associated with case-control status. SARS-CoV-2 WGS data did not appreciably change the results of the above risk factor analysis, though infection with clade 20A was associated with a higher risk of severe disease, after adjusting for confounder variables (p = 0.024, OR = 3.25; 95%CI: 1.31-8.06). CONCLUSIONS: Among people hospitalized with COVID-19, older age, higher BMI, earlier test positive period, history of chronic heart failure, atrial fibrillation, or diabetes, and infection with clade 20A SARS-CoV-2 strains can predict severe COVID-19.

Effectiveness of Casirivimab-Imdevimab and Sotrovimab During a SARS-CoV-2 Delta Variant Surge: A Cohort Study and Randomized Comparative Effectiveness Trial.

Importance: The effectiveness of monoclonal antibodies (mAbs), casirivimab-imdevimab and sotrovimab, is unknown in patients with mild to moderate COVID-19 caused by the SARS-CoV-2 Delta variant. Objective: To evaluate the effectiveness of mAb against the Delta variant compared with no mAb treatment and to ascertain the comparative effectiveness of casirivimab-imdevimab and sotrovimab. Design, Setting, and Participants: This study comprised 2 parallel studies: (1) a propensity score-matched cohort study of mAb treatment vs no mAb treatment and (2) a randomized comparative effectiveness trial of casirivimab-imdevimab and sotrovimab. The cohort consisted of patients who received mAb treatment at the University of Pittsburgh Medical Center outpatient infusion centers and emergency departments from July 14 to September 29, 2021. Participants were patients with a positive SARS-CoV-2 test result who were eligible to receive mAbs according to emergency use authorization criteria. Exposure: For the trial, patients were randomized to either intravenous casirivimab-imdevimab or sotrovimab according to a system therapeutic interchange policy. Main Outcomes and Measures: For the cohort study, risk ratio (RR) estimates for the primary outcome of hospitalization or death by 28 days were compared between mAb treatment and no mAb treatment using propensity score-matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospitalization) within 28 days after mAb treatment, where patients who died were assigned -1 day in a bayesian cumulative logistic model adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio (OR) less than 1. Equivalence was defined as a 95% posterior probability that the OR was within a given bound. Results: A total of 3069 patients (1023 received mAb treatment: mean [SD] age, 53.2 [16.4] years; 569 women [56%]; 2046 had no mAb treatment: mean [SD] age, 52.8 [19.5] years; 1157 women [57%]) were included in the prospective cohort study, and 3558 patients (mean [SD] age, 54 [18] years; 1919 women [54%]) were included in the randomized comparative effectiveness trial. In propensity score-matched models, mAb treatment was associated with reduced risk of hospitalization or death (RR, 0.40; 95% CI, 0.28-0.57) compared with no treatment. Both casirivimab-imdevimab (RR, 0.31; 95% CI, 0.20-0.50) and sotrovimab (RR, 0.60; 95% CI, 0.37-1.00) were associated with reduced hospitalization or death compared with no mAb treatment. In the clinical trial, 2454 patients were randomized to receive casirivimab-imdevimab and 1104 patients were randomized to receive sotrovimab. The median (IQR) hospital-free days were 28 (28-28) for both mAb treatments, the 28-day mortality rate was less than 1% (n = 12) for casirivimab-imdevimab and less than 1% (n = 7) for sotrovimab, and the hospitalization rate by day 28 was 12% (n = 291) for casirivimab-imdevimab and 13% (n = 140) for sotrovimab. Compared with patients who received casirivimab-imdevimab, those who received sotrovimab had a median adjusted OR for hospital-free days of 0.88 (95% credible interval, 0.70-1.11). This OR yielded 86% probability of inferiority for sotrovimab vs casirivimab-imdevimab and 79% probability of equivalence. Conclusions and Relevance: In this propensity score-matched cohort study and randomized comparative effectiveness trial, the effectiveness of casirivimab-imdevimab and sotrovimab against the Delta variant was similar, although the prespecified criteria for statistical inferiority or equivalence were not met. Both mAb treatments were associated with a reduced risk of hospitalization or death in nonhospitalized patients with mild to moderate COVID-19 caused by the Delta variant. Trial Registration: ClinicalTrials.gov Identifier: NCT04790786.