Faculty Bibliography

IMPORTANCE/UNASSIGNED:A substantial number of individuals worldwide experience long COVID, or post-COVID condition. Other postviral and autoimmune conditions have a female predominance, but whether the same is true for long COVID, especially within different subgroups, is uncertain. OBJECTIVE/UNASSIGNED:To evaluate sex differences in the risk of developing long COVID among adults with SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study used data from the National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER)-Adult cohort, which consists of individuals enrolled in and prospectively followed up at 83 sites in 33 US states plus Washington, DC, and Puerto Rico. Data were examined from all participants enrolled between October 29, 2021, and July 5, 2024, who had a qualifying study visit 6 months or more after their initial SARS-CoV-2 infection. EXPOSURE/UNASSIGNED:Self-reported sex (male, female) assigned at birth. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Development of long COVID, measured using a self-reported symptom-based questionnaire and scoring guideline at the first study visit that occurred at least 6 months after infection. Propensity score matching was used to estimate risk ratios (RRs) and risk differences (95% CIs). The full model included demographic and clinical characteristics and social determinants of health, and the reduced model included only age, race, and ethnicity. RESULTS/UNASSIGNED:Among 12 276 participants who had experienced SARS-CoV-2 infection (8969 [73%] female; mean [SD] age at infection, 46 [15] years), female sex was associated with higher risk of long COVID in the primary full (RR, 1.31; 95% CI, 1.06-1.62) and reduced (RR, 1.44; 95% CI, 1.17-1.77) models. This finding was observed across all age groups except 18 to 39 years (RR, 1.04; 95% CI, 0.72-1.49). Female sex was associated with significantly higher overall long COVID risk when the analysis was restricted to nonpregnant participants (RR, 1.50; 95%: CI, 1.27-1.77). Among participants aged 40 to 54 years, the risk ratio was 1.42 (95% CI, 0.99-2.03) in menopausal female participants and 1.45 (95% CI, 1.15-1.83) in nonmenopausal female participants compared with male participants. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this prospective cohort study of the NIH RECOVER-Adult cohort, female sex was associated with an increased risk of long COVID compared with male sex, and this association was age, pregnancy, and menopausal status dependent. These findings highlight the need to identify biological mechanisms contributing to sex specificity to facilitate risk stratification, targeted drug development, and improved management of long COVID.

In 2001, the Centers for Medicare and Medicaid Services established the New Technology Add-On Payment (NTAP) program to incentivize access to costly new technologies for Medicare beneficiaries. These technologies, authorized by the Food and Drug Administration (FDA), must demonstrate "substantial clinical improvement" when compared to existing technologies. However, in FY2021, the FDA introduced two expedited authorization pathways, allowing technologies with either designation to bypass the "substantial clinical improvement" criterion. We describe the services and payments associated with NTAPs following this policy change.

IMPORTANCE/UNASSIGNED:The emergency department (ED) offers an opportunity to initiate palliative care for older adults with serious, life-limiting illness. OBJECTIVE/UNASSIGNED:To assess the effect of a multicomponent intervention to initiate palliative care in the ED on hospital admission, subsequent health care use, and survival in older adults with serious, life-limiting illness. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Cluster randomized, stepped-wedge, clinical trial including patients aged 66 years or older who visited 1 of 29 EDs across the US between May 1, 2018, and December 31, 2022, had 12 months of prior Medicare enrollment, and a Gagne comorbidity score greater than 6, representing a risk of short-term mortality greater than 30%. Nursing home patients were excluded. INTERVENTION/UNASSIGNED:A multicomponent intervention (the Primary Palliative Care for Emergency Medicine intervention) included (1) evidence-based multidisciplinary education; (2) simulation-based workshops on serious illness communication; (3) clinical decision support; and (4) audit and feedback for ED clinical staff. MAIN OUTCOME AND MEASURES/UNASSIGNED:The primary outcome was hospital admission. The secondary outcomes included subsequent health care use and survival at 6 months. RESULTS/UNASSIGNED:There were 98 922 initial ED visits during the study period (median age, 77 years [IQR, 71-84 years]; 50% were female; 13% were Black and 78% were White; and the median Gagne comorbidity score was 8 [IQR, 7-10]). The rate of hospital admission was 64.4% during the preintervention period vs 61.3% during the postintervention period (absolute difference, -3.1% [95% CI, -3.7% to -2.5%]; adjusted odds ratio [OR], 1.03 [95% CI, 0.93 to 1.14]). There was no difference in the secondary outcomes before vs after the intervention. The rate of admission to an intensive care unit was 7.8% during the preintervention period vs 6.7% during the postintervention period (adjusted OR, 0.98 [95% CI, 0.83 to 1.15]). The rate of at least 1 revisit to the ED was 34.2% during the preintervention period vs 32.2% during the postintervention period (adjusted OR, 1.00 [95% CI, 0.91 to 1.09]). The rate of hospice use was 17.7% during the preintervention period vs 17.2% during the postintervention period (adjusted OR, 1.04 [95% CI, 0.93 to 1.16]). The rate of home health use was 42.0% during the preintervention period vs 38.1% during the postintervention period (adjusted OR, 1.01 [95% CI, 0.92 to 1.10]). The rate of at least 1 hospital readmission was 41.0% during the preintervention period vs 36.6% during the postintervention period (adjusted OR, 1.01 [95% CI, 0.92 to 1.10]). The rate of death was 28.1% during the preintervention period vs 28.7% during the postintervention period (adjusted OR, 1.07 [95% CI, 0.98 to 1.18]). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This multicomponent intervention to initiate palliative care in the ED did not have an effect on hospital admission, subsequent health care use, or short-term mortality in older adults with serious, life-limiting illness. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03424109.

BACKGROUND:Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may occur after infection. How often people develop ME/CFS after SARS-CoV-2 infection is unknown. OBJECTIVE:To determine the incidence and prevalence of post-COVID-19 ME/CFS among adults enrolled in the Researching COVID to Enhance Recovery (RECOVER-Adult) study. DESIGN, SETTING, AND PARTICIPANTS/METHODS:RECOVER-Adult is a longitudinal observational cohort study conducted across the U.S. We included participants who had a study visit at least 6 months after infection and had no pre-existing ME/CFS, grouped as (1) acute infected, enrolled within 30 days of infection or enrolled as uninfected who became infected (n=4515); (2) post-acute infected, enrolled greater than 30 days after infection (n=7270); and (3) uninfected (1439). MEASUREMENTS/METHODS:Incidence rate and prevalence of post-COVID-19 ME/CFS based on the 2015 Institute of Medicine ME/CFS clinical diagnostic criteria. RESULTS:The incidence rate of ME/CFS in participants followed from time of SARS-CoV-2 infection was 2.66 (95% CI 2.63-2.70) per 100 person-years while the rate in matched uninfected participants was 0.93 (95% CI 0.91-10.95) per 100 person-years: a hazard ratio of 4.93 (95% CI 3.62-6.71). The proportion of all RECOVER-Adult participants that met criteria for ME/CFS following SARS-CoV-2 infection was 4.5% (531 of 11,785) compared to 0.6% (9 of 1439) in uninfected participants. Post-exertional malaise was the most common ME/CFS symptom in infected participants (24.0%, 2830 of 11,785). Most participants with post-COVID-19 ME/CFS also met RECOVER criteria for long COVID (88.7%, 471 of 531). LIMITATIONS/CONCLUSIONS:The ME/CFS clinical diagnostic criteria uses self-reported symptoms. Symptoms can wax and wane. CONCLUSION/CONCLUSIONS:ME/CFS is a diagnosable sequela that develops at an increased rate following SARS-CoV-2 infection. RECOVER provides an unprecedented opportunity to study post-COVID-19 ME/CFS.

IMPORTANCE/UNASSIGNED:Classification of persons with long COVID (LC) or post-COVID-19 condition must encompass the complexity and heterogeneity of the condition. Iterative refinement of the classification index for research is needed to incorporate newly available data as the field rapidly evolves. OBJECTIVE/UNASSIGNED:To update the 2023 research index for adults with LC using additional participant data from the Researching COVID to Enhance Recovery (RECOVER-Adult) study and an expanded symptom list based on input from patient communities. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Prospective, observational cohort study including adults 18 years or older with or without known prior SARS-CoV-2 infection who were enrolled at 83 sites in the US and Puerto Rico. Included participants had at least 1 study visit taking place 4.5 months after first SARS-CoV-2 infection or later, and not within 30 days of a reinfection. The study visits took place between October 2021 and March 2024. EXPOSURE/UNASSIGNED:SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Presence of LC and participant-reported symptoms. RESULTS/UNASSIGNED:A total of 13 647 participants (11 743 with known SARS-CoV-2 infection and 1904 without known prior SARS-CoV-2 infection; median age, 45 years [IQR, 34-69 years]; and 73% were female) were included. Using the least absolute shrinkage and selection operator analysis regression approach from the 2023 model, symptoms contributing to the updated 2024 index included postexertional malaise, fatigue, brain fog, dizziness, palpitations, change in smell or taste, thirst, chronic cough, chest pain, shortness of breath, and sleep apnea. For the 2024 LC research index, the optimal threshold to identify participants with highly symptomatic LC was a score of 11 or greater. The 2024 index classified 20% of participants with known prior SARS-CoV-2 infection and 4% of those without known prior SARS-CoV-2 infection as having likely LC (vs 21% and 5%, respectively, using the 2023 index) and 39% of participants with known prior SARS-CoV-2 infection as having possible LC, which is a new category for the 2024 model. Cluster analysis identified 5 LC subtypes that tracked quality-of-life measures. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The 2024 LC research index for adults builds on the 2023 index with additional data and symptoms to help researchers classify symptomatic LC and its symptom subtypes. Continued future refinement of the index will be needed as the understanding of LC evolves.

BACKGROUND:Patients hospitalized with COVID-19 can clinically deteriorate after a period of initial stability, making optimal timing of discharge a clinical and operational challenge. OBJECTIVE:To determine risks for post-discharge readmission and death among patients hospitalized with COVID-19. DESIGN/METHODS:Multicenter retrospective observational cohort study, 2020-2021, with 30-day follow-up. PARTICIPANTS/METHODS:Adults admitted for care of COVID-19 respiratory disease between March 2, 2020, and February 11, 2021, to one of 180 US hospitals affiliated with the HCA Healthcare system. MAIN MEASURES/METHODS:Readmission to or death at an HCA hospital within 30 days of discharge was assessed. The area under the receiver operating characteristic curve (AUC) was calculated using an internal validation set (33% of the HCA cohort), and external validation was performed using similar data from six academic centers associated with a hospital medicine research network (HOMERuN). KEY RESULTS/RESULTS:The final HCA cohort included 62,195 patients (mean age 61.9 years, 51.9% male), of whom 4704 (7.6%) were readmitted or died within 30 days of discharge. Independent risk factors for death or readmission included fever within 72 h of discharge; tachypnea, tachycardia, or lack of improvement in oxygen requirement in the last 24 h; lymphopenia or thrombocytopenia at the time of discharge; being ≤ 7 days since first positive test for SARS-CoV-2; HOSPITAL readmission risk score ≥ 5; and several comorbidities. Inpatient treatment with remdesivir or anticoagulation were associated with lower odds. The model's AUC for the internal validation set was 0.73 (95% CI 0.71-0.74) and 0.66 (95% CI 0.64 to 0.67) for the external validation set. CONCLUSIONS:This large retrospective study identified several factors associated with post-discharge readmission or death in models which performed with good discrimination. Patients 7 or fewer days since test positivity and who demonstrate potentially reversible risk factors may benefit from delaying discharge until those risk factors resolve.

Electronic health record (EHR)-embedded tools are known to improve prescribing of guideline-directed medical therapy (GDMT) for patients with heart failure. However, physicians may perceive EHR tools to be unhelpful, and may be therefore hesitant to implement these in their practice. We surveyed cardiologists about two effective EHR-tools to improve heart failure care, and they perceived the EHR tools to be easy to use, helpful, and improve the overall management of their patients with heart failure.