Effectiveness of BNT162b2 BA.4/5 Bivalent mRNA Vaccine Against Symptomatic COVID-19 Among Immunocompetent Individuals Testing at a Large US Retail Pharmacy.

BACKGROUND: Data on the effectiveness of BA.4/5 bivalent vaccine stratified by age and prior infection are lacking. METHODS: This test-negative study used data from individuals ≥5 years of age testing for SARS-CoV-2 with symptoms (15 September 2022 to 31 January 2023) at a large national retail pharmacy chain. The exposure was receipt of 2-4 wild-type doses and a BNT162b2 BA.4/5 bivalent vaccine (>2 months since last wild-type dose). The outcome was a positive SARS-CoV-2 test. Absolute (vs unvaccinated) and relative (vs 2-4 wild-type doses) vaccine effectiveness (VE) were calculated as (1 - adjusted odds ratio from logistic regression) × 100. VE was stratified by age and self-reported prior infection. RESULTS: Overall, 307 885 SARS-CoV-2 tests were included (7916 aged 5-11, 16 329 aged 12-17, and 283 640 aged ≥18 years). SARS-CoV-2 positivity was 39%; 21% were unvaccinated, 70% received 2-4 wild-type doses with no bivalent vaccine, and 9% received a BNT162b2 BA.4/5 bivalent dose. At a median of 1-2 months after BNT162b2 BA.4/5 bivalent vaccination, depending on age group, absolute VE was 22%-60% and was significantly higher among those reporting prior infection (range, 55%-79%) than not (range, no protection to 50%). Relative VE was 31%-64%. CONCLUSIONS: BNT162b2 BA.4/5 bivalent showed early additional protection against Omicron-related symptomatic COVID-19, with hybrid immunity offering greater protection.

Coronavirus Disease 2019 Severity and Risk of Subsequent Cardiovascular Events.

BACKGROUND: Little is known about the relationship between coronavirus disease 2019 (COVID-19) severity and subsequent risk of experiencing a cardiovascular event (CVE) after COVID-19 recovery. We evaluated this relationship in a large cohort of United States adults. METHODS: Using a claims database, we performed a retrospective cohort study of adults diagnosed with COVID-19 between 1 April 2020 and 31 May 2021. We evaluated the association between COVID-19 severity and risk of CVE >30 days after COVID-19 diagnosis using inverse probability of treatment-weighted competing risks regression. Severity was based on level of care required for COVID-19 treatment: intensive care unit (ICU) admission, non-ICU hospitalization, or outpatient care only. RESULTS: A total of 1 357 518 COVID-19 patients were included (2% ICU, 3% non-ICU hospitalization, and 95% outpatient only). Compared to outpatients, there was an increased risk of any CVE for patients requiring ICU admission (adjusted hazard ratio [aHR], 1.80 [95% confidence interval {CI}, 1.71-1.89]) or non-ICU hospitalization (aHR, 1.28 [95% CI, 1.24-1.33]). Risk of subsequent hospitalization for CVE was even higher (aHRs, 3.47 [95% CI, 3.20-3.76] for ICU and 1.96 [95% CI, 1.85-2.09] for non-ICU hospitalized vs outpatient only). CONCLUSIONS: COVID-19 patients hospitalized or requiring critical care had a significantly higher risk of experiencing and being hospitalized for post-COVID-19 CVE than patients with milder COVID-19 who were managed solely in the outpatient setting, even after adjusting for differences between these groups. These findings underscore the continued importance of preventing severe acute respiratory syndrome coronavirus 2 infection from progressing to severe illness to reduce potential long-term cardiovascular complications.

Effectiveness of oseltamivir treatment on clinical failure in hospitalized patients with lower respiratory tract infection.

BACKGROUND: Influenza is associated with excess morbidity and mortality of individuals each year. Few therapies exist for treatment of influenza infection, and each require initiation as early as possible in the course of infection, making efficacy difficult to estimate in the hospitalized patient with lower respiratory tract infection. Using causal machine learning methods, we re-analyze data from a randomized trial of oseltamivir versus standard of care aimed at reducing clinical failure in hospitalized patients with lower respiratory tract infection during the influenza season. METHODS: This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS). Conditional average treatment effects (CATE) and 95% confidence intervals were computed from causal forest including 85 clinical and demographic variables. RETOS was a multicenter, randomized, unblinded, trial of adult patients hospitalized with lower respiratory tract infections in Kentucky from 2009 through 2012. Adult hospitalized patients with lower respiratory tract infection were randomized to standard of care or standard of care plus oseltamivir as early as possible after hospital admission but within 24 h of enrollment. After randomization, oseltamivir was initiated in the treatment arm per package insert. The primary outcome was clinical failure, a composite measure including failure to reach clinical improvement within 7 days, transfer to intensive care 24 h after admission, or rehospitalization or death within 30 days. RESULTS: A total of 691 hospitalized patients with lower respiratory tract infections were included in the study. The only subgroup of patients with a statistically significant CATE was those with laboratory-confirmed influenza infection with a 26% lower risk of clinical failure when treated with oseltamivir (95% CI 3.2-48.0%). CONCLUSIONS: This study suggests that addition of oseltamivir to standard of care may decrease clinical failure in hospitalized patients with influenza-associated lower respiratory tract infection versus standard of care alone. These results are supportive of current recommendations to initiate antiviral treatment in hospitalized patients with confirmed or suspected influenza as soon as possible after admission. Trial registration Original trial: Clinical Trials.Gov; Rapid Empiric Treatment With Oseltamivir Study (RETOS) (RETOS); ClinicalTrials.gov Identifier: NCT01248715 https://clinicaltrials.gov/ct2/show/NCT01248715.

Thresholds versus Anomaly Detection for Surveillance of Pneumonia and Influenza Mortality.

Computational surveillance of pneumonia and influenza mortality in the United States using FluView uses epidemic thresholds to identify high mortality rates but is limited by statistical issues such as seasonality and autocorrelation. We used time series anomaly detection to improve recognition of high mortality rates. Results suggest that anomaly detection can complement mortality reporting.

Machine Learning in Epidemiology and Health Outcomes Research.

Machine learning approaches to modeling of epidemiologic data are becoming increasingly more prevalent in the literature. These methods have the potential to improve our understanding of health and opportunities for intervention, far beyond our past capabilities. This article provides a walkthrough for creating supervised machine learning models with current examples from the literature. From identifying an appropriate sample and selecting features through training, testing, and assessing performance, the end-to-end approach to machine learning can be a daunting task. We take the reader through each step in the process and discuss novel concepts in the area of machine learning, including identifying treatment effects and explaining the output from machine learning models.

Intraprocedural Superior Hypogastric Nerve Block Allows Same-Day Discharge following Uterine Artery Embolization.

In a single-arm, nonrandomized, retrospective case-control study, 39 patients (mean age, 44 y) who underwent elective outpatient uterine artery embolization with the use of superior hypogastric nerve block (SNHB) for pain control over a period of 3 years were identified. Technical success of SNHB was 87%. Of the 34 patients who received SNHB, 97% did not need a patient-controlled analgesia pump. The median opioid requirement for the 17 patients who needed opioid agents was 7.5 morphine milligram equivalents (interquartile range [IQR], 10). The median length of stay was 2.2 hours (IQR, 1.7 h). SHNB offers a safe and effective intervention that significantly reduces pain and the need for opiate agents and allows same-day discharge after uterine artery embolization.

Association of Clinician Health System Affiliation With Outpatient Performance Ratings in the Medicare Merit-based Incentive Payment System.

Importance: Integration of physician practices into health systems composed of hospitals and multispecialty practices is increasing in the era of value-based payment. It is unknown how clinicians who affiliate with such health systems perform under the new mandatory Centers for Medicare & Medicaid Services Merit-based Incentive Payment System (MIPS) relative to their peers. Objective: To assess the relationship between the health system affiliations of clinicians and their performance scores and value-based reimbursement under the 2019 MIPS. Design, Setting, and Participants: Publicly reported data on 636 552 clinicians working at outpatient clinics across the US were used to assess the association of the affiliation status of clinicians within the 609 health systems with their 2019 final MIPS performance score and value-based reimbursement (both based on clinician performance in 2017), adjusting for clinician, patient, and practice area characteristics. Exposures: Health system affiliation vs no affiliation. Main Outcomes and Measures: The primary outcome was final MIPS performance score (range, 0-100; higher scores intended to represent better performance). The secondary outcome was MIPS payment adjustment, including negative (penalty) payment adjustment, positive payment adjustment, and bonus payment adjustment. Results: The final sample included 636 552 clinicians (41% female, 83% physicians, 50% in primary care, 17% in rural areas), including 48.6% who were affiliated with a health system. Compared with unaffiliated clinicians, system-affiliated clinicians were significantly more likely to be female (46% vs 37%), primary care physicians (36% vs 30%), and classified as safety net clinicians (12% vs 10%) and significantly less likely to be specialists (44% vs 55%) (P < .001 for each). The mean final MIPS performance score for system-affiliated clinicians was 79.0 vs 60.3 for unaffiliated clinicians (absolute mean difference, 18.7 [95% CI, 18.5 to 18.8]). The percentage receiving a negative (penalty) payment adjustment was 2.8% for system-affiliated clinicians vs 13.7% for unaffiliated clinicians (absolute difference, -10.9% [95% CI, -11.0% to -10.7%]), 97.1% vs 82.6%, respectively, for those receiving a positive payment adjustment (absolute difference, 14.5% [95% CI, 14.3% to 14.6%]), and 73.9% vs 55.1% for those receiving a bonus payment adjustment (absolute difference, 18.9% [95% CI, 18.6% to 19.1%]). Conclusions and Relevance: Clinician affiliation with a health system was associated with significantly better 2019 MIPS performance scores. Whether this represents differences in quality of care or other factors requires additional research.

Skin antiseptics in healthcare facilities: is a targeted approach necessary?

BACKGROUND: Skin antisepsis occurs in every healthcare environment. From basic hand hygiene, to antiseptic bathing and pre surgical care with alcohol/chlorhexidine, use of antimicrobial agents to reduce the skin microflora has skyrocketed in the past several years. Although used in hopes of reducing the likelihood of infection in patients, many products have been identified as the source of infection in several outbreaks, sometimes due to the nonsterile nature of the many readily available antiseptics. BODY: Intrinsic contamination of antiseptics during the manufacturing process is common. In fact, since the majority of these products are sold as nonsterile, they are allowed some level of microbial contamination based on the United States Pharmacopeia documents 61 and 62. Unfortunately, sometimes this contamination is with microorganisms resistant to the antiseptic and/or with those pathogenic to humans. In this scenario, healthcare-associated infections may occur, leaving the patient at higher risk of mortality and increasing costs of care substantially. Although antibiotic stewardship programs throughout the world suggest targeting use of antibiotics to limit resistance, few healthcare environments include other antimicrobial agents (such as antiseptics) in their programs. CONCLUSION: Due to the potential for contamination with pathogenic organisms and the increased likelihood of selecting for resistant organisms with widespread use of broad-spectrum agents with non-specific mechanisms of action, a discussion around including skin antiseptics in stewardship programs is necessary, particularly those labeled as nonsterile. At minimum, debating the pros and cons of targeting use of daily antiseptic bathing in hospitalized patients should occur. Through mindfully incorporating any antimicrobial agent, sterile or not, into our repertoire of anti-infectives, we can save patient lives, reduce infection, and save costs.

Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Hospitalization for Community-Acquired Pneumonia in Older US Adults: A Test-Negative Design.

Background: Following universal recommendation for use of 13-valent pneumococcal conjugate vaccine (PCV13) in US adults aged ≥65 years in September 2014, we conducted the first real-world evaluation of PCV13 vaccine effectiveness (VE) against hospitalized vaccine-type community-acquired pneumonia (CAP) in this population. Methods: Using a test-negative design, we identified cases and controls from a population-based surveillance study of adults in Louisville, Kentucky, who were hospitalized with CAP. We analyzed a subset of CAP patients enrolled 1 April 2015 through 30 April 2016 who were aged ≥65 years and consented to have their pneumococcal vaccination history confirmed by health insurance records. Cases were defined as hospitalized CAP patients with PCV13 serotypes identified via culture or serotype-specific urinary antigen detection assay. Remaining CAP patients served as test-negative controls. Results: Of 2034 CAP hospitalizations, we identified PCV13 serotypes in 68 (3.3%) participants (ie, cases), of whom 6 of 68 (8.8%) had a positive blood culture. Cases were less likely to be immunocompromised (29.4% vs 46.4%, P = .02) and overweight or obese (41.2% vs 58.6%, P = .01) compared to controls, but were otherwise similar. Cases were less likely to have received PCV13 than controls (3/68 [4.4%] vs 285/1966 [14.5%]; unadjusted VE, 72.8% [95% confidence interval, 12.8%-91.5%]). No confounding was observed during adjustment for patient characteristics, including immunocompromised status, body mass index, and history of influenza and pneumococcal polysaccharide vaccination (adjusted VE range, 71.1%-73.3%). Conclusions: Our study is the first to demonstrate real-world effectiveness of PCV13 against vaccine-type CAP in adults aged ≥65 years following introduction into a national immunization program.

Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and Mortality.

BACKGROUND: Understanding the burden of community-acquired pneumonia (CAP) is critical to allocate resources for prevention, management, and research. The objectives of this study were to define incidence, epidemiology, and mortality of adult patients hospitalized with CAP in the city of Louisville, and to estimate burden of CAP in the US adult population. METHODS: This was a prospective population-based cohort study of adult residents in Louisville, Kentucky, from 1 June 2014 to 31 May 2016. Consecutive hospitalized patients with CAP were enrolled at all adult hospitals in Louisville. The annual population-based CAP incidence was calculated. Geospatial epidemiology was used to define ecological associations among CAP and income level, race, and age. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. RESULTS: During the 2-year study, from a Louisville population of 587499 adults, 186384 hospitalizations occurred. A total of 7449 unique patients hospitalized with CAP were documented. The annual age-adjusted incidence was 649 patients hospitalized with CAP per 100000 adults (95% confidence interval, 628.2-669.8), corresponding to 1591825 annual adult CAP hospitalizations in the United States. Clusters of CAP cases were found in areas with low-income and black/African American populations. Mortality during hospitalization was 6.5%, corresponding to 102821 annual deaths in the United States. Mortality at 30 days, 6 months, and 1 year was 13.0%, 23.4%, and 30.6%, respectively. CONCLUSIONS: The estimated US burden of CAP is substantial, with >1.5 million unique adults being hospitalized annually, 100000 deaths occurring during hospitalization, and approximately 1 of 3 patients hospitalized with CAP dying within 1 year.

Effect of Postoperative Dressing on Excisions Performed on the Leg: A Comparison Between Zinc Oxide Compression Dressings Versus Standard Wound Care.

BACKGROUND: Wound healing on the legs may be complicated by delayed healing and other postoperative problems. Two potential postoperative wound care regimens for sutured excisions on the legs include a standard pressure dressing and zinc oxide compression dressings. Limited data exist comparing the efficacy of these 2 options. OBJECTIVE: To compare outcomes of standard postoperative wound care dressing versus postoperative use of a zinc oxide compression dressings for sutured repairs on the legs. METHODS: In this retrospective cohort study, healing time and complication rate of 44 patients treated with standard dressing and 36 patients treated with zinc oxide compression dressings were compared. RESULTS: At 19 days, 91.7% of patients receiving zinc oxide dressing were fully healed, whereas only 65.9% of patients receiving standard wound care were healed. Complications were noted in 6 of the patients receiving standard dressing (13.6%); no complications occurred in the zinc oxide dressing group. CONCLUSION: Zinc oxide compression dressings were a practical option for postoperative wound care, with decreased incidence of delayed wound healing, and fewer complications versus standard postoperative wound dressing.

The Effects of Kentucky's Comprehensive Opioid Legislation on Patients Presenting with Prescription Opioid or Heroin Abuse to One Urban Emergency Department.

BACKGROUND: Prescription opioid abuse has increased to epidemic proportions in the United States. Kentucky, along with other states, passed comprehensive legislation to monitor and curb opioid prescribing. OBJECTIVES: This paper characterizes patients who presented to the emergency department (ED) after abusing prescription opioids and heroin prior to and after the passage of House Bill 1 (HB1) in April 2012. METHODS: Based on a retrospective review of ED visits from 2009-2014 in one urban adult facility, patients were included if the chief complaint or diagnosis was directly related to prescription opioid or heroin abuse. The primary outcome is the number and type of substance abused by each ED patient. RESULTS: From 2009-2014, 2945 patients presented to the ED after prescription opioid or heroin abuse. The number of prescription opioid patients decreased from 215 (of 276 patients) in 2009 to 203 (of 697 patients) in 2014; 77.9% of patients abused opioids in 2009, vs. 29% in 2014 (a 63% decrease). The number of heroin patients increased from 61 in 2009 to 494 in 2014; 22% of patients in 2009 abused heroin, vs. 71% in 2014 (a 221% increase). Both piecewise regression and autoregressive integrated moving average trend models showed an increased trend in patient heroin abuse beginning in 2011-2012. CONCLUSIONS: Our facility experienced a decrease in the number of patients who abused prescription opioids and an increase in the number of patients who abused heroin over the study period. The transition seemed to occur just prior to, or concurrent with, enforcement of statewide opioid legislation.

Trends in Pneumonia Mortality Rates and Hospitalizations by Organism, United States, 2002-2011(1).

Because the epidemiology of pneumonia is changing, we performed an updated, population-based analysis of hospitalization and case-fatality rates for pneumonia patients in the United States. From 2002 to 2011, hospitalization rates decreased significantly for pneumonia caused by pneumococcus and Haemophilus influenzae but increased significantly for Pseudomonas spp., Staphylococcus aureus, and influenza virus.

Macrolide Use and Neutrophil Function/Cytokine Levels in Hospitalized Patients with Community-Acquired Pneumonia: A Pilot Study.

PURPOSE: The objective of this study was to measure plasma cytokine levels and blood neutrophil functions as well as clinical outcomes in hospitalized patients with community-acquired pneumonia (CAP) treated with or without macrolide use--a known modulator of inflammatory response. METHODS: Subjects with CAP had peripheral blood analyzed for some neutrophil functions (degranulation of secretory vesicles and specific granules, respiratory burst response and phagocytosis) and ten cytokine levels measured in serum and sputum supernatants. Neutrophil function in healthy volunteers was also measured for reference. Values were measured on the day of enrollment, days 2-4 and 5-7, depending on a patient's length of stay. Early and late clinical outcomes were also evaluated. All values were compared between those treated with or without a macrolide. RESULTS: A total of 40 subjects were in this study; 14 received macrolide treatment, and 26 did not. Neutrophil function in the macrolide group was not significantly different compared to the non-macrolide group. None of the median cytokine levels or IQRs were statistically significant between the groups. However, a trend toward decreased IL-6, IL-8, and IFN-γ levels, and favorable clinical outcomes were present in the macrolide group. CONCLUSIONS: This pilot study showed no statistical difference between cytokine levels or neutrophil activity for CAP patients prescribed a macrolide containing regimen. Considering the trend of lower cytokine levels in the macrolide group when comparing the 5- to 7-day time period with the non-macrolide group, a full study with an appropriate sample size may be warranted.

Visual grids for managing data completeness in clinical research datasets.

Missing data arise in clinical research datasets for reasons ranging from incomplete electronic health records to incorrect trial data collection. This has an adverse effect on analysis performed with the data, but it can also affect the management of a clinical trial itself. We propose two graphical visualization schemes to aid in managing the completeness of a clinical research dataset: the binary completeness grid (BCG) for single patient observation, and the gradient completeness grid (GCG) for an entire dataset. We use these tools to manage three clinical trials. Two are ongoing observational trials, while the other is a cohort study that is complete. The completeness grids revealed unexpected patterns in our data and enabled us to identify records that should have been purged and identify missing follow-up data from sets of observations thought to be complete. Binary and gradient completeness grids provide a rapid, convenient way to visualize missing data in clinical datasets.

Prevalence of Clostridium difficile infection presenting to US EDs.

OBJECTIVE: The objective of the study is to determine the prevalence of Clostridium difficile infection (CDI) presenting to emergency departments (EDs) in the United States. Secondary objectives included defining the burden of CDI. METHODS: This is a retrospective, observational cohort study of 2006-2010 Nationwide Emergency Department Sample database of 980 US hospital EDs in 29 states. Prevalence, mortality rate, length of stay, hospital charges, and endemicity were measured. RESULTS: A total of 474513 patients with CDI-related ED visits were identified. From 2006 to 2010, the prevalence of CDI increased from 26.2 to 33.1 per 100,000 population (P<.001). The number of CDI-related ED cases increased 26.1% (P<.001) over the study period: 18.6% from 2006 to 2007 (P<.001), 4.3% from 2007 to 2008 (P=.46), 1.8% from 2008 to 2009 (P=.73), and 0.13% from 2009 to 2010 (P=.95). Emergency department visits occurred more frequently with individuals 85 years or older (relative risk [RR], 13.74; P<.001), females (RR, 1.77; P<.001) and in the northeast United States (RR, 1.42; P<.001). From 2009 to 2010, the mortality rate decreased 17.9% (P=.01). CONCLUSIONS: The prevalence of CDI presenting to EDs increased each year from 2006 to 2010; however, the rate of increase slowed from each year to the next. The mortality rate increased from 2006 to 2009 and decreased significantly from 2009 to 2010. C difficile infection visits presenting to EDs occurred more frequently with older individuals, females, and in the northeast.

Higher clinical success in patients with ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus treated with linezolid compared with vancomycin: results from the IMPACT-HAP study.

INTRODUCTION: Controversy exists regarding optimal treatment for ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA). The primary objective of this study was to compare clinical success of linezolid versus vancomycin for the treatment of patients with MRSA VAP. METHODS: This was a multicenter, retrospective, observational study of patients with VAP (defined according to Centers for Disease Control and Prevention criteria) due to MRSA who were treated with linezolid or vancomycin. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. Clinical success was evaluated by assessing improvement or resolution of signs and symptoms of VAP by day 14. After matching on confounding factors, logistic regression models were used to determine if an association existed between treatment arm and clinical success. RESULTS: A total of 188 patients were evaluated (101 treated with linezolid and 87 with vancomycin). The mean ± standard deviation Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21 ± 11 for linezolid- and 19 ± 9 for vancomycin-treated patients (P = 0.041). Clinical success occurred in 85% of linezolid-treated patients compared with 69% of vancomycin-treated patients (P = 0.009). After adjusting for confounding factors, linezolid-treated patients were 24% more likely to experience clinical success than vancomycin-treated patients (P = 0.018). CONCLUSIONS: This study adds to the evidence indicating that patients with MRSA VAP who are treated with linezolid are more likely to respond favorably compared with patients treated with vancomycin.

Assisting the infection preventionist: Use of artificial intelligence for health care-associated infection surveillance.

BACKGROUND: Health care-associated infection (HAI) surveillance is vital for safety in health care settings. It helps identify infection risk factors, enhancing patient safety and quality improvement. However, HAI surveillance is complex, demanding specialized knowledge and resources. This study investigates the use of artificial intelligence (AI), particularly generative large language models, to improve HAI surveillance. METHODS: We assessed 2 AI agents, OpenAI's chatGPT plus (GPT-4) and a Mixtral 8×7b-based local model, for their ability to identify Central Line-Associated Bloodstream Infection (CLABSI) and Catheter-Associated Urinary Tract Infection (CAUTI) from 6 National Health Care Safety Network training scenarios. The complexity of these scenarios was analyzed, and responses were matched against expert opinions. RESULTS: Both AI models accurately identified CLABSI and CAUTI in all scenarios when given clear prompts. Challenges appeared with ambiguous prompts including Arabic numeral dates, abbreviations, and special characters, causing occasional inaccuracies in repeated tests. DISCUSSION: The study demonstrates AI's potential in accurately identifying HAIs like CLABSI and CAUTI. Clear, specific prompts are crucial for reliable AI responses, highlighting the need for human oversight in AI-assisted HAI surveillance. CONCLUSIONS: AI shows promise in enhancing HAI surveillance, potentially streamlining tasks, and freeing health care staff for patient-focused activities. Effective AI use requires user education and ongoing AI model refinement.

Using a data-driven approach to define post-COVID conditions in US electronic health record data.

OBJECTIVE: To create a data-driven definition of post-COVID conditions (PCC) by directly measure changes in symptomatology before and after a first COVID episode. MATERIALS AND METHODS: Retrospective cohort study using Optum® de-identified Electronic Health Record (EHR) dataset from the United States of persons of any age April 2020-September 2021. For each person with COVID (ICD-10-CM U07.1 "COVID-19" or positive test result), we selected up to 3 comparators. The final COVID symptom score was computed as the sum of new diagnoses weighted by each diagnosis' ratio of incidence in COVID group relative to comparator group. For the subset of COVID cases diagnosed in September 2021, we compared the incidence of PCC using our data-driven definition with ICD-10-CM code U09.9 "Post-COVID Conditions", first available in the US October 2021. RESULTS: The final cohort contained 588,611 people with COVID, with mean age of 48 years and 38% male. Our definition identified 20% of persons developed PCC in follow-up. PCC incidence increased with age: (7.8% of persons aged 0-17, 17.3% aged 18-64, and 33.3% aged 65+) and did not change over time (20.0% among persons diagnosed with COVID in 2020 versus 20.3% in 2021). For cases diagnosed in September 2021, our definition identified 19.0% with PCC in follow-up as compared to 2.9% with U09.9 code in follow-up. CONCLUSION: Symptom and U09.9 code-based definitions alone captured different populations. Maximal capture may consider a combined approach, particularly before the availability and routine utilization of specific ICD-10 codes and with the lack consensus-based definitions on the syndrome.

Nirmatrelvir/Ritonavir Utilization for the Treatment of Non-hospitalized Adults with COVID-19 in the National Veterans Affairs (VA) Healthcare System.

INTRODUCTION: Limited data exist regarding real-world utilization of nirmatrelvir/ritonavir. We identified predictors of nirmatrelvir/ritonavir use among Veterans Affairs (VA) outpatients nationally. METHODS: We conducted a retrospective cohort study among outpatients with coronavirus disease 2019 (COVID-19) who were eligible to receive nirmatrelvir/ritonavir between January and December of 2022, to identify factors associated with nirmatrelvir/ritonavir use (i.e., demographics, medical history, prior medication and healthcare exposures, frailty, and other clinical characteristics) using multivariable logistic regression. RESULTS: We included 309,755 outpatients with COVID-19 who were eligible for nirmatrelvir/ritonavir, of whom 12.2% received nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir uptake increased from 1.1% to 23.2% over the study period. Factors associated with nirmatrelvir/ritonavir receipt included receiving a COVID-19 booster vs. none (adjusted odds ratio [aOR] 2.19 [95% confidence interval [CI] 2.12-2.26]), age ≥ 50 vs. 18-49 years (aORs > 1.5 for all age groups ≥ 50 years), having HIV (aOR 1.36 [1.22-1.51]), being non-frail vs. severely frail (aOR 1.22 [1.13-1.33]), and having rheumatoid arthritis (aOR 1.12 [1.04-1.21). Those with concomitant use of potentially interacting antiarrhythmics (aOR 0.35 [0.28-0.45]), anticoagulants/antiplatelets (aOR 0.42 [0.40-0.45]), and/or psychiatric/sedatives (aOR 0.84 [0.81-0.87]) were less likely to receive nirmatrelvir/ritonavir. CONCLUSIONS: Despite increases over time, overall utilization of nirmatrelvir/ritonavir was low. Predictors of nirmatrelvir/ritonavir utilization were consistent with known risk factors for progression to severe COVID-19, including older age and underlying medical conditions. Unvaccinated and undervaccinated patients and those receiving potentially interacting medications for cardiovascular or mental health conditions (antiarrhythmic, alpha-1 antagonist, anticoagulant/antiplatelet, sedative/hypnotic/psychiatric) were less likely to receive nirmatrelvir/ritonavir. Further education of prescribers and patients about nirmatrelvir/ritonavir treatment guidelines is needed to improve overall uptake and utilization in certain high-risk subpopulations.