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.