Introduction Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown. Methods Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission. Results Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06–1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04–1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50–0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16–0.66) and former smokers (aOR, 0.47; 95% CI, 0.39–0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66–0.83) than never smokers (aOR, 0.87; 95% CI, 0.79–0.97). Conclusions Former but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers. Implications Prior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

Main objective There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic. Study design and methods University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission. Results and significance The 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months. Conclusions Mortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes. Trial registration ClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528).

Background: In dogs, antiepileptic drugs (AED) cause lethargy but quantitative data regarding the effects of AED on activity levels are not available, and little is known about how AEDs affect sleep quality.Objective: To quantitatively compare activity levels and nocturnal activity in dogs previously diagnosed with idiopathic epilepsy (IE) receiving AEDs compared to ageand breed-matched control dogs.Animals: Sixty-two dogs with IE and 310 control dogs.Methods: This is a 3-month prospective parallel observational study. An activity monitoring device for dogs was used to measure daily activity levels and sleep scores in all dogs.Results: Dogs with IE treated with AEDs had an 18% average lower baseline activity level compared to control dogs (P = .005; point estimate = 0.82, 95% confidence interval [CI], 0.75-0.90). The combination of phenobarbital and potassium bromide (KBr) was associated with an average 28% decrease in activity in dogs with IE compared to control dogs (P = .03; point estimate = 0.72; CI, 0.62-0.82). Mean sleep scores were not significantly different in dogs with IE receiving AEDs compared to control dogs (P = .43). However, higher dosages of KBr were associated with lower sleep scores (P = .01). Conclusions: Dogs with IE receiving AEDs have lower activity levels, but no difference in sleep scores, compared to controls. The combination of phenobarbital and KBr had the largest decrease in activity between groups. Higher doses of KBr may affect nocturnal activity in epileptic dogs. K E Y W O R D S antiepileptic drugs, canine activity monitoring device 1 | INTRODUCTION Idiopathic epilepsy (IE) is a common neurologic condition in dogs, and currently, antiepileptic drugs (AEDs) are the mainstay of treatment.

Background: There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics. Methods: Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined. Results: 6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aORs) for mortality were 1.58 (95% CI: 1.46, 1.70) and 1.04 (95% CI: 0.96, 1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and amongst those with current cancer (aOR = 0.69, 95% CI = 0.53 to 0.90). Conclusions: Current cancer, especially amongst younger patients, posed a substantially increased risk for death and ICU admission among COVID-19 patients; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types. Impact: This study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic.

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