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Nirmatrelvir/ritonavir (Paxlovid) is a combination protease inhibitor that blocks replication of SARS-CoV-2 (the virus that causes COVID-19) and has been shown to reduce the risk for hospitalization and death among patients with mild to moderate COVID-19 who are at risk for progression to severe disease* (1). In December 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for early treatment with Paxlovid among persons with mild to moderate cases of COVID-19 who are at high risk for progression to severe disease (2). FDA and a small number of published case reports have documented recurrence of COVID-19 symptoms or a positive viral test result (COVID-19 rebound) 2-8 days after recovery or a negative SARS-CoV-2 test result among patients treated with Paxlovid (3-7); however, large-scale studies investigating severe illness after Paxlovid treatment are limited. This study used electronic health record (EHR) data from a large integrated health care system in California (Kaiser Permanente Southern California [KPSC]) to describe hospital admissions and emergency department (ED) encounters related to SARS-CoV-2 infections during the 5-15 days after pharmacy dispensation of a 5-day treatment course of Paxlovid. Among 5,287 persons aged ≥12 years who received Paxlovid during December 31, 2021-May 26, 2022, 73% had received ≥3 doses of COVID-19 vaccine†, and 8% were unvaccinated. During the 5-15 days after Paxlovid treatment was dispensed, six hospitalizations and 39 ED encounters considered to be related to SARS-CoV-2 infection were identified, representing <1% of all patients to whom Paxlovid treatment was dispensed during the study period. Among these 45 persons, 21 (47%) were aged ≥65 years, and 35 (78%) had at least one underlying medical condition§ (8). This study found that hospitalization or ED encounters for COVID-19 during the 5-15 days after Paxlovid treatment was dispensed for mild to moderate COVID-19 illness were rarely identified. When administered as an early-stage treatment, Paxlovid might prevent COVID-19-related hospitalization among persons with mild to moderate cases of COVID-19 who are at risk for progression to severe disease. [ABSTRACT FROM AUTHOR]

Background: The underlying mechanisms leading to dementia and Alzheimer's disease (AD) are unclear. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, may be associated with cognitive decline, but population-based evidence is lacking.Methods: Change in cognitive performance was assessed in participants of the Aberdeen Birth Cohort of 1936 using longitudinal Raven's progressive matrices (RPM) between 2000 and 2004. Multiple linear regression was used to estimate the association between ADMA concentrations in 2000 and change in cognitive performance after adjustment for potential confounders.Results: A total of 93 participants had complete information on cognitive performance between 2000 and 2004. Mean plasma ADMA concentrations were approximately 0.4 μmol/L lower in those participants with stable or improved RPM scores over follow-up compared with participants whose cognitive performance worsened. In confounder-adjusted analysis, one SD (0.06 μmol/L) increase in ADMA at 63 years of age was associated with an average reduction in RPM of 1.26 points (95% CI 0.14-2.26) after 4 years.Conclusion: Raised plasma ADMA concentrations predicted worsening cognitive performance after approximately 4 years in this cohort of adults in late-middle age. These findings have implications for future research, including presymptomatic diagnosis or novel therapeutic targets for dementia and AD. [ABSTRACT FROM AUTHOR]