IntroductionDecreased production of cathelicidin antimicrobial protein-18 (hCAP18) has been proposed to be a key mechanism linking decreased 25-hydroxyvitamin D (25D) levels with adverse outcomes among critically ill patients. However, few studies in humans have directly assessed plasma hCAP18 levels, and no study has evaluated the association between hCAP18 levels and adverse outcomes among critically ill patients.MethodsWe performed a single-center, prospective cohort study among 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012. We measured plasma hCAP18, 25D, D-binding protein, and parathyroid hormone levels on ICU day 1. The primary endpoint was 90-day mortality. Secondary endpoints included hospital mortality, sepsis, acute kidney injury, duration of mechanical ventilation, and hospital length of stay.ResultsICU day 1 hCAP18 levels were directly correlated with 25D levels (Spearman’s rho (rs) = 0.30, P = 0.001). In multivariate analyses adjusted for age and Acute Physiology and Chronic Health Evaluation II (APACHE II) score, patients with hCAP18 levels in the lowest compared to highest tertile on ICU day 1 had a 4.49 (1.08 to 18.67) greater odds of 90-day mortality, and also had greater odds of sepsis. ICU day 1 levels of other analytes were not associated with 90-day mortality.ConclusionsLower 25D levels on ICU day 1 are associated with lower hCAP18 levels, which are in turn associated with a greater risk of 90-day mortality. These findings provide a potential mechanistic basis for the frequently observed association between low 25D levels and poor outcomes in critically ill patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0812-1) contains supplementary material, which is available to authorized users.
ObjectiveTo describe the pattern of hydroxychloroquine use and examine the association between hydroxychloroquine use and clinical outcomes arising from changes in the US Food and Drug Administration (FDA)’s recommendation during the coronavirus disease 2019 (COVID-19) pandemic.DesignA retrospective cross-sectional analysis.Setting and participantsWe included hospitalised adult patients at Northwell Health hospitals with confirmed COVID-19 infections between 1 March 2020 and 11 May 2020. We categorised changes in the FDA’s recommendation as pre-FDA approval (1 March 2020–27 March 2020), FDA approval (28 March 2020–23 April 2020), and FDA warning (24 April 2020–11 May 2020). The hydroxychloroquine-treated group received at least one dose within 48 hours of hospital admission.Primary outcomeA composite of intubation and inpatient death.ResultsThe percentages of patients who were treated with hydroxychloroquine were 192/2202 (8.7%) pre-FDA approval, 2902/6741 (43.0%) FDA approval, and 176/1066 (16.5%) FDA warning period (p<0.001). Using propensity score matching, there was a higher rate of the composite outcome among patients treated with hydroxychloroquine (49/192, 25.5%) compared with no hydroxychloroquine (66/384, 17.2%) in the pre-FDA approval period (p=0.03) but not in the FDA approval period (25.5% vs 22.6%, p=0.08) or the FDA warning (21.0% vs 15.1%, p=0.11) periods. Coincidently, there was an increase in number of patients with COVID-19 and disease severity during the FDA approval period (24.1% during FDA approval vs 21.4% during pre-FDA approval period had the composite outcome). Hydroxychloroquine use was associated with increased odds of the composite outcome during the pre-FDA approval period (OR=1.65 (95% CI 1.09 to 2.51)) but not during the FDA approval (OR=1.17 (95% CI 0.99 to 1.39)) and FDA warning (OR=1.50 (95% CI 0.94 to 2.39)) periods.ConclusionsHydroxychloroquine use was associated with adverse clinical outcomes only during the pre-FDA approval period but not during the FDA approval and warning periods, even after adjusting for concurrent changes in the percentage of patients with COVID-19 treated with hydroxychloroquine and the number (and disease severity) of hospitalised patients with COVID-19 infections.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.