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BackgroundACEi/ARB medications have been hypothesized to have potential benefit in COVID-19. Despite concern for increased ACE-2 expression in some animal models, preclinical and observational-retrospective and uncontrolled trials suggested possible benefit. Two RCTs of the ARB losartan from University of Minnesota showed no benefit yet safety signals for losartan in outpatient and hospitalized COVID-19 patients. COVID MED, started early in the pandemic, also assessed losartan in a RCT in hospitalized patients with COVID-19.MethodsCOVID MED was a double-blinded, placebo-controlled, multicenter, platform randomized clinical trial (RCT). Hospitalized COVID-19 patients were randomized to receive standard care and hydroxychloroquine, lopinavir/ritonavir, losartan, or placebo. Hydroxychloroquine and lopinavir/ritonavir arms were discontinued after RCTs showed no benefit. We report data from the losartan arm compared to combined (lopinavir-ritonavir and placebo) and prespecified placebo-only controls. The primary endpoint, the mean COVID-19 Ordinal Severity Score (COSS) slope of change, was compared with the Student’s t-test. Slow enrollment prompted early termination.ResultsOf 448 screened patients, 15 (3.5%) were randomized/enrolled, 9 to receive losartan and 6 to receive control (lopinavir/ritonavir [N=2], placebo [N=4]); 1 patient who withdrew prior to study drug was excluded yielding 14 patients for analysis (losartan [N=9] vs. control [N=5] [lopinavir/ritonavir [N=2], placebo [N=3]]). Most baseline parameters were balanced. Treatment with losartan was not associated with a difference in mean COSS slope of change in comparison with combined control (p=0.4) or placebo-only control (p=0.05) (trend favoring placebo). 60-day mortality and overall AE and SAE rates were numerically but not significantly higher with losartan.ConclusionsIn this small blinded RCT in hospitalized COVID-19 patients, losartan did not improve outcome vs. control comparisons and was associated with adverse safety signals.

This retrospective study used data obtained from medical records of 530 stranded free-ranging harbor (Phoca vitulina), grey (Halichoerus grypus), harp (Pagophilus groenlandicus), and hooded seals (Cystophora cristata) presented to the Marine Mammal Stranding Center in Brigantine, New Jersey from January 1998 through December 2016. The objective was to identify hematological and plasma biochemical parameters of seals at time of presentation that were associated with successful rehabilitation and with duration of hospitalization using univariate and multivariate logistic regressions. At presentation, animals that subsequently survived rehabilitation had greater alkaline phosphatase activity and absolute lymphocyte and total calcium concentrations and lower blood urea nitrogen, sodium, chloride, phosphorus, and total bilirubin concentrations and lower aspartate aminotransferase and alanine aminotransferase activities than animals that eventually died or were euthanized while under care. Results suggest that young, actively growing animals are more likely to survive rehabilitation and that bloodwork consistent with dehydration, systemic disease, and exhaustion are negative prognostic indicators. These results provide prognostic indicators that may aid clinical decision-making for seals presented for rehabilitation.

OBJECTIVES To determine if baseline characteristics, treatment efficacy, psychosocial outcomes or tolerability were associated with patient preference for sildenafil citrate (sildenafil) or tadalafil for treating erectile dysfunction (ED) in men naive to phosphodiesterase 5 inhibitor therapy. PATIENTS AND METHODS In an open-label, crossover study of sildenafil (25, 50 or 100 mg) and tadalafil (10 or 20 mg), dosed as needed, after a 4-week baseline assessment, 367 men with ED were randomly assigned to sildenafil followed by tadalafil or vice versa (8-week dose optimization and 4-week assessment phase for each treatment period). Patients completing both periods chose which treatment they preferred for an 8-week extension phase. Bivariate logistic regression and stepwise logistic regression were used to determine if any baseline characteristics or post-baseline measurements were associated with the patients’ treatment preference. Baseline variables examined were age, race, ED aetiology/duration, body mass index, smoking status, alcohol consumption, vital signs, comorbid medical conditions, and baseline scores for the International Index of Erectile Function (IIEF) domains, Psychological and Interpersonal Relationship Scales (PAIRS) domains, and Sexual Encounter Profile (SEP) diary questions. Post-baseline variables examined were therapy sequence, dosage, and differences in IIEF and PAIRS domains, SEP scores, in number/timing of sexual attempts and in the severity of side-effects (overall patient perception). RESULTS Of 291 patients completing both treatments and indicating a preference, 85 (29%) preferred sildenafil and 206 (71%) preferred tadalafil. Variables were individually analysed using bivariate analysis; one baseline characteristic (presence/absence of hyperlipidaemia) and 13 post-baseline measurements were significantly associated with the patients’ treatment preference. Variables were analysed as a group using stepwise logistic regression; a set of six post-baseline factors was identified as significantly associated with patient preference. Dosage choice, reductions in the PAIRS time concerns domain, IIEF intercourse satisfaction domain improvements, smaller side-effect severity scores, more sexual attempts, and increased SEP4 scores (satisfaction with erection hardness) during the tadalafil or sildenafil treatment periods were all significantly associated with preference for tadalafil or sildenafil. CONCLUSIONS We identified no baseline characteristics that prospectively distinguish patients who will prefer tadalafil or sildenafil. Patient differences in time concerns, dosage choice, intercourse satisfaction, treatment tolerability, number of sexual attempts and satisfaction with erection hardness were the set of factors most significantly associated with treatment preference, and the preference observed for tadalafil (71%) or sildenafil (29%) might be substantially accounted for by differences in these factors during the tadalafil and sildenafil treatment periods.