ABSTRACT
BackgroundCurrent strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are limited to non-pharmacological interventions. Hydroxychloroquine (HCQ) has been proposed as a postexposure therapy to prevent Coronavirus disease 2019 (Covid-19) but definitive evidence is lacking. MethodsWe conducted an open-label, cluster-randomized trial including asymptomatic contacts exposed to a PCR-positive Covid-19 case in Catalonia, Spain. Clusters were randomized to receive no specific therapy (control arm) or HCQ 800mg once, followed by 400mg daily for 6 days (intervention arm). The primary outcome was PCR-confirmed symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, either symptomatically compatible or a PCR-positive result regardless of symptoms. Adverse events (AEs) were assessed up to 28 days. ResultsThe analysis included 2,314 healthy contacts of 672 Covid-19 index cases identified between Mar 17 and Apr 28, 2020. A total of 1,198 were randomly allocated to usual care and 1,116 to HCQ therapy. There was no significant difference in the primary outcome of PCR-confirmed, symptomatic Covid-19 disease (6.2% usual care vs. 5.7% HCQ; risk ratio 0.89 [95% confidence interval 0.54-1.46]), nor evidence of beneficial effects on prevention of SARS-CoV-2 transmission (17.8% usual care vs. 18.7% HCQ). The incidence of AEs was higher in the intervention arm than in the control arm (5.9% usual care vs 51.6% HCQ), but no treatment-related serious AEs were reported. ConclusionsPostexposure therapy with HCQ did not prevent SARS-CoV-2 disease and infection in healthy individuals exposed to a PCR-positive case. Our findings do not support HCQ as postexposure prophylaxis for Covid-19. ClinicalTrials.gov registration numberNCT04304053
ABSTRACT
PURPOSE: The purpose of this study was to demonstrate the existence of a bimodal survival pattern in metastatic uveal melanoma. Secondary aims were to identify the characteristics and prognostic factors associated with long-term survival and to develop a clinical decision tree. MATERIALS AND METHODS: The medical records of 99 metastatic uveal melanoma patients were retrospectively reviewed. Patients were classified as either short (≤ 12 months) or long-term survivors (> 12 months) based on a graphical interpretation of the survival curve after diagnosis of the first metastatic lesion. Ophthalmic and oncological characteristicswere assessed in both groups. RESULTS: Of the 99 patients, 62 (62.6%) were classified as short-term survivors, and 37 (37.4%) as long-term survivors. The multivariate analysis identified the following predictors of long-term survival: age ≤ 65 years (p=0.012) and unaltered serum lactate dehydrogenase levels (p=0.018); additionally, the size (smaller vs. larger) of the largest liver metastasis showed a trend towards significance (p=0.063). Based on the variables significantly associated with long-term survival, we developed a decision tree to facilitate clinical decision-making. CONCLUSION: The findings of this study demonstrate the existence of a bimodal survival pattern in patients with metastatic uveal melanoma. The presence of certain clinical characteristics at diagnosis of distant disease is associated with long-term survival. A decision tree was developed to facilitate clinical decision-making and to counsel patients about the expected course of disease.