RESUMO
Background: An in silico screen was performed to identify FDA approved drugs that inhibit SARS-CoV-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods: A 2-center, randomized, double-blind, placebo-controlled trial was performed among patients hospitalized with COVID-19 infection. Enrolled patients were randomized 2:1 to atovaquone 1500 mg BID versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Saliva was collected at baseline and twice per day for up to 10 days for RNA extraction for SARS-CoV-2 viral load measurement by quantitative reverse-transcriptase PCR. The primary outcome was the between group difference in log-transformed viral load (copies/mL) using a generalized linear mixed-effect models of repeated measures from all samples. Results: Of the 61 patients enrolled; 41 received atovaquone and 19 received placebo. Overall, the population was predominately male (63%) and Hispanic (70%), with a mean age of 51 years, enrolled a mean of 5 days from symptom onset. The log10 viral load was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Change in viral load did not differ over time between the atovaquone plus standard of care arm versus the placebo plus standard of care arm. Pharmacokinetic (PK) studies of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, with an inverse correlation between BMI and atovaquone levels, (Rho -0.45, p = 0.02). In post hoc analysis, an inverse correlation was observed between atovaquone levels and viral load (Rho -0.54, p = 0.005). Conclusion: In this prospective, randomized, placebo-controlled trial, atovaquone did not demonstrate evidence of enhanced SARS-CoV-2 viral clearance compared with placebo. However, based on the observed inverse correlation between atovaquone levels and viral load, additional PK-guided studies may be warranted to examine the antiviral effect of atovaquone in COVID-19 patients.
RESUMO
PURPOSE: To report the outcomes on the Boston Type 1 Keratoprosthesis at our institution. DESIGN: Retrospective analysis case series. PARTICIPANTS: We analyzed 54 eyes of 53 patients who previously underwent Boston Type 1 Keratoprosthesis surgery at our institution from July 2006 to March 2011. METHODS: Preoperative and postoperative parameters were collected and analyzed. MAIN OUTCOME MEASURES: Visual acuity and keratoprosthesis stability. RESULTS: Common preoperative diagnoses were penetrating keratoplasty failure in 49 eyes (90.7%), chronic keratitis in 2 eyes (3.7%), ocular cicatricial pemphigoid in 1 eye (1.85%), Stevens Johnson syndrome in 1 eye (1.85%) and corneal vascularization in 1 eye (1.85%). Additionally, 40 eyes (74%) had preoperative glaucoma, and an Ahmed valve was implanted in 55% of them. Preoperative BCVA ranged from 20/200 to light perception. At an average follow-up of 20.15 months ± 12.7 (range, 1-56), postoperative vision improved to ⩾20/200 in 18 eyes (33.3%) and ⩾20/50 in 4 eyes (7.4%). The graft retention was 96%. CONCLUSIONS: The Boston Type 1 keratoprosthesis is a valid option for high-risk patients. The design improvements in the Boston keratoprosthesis, as well as the daily implementation of the therapeutic methods, have notably diminished occurrence of the most serious complications, such as corneal necrosis and endophthalmitis. As such, glaucoma and its subsequent complications now stand as the most prevalent prognostic factor in the long term.
RESUMO
El concepto de salud ha evolucionado de manera significativa, pasando de una interpretación basada en lobiológico que ubica en un extremo la enfermedad y en el otro la salud como no enfermedad; a una donde seentiende como un fenómeno estrechamente ligado a las condiciones generales de vida de la población (1)donde intervienen diversos factores o determinantes relacionados con el bienestar: acceso a servicios, vivienda, entre otros. En este orden de ideas teniendo en cuenta los factores que intervienen en el bienestar o salud, el desequilibrio puede contribuir a la aparición de algunas enfermedades parasitarias.