Objectives Sofosbuvir and daclatasvir are direct-acting antivirals highly effective against hepatitis C virus. There is some in silico and in vitro evidence that suggests these agents may also be effective against SARS-CoV-2. This trial evaluated the effectiveness of sofosbuvir in combination with daclatasvir in treating patients with COVID-19. Methods Patients with a positive nasopharyngeal swab for SARS-CoV-2 on RT–PCR or bilateral multi-lobar ground-glass opacity on their chest CT and signs of severe COVID-19 were included. Subjects were divided into two arms with one arm receiving ribavirin and the other receiving sofosbuvir/daclatasvir. All participants also received the recommended national standard treatment which, at that time, was lopinavir/ritonavir and single-dose hydroxychloroquine. The primary endpoint was time from starting the medication until discharge from hospital with secondary endpoints of duration of ICU stay and mortality. Results Sixty-two subjects met the inclusion criteria, with 35 enrolled in the sofosbuvir/daclatasvir arm and 27 in the ribavirin arm. The median duration of stay was 5 days for the sofosbuvir/daclatasvir group and 9 days for the ribavirin group. The mortality in the sofosbuvir/daclatasvir group was 2/35 (6%) and 9/27 (33%) for the ribavirin group. The relative risk of death for patients treated with sofosbuvir/daclatasvir was 0.17 (95% CI 0.04–0.73, P = 0.02) and the number needed to treat for benefit was 3.6 (95% CI 2.1–12.1, P < 0.01). Conclusions Given these encouraging initial results, and the current lack of treatments proven to decrease mortality in COVID-19, further investigation in larger-scale trials seems warranted.
This study was carried out to determine the effects of magnesium and vitamin E co-supplementation on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). The current randomized, double-blind, placebo-controlled trial was conducted among 57 patients with grade 3 DFU. Participants were randomly divided into two groups to take either 250 mg magnesium oxide plus 400 IU vitamin E (n = 29) or placebo per day (n = 28) for 12 weeks. Compared with the placebo, taking magnesium plus vitamin E supplements reduced ulcer length (β [difference in the mean of outcomes measures between treatment groups] −0.56 cm; 95% CI, −0.92, −0.20; p = 0.003), width (β −0.35 cm; 95% CI, −0.64, −0.05; p = 0.02) and depth (β −0.18 cm; 95% CI, −0.33, −0.02; p = 0.02). In addition, co-supplementation led to a significant reduction in fasting plasma glucose (β −13.41 mg/dL; 95% CI, −20.96, −5.86; p = 0.001), insulin (β −1.45 μIU/ml; 95% CI, −2.37, −0.52; p = 0.003), insulin resistance (β −0.60; 95% CI, −0.99, −0.20; p = 0.003) and HbA1c (β −0.32%; 95% CI, −0.48, −0.16; p < 0.003), and a significant elevation in insulin sensitivity (β 0.007; 95% CI, 0.003, 0.01; p < 0.001) compared with the placebo. Additionally, compared with the placebo, taking magnesium plus vitamin E supplements decreased triglycerides (β −10.08 mg/dL; 95% CI, −19.70, −0.46; p = 0.04), LDL-cholesterol (β −5.88 mg/dL; 95% CI, −11.42, −0.34; p = 0.03), high sensitivity C-reactive protein (hs-CRP) (β −3.42 mg/L; 95% CI, −4.44, −2.41; p < 0.001) and malondialdehyde (MDA) (β −0.30 μmol/L; 95% CI, −0.45, −0.15; p < 0.001), and increased HDL-cholesterol (β 2.62 mg/dL; 95% CI, 0.60, 4.63; p = 0.01) and total antioxidant capacity (TAC) levels (β 53.61 mmol/L; 95% CI, 4.65, 102.57; p = 0.03). Overall, magnesium and vitamin E co-supplementation for 12 weeks to patients with DFU had beneficial effects on ulcer size, glycemic control, triglycerides, LDL-and HDL-cholesterol, hs-CRP, TAC, and MDA levels.The diabetic foot ulcer (DFU) is a chronic consequence of diabetes mellitus which mainly caused by neuropathy, different grades of ischemia, and infection that coincide with poor glycemic control and diminished neutrophil function. 1 The mortality rate among diabetic patients with DFU is higher than twofold compared with nonulcer patients. 2 Based on the previous evidence, the effective management of diabetes and timely treatment of foot ulcer are implicated for decrease the morbidity and mortality of DFU. 3 The nutritional status of diabetic patients correlates with the severity of ulcer and play an important role in the reversing of wound risk. 4 According to the prior studies, the alternation of magnesium metabolism is a common feature in diabetic patients which interference with glycemic control and contributes to impaired insulin sensitivity and chronic inflammatory status. 5In addition, observational evidence shown that there is an inverse association between magnesium levels and the occurrence of foot ulcers, nephropathy and retinopathy. 6 Similarly, it is repo...
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