Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Efficacy of Oral Mucoadhesive N-Acetylcysteine Tablets in Treatment of Recurrent Aphthous Stomatitis: A Randomized Double-Blind, Placebo-Controlled Clinical Trial.

Objectives: This study aimed to assess the efficacy of oral mucoadhesive N-acetylcysteine (NAC) tablets for treatment of recurrent aphthous stomatitis (RAS). Materials and Methods: Forty-nine patients with RAS were randomized to receive mucoadhesive NAC tablets (n=25) or placebo (n=24). Tablets were prescribed three times a day for 7 days in each group. Pain intensity was evaluated with visual analog scale (VAS) three times a day from day 1 to day 7. Also, patients were clinically examined on days 0 (before entering the study), 3, 5, and 7 using a metal caliper to measure the diameter of the lesions. The data were statistically analyzed and P<0.05 was considered statistically significant. Results: Regarding the VAS score, all participants in the treatment group showed complete recovery on day 7 (P<0.01). Also, the diameter of the lesions was significantly smaller in the treatment group than the placebo group at the end of the study (P<0.001). Conclusion: The results of this clinical trial showed for the first time that mucoadhesive NAC tablets can significantly decrease pain and the diameter of RAS lesions without any systemic complications.

Prevalence of Thromboembolic Events, Including Venous Thromboembolism and Arterial Thrombosis, in Patients with COVID-19: A Systematic Review with Meta-Analysis.

Background: Many studies have evaluated thromboembolic events in COVID-19 patients, and most of them have reported a high estimation of the prevalence of such events. The present study sought to evaluate the prevalence of thromboembolic events in patients with COVID-19. Methods: This study is a systematic review with meta-analysis that investigated thromboembolic events in patients with COVID-19 from the start of the pandemic to August 31, 2021. The 4 main databases for collecting articles were Medline, Scopus, Google Scholar, and Web of Science. Deep vein thrombosis, pulmonary embolism, arterial thrombosis, and the overall rate of thromboembolic events were considered primary outcomes. Results: In a total of 63 studies (104 920 patients with COVID-19), the overall thrombosis rate was 21% (95% CI, 18% to 25%), the rate of deep vein thrombosis was 20% (95% Cl, 16% to 25%), the rate of pulmonary embolism was 8% (95% Cl, 6% to 10%), and the rate of arterial thrombosis was 5% (95% Cl, 3% to 7%). The prevalence of all primary outcomes in critically ill patients admitted to the intensive care unit (ICU) was significantly higher (P<0.05). In older patients, the prevalence of overall thrombosis, pulmonary embolism, or deep vein thrombosis was significantly higher (P<0.05). Conclusion: This study showed that COVID-19 increases the risk of thromboembolic events, especially in elderly and critically ill patients admitted to the ICU. Therefore, more strategies are needed to prevent thromboembolic events in patients with COVID-19, especially in ICU-admitted and elderly patients.

Heavy head lice infestation in an adolescent girl following benzodiazepine poisoning.

Loss of consciousness (LOC) is one of the most common causes of emergency department (ED) visits. It may be due to intoxication or hypoglycemia. We present a 15-year-old girl who was referred with heavy head lice and LOC to the ED in the north of Iran.

Mycophenolate mofetil-induced peripheral neuropathy in the treatment of membranous glomerulonephropathy: A case report.

Mycophenolate mofetil (MMF) as an immunosuppressive agent is widely used in the management of Membranous Glomerulonephropathy (MGN). In this report, we described a 66-year-old male MGN case treated with MMF and revealed acquired sensory-motor axonal polyneuropathy, which is rare and has not been reported before.

A narrative review on adverse effects of dasatinib with a focus on pharmacotherapy of dasatinib-induced pulmonary toxicities.

Chronic myeloid leukemia (CML), a myeloproliferative disorder caused by the over activity of BCR-ABL1 (breakpoint cluster region-Abelson), has been successfully treated by Tyrosine kinase inhibitors (TKIs). While imatinib is known as the first-line treatment of CML, in some cases other TKIs including dasatinib, nilotinib, bosutinib, and ponatinib may be preferred. Dasatinib, a second-generation TKI, inhibits multiple family kinases including BCR-ABL, SRC family kinases, receptor kinases, and TEC family kinases. It is effective against most imatinib-resistant cases except T315I mutation. Despite the superiority of dasatinib in its hematologic and cytogenetic responses in CML compared to imatinib, its potentially harmful pulmonary complications including pleural effusion (PE) and pulmonary arterial hypertension (PAH) may limit its use. Appropriate management of these serious adverse reactions is critical in both improving the quality of life and the outcome of the patient. In this narrative review, we will scrutinize the pulmonary complications of dasatinib and focus on the management of these toxicities.

Fulminant hepatorenal syndrome due to Acetaminophen toxicity: A case report.

HRS is a rare and poor prognosis complication of chronic acetaminophen toxicity, which presents by progressive decline in renal function secondary to liver failure.

Suicide attempt using zinc phosphide rodenticide: A case report and literature review.

The patients with a history of intentional or unintentional consumption of rodenticide compounds, especially ZnP, it is necessary to assess ABG and abdominal radiography.

Comparison of the Efficacy and Safety of Atazanavir/Ritonavir Plus Hydroxychloroquine with Lopinavir/Ritonavir Plus Hydroxychloroquine in Patients with Moderate COVID-19, A Randomized, Double-blind Clinical Trial.

This was a randomized, double-blind clinical trial to compare the efficacy and safety of Atazanavir/Ritonavir (ATZ/RTV) with Lopinavir/Ritonavir (LPV/RTV) in moderate Coronavirus disease 2019 (COVID-19). Participants were randomly assigned to receive a single dose of hydroxychloroquine (HCQ) plus ATZ/RTV or LPV/RTV for a minimum of 5 to a maximum of 10 days. The primary outcomes were the reduced length of hospital stay and clinical recovery within 10 days from starting the intervention. The rate of intensive care unit (ICU) admission, intubation, and mortality, the lengths of ICU stay and being intubated, recovery within 14 days, and the frequency of adverse reactions were considered as secondary outcomes. Among 132 enrolled patients, 62 cases in each arm were analyzed at the end of the intervention. Fifty-one (82.3%) cases in the ATZ/RTV arm versus 41 (66.1%) in the LPV/RTV arm were discharged within 10 days (P = 0.06). The median number of the intervention days was 6 (IQR: 5-8) in ATZ/RTV arm versus 7 (IQR: 6-9) in LPV/RTV arm (P = 0.01). The rate and length of ICU admission and intubation (P ≥ 0.99), rate of mortality (P = 0.49), and recovery within 14 days (P = 0.09) were not statistically different between groups. The most reported adverse reactions were nausea and vomiting that all cases were in the LPV/RTV arm (P = 0.006). ATZ/RTV is better tolerated in comparison with LPV/RTV; however, it did not show more efficacy than LPV/RTV in clinical outcomes of COVID-19 in this study.