Effect of Famotidine on COVID-19: Killing Virus or Opposing ARDS?

Since the first detection of SARS-CoV-2 in China, COVID-19 (Corona Virus Disease 2019) has taken the lives of more than six million people. Although some antivirals seem proper for treatment, the investigation of finding the best therapeutic approach for COVID-19 is still continuing. Some observational research showed that famotidine has promising effects in addition to its acid-suppressing characteristics in the treatment of COVID-19. The definite viricidal effect of famotidine is not established. Opposing acute respiratory distress syndrome (ARDS) can be proposed as a probable mechanism for the action of famotidine, due to its inhibitory effect on histamine release, inhibition of transmembrane protease serine S (TMPRSS) and stabilizing glycocalyx. These hypotheses should be under investigation in the future.

Remdesivir Administration in COVID-19 Patients With Renal Impairment: A Systematic Review.

BACKGROUND: Remdesivir (RDV) is the main antiviral for the treatment of moderate to severe forms of Coronavirus disease 2019 (COVID-19). Several studies revealed a shortening time to clinical improvement of COVID-19 and mortality benefits in patients receiving RDV. The patients with renal disease were excluded from large clinical trials of RDV, and the probable nephrotoxicity of the drug, its metabolites, and the vehicle (sulfobutylether-ß-cyclodextrin) have led to the recommendation against using RDV in patients with an estimated glomerular filtration rate of <30 mL/min. AREAS OF UNCERTAINTY: This systematic review aimed to collect data about the necessity and safety administration of RDV in the setting of renal impairment. DATA SOURCES: Search through databases including MEDLINE, ScienceDirect, Cochrane Library, and PubMed was performed. The studies were carried out in adults and enrolled patients with different types of renal impairment (ie, acute kidney injury, chronic kidney disease, kidney transplant, and renal replacement therapy) were included. Eligible studies were assessed, and required data were extracted. RESULTS: Twenty-two cross-sectional studies, cohorts, case reports, and case series were included in this review. The mortality rate was between 7.3% and 50%, and various severity of COVID-19 was included in the studies. None of them reported an increase in adverse effects attributed to RDV administration. A decrease in inflammatory mediators and other benefits were obvious. CONCLUSIONS: Although the manufacturer's labeling does not recommend RDV administration in patients with severe renal impairment, it seems that nephrotoxicity is less concerning in the population of these patients. Moreover, RDV may be helpful in acute kidney injury induced by the viral invasion of COVID-19. To the best of our knowledge, this is the first systematic review of the use of RDV in kidney failure. Larger, well-designed, and pharmacokinetic studies are required to have a safe and logical recommendation about the use of RDV in patients with renal disorders.

Management of a critically ill patient with COVID-19-related fulminant myocarditis: A case report.

A 78-year-old man with COVID-19 infection was admitted. Initial echocardiography indicated left ventricular ejection fraction (LVEF) of 15%, high pulmonary arterial pressure, severe left ventricular dysfunction, mild diastolic dysfunction, mild regurgitation mitral valve, and normal septal thickness. Considering the probable diagnosis of COVID-19-related myocarditis, the patient was early managed with the antivirals, immunomodulatory agents, a high dose of ascorbic acid, melatonin, and immunoglobulin therapy. His clinical condition was improved and his last echocardiography revealed LVEF of 40% and improvement in systolic and diastolic dysfunction. The clinicians should be aware of the potentially lethal cardiac complication of COVID-19, especially in geriatrics.

Comparing efficacy and safety of different doses of dexamethasone in the treatment of COVID-19: a three-arm randomized clinical trial.

BACKGROUND AND OBJECTIVES: Corticosteroids are commonly used in the treatment of hospitalized patients with COVID-19. The goals of the present study were to compare the efficacy and safety of different doses of dexamethasone in the treatment of patients with a diagnosis of moderate to severe COVID-19. METHODS: Hospitalized patients with a diagnosis of moderate to severe COVID-19 were assigned to intravenous low-dose (8 mg once daily), intermediate-dose (8 mg twice daily) or high-dose (8 mg thrice daily) dexamethasone for up to 10 days or until hospital discharge. Clinical response, 60-day survival and adverse effects were the main outcomes of the study. RESULTS: In the competing risk survival analysis, patients in the low-dose group had a higher clinical response than the high-dose group when considering death as a competing risk (HR = 2.03, 95% CI: 1.23-3.33, p = 0.03). Also, the survival was significantly longer in the low-dose group than the high-dose group (HR = 0.36, 95% CI = 0.15-0.83, p = 0.02). Leukocytosis and hyperglycemia were the most common side effects of dexamethasone. Although the incidence was not significantly different between the groups, some adverse effects were numerically higher in the intermediate-dose and high-dose groups than in the low-dose group. CONCLUSIONS: Higher doses of dexamethasone not only failed to improve efficacy but also resulted in an increase in the number of adverse events and worsen survival in hospitalized patients with moderate to severe COVID-19 compared to the low-dose dexamethasone. (IRCT20100228003449N31).

The effect of midodrine on lactate clearance in patients with septic shock: a pilot study.

Background: The effect of midodrine on lactate clearance has not been assessed in critically ill patients yet. Objective: The goal of this study was to assess the effect of adjunctive midodrine therapy on lactate clearance in patients with septic shock. Materials & methods: Patients with septic shock were assigned to receive either adjunctive midodrine 10 mg three-times a day for 5 days (midodrine group = 15 patients) or not (control group = 13 patients). Results: The lactate clearance was significantly faster in the midodrine group than the control group (p = 0.049) with a large effect size (ηp2 = 0.141). Conclusion: When midodrine was added to intravenous vasopressors, it significantly accelerated lactate clearance in patients with septic shock. Trial registration number: IRCT20100228003449N25 (Clinicaltrials.gov).

Comparing outcomes of hospitalized patients with moderate and severe COVID-19 following treatment with hydroxychloroquine plus atazanavir/ritonavir.

BACKGROUND: The role of the antiviral therapy in treatment of COVID-19 is still a matter to be investigated. Also efficacy and safety of antiviral regimens were not compared according severity of the disease. In this study the efficacy and safety of hydroxychloroquine plus atazanavir/ritonavir was compared in patients with moderate and severe COVID-19. METHODS: We prospectively evaluated the clinical outcomes of 213 patients with COVID-19 during the hospitalization course and up to 56 days after the hospital discharge. The disease was categorized to moderate and severe based on the severity of pneumonia and peripheral oxygen saturation (SpO2). The patients received the national treatment protocol containing hydroxychloroquine (400 mg BD in first day and then 200 mg BD) plus atazanavir/ritonavir (300/100 mg daily) for 7 days. Main outcomes included discharge rates at day 7, 14 and 28, 28-day mortality, rate of intensive care unit (ICU) admission and intubation, length of hospital and ICU stay and incidence of adverse events. RESULTS: The mean (SD) age of patients was 60(14) years and 53% were male. According to WHO definition, 51.64% and 48.36% of the patients had moderate (SpO2 ≥ 90%) and severe disease (SpO2 < 90%) at baseline, respectively. The discharge rate of the moderate group was significantly higher than the severe group at day 7, 14 and 28 (HR = 0.49; 95% CI: 0.35-0.69, p = < 0.001 at day 7, HR = 0.48; 95% CI: 0.35-0.66, p = < 0.001 at day 14 and HR = 0.49; 95% CI: 0.36-0.67, p = < 0.001at day 28). The 28-day mortality of the severe group was six times higher than the moderate group (HR = 6.00; 95% CI: 2.50-14.44), p = < 0.001). The need of admission in ICU for the severe group and the moderate group was 37.86% and 18.18% of the patients. Length of hospital stay was significantly shorter in the moderate group in comparison with the severe group (5 ± 4 vs. 8 ± 6 days, p < 0.001). Patients in the moderate group experienced the serious adverse events and complications less than the severe group. The discharged patients were followed up to 56 days after discharge. Some of the patients complained of symptoms such as exertional dyspnea, weakness and new-onset hair loss. CONCLUSION: Our study did not support the use of hydroxychloroquine plus atazanavir/ritonavir in patients who had SpO2 < 90% at the time of hospital admission. SpO2 was the only predictor of clinical outcomes (duration of hospital stay, discharge from the hospital and mortality) in patients treated with hydroxychloroquine plus atazanavir/ritonavir.

Interferon ß-1b in treatment of severe COVID-19: A randomized clinical trial.

In this study, efficacy and safety of interferon (IFN) ß-1b in the treatment of patients with severe COVID-19 were evaluated. Among an open-label, randomized clinical trial, adult patients (≥18 years old) with severe COVID-19 were randomly assigned (1:1) to the IFN group or the control group. Patients in the IFN group received IFN ß-1b (250 mcg subcutaneously every other day for two consecutive weeks) along with the national protocol medications while in the control group, patients received only the national protocol medications (lopinavir/ritonavir or atazanavir/ritonavir plus hydroxychloroquine for 7-10 days). The primary outcome of the study was time to clinical improvement. Secondary outcomes were in-hospital complications and 28-daymortality. Between April 20 and May 20, 2020, 80 patients were enrolled and finally 33 patients in each group completed the study. Time to clinical improvment in the IFN group was significantly shorter than the control group ([9(6-10) vs. 11(9-15) days respectively, p = 0.002, HR = 2.30; 95% CI: 1.33-3.39]). At day 14, the percentage of discharged patients was 78.79% and 54.55% in the IFN and control groups respectively (OR = 3.09; 95% CI: 1.05-9.11, p = 0.03). ICU admission rate in the control group was significantly higher than the IFN group (66.66% vs. 42.42%, p = 0.04). The duration of hospitalization and ICU stay were not significantly different between the groups All-cause 28-day mortality was 6.06% and 18.18% in the IFN and control groups respectively (p = 0.12). IFN ß-1b was effective in shortening the time to clinical improvement without serious adverse events in patients with severe COVID-19. Furthermore, admission in ICU and need for invasive mechanical ventilation decreased following administration of IFN ß-1b. Although 28-day mortality was lower in the IFN group, further randomized clinical trials with large sample size are needed for exact estimation of survival benefit of IFN ß-1b.

A Randomized Clinical Trial of the Efficacy and Safety of Interferon ß-1a in Treatment of Severe COVID-19.

To the best of our knowledge, there is no published study on the use of interferon ß-1a (IFN ß-1a) in the treatment of severe COVID-19. In this randomized clinical trial, the efficacy and safety of IFN ß-1a were evaluated in patients with severe COVID-19. Forty-two patients in the interferon group received IFN ß-1a in addition to the national protocol medications (hydroxychloroquine plus lopinavir-ritonavir or atazanavir-ritonavir). Each 44-µg/ml (12 million IU/ml) dose of interferon ß-1a was subcutaneously injected three times weekly for two consecutive weeks. The control group consisted of 39 patients who received only the national protocol medications. The primary outcome of the study was time to reach clinical response. Secondary outcomes were duration of hospital stay, length of intensive care unit stay, 28-day mortality, effect of early or late administration of IFN on mortality, adverse effects, and complications during the hospitalization. Between 29 February and 3 April 2020, 92 patients were recruited, and a total of 42 patients in the IFN group and 39 patients in the control group completed the study. As the primary outcome, time to the clinical response was not significantly different between the IFN and the control groups (9.7 ± 5.8 versus 8.3 ± 4.9 days, respectively, P = 0.95). On day 14, 66.7% versus 43.6% of patients in the IFN group and the control group, respectively, were discharged (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.05 to 6.37). The 28-day overall mortality was significantly lower in the IFN than the control group (19% versus 43.6%, respectively, P = 0.015). Early administration significantly reduced mortality (OR, 13.5; 95% CI, 1.5 to 118). Although IFN did not change the time to reach the clinical response, adding it to the national protocol significantly increased discharge rate on day 14 and decreased 28-day mortality. (This study is in the Iranian Registry of Clinical Trials under identifier IRCT20100228003449N28.).

A Case Series of Severe Hyperammonemia Encephalopathy Related to Valproate: Can Antipsychotics Increase the Risk?

Valproate-induced hyperammonemia is a common side effect of valproate, which may occur either without any symptoms or may rarely cause symptoms of encephalopathy. Different risk factors have been defined for this side effect, including some nutritional deficiencies and polypharmacy (eg, other anticonvulsants). Three cases with psychiatric disorder who showed symptoms of severe hyperammonemia encephalopathy and had taken valproate with antipsychotics, especially risperidone, are presented here. In all cases, the symptoms were improved by discontinuation of valproate. Administration of antipsychotic may be considered as a risk factor for hyperammonemic encephalopathy related to valproate, specifically in some prone populations.

The threat of carbapenem-resistant gram-negative bacteria in a Middle East region.

Data on the status of carbapenem-resistant microorganisms in the Middle East countries are scarce. The aim of this review was to collect available data regarding resistance to carbapenems in a Middle East region. Available data regarding carbapenem-resistant isolates were considered for evaluation in this review. Biomedical electronic databases were systematically searched to find related articles. The key terms used were "carbapenem-resistant, resistant gram-negative bacilli, Enterobacteriaceae, fermenting and non-fermenting gram-negative bacilli, Pseudomonas, Acinetobacter, Klebsiella and Iran". After primary screening, 275 relevant articles were selected to be assessed thoroughly. Resistance rate to carbapenems was reported between 1% and 86% during years 2006-2018. Most of the carbapenem-resistant microorganisms were isolated from burn patients. Modified Hodge test was a commonly used phenotypic test. Only in few studies, genotypic assays were considered. Pattern of antibiotic use can affect emergence of resistant microorganisms. Rational use of drugs, and specifically, antibiotics is a challenging issue in developing countries. Mean number of drugs per prescription in these countries was higher than the World Health Organization standards. Overuse of antibiotics, especially injectable ones, and easy access to antibiotics without prescription is a warning alarm for future antibiotic resistance in developing countries. Establishing antimicrobial stewardship's programs is new in the hospitals. Unfortunately, rules and regulatory issues to restrict antibiotic access in community pharmacies and prescription by general physicians are limited.