Among Patients with COVID-19, should Remdesivir be Used for Treatment? A Systematic Review and Meta-analysis.

Background: Remdesivir is an intravenously administered antiviral drug that inhibits RNA-dependent RNA polymerase. In vitro studies have shown that remdesivir can inhibit the growth of the COVID-19 virus in infected Vero cells and can inhibit infection in human cell lines. Objective: To determine the efficacy and safety of remdesivir in treating patients with COVID-19 infection. Methods: A systematic search of electronic medical literature databases was done from inception until September 4, 2022. Search for ongoing studies and preprints was also done. Risk of bias assessment was done using Cochrane risk of bias tool version 2.0. Measures of effect used were relative risk (RR) and 95% confidence interval (CI). Subgroup analysis by disease severity was preplanned. The estimates for efficacy and safety of remdesivir was calculated using Review Manager 5.4 software. Results: Nine randomized controlled trials with 13,085 participants were identified. Eight of the included studies recruited confirmed COVID-19 patients needing hospitalization, while one study limited recruitment to non-hospitalized patients. Remdesivir showed significant benefit for outpatients with mild to moderate disease with at least one risk factor for disease progression in terms of COVID 19-related hospitalization (RR 0.13 95% CI 0.03 to 0.59), all-cause hospitalization (RR 0.28, 95% CI 0.10 to 0.75), and need for medically-attended visits (RR 0.19, 95% CI 0.07 to 0.56). For hospitalized patients, remdesivir had a slight benefit in reducing all-cause mortality at day 28 (RR 0.90, 95% CI 0.83 to 0.98). Subgroup analysis by disease severity showed a trend towards reduction in mortality among those with severe disease (RR 0.61, 95% CI 0.35 to 1.07), with no effect on those with critical disease (RR 0.96, 95% CI 0.87 to 1.04), and inconclusive effect for those with mild-moderate disease (RR 0.74, 95% CI 0.49 to 1.11). Remdesivir showed benefit in decreasing clinical deterioration (RR 0.75, 95% CI 0.61 to 0.89), improving recovery rate (RR 1.07, 95% CI 1.01 to 1.13), and reducing the need for mechanical ventilation (RR 0.68, 95% CI 0.51 to 0.90). There was inconclusive effect on the need for ICU admission (RR 0.98, 95% CI 0.43 to 2.22). No increased risk of adverse events (RR 0.98, 95% CI 0.91 to 1.06), including serious adverse events (RR 0.77, 95% CI 0.57 to 1.03), was seen. Discussion: Based on the available evidence, remdesivir shows benefit in the treatment for patients with mild, moderate, and severe COVID-19 infection. However, there was no benefit in mortality noted among those with critical disease requiring mechanical ventilation. Remdesivir demonstrated a good safety profile, with no increased risk of adverse events compared to control. These results are consistent with the international agencies' recommendations for the use of remdesivir among patients with mild, moderate or severe COVID-19 infection, but not for those with critical infection. Conclusion: Current evidence supports the use of remdesivir as treatment for selected patients with COVID-19.

Comparative effectiveness of probiotic strains on the prevention of pediatric atopic dermatitis: A systematic review and network meta-analysis.

BACKGROUND: Atopic dermatitis is the most common chronic skin disease affecting the pediatric population. Probiotics have been proposed to be effective in preventing the development of pediatric atopic dermatitis. Although studies show promise for the use of probiotics, the evidence is still inconclusive due to significant heterogeneity and imprecision. OBJECTIVE: To determine the comparative effectiveness of the different types of probiotic strains in preventing the development of atopic dermatitis among pediatric patients. METHODOLOGY: A systematic search of Cochrane Library, MEDLINE, TRIP Database, and Centre for Research and Dissemination was conducted. Manual search of the reference lists and search for unpublished articles were also done. All randomized controlled trials available from inception until April 12, 2020, on the use of probiotics in the prevention of atopic dermatitis among children were included. The comparator groups considered are other probiotic strains and placebo. The primary outcome of interest was the development of atopic dermatitis. Two authors independently searched for articles, screened the articles for inclusion, appraised the articles using the Cochrane risk of bias tool version 2, and extracted the data. In case of disagreement, the two authors discussed the source of disagreement until consensus was reached. If consensus was not reached, an independent third party reviewer was consulted. Frequentist network meta-analysis was conducted using STATA 14 software. The ranking probabilities and surface under the cumulative ranking curve (SUCRA) values were obtained to determine ranking of the different probiotic strains based on efficacy and safety data. RESULTS: We included 21 original studies represented by 35 records and a total of 5406 children with atopic dermatitis as diagnosed by clinicians or fulfillment of validated diagnostic criteria. All studies were randomized placebo-controlled trials. The top 3 probiotic preparations in terms of efficacy in reducing the risk of atopic dermatitis are Mix8 (Lactobacillus paracasei ST11, Bifidobacterium longum BL999), LP (Lactobacillus paracasei ssp paracasei F19) and Mix3 (Lactobacillus rhamnosus GG, Bifidobacterium animalis ssp lactis Bb-12). Mix8 compared with placebo probably reduces the risk of atopic dermatitis based on low-quality evidence (RR = 0.46, 95% CI 0.25-0.85). Mix3 compared with placebo also probably reduces the risk of atopic dermatitis based on low-quality evidence (RR = 0.50, 95% CI 0.27-0.94). It is uncertain whether LP compared with placebo reduces the risk of atopic dermatitis due to very-low-quality certainty of evidence (RR = 0.49, 95% CI 0.20-1.19). In terms of adverse events, LGG may slightly lead to less adverse events compared with placebo based on low-quality evidence (RR = 0.70, 95% CI 0.32-1.52). Mix4 may slightly lead to more adverse events compared with placebo based on low-quality evidence (RR = 1.06, 95% CI 0.02-51.88). Based on subgroup analysis of studies involving infants, Mix3 compared with placebo probably reduces the risk of atopic dermatitis based on low-quality evidence (RR = 0.46, 95% CI 0.22-0.97). In the subgroup analysis of studies where probiotics were administered to pregnant women and to infants, LRH compared with placebo probably reduces the risk of atopic dermatitis based on moderate-quality evidence (RR = 0.54, 95% CI 0.26-1.11). CONCLUSION: Certain probiotic preparations demonstrate efficacy in reducing the risk of developing atopic dermatitis when administered to pregnant women, infants, or both.

Comparative effectiveness of probiotic strains for the treatment of pediatric atopic dermatitis: A systematic review and network meta-analysis.

BACKGROUND: The current evidence on the use of probiotics in treating atopic dermatitis is inconclusive. This study determined the comparative effectiveness of the different types of probiotic strains in treating pediatric atopic dermatitis. METHODOLOGY: Systematic and manual search for all randomized controlled trials available from inception until January 31, 2020, was done. Two independent authors conducted the search, screening, appraisal, and data abstraction. Network meta-analysis was conducted using STATA 14 software. RESULTS: Twenty-two studies involving 28 different probiotic strains were included. The top three ranked probiotic strains in terms of efficacy are Mix1 (Bifidobacterium animalis subsp lactis CECT 8145, Bifidobacterium longum CECT 7347, and Lactobacillus casei CECT 9104); Lactobacillus casei DN-114001; and Mix6 (Bifidobacterium bifidum, Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus salivarius). Compared with placebo, Mix1 reduces atopic dermatitis symptoms with high certainty evidence (SMD -1.94, 95% CI -2.65 to -1.24; 47 participants). Mix6 compared with placebo probably reduces atopic dermatitis symptoms based on moderate certainty evidence (SMD -0.85, 95% CI -1.50 to -0.20; 40 participants). Lactobacillus casei DN-114001 compared with placebo may reduce atopic dermatitis symptoms based on low certainty evidence (SMD -1.35, 95% CI -2.04 to -0.65). In terms of safety, the highest ranked strain is Lactobacillus fermentum VRI-003, while the lowest ranked strain is Lactobacillus rhamnosus GG. CONCLUSION: Certain probiotic preparations show benefit in reducing allergic symptoms in pediatric atopic dermatitis.

Probiotics as treatment for food allergies among pediatric patients: a meta-analysis.

BACKGROUND: The burden of disease of food allergy is increasing worldwide. The standard of management is allergen avoidance and symptomatic treatment. Probiotics have been proposed to be beneficial for treatment and prevention of food allergy. OBJECTIVE: To determine the effectiveness of probiotic administration in treating food allergies among pediatric patients. METHODS: A systematic search of electronic medical literature databases was conducted. Manual search of the reference lists and search for unpublished articles were also done. All randomized controlled trials available from inception until February 19, 2018 were retrieved. The primary outcome of interest was relief of allergic symptoms, while the secondary outcome of interest was inducement of tolerance. Two independent authors did the search, screening, appraisal, and data abstraction. Data analysis and synthesis were done using RevMan 5.3 software. Subgroup analysis was done based on the probiotic strains and time periods in measuring the outcome. Exclusion sensitivity analysis was also done. RESULTS: Nine trials involving 895 pediatric patients with cow's milk allergy (CMA) were included in the review. The primary outcome of interest, relief of symptoms, was measured using the scoring index for eczema. Pooled results from two studies showed larger reduction in the scoring index among patients given probiotics, but this effect was imprecise (MD -1.30, 95% CI -3.88, 1.28). For the secondary outcome of interest, pooled results from four studies showed benefit of probiotics in inducing tolerance, but again this result is imprecise with significant heterogeneity (RR 0.58, 95% CI 0.34, 1.00). Subgroup analysis per probiotic strain showed benefit of Lactobacillus rhamnosus GG in inducing tolerance based on two studies involving infants with suspected cow's milk allergy (RR = 0.41, 95% CI 0.28 to 0.62). Another subgroup analysis showed a duration-dependent effect associated with probiotic usage, with inducement of tolerance noted after at least 2 years (RR = 0.44, 95% CI 0.29 to 0.67). CONCLUSION: Analysis of available evidence shows moderate certainty that the use of probiotics can relieve symptoms of children with cow's milk allergy. The reduction in certainty is due to imprecise results. Moreover, there is low certainty that probiotics can induce tolerance among children with cow's milk allergy, due to problems of imprecision and attrition bias. In the subgroup analysis, Lactobacillus rhamnosus GG administration likely results in inducing tolerance among infants with suspected cow's milk allergy. Only studies on CMA were analyzed since no studies were found on probiotics as treatment for other types of food allergy among children.