Efficacy and safety of chloroquine and hydroxychloroquine for COVID-19: A comprehensive evidence synthesis of clinical, animal, and in vitro studies.

Background: The world is facing a pandemic of COVID-19, a respiratory disease caused by a novel coronavirus which is now called SARS-CoV-2. Current treatment recommendations for the infection are mainly repurposed drugs based on experience with other clinically similar conditions and are not backed by direct evidence. Chloroquine (CQ) and its derivative Hydroxychloroquine (HCQ) are among the candidates. We aimed to synthesize current evidence systematically for in vitro, animal, and human studies on the efficacy and safety of chloroquine in patients with COVID-19. Methods: The Cochrane Library, Google Scholar, PubMed (via Medline), Embase, Scopus, and Web of Science, MedRxiv, clinical trial registries including clinicaltrials.gov, ChiCTR (Chinese Clinical Trial Registry), IRCT (Iranian Registry of Clinical Trials), and the EU Clinical Trials Register. We used the Cochrane tool for risk of bias assessment in randomized studies, the ROBINS tool for non-randomized studies, and the GRADE methodology to summarize the evidence and certainty in effect estimates. Results: The initial database searching retrieved 24,752 studies. Of these, 15,435 abstracts were screened and 115 were selected for full-text review. Finally, 20 human studies, 3 animal studies, and 4 in vitro studies were included in this systematic review. The risk of bias within studies was unclear to high and the overall certainty in evidence-based on GRADES- was very low. HCQ may be effective in clinical improvement in a subset of patients with COVID-19. However, the frequency of adverse events was higher in patients taking HCQ compared to standard of care alone. In contrast, animal studies, did not report any adverse effects. Furthermore, clear benefit of the drug in the survival of the animals has been reported. Most in vitro studies indicated a high selectivity index for the drug and one study that used a human coronavirus reported blockage of virus replication. Conclusion: Current evidence background is limited to six poorly conducted clinical studies with inconsistent findings which fail to show significant efficacy for HCQ. Safety data is also limited but the drug may increase adverse outcomes. Routine use of the drug is not recommended based on limited efficacy and concerns about the drug safety especially in high-risk populations.

Prevalence of stunting in Iranian children under five years of age: Systematic review and meta-analysis.

Background: Children in all countries, especially in developing countries, constitute a vulnerable group. Therefore, attention to their health issues is very important. The aim of this study was to determine the prevalence of stunting in Iranian children under-five years. Methods: All original studies were searched by complex search syntax from international databases including Medline (PubMed), Web of sciences, Google scholar, Scopus, CINHAL and the Iranian databases consist of SID (Scientific Information Database, www.sid.ir), Irandoc (Iranian Research Institute for Information Science and Technology, Irandoc.ac.ir), Iranmedex (www.iranmedex.com), and Magiran (www.magiran.com) from January 1989 to August 2017. Two independent reviewers identified relevant studies in several steps. We employed a random effect model to generate a pooled prevalence. The reported prevalence is presented as percent and 95% confidence interval (CI). Sources of heterogeneity among the studies were determined using subgroup analysis and meta-regression. Results: Finally, 16 studies from different settings remained for meta-analysis in order to have a pooled prevalence estimate, which prevalence of total stunting was 12% (95%CI: 10-14). Subgroup analysis for gender showed that the prevalence of stunting in both boys and girls children were equal to 10% (95%CI: 8-11) and 9% (CI 95% 8-10), respectively. Also pooled prevalence of stunting in southern provinces are higher than other provinces. Conclusion: The prevalence of stunting in some regions of Iran is higher than others. Although, in recent years much effort has been made to address deprivation such as economical, nutritional and social supporting, improvement of the quality of life, there are still nutritional problems in these areas of Iran.

Nonsteroidal anti-inflammatory drugs in acute viral respiratory tract infections: An updated systematic review.

In this systematic review, we aimed to assess the efficacy and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) in treating respiratory tract infections in adults and children. PubMed, Scopus, Web of Science, Cochrane, and Embase databases were searched. A total of 34 randomized clinical trials were included in this systematic review. We assessed the risk of bias of all included studies using the Cochrane tool for risk of bias assessment. The evidence on ibuprofen, naproxen, aspirin, diclofenac, and other NSAIDs were rated for degree of uncertainty for each of the study outcomes and summarized using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Our findings suggest that high-quality evidence supports the use of NSAIDs to reduce fever in both adults and children. However, the evidence was uncertain for the use of NSAIDs to reduce cough. Most studies showed that NSAIDs significantly relieved sore throat. The evidence for mortality and oxygenation is limited. Regarding the adverse events, gastrointestinal discomfort was more frequently reported in children. For adults, our overall certainty in effect estimates was low and the increase in gastrointestinal adverse events was not clinically significant. In conclusion, NSAIDs seem to be beneficial in the outpatient management of fever and sore throat in adults and children. Although the evidence does not support their use to decrease mortality nor improve oxygenation in inpatient settings, the use of NSAIDs did not increase the rate of death or the need for ventilation in patients with respiratory tract infections. Further studies with a robust methodology and larger sample sizes are recommended.

Medicinal plants in the adjunctive treatment of patients with type-1 diabetes: a systematic review of randomized clinical trials.

PROPOSE: This study aims to systematically review the randomized controlled trials that address the effectiveness and safety of herbal medicine in patients with type 1 diabetes. METHODS: The Cochrane Library (latest issue); MEDLINE (until recent); EMBASE (until recent); AMED (Allied and Complementary Medicine Database) (until recent); and CINHAL (until recent) were searched electronically for the identification of trials until October 2019. Articles were initially screened based on title and abstract and then by full text by two independent authors. References of retrieved studies were hand-searched for further studies. Risk of bias was assessed according to the Cochrane handbook of systematic reviews of interventions. The results were summarized into GRADE (grading of recommendations, assessment, development and evaluation) tables. No meta-analysis was applicable as only one study was found for each intervention. RESULTS: Four RCTs were finally included in the systematic review with an overall moderate quality of conduct and low quality of reporting. The sample sizes were very small. The results of these RCTs show that cinnamon pills and Berberine/Silymarine compound capsules may decrease blood glucose indices from baseline, while fenugreek seeds and fig leaf decoction do not show any statistically significant effect. CONCLUSIONS: The evidence is scarce and no recommendations can be made based on current evidence. Further trials with more rigorous methodology and stronger quality of reporting are needed to make conclusions.