How Robust are the Evidences that Formulate Surviving Sepsis Guidelines? An Analysis of Fragility and Reverse Fragility of Randomized Controlled Trials that were Referred in these Guidelines.

OBJECTIVES: "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016" provides guidelines in regard to prompt management and resuscitation of sepsis or septic shock. The study is aimed to assess the robustness of randomized controlled trials (RCTs) that formulate these guidelines in terms of fragility index and reverse fragility index. METHOD: RCTs that contributed to these guidelines having parallel two-group design, 1:1 allocation ratio, and at least one dichotomous outcome were included in the study. The median fragility index was calculated for RCTs with significant statistical outcomes, whereas the median reverse fragility index was calculated for RCTs with nonsignificant statistical results. RESULTS: Hundred RCTs that met the inclusion criteria were analyzed. The median fragility index was 5.5 [95% confidence interval (CI) 1-30] and median reverse fragility index was 13 (95% CI 12.07-16.8) at a p value of 0.05. The median reverse fragility index was 16 (95% CI 10-26) at a p value of 0.01. Most of the RCTs included in this analysis were of good quality, having a median Jadad score of 6. CONCLUSION: This analysis found that the surviving sepsis guidelines were based on highly robust RCTs with statistically insignificant results and on some moderately robust RCTs with statistically significant results. RCTs with statistically insignificant results were more robust than RCTs with statistically significant results in regard to these guidelines. HIGHLIGHTS: The study assessed the robustness of randomized controlled trials (RCTs) that were used to formulate surviving sepsis guidelines. Most RCTs showed statistically nonsignificant results. RCTs with statistically significant results were moderately fragile whereas RCTs with nonsignificant results were more robust. HOW TO CITE THIS ARTICLE: Choupoo NS, Das SK, Saikia P, Dey S, Ray S. How Robust are the Evidences that Formulate Surviving Sepsis Guidelines? An Analysis of Fragility and Reverse Fragility of Randomized Controlled Trials that were Referred in these Guidelines. Indian J Crit Care Med 2021;25(7):773-779.

Evaluating the Efficacy and Safety of the Existing Repurposed Pharmacological Agents for Treating COVID-19: A Meta-analysis and Systematic Review of Clinical Trials.

PURPOSE: The present study systematically searched important medical databases, assessed the quality of available pieces of evidence, and performed a meta-analysis to test the efficacy of different therapeutic options currently available for treating COVID-19. MATERIALS AND METHODS: PubMed, CNKI, LILACS, Koreamed, WHO clinical trial registry, and medRxiv were searched since December 2019. Any observational or controlled study that tested the efficacy of any pharmacological intervention in COVID-19 patients either prospectively or retrospectively was included in the qualitative analysis. We assessed outcomes as dichotomous variables, i.e., a patient having a positive clinical outcome. Relative risks/risk ratios (RR) having a 95% confidence interval (CI) were derived. Studies conforming to inclusion criteria were pooled using the random-effect model. RESULTS: Nine trials on hydroxychloroquine (HCQ), six studies on antiviral, four studies on monoclonal antibodies, two on corticosteroids, two on convalescent plasma (CP), and one on interferon-α2b were included in the systematic review. Meta-analysis containing six scientific trials and analyzing 522 patients revealed that the relative risk of positive clinical outcomes with HCQ treatment was 1.042 (95% CI, 0.884 to 1.874) with a number needed to treat (NNT) of 12.6. A meta-analysis of two studies analyzing 285 patients showed that the relative risk of clinical resolution with lopinavir and ritonavir combination was 1.152 (95% CI 0.709 to 1.87). Out of various antiviral used, the only remdesivir showed a positive result in a case series. Monoclonal antibodies showed decreased C-reactive protein, decreased oxygen, and ventilator requirements. A corticosteroid may increase mortality with increased dose. Two small case series on CP showed some promising results. CONCLUSION: The study showed slightly favorable results with HCQ, monoclonal antibodies, remdesivir, and CP in treating COVID-19 patients. Further research is warranted in establishing the efficacy of studied interventions. PROSPERO IDENTIFIER: CRD42020180979. HOW TO CITE THIS ARTICLE: Choupoo NS, Das SK, Haldar R, Sarkar H, Tewari R, Ray S. Evaluating the Efficacy and Safety of the Existing Repurposed Pharmacological Agents for Treating COVID-19: A Meta-analysis and Systematic Review of Clinical Trials. Indian J Crit Care Med 2020;24(11):1106-1113.

Diagnostic accuracy of inferior vena caval respiratory variation in detecting fluid unresponsiveness: A systematic review and meta-analysis.

BACKGROUND: The accuracy of respiratory variation of the inferior vena cava (rvIVC) in predicting fluid responsiveness, particularly in spontaneously breathing patients is unclear. OBJECTIVES: To consider the evidence to support the accuracy of rvIVC in identifying patients who are unlikely to benefit from fluid administration. DESIGN: Systematic review and meta-analysis. DATA SOURCE: We searched MEDLINE, EMBASE, Cochrane Library, KoreaMed, LILCAS and WHO Clinical Trial Registry from inception to June 2017. ELIGIBILITY CRITERIA: Case-control or cohort studies that evaluated the accuracy of rvIVC in living adult humans were included. A study was included in the meta-analysis if data enabling construction of 2 × 2 tables were reported, calculated or could be obtained from authors and met the above cited criteria. RESULT: A total of 23 studies including 1574 patients were included in qualitative analysis. The meta-analysis involved 20 studies and 761 patients. Pooled sensitivity and specificity of rvIVC in 330 spontaneously breathing patients were 0.80 [95% confidence interval (CI) 0.68 to 0.89] and 0.79 (95% CI 0.60 to 0.90). Pooled sensitivity and specificity of rvIVC in 431 mechanically ventilated patients were 0.79 (95% CI 0.67 to 0.86) and 0.70 (95% CI 0.63 to 0.76). CONCLUSION: Decreased inferior vena caval respiratory variation is moderately accurate in predicting fluid unresponsiveness both in spontaneous and mechanically ventilated patients. The findings of this review should be used in the appropriate clinical context and in conjunction with other clinical assessments of fluid status. IDENTIFIER: CRD 42017068028.

Water, sanitation and hygiene: The unfinished agenda in the World Health Organization South-East Asia Region.

Access to adequate water, sanitation and hygiene (WASH) is essential for the health, well-being and dignity of all people. The World Health Organization South-East Asia Region has made considerable progress in WASH provision during the past two decades. However, compared with increases in coverage of improved drinking water, in some parts of the region, access to adequate sanitation remains low, with continued prevalence of open defecation. The Sustainable Development Goals (SDGs) have set ambitious targets for WASH services to be achieved by 2030. Examples of major health outcomes that would benefit from meeting these targets are diarrhoea and nutrition status. Although the total number of deaths attributable to diarrhoea declined substantially between 1990 and 2012, inadequate WASH still accounts for more than 1000 child deaths each day worldwide. And, despite the reductions in mortality, diarrhoea morbidity attributable to diarrhoea remains unchanged at around 1.7 billion cases per year. It has been known for decades that repeated episodes of diarrhoea increase a child's risk of long-term undernutrition, reduced growth and impaired cognitive development. Nutritional effects of inadequate WASH also include environmental enteropathy, leading to chronic intestinal inflammation, malnutrition and developmental deficits in young children. Inadequate WASH also contributes to iron deficiency anaemia resulting from infestation with soil-transmitted helminths. The cross-sectoral emphasis of the SDGs should act as a stimulus for intersectoral collaboration on research and interventions to reduce all inequities that result from inadequate WASH.

Evaluating the role of flupirtine for postcraniotomy pain and compare it with diclofenac sodium: a prospective, randomized, double blind, placebo-controlled study.

BACKGROUND: Patients undergoing craniotomy, experience moderate to severe pain in postoperative period. Flupirtine does not have side effects like sedation and increase postoperative bleeding, so it may be a useful analgesic in neurosurgical patients. We designed this prospective, randomized, double blind, placebo-controlled study to evaluate the role of flupirtine for postcraniotomy pain and compare it with diclofenac sodium. MATERIALS AND METHODS: A total of 390 adults (18 to 70 y), American Society of Anaesthesiologists I and II, of either sex, undergoing elective craniotomy, were randomly divided into 3 equal groups of 130 each. Group 1 (control) received placebo, group 2 (diclofenac) received tablet diclofenac 50 mg, and group 3 (flupirtine) received capsule flupirtine 100 mg. All medications were given 8 hourly on second postoperative day for 48 hours. Visual Analogue Scale score, level of sedation and incidence of side effects were observed. RESULTS: Nineteen patients were dropped from the study and therefore subsequent analysis was carried out for 371 patients only. There was significant reduction of Visual Analogue Scale score in flupirtine and diclofenac group when compared to control (P<0.0001). Pain relief observed in control, flupirtine, and diclofenac group was 69.8%, 90.2%, and 90.5%, respectively. Need of rescue analgesia was significantly less in flupirtine and diclofenac group as compared to control (P<0.0001). No significant difference was observed among the groups in regards to adverse effects. CONCLUSION: We conclude that oral flupirtine 100 mg is safe and as effective as oral diclofenac sodium 50 mg in reducing postcraniotomy pain.