Potentially effective drugs for the treatment of COVID-19 or MIS-C in children: a systematic review.

The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone. CONCLUSIONS: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. WHAT IS KNOWN: • The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. WHAT IS NEW: • Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C. • We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.

Epidemiological and clinical characteristics of severe hand-foot-and-mouth disease (HFMD) among children: a 6-year population-based study.

BACKGROUND: Hand-foot-and-mouth disease (HFMD) is considered to be self-limited, however, severe HFMD is a deadly threat for children worldwide, therefore, it is essential to define the clinical and epidemiologic characteristics of children with severe HFMD and identify the risk factors of death. METHODS: Between 2013 and 2018, children who diagnosed with severe HFMD from Chongqing, China were enrolled in this population-based study. A total of 459 severe HFMD children cases were identified during the study period, including 415 survivors and 44 fatal cases. Demographic, geographical, epidemiological and clinical data of the cases were acquired and analyzed. RESULTS: Risk factors of the death because of severe HFMD children included female, aged 1 ~ 3 years, enterovirus 71 infection, falling ill in winter, more than one children in home, being taken care of by grandparents, the caregivers' education not more than 9 years, having fever more than 3 days, consciousness disorders, general weakness, vomiting, general weakness, abnormal pupillary light reflex, repeated cough, tachypnea, moist rales, white frothy sputum, pink frothy sputum, and cyanosis on lips or the whole body, tachycardia, arrhythmia, cold limbs, pale complexion, weakened pulse. (all p < 0.05). Spatial-temporal analysis detected high-value clusters, the most likely cluster located at rural countries in the northern parts of Chongqing, from January, 2015 to July, 2017. (p < 0.01). Besides, some urban districts were also found high incidence of severe HFMD cases according to the incidence maps. CONCLUSIONS: The detection of clinical risk factors and the temporal, spatial and socio-demographic distribution epidemiological characteristics of severe HFMD contribute to the timely diagnosis and intervention, the results of this study can be the reference of further clinical and public health practice.

Comparative Study of Pulsed Versus Continuous High-Intensity Focused Ultrasound Ablation Using In Vitro and In Vivo Models.

OBJECTIVES: To compare the efficacy of pulsed high-intensity focused ultrasound (PHIFU) versus continuous high-intensity focused ultrasound (CHIFU) ablation at identical doses. METHODS: Continuous and pulsed HIFU (1200 J) at duty cycles (DCs) of 60% and 20% were examined for their capacity to ablate bovine liver tissue in vitro and rabbit liver tissue in vivo. After ablation, grayscale changes and pathologic characteristics were observed or measured, and the tissue necrosis volume, energy efficiency factor, and average grayscale density were calculated. RESULTS: The pulsed mode generated greater liquefaction necrosis. An inconspicuous grayscale change was observed for PHIFU at a DC of 20% in some samples, which appeared as an elliptical cavity. The energy efficiency factor of PHIFU at a DC of 60% was significantly lower than that of CHIFU, as observed both in vitro and in vivo (P < .05). The grayscale value and average grayscale density in response to CHIFU were significantly greater than those in response to PHIFU (60% or 20%; P < .05). Histopathologic analysis revealed liquefaction necrosis in all PHIFU groups. CONCLUSIONS: At identical doses, compared with CHIFU, a single session of PHIFU can generate liquefaction necrosis and at a higher DC can improve ablation efficiency. This increased efficacy of PHIFU may involve enhancement of tissue destruction by cavitation effects and a reduction in the obstruction effect of endogenous microbubbles through cavitation effects or a more effective diffusion of heat.

Use of non-steroidal anti-inflammatory drugs and adverse outcomes during the COVID-19 pandemic: A systematic review and meta-analysis.

Background: There are concerns that the use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse outcomes among patients with coronavirus COVID-19. This study aimed to synthesize the evidence on associations between the use of NSAIDs and adverse outcomes. Methods: A systematic search of WHO COVID-19 Database, Medline, the Cochrane Library, Web of Science, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Database for all articles published from January 1, 2020, to November 7, 2021, as well as a supplementary search of Google Scholar. We included all comparative studies that enrolled patients who took NSAIDs during the COVID-19 pandemic. Data extraction and quality assessment of methodology of included studies were completed by two reviewers independently. We conducted a meta-analysis on the main adverse outcomes, as well as selected subgroup analyses stratified by the type of NSAID and population (both positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or not). Findings: Forty comparative studies evaluating 4,867,795 adult cases were identified. Twenty-eight (70%) of the included studies enrolled patients positive to SARS-CoV-2 tests. The use of NSAIDs did not reduce mortality outcomes among people with COVID-19 (number of studies [N] = 29, odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.75 to 1.14, I2  = 89%). Results suggested that the use of NSAIDs was not significantly associated with higher risk of SARS-CoV-2 infection in patients with or without COVID-19 (N = 10, OR = 0.96, 95% CI: 0.86 to 1.07, I2  = 78%; N = 8, aOR = 1.01, 95% CI: 0.94 to 1.09, I2  = 26%), or an increased probability of intensive care unit (ICU) admission (N = 12, OR = 1.28, 95% CI: 0.94 to 1.75, I2  = 82% ; N = 4, aOR = 0.89, 95% CI: 0.65 to 1.22, I2  = 60%), requiring mechanical ventilation (N = 11, OR = 1.11, 95% CI: 0.79 to 1.54, I2  = 63%; N = 5, aOR = 0.80, 95% CI: 0.52 to 1.24, I2  = 66%), or administration of supplemental oxygen (N = 5, OR = 0.80, 95% CI: 0.52 to 1.24, I2  = 63%; N = 2, aOR = 1.00, 95% CI: 0.89 to 1.12, I2  = 0%). The subgroup analysis revealed that, compared with patients not using any NSAIDs, the use of ibuprofen (N = 5, OR = 1.09, 95% CI: 0.50 to 2.39; N = 4, aOR = 0.95, 95% CI: 0.78 to 1.16) and COX-2 inhibitor (N = 4, OR = 0.62, 95% CI: 0.35 to 1.11; N = 2, aOR = 0.73, 95% CI: 0.45 to 1.18) were not associated with an increased risk of death. Interpretation: Data suggests that NSAIDs such as ibuprofen, aspirin and COX-2 inhibitor, can be used safely among patients positive to SARS-CoV-2. However, for some of the analyses the number of studies were limited and the quality of evidence was overall low, therefore more research is needed to corroborate these findings. Funding: There was no funding source for this study.