Sources of Heterogeneity in Trials Reporting Hydroxyethyl Starch 130/0.4 or 0.42 Associated Excess Mortality in Septic Patients： A Systematic Review and Meta-regression

Background： This meta-analysis was to determine the association of the cumulative dose of 130/0.4 or 0.42 （hydroxyethyl starch [HES] 130/0.4＊） or delta daily fluid balance （i.e., daily fluid balance in HES group over or below control group） with the heterogeneity of risk ratio （RR） for mortality in randomized control trials （RCTs）. Methods： Three databases （PubMed, EMBASE, Cochrane） were searched to identify prospective RCTs reporting mortality in adult patients with sepsis to compare HES 130/0.4＊ with crystalloids or albumin. Meta-analysis was performed using random effects. Sensitivity and meta-regression analyses were used to examine the heterogeneity sources of RR for mortality, Results： A total number of 4408 patients from 11 RCTs were included. The pooled RR showed no significant difference for overall mortality in patients with administration of liES130/0.4＂ compared with treatment of control fluids （RR： 1.02, 95% confidence interval： 0.9-1.17; P = 0.73）. Heterogeneity was moderate across recruited trials （l^2 = 34%, P = 0.13）. But, a significant variation was demonstrated in subgroup with crystalloids as control fluids （l^2 = 42%, P 〈 0.1）. Sensitivity analysis revealed that trials with high risk of bias did not significantly impact the pooled estimates for mortality. Meta-regression analysis also did not determine a dose-effect relationship of HES 130/0.4＊ with mortality （P - 0.298）, but suggested daily delta fluid balance being likely associated with mortality in septic patients receiving HES130/130/0.4＊ （P = 0.079）.Conclusions： Inappropriate daily positive fluid balance was likely an important source of heterogeneity in these trials reporting HES 130/0.4＊ associated with excess mortality in septic patients.

Acute gastroenteritis outbreaks caused by human astrovirus,1978-2021:A systematic review

Human astrovirus(HAstV)is one of the main pathogens that cause sporadic cases of acute gastroenteritis,sometimes leading to outbreaks.This study aimed to elucidate the epidemiological and etiological character-istics of HAstV outbreaks worldwide.Literature on HAstV outbreaks published before January 2022 was retrieved from the China National Knowledge Infrastructure,WanFang,WeiPu,PubMed,and Web of Science databases.Date,region,population,settings,transmission modes,clinical symptoms,and etiological characteristics of the outbreaks were collected and analyzed.Thirty-one articles on 32 HAstV outbreaks reported between November 1978 and October 2018 were included.The outbreaks mainly occurred in autumn(14/32,43.75%),and more of them were reported in 1996,2004,and 2017.Outbreaks were primarily dis-tributed in the Northern Hemisphere and mainly occurred in nursery centers and kindergartens(9/29,31.03%),hospitals(5/29,17.24%),and schools(4/29,13.79%).Viral genotypes were identified during 19 outbreaks,and HAstV-1 was predominant(8/19,42.10%).Eleven outbreaks were caused by mixed infection,and norovirus(9/11,81.82%)and rotavirus(5/11,45.45%)were the most common mixed pathogens.The transmission routes were reported in 9 outbreaks of mixed infection,and most(7/9)were related to water-borne and foodborne transmission.Although HAstV outbreaks are infrequently reported,it is necessary to con-sider HAstV in norovirus-negative gastroenteritis outbreaks.In addition,local Centers for Disease Control and Prevention should have the capacity to handle HAstV outbreaks and identify pathogens.

Incomparable Subsequent Effects between Study and Control Fluids Might Cause Questionable Results in Randomized Controlled Trials

Dr. Wiedermann commented on our systematic review and meta-regression tbr the sources of heterogeneity in trials reporting H ES 130/0.4 or 0.42 associated excess mortality in septic patients that the pooled analysis of mortality, which showed neither benefit nor harm, might be influenced by trials of low-quality. Statistically, we agree with this conclusion if two of the recruited trials judged as the intermediate risk of bias are precluded.