The effectiveness and safety of treatments used for acute diarrhea and acute gastroenteritis in children: protocol for a systematic review and network meta-analysis

Abstract

BackgroundAcute diarrhea and acute gastroenteritis (AD/AGE) are common among children in low- and middle-income countries (LMIC) and high-income countries (HIC). Supportive therapy including maintaining feeding, prevention of dehydration, and use of oral rehydration solution (ORS), is the mainstay of treatment in all children. Several additional treatments aiming to reduce the episode duration have been compared to placebo, but the differences in effectiveness among them are unknown.Methods and analysisWe will conduct a systematic review of all randomized controlled trials evaluating the use of zinc, vitamin A, probiotics, prebiotics, synbiotics, racecadotril, smectite, and fermented and lactose-free milk/formula for AD/AGE treatment in children. The primary outcomes are diarrhea duration and mortality. Secondary outcomes are diarrhea lasting 3 or 7 days, stool frequency, treatment failure, hospitalizations, and adverse events. We will search MEDLINE, Ovid EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), and LILACS through Ovid, as well as grey literature resources. Two reviewers will independently screen titles and abstracts, review full texts, extract information, and assess the risk of bias (ROB) and the confidence in the estimate (with the grading of recommendations, assessment, development, and evaluation [GRADE] approach). Results will be summarized narratively and statistically. Subgroup analysis according to HIC vs. LMIC, age, nutrition status, and ROB is planned. We will perform a Bayesian network meta-analysis to combine the pooled direct and indirect treatment effect estimates for each outcome, if adequate data is available.DiscussionThis is the first systematic review and network meta-analysis that aims to determine the relative effectiveness of pharmacological and nutritional treatments for reducing the duration of AD/AGE in children. The results will help to reduce the uncertainty of the effectiveness of the interventions, find knowledge gaps, and/or encourage further research for other therapeutic options.Systematic review registrationPROSPERO registration number: CRD42015023778.

The Lancet Commission on pollution and health

“…11 Thus deaths from pneumonia and diarrhoeal diseases-the diseases associated with household air pollution, water pollution, and poor sanitation-are slowly declining worldwide, although they still kill millions of people, particularly children in poor countries. These declines reflect reductions in the forms of pollution associated with traditional lifestyles in low-income and middle-income countries, and the advent of new vaccines such as the pneumococcal vaccine and the rotavirus vaccine; 59 new approaches to paediatric GBD study best estimate (95% CI) WHO best estimate (95% CI)…”

“…49,50 Work to control the biological contamination of drinking water [51][52][53][54] and to curb household air pollution produced by poorly ventilated cookstoves [55][56][57] has occurred over many years and those efforts, along with new vaccines, antibiotics, and treatment protocols, have contributed to promising reductions in the morbidity and mortality associated with the traditional forms of pollution. [58][59][60] However, the burgeoning problems of air, water, and soil pollution produced by modern industry, electricity generation, mining, smelting, petroleum-powered motor vehicles, and chemical and pesticide releases in low-income and middle-income countries have received almost no international attention or resources. 49,50 Budgets for foreign aid from the European Commission, the US Agency for International Development, and most bilateral development agencies, private philanthropists, and major foundations have not included substantive funding for control of industrial, mining and transport-related pollution.…”

Comparison of Regular and Probiotic Yogurts in Treatment of Acute Watery Diarrhea in Children

“…Recently, researchers have supported the importance of microorganisms in the management of diarrhea and reported that some microorganisms or bacteria, such as probiotics, may help treatment and prevention of diarrhea [34]. In this regard, Dinleyici et al, Florez et al and Canani et al in their studies assessed the effects of probiotics on clinical outcomes of children with infectious diarrhea [25,35,36]. They reported the significant effects of probiotics on the clinical outcomes of diarrhea, such as duration and frequency.…”

Rotavirus infection

“…As ~50% of parents of children with rotavirus disease develop rotavirus infections, and half of these develop mild disease, levels of rotavirus-specific CD4 + T cells and neutralizing antibodies might decrease over time and become insufficient to fully prevent reinfections 99 . When compared directly to influenza virus CD4 + T cell responses or tetanus toxin CD4 + T cell responses, the frequencies of rotavirus-specific CD4 + T cells in healthy adults have been shown to be low 97 but similar to levels of CD4 + T cells specific for other mucosal respiratory viruses 91 .…”

“…Combination trials evaluating the simultaneous use of several treatments are lacking 99 . Indeed, improvements in treatment strategies are needed, especially in regions where rotavirus-associated deaths occur and where vaccines are underutilized.…”