ABSTRACT
In December 2019, an outbreak of a respiratory desease caused by a new coronavirus strain was detected in Wuhan, China. The disease spread rapidly around the world and was recognized as a pandemic by the World Health Organization in March 2020. From the very beginning of the pandemic, society was faced with a scenario fraught with uncertainty: a new disease with severe effects on some patients and no specific treatment. The medical community reacted promptly and undertook the quest for treatment options, some based on prior experiences with diseases caused by other coronavirus strains or related viruses, and other approaches based on potential pathophysiological mechanisms promising at the time but without any supporting scientific evidence.
En diciembre de 2019, se detectó en Wuhan (China) un brote de una enfermedad respiratoria causada por una nueva cepa de coronavirus. La enfermedad se extendió rápidamente por todo el mundo y fue reconocida como pandemia por la Organización Mundial de la Salud en marzo de 2020. Desde el principio de la pandemia, la sociedad se enfrentó a un escenario cargado de incertidumbre: una nueva enfermedad con graves efectos en algunos pacientes y sin tratamiento específico. La comunidad médica reaccionó rápidamente y emprendió la búsqueda de opciones de tratamiento, algunas basadas en experiencias previas con enfermedades causadas por otras cepas de coronavirus o virus relacionados, y otras aproximaciones basadas en posibles mecanismos fisiopatológicos prometedores en ese momento pero sin ninguna evidencia científica que los respaldara.
Subject(s)
Humans , Respiratory Tract Diseases , Decision Making , SARS-CoV-2 , Societies , Pharmaceutical Preparations/administration & dosage , Pandemics , COVID-19ABSTRACT
OBJECTIVE: To determine the effectiveness and safety of gelatin tannate (GT) for reducing the duration of the acute diarrhoea and gastroenteritis (ADG) in children. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, LILACS and grey literature, published from inception to October 2018. No language restrictions. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials in children with ADG, comparing GT with placebo. RESULTS: Of 797 titles identified, we included three studies (276 children). We performed a random effects model meta-analysis for the main outcome (diarrhoea duration). We did not find significant differences between GT and placebo for diarrhoea duration (mean difference (MD)=-15.85 hours; 95% CI -42.24 to 14.82, I2=92%; three studies), stool frequency at day 2 (MD=0.11 stools/day; 95% CI -0.39 to 0.62: I2=26%; two studies), diarrhoea at day 3 (risk ratio [RR]=0.46; 95% CI 0.06 to 3.47: I2=73%; two studies), vomiting (RR=1.31; 95% CI 0.95 to 1.80: I2=0%; two studies) or adverse events (RR=0.86; 95% CI 0.27 to 2.66: I2=0%; two studies). Most common adverse events included abdominal pain and nausea. CONCLUSION: The effect of GT was no different to placebo for mean diarrhoea duration (low certainty on the evidence) and stool frequency at day 2 (high certainty) and for the presence of diarrhoea at day 3 (very low certainty) of vomiting (moderate certainty) and of adverse events (low certainty). PROSPERO REGISTRATION NUMBER: CRD42018087902.
Subject(s)
Diarrhea/drug therapy , Gastroenteritis/drug therapy , Gelatin/therapeutic use , Tannins/therapeutic use , Acute Disease , Child , Gelatin/adverse effects , Humans , Tannins/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: Many interventions have shown effectiveness in reducing the duration of acute diarrhea and gastroenteritis (ADG) in children. Yet, there is lack of comparative efficacy of interventions that seem to be better than placebo among which, the clinicians must choose. Our aim was to determine the comparative effectiveness and safety of the pharmacological and nutritional interventions for reducing the duration of ADG in children. METHODS: Data sources included Medline, Embase, CENTRAL, CINAHL, LILACS, and Global-Health up to May 2017. Eligible trials compared zinc (ZN), vitamin A, micronutrients (MN), probiotics, prebiotics, symbiotics, racecadotril, smectite(SM), loperamide, diluted milk, lactose-free formula(LCF), or their combinations, to placebo or standard treatment (STND), or among them. Two reviewers independently performed screening, review, study selection and extraction. The primary outcome was diarrhea duration. Secondary outcomes were stool frequency at day 2, diarrhea at day 3, vomiting and side effects. We performed a random effects Bayesian network meta-analysis to combine the direct and indirect evidence for each outcome. Mean differences and odds ratio with their credible intervals(CrI) were calculated. Coherence and transitivity assumptions were assessed. Meta-regression, subgroups and sensitivity analyses were conducted to explore the impact of effect modifiers. Summary under the cumulative curve (SUCRA) values with their CrI were calculated. We assessed the evidence quality and classified the best interventions using the Grading of Recommendations, Assessment, Development & Evaluation (GRADE) approach for each paired comparison. RESULTS: A total of 174 studies (32,430 children) proved eligible. Studies were conducted in 42 countries of which most were low-and middle-income countries (LMIC). Interventions were grouped in 27 categories. Most interventions were better than STND. Reduction of diarrhea varied from 12.5 to 51.1 hours. The combinations Saccharomyces boulardii (SB)+ZN, and SM+ZN were considered the best interventions (i.e., GRADE quality of evidence: moderate to high, substantial superiority to STND, reduction in duration of 35 to 40 hours, and large SUCRA values), while symbiotics (combination of probiotics+prebiotics), ZN, loperamide and combinations ZN+MN and ZN+LCF were considered inferior to the best and better than STND [Quality: moderate to high, superior to STND, and reduction of 17 to 25 hours]. In subgroups analyses, effect of ZN was higher in LMIC and was not present in high-income countries (HIC). Vitamin A, MN, prebiotics, kaolin-pectin, and diluted milk were similar to STND [Quality: moderate to high]. The remainder of the interventions had low to very-low evidence quality. Loperamide was the only intervention with more side effects than STND [Quality: moderate]. DISCUSSION/CONCLUSION: Most interventions analyzed (except vitamin A, micronutrients, prebiotics, and kaolin-pectin) showed evidence of superiority to placebo in reducing the diarrhea. With moderate-to high-quality of evidence, SB+ZN and SM+ZN, demonstrated the best combination of evidence quality and magnitude of effect while symbiotics, loperamide and zinc proved being the best single interventions, and loperamide was the most unsafe. Nonetheless, the effect of zinc, SB+ZN and SM+ZN might only be applied to children in LMIC. Results suggest no further role for studies comparing interventions against no treatment or placebo, or studies testing loperamide, MN, kaolin-pectin, vitamin A, prebiotics and diluted milk. PROSPERO REGISTRATION: CRD42015023778.
Subject(s)
Diarrhea/therapy , Gastroenteritis/therapy , Antidiarrheals/therapeutic use , Bayes Theorem , Child , Humans , Loperamide/therapeutic use , Network Meta-Analysis , Prebiotics , Probiotics/therapeutic use , Saccharomyces boulardii , Treatment Outcome , Zinc/therapeutic useABSTRACT
RESUMEN Objetivo Evaluar los costos de las terapias de rehidratación oral (TRO) y de rehidratación nasogástrica (TRN) comparadas con la terapia de rehidratación endovenosa (TRE) para corregir la deshidratación por diarrea en niños. Metodología Análisis de minimización de costos desde la perspectiva del Sistema de Salud colombiano comparando TRO (seguida de TRN ante falla de la TRO), con la TRE. El horizonte temporal fue la duración de la rehidratación. La medida de efectividad se extrajo de una revisión sistemática de literatura. Para determinar costos, se construyó un caso típico y un árbol de decisiones, a partir de revisión de guías e historias clínicas, validado con expertos. Los costos unitarios se obtuvieron de bases de datos colombianas. Costos fueron calculados en pesos colombianos (COP) y dólares americanos (USD). Se realizaron análisis de sensibilidad de una y dos vías. Resultados La TRO y la TRE son similares en efectividad para prevenir hospitalización y lograr rehidratación. En el caso base, el costo de la TRO fue $91,221COP (40.5 USD) y para TRE $112,944COP (50.14USD), es decir, un ahorro de $21,723 COP (9.64 USD). En los análisis de sensibilidad por regímenes de aseguramiento y complejidad del hospital, la TRO suele ser la estrategia menos costosa. Discusión Ambas intervenciones son similares en efectividad, pero la TRO, seguida de TRN ante falla de la primera resulta menos costosa que la TRE. La TRO es recomendable como primera opción para corregir la deshidratación. Deberían continuarse esfuerzos por implementar TRO y TRN en los servicios de salud en Colombia.(AU)
ABSTRACT Objective To evaluate the costs of oral rehydration therapy (ORT) and nasogastric rehydration therapy (NRT) compared with intravenous rehydration therapy (IRT) to treat dehydration in children under 5 years of age with diarrhea. Methodology Cost-minimization analysis from the perspective of the Colombian Health System, comparing ORT, (followed by NRT when ORT fails), with IRT. The time horizon was the duration of rehydration. The effectiveness measure was obtained from a systematic review of the literature. To determine costs, a typical case was created based on current guidelines and medical records; this case was validated by experts. Unit costs were obtained from Colombian databases and were provided in Colombian pesos (COP) and US dollars (USD) for 2010. One- and two-way sensitivity analyzes were performed. Results ORT and ERT are similarly effective to prevent hospitalization and to achieve rehydration. In the base case, the expected cost of ORT was $91,221 COP (40.5 USD) and for IRT was $112,944 COP ($50.14 USD), saving $21,723 COP ($9.64 USD) per case. In the sensitivity analyzes by health insurance and hospital level, ORT is often the least costly strategy. Discussion Both interventions are similarly effective, but ORT, followed by NRT when ORT fails, is less costly than IRT. ORT is recommended as the first option to treat dehydration since it is effective and less expensive. Efforts should be continued to implement TRO and NRT in the health services of Colombia.(AU)
Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Rehydration Solutions , Diarrhea, Infantile/therapy , Fluid Therapy/instrumentation , Colombia/epidemiology , Costs and Cost Analysis/methodsABSTRACT
OBJECTIVE: To evaluate the costs of oral rehydration therapy (ORT) and nasogastric rehydration therapy (NRT) compared with intravenous rehydration therapy (IRT) to treat dehydration in children under 5 years of age with diarrhea. METHODOLOGY: Cost-minimization analysis from the perspective of the Colombian Health System, comparing ORT, (followed by NRT when ORT fails), with IRT. The time horizon was the duration of rehydration. The effectiveness measure was obtained from a systematic review of the literature. To determine costs, a typical case was created based on current guidelines and medical records; this case was validated by experts. Unit costs were obtained from Colombian databases and were provided in Colombian pesos (COP) and US dollars (USD) for 2010. One- and two-way sensitivity analyzes were performed. RESULTS: ORT and ERT are similarly effective to prevent hospitalization and to achieve rehydration. In the base case, the expected cost of ORT was $91,221 COP (40.5 USD) and for IRT was $112,944 COP ($50.14 USD), saving $21,723 COP ($9.64 USD) per case. In the sensitivity analyzes by health insurance and hospital level, ORT is often the least costly strategy. DISCUSSION: Both interventions are similarly effective, but ORT, followed by NRT when ORT fails, is less costly than IRT. ORT is recommended as the first option to treat dehydration since it is effective and less expensive. Efforts should be continued to implement TRO and NRT in the health services of Colombia.
OBJETIVO: Evaluar los costos de las terapias de rehidratación oral (TRO) y de rehidratación nasogástrica (TRN) comparadas con la terapia de rehidratación endovenosa (TRE) para corregir la deshidratación por diarrea en niños. METODOLOGÍA: Análisis de minimización de costos desde la perspectiva del Sistema de Salud colombiano comparando TRO (seguida de TRN ante falla de la TRO), con la TRE. El horizonte temporal fue la duración de la rehidratación. La medida de efectividad se extrajo de una revisión sistemática de literatura. Para determinar costos, se construyó un caso típico y un árbol de decisiones, a partir de revisión de guías e historias clínicas, validado con expertos. Los costos unitarios se obtuvieron de bases de datos colombianas. Costos fueron calculados en pesos colombianos (COP) y dólares americanos (USD). Se realizaron análisis de sensibilidad de una y dos vías. RESULTADOS: La TRO y la TRE son similares en efectividad para prevenir hospitalización y lograr rehidratación. En el caso base, el costo de la TRO fue $91,221COP (40.5 USD) y para TRE $112,944COP (50.14USD), es decir, un ahorro de $21,723 COP (9.64 USD). En los análisis de sensibilidad por regímenes de aseguramiento y complejidad del hospital, la TRO suele ser la estrategia menos costosa. DISCUSIÓN: Ambas intervenciones son similares en efectividad, pero la TRO, seguida de TRN ante falla de la primera resulta menos costosa que la TRE. La TRO es recomendable como primera opción para corregir la deshidratación. Deberían continuarse esfuerzos por implementar TRO y TRN en los servicios de salud en Colombia.
ABSTRACT
BACKGROUND: Acute 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 ANALYSIS: We 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. DISCUSSION: This 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 REGISTRATION: PROSPERO registration number: CRD42015023778.
Subject(s)
Diarrhea/therapy , Gastroenteritis/therapy , Acute Disease , Antidiarrheals/therapeutic use , Child Nutritional Physiological Phenomena , Child, Preschool , Dehydration/prevention & control , Diarrhea/complications , Gastroenteritis/complications , Humans , Nutritional Status , Nutritional Support , Probiotics/therapeutic use , Randomized Controlled Trials as Topic , Research Design , Systematic Reviews as Topic , Treatment OutcomeABSTRACT
OBJECTIVE: The objective of this study was to determine the cost-effectiveness of zinc supplementation for the treatment of acute diarrhea (AD) in children younger than 5 years in Colombia. METHODS: The cost-effectiveness analysis was performed from the perspective of the Colombian health system. The standard treatment with the addition of zinc was compared with the standard treatment without zinc in children younger than 5 years. The time horizon was 1 month. Effectiveness was extracted from a systematic review of literature. The specific data for Colombia were taken from local databases and observational studies. To determine the costs, a typical case was constructed by reviewing guidelines and medical records and validated by experts. To evaluate the resources consumed, Colombian tariff manuals were used. Costs were stated in Colombian pesos (COP) and US dollar (USD) for 2010. Deterministic sensitivity analysis was performed to evaluate the impact of changes in cost and effectiveness of the strategies on the results from the model. RESULTS: The results from the model indicate that zinc supplementation is a dominant strategy; it is less costly and more effective than standard treatment without zinc (reduction of $15,210 COP [8.14 USD] per child). The results are sensitive to changes in the probability of hospitalization and of persistent diarrhea. CONCLUSIONS: Zinc for the treatment of AD is a highly cost-effective strategy and is recommended for inclusion in the benefit plan of the Colombian health system. This intervention is more cost-effective in children with a higher risk of persistent diarrhea and hospitalization.
