Eficacia y seguridad de colestiramina para el tratamiento de diarrea por malabsorción de ácidos biliares secundaria a resección ileal en población pediátrica / Efficacy and safety of cholestyramine for treatment of diarrhea by acid malabsorption bile ducts secondary to ileal resection in population pediatric

INTRODUCCIÓN: Este documento técnico se realizó en el marco de la Guía de Práctica Clínica para pacientes pediátricos con falla intestinal; la pregunta PICO fue la siguiente: P: pacientes de 0-18 años con resección ileal por cualquier causa; I: colestiramina; C: placebo, colestipol, colesevelam, dietas modificadas o suplementos dietéticos; O: frecuencia de deposiciones, cambio en el peso o masa de las heces y eventos adversos. a. Cuadro clínico: Los ácidos biliares son moléculas cuya función principal es ayudar en la digestión y absorción de lípidos. En personas sanas, más del 95% de ácidos biliares se reabsorben en el íleon terminal. La reabsorción insuficiente de ácidos biliares en el íleon terminal incrementa la concentración en el colon, produciendo diarrea secretora. Se estima que la malabsorción de ácidos biliares (MAB) afecta al 1% de la población de países occidentales y cerca del 90% de pacientes con resección ileal. El tratamiento de la diarrea por MAB consiste en un manejo dietético y farmacológico. Los pacientes con diarrea y esteatorrea moderada deben someterse a una dieta baja en grasas (30 g/día) con o sin adición de triglicéridos de cadena media. El tratamiento farmacológico se basa en secuestrantes de ácidos biliares como colestiramina, colestipol o colesevelam. b. Tecnología sanitaria: Colestiramina es un secuestrante de ácidos biliares que se une con alta afinidad a los ácidos biliares en el intestino para formar un complejo estable e insoluble que se excreta en las heces. Pese a no ser una indicación aprobada, se emplea hace varias décadas para el tratamiento de MAB. Su forma de presentación consiste en sachets conteniendo 4 gr de polvo. Las dosis empleadas para la diarrea por MAB deben adaptarse a la respuesta del paciente, con una dosis máxima de 36 gr al día. Los eventos adversos suelen ser dependientes de la dosis, siendo los más frecuentes: malestar gastrointestinal, dispepsia, flatulencia, estreñimiento, náuseas y vómitos. Colestiramina cuenta en Perú con un registro sanitario vigente. Según el observatorio de precios de medicamentos de DIGEMID, el costo más bajo en el sector privado de 100 sobres de colestiramina asciende a S/. 13.00 (S/. 0.13 por cada sobre) mientras que no se hallaron precios disponibles en el sector público. OBJETIVO: Describir la evidencia científica sobre la eficacia y seguridad de colestiramina para el tratamiento de diarrea por malabsorción de ácidos biliares secundaria a resección ileal en población pediátrica. METODOLOGÍA: La búsqueda de evidencia se desarrolló en Medline, Web of Science, The Cochrane Library y LILACS hasta el 04 de octubre de 2021, limitado a estudios en español o inglés. La búsqueda de guías de práctica clínica (GPC) y evaluaciones de tecnología sanitaria (ETS) se desarrolló en repositorios digitales de agencias elaboradoras de estos documentos. Adicionalmente, se realizó una búsqueda de GPC en PubMed. Se valoró el riesgo de sesgo empleado la herramienta de la Colaboración Cochrane. RESULTADOS: No se identificó ningún estudio en población pediátrica. Se consideró como evidencia indirecta cuatro estudios primarios desarrollados en adultos. Frecuencia de deposiciones: El estudio de Hofmann (1969) reportó una reducción en la frecuencia diaria de deposiciones (p<0.05) durante el tratamiento con colestiramina en pacientes con <100 cm de resección ileal, comparado con placebo. En pacientes con >100 cm de íleon resecado (n=8) no se observaron diferencias. Un segundo estudio de Hofmann (1972) reportó una disminución en la frecuencia de deposiciones diarias de pacientes con resección ileal <100 cm tratados con colestiramina y triglicéridos de cadena larga (TCL) o media (TCM), en comparación con solo TCL o TCM. En pacientes con resección ileal >100 cm, colestiramina redujo la frecuencia de deposiciones, aunque la mayor reducción se observó cuando se reemplazó TCL por TCM, ambos sin colestiramina (p<0.025). El estudio de Jacobsen reportó una reducción del número de evacuaciones fecales durante el tratamiento con colestiramina comparado con placebo (15 vs 23, p<0.05). El estudio de Williams reportó una disminución del número de deposiciones al día en pacientes tratados colestiramina comparado con una dieta control (2.3 vs 4.6; p=0.027). Volumen de masa fecal El estudio de Hofmann (1969) reportó que 4 de 6 pacientes con <100 cm de resección ileal alcanzaron una reducción significativa de la masa fecal comparado con placebo (p<0.05). En pacientes con >100 cm de íleon resecado (n=3), colestiramina no produjo reducción significativa de la masa fecal en ningún participante. El estudio de Jacobsen reportó una reducción del volumen de masa fecal durante el tratamiento con colestiramina comparado con placebo (p<0.05). El estudio de Williams reportó una disminución significativa de la masa fecal en pacientes tratados colestiramina comparado con una dieta control de 2000 Kcal con TCL (media: 394 gr/día vs 568 gr/día; p=0.027). Eventos adversos: Ningún estudio informó sobre la presencia de eventos adversos. Recomendaciones en GPC: Las GPC de la Asociación Argentina de Nutrición Enteral y Parenteral (AANEP) y de la Canadian Association of Gastroenterology (CAG) recomiendan colestiramina para el manejo de la MAB. Las GPC de la European Society for Clinical Nutrition and Metabolism (ESPEN), Cleveland Clinic, British Society of Gastroenterology (BSG), y American Gastroenterological Association (AGA) no recomiendan su uso en pacientes con resección ileal extensa. Evaluaciones de Tecnología Sanitaria: Una ETS desarrollada por IETSI concluyó con evidencia limitada aprobar el uso de colestiramina para el tratamiento de pacientes con diarrea crónica por MAB. Sin embargo, su aprobación fue revocada un año después por tratarse de una indicación terapéutica "fuera de etiqueta". Evaluación de la calidad metodológica: Tres estudios tuvieron alto riesgo de sesgo de selección. Dos estudios tuvieron alto riesgo de sesgo de realización y detección. El riesgo de sesgo de reporte fue considerado poco claro en todos los estudios. Todos los estudios fueron considerados como alto riesgo de otro tipo de sesgos por un reporte insuficiente o nulo de las fuentes de financiamiento y el conflicto de interés de los autores. CONCLUSIONES: Los hallazgos sobre la eficacia de colestiramina no fueron concluyentes. Dos estudios reportaron una reducción en la frecuencia de deposiciones y volumen fecal en pacientes tratados con colestiramina, mientras que otros dos estudios mostraron una reducción significativa solo en pacientes con resección ileal <100 cm, y un efecto limitado o nulo en pacientes con resección ileal extensa (>100 cm). No se informaron resultados sobre la seguridad de colestiramina. Los estudios incluidos enrolaron un número pequeño de participantes, con periodos cortos de seguimiento, presentaron alta heterogeneidad en el diseño, características de los participantes e intervenciones, y tuvieron un alto riesgo de sesgo en la mayoría de dimensiones evaluadas. Dos GPC consideran el uso de colestiramina como terapia para pacientes con diarrea por MAB, mientras que cuatro GPC recomiendan limitar su uso en pacientes con resección ileal extensa. Una ETS realizada por IETSI (Perú) concluyó aprobar el uso de colestiramina para el tratamiento de pacientes con diarrea crónica por MAB. Sin embargo, su aprobación fue revocada un año después por tratarse de una indicación terapéutica "fuera de etiqueta".

Antibiotic exposure among young infants suffering from diarrhoea in Bangladesh.

AIMS: Appropriate rehydration has always been significant in treating diarrhoeal diseases in children. Irrational antibiotic use among diarrhoeal children has remained a major public health concern. Information regarding antibiotic use in young infants suffering from diarrhoea is very limited and a unique aspect of research. We aimed to investigate the prevalence of antibiotic use in the community among 2-6 months infants with diarrhoeal illnesses and having different nutritional status. METHODS: We investigated a total of 5279 infants aged 2-6 months at Dhaka hospital, International Centre for Diarrhoeal Disease Research, Bangladesh, between September 2018 and June 2019. Among them, 257 infants were suffering from severe acute malnutrition (SAM). History of taking antibiotics was ascertained by direct observation of a prescription by a physician, the bottle of antibiotic or asking the caregiver about the name of antibiotic or its price that is very close to the usual market price of an antibiotic. RESULTS: Overall, 52% of infants received antibiotics before hospital admission. Non-SAM infants had higher odds of receiving antibiotics (adjusted odds ratio [aOR] = 1.52, 95% confidence interval: 1.18, 1.97, P value = 0.003) compared to infants with SAM and use of antibiotics increased with age (aOR = 1.11, 95% confidence interval: 1.06, 1.17, P value<0.001). Commonly used antibiotics were azithromycin (13.3%), ciprofloxacin (7.7%), erythromycin (7.7%) and metronidazole (2.6%). The proportion of receiving ciprofloxacin was significantly lower in infants with SAM compared to their non-SAM counterparts (2.7% vs. 7.97%, P value = 0.004). CONCLUSIONS: The study underscores the excessive use of antibiotics among diarrhoeal infants, which is already a major public health concern in low- and middle-income countries.

Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial.

BACKGROUND: The World Health Organization recommends 20 mg of zinc per day for 10 to 14 days for children with acute diarrhea; in previous trials, this dosage decreased diarrhea but increased vomiting. METHODS: We randomly assigned 4500 children in India and Tanzania who were 6 to 59 months of age and had acute diarrhea to receive 5 mg, 10 mg, or 20 mg of zinc sulfate for 14 days. The three primary outcomes were a diarrhea duration of more than 5 days and the number of stools (assessed in a noninferiority analysis) and the occurrence of vomiting (assessed in a superiority analysis) within 30 minutes after zinc administration. RESULTS: The percentage of children with diarrhea for more than 5 days was 6.5% in the 20-mg group, 7.7% in the 10-mg group, and 7.2% in the 5-mg group. The difference between the 20-mg and 10-mg groups was 1.2 percentage points (upper boundary of the 98.75% confidence interval [CI], 3.3), and that between the 20-mg and 5-mg groups was 0.7 percentage points (upper boundary of the 98.75% CI, 2.8), both of which were below the noninferiority margin of 4 percentage points. The mean number of diarrheal stools was 10.7 in the 20-mg group, 10.9 in the 10-mg group, and 10.8 in 5-mg group. The difference between the 20-mg and 10-mg groups was 0.3 stools (upper boundary of the 98.75% CI, 1.0), and that between the 20-mg and 5-mg groups was 0.1 stools (upper boundary of the 98.75% CI, 0.8), both of which were below the noninferiority margin (2 stools). Vomiting within 30 minutes after administration occurred in 19.3%, 15.6%, and 13.7% of the patients in the 20-mg, 10-mg, and 5-mg groups, respectively; the risk was significantly lower in the 10-mg group than in the 20-mg group (relative risk, 0.81; 97.5% CI, 0.67 to 0.96) and in the 5-mg group than in the 20-mg group (relative risk, 0.71; 97.5% CI, 0.59 to 0.86). Lower doses were also associated with less vomiting beyond 30 minutes after administration. CONCLUSIONS: Lower doses of zinc had noninferior efficacy for the treatment of diarrhea in children and were associated with less vomiting than the standard 20-mg dose. (Funded by the Bill and Melinda Gates Foundation; ZTDT ClinicalTrials.gov number, NCT03078842.).

Clinical efficacy of oral immunoglobulin Y in infant rotavirus enteritis: Systematic review and meta-analysis.

BACKGROUND: Rotavirus (RV) can cause vomiting and diarrhea in infants and children, and could be treated clinically with immunoglobulin Y (IgY), which is an immunoglobulin extracted from chicken yolk. There is no systematic evaluation of immunoglobulin in the treatment of rotavirus enteritis. Therefore, we systematically evaluated rotavirus enteritis with oral immunoglobulin Y therapy using meta-analysis. METHODS: We conducted a systematic search in CNKI, WANFANG DATA, VIP, PubMed, and the Cochrane Library databases (up to April 30, 2018). Using Revman 5.3 software for meta-analysis. RESULTS: A total of 2626 subjects with rotavirus diarrhea from 17 randomized clinical trials were included in the meta-analysis. Of these, 1347 subjects received oral immunoglobulin Y and 1279 subjects received conventional treatment. The results of the meta-analysis indicated that the total number of effective cases and effective rates of immunoglobulin Y in treatment of rotavirus enteritis in infants and children was statistically different from that in the control group (odds ratio [OR] = 3.87, 95% confidence interval [CI] (3.17, 4.74), P < .00001) and (OR = 3.63, 95% CI [2.75, 4.80], P < .00001). CONCLUSIONS: Immunoglobulin Y is effective in the treatment of infantile rotavirus enteritis. Oral immunoglobulin Y can be widely used in the treatment of rotavirus enteritis in clinic.

Prescription of medications for acute diarrhea in infants in Antananarivo, Madagascar.

AIM: To evaluate the professional practices of physicians in Antananarivo in managing acute diarrhea in infants. METHODS: This prospective study was conducted from March 19 to April 21, 2012, as an anonymous survey of randomly selected general practitioners and pediatricians working in the public or private sector in the city of Antananarivo. RESULTS: The survey included 125 physicians: 105 general practitioners, 11 pediatricians, and 9 other specialist physicians (7.2%) with pediatric activity. Only 4.8% of the physicians questioned had not received training about diarrhea in the previous two years. One doctor in 4 (25.6%) did not prescribe oral rehydration solution. The reasons given were lack of signs of dehydration (50%) and recommendation of other beverages (15.5%). Zinc prescription was rare (9.6%). Early refeeding was recommended by 41.6% of physicians. Almost half (47.2%) routinely use antibiotics, and 86.4% prescribe antidiarrheal medications. CONCLUSION: The WHO recommendations for the treatment of acute diarrhea in children are not followed. Continuing and repeated medical education is necessary.

High doses of Antisecretory Factor stop diarrhea fast without recurrence for six weeks post treatment.

BACKGROUND: Diarrheal illnesses in young children cause morbidity and preventable deaths in developing countries. We evaluated two high doses of Salovum® [Antisecretory Factor] to treat diarrhea in young children and followed up for recurrence 6 weeks post treatment. METHODS: Forty children, 6-24 months old, admitted with acute diarrhea, to the Outpatient Department of Children's Hospital in Lahore, Pakistan were selected. The patients were randomly allocated to either Group A given 2 sachets, or to Group B, given 4 sachets. Each sachet contained 4gram of Salovum® and was mixed with Oral Rehydration Salt solution. This mixture was administered perorally within the first 30min of treatment. The trained nursing staff observed them for number of stools and consistency over every half hour for a total of 4hours. Follow up for 6 weeks was done daily by telephone, or visits by the mothers. The results demonstrate that Salovum provides a protective effect irrespective of the diarrhea causes. RESULTS: Group B, given 4 sachets of Salovum® showed improved fecal consistency in 80% of the children compared to 50% in Group A within 30minutes of treatment, p=0.004. The number of diarrheal stools decreased over this time from seven to one/two over 4hours in the two groups [p=0.234]. None of the children showed a recurrence of diarrhea over the follow up period. CONCLUSION: Peroral high doses of Salovum® rapidly and safely counteract diarrhea in children followed by a diarrhea-free period of 6 weeks.

Meta-analysis of the effects of Bifidobacterium preparations for the prevention and treatment of pediatric antibiotic-associated diarrhea in China.

Bifidobacterium preparations are increasingly used for pediatric antibiotic-associated diarrhea (AAD) in China. The aim of this study was to review existing evidence on the efficacy of Bifidobacterium preparations for the prevention and treatment of pediatric AAD in China. Searches were performed with Medline, Embase, Cochrane Central Register of Controlled Trials, CNKI, and CBM databases. Thirty trials met the inclusion criteria. Of the 30 trials, five Bifidobacterium preparations were included. The preparations were all Bifidobacterium based, in combined with Lactobacillus, Enterococcus, Bacillus, Streptococcus or Clostridium strains. The pooled results of the 30 trials, which included 7225 participants, indicated a statistically significant association of Bifidobacterium preparations administration with reduction in pediatric AAD (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.29-0.39; P<0.01). When the meta-analysis was re-performed according to the trials explicitly aiming to prevent or treat pediatric AAD, respectively, the pooled results were similar (Bifidobacterium preparations use for preventing pediatric AAD (n=21): pooled OR, 0.34, 95% CI, 0.28-0.41, P<0.01; Bifidobacterium preparations use for treating pediatric AAD (n=9): pooled OR, 0.32, 95% CI, 0.23-0.43, P<0.01). Subgroup analyses which based on Bifidobacterium preparations variety, clinical condition, or participant's age also showed statistically significant benefit of adjunct Bifidobacterium preparations for the prevention and treatment of pediatric AAD in China. The pooled evidence suggested that Bifidobacterium preparations might be efficacious for the prevention and treatment of pediatric AAD in China.

The role of maternal anxiety and depressive disorders prior to and during pregnancy and perinatal psychopathological symptoms for early infant diseases and drug administration.

BACKGROUND: Maternal mental health prior to and during pregnancy has been shown to be associated with inflammatory diseases and gastrointestinal complaints in the offspring. Unfortunately, many studies merely focused on perinatal distress without consideration of lifetime anxiety and depressive disorders. AIMS: To prospectively investigate associations of anxiety and depressive disorders prior to and during pregnancy as well as perinatal distress with infants' inflammatory diseases, gastrointestinal complaints and corresponding drug administration. STUDY DESIGN: Prospective-longitudinal study initiated in 2009/2010. SUBJECTS: N=306 (expectant) mothers with and without DSM-IV lifetime anxiety and depressive disorders (Composite International Diagnostic Interview for Women) and low vs. high severity of psychopathological symptoms during pregnancy (Brief Symptom Inventory) enrolled in early pregnancy and repeatedly assessed during peripartum period. OUTCOME MEASURES: Infant inflammatory diseases, gastrointestinal complaints and drug administration assessed via questionnaire (maternal report) at four months postpartum (n=279). RESULTS: Severe psychopathological symptoms during pregnancy were associated with inflammatory diseases and anti-infective medication, whereas anxiety and depressive disorders prior to and during pregnancy were related to gastrointestinal complaints (diarrhea, colic complaints) and corresponding medication. CONCLUSIONS: These results have to be discussed with caution, because information on infants' diseases were based exclusively on maternal self-reports. However, they suggest promising directions regarding our current knowledge about the relevance of maternal perinatal distress for infant inflammatory diseases (e.g. fetal programming). Moreover, the association between maternal anxiety and depressive disorders and infant gastrointestinal complaints may be explained by an anxious misinterpretation of 'normal' infant signals or a transmission of adverse gut microbiota, respectively.

IBD-Like Features in Syndromic Diarrhea/Trichohepatoenteric Syndrome.

BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) (inflammatory bowel disease [IBD] before 6 years of age) may manifest as a monogenic disease affecting the gastrointestinal tract. Syndromic diarrhea/trichohepatoenteric syndrome (SD/THE), a rare disorder caused by alteration of a complex involved in RNA degradation, has been reported to present with some degree of colitis and in some cases an IBD-like presentation. METHODS: We reviewed clinical and biological data of 4 previously published cases and added detailed data of 2 new cases of SD/THE with an IBD-like presentation. RESULTS: All the 6 patients presented with typical intractable diarrhea and hair abnormalities. The colon was affected in all of the patients: 1 had ileitis, 2 had panenteritis, and 2 presented with perianal disease. Fecal calprotectin level and erythrosedimentation rate were elevated in 2 cases each. All the therapeutic classes of IBD treatment (mesalazine, steroids, immunomodulators, and biological therapy) were used in the 6 cases. In 2 patients, treatment had no effect. Three showed a partial effect, and 1 patient sustained only a transient effect. CONCLUSIONS: SD/THE can have a similar presentation as VEOIBD, often as pancolitis. IBD treatments appear to have little efficacy for SD/THE, suggesting a different pathogenesis for the IBD-like features in SD/THE compared with classical IBD.

Oral zinc for treating diarrhoea in children.

BACKGROUND: In developing countries, diarrhoea causes around 500,000 child deaths annually. Zinc supplementation during acute diarrhoea is currently recommended by the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF). OBJECTIVES: To evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library 2016, Issue 5), MEDLINE, Embase, LILACS, CINAHL, mRCT, and reference lists up to 30 September 2016. We also contacted researchers. SELECTION CRITERIA: Randomized controlled trials (RCTs) that compared oral zinc supplementation with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery. DATA COLLECTION AND ANALYSIS: Both review authors assessed trial eligibility and risk of bias, extracted and analysed data, and drafted the review. The primary outcomes were diarrhoea duration and severity. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses (using either a fixed-effect or random-effects model) and assessed heterogeneity.We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: Thirty-three trials that included 10,841 children met our inclusion criteria. Most included trials were conducted in Asian countries that were at high risk of zinc deficiency. Acute diarrhoeaThere is currently not enough evidence from well-conducted RCTs to be able to say whether zinc supplementation during acute diarrhoea reduces death or number of children hospitalized (very low certainty evidence).In children older than six months of age, zinc supplementation may shorten the average duration of diarrhoea by around half a day (MD -11.46 hours, 95% CI -19.72 to -3.19; 2581 children, 9 trials, low certainty evidence), and probably reduces the number of children whose diarrhoea persists until day seven (RR 0.73, 95% CI 0.61 to 0.88; 3865 children, 6 trials, moderate certainty evidence). In children with signs of malnutrition the effect appears greater, reducing the duration of diarrhoea by around a day (MD -26.39 hours, 95% CI -36.54 to -16.23; 419 children, 5 trials, high certainty evidence).Conversely, in children younger than six months of age, the available evidence suggests zinc supplementation may have no effect on the mean duration of diarrhoea (MD 5.23 hours, 95% CI -4.00 to 14.45; 1334 children, 2 trials, moderate certainty evidence), or the number of children who still have diarrhoea on day seven (RR 1.24, 95% CI 0.99 to 1.54; 1074 children, 1 trial, moderate certainty evidence).None of the included trials reported serious adverse events. However, zinc supplementation increased the risk of vomiting in both age groups (children greater than six months of age: RR 1.57, 95% CI 1.32 to 1.86; 2605 children, 6 trials, moderate certainty evidence; children less than six months of age: RR 1.54, 95% CI 1.05 to 2.24; 1334 children, 2 trials, moderate certainty evidence). Persistent diarrhoeaIn children with persistent diarrhoea, zinc supplementation probably shortens the average duration of diarrhoea by around 16 hours (MD -15.84 hours, 95% CI -25.43 to -6.24; 529 children, 5 trials, moderate certainty evidence). AUTHORS' CONCLUSIONS: In areas where the prevalence of zinc deficiency or the prevalence of malnutrition is high, zinc may be of benefit in children aged six months or more. The current evidence does not support the use of zinc supplementation in children less six months of age, in well-nourished children, and in settings where children are at low risk of zinc deficiency.

Correlation of Clinical Outcomes With Multiplex Molecular Testing of Stool From Children Admitted to Hospital With Gastroenteritis in Botswana.

BACKGROUND: Diarrheal disease is a leading cause of death for young children. Most pediatric gastroenteritis is caused by viral pathogens; consequently, current recommendations advocate against routine antibacterial therapy if children present without bloody stools. METHODS: In this prospective cohort study, we enrolled children with severe acute gastroenteritis admitted to hospital in Botswana. Details of presenting history, physical examination, and course in the hospital were recorded. Stool samples were characterized using a 15 pathogen polymerase chain reaction assay. RESULTS: There were 671 participants with a median age of 8.3 months; 77 (11%) had severe acute malnutrition. Only 74 children had bloody stools, of whom 48 (65%) had a detectable bacterial pathogen, compared to 195 of 592 (33%) of those without. There were 26 deaths (3.9%). Covariates associated with death in multivariable logistic regression were the detection of any of Campylobacter/Shigella/enterotoxigenic Escherichia coli (odds ratio [OR] 2.57, 95% confidence interval [CI] 1.07-6.17), severe acute malnutrition (OR 4.34, 95% CI 1.79-10.5), and antibiotic therapy (OR 8.82, 95% CI 2.03-38.2). There was no significant association between bloody stools and death, and the effect of Campylobacter/Shigella/enterotoxigenic E. coli infection on death was not modified by the presence of bloody stools. CONCLUSIONS: Detection of bacterial enteropathogens is associated with increased mortality in children in sub-Saharan Africa. Unfortunately, most children with these infections do not have bloody stools, and bloody dysentery was not found to be associated with worse outcomes. Clinical trials evaluating outcomes associated with more aggressive diagnostic strategies in children presenting with severe acute gastroenteritis in sub-Saharan Africa should be undertaken.

The Influence of Episode Severity on Caregiver Recall, Care-seeking, and Treatment of Diarrhea Among Children 2-59 Months of Age in Bihar, Gujarat, and Uttar Pradesh, India.

Increased diarrheal episode severity has been linked to better 2-week recall and improved care-seeking and treatment among caregivers of children under five. Using cross-sectional data from three Indian states, we sought to assess the relationship between episode severity and the recall, care-seeking, and treatment of childhood diarrhea. Recall error was higher for episodes with onset 8-14 days (31.2%) versus 1-7 days (4.8%) before the survey, and logistic regression analysis showed a trend toward increased severity of less recent compared with more recent episodes. This finding indicates that data collection with 2-week recall underestimates diarrhea prevalence while overestimating the proportion of severe episodes. There was a strong correlation between care-seeking and dehydration, fever, vomiting, and increased stool frequency and duration. Treatment with oral rehydration salts was associated with dehydration, vomiting, and higher stool frequency, and trends were established between therapeutic zinc supplementation and increased duration and stool frequency. However, state and care-seeking sector were stronger determinants of treatment than episode severity, illustrating the need to address disparities in treatment quality across regions and delivery channels. Our findings are of importance to researchers and diarrhea management program evaluators aiming to produce accurate estimates of diarrheal outcomes and program impact in low- and middle-income countries.

Efficacy and safety of diosmectite in acute childhood diarrhoea: a meta-analysis.

OBJECTIVE: We evaluated the role of diosmectite as an add-on treatment to the 'recommended treatment' of acute diarrhoea in children. METHODS: We searched all published literature through the major databases: Medline via Ovid, PubMed, CENTRAL, Embase and Google Scholar till May 2014. Randomised clinical trials comparing diosmectite versus placebo were included (PROSPERO registration: CRD42014013783). MAIN OUTCOME MEASURES: The primary outcome measures were duration of acute diarrhoea (h), and day-to-day cure rates (%). The secondary outcome measures were stool output (volume), stool output (frequency) and adverse events. RESULTS: Of 384 citations retrieved, a total of 13 randomised clinical trials (2164 children, 1-60 months old) were included in the meta-analysis. A dose of 3-6 grams per day of diosmectite was given for a duration from 3 days until recovery. Compared with placebo, diosmectite significantly decreased the duration of acute diarrhoea (mean difference, -23.39; 95% CI -28.77 to -18.01), and increased the cure rate (%) at day 5 (OR, 4.44; 95% CI 1.66 to 11.84), without any increases in the risk of adverse events. Diosmectite was effective in all types of acute childhood diarrhoea except dysentery. Because, most of the trials were open-label, and there was a high possibility of publication bias, the GRADE evidence generated was of 'low quality'. CONCLUSIONS: Diosmectite may be a useful additive in the treatment of acute childhood diarrhoea. As the evidence generated was of 'low quality', future research is needed with higher quality designs before any firm recommendations can be made. TRIAL REGISTRATION NUMBER: PROSPERO registration: CRD42014013783.

Diarrheagenic Escherichia coli phylogroups are associated with antibiotic resistance and duration of diarrheal episode.

Conventionally, in Escherichia coli, phylogenetic groups A and B1 are associated with commensal strains while B2 and D are associated with extraintestinal strains. The aim of this study was to evaluate diarrheagenic (DEC) and commensal E. coli phylogeny and its association with antibiotic resistance and clinical characteristics of the diarrheal episode. Phylogenetic groups and antibiotic resistance of 369 E. coli strains (commensal strains and DEC from children with or without diarrhea) isolated from Peruvian children <1 year of age were determined by a Clermont triplex PCR and Kirby-Bauer method, respectively. The distribution of the 369 E. coli strains among the 4 phylogenetic groups was A (40%), D (31%), B1 (21%), and B2 (8%). DEC-control strains were more associated with group A while DEC-diarrhea strains were more associated with group D (P < 0.05). There was a tendency (P = 0.06) for higher proportion of persistent diarrhea (≥ 14 days) among severe groups (B2 and D) in comparison with nonsevere groups (A and B1). Strains belonging to group D presented significantly higher percentages of multidrug resistance than the rest of the groups (P > 0.01). In summary, DEC-diarrhea strains were more associated with group D than strains from healthy controls.

Guía de práctica clínica ibero-latinoamericana sobre el manejo de la gastroenteritis aguda en menores de 5 años: tratamiento farmacológico / No disponible

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[A multicenter randomized parallel-controlled study on the efficacy and safety of er xie ting granules in children with acute diarrhea].

OBJECTIVE: To evaluate the efficacy and safety of ER XIE TING GRANULES in children with acute diarrhea. METHOD: A multicenter, randomized, open-label, parallel-controlled clinical trial was carried out in 15 hospitals during March 2011 to July 2012. A total of 1489 children with acute diarrhea were enrolled and divided randomly into two groups and treated with ER XIE TING GRANULES (treatment group) and smectite powder (control group). The therapeutic efficacy and adverse drug reactions were evaluated after three-day and seven-day therapy.Superiority or non-inferiority test was done for effectiveness of the treatment based on efficacy differ by more than 10% regarded as the superiority. RESULT: Totally 1458 children completed the study, in whom 726 children received ER XIE TING GRANULES and 732 received smectite powder. After three-day and seven-day therapy, cure rates and total efficacy rates of the treatment group were 44.2%, 94.1%, 88.8%, and 97.9% separately and higher than those of control group (39.3%, 88.4%, 83.9%, 97.4%) ( Z = 3.2, P < 0.01; Z = 2.46, P < 0.05). There were 520 children with rotavirus infection and in whom 266 cases received ER XIE TING GRANULES and 254 received smectite powder. For rotavirus enteritis, cure rates and total efficacy rates of the treatment group after three-day and seven-day therapy were 40.6%, 95.1%, 89.9%, and 98.9% separately and higher than those of control group (26.4%, 84.3%, 78.8%, and 96.8%) (Z = 4.807, P < 0.01;Z = 3.519, P < 0.01). The lower limits of the 95% confidence interval of difference of cure rate and total efficacy rates after three-day and seven-day therapy between two groups were less than 10%.No obvious drug related adverse reactions were found during the study. CONCLUSION: ER XIE TING GRANULES has the same effect for treatment of acute diarrhea and rotavirus enteritis in children.No obvious drug related adverse reactions were found.

[Meta analysis of effectiveness of acupoint application therapy for infantile diarrhea].

OBJECTIVE: To analyze the effectiveness of acupoint application therapy for infantile diarrhea so as to provide an objective evidence for clinical decision making. METHODS: The authors of the present paper did a literature retrieval using The China National Knowledge Infrastructure (CNKI) database, Chinese bio-medical database and Wanfang database covering the period of January 1, 1990-June 30, 2012, and made a systemic evaluation on the retrieved randomized controlled clinical trials (RCTs) of acupoint application therapy for infantile diarrhea using Cochrane system evaluation method. Following excluding the repetitive, irrelevant and non-randomized controlled trials, those meeting the standards of randomized controlled trials were collected. Trial quality was assessed using the Jadad score which evaluates the randomization process, blinding, and the description of withdrawals or dropouts. The RevMan 5. 1 software was used to make statistical analysis. RESULTS: A total of 16 papers (2,151 patients) were included in the Meta analysis. The homogeneity test was better (chi2 = 8.09, P = 0.92, I2 = 0%), displaying a homogenicity of most studies. Meta analysis showed the merger effect quantity odds ratio (OR) = 4.68, and 95% confidence intervals (CIs): 3.41, 6.42, and the merger effect value test Z = 9.58, P < 0.00001. Statistical difference indicates a better therapeutic effect of acupoint application group than the control group, providing evidence in favor of acupoint application therapy for infantile diarrhea. Funnel chart displays that the researched object distribution is symmetric, being smaller in the bias. But the potential publication bias still possibly exists. CONCLUSION: Acupoint application therapy for infantile diarrhea has some advantages, which needs further confirmation due to lower quality of the collected literatures. Larger sample, high quality and randomized controlled clinical trials are highly recommended.

Vitamin D3supplementation and childhood diarrhea: a randomized controlled trial.

OBJECTIVE: To investigate the effect of vitamin D3 supplementation on the incidence and risk for first and recurrent diarrheal illnesses among children in Kabul, Afghanistan. METHODS: This double-blind placebo-controlled trial randomized 3046 high-risk 1- to 11-month-old infants to receive 6 quarterly doses of oral vitamin D3 (cholecalciferol 100000 IU) or placebo in inner city Kabul. Data on diarrheal episodes (≥ 3 loose/liquid stools in 24 hours) was gathered through active and passive surveillance over 18 months of follow-up. Time to first diarrheal illness was analyzed by using Kaplan-Meier plots. Incidence rates and hazard ratios (HRs) were calculated by using recurrent event Poisson regression models. RESULTS: No significant difference existed in survival time to first diarrheal illness (log rank P = .55). The incidences of diarrheal episodes were 3.43 (95% confidence interval [CI], 3.28-3.59) and 3.59 per child-year (95% CI, 3.44-3.76) in the placebo and intervention arms, respectively. Vitamin D3 supplementation was found to have no effect on the risk for recurrent diarrheal disease in either intention-to-treat (HR, 1.05; 95% CI, 0.98-1.17; P = .15) or per protocol (HR, 1.05; 95% CI, 0.98-1.12; P = .14) analyses. The lack of preventive benefit remained when the randomized population was stratified by age groups, nutritional status, and seasons. CONCLUSIONS: Quarterly supplementation with vitamin D3 conferred no reduction on time to first illness or on the risk for recurrent diarrheal disease in this study. Similar supplementation to comparable populations is not recommended. Additional research in alternative settings may be helpful in elucidating the role of vitamin D3 supplementation for prevention of diarrheal diseases.