Polymer-based oral rehydration solution for treating acute watery diarrhoea.

BACKGROUND: Acute diarrhoea is one of the main causes of morbidity and mortality among children in low-income countries. Glucose-based oral rehydration solution (ORS) helps replace fluid and prevent further dehydration from acute diarrhoea. Since 2004, the World Health Organization (WHO) has recommended the osmolarity of less than 270 mOsm/L (ORS ≤ 270) versus greater than 310 mOsm/L formulation (ORS ≥ 310). Polymer-based ORS (for example, prepared using rice or wheat) slowly releases glucose and may be superior to glucose-based ORS. OBJECTIVES: To compare polymer-based oral rehydration solution (polymer-based ORS) with glucose-based oral rehydration solution (glucose-based ORS) for treating acute watery diarrhoea. SEARCH METHODS: We searched the following sources up to 5 September 2016: the Cochrane Infectious Diseases Group (CIDG) Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 9), MEDLINE (1966 to 5 September 2016), EMBASE (1974 to 5 September 2016), LILACS (1982 to 5 September 2016), and mRCT (2007 to 5 September 2016). We also contacted researchers, organizations, and pharmaceutical companies, and searched reference lists. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of people with acute watery diarrhoea (cholera and non-cholera associated) that compared polymer-based and glucose-based ORS (with identical electrolyte contents). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results and risk of bias, and extracted data. In multiple-treatment arms with two or more treatment groups, we combined outcomes as appropriate and compared collectively with the control group. MAIN RESULTS: Thirty-five trials that included 4284 participants met the inclusion criteria: 28 trials exclusively included children, five included adults, and two included both adults and children. Polymer-based ORS versus glucose-based ORS (osmolarity ≤ 270) Eight trials (752 participants) evaluated this comparison, and seven trials used rice as a polymer source. Polymer-based ORS may decrease mean stool output in the first 24 hours by 24 mL/kg (mean difference (MD) -24.60 mL/kg, 95% CI -40.69 to -8.51; one trial, 99 participants, low quality evidence). The average duration of diarrhoea may be reduced by eight hours (MD -8.24 hours, 95% CI -13.17 to -3.30; I² statistic = 86%, five trials, 364 participants, low quality evidence) with polymer ORS but results are heterogeneous. Limited trials showed no observed difference in the risk of unscheduled use of intravenous fluid (RR 0.66, 95% CI 0.43 to 1.02; I² statistic = 30%; four trials, 376 participants, very low quality evidence), vomiting (very low quality evidence), and hyponatraemia (very low quality evidence). Polymer-based ORS versus glucose-based ORS (osmolarity ≥ 310) Twenty-seven trials (3532 participants) evaluated this comparison using a variety of polymers. On average, polymer ORS may reduce the total stool output in the first 24 hours by around 65 mL/kg (MD -65.47 mL/kg, 95% CI -83.92 to -47.03; 16 trials, 1483 participants, low quality evidence), and may reduce the duration of diarrhoea by around eight hours (MD -8.57 hours; SD -13.17 to -4.03; 16 trials, 1137 participants, low quality evidence) with substantial heterogeneity. The proportion of participants that required intravenous hydration was low in most trials with fewer in the polymer ORS group (RR 0.75, 95% CI 0.57 to 0.98; 19 trials, 1877 participant, low quality evidence) . Subgroup analysis by type of pathogen suggested an effect on unscheduled intravenous fluid in those infected with mixed pathogens (RR 0.63, 95% CI 0.41 to 0.96; 11 trials, 928 participants, low quality evidence), but not in participants positive for Vibrio cholerae (RR 0.94, 95% CI 0.66 to 1.34; 7 trials, 535 participants, low quality evidence). No difference was observed in the number of patients who developed vomiting (RR 0.91, 95% CI 0.72 to 1.14; 10 trials, 584 participants, very low quality evidence), hyponatraemia (RR 1.82, 95% CI 0.52 to 6.44; 4 trials, 385 participants, very low quality evidence), hypokalaemia (RR 1.29, 95% CI 0.74 to 2.25; 2 trials, 260 participants, low quality evidence), or persistent diarrhoea (RR 1.28, 95% CI 0.68 to 2.41; 2 trials, 885 participants, very low quality evidence). AUTHORS' CONCLUSIONS: Polymer-based ORS shows advantages compared to glucose-based ORS (at ≥ 310 mOsm/L). Comparisons favoured polymer-based ORS over ORS ≤ 270 but analysis was underpowered.

Congenital Tonic Pupils Associated With Congenital Central Hypoventilation Syndrome and Hirschsprung Disease.

Autonomic dysfunction can be associated with pupillary abnormalities. We describe a rare association of tonic pupils, congenital central hypoventilation syndrome, and Hirschsprung disease in a newborn with a mutation in the PHOX2B gene, a key regulator of neural crest cells. Hirschsprung disease is characterized by the congenital absence of neural crest-derived intrinsic ganglion cells. Tonic pupils may result from an abnormality of the ciliary ganglion, another structure of neural crest origin. The close association of these conditions in this child suggests a common abnormality in neural crest migration and differentiation.

Estrogen Metabolite 16α-Hydroxyestrone Exacerbates Bone Morphogenetic Protein Receptor Type II-Associated Pulmonary Arterial Hypertension Through MicroRNA-29-Mediated Modulation of Cellular Metabolism.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a proliferative disease of the pulmonary vasculature that preferentially affects women. Estrogens such as the metabolite 16α-hydroxyestrone (16αOHE) may contribute to PAH pathogenesis, and alterations in cellular energy metabolism associate with PAH. We hypothesized that 16αOHE promotes heritable PAH (HPAH) via microRNA-29 (miR-29) family upregulation and that antagonism of miR-29 would attenuate pulmonary hypertension in transgenic mouse models of Bmpr2 mutation. METHODS AND RESULTS: MicroRNA array profiling of human lung tissue found elevation of microRNAs associated with energy metabolism, including the miR-29 family, among HPAH patients. miR-29 expression was 2-fold higher in Bmpr2 mutant mice lungs at baseline compared with controls and 4 to 8-fold higher in Bmpr2 mice exposed to 16αOHE 1.25 µg/h for 4 weeks. Blot analyses of Bmpr2 mouse lung protein showed significant reductions in peroxisome proliferator-activated receptor-γ and CD36 in those mice exposed to 16αOHE and protein derived from HPAH lungs compared with controls. Bmpr2 mice treated with anti-miR-29 (20-mg/kg injections for 6 weeks) had improvements in hemodynamic profile, histology, and markers of dysregulated energy metabolism compared with controls. Pulmonary artery smooth muscle cells derived from Bmpr2 murine lungs demonstrated mitochondrial abnormalities, which improved with anti-miR-29 transfection in vitro; endothelial-like cells derived from HPAH patient induced pluripotent stem cell lines were similar and improved with anti-miR-29 treatment. CONCLUSIONS: 16αOHE promotes the development of HPAH via upregulation of miR-29, which alters molecular and functional indexes of energy metabolism. Antagonism of miR-29 improves in vivo and in vitro features of HPAH and reveals a possible novel therapeutic target.

A randomized controlled trial on the efficacy and safety of a modified ready to use therapeutic food among malnourished children

RATIONALE: In the Philippines, 25% of children OBJECTIVE: To determine the efficacy, safety and acceptability of a modified RUTF (mRUTF) to supplement caloric intake. METHOD: One hundred (100) children 18 months to 10 years old with mild to moderate malnutrition were randomized to either mRUTF or control group. The treatment arm received mRUTF during weekdays for 5 weeks while controls had no supplementation. Anthropometric measurements were taken at baseline, weekly for 5 weeks and 2 weeks post-supplementation. RESULTS: The two groups were comparable at baseline. At five weekly intervals, there was no significant difference in weight, height and mid upper arm circumference between groups, although the mean percentage weight gain of the mRUTF group was higher compared with controls (8% vs 2.6%, p=0.15). Cessation of supplementation resulted in weight loss in the mRUTF group. [mRUTF: -0.40 (0.33) vs -0.03 (0.35), p=0.00]. The taste of mRUTF was acceptable. CONCLUSION: Ready-to-use-therapeutic food is an effective, safe and acceptable alternative supplement for children, 18 months to 10 years old, with mild to moderate malnutrition.

A five year review of pancreatitis among Filipino children

BACKGROUND: Pancreatitis is uncommon in childhood and there is presently no study among Filipino children. OBJECTIVE: To determine the clinical features and outcome of pancreatitis among Filipino children. METHOD: Review of medical records of all patients diagnosed to have pancreatitis based on standard criteria from 2005 to 2009. RESULTS: A total of 23 children (mean age: 12 years; 13 male, 10 female) were included, 21 with acute and two with chronic pancreatitis. Twenty one (91%) presented with abdominal pain and two with jaundice. Nine had idiopathic pancreatitis. In 14 patients, the etiology was identified: bile duct obstruction (7), trauma (2), drugs (2), infection (2) and hypertriglyceridemia (1). Only four of 20 patients with ultrasound examination showed an enlarged pancreas. Complications were pseudocyst formation (6), pancreatic abscess (4), diabetes mellitus (2) and hypocalcemia (1). Of the 23 patients, eight required surgery: pancreatic debridement (4), choledochal cyst excision (2), cholecystectomy (1) and Whipple's procedure (1). All pseudocyst resolved spontaneously. One patient with pancreatic tumor declined surgery and another with pancreatitis due to choledochal cyst died of sepsis. CONCLUSIONS: In our study, severe abdominal pain was the most frequent presenting symptom of childhood pancreatitis. Sixty percent had an identifiable cause for pancreatitis. A favorable outcome was observed.

Probiotics for treating acute infectious diarrhoea.

BACKGROUND: Probiotics may offer a safe intervention in acute infectious diarrhoea to reduce the duration and severity of the illness. OBJECTIVES: To assess the effects of probiotics in proven or presumed acute infectious diarrhoea. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group's trials register (July 2010), the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2010), MEDLINE (1966 to July 2010), EMBASE (1988 to July 2010), and reference lists from studies and reviews. We also contacted organizations and individuals working in the field, and pharmaceutical companies manufacturing probiotic agents. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of the trial and extracted data. Primary outcomes were the mean duration of diarrhoea, stool frequency on day 2 after intervention and ongoing diarrhoea on day 4. A random-effects model was used. MAIN RESULTS: Sixty-three studies met the inclusion criteria with a total of 8014 participants. Of these, 56 trials recruited infants and young children. The trials varied in the definition used for acute diarrhoea and the end of the diarrhoeal illness, as well as in the risk of bias. The trials were undertaken in a wide range of different settings and also varied greatly in organisms tested, dosage, and participants' characteristics. No adverse events were attributed to the probiotic intervention.Probiotics reduced the duration of diarrhoea, although the size of the effect varied considerably between studies.The average of the effect was significant for mean duration of diarrhoea (mean difference 24.76 hours; 95% confidence interval 15.9 to 33.6 hours; n=4555, trials=35) diarrhoea lasting ≥4 days (risk ratio 0.41; 0.32 to 0.53; n=2853, trials=29) and stool frequency on day 2 (mean difference 0.80; 0.45 to 1.14; n=2751, trials=20).The differences in effect size between studies was not explained by study quality, probiotic strain, the number of different strains, the viability of the organisms, dosage of organisms, the causes of diarrhoea, or the severity of the diarrhoea, or whether the studies were done in developed or developing countries. AUTHORS' CONCLUSIONS: Used alongside rehydration therapy, probiotics appear to be safe and have clear beneficial effects in shortening the duration and reducing stool frequency in acute infectious diarrhoea. However, more research is needed to guide the use of particular probiotic regimens in specific patient groups.

Antiamoebic drugs for treating amoebic colitis.

BACKGROUND: Entamoeba histolytica infection is common in developing countries, and up to 100,000 individuals with severe disease die every year. Adequate therapy for amoebic colitis is necessary to reduce the severity of illness, prevent development of complicated disease and extraintestinal spread, and decrease transmission. OBJECTIVES: To evaluate antiamoebic drugs for treating amoebic colitis. SEARCH STRATEGY: In September 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (2008, Issue 3), MEDLINE, EMBASE, LILACS, mRCT, and conference proceedings. We contacted individual researchers, organizations, and pharmaceutical companies, and checked reference lists. SELECTION CRITERIA: Randomized controlled trials of antiamoebic drugs given alone or in combination, compared with placebo or another antiamoebic drug for treating adults and children diagnosed with amoebic colitis. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the eligibility and methodological quality of trials, and extracted and analysed the data. We calculated clinical and parasitological failure rates, relapse, and adverse events as risk ratios (RR) with 95% confidence intervals (CIs), using a random-effects model. We determined statistical heterogeneity and explored possible sources of heterogeneity using subgroup analyses. We carried out sensitivity analysis using trial quality to assess the robustness of the results. MAIN RESULTS: Thirty-seven trials, enrolling 4487 participants, met the inclusion criteria. Only one trial used adequate methods for randomization and allocation concealment, was blinded, and analysed all randomized participants. Only one trial used a E. histolytica stool antigen test. Tinidazole reduced clinical failure compared with metronidazole (RR 0.28, 95% CI 0.15 to 0.51; 477 participants, eight trials) and was associated with fewer adverse events. Compared with metronidazole, combination therapy resulted in fewer parasitological failures (RR 0.36, 95% CI 0.15 to 0.86; 720 participants, 3 trials). AUTHORS' CONCLUSIONS: Tinidazole is more effective in reducing clinical failure compared with metronidazole and has fewer associated adverse events. Combination drug therapy is more effective in reducing parasitological failure compared with metronidazole alone. However, these results are based on trials with poor methodological quality so there is uncertainty in these conclusions. Further trials of the efficacy of antiamoebic drugs, with better methodological quality, are recommended. More accurate tests to detect E. histolytica are needed, particularly in countries where concomitant infection with other bacteria and parasites is common.

Polymer-based oral rehydration solution for treating acute watery diarrhoea.

BACKGROUND: Acute diarrhoea is one of the principal causes of morbidity and mortality among children in low-income countries. Glucose-based ORS helps replace fluid and prevent further dehydration from acute diarrhoea. Since 2004, the World Health Organization has recommended the osmolarity < 270 mOsm/L (ORS 310 mOsm/L formulation (ORS >/= 310). Glucose polymer-based ORS (eg prepared using rice or wheat) slowly releases glucose and may be superior. OBJECTIVES: To compare polymer-based ORS with glucose-based ORS for treating acute watery diarrhoea. SEARCH STRATEGY: In September 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 3), MEDLINE, EMBASE, LILACS, and mRCT. We also contacted researchers, organizations, and pharmaceutical companies, and searched reference lists. SELECTION CRITERIA: Randomized controlled trials of people with acute watery diarrhoea (cholera and non-cholera associated) comparing polymer-based and glucose-based ORS (with identical electrolyte contents). DATA COLLECTION AND ANALYSIS: Two authors independently assessed the search results and risk of bias, and extracted data. In multiple treatment arms with two or more treatment groups, we combined outcomes as appropriate and compared collectively with the control group. MAIN RESULTS: Thirty-four trials involving 4214 participants met the inclusion criteria: 27 in children, five in adults and two in both. Twelve trials used adequate methods to conceal allocation. Most compared polymer-based ORS with ORS >/= 310. There were fewer unscheduled intravenous infusions in the polymer-based ORS group compared with glucose-based ORS (ORS >/= 310 and /= 310 for treating all-cause diarrhoea, and in diarrhoea caused by cholera. Comparisons favoured the polymer-based ORS over ORS

Amoebic dysentery.

INTRODUCTION: Amoebic dysentery is caused by the protozoan parasite Entamoeba histolytica. It is transmitted in areas where poor sanitation allows contamination of drinking water and food with faeces. In these areas, up to 40% of people with diarrhoea may have amoebic dysentery. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of drug treatments for amoebic dysentery in endemic areas? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 11 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: emetine, metronidazole, ornidazole, paromomycin, secnidazole, and tinidazole.