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To improve our understanding of adherence to discharge medications in the ED and within research trials, we sought to quantify medication adherence and identify predictors thereof in children with acute gastroenteritis (AGE). We conducted a secondary analysis of a randomized trial of twice daily probiotic for 5 days. The population included previously healthy children aged 3-47 months with AGE. The primary outcome was patient-reported adherence to the treatment regimen, defined a priori as having received >70% of the prescribed doses. Secondary outcomes included predictors of treatment adherence and concordance between patient-reported adherence and the returned medication sachet counts. After excluding participants with missing data on adherence, 760 participants were included in this analysis: 383 in the probiotic arm (50.4%); and 377 in the placebo arm (49.6%). Self-reported adherence was similar in both groups (77.0% in probiotic versus 80.3% in placebo). There was good agreement between self-reported adherence and sachet counts (87% within limits of agreement (-2.9 to 3.5 sachets) on the Bland-Altman plots). In the multivariable regression model, covariates associated with adherence were greater number of days of diarrhea post-emergency department visit, and the study site; covariates negatively associated with adherence were age 12-23 months, severe dehydration and greater total number of vomiting and diarrhea episodes after enrolment. Longer duration of diarrhea and study site were associated with higher probiotic adherence. Age 12-23 months, severe dehydration and greater number of vomiting and diarrhea episodes post enrolment negatively predicted treatment adherence.

PurposeWhilst there is evidence to suggest that hypohydration caused by physical work in the heat increases renal injury, whether this is the case during exercise in temperate conditions remains unknown. This study investigated the effect of manipulating hydration status during high-intensity intermittent running on biomarkers of renal injury.MethodsAfter familiarisation, 14 males (age: 33 ± 7 years; V̇O2peak: 57.1 ± 8.6 ml/kg/min; mean ± SD) completed 2 trials in a randomised cross-over design, each involving 6, 15 min blocks of shuttle running (modified Loughborough Intermittent Shuttle Test protocol) in temperate conditions (22.3 ± 1.0 °C; 47.9 ± 12.9% relative humidity). During exercise, subjects consumed either a volume of water equal to 90% of sweat losses (EU) or 75 mL water (HYP). Body mass, blood and urine samples were taken pre-exercise (baseline/pre), 30 min post-exercise (post) and 24 h post-baseline (24 h).ResultsPost-exercise, body mass loss, serum osmolality and urine osmolality were greater in HYP than EU (P ≤ 0.024). Osmolality-corrected urinary kidney injury molecule-1 (uKIM-1) concentrations were increased post-exercise (P ≤ 0.048), with greater concentrations in HYP than EU (HYP: 2.76 [1.72–4.65] ng/mOsm; EU: 1.94 [1.1–2.54] ng/mOsm; P = 0.003; median [interquartile range]). Osmolality-corrected urinary neutrophil gelatinase-associated lipocalin (uNGAL) concentrations were increased post-exercise (P < 0.001), but there was no trial by time interaction effect (P = 0.073).ConclusionThese results suggest that hypohydration produced by high-intensity intermittent running increases renal injury, compared to when euhydration is maintained, and that the site of this increased renal injury is at the proximal tubules.

Purpose Hypohydration has been suggested as a predisposing factor for several pathologies including cardiovascular diseases (CVD). While CVD are the leading cause of death worldwide, no study has investigated whether acute hypohydration affects endothelial function and cardiovascular function. Methods Ten young, healthy males participated in this crossover study (age: 24.3 ± 2.3 year; weight: 80.8 ± 5.3 kg; BMI: 24.3 ± 0.4 kg m −2 ). Each subject completed two measurements of endothelial function by flow-mediated dilation (FMD) in euhydrated and hypohydrated state separated by 24 h. Following baseline assessment of hydration status and FMD, the subjects completed 100 min of low-intensity intermittent walking exercise to achieve hypohydration of −2 % of individual body mass. For the rest of the day, a standardized, low water content diet was provided. The following morning, hydration markers and endothelial function were recorded. Results Hypohydration by −1.9 ± 0.1 % of body mass resulted in decreased plasma volume by −3.5 ± 1.8 % and increased plasma osmolality by 9 ± 2 mmol kg −1 ( P  < 0.001). FMD as a response to hypohydration decreased by −26.8 ± 3.9 % ( P  < 0.05). Conclusion The data suggested that a small degree of hypohydration induced by moderate exercise and fluid restriction significantly impaired endothelial function.

World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth. To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear growth. The Antibiotics for Children with Diarrhea (ABCD) trial was a multicountry, randomized, double-blind, clinical trial among 8266 high-risk children aged 2 to 23 months presenting with acute nonbloody diarrhea. Participants were recruited between July 1, 2017, and July 10, 2019, from 36 outpatient hospital departments or community health centers in a mixture of urban and rural settings in Bangladesh, India, Kenya, Malawi, Mali, Pakistan, and Tanzania. Each participant was followed up for 180 days. Primary analysis included all randomized participants by intention to treat. Enrolled children were randomly assigned to receive either oral azithromycin, 10 mg/kg, or placebo once daily for 3 days in addition to standard WHO case management protocols for the management of acute watery diarrhea. Primary outcomes included all-cause mortality up to 180 days after enrollment and linear growth faltering 90 days after enrollment. A total of 8266 children (4463 boys [54.0%]; mean [SD] age, 11.6 [5.3] months) were randomized. A total of 20 of 4133 children in the azithromycin group (0.5%) and 28 of 4135 children in the placebo group (0.7%) died (relative risk, 0.72; 95% CI, 0.40-1.27). The mean (SD) change in length-for-age z scores 90 days after enrollment was -0.16 (0.59) in the azithromycin group and -0.19 (0.60) in the placebo group (risk difference, 0.03; 95% CI, 0.01-0.06). Overall mortality was much lower than anticipated, and the trial was stopped for futility at the prespecified interim analysis. The study did not detect a survival benefit for children from the addition of azithromycin to standard WHO case management of acute watery diarrhea in low-resource settings. There was a small reduction in linear growth faltering in the azithromycin group, although the magnitude of this effect was not likely to be clinically significant. In low-resource settings, expansion of antibiotic use is not warranted. Adherence to current WHO case management protocols for watery diarrhea remains appropriate and should be encouraged. ClinicalTrials.gov Identifier: NCT03130114.

ObjectiveThe objective was to assess the association between nutritional and clinical characteristics and quantitative PCR (qPCR)-diagnosis of bacterial diarrhoea in a multicentre cohort of children under 2 years of age with moderate to severe diarrhoea (MSD).DesignA secondary cross-sectional analysis of baseline data collected from the AntiBiotics for Children with Diarrhoea trial (NCT03130114).PatientsChildren with MSD (defined as >3 loose stools within 24 hours and presenting with at least one of the following: some/severe dehydration, moderate acute malnutrition (MAM) or severe stunting) enrolled in the ABCD trial and collected stool sample.Study periodJune 2017–July 2019.InterventionsNone.Main outcome measuresLikely bacterial aetiology of diarrhoea. Secondary outcomes included specific diarrhoea aetiology.ResultsA total of 6692 children with MSD had qPCR results available and 28% had likely bacterial diarrhoea aetiology. Compared with children with severe stunting, children with MAM (adjusted OR (aOR) (95% CI) 1.56 (1.18 to 2.08)), some/severe dehydration (aOR (95% CI) 1.66 (1.25 to 2.22)) or both (aOR (95% CI) 2.21 (1.61 to 3.06)), had higher odds of having likely bacterial diarrhoea aetiology. Similar trends were noted for stable toxin-enterotoxigenic Escherichia coli aetiology. Clinical correlates including fever and prolonged duration of diarrhoea were not associated with likely bacterial aetiology; children with more than six stools in the previous 24 hours had higher odds of likely bacterial diarrhoea (aOR (95% CI) 1.20 (1.05 to 1.36)) compared with those with fewer stools.ConclusionThe presence of MAM, dehydration or high stool frequency may be helpful in identifying children with MSD who might benefit from antibiotics.

The objective of this study was to examine the effect of fluid intake and possible dehydration on cognitive flight performance of pilots. A repeated-measures, counterbalanced, mixed study design was used to examine differences in working memory, spatial orientation, and cognitive flight performance of 40 randomly selected healthy pilots after having high and low fluid intakes. Serial weights were also analyzed to determine differences in cognitive flight performance of the dehydrated (1-3% weight loss) and hydrated study participants. Results showed flight performance and spatial cognition test scores were significantly (p < 0.05) poorer for pilots who had low fluid intakes and experienced dehydration in comparison to the hydrated pilots. These findings indicate fluid intake differences resulting in dehydration may have safety implications because peak cognitive performance among pilots is critical for flight safety.

Stearns, RL, Casa, DJ, Lopez, RM, McDermott, BP, Ganio, MS, Decher, NR, Scruggs, IC, West, AE, Armstrong, LE, and Maresh, CM. Influence of hydration status on pacing during trail running in the heat. J Strength Cond Res 23(9)2533-2541, 2009-The purpose of this study was to determine the influence of hydration status on pacing of trail runners in the heat (wet bulb globe temperature = 26.2 ± 1.8°C). A randomized, crossover design was used and the participation occurred within a 2-week period. Seventeen competitive, well-trained distance runners (9 men, 8 women, age 27 ± 7 years, height 171 ± 9 cm, weight 64.2 ± 9.0 kg, body fat 14.6 ± 5.5%) completed the study. Subjects started maximum effort trials that were either hydrated (HYR) and dehydrated (DHR). Each trial subjects ran three 4-km loops with a 4-minute rest between loops. Significance was set at p ≤ 0.05. The DHR had a significantly greater body mass loss at the pre- and posttrial time points (−2.05 ± 1.25 and −4.3 ± 1.25%, respectively) vs. HYR (−0.79 ± 0.95 and −2.05 ± 1.09%, respectively). Subjects ran the 12 km faster (p < 0.001) in HYR (3,191 ± 366 seconds) vs. DHR (3,339 ± 450 seconds). Differences between fastest and slowest loops during HYR (54 ± 40 seconds) were significantly smaller than DHR (111 ± 93 seconds; p = 0.041). Additionally, loop times were slower for loop 1 (HYR 1,039 ± 116 seconds vs. DHR 1,071 ± 123 seconds; p = 0.028), loop 2 (HYR 1,066 ± 123 seconds vs. DHR 1,105 ± 148 seconds; p = 0.01) and loop 3 (HYR 1,081 ± 132 seconds vs. DHR 1,168 ± 189 seconds; p = 0.003) when dehydrated. Percent of the race completed by loop as calculated by finishing time was significantly different at loop 2 between HYR (33.6 ± 0.36%) and DHR (33.1 ± 0.35%, p = 0.002) and loop 3 (33.8 ± 0.75% vs. 34.9 ± 1.35%, respectively, p = 0.01). Total variation from the mean pace for the duration of the HYR compared to the DHR approached significance (p = 0.064). Average percent of variance approached significance between trials (p = 0.057). Differences between the fastest and slowest loops between trials demonstrated an increased ability for hydrated individuals to evenly pace themselves. While total variation from the mean pace was not significantly different, it could have practical applicability. These findings reveal that dehydration is associated with decreases in a runnersʼ ability to evenly pace themselves during a competitive situation.

Four vocally untrained healthy adults, 2 men and 2 women, completed the study. A double-blind placebo-controlled approach was used to administer three treatments to each participant on separate days. Drugs treatments involved a single 60-mg dose of a diuretic, Lasix (LA), on one day, and a single 50-mg dose of an oral antihistamine, diphenhydramine hydrochloride (DH), on another day. A third day involved the administration of a placebo, sugar pills (SP). Critical posttreatment measures were weight (kg), which estimated systemic dehydration, saliva viscosity (centipoise), which estimated secretion dehydration, and phona-tion threshold pressure (PTP, in cm H 2 O), at high pitches, which indicated pulmonary drive for phonation. The central experimental question was: Does systemic dehydration, or secretory dehydration, or both, mediate increases in PTP that are known to occur following dehydration treatments? The results showed that LA induced systemic dehydration, as shown by a decrease in total body mass of about 1%. Weight losses were seen during a 1- to 4-hour block following drug administration and persisted for at least 8 hours thereafter. PTPs also increased in that condition, about 23% relative to baseline, but only several hours after whole-body dehydration was initially seen (5–12 hours after drug administration). In contrast, no evidence was seen that DH accomplished either secretory dehydration or PTP shifts. The results indicate that systemic dehydration can mediate PTP increases. The influence of secretory dehydration on PTP is unclear.

Healthy children from 7 months to 7 years are known to be at risk for developing hypoglycaemia during prolonged fasting, particularly during acute illness with decreased oral intake. Our study aimed to identify additional factors associated with hypoglycaemia in children with acute vomiting and dehydration. Our retrospective single-centre study included 560 healthy children and adolescents (aged 29 days to 17.96 years) without known metabolic disorders admitted to hospital with dehydration due to acute illness with vomiting or poor oral intake. Historical and anthropometric parameters were evaluated as potential factors associated with hypoglycaemia. A total of 171 (30.5%) participants (aged 0.6-10.7, median 3.8 years) experienced hypoglycaemia (≤3.3 mmol/l). Besides known factors such as a higher degree of dehydration (OR 2.505, 95% CI 1.532-4.095) and complete absence of oral intake (OR 2.185, 95% CI 1.331-3.586), additional factors independently associated with hypoglycaemia included diarrhoea (OR 0.178, 95% CI 0.068-0.468) and lower body mass index (BMI) (OR 0.011, 95% CI 0.000-0.605). Children with hypoglycaemia had a significantly lower BMI (median 14.29 vs 15.46 kg/m2, p < 0.001) than children without hypoglycaemia. Only one child with hypoglycaemia was obese. The highest rate of hypoglycaemia (37.5-51.6%) was observed in the 2-7-year age groups, who also had the lowest median BMI values (13.9-14.8). Low BMI and absence of diarrhoea were associated with increased odds of hypoglycaemia. The typical BMI curve for children with physiologically low values at 2-7 years of age may partially explain the high incidence of hypoglycaemia in otherwise healthy children with decreased oral intake at this age.

Key Points Diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar state (HHS) are serious acute metabolic complications of diabetes mellitus, representing points along a spectrum of hyperglycaemic emergencies caused by poor glycaemic control DKA comprises hyperglycaemia, hyperketonaemia and metabolic acidosis; diagnostic criteria for HHS include a plasma glucose level >33.3 mmol/l, serum osmolality >320 mmol/kg and no appreciable metabolic acidosis and ketonaemia Management objectives for DKA and HHS include restoration of circulatory volume and tissue perfusion; correction of hyperglycaemia, ketogenesis and electrolyte imbalance; and identification and treatment of the precipitating event Hypoglycaemia is defined as a blood glucose level <3.9 mmol/l in both the inpatient and outpatient settings Severe hypoglycaemic events can negate the beneficial effects of intensive glycaemic management strategies that target near normoglycaemia among patients with diabetes mellitus Patient and family education regarding the signs and symptoms of hypoglycaemia, as well as the methods available for treatment, can effectively reduce the risk of severe hypoglycaemic episodes Diabetic ketoacidosis, hyperglycaemic osmolar state and hypoglycaemia are serious complications of diabetes mellitus. Here, Guillermo Umpierrez and Mary Korytkowski discuss the clinical presentation, precipitating causes, diagnosis and acute management of these diabetic emergencies and suggest practical strategies for their prevention. Diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS) and hypoglycaemia are serious complications of diabetes mellitus that require prompt recognition, diagnosis and treatment. DKA and HHS are characterized by insulinopaenia and severe hyperglycaemia; clinically, these two conditions differ only by the degree of dehydration and the severity of metabolic acidosis. The overall mortality recorded among children and adults with DKA is <1%. Mortality among patients with HHS is ∼10-fold higher than that associated with DKA. The prognosis and outcome of patients with DKA or HHS are determined by the severity of dehydration, the presence of comorbidities and age >60 years. The estimated annual cost of hospital treatment for patients experiencing hyperglycaemic crises in the USA exceeds US$2 billion. Hypoglycaemia is a frequent and serious adverse effect of antidiabetic therapy that is associated with both immediate and delayed adverse clinical outcomes, as well as increased economic costs. Inpatients who develop hypoglycaemia are likely to experience a long duration of hospital stay and increased mortality. This Review describes the clinical presentation, precipitating causes, diagnosis and acute management of these diabetic emergencies, including a discussion of practical strategies for their prevention.