Association between hydration status and the risk and all-cause mortality of diabetic kidney disease.

BACKGROUND: This cohort study aimed to explore the relationship between hydration status and the risk of diabetic kidney disease (DKD) as well as all-cause death in DKD patients. METHODS: Weighted univariable and multivariable logistic regression models were used to explore the association between hydration status and DKD risk in diabetic population while weighted univariable and multivariable Cox regression models were used to identify the association between hydration status and all-cause mortality in DKD patients. Kaplan-Meier curve was plotted to present the survival probability of patients with different hydration status. Estimates were presented as odds ratio (OR), and hazard ratio (HR) with 95% confidence interval (CI). RESULTS: The mean follow-up time was 79.74 (±1.89) months. There were 2041 participants with DKD, and 2889 participants without. At the end of the follow-up, 965 participants were alive. The risk of DKD was increased as the increase of osmolarity level (OR = 1.07, 95%CI: 1.05-1.08). The elevated risk of DKD was observed in patients with impending dehydration (OR = 1.49, 95%CI: 1.19-1.85) or current dehydration (OR = 2.69, 95%CI: 2.09-3.46). The association between increased osmolarty level and elevated risk of all-cause mortality in DKD patients was statistically different (HR = 1.02, 95%CI: 1.01-1.03). Current dehydration was correlated with increased all-cause mortality risk in DKD patients (HR = 1.27, 95%CI: 1.01-1.61). Compared to DKD patients with normal hydration, the survival probability of DKD patients with current dehydration was significant lower (p < 0.001). CONCLUSION: Increased osmolarity level was associated with increased risk of DKD and elevated risk of all-cause mortality in DKD patients.

Mapping evaporative water loss in desert passerines reveals an expanding threat of lethal dehydration.

Extreme high environmental temperatures produce a variety of consequences for wildlife, including mass die-offs. Heat waves are increasing in frequency, intensity, and extent, and are projected to increase further under climate change. However, the spatial and temporal dynamics of die-off risk are poorly understood. Here, we examine the effects of heat waves on evaporative water loss (EWL) and survival in five desert passerine birds across the southwestern United States using a combination of physiological data, mechanistically informed models, and hourly geospatial temperature data. We ask how rates of EWL vary with temperature across species; how frequently, over what areas, and how rapidly lethal dehydration occurs; how EWL and die-off risk vary with body mass; and how die-off risk is affected by climate warming. We find that smaller-bodied passerines are subject to higher rates of mass-specific EWL than larger-bodied counterparts and thus encounter potentially lethal conditions much more frequently, over shorter daily intervals, and over larger geographic areas. Warming by 4 °C greatly expands the extent, frequency, and intensity of dehydration risk, and introduces new threats for larger passerine birds, particularly those with limited geographic ranges. Our models reveal that increasing air temperatures and heat wave occurrence will potentially have important impacts on the water balance, daily activity, and geographic distribution of arid-zone birds. Impacts may be exacerbated by chronic effects and interactions with other environmental changes. This work underscores the importance of acute risks of high temperatures, particularly for small-bodied species, and suggests conservation of thermal refugia and water sources.

Diarrhea, Dehydration, and the Associated Mortality in Children with Complicated Severe Acute Malnutrition: A Prospective Cohort Study in Uganda.

OBJECTIVE: To assess predictors of diarrhea and dehydration and to investigate the role of diarrhea in mortality among children with complicated severe acute malnutrition. STUDY DESIGN: A prospective cohort study, nested in a probiotic trial, was conducted in children with complicated severe acute malnutrition. Children were treated according to World Health Organization and national guidelines, and diarrhea and dehydration were assessed daily. Multiple linear and log-linear Poisson regression models were used to identify predictors of days with diarrhea and dehydration, respectively, and multiple logistic regression was used to assess their role in mortality. RESULTS: Among 400 children enrolled, the median (IQR) age was 15.0 months (11.2-19.2 months), 58% were boys, and 61% had caregiver-reported diarrhea at admission. During hospitalization, the median (range) number of days with diarrhea was 5 (0-31), the median duration of hospitalization was 17 days (1-69 days), and 39 (10%) died. Of 592 diarrhea episodes monitored, 237 were admission episodes and 355 were hospital acquired. During hospitalization, young age was associated with days with diarrhea, and young age and HIV infection were associated with dehydration. Both days with diarrhea and dehydration predicted duration of hospitalization as well as mortality. The odds of mortality increased by a factor of 1.4 (95% CI, 1.2-1.6) per day of diarrhea and 3.5 (95% CI, 2.2-6.0) per unit increase in dehydration score. CONCLUSIONS: Diarrhea is a strong predictor of mortality among children with complicated severe acute malnutrition. Improved management of diarrhea and prevention of hospital-acquired diarrhea may be critical to decreasing mortality.

Hyaluronidase-Assisted Resuscitation in Kenya for Severely Dehydrated Children.

BACKGROUND: Dehydration, mainly due to diarrheal illnesses, is a leading cause of childhood mortality worldwide. Intravenous (IV) therapy is the standard of care for patients who were unable to tolerate oral rehydration; however, placing IVs in fragile, dehydrated veins can be challenging. Studies in resource-rich settings comparing hyaluronidase-assisted subcutaneous rehydration with standard IV rehydration in children have demonstrated several benefits of subcutaneous rehydration, including time and success of line placement, ease of use, satisfaction, and cost-effectiveness. METHODS: A single-arm trial assessing the feasibility of hyaluronidase-assisted subcutaneous resuscitation for the treatment of moderately to severely dehydrated individuals in western Kenya was conducted. Children aged 2 months or older who presented with moderately to severely dehydration clinically warranting parenteral rehydration and had at least 2 failed IV attempts were eligible. Study staff received training on standard dehydration management and hyaluronidase infusion processes. Children received all other standards of care. They were monitored from presentation and through discharge, with a 1-week phone follow-up. Predischarge surveys were completed by caregivers, and semistructured interviews with providers were performed. RESULTS: A total of 51 children were enrolled (median age, 13.0 months; interquartile range of 18 months). Fifty-one patients (100%) had severe dehydration. The median length of subcutaneous infusion was 3.0 hours (interquartile range [IQR], 2.95). The median total subcutaneous infusion was 700.0 mL (IQR, 420 mL). Median time to resolution of moderate to severe dehydration symptoms was 3.0 hours (IQR, 2.95 hours). There were no significant complications. CONCLUSIONS: Hyaluronidase-assisted subcutaneous resuscitation is a feasible alternative to IV hydration in moderately to severely dehydrated children with difficult to obtain IV access in resource-limited areas.

Overhydration, underhydration, and total body sodium: A tricky "ménage a trois" in dialysis patients.

Overhydration is a frequent complication in dialysis patients. It has been linked with hypertension, left ventricular hypertrophy, arterial stiffness, atherosclerosis uremic cardiomyopathy, and all-cause mortality or cardiovascular morbidity. In addition, predialysis underhydration is also associated with increased risk of death in ESRD patients. In this context, the optimal evaluation of hydration status is a must. However, this mission is not easy or accurate. In the last 10 years, several new methods have been tested in dialysis patients, particularly bioimpedance and lung ultrasonography. The precise clinical value of these techniques in the daily care of hemodialysis patients is not obvious yet. Sodium is also an important piece of this puzzle. Salt intake and/or removal of sodium during dialysis are essential determinants of optimal hydration status. Recent studies have revealed that salt and water homeostasis is also dependent of tissue sodium storage-increased in hemodialysis patients. However, the significance of increased sodium tissue storage as a cardiovascular risk factor and the relationship between tissue sodium content and hard CV endpoint have not yet been elucidated yet.

Global challenges in acute diarrhea.

PURPOSE OF REVIEW: Childhood diarrhea is the most common cause of morbidity and mortality, especially in the low and middle-income countries. The burden of child mortality because of diarrhea has declined, but still a lot is desired not only to reduce diarrhea-specific mortality but reduce the overall incidence, and hence the morbidity associated with childhood diarrhea. RECENT FINDINGS: A recent Lancet series on diarrhea suggests that amplification of the current interventions can eliminate virtually all preventable diarrhea deaths. A refocused attention and strategy and collective effort from the multilateral entities to promote water sanitation and hygiene, rotavirus vaccination, nutrition, and improved case management can bridge gaps and tackle the existing undue burden of deaths because of diarrhea. SUMMARY: Investment toward preventing and controlling childhood diarrhea should be a priority, especially when the existing solution is plausible for implementation at scale and in underprivileged settings.

Hydration and outcome in older patients admitted to hospital (The HOOP prospective cohort study).

BACKGROUND: Older adults are susceptible to dehydration due to age-related pathophysiological changes. We aimed to investigate the prevalence of hyperosmolar dehydration (HD) in hospitalised older adults, aged ≥65 years, admitted as an emergency and to assess the impact on short-term and long-term outcome. METHODS: This prospective cohort study was performed on older adult participants who were admitted acutely to a large U.K. teaching hospital. Data collected included the Charlson comorbidity index (CCI), national early warning score (NEWS), Canadian Study of Health and Aging (CSHA) clinical frailty scale and Nutrition Risk Screening Tool (NRS) 2002. Admission bloods were used to measure serum osmolality. HD was defined as serum osmolality >300 mOsmol/kg. Participants who were still in hospital 48 h after admission were reviewed, and the same measurements were repeated. RESULTS: A total of 200 participants were recruited at admission to hospital, 37% of whom were dehydrated. Of those dehydrated, 62% were still dehydrated when reviewed at 48 h after admission. Overall, 7% of the participants died in hospital, 79% of whom were dehydrated at admission (P = 0.001). Cox regression analysis adjusted for age, gender, CCI, NEWS, CSHA and NRS demonstrated that participants dehydrated at admission were 6 times more likely to die in hospital than those euhydrated, hazards ratio (HR) 6.04 (1.64-22.25); P = 0.007. CONCLUSIONS: HD is common in hospitalised older adults and is associated with poor outcome. Coordinated efforts are necessary to develop comprehensive hydration assessment tools to implement and monitor a real change in culture and attitude towards hydration in hospitalised older adults.

Fluid retention index predicts the 30-day mortality in geriatric care.

The incidence and medical consequences of dehydration and fluid retention in senior citizens are unclear. The present study used urine sampling to detect renal conservation of water, which is an early sign of dehydration, and assessed its relationship to mortality in elderly patients admitted for acute hospital care. A urine sample was collected from 256 patients (mean age 82 years) and analyzed for color, specific gravity and osmolality. These markers were used to calculate a composite index of fluid retention, which was indicated by urine color ≥ 4, specific gravity ≥ 1.020 and osmolality ≥ 600 mOsmol/kg as suggested from eight previous studies of exercise-induced dehydration, of which one extends to age 69. Concentrated urine consistent with dehydration was present in 39 (16%) of the patients. This finding was relatively more common among those with confusion and/or dementia, but less common in patients with medical disease, and in those taking diuretics daily. Patients with such fluid retention had a higher 30-day mortality when compared to those who were euhydrated (21% versus 8%; p < 0.03). A difference of 10% remained at three months and one year after the admission to hospital. Concentrated urine consistent with fluid retention was found in 16% of the geriatric patients admitted to hospital for acute care. In these patients the mortality within 30 days was almost tripled compared to those who were euhydrated.

Dehydration in the Older Adult.

Dehydration affects 20% to 30% of older adults. It has a greater negative outcome in this population than in younger adults and increases mortality, morbidity, and disability. Dehydration is often caused by water deprivation in older adults, although excess water loss may also be a cause. Traditional markers for dehydration do not take into consideration many of the physiological differences present in older adults. Clinical assessment of dehydration in older adults poses different findings, yet is not always diagnostic. Treatment of dehydration should focus on prevention and early diagnosis before it negatively effects health and gives rise to comorbidities. The current article discusses what has most thoroughly been studied; the best strategies and assessment tools for evaluation, diagnosis, and treatment of dehydration in older adults; and what needs to be researched further. [Journal of Gerontological Nursing, 41(9), 8-13.].

Global burden of childhood diarrhea and interventions.

PURPOSE OF REVIEW: Diarrhea is a leading cause of morbidity and mortality among children under 5 years in low-income and middle-income countries. Over the past 2 decades under-five mortality has decreased substantially, but reductions have been uneven and unsatisfactory in resource-poor regions. RECENT FINDINGS: There are known interventions which can prevent diarrhea or manage children who suffer from it. Interventions with proven effectiveness at the prevention level include water, sanitation, and hygiene interventions, breastfeeding, complementary feeding, vitamin A and zinc supplementation, and vaccines for diarrhea (rotavirus and cholera). Oral rehydration solution, zinc treatment, continued feeding, and antibiotic treatment for certain strains of diarrhea (cholera, Shigella, and cryptosporidiosis) are effective strategies for treatment of diarrhea. The recent Lancet series using the 'Lives Saved' tool suggested that if these identified interventions were scaled up to a global coverage to at least 80%, and immunizations to at least 90%; almost all deaths due to diarrhea could be averted. SUMMARY: The current childhood mortality burden highlights the need of a focused global diarrhea action plan. The findings suggest that with proper packaging of interventions and delivery platforms, the burden of childhood diarrhea can be reduced to a greater extent. All that is required is greater attention and steps toward right direction.

Adipsia increases risk of death in patients with central diabetes insipidus.

Central diabetes insipidus (CDI) is caused by deficiency of arginine vasopressin, an antidiuretic hormone. Patients with CDI manifest polyuria which is usually compensated for by increases in water intake. However, some patients are not able to sense thirst due to the destruction of osmoreceptors in the hypothalamus. These adipsic CDI patients are easily dehydrated and the consequent dehydration could be life-threatening. The objective of this study was to investigate the prognosis of adipsic CDI patients. We have reviewed 149 patients with CDI in three hospitals using databases of the electronic medical recording systems, and examined whether adipsia could affect the morbidity and mortality in CDI patients with multivariable analyses. Twenty-three patients with CDI were adipsic while the remaining 126 patients were non-adipsic. The multivariate analyses showed that the incidence of serious infections which required hospitalization was significantly higher in the adipsic CDI patients compared to that in non-adipsic CDI patients (p <0.001). A total of 6 patients with CDI died during the follow-up (median duration; 60 months, range 1 to 132 months). Four of them were adipsic, three of whom died of infection. The statistical analyses revealed that the risk of death in adipsic CDI patients was significantly higher than in non-adipsic patients (p =0.007). It is thus suggested that adipsic CDI patients were susceptible to serious infections which could be the causes of death.

Livestock mortality in pastoralist herds in Ethiopia and implications for drought response.

Participatory epidemiology methods were employed retrospectively in three pastoralist regions of Ethiopia to estimate the specific causes of excess livestock mortality during drought. The results showed that starvation/dehydration accounted for between 61.5 and 100 per cent of excess livestock mortality during drought, whereas disease-related mortality accounted for between 0 and 28.1 per cent of excess mortality. Field observations indicate that, in livestock, disease risks and mortality increase in the immediate post-drought period, during rain. The design of livelihoods-based drought response programmes should include protection of core livestock assets, and it should take account of the specific causes of excess livestock mortality during drought and immediately afterwards. This study shows that, when comparing livestock feed supplementation and veterinary support, relatively more aid should be directed at the former if the objective is to protect core livestock during drought. Veterinary support should consider disease-related mortality in the immediate post-drought period, and tailor inputs accordingly.

Acute kidney injury in nonagenarians: clinical characteristics and mortality.

INTRODUCTION: Nonagenarians constitute a rising percentage of inpatients, with acute kidney injury (AKI) being frequent in this population. Thus, it is important to analyze the clinical characteristics of this demographic and their impact on mortality. METHODS: Retrospective study of nonagenarian patients with AKI at a tertiary hospital between 2013 and 2022. Only the latest hospital admission was considered, and patients with incomplete data were excluded. A logistic regression analysis was conducted to define risk factors for mortality. A p-value < 0.05 was considered statistically significant. RESULTS: A total of 150 patients were included, with a median age of 93.0 years (91.2-95.0), and males accounting for 42.7% of the sample. Sepsis was the most common cause of AKI (53.3%), followed by dehydration/hypovolemia (17.7%), and heart failure (17.7%). ICU admission occurred in 39.3% of patients, mechanical ventilation in 14.7%, vasopressors use in 22.7% and renal replacement therapy (RRT) in 6.7%. Death occurred in 56.7% of patients. Dehydration/hypovolemia as an etiology of AKI was associated with a lower risk of mortality (OR 0.18; 95% CI 0.04-0.77, p = 0.020). KDIGO stage 3 (OR 3.15; 95% CI 1.17-8.47, p = 0.023), ICU admission (OR 12.27; 95% CI 3.03-49.74, p < 0.001), and oliguria (OR 5.77; 95% CI 1.98-16.85, p = 0.001) were associated with mortality. CONCLUSION: AKI nonagenarians had a high mortality rate, with AKI KDIGO stage 3, oliguria, and ICU admission being associated with death.

Perceptions regarding oral rehydration solutions for the management of diarrhea in Guatemalan children: implications for diarrheal management in the Americas.

OBJECTIVE: To describe knowledge and perceptions regarding the use of oral rehydration solution (ORS) for the management of diarrheal diseases among formal and informal health care providers and community caregivers in the Guatemalan department of Santa Rosa, and to recommend strategies to increase ORS use for management of diarrhea in children. METHODS: From July to September 2008, in-depth, semi-structured interviews were conducted with formal health care providers; open-ended interviews were conducted with informal health care providers; and focus group discussions and pile sorting were carried out with community caregivers. RESULT: The study participants attributed episodes of diarrhea in children to culturally recognized or folk ailments (empacho, cuajo, and varillas) that are primarily treated by traditional healers. There were knowledge deficits about 1) dehydration as a manifestation of diarrhea, and 2) management of dehydration, including the use of ORS and the need to continue feedings during diarrheal episodes. Caregivers perceived bottled/ready-made ORS products and the more expensive over-the-counter antidiarrheal medications as superior to ORS packets in the treatment of diarrhea. CONCLUSIONS: In Guatemala, folk etiologies of disease differ from those of the biomedical establishment and influence the decisions made by caregivers when treating ill children, including those related to the use of ORS. Public health campaigns addressing the treatment and management of diarrheal diseases in Santa Rosa should recognize the ailments known as empacho, cuajo, and varillas and target them for ORS use by community caregivers as well as health care providers in both the formal and informal health sectors.

What is the safe approach for neonatal hypernatremic dehydration? A retrospective study from a neonatal intensive care unit.

OBJECTIVES: The aims of this study were to evaluate the prevalence, complications, and mortality of hypernatremic dehydration in neonates and to compare the effect of correction rate at 48 hours on mortality and on neurological outcome in the short term. METHODS: This retrospective study was conducted between January 2007 and 2011 in the neonatal intensive care unit. Term neonates were included. The patients were grouped as follows: group 1 = 150 to 160 mmol/L, group 2 = 161 to 170 mmol/L and group 3 = 171 to 189 mmol/L. RESULTS: Among 4280 neonates, 81 cases (1.8%) had hypernatremic dehydration. Groups 1, 2, and 3 consisted of 55, 23, and 3 patients, respectively. Mortality rates were as follows: 3.6%, 17.3%, and 66.6%. Mean serum sodium (Na) correction rates at 0 to 24 hours and 24 to 48 hours were 0.48 ± 0.2 versus 0.38 ± 0.31 mmol/L per hour (group 1) and 0.49 ± 0.21 versus 0.52 ± 0.28 mmol/L per hour (group 2), respectively. In 32 patients (58.1%) from group 1 and in 13 patients (56.5%) from group 2, correction rate of 0.5 mmol/L per hour or less was achieved. Twenty-two patients developed convulsions, which was the most common complication during therapy. Serum Na greater than 160 mmol/L at admission (odds ratio, 1.9; 95% confidence interval, 1.3-3.7) and serum Na correction rate of greater than 0.5 mmol/L per hour (odds ratio, 4.3; 95% confidence interval, 1.2-6.5) were independent risk factors for death or convulsion. There was a significant difference between groups 1 and 2 in Denver Developmental Screening Test II results (64.1% vs 30.7 %, P = 0.001). CONCLUSION: Hypernatremic dehydration is an important problem that should be managed properly to avoid adverse outcomes.

Emergency department visits, ambulance calls, and mortality associated with an exceptional heat wave in Sydney, Australia, 2011: a time-series analysis.

BACKGROUND: From January 30-February 6, 2011, New South Wales was affected by an exceptional heat wave, which broke numerous records. Near real-time Emergency Department (ED) and ambulance surveillance allowed rapid detection of an increase in the number of heat-related ED visits and ambulance calls during this period. The purpose of this study was to quantify the excess heat-related and all-cause ED visits and ambulance calls, and excess all-cause mortality, associated with the heat wave. METHODS: ED and ambulance data were obtained from surveillance and administrative databases, while mortality data were obtained from the state death registry. The observed counts were compared with the average counts from the same period from 2006/07 through 2009/10, and a Poisson regression model was constructed to calculate the number of excess ED visits, ambulance and deaths after adjusting for calendar and lag effects. RESULTS: During the heat wave there were 104 and 236 ED visits for heat effects and dehydration respectively, and 116 ambulance calls for heat exposure. From the regression model, all-cause ED visits increased by 2% (95% CI 1.01-1.03), all-cause ambulance calls increased by 14% (95% CI 1.11-1.16), and all-cause mortality increased by 13% (95% CI 1.06-1.22). Those aged 75 years and older had the highest excess rates of all outcomes. CONCLUSIONS: The 2011 heat wave resulted in an increase in the number of ED visits and ambulance calls, especially in older persons, as well as an increase in all-cause mortality. Rapid surveillance systems provide markers of heat wave impacts that have fatal outcomes.

Normal saline is a safe initial rehydration fluid in children with diarrhea-related hypernatremia.

UNLABELLED: To demonstrate safety and efficacy of using normal saline (NS) for initial volume expansion (IVE) and rehydration in children with diarrhea-related hypernatremic dehydration (DR-HD), forty eight patients with DR-HD were retrospectively studied. NS was used as needed for IVE and for initial rehydration. Fluid deficit was given over 48 h. Median Na(+) level on admission was 162.9 mEq/L (IQR 160.8-165.8). The median average hourly drop at 6 and 24 h was 0.53 mEq/L/h (0.48-0.59) and 0.52 mEq/L/h (0.47-0.57), respectively. Compared to children not needing IVE, receiving ≥40 ml/kg IVE was associated with a higher average hourly drop of Na(+) at 6 h (0.51 vs. 0.58 mEq/L/h, p = 0.013) but not at 24 h (p = 0.663). The three patients (6.3%) with seizures had a higher average hourly drop of Na(+) at 6 and 24 h (p = 0.084 and 0.021, respectively). Mortality (4/48, 8.3%) was not related to Na(+) on admission or to its average hourly drop at 6 or 24 h. Children receiving ≥40 ml/kg IVE were more likely to die (OR 3.3; CI, 1.5-7.2). CONCLUSION: In children with DR-HD, NS is a safe rehydration fluid with a satisfactory rate of Na(+) drop and relatively low incidence of morbidity and mortality. Judicious use of IVE should be exerted and closer monitoring should be guaranteed for children requiring large volumes for IVE and for those showing rapid initial drop of serum Na(+) to avoid neurological complications and poor outcome.

Low temperature survival in different life stages of the Iberian slug, Arion lusitanicus.

The slug Arion lusitanicus Mabille (Gastropoda: Pulmonata: Arionidae) is an invasive species which has spread to most parts of Europe. The area of origin is unknown, but A. lusitanicus seems to cope well with the local conditions in the countries to which it has migrated. It spreads rapidly, occurs often in high densities and has become a serious pest in most European countries. Therefore there is an urgent need for better knowledge of the ecophysiology of A. lusitanicus, such as the influence of climatic conditions, in order to develop prognostic models and strategies for novel pest management practises. The aim of our study was to investigate the influence of subzero temperatures in relation to winter survival. A. lusitanicus is shown to be freeze-tolerant in some life stages. Most juveniles and some adult slugs survived being frozen at -1.3°C for 3days, but none of the slugs survived freezing at -3°C. The eggs survived subzero temperatures (down to -2°C) probably by supercooling. Juveniles and adults may also survive in a supercooled state (down to -3°C) but are generally poor supercoolers. Therefore, the winter survival of A. lusitanicus depends to a high degree on migration to habitats protected from low winter temperatures, e.g. under plant litter, buried in the soil or in compost heaps.

Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings: A Randomized Clinical Trial.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: Primary outcomes included all-cause mortality up to 180 days after enrollment and linear growth faltering 90 days after enrollment. Results: 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. Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT03130114.

The epidermal barrier function is dependent on the serine protease CAP1/Prss8.

Serine proteases are proteolytic enzymes that are involved in the regulation of various physiological processes. We generated mice lacking the membrane-anchored channel-activating serine protease (CAP) 1 (also termed protease serine S1 family member 8 [Prss8] and prostasin) in skin, and these mice died within 60 h after birth. They presented a lower body weight and exhibited severe malformation of the stratum corneum (SC). This aberrant skin development was accompanied by an impaired skin barrier function, as evidenced by dehydration and skin permeability assay and transepidermal water loss measurements leading to rapid, fatal dehydration. Analysis of differentiation markers revealed no major alterations in CAP1/Prss8-deficient skin even though the epidermal deficiency of CAP1/Prss8 expression disturbs SC lipid composition, corneocyte morphogenesis, and the processing of profilaggrin. The examination of tight junction proteins revealed an absence of occludin, which did not prevent the diffusion of subcutaneously injected tracer (approximately 600 D) toward the skin surface. This study shows that CAP1/Prss8 expression in the epidermis is crucial for the epidermal permeability barrier and is, thereby, indispensable for postnatal survival.