Multimorbidity among the Indigenous population: A systematic review and meta-analysis.

BACKGROUND: Multimorbidity, the concurrent presence of multiple chronic health conditions in an individual, represents a mounting public health challenge. Chronic illnesses are prevalent in the Indigenous populations, which contributes to multimorbidity. However, the epidemiology of multimorbidity in this population is not well studied. This review aimed to elucidate the extent, determinants, consequences, and prevention of multimorbidity within Indigenous populations globally, contrasting findings with non-Indigenous populations. METHODS: Adhering to the PRISMA guidelines, this systematic review assimilated peer-reviewed articles and grey literature, focusing on the prevalence, determinants, implications, and preventive strategies of multimorbidity in global Indigenous populations. Emphasis was given to original, English-language, full-text articles, excluding editorials, and conference abstracts. FINDINGS: Of the 444 articles identified, 13 met the inclusion criteria. Five studies are from Australia, and the rest are from the USA, Canada, New Zealand, and India. The study indicated a higher multimorbidity prevalence among Indigenous populations, with consistent disparities observed across various age groups. Particularly, Indigenous individuals exhibited a 2-times higher likelihood of multimorbidity compared to non-Indigenous populations. Noteworthy findings underscored the elevated severity of certain comorbid conditions, especially strokes, within Indigenous groups, with further revelations highlighting their significant pairing with conditions such as heart diseases and diabetes. INTERPRETATION: The findings affirm the elevated burden of multimorbidity among Indigenous populations. Prevalence and risk of developing multimorbidity are significantly higher in this population compared to their non-Indigenous counterparts. Future research should prioritize harmonized research methodologies, fostering insights into the multimorbidity landscape, and promoting strategies to address health disparities in Indigenous populations.

Trajectories of psychosocial environmental factors and their associations with asthma symptom trajectories among children in Australia.

INTRODUCTION: Several psychosocial factors, such as maternal mental health and parents' financial hardship, are associated with asthma symptoms among children. So, we aim to investigate the changing patterns of important psychosocial environmental factors and their associations with asthma symptom trajectories among children in Australia. METHODS: We considered asthma symptoms as wheezing (outcome) and psychosocial environmental factors (exposures) from 0/1 year to 14/15 years of the participants from the "Longitudinal Study of Australian Children (LSAC)" for this study. We used group-based trajectory modeling to identify the trajectory groups for both exposure and outcome variables. Associations between psychosocial factors and three distinct asthma symptom trajectories were assessed by multivariable logistic regression. RESULTS: We included 3917 children from the LSAC birth cohort in our study. We identified distinct trajectories for maternal depression, parents' financial hardship, parents' stressful life events and parents' availability to their children from birth to 14/15 years of age. Compared to the "low/no" asthma symptom trajectory group, children exposed to a "moderate & increasing" maternal depression, "moderate & declining" parents' financial hardship, and "moderate & increasing" parents' stressful life events were significantly associated (relative risk ratio [RRR]: 1.55, 95% confidence interval [CI]: 1.27, 1.91; RRR: 1.40, 95%; CI: 1.15, 1.70; RRR: 1.77, 95%; CI: 1.45, 2.16) with "persistent high" asthma symptom trajectory. CONCLUSION: Several psychosocial factors that are potential stressors for mental health increase the risk of having an adverse asthma symptom trajectory during childhood. Further attention should be given to reducing exposure to maternal depression, parents' financial hardship, and parents' stressful live events for long-term asthma control in children.

Feasibility and acceptability of bubble continuous positive airway pressure oxygen therapy for the treatment of childhood severe pneumonia and hypoxaemia in Bangladeshi children.

Background: Effective management of hypoxaemia is key to reducing pneumonia deaths in children. In an intensive care setting within a tertiary hospital in Bangladesh, bubble continuous positive airway pressure (bCPAP) oxygen therapy was beneficial in reducing deaths in this population. To inform a future trial, we investigated the feasibility of introducing bCPAP in this population in non-tertiary/district hospitals in Bangladesh. Methods: We conducted a qualitative assessment using a descriptive phenomenological approach to understand the structural and functional capacity of the non-tertiary hospitals (Institute of Child and Mother Health and Kushtia General Hospital) for the clinical use of bCPAP. We conducted interviews and focus group discussions (23 nurses, seven physicians, 14 parents). We retrospectively (12 months) and prospectively (three months) measured the prevalence of severe pneumonia and hypoxaemia in children attending the two study sites. For the feasibility phase, we enrolled 20 patients with severe pneumonia (age two to 24 months) to receive bCPAP, putting in place safeguards to identify risk. Results: Retrospectively, while 747 of 3012 (24.8%) children had a diagnosis of severe pneumonia, no pulse oxygen saturation information was available. Of 3008 children prospectively assessed with pulse oximetry when attending the two sites, 81 (3.7%) had severe pneumonia and hypoxaemia. The main structural challenges to implementation were the inadequate number of pulse oximeters, lack of power generator backup, high patient load with an inadequate number of hospital staff, and inadequate and non-functioning oxygen flow meters. Functional challenges were the rapid turnover of trained clinicians in the hospitals, limited post-admission routine care for in-patients by hospital clinicians due to their extreme workload (particularly after official hours). The study implemented a minimum of four hourly clinical reviews and provided oxygen concentrators (with backup oxygen cylinders), and automatic power generator backup. Twenty children with a mean age of 6.7 (standard deviation (SD) = 5.0)) months with severe pneumonia and hypoxaemia (median (md) SpO2 = 87% in room air, interquartile range (IQR) = 85-88)) with cough (100%) and severe respiratory difficulties (100%) received bCPAP oxygen therapy for a median of 16 hours (IQR = 6-16). There were no treatment failures or deaths. Conclusions: Implementation of low-cost bCPAP oxygen therapy is feasible in non-tertiary/district hospitals when additional training and resources are allocated.

Vaccination following the expanded programme on immunization schedule could help to reduce deaths in children under five hospitalized for pneumonia and severe pneumonia in a developing country.

Background: Worldwide, pneumonia is the leading cause of mortality in children under the age of five. An expanded program on immunization (EPI) is one kind of evidence-based tool for controlling and even eradicating infectious diseases. Objectives: This study aimed to explore the impact of EPI vaccination, including BCG, DPT-Hib-Hep B, OPV, IPV, and PCV-10, among children from the age of 4 to 59 months hospitalized for pneumonia and severe pneumonia. Additionally, we evaluated the role of 10 valent pneumococcal conjugate vaccines alone on clinical outcomes in such children. Methods: In this retrospective chart review, children from the age of 4 to 59 months with WHO-defined pneumonia and severe pneumonia admitted to the Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) between August 2013 and December 2017 who had the information on immunization as per EPI schedule by 4 months of age were included in the analysis. A comparison was made between the children who were fully immunized (immunization with BCG, DPT-Hib-Hep B, OPV, and IPV from 2013 to 2015 and PCV-10 from 2015 to 2017) and who were not immunized (consisting of partial immunization and no immunization) during the study period. Results: A total of 4,625 children had pneumonia and severe pneumonia during the study period. Among them, 2,605 (56.3%) had received the information on immunization; 2,195 (84.3%) were fully immunized by 4 months of age according to the EPI schedule and 410 were not immunized. In the log-linear binomial regression analysis, immunization of children from 4 to 59 months of age was found to be associated with a lower risk of diarrhea (p = 0.033), severe pneumonia (p = 0.001), anemia (p = 0.026), and deaths (p = 0.035). Importantly, the risk of developing severe pneumonia (1054/1,570 [67%] vs. 202/257 [79%], p < 0.001) and case-fatality rate (57/1,570 [3.6%] vs. 19/257 [7.4%], p = 0.005) was still significantly lower among those who were immunized with PCV-10 than those who were not. Conclusion: Children immunized as per the EPI schedule were at a lower risk of diarrhea, severe pneumonia, anemia, and death, compared to unvaccinated children. In addition, PCV-10 was found to be protective against severe pneumonia and deaths in vaccinated children. The overall results underscored the importance of the continuation of immunization, scrupulously adhering to the EPI schedule to reduce the risk of morbidities and mortalities in children, especially in resource-limited settings.

Trajectories of neighborhood environmental factors and their associations with asthma symptom trajectories among children in Australia: evidence from a national birth cohort study.

Purpose: This study aims to investigate the prospective associations of neighborhood environmental exposure trajectories with asthma symptom trajectories during childhood developmental stages. Methods: We considered asthma symptom, neighborhood environmental factors, and socio-demographic data from the "Longitudinal Study of Australian Children (LSAC)". Group-based trajectory modeling was applied to identify the trajectories of asthma symptom, neighborhood traffic conditions, and neighborhood livability scales (considered for safety and facilities). We used multivariable logistic regression models to assess associations between various neighborhood environmental factors and asthma symptom trajectories. Results: We included 4,174 children from the LSAC cohort in our study. Three distinct trajectories for asthma symptom were the outcome variables of this study. Among the neighborhood environmental factors, we identified two distinct trajectories for the prevalence of heavy traffic on street, and two trajectories of neighborhood liveability scale. Compared to the 'Low/no' asthma symptoms trajectory group, children exposed to a 'persistently high' prevalence of heavy traffic on street was also significantly associated with both 'transient high' [relative risk ratio (RRR):1.40, 95% CI:1.25,1.58) and 'persistent high' (RRR: 1.33, 95% CI:1.17,1.50)] asthma symptom trajectory groups. Trajectory of moderate and static neighborhood liveability score was at increased risk of being classified as 'transient high' (RRR:1.16, 95% CI:1.07,1.25) and 'persistent high' (RRR:1.38, 95% CI:1.27,1.50) trajectories of asthma symptom. Conclusion: Exposure to heavy traffic and poor neighborhood liveability increased the risk of having an unfavourable asthma symptom trajectory in childhood. Reducing neighborhood traffic load and improving neighborhood safety and amenities may facilitate a favorable asthma symptom trajectory among these children. Supplementary Information: The online version contains supplementary material available at 10.1007/s40201-022-00824-z.

Death in severely malnourished hospitalized children presenting with diarrhea and vomiting.

INTRODUCTION: There is lack of data on outcomes of severely malnourished children who are hospitalized with concomitant diarrhea and vomiting. We sought to evaluate outcomes of such children. METHODOLOGY: In this retrospective chart review, we used electronic databases to evaluate children aged 0-59 months and admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, with diarrhea and severe malnutrition between April 2011 and August 2012. Outcomes of children with and without vomiting were compared. The primary outcome was death. A probability of ≤ 0.05 was considered statistically significant. RESULTS: Out of 306 enrolled children, 51 (17%) had vomiting and 255 (83%) did not have vomiting. A total of 31 (10%) children died, 12 (24%) of them had vomiting and 19 (8%) did not have vomiting. Death was significantly higher in severely malnourished diarrheal children with vomiting (12/51 (24%)) compared to those without vomiting (19/255 (8%)) (Relative risk [RR] 2.73, 95% confidence interval [CI] 1.61-4.64; p < 0.001). We used Log linear bi-nominal regression after adjusting for potential confounders such as metabolic acidosis and hypoglycemia, and found that vomiting was significantly associated with deaths in severely malnourished diarrheal children (RR 1∙89, 95% CI 1.01-1.33; p = 0.05). CONCLUSIONS: Our analysis showed that children with diarrhea and severe malnutrition who had vomiting during hospitalization were at a higher risk of death compared to those without vomiting. The results underscore the importance of prompt identification and management of vomiting to reduce deaths in such children.

Trajectories of asthma symptom presenting as wheezing and their associations with family environmental factors among children in Australia: evidence from a national birth cohort study.

OBJECTIVES: Asthma is one of the greatest health burdens, yet contributors to asthma symptom trajectories are understudied in Australian children. We aimed to assess the trajectories of asthma symptom and their associations with several family environmental factors during the childhood period in Australia. DESIGN: Secondary analysis from a cross-sequential cohort study. SETTING: Nationwide representative data from the 'Longitudinal Study of Australian Children (LSAC)'. PARTICIPANTS: Participants from the LSAC birth cohort. OUTCOME MEASURES: Asthma symptom trajectory groups. METHODS: Asthma symptom presenting as wheezing, family environmental factors and sociodemographic data (2004-2018) were obtained from the LSAC. Group-based trajectory modelling was applied to identify asthma symptom trajectories and multivariable logistic regression models were used to assess the associations between these and environmental factors. RESULTS: Of 5107 children in the LSAC cohort, 3846 were included in our final analysis. We identified three distinct asthma symptom trajectories from age 0/1 year to 14/15 years: 'low/no' (69%), 'transient high' (17%) and 'persistent high' (14%). Compared with the 'low/no' group, children exposed to 'moderate and declining' (relative risk ratio (RRR): 2.22, 95% CI 1.94 to 2.54; RRR: 1.26, 95% CI 1.08 to 1.46) and 'high and persistent' prevalence of maternal smoking (RRR: 1.41, 95% CI 1.23 to 1.60; RRR: 1.26, 95% CI 1.10 to 1.44) were at increased risk of being classified into the 'transient high' and 'persistent high' trajectories of asthma symptom. Persistently bad external dwelling conditions (RRR: 1.27, 95% CI 1.07 to 1.51) were associated with 'transient high' trajectory while 'moderate and increasing' conditions of cluttered homes (RRR: 1.37, 95% CI 1.20 to 1.56) were associated with 'persistent high' trajectory of asthma symptom. Exposure to tobacco smoke inside the house also increased the risk of being in the 'persistent high' trajectory group (RRR: 1.30, 95% CI 1.12 to 1.50). CONCLUSION: Poor home environment increased the risk of asthma symptom during childhood. Improving home environment and reducing exposure to tobacco smoke may facilitate a favourable asthma symptom trajectory during childhood.

Prevalence and outcome of anemia among children hospitalized for pneumonia and their risk of mortality in a developing country.

Data are limited on the prevalence and outcome of anemia and its risk on mortality among children under five years of age hospitalized for pneumonia/severe pneumonia. Thus, we conducted a secondary analysis of data extracted from Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh to address the evidence gap. Among 3468 children fulfilling the study criteria,1712 (49.4%) had anemia. If children aged ≤ 1.0, > 1.0 to 2.0, > 2.0 to < 6.0, and ≥ 6.0 to 59 months had blood hemoglobin (Hb) value of ≤ 10.7 g/dL, ≤ 9.4 g/dL, ≤ 9.5 g/dL, and ≤ 11 g/dl respectively; we considered them anemic. The trend of prevalence of anemia was found to be inversely related to increasing age (Chi-square for linear trend analysis was done to understand the relation of anemia with increasing age, which was = 6.96; p = 0.008). During hospitalization anemic children more often developed respiratory failure (7.2% vs. 4.4%, p < 0.001) and fatal outcome (7.1.0% vs. 4.2%, p < 0.001) than the children who did not have anemia. After adjusting for potential confounders, such as female sex, lack of immunization, abnormal mental status, severe acute malnutrition, dehydration, hypoxemia, severe sepsis, and bacteremia using multivariable logistic regression analysis, anemia was found to be independently associated with fatal outcome (OR = 1.88, 95% CI 1.23-2.89, p = 0.004). Thus, future interventional studies on the early management of anemia may be warranted to understand whether the intervention reduces the morbidity and deaths in such children.

Prevalence, Predictive Factors, and Outcomes of Respiratory Failure in Children With Pneumonia Admitted in a Developing Country.

Background: Pneumonia has been the leading infectious cause of morbidity and mortality in children under 5 years of age for the last several decades. Although most of these deaths occur due to respiratory failure, published data are limited regarding predicting factors and outcomes of respiratory failure in children hospitalized with pneumonia or severe pneumonia. Objective: This study aimed to explore the prevalence, predicting factors, and outcomes of respiratory failure in children under-five with pneumonia or severe pneumonia. Methods: In this retrospective chart analysis, we enrolled children under 5 years of age hospitalized with pneumonia or severe pneumonia in the Dhaka Hospital of International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) between August 2013 and December 2017. Comparisons were made between children with respiratory failure (n = 212) and those without respiratory failure (n = 4,412). Respiratory failure was defined when the oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) was <315. Results: A total of 4,625 children with pneumonia or severe pneumonia were admitted during this study period. Among them, 212 (4.6%) children developed respiratory failure and formed the case group. A total of 4,412 (95.3%) children did not develop respiratory failure and formed the comparison group. In logistic regression analysis, after adjusting with potential confounders, severe sepsis [adjusted odds ratio (aOR): 12.68, 95% CI: 8.74-18.40], convulsion (aOR: 4.52, 95% CI: 3.06-6.68), anemia (aOR: 1.76, 95% CI: 1.20-2.57), and severe underweight (aOR: 1.97, 95% CI: 1.34-2.89) were found to be independently associated with respiratory failure. As expected, children with respiratory failure more often had fatal outcome than without respiratory failure (74, 1%, p < 0.001). Conclusion: The results of our analyses revealed that prevalence of respiratory failure was 4.6% among under-five children hospitalized for pneumonia or severe pneumonia. Severe sepsis, convulsion, anemia, and severe underweight were the independent predictors for respiratory failure in such children and their case-fatality rate was significantly higher than those without respiratory failure. Early recognition of these predicting factors of respiratory failure may help clinicians imitating prompt treatment that may further help to reduce deaths in such children, especially in resource-limited settings.

Physical Quality of Life of Sepsis Survivor Severely Malnourished Children after Hospital Discharge: Findings from a Retrospective Chart Analysis.

BACKGROUND: Quality of life (QoL) among pediatric sepsis survivors in resource-limited countries is poorly understood. We aimed to evaluate the QoL among sepsis survivors, by comparing them with non-sepsis survivors three months after hospital discharge. METHODOLOGY: In this retrospective chart analysis with a case-control design, we compared children having sepsis and non-sepsis at hospital admission and during their post-hospitalization life, where the study population was derived from a hospital cohort of 405 severely malnourished children having pneumonia. RESULTS: The median age (months, inter-quartile range) of the children having sepsis and non-sepsis was 10 (5, 17) and 9 (5, 18), respectively. Approximately half of the children among the sepsis survivors had new episodes of respiratory symptoms at home. Though death was significantly higher (15.8% vs. 2.7%, p ≤ 0.001) at admission among the sepsis group, deaths during post-hospitalization life (7.8% vs. 8.8%, p = 0.878) were comparable. A verbal autopsy revealed that before death, most of the children from the sepsis group had respiratory complaints, whereas gastrointestinal complaints were more common among the non-sepsis group. CONCLUSIONS: Pediatric sepsis is life-threatening both during hospitalization and post-discharge. The QoL after sepsis is compromised, including re-hospitalization and the development of new episodes of respiratory symptoms especially before death.

Family, neighborhood and psychosocial environmental factors and their associations with asthma in Australia: a systematic review and Meta-analysis.

OBJECTIVE: Various associations between different environmental exposures and asthma have been reported in different countries and populations. We aimed to investigate the associations between family, neighborhood and psychosocial environmental factors and asthma-symptoms in Australia by conducting a systematic review and meta-analysis. DATA SOURCES: We analyzed the primary research studies conducted in Australia across multiple databases, including PubMed, EMBASE and Scopus, published between 2000 and 2020. STUDY SELECTIONS: The reviews and analyses focused on the overall association of different environmental exposures with the exacerbation of asthma-symptoms or asthma-related hospital visits. Quality-effect meta-analysis was done to estimate the pooled odds ratio for different environmental exposures for asthma-symptoms. RESULTS: Among the 4799 unique published articles found, 46 were included here for systematic review and 28 for meta-analysis. Our review found that psychosocial factors, including low socioeconomic condition, maternal depression, mental stress, ethnicity, and discrimination, are associated with asthma-symptoms. Pooled analysis was conducted on family and neighborhood environmental factors and revealed that environmental tobacco smoking (ETS) (OR 1·69, 95% CI 1·19-2·38), synthetic bedding (OR 1·91, 95% CI 1·48-2·47) and gas heaters (OR 1·40, 95% CI 1·12-1·76) had significant overall associations with asthma-symptoms in Australia. CONCLUSION: Although the studies were heterogeneous, both systematic review and meta-analysis found several psychosocial and family environmental exposures significantly associated with asthma-symptoms. Further study to identify their causal relationship and modification may reduce asthma-symptoms in the Australian population.

Risk Factors and Outcomes of Hospital Acquired Pneumonia in Young Bangladeshi Children.

Hospital acquired pneumonia (HAP) is common and often associated with high mortality in children aged five or less. We sought to evaluate the risk factors and outcome of HAP in such children. We compared demographic, clinical, and laboratory characteristics in children <5 years using a case control design during the period of August 2013 and December 2017, where children with HAP were constituted as cases (n = 281) and twice as many randomly selected children without HAP were constituted as controls (n = 562). HAP was defined as a child developing a new episode of pneumonia both clinically and radiologically after at least 48 h of hospitalization. A total of 4101 children were treated during the study period. The mortality was significantly higher among the cases than the controls (8% vs. 4%, p = 0.014). In multivariate logistic regression analysis, after adjusting for potential confounders, it was found that persistent diarrhea (95% CI = 1.32-5.79; p = 0.007), severe acute malnutrition (95% CI = 1.46-3.27; p < 0.001), bacteremia (95% CI = 1.16-3.49; p = 0.013), and prolonged hospitalization of >5 days (95% CI = 3.01-8.02; p < 0.001) were identified as independent risk factors for HAP. Early identification of these risk factors and their prompt management may help to reduce HAP-related fatal consequences, especially in resource limited settings.

Characteristics of Rotavirus, ETEC, and Vibrio Cholerae Among Under 2-year Children Attending an Urban Diarrheal Disease Hospital in Bangladesh.

BACKGROUND: Information on comparative clinical and host characteristics of under-2 children with watery diarrhea caused by rotavirus, Enterotoxigenic Escherichia coli (ETEC), and Vibrio cholerae as single pathogens is lacking. We sought to investigate the sociodemographic, clinical, and host characteristics of under-2 children hospitalized due to these pathogens. METHODOLOGY: We conducted a hospital-based case-control study using the icddr,b Diarrheal Diseases Surveillance System. Children of either sex, <2 years with diarrhea, who attended the hospital during 2014 to 2018, constituted the study population. Stool specimens having a single pathogen like rotavirus, ETEC, or Vibrio cholerae constituted the cases and stool specimens having no detectable common enteropathogens comprised the controls. Multinomial logistic regression analysis was done where control was the reference group. RESULTS: A total of 14 889 patients were enrolled, 6939 of whom were under-2 children, and 5245 (76%) constituted our study population. Among them 48% (n = 2532), 3% (n = 148) and 1% (n = 49) had rotavirus, ETEC, and Vibrio cholera, respectively. A control group (diarrhea without these 3 or Shigella, Salmonella, Aeromonas) accounted for 48% (n = 2516). In multinomial regression model, children with rotavirus (adjusted odds ratio [aOR], 1.36; 95% confidence interval [95% CI], 1.19-1.55) less often presented with dehydrating diarrhea compared to those with ETEC (aOR, 1.54; 95% CI, 1.05-2.26) and cholera (aOR, 2.25; 95% CI, 1.11-4.57). Rotavirus diarrhea was associated (aOR, 1.25; 95% CI, 1.07-1.46) with those who received antimicrobials prior to hospital admission and protectively associated with drinking tap water (aOR, 0.84; 95% CI, 0.73-0.95); however, ETEC diarrhea had protective association (aOR, 0.62; 95% CI, 0.43-0.92) with children who received antimicrobials prior to hospital admission and was associated with drinking tap water (aOR, 1.78; 95% CI, 1.19-2.66). Use of intravenous fluid was associated with cholera (aOR, 10.36; 95% CI, 4.85-22.16) and had protective association with rotavirus episodes (aOR, 0.64; 95% CI, 0.45-0.91). CONCLUSIONS: Clinical presentations and host characteristics of rotavirus, ETEC, and Vibrio cholerae diarrhea differed from each other and the information may be helpful for clinicians for better understanding and proper management of these children.

Topical emollient therapy with sunflower seed oil alters the skin microbiota of young children with severe acute malnutrition in Bangladesh: A randomised, controlled study.

BACKGROUND: Topical emollient therapy with sunflower seed oil (SSO) reduces risk of sepsis and mortality in very preterm infants in low- or middle-income countries (LMICs). Proposed mechanisms include modulation of skin and possibly gut barrier function. The skin and gut microbiota play important roles in regulating barrier function, but the effects of emollient therapy on these microbiotas are poorly understood. METHODS: We characterised microbiota structure and diversity with 16S rRNA gene amplicon sequence data and ecological statistics in 20 children with severe acute malnutrition (SAM) aged 2-24 months, at four skin sites and in stool, during a randomised, controlled trial of emollient therapy with SSO in Bangladesh. Microbes associated with therapy were identified with tree-based sparse discriminant analysis. RESULTS: The skin microbiota of Bangladeshi children with SAM was highly diverse and displayed significant variation in structure as a function of physical distance between sites. Microbiota structure differed between the study groups (P = 0.005), was more diverse in emollient-treated subjects-including on the forehead which did not receive direct treatment-and changed with each day (P = 0.005) at all skin sites. Overall, Prevotellaceae were the most differentially affected by emollient treatment; several genera within this family became more abundant in the emollient group than in the controls across several skin sites. Gut microbiota structure was associated with sample day (P = 0.045) and subject age (P = 0.045), but was not significantly affected by emollient treatment (P = 0.060). CONCLUSIONS: Emollient therapy altered the skin microbiota in a consistent and temporally coherent manner. We speculate that therapy with SSO enhances skin barrier function in part through alterations in the microbiota, and through systemic mechanisms. Strategies to strengthen skin and gut barrier function in populations at risk, such as children in LMICs like Bangladesh, might include deliberate manipulation of their skin microbiota. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02616289.

Antibiotic-Resistant Bacteremia in Young Children Hospitalized With Pneumonia in Bangladesh Is Associated With a High Mortality Rate.

BACKGROUND: Pneumonia is a leading cause of sepsis and mortality in children under 5 years. However, our understanding of the causes of bacteremia in children with pneumonia is limited. METHODS: We characterized risk factors for bacteremia and death in a cohort of children admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) between 2014 and 2017 with radiographically confirmed pneumonia. RESULTS: A total of 4007 young children were hospitalized with pneumonia over the study period. A total of 1814 (45%) had blood cultures obtained. Of those, 108 (6%) were positive. Gram-negative pathogens predominated, accounting for 83 (77%) of positive cultures. These included Pseudomonas (N = 22), Escherichia coli (N = 17), Salmonella enterica (N = 14, including 11 Salmonella Typhi), and Klebsiella pneumoniae (N = 11). Gram-positive pathogens included Pneumococcus (N = 7) and Staphylococcus aureus (N = 6). Resistance to all routinely used empiric antibiotics (ampicillin, gentamicin, ciprofloxacin, and ceftriaxone) for children with pneumonia at the icddr,b was observed in 20 of the 108 isolates. Thirty-one of 108 (29%) children with bacteremia died, compared to 124 of 1706 (7%) who underwent culture without bacteremia (odds ratio [OR], 5.1; 95% confidence interval [CI], 3.3-8.1; P < .001). Children infected with bacteria resistant to all routinely used empiric antibiotics were at greater risk of death compared to children without bacteremia (OR, 17.3; 95% CI, 7.0-43.1; P < .001). CONCLUSIONS: Antibiotic-resistant Gram-negative bacteremia in young children with pneumonia in Dhaka, Bangladesh was associated with a high mortality rate. The pandemic of antibiotic resistance is shortening the lives of young children in Bangladesh, and new approaches to prevent and treat these infections are desperately needed.

Effect of topical applications of sunflower seed oil on systemic fatty acid levels in under-two children under rehabilitation for severe acute malnutrition in Bangladesh: a randomized controlled trial.

BACKGROUND: Children with severe acute malnutrition (SAM) have inadequate levels of fatty acids (FAs) and limited capacity for enteral nutritional rehabilitation. We hypothesized that topical high-linoleate sunflower seed oil (SSO) would be effective adjunctive treatment for children with SAM. METHODS: This study tested a prespecified secondary endpoint of a randomized, controlled, unblinded clinical trial with 212 children with SAM aged 2 to 24 months in two strata (2 to < 6 months, 6 to 24 months in a 1:2 ratio) at Dhaka Hospital of icddr,b, Bangladesh between January 2016 and December 2017. All children received standard-of-care management of SAM. Children randomized to the emollient group also received whole-body applications of 3 g/kg SSO three times daily for 10 days. We applied difference-in-difference analysis and unsupervised clustering analysis using t-distributed stochastic neighbor embedding (t-SNE) to visualize changes in FA levels in blood from day 0 to day 10 of children with SAM treated with emollient compared to no-emollient. RESULTS: Emollient therapy led to systematically higher increases in 26 of 29 FAs over time compared to the control. These effects were driven primarily by changes in younger subjects (27 of 29 FAs). Several FAs, especially those most abundant in SSO showed high-magnitude but non-significant incremental increases from day 0 to day 10 in the emollient group vs. the no-emollient group; for linoleic acid, a 237 µg/mL increase was attributable to enteral feeding and an incremental 98 µg/mL increase (41%) was due to emollient therapy. Behenic acid (22:0), gamma-linolenic acid (18:3n6), and eicosapentaenoic acid (20:5n3) were significantly increased in the younger age stratum; minimal changes were seen in the older children. CONCLUSIONS: SSO therapy for SAM augmented the impact of enteral feeding in increasing levels of several FAs in young children. Further research is warranted into optimizing this novel approach for nutritional rehabilitation of children with SAM, especially those < 6 months. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02616289 .

Seizure in Children Under Five Presenting With Pneumonia in a Critical Care Ward in Bangladesh: Prevalence, Associated Factors, and Outcome.

BACKGROUND: Pneumonia is the leading infectious cause of deaths in children under 5 for the last few decades. Development of seizure in those children is common and associated with increased risk of deaths. We therefore investigated the prevalence, associated factors and outcome of seizure in children hospitalized with pneumonia. METHODS: We conducted a retrospective chart analysis in the intensive care unit of the Dhaka Hospital of icddr,b. Children under 5 with World Health Organization (WHO) classified clinical (excluding seizure as 1 of the clinical diagnostics) and radiologic pneumonia, admitted to the intensive care unit at Dhaka Hospital of icddr,b between August 2013 and December 2017 were analyzed. We initially identified the children with pneumonia who had seizure. For comparison, we have taken 2 folds randomly selected controls from rest of the children with pneumonia having no seizure. Prevalence and outcome of children with pneumonia and seizure were measured. Factors associated with seizure in children with pneumonia compared with those without seizure were also identified. Seizure was characterized by sudden, violent, involuntary, and abnormal repetitive movements with or without loss or impairment of consciousness confirmed by attending physician. RESULTS: Among a total of 4101 children with pneumonia, 514 (12.5%) had seizure. Compared with children with pneumonia alone children having pneumonia and seizure more often developed respiratory failure (18% vs. 3%, P < 0.001) and died (13% vs. 3%, P < 0.001) during hospitalization. In logistic regression analysis hypoxemia (95% CI: 1.59-3.17, P < 0.001), severe pneumonia (95% CI: 2.13-6.52, P < 0.001), severe sepsis (95% CI: 1.30-2.88, P = 0.001), and hypernatremia (95% CI: 5.31-10.93, P < 0.001) were found to be independent risk factors for seizure. On the contrary, children with pneumonia having seizure were less likely to have severe acute malnutrition (95% CI: 0.26-0.50, P < 0.001). CONCLUSIONS: Early identification of risk factors for seizure in children with pneumonia may be helpful for clinicians to promptly treat them and therefore may have potential to reduce deaths in those children especially in resource limited settings.

Early management of hypokalaemia in severely malnourished children under five could help to reduce deaths in developing countries.

AIM: This study evaluated the factors associated with hypokalaemia and their outcomes, in severely malnourished children under 5 years of age. METHODS: We focused on 407 severely malnourished children under five who were admitted to the Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh, from April 2011 to June 2012. The cases were 139 with hypokalaemia, and the comparisons were 268 without hypokalaemia. RESULTS: Cases were older than the comparisons, with a poor socio-economic status and a higher death rate of 12% vs 7%. They were more likely to present with a history of measles, diarrhoea, lethargy, lower pulse rates, hyponatraemia, metabolic acidosis, hypocalcaemia, hypomagnesaemia, higher height or length, severe underweight, severe wasting and leucocytosis on admission. At discharge, cases had lower potassium levels and a higher proportion had persistent hypokalaemia. Cases received longer treatment with ampicillin and micronutrients. After adjusting for confounders, hypokalaemia was independently associated with poor socio-economic status, diarrhoea, lower pulse rates, hypocalcaemia, metabolic acidosis and leucocytosis. CONCLUSION: Identifying simple clinical signs, like diarrhoea and lower pulse rates, and laboratory parameters, such as hypocalcaemia and metabolic acidosis, may enable the early management of hypokalaemia in severely malnourished children under 5 years. This could reduce morbidity and mortality.

Clinical and laboratory characteristics of children under five hospitalized with diarrhea and bacteremia.

BACKGROUND: Diarrhea is one of the leading causes of mortality in children under five globally. When it is associated with bacteremia, mortality is even higher. However, bacteraemia in diarrheal children has gained little attention in spite of its deleterious impact in under-five mortality. So, we aimed to evaluate associated clinical and laboratory factors for death in under-five children hospitalized with both diarrhea and bacteremia. METHODS: In this retrospective cross-sectional study, we used patients' electronic database of Dhaka Hospital of 'icddr,b', and enrolled all under-five children with diarrhea and bacterial growth in their blood samples on admission between June-2014 and May-2017. Clinical and laboratory characteristics were compared between those who died and who survived with a special attention to bacterial pathogens related to deaths and their sensitivity pattern. RESULTS: In a total of 401 diarrheal children with bacteraemia, 45 (11%) died. Although Salmonella Typhi (34%) was the most predominant isolate followed by Staphylococcus species (16%) and Pseudomonas species (9%), children who died more often had E. coli (OR = 5.69, 95% CI = 2.42-13.39, p = <0.001) and Klebsiella bacteraemia (OR = 4.59, 95% CI = 1.84-11.46, p = 0.001) compared to those who survived. However, none of them was significantly associated with deaths in regression analysis when adjusted with other potential confounders. E. coli was 100% resistant to ampicillin, 41% to gentamicin, and 73% to ceftriaxone and Klebsiella species was 96% resistant to ampicillin, 42% to gentamicin, and 62% to ceftriaxone. Study children who died had significantly higher overall resistance pattern shown in World Health Organization (WHO) recommended one of the first line antibiotics in treating childhood sepsis such as ampicillin (80% vs. 50%, p = 0.001) and in second line antibiotic such as ceftriaxone (49% vs. 22%, p = 0.001) compared to the survivors. In logistic regression analysis, after adjusting for potential confounders, we found that clinical sepsis (aOR 3.79, 95% CI 1.60-8.96, p = 0.002), hypoxemia (aOR 4.20, 95% CI 1.74-10.12, p = 0.001), and hyperkalaemia (aOR 2.69, 95% CI 1.05-6.91, p = 0.039) were found to be independent predictors of deaths and receipt of sensitive antibiotic (aOR 0.42, 95% CI 0.18-0.99, p = 0.048) was revealed as the independent protective factor for deaths in this population. CONCLUSION AND SIGNIFICANCE: The results of our data suggest that diarrheal children with bacteremia who died more often had gram negative bacteremia compared to those who survived and these pathogens are highly resistant to WHO recommended first line and second line antibiotics. The results further emphasize the critical importance of early identification of important clinical problems such as clinical sepsis, hypoxemia and hyperkalaemia in diarrheal children and treat them with potential sensitive antibiotic(s) in order to reduce bacteremia related mortality in children with diarrhea, especially in resource limited settings.

Topical emollient therapy in the management of severe acute malnutrition in children under two: A randomized controlled clinical trial in Bangladesh.

BACKGROUND: Topical emollient therapy can improve neonatal health and growth and potentially provides an additional avenue for augmenting the provision of nutrition to children with severe acute malnutrition (SAM). We hypothesised that topical treatment of hospitalised children with SAM using sunflower seed oil (SSO), in addition to standard-of-care for SAM, would improve skin barrier function and weight gain, reduce risk of infection, and accelerate clinical recovery. METHODS: We conducted a randomised, two-arm, controlled, unblinded clinical trial in 212 subjects aged 2 to 24 months who were admitted for care of SAM at the 'Dhaka Hospital' of icddr,b during January 2016 to November 2017. Enrollment was age-stratified into 2 to <6 months and 6 to 24 months age groups in a 1:2 ratio. All children received SAM standard-of-care, and the SSO group was also treated with 3 g of SSO per kg body weight three times daily for 10 days. Primary outcome was rate of weight gain over the 10-day study period. Secondary endpoints included rate of nosocomial infection, time to recovery from acute illness, skin condition score, rate of transepidermal water loss (TEWL) and C-reactive protein (CRP) level. RESULTS: Rate of weight gain was higher in the SSO than the control group (adjusted mean difference, AMD = 0.90 g/kg/d, 95% confidence interval (CI) = -1.22 to 3.03 in the younger age stratum), but did not reach statistical significance. Nosocomial infection rate was significantly lower in the SSO group in the older age stratum (adjusted odds ratio (OR) = 0.41, 95% CI = 0.19 to 0.85; P = 0.017), but was comparable in the younger age stratum and overall. Skin condition score improved (AMD = -14.88, 95% CI = -24.12 to -5.65, P = 0.002) and TEWL was reduced overall (AMD = -2.59, 95% CI = -3.86 to -1.31, P < 0.001) in the SSO group. Reduction in CRP level was significantly greater in the SSO group (median: -0.28) than the control group (median 0.00) (P = 0.019) in the younger age stratum. CONCLUSIONS: Topical therapy with SSO was beneficial for children with SAM when applied as adjunctive therapy. A community-based trial with a longer intervention period is recommended to validate these results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02616289.