Implementation of bubble continuous positive airway pressure for children with severe pneumonia and hypoxemia in intensive care unit of Dhaka Hospital, Bangladesh-Effect on pneumonia mortality.

BACKGROUND: After the completion of a randomized trial at Dhaka Hospital in 2013, bubble continuous positive airway pressure (BCPAP) oxygen therapy was incorporated as the part of the standard treatment for children with severe pneumonia with hypoxemia in an intensive care unit at Dhaka Hospital in August 2013 instead of World Health Organization (WHO) standard low flow oxygen therapy. OBJECTIVE: To understand the long-term effectiveness of the introduction of bCPAP oxygen therapy by comparing pneumonia mortality in the post-trial period (August 2013 to December 2017) with the pre-trial (February 2009 to July 2011) and trial periods (August 2011 to July 2013). METHODS: It was a retrospective analysis of prospectively collected hospital data of all admissions. Mortality rates of all children with WHO-defined pneumonia, and the subset of children with severe pneumonia and hypoxemia (oxygen saturation <90%) were evaluated. RESULTS: The analysis covered 10,107 children with pneumonia: 2523 in the pre-trial (414 with severe pneumonia and hypoxemia; none of them received bCPAP), 2959 during the trial (376 with severe pneumonia and hypoxemia; 79 received bCPAP), and 4625 in the post-trial period (1208 with severe pneumonia and hypoxemia; 1125 had bCPAP). The risk of death from pneumonia in the post-trial period was lower than in pre-trial (adjusted risk ratio [RR] = 0.73, 95% confidence interval [CI] = 0.58-0.92; p = 0.007), among children with severe pneumonia and hypoxemia, the risk of death was lower in the post-trial period than in the pre-trial (adjusted RR = 0.46, 95% CI = 0.37-0.58, p < 0.001), and the trial period (adjusted RR = 0.70, 95% CI = 0.51-0.95; p = 0.023). CONCLUSION: After the introduction of bCPAP oxygen therapy as part of the routine management of severe pneumonia and hypoxemia in the ICU of the Dhaka hospital, we observed significantly lower mortality, even after accounting for measurable confounding.

Clinical and Genomic Characterization of a Cohort of Patients With Klebsiella pneumoniae Bloodstream Infection.

BACKGROUND: The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a record review and whole-genome sequencing to investigate the clinical characteristics, bacterial diversity, determinants of antimicrobial resistance, and risk factors for in-hospital death in a cohort of patients with K. pneumoniae BSI. METHODS: We identified 562 patients at Massachusetts General Hospital with K. pneumoniae BSIs between 2016 and 2022. We collected data on comorbid conditions, infection source, clinical outcomes, and antibiotic resistance and performed whole-genome sequencing on 108 sequential BSI isolates from 2021 to 2022. RESULTS: Intra-abdominal infection was the most common source of infection accounting for 34% of all BSIs. A respiratory tract source accounted for 6% of BSIs but was associated with a higher in-hospital mortality rate (adjusted odds ratio, 5.4 [95% confidence interval, 2.2-12.8]; P < .001 for comparison with other sources). Resistance to the first antibiotic prescribed was also associated with a higher risk of death (adjusted odds ratio, 5.2 [95% confidence interval, 2.2-12.4]; P < .001). BSI isolates were genetically diverse, and no clusters of epidemiologically and genetically linked cases were observed. Virulence factors associated with invasiveness were observed at a low prevalence, although an unexpected association between O-antigen type and the source of infection was found. CONCLUSIONS: These observations demonstrate the versatility of K. pneumoniae as an opportunistic pathogen and highlight the need for new approaches for surveillance and the rapid identification of patients with invasive antimicrobial-resistant K. pneumoniae infection.

Smokeless tobacco consumption and its association with risk factors of chronic kidney disease in rural and peri-urban Bangladesh.

INTRODUCTION: Compared to smoking, which has major consequences in chronic kidney disease (CKD) initiation and progression, smokeless tobacco (SLT) consumption is considered to have fewer health consequences. We investigated the prevalence of SLT consumption and its association with risk factors of CKD in a rural and peri-urban Bangladeshi population. METHODS: Using random sampling we recruited 872 adults in 2020, from the Mirzapur Demographic Surveillance System of Bangladesh, who had resided in the area for at least five years. Interviews using a semi-structured questionnaire, physical examination and anthropometric measurements were done, followed by blood and urine testing. The blood and urine tests were repeated in selected participants after three months as per the CKD Epidemiology Collaboration equation. RESULTS: The prevalence of SLT consumption was 29%. Being aged ≥46 years (OR=7.10; 95% CI: 4.79-10.94), female (OR=1.64; 95% CI: 1.21-2.22), housewife (OR=1.82; 95% CI: 1.35-2.45), farmer (OR=1.71; 95% CI: 1.06-2.76), widow (OR=3.40; 95% CI: 2.24-5.17), and having no formal schooling (OR=4.91; 95% CI: 3.59-6.72), family income of <$100/month (OR=1.66; 95% CI: 1.13-2.43), sleeping duration <7 hours per day (OR=2.33; 95% CI: 1.70-3.19), were associated with a significantly higher odds of SLT consumption. However, being aged 31-45 years (OR=0.25; 95% CI: 0.16-0.38) had significantly lower odds of being an SLT consumer. Among the diseases investigated, undernutrition (OR=1.63; 95% CI: 1.15-2.33), hypertension (OR=1.52; 95% CI: 1.13-2.05), anemia (OR=1.94; 95% CI: 1.39-2.71) and CKD (OR=1.62; 95% CI: 1.15-2.27) were significantly associated with SLT consumption. In the multivariable analysis, being aged 31-45 years (AOR=3.06; 95% CI: 1.91-4.90), ≥46 years (AOR=15.69; 95% CI: 4.64-53.09) and having no formal schooling (AOR=2.47; 95% CI: 1.72-3.55) were found to have a significant association with being an SLT consumer. CONCLUSIONS: SLT consumption is associated with most of the established risk factors of CKD within the studied population.

Effectiveness, safety and economic viability of daycare versus usual hospital care management of severe pneumonia with or without malnutrition in children using the existing health system of Bangladesh: a cluster randomised controlled trial.

Background: We aimed to define clinical and cost-effectiveness of a Day Care Approach (DCA) alternative to Usual Care (UC, comparison group) within the Bangladesh health system to manage severe childhood pneumonia. Methods: This was a cluster randomised controlled trial in urban Dhaka and rural Bangladesh between November 1, 2015 and March 23, 2019. Children aged 2-59 months with severe pneumonia with or without malnutrition received DCA or UC. The DCA treatment settings comprised of urban primary health care clinics run by NGO under Dhaka South City Corporation and in rural Union health and family welfare centres under the Ministry of Health and Family welfare Services. The UC treatment settings were hospitals in these respective areas. Primary outcome was treatment failure (persistence of pneumonia symptoms, referral or death). We performed both intention-to-treat and per-protocol analysis for treatment failure. Registered at www.ClinicalTrials.gov, NCT02669654. Findings: In total 3211 children were enrolled, 1739 in DCA and 1472 in UC; primary outcome data were available in 1682 and 1357 in DCA and UC, respectively. Treatment failure rate was 9.6% among children in DCA (167 of 1739) and 13.5% in the UC (198 of 1472) (group difference, -3.9 percentage point; 95% confidence interval (CI), -4.8 to -1.5, p = 0.165). Treatment success within the health care systems [DCA plus referral vs. UC plus referral, 1587/1739 (91.3%) vs. 1283/1472 (87.2%), group difference 4.1 percentage point, 95% CI, 3.7 to 4.1, p = 0.160)] was better in DCA. One child each in UC of both urban and rural sites died within day 6 after admission. Average cost of treatment per child was US$94.2 (95% CI, 92.2 to 96.3) and US$184.8 (95% CI, 178.6 to 190.9) for DCA and UC, respectively. Interpretation: In our population of children with severe pneumonia with or without malnutrition, >90% were successfully treated at Day care Clinics at 50% lower cost. A modest investment to upgrade Day care facilities may provide a cost-effective, accessible alternative to hospital management. Funding: UNICEF, Botnar Foundation, UBS Optimus Foundation, and EAGLE Foundation, Switzerland.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

The Role of Food Insecurity and Dietary Diversity on Recovery from Wasting among Hospitalized Children Aged 6-23 Months in Sub-Saharan Africa and South Asia.

Background: Current guidelines for the management of childhood wasting primarily focus on the provision of therapeutic foods and the treatment of medical complications. However, many children with wasting live in food-secure households, and multiple studies have demonstrated that the etiology of wasting is complex, including social, nutritional, and biological causes. We evaluated the contribution of household food insecurity, dietary diversity, and the consumption of specific food groups to the time to recovery from wasting after hospital discharge. Methods: We conducted a secondary analysis of the Childhood Acute Illness Network (CHAIN) cohort, a multicenter prospective study conducted in six low- or lower-middle-income countries. We included children aged 6−23 months with wasting (mid-upper arm circumference [MUAC] ≤ 12.5 cm) or kwashiorkor (bipedal edema) at the time of hospital discharge. The primary outcome was time to nutritional recovery, defined as a MUAC > 12.5 cm without edema. Using Cox proportional hazards models adjusted for age, sex, study site, HIV status, duration of hospitalization, enrollment MUAC, referral to a nutritional program, caregiver education, caregiver depression, the season of enrollment, residence, and household wealth status, we evaluated the role of reported food insecurity, dietary diversity, and specific food groups prior to hospitalization on time to recovery from wasting during the 6 months of posthospital discharge. Findings: Of 1286 included children, most participants (806, 63%) came from food-insecure households, including 170 (13%) with severe food insecurity, and 664 (52%) participants had insufficient dietary diversity. The median time to recovery was 96 days (18/100 child-months (95% CI: 17.0, 19.0)). Moderate (aHR 1.17 [0.96, 1.43]) and severe food insecurity (aHR 1.14 [0.88, 1.48]), and insufficient dietary diversity (aHR 1.07 [0.91, 1.25]) were not significantly associated with time to recovery. Children who had consumed legumes and nuts prior to diagnosis had a quicker recovery than those who did not (adjusted hazard ratio (aHR): 1.21 [1.01,1.44]). Consumption of dairy products (aHR 1.13 [0.96, 1.34], p = 0.14) and meat (aHR 1.11 [0.93, 1.33]), p = 0.23) were not statistically significantly associated with time to recovery. Consumption of fruits and vegetables (aHR 0.78 [0.65,0.94]) and breastfeeding (aHR 0.84 [0.71, 0.99]) before diagnosis were associated with longer time to recovery. Conclusion: Among wasted children discharged from hospital and managed in compliance with wasting guidelines, food insecurity and dietary diversity were not major determinants of recovery.

Factors associated with community acquired severe pneumonia among under five children in Dhaka, Bangladesh: A case control analysis.

BACKGROUND: Pneumonia is the leading cause of death in children globally with the majority of these deaths observed in resource-limited settings. Globally, the annual incidence of clinical pneumonia in under-five children is approximately 152 million, mostly in the low- and middle-income countries. Of these, 8.7% progressed to severe pneumonia requiring hospitalization. However, data to predict children at the greatest risk to develop severe pneumonia from pneumonia are limited. METHOD: Secondary data analysis was performed after extracting relevant data from a prospective cluster randomized controlled clinical trial; children of either sex, aged two months to five years with pneumonia or severe pneumonia acquired in the community were enrolled over a period of three years in 16 clusters in urban Dhaka city. RESULTS: The analysis comprised of 2,597 children aged 2-59 months. Of these, 904 and 1693 were categorized as pneumonia (controls) and severe pneumonia (cases), respectively based on WHO criteria. The median age of children was 9.2 months (inter quartile range, 5.1-17.1) and 1,576 (60%) were male. After adjustment for covariates, children with temperature ≥38°C, duration of illness ≥3 days, male sex, received prior medical care and severe stunting showed a significantly increased likelihood of developing severe pneumonia compared to those with pneumonia. Severe pneumonia in children occurred more often in older children who presented commonly from wealthy quintile families, and who often sought care from private facilities in urban settings. CONCLUSION AND RECOMMENDATION: Male sex, longer duration of illness, fever, received prior medical care, and severe stunting were significantly associated with development of WHO-defined severe childhood pneumonia in our population. The results of this study may help to develop interventions target to reduce childhood morbidity and mortality of children suffering from severe pneumonia.

Health and nutritional status of children hospitalized during the COVID-19 pandemic, Bangladesh.

OBJECTIVE: To compare the health and nutrition of children younger than 5 years admitted to hospital during and before the coronavirus disease 2019 (COVID-19) pandemic in Bangladesh. METHODS: We collected data from hospital records of children 0-59 months admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh in March 2020-February 2021 (COVID-19 period; n = 2552) and March 2019-February 2020 (pre-COVID-19 period; n = 6738). Data collected included sociodemographic, anthropometric, clinical and biochemical characteristics. We compared these data for child admissions in the COVID-19 and pre-COVID-19 periods, including infants 0-11 months born during and before the pandemic and admitted to hospital. FINDINGS: Admissions of children as a percentage of total admissions were lower in March 2020 (2.47%; 63/2552) than March 2019 (8.30%; 559/6738), but increased to 20.61% (526/2552) in February 2021, three times greater than in the pre-COVID-19 period (6.69%; 451/6738). Children admitted during the COVID-19 period were significantly more likely to have dehydration, severe sepsis or septic shock, convulsions, hypernatraemia and raised creatinine than children admitted before the pandemic (P < 0.05). In infants < 6 months and those born during the pandemic, stunting and wasting were significantly higher than in infants in the pre-COVID-19 period (P < 0.05). The risk of death was higher in infants < 6 months during the pandemic (odds ratio: 1.66; 95% confidence interval: 0.95-2.92). CONCLUSION: During the pandemic, children presented with more severe illness and poorer nutrition. Efforts are needed to reduce the adverse effects of the pandemic on the health and well-being of children.

Continuous positive airway pressure for children in resource-limited settings, effect on mortality and adverse events: systematic review and meta-analysis.

OBJECTIVE: Determine non-invasive ventilation with continuous positive airway pressure (CPAP) outcomes for paediatric respiratory distress in low-income and middle-income countries (LMICs). DESIGN: Systematic review and meta-analysis. SETTING: LMIC hospitals. PATIENTS: One month to 15 year olds with respiratory distress. INTERVENTIONS: We searched Medline, Embase, LILACS, Web of Science and Scopus on 7 April 2020. Included studies assessed CPAP safety, efficacy or effectiveness. All study types were included; neonatal only studies were excluded. Data were extracted by two reviewers and bias was assessed. Certainty of evidence was evaluated, and risk ratios (RR) were produced for meta-analyses. (PROSPERO protocol CRD42018084278). RESULTS: 2174 papers were screened, 20 were included in the systematic review and 3 were included in two separate meta-analyses of mortality and adverse events. Studies suitable for meta-analysis were randomised controlled trials (RCTs) from Bangladesh, Ghana and Malawi. For meta-analyses comparing death or adverse events between CPAP and low-flow oxygen recipients, we found no clear CPAP effect on mortality (RR 0.75, 95% CI 0.33 to 1.72) or adverse events (RR 1.52, CI 0.71 to 3.26). We downgraded the certainty of evidence for both death and adverse events outcomes to 'low' due to design issues and results discrepancies across RCTs. CONCLUSIONS: Evidence for CPAP efficacy against mortality and adverse events has low certainty and is context dependent. Hospitals introducing CPAP need to have mechanisms in place to optimise safety in the context it is being used; this includes the location (a high dependency or intensive care area), adequate numbers of staff trained in CPAP use, close monitoring and mechanisms for escalation, daily direct physician supervision, equipment that is age appropriate and user-friendly and continuous monitoring of outcomes and quality of care.

Early childhood malnutrition trajectory and lung function at preadolescence.

OBJECTIVE: Chronic undernutrition is a common phenomenon in Bangladesh. However, information is grossly lacking to report the correlation between chronic undernutrition trajectory and lung function in children. The aim of the current study was to understand the association between early-childhood chronic undernutrition trajectory and lung function at preadolescence. DESIGN: The current study is a part of the 9-year follow-up of a large-scale cohort study called the Maternal and Infant Nutrition Interventions in Matlab. SETTINGS: The current study was conducted in Matlab, a sub-district area of Bangladesh that is located 53 km south of the capital, Dhaka. PARTICIPANTS: A total of 517 children participated in lung function measured with a spirometer at the age of 9 years. Weight and height were measured at five intervals from birth till the age of 9 years. RESULTS: Over half of the cohort have experienced a stunting undernutrition phenomenon up to 9 years of age. Children who were persistently or intermittently stunted showed lower forced expiratory volume (ml/s) than normal-stature children (P < 0·05). Children who exhibited catch-up growth throughout 4·5 years from the stunted group showed similar lung function with normal counterparts, and a better lung function than in children with the same growth velocity or who had faltering growth. In the multivariable models, similar associations were observed in children who experienced catch-up growth than their counterparts after adjusting for covariates. CONCLUSION: Our data suggest that catch-up growth in height during early childhood is associated with a better lung function at preadolescence.

Electronic decision support and diarrhoeal disease guideline adherence (mHDM): a cluster randomised controlled trial.

BACKGROUND: Acute diarrhoeal disease management often requires rehydration alone without antibiotics. However, non-indicated antibiotics are frequently ordered and this is an important driver of antimicrobial resistance. The mHealth Diarrhoea Management (mHDM) trial aimed to establish whether electronic decision support improves rehydration and antibiotic guideline adherence in resource-limited settings. METHODS: A cluster randomised controlled trial was done at ten district hospitals in Bangladesh. Inclusion criteria were patients aged 2 months or older with uncomplicated acute diarrhoea. Admission orders were observed without intervention in the pre-intervention period, followed by randomisation to electronic (rehydration calculator) or paper formatted WHO guidelines for the intervention period. The primary outcome was rate of intravenous fluid ordered as a binary variable. Generalised linear mixed-effect models, accounting for hospital clustering, served as the analytical framework; the analysis was intention to treat. The trial is registered with ClinicalTrials.gov (NCT03154229) and is completed. FINDINGS: From March 11 to Sept 10, 2018, 4975 patients (75·6%) of 6577 screened patients were enrolled. The intervention effect for the primary outcome showed no significant differences in rates of intravenous fluids ordered as a function of decision-support type. Intravenous fluid orders decreased by 0·9 percentage points for paper electronic decision support and 4·2 percentage points for electronic decision support, with a 4·2-point difference between decision-support types in the intervention period (paper 98·7% [95% CI 91·8-99·8] vs electronic 94·5% [72·2-99·1]; pinteraction=0·31). Adverse events such as complications and mortality events were uncommon and could not be statistically estimated. INTERPRETATION: Although intravenous fluid orders did not change, electronic decision support was associated with increases in the volume of intravenous fluid ordered and decreases in antibiotics ordered, which are consistent with WHO guidelines. FUNDING: US National Institutes of Health.

Clinical and laboratory predictors of 30-day mortality in severe acute malnourished children with severe pneumonia.

OBJECTIVE: To determine the predictors of mortality within 30 days of hospital admission in a diarrhoeal disease hospital in Bangladesh. METHODS: Cohort study of hospitalised children aged 0-59 months with severe acute malnutrition (SAM) and severe pneumonia in Dhaka Hospital, icddr,b, Bangladesh from April 2015 to March 2017. Those discharged were followed up, and survival status at 30 days from admission was determined. Children who died were compared with the survivors in terms of clinical and laboratory biomarkers. Multivariable logistic regression analysis was used for calculating adjusted odds ratio for death within 30 days of hospital admission. RESULTS: We enrolled 191 children. Mortality within 30 days of admission was 6% (14/191). After adjusting for potential confounders (hypoxia, CRP and haematocrit) in logistic regression analysis, independent factors associated with death were female sex (aOR = 5.80, 95% CI: 1.34-25.19), LAZ <-4 (aOR = 6.51, 95% CI: 1.49-28.44) and Polymorphonuclear Leucocytes (PMNL) (>6.0 × 109 /L) (aOR = 1.06, 95% CI: 1.01-1.11). Using sex, Z-score for length for age (LAZ), and PMNL percentage, we used random forest and linear regression models to achieve a cross-validated AUC of 0.83 (95% CI: 0.82, 0.84) for prediction of 30-day mortality. CONCLUSIONS: The results of our data suggest that female sex, severe malnutrition (<-4 LAZ) and higher PMNL percentage were prone to be associated with 30-day mortality in children with severe pneumonia. Association of these factors may be used in clinical decision support for prompt identification and appropriate management for prevention of mortality in this population.

OBJECTIF: Déterminer les prédicteurs de mortalité dans les 30 jours suivant l'admission à l'hôpital dans un hôpital pour maladies diarrhéiques au Bangladesh. MÉTHODES: Etude de cohorte d'enfants hospitalisés âgés de 0 à 59 mois atteints de malnutrition aiguë sévère (MAS) et de pneumonie sévère à l'hôpital de Dhaka, icddr,b, au Bangladesh d'avril 2015 à mars 2017. Ceux qui ont été libérés ont été suivis et leur état de survie à 30 jours de l'admission a été déterminé. Les enfants décédés ont été comparés aux survivants en termes de biomarqueurs cliniques et de laboratoire. Une analyse de régression logistique multivariée a été utilisée pour calculer le rapport de cotes ajusté pour le décès dans les 30 jours suivant l'admission à l'hôpital. RÉSULTATS: Nous avons inscrit 191 enfants. La mortalité dans les 30 jours suivant l'admission était de 6% (14/191). Après ajustement pour les facteurs confusionnels potentiels (hypoxie, CRP et hématocrite) dans l'analyse de régression logistique, les facteurs indépendants associés au décès étaient le sexe féminin (aOR = 5,80 ; IC95%: 1,34 à 25,19), LAZ <-4 (aOR = 6,51 ; IC95%: 1,49-28,44) et leucocytes polymorphonucléaires (LPMN) (>6,0 x 109 /L) (aOR = 1,06 ; IC95%: 1,01-1,11). En utilisant le sexe, le score Z de la taille pour l'âge (LAZ) et le pourcentage de LPMN, nous avons utilisé des modèles de régression linéaire et de forest aléatoires pour obtenir une AUC validée croisée de 0,83 (IC95%: 0,82-0,84) pour la prédiction de la mortalité à 30 jours. CONCLUSIONS: Les résultats de nos données suggèrent que le sexe féminin, la malnutrition sévère (LAZ <-4) et un pourcentage plus élevé de LPMN étaient susceptibles d'être associés à la mortalité à 30 jours chez les enfants atteints de pneumonie sévère. L'association de ces facteurs peut être utilisée dans l'aide à la décision clinique pour une identification rapide et une prise en charge appropriée pour la prévention de la mortalité dans cette population.

The effect of acute malnutrition on enteric pathogens, moderate-to-severe diarrhoea, and associated mortality in the Global Enteric Multicenter Study cohort: a post-hoc analysis.

BACKGROUND: Host vulnerabilities associated with acute malnutrition could facilitate the ability of specific enteric pathogens to cause diarrhoea and associated mortality. Using data from the Global Enteric Multicenter Study, we assessed whether acute malnutrition modifies the association between common enteric pathogens and moderate-to-severe diarrhoea, and whether associations between enteric pathogens and death were modified by acute malnutrition. METHODS: Children with moderate-to-severe diarrhoea and age-matched and community-matched controls were included in this post-hoc analysis if their mid-upper arm circumference had been measured and if they were older than 6 months of age. Acute malnutrition was defined as mid-upper arm circumference below 12·5 cm, capturing both severe acute malnutrition (<11·5 cm) and moderate acute malnutrition (≥11·5 cm and <12·5 cm). We tested whether acute malnutrition modified associations between enteric pathogens and moderate-to-severe diarrhoea in conditional logistic regression models. Among children with moderate-to-severe diarrhoea, Cox proportional hazards regression evaluated the modifying effect of acute malnutrition on the relationship between pathogens and 60-day fatality rate. FINDINGS: The age, site, and co-infection adjusted odds ratios (aORs) for moderate-to-severe diarrhoea associated with typical enteropathogenic Escherichia coli among children aged 6-11 months was 2·08 (95% CI 1·14-3·79) in children with acute malnutrition, and 0·97 (0·77-1·23) in children with better nutritional status, compared with healthy controls. Enterotoxigenic E coli producing heat-stable toxin among children aged 12-23 months also had a stronger association with moderate-to-severe diarrhoea in children with acute malnutrition (aOR 7·60 [2·63-21·95]) than among similarly aged children with better nutritional status (aOR 2·39 [1·76-3·25]). Results for Shigella spp, norovirus, and sapovirus suggested they had a stronger association with moderate-to-severe diarrhoea than other pathogens among children with better nutritional status, although Shigella spp remained associated with moderate-to-severe diarrhoea in both nutritional groups. 92 (64%) of 144 children with moderate-to-severe diarrhoea who died had acute malnutrition. Pathogen-specific 60-day fatality rates for all pathogens were higher among children with acute malnutrition, but no individual pathogen had a significantly larger increase in its relative association with mortality. INTERPRETATION: Acute malnutrition might strengthen associations between specific pathogens and moderate-to-severe diarrhoea. However, the strong link between acute malnutrition and mortality during moderate-to-severe diarrhoea in children is not limited to specific infections, and affects a broad spectrum of enteric pathogens. Interventions addressing acute malnutrition could be an effective way to lower the mortality of both childhood malnutrition and diarrhoea. FUNDING: The Bill & Melinda Gates Foundation.

Day clinic vs. hospital care of pneumonia and severe malnutrition in children under five: a randomised trial.

OBJECTIVES: To evaluate the clinical outcomes and costs of managing pneumonia and severe malnutrition in a day clinic (DC) management model (outpatient) vs. hospital care (inpatient). METHODS: Randomised clinical trial where children aged 2 months to 5 years with pneumonia and severe malnutrition were randomly allocated to DC or inpatient hospital care. We used block randomisation of variable length from 8 to 20 and produced computer-generated random numbers that were assigned to one of the two interventions. Successful management was defined as resolution of clinical signs of pneumonia and being discharged from the model of care (DC or hospital) without need for referral to a hospital (DC), or referral to another hospital. All the children in both DC and hospital received intramuscular ceftriaxone, daily nutrition support and micronutrients. RESULTS: Four hundred and seventy children were randomly assigned to either DC or hospital care. Successful management was achieved for 184 of 235 (78.3%) by DC alone, vs. 201 of 235 (85.5%) by hospital inpatient care [RR (95% CI) = 0.79 (0.65-0.97), P = 0.02]. During 6 months of follow-up, 30/235 (12.8%) in the DC group and 36/235 (15.3%) required readmission to hospital in the hospital care group [RR (95% CI) = 0.89 (0.67-1.18), P = 0.21]. The average overall healthcare and societal cost was 34% lower in DC (US$ 188 ± 11.7) than in hospital (US$ 285 ± 13.6) (P < 0.001), and costs for households were 33% lower. CONCLUSIONS: There was a 7% greater probability of successful management of pneumonia and severe malnutrition when inpatient hospital care rather than the outpatient day clinic care was the initial method of care. However, where timely referral mechanisms were in place, 94% of children with pneumonia and severe malnutrition were successfully managed initially in a day clinic, and costs were substantially lower than with hospital admission.

OBJECTIFS: Evaluer les résultats cliniques et les coûts de la prise en charge de la pneumonie et de la malnutrition sévère dans un modèle de prise en charge en clinique de jour (CJ) (patients ambulatoires) par rapport à des soins hospitaliers (patients hospitalisés). MÉTHODES: Essai clinique randomisé où les enfants âgés de 2 mois à 5 ans avec une pneumonie et une malnutrition sévère ont été répartis de façon aléatoire en CJ ou à des soins hospitaliers. Nous avons utilisé la randomisation par blocs de longueur variable de 8 à 20 et avons généré des nombres aléatoires par ordinateur qui ont été attribués à l'une des deux interventions. Une prise en charge réussie a été définie comme la résolution des signes cliniques de pneumonie et la sortie du modèle de soins (CJ ou hospitalisation) sans nécessiter un transfert à un hôpital (CJ), ni à un autre hôpital. Tous les enfants du bras CJ et du bras soins hospitaliers ont reçu de la ceftriaxone par voie intramusculaire, un soutien nutritionnel quotidien et des micronutriments. RÉSULTATS: 470 enfants ont été assignés aléatoirement soit à des soins en CJ ou hospitaliers. Une prise en charge réussie a été obtenue pour 184 patients sur 235 (78,3%) en CJ seule contre 201 sur 235 (85,5%) en soins hospitaliers [RR (IC95%) = 0,79 (0,65 - 0,97), p = 0,02]. Au cours des six mois de suivi, 30/235 (12,8%) du groupe CJ et 36/235 (15,3%) du groupe soins hospitaliers ont nécessité une réadmission à l'hôpital [RR (IC95%) = 0,89 (0,67 - 1,18), p = 0,21]. Le coût moyen global des soins de santé et pour la société était de 34% plus faible dans le groupe CJ (188 ± 11,7 USD) que dans le groupe soins hospitaliers (285 ± 13,6 USD) (p < 0,001) et les coûts pour les ménages étaient de 33% inférieurs. CONCLUSIONS: La probabilité d'une prise en charge réussie de la pneumonie et de la malnutrition sévère était 7% plus élevée lorsque les soins hospitaliers plutôt que les soins en CJ étaient les moyens initiaux. Cependant, là où des mécanismes de référence rapides étaient en place, 94% des enfants atteints de pneumonie et de malnutrition sévère ont été pris en charge avec succès dans une clinique de jour et les coûts étaient nettement inférieurs à ceux de soins hospitaliers.

A mixed method multi-country assessment of barriers to implementing pediatric inpatient care guidelines.

INTRODUCTION: Accelerating progress in reducing child deaths is needed in order to achieve the Sustainable Development Goal child mortality target. This will require a focus on vulnerable children-including young children, those who are undernourished or with acute illnesses requiring hospitalization. Improving adherence to inpatient guidelines may be an important strategy to reduce child mortality, including among the most vulnerable. The aim of our assessment of nine sub-Saharan African and South Asian hospitals was to determine adherence to pediatric inpatient care recommendations, in addition to capacity for and barriers to implementation of guideline-adherent care prior to commencing the Childhood Acute Illness and Nutrition (CHAIN) Cohort study. The CHAIN Cohort study aims to identify modifiable risk factors for poor inpatient and post discharge outcomes above and beyond implementation of guidelines. METHODS: Hospital infrastructure, staffing, durable equipment, and consumable supplies such as medicines and laboratory reagents, were evaluated through observation and key informant interviews. Inpatient medical records of 2-23 month old children were assessed for adherence to national and international guidelines. The records of children with severe acute malnutrition (SAM) were oversampled to reflect the CHAIN study population. Seven core adherence indicators were examined: oximetry and oxygen therapy, fluids, anemia diagnosis and transfusion, antibiotics, malaria testing and antimalarials, nutritional assessment and management, and HIV testing. RESULTS: All sites had facilities and equipment necessary to implement care consistent with World Health Organization and national guidelines. However, stockouts of essential medicines and laboratory reagents were reported to be common at some sites, even though they were mostly present during the assessment visits. Doctor and nurse to patient ratios varied widely. We reviewed the notes of 261 children with admission diagnoses of sepsis (17), malaria (47), pneumonia (70), diarrhea (106), and SAM (119); 115 had multiple diagnoses. Adherence to oxygen therapy, antimalarial, and malnutrition refeeding guidelines was >75%. Appropriate antimicrobials were prescribed for 75% of antibiotic-indicative conditions. However, 20/23 (87%) diarrhea and 20/27 (74%) malaria cases without a documented indication were prescribed antibiotics. Only 23/122 (19%) with hemoglobin levels meeting anemia criteria had recorded anemia diagnoses. HIV test results were infrequently documented even at hospitals with universal screening policies (66/173, 38%). Informants at all sites attributed inconsistent guideline implementation to inadequate staffing. CONCLUSION: Assessed hospitals had the infrastructure and equipment to implement guideline-consistent care. While fluids, appropriate antimalarials and antibiotics, and malnutrition refeeding adherence was comparable to published estimates from low- and high-resource settings, there were inconsistencies in implementation of some other recommendations. Stockouts of essential therapeutics and laboratory reagents were a noted barrier, but facility staff perceived inadequate human resources as the primary constraint to consistent guideline implementation.

Clinical outcomes and mortality before and after implementation of a pediatric sepsis protocol in a limited resource setting: A retrospective cohort study in Bangladesh.

BACKGROUND: Pediatric sepsis has a high mortality rate in limited resource settings. Sepsis protocols have been shown to be a cost-effective strategy to improve morbidity and mortality in a variety of populations and settings. At Dhaka Hospital in Bangladesh, mortality from pediatric sepsis in high-risk children previously approached 60%, which prompted the implementation of an evidenced-based protocol in 2010. The clinical effectiveness of this protocol had not been measured. We hypothesized that implementation of a pediatric sepsis protocol improved clinical outcomes, including reducing mortality and length of hospital stay. MATERIALS AND METHODS: This was a retrospective cohort study of children 1-59 months old with a diagnosis of sepsis, severe sepsis or septic shock admitted to Dhaka Hospital from 10/25/2009-10/25/2011. The primary outcome was inpatient mortality pre- and post-protocol implementation. Secondary outcomes included fluid overload, heart failure, respiratory insufficiency, length of hospital stay, and protocol compliance, as measured by antibiotic and fluid bolus administration within 60 minutes of hospital presentation. RESULTS: 404 patients were identified by a key-word search of the electronic medical record; 328 patients with a primary diagnosis of sepsis, severe sepsis, or septic shock were included (143 pre- and185 post-protocol) in the analysis. Pre- and post-protocol mortality were similar and not statistically significant (32.17% vs. 34.59%, p = 0.72). The adjusted odds ratio (AOR) for post-protocol mortality was 1.55 (95% CI, 0.88-2.71). The odds for developing fluid overload were significantly higher post-protocol (AOR 3.45, 95% CI, 2.04-5.85), as were the odds of developing heart failure (AOR 4.52, 95% CI, 1.43-14.29) and having a longer median length of stay (AOR 1.81, 95% CI 1.10-2.96). There was no statistically significant difference in respiratory insufficiency (pre- 65.7% vs. post- 70.3%, p = 0.4) or antibiotic administration between the cohorts (pre- 16.08% vs. post- 12.43%, p = 0.42). CONCLUSIONS: Implementation of a pediatric sepsis protocol did not improve all-cause mortality or length of stay and may have been associated with increased fluid overload and heart failure during the study period in a large, non-governmental hospital in Bangladesh. Similar rates of early antibiotic administration may indicate poor protocol compliance. Though evidenced-based protocols are a potential cost-effective strategy to improve outcomes, future studies should focus on optimal implementation of context-relevant sepsis protocols in limited resource settings.