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.

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.

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.

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.

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.

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.

Efficacy of World Health Organization guideline in facility-based reduction of mortality in severely malnourished children from low and middle income countries: A systematic review and meta-analysis.

AIM: Globally more than 19 million under-five children suffer from severe acute malnutrition (SAM). Data on efficacy of World Health Organization's (WHO's) guideline in reducing SAM mortality are limited. We aimed to assess the efficacy of WHO's facility-based guideline for the reduction of under-five SAM children mortality from low and middle income countries (LMICs). METHODS: A systematic search of literature published in 1980-2015 was conducted using electronic databases. Additional articles were identified from the reference lists and grey literature. Studies from LMICs where SAM children (0-59 months) were managed in facilities according to WHO's guideline were included. Outcome was reduction in SAM mortality measured by case fatality rate (CFR). The review was reported following the Grading of Recommendations Assessment Development and Evaluation and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline and meta-analyses done using RevMan 5.3®. RESULTS: This review identified nine studies, which demonstrated reductions in SAM mortality. CFR ranged from 8 to 16% where WHO guideline applied. High rates of poverty, malnutrition, severe co-morbid condition, lack of resources and differences in treatment practices played a key role in large CFR variation. Most death occurred within 48 h of admission in Asia, between 4 days and 4 weeks in Africa and in Latin America. CFR was reduced by 41% (odds ratio: 0.59; 95% confidence interval: 0.46-0.76) when WHO guideline were applied. A 45% reduction in CFR was achieved after excluding human immunodeficiency virus positive cases. Dietary management also differed among WHO and conventional management. CONCLUSION: Children receiving SAM inpatient care as per WHO guideline have reduced CFR compared to conventional treatment.

Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: an open, randomised controlled trial.

BACKGROUND: In developing countries, mortality in children with very severe pneumonia is high, even with the provision of appropriate antibiotics, standard oxygen therapy, and other supportive care. We assessed whether oxygen therapy delivered by bubble continuous positive airway pressure (CPAP) improved outcomes compared with standard low-flow and high-flow oxygen therapies. METHODS: This open, randomised, controlled trial took place in Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. We randomly assigned children younger than 5 years with severe pneumonia and hypoxaemia to receive oxygen therapy by either bubble CPAP (5 L/min starting at a CPAP level of 5 cm H2O), standard low-flow nasal cannula (2 L/min), or high-flow nasal cannula (2 L/kg per min up to the maximum of 12 L/min). Randomisation was done with use of the permuted block methods (block size of 15 patients) and Fisher and Yates tables of random permutations. The primary outcome was treatment failure (ie, clinical failure, intubation and mechanical ventilation, death, or termination of hospital stay against medical advice) after more than 1 h of treatment. Primary and safety analyses were by intention to treat. We did two interim analyses and stopped the trial after the second interim analysis on Aug 3, 2013, as directed by the data safety and monitoring board. This trial is registered at ClinicalTrials.gov, number NCT01396759. FINDINGS: Between Aug 4, 2011, and July 17, 2013, 225 eligible children were recruited. We randomly allocated 79 (35%) children to receive oxygen therapy by bubble CPAP, 67 (30%) to low-flow oxygen therapy, and 79 (35%) to high-flow oxygen therapy. Treatment failed for 31 (14%) children, of whom five (6%) had received bubble CPAP, 16 (24%) had received low-flow oxygen therapy, and ten (13%) had received high-flow oxygen therapy. Significantly fewer children in the bubble CPAP group had treatment failure than in the low-flow oxygen therapy group (relative risk [RR] 0·27, 99·7% CI 0·07-0·99; p=0·0026). No difference in treatment failure was noted between patients in the bubble CPAP and those in the high-flow oxygen therapy group (RR 0·50, 99·7% 0·11-2·29; p=0·175). 23 (10%) children died. Three (4%) children died in the bubble CPAP group, ten (15%) children died in the low-flow oxygen therapy group, and ten (13%) children died in the high-flow oxygen therapy group. Children who received oxygen by bubble CPAP had significantly lower rates of death than the children who received oxygen by low-flow oxygen therapy (RR 0·25, 95% CI 0·07-0·89; p=0·022). INTERPRETATION: Oxygen therapy delivered by bubble CPAP improved outcomes in Bangladeshi children with very severe pneumonia and hypoxaemia compared with standard low-flow oxygen therapy. Use of bubble CPAP oxygen therapy could have a large effect in hospitals in developing countries where the only respiratory support for severe childhood pneumonia and hypoxaemia is low-flow oxygen therapy. The trial was stopped early because of higher mortality in the low-flow oxygen group than in the bubble CPAP group, and we acknowledge that the early cessation of the trial reduces the certainty of the findings. Further research is needed to test the feasibility of scaling up bubble CPAP in district hospitals and to improve bubble CPAP delivery technology. FUNDING: International Centre for Diarrhoeal Disease Research, Bangladesh, and Centre for International Child Health, University of Melbourne.

Anti-rotavirus protein reduces stool output in infants with diarrhea: a randomized placebo-controlled trial.

BACKGROUND & AIMS: Rotavirus infection is a leading cause of morbidity and mortality in children younger than 5 years of age. Current treatment options are limited. We assessed the efficacy of a llama-derived, heavy-chain antibody fragment called anti-rotavirus protein (ARP1), in modifying the severity and duration of diarrhea in male infants with rotavirus infection. METHODS: We performed a double-blind, placebo-controlled trial of 176 male infants (6-24 months old) with severe rotavirus-associated diarrhea at Dhaka Hospital, Bangladesh. The infants were randomly assigned to groups given oral ARP1 (15-30 mg/kg/day, n = 88) or placebo (maltodextrin, n = 88) for a maximum of 5 days. The primary outcomes were severity (stool output) and duration of diarrhea and fecal excretion of rotavirus. Secondary outcomes were intake of oral rehydration salt solution, severity of vomiting, and serum levels of rotavirus-specific IgA. RESULTS: In infants with only rotavirus infection, total cumulative stool output was 305.47 g/kg body weight among those given placebo (n = 63) and 237.03 g/kg body weight among those given ARP1 (n = 61) (a difference of 68.44 g/kg body weight or 22.5%; 95% confidence interval: 18.27-118.59 g/kg body weight; P =.0079). There was a significant reduction in rate of stool output (g/kg/d) in the ARP1 group compared with the placebo group (61%; P = .002). ARP1 had no significant effect in infants with concomitant infections or on any other measured outcomes. No adverse events could be linked to ARP1. CONCLUSIONS: In a placebo-controlled trial, ARP1 reduced stool output in male infants with severe rotavirus-associated diarrhea. Clinicaltrials.gov number: NCT01259765.

Specialist hospital study shows that septic shock and drowsiness predict mortality in children under five with diarrhoea.

AIM: To evaluate the clinical characteristics and outcome in children hospitalised with diarrhoea, comparing those developed septic shock with those who did not. METHODS: We carried out a retrospective chart review on children aged 0-59 months admitted to the Dhaka Hospital, International Centre for Diarrhoeal Diseases Research, Bangladesh, with diarrhoea between October 2010 and September 2011. They were included if they had severe sepsis defined as tachycardia plus hyperthermia or hypothermia or an abnormal white blood cell count plus poor peripheral perfusion in absence of dehydration. Patients unresponsive to fluid and boluses, who required inotropes, were categorised as having septic shock (n = 88). The controls were those without septic shock (n = 116). RESULTS: Death was significantly higher among the children with septic shock (67%) than the controls (14%) (p < 0.001). A logistic regression analysis, adjusted for potential confounders, found that children with septic shock were more likely to be drowsy on admission and received blood transfusions and mechanical ventilation (all p < 0.05). CONCLUSION: Children hospitalised for diarrhoea with septic shock were more likely to die, be drowsy on admission and receive blood transfusions and mechanical ventilation. A randomised clinical trial on inotropes in children with diarrhoea, severe sepsis and drowsiness may expedite their use and prevent mechanical ventilation and deaths.

Observational follow-up study on a cohort of children with severe pneumonia after discharge from a day-care clinic in Dhaka, Bangladesh.

Compliance, morbidity, mortality, and hospitalization during fortnightly follow-up were evaluated by an observational study on a cohort of children with severe and very severe pneumonia after day-care treatment at an urban clinic. The primary outcome measures were proportions of success (compliance) and failure (non-compliance) of follow-up visits at the day-care clinic. In total, 251 children were followed up, with median (IQR) age of 5.0 (3.0-9.0) months, and their compliance dropped from 92% at the first to 85% at the sixth visit. Cough (28%), fever (20%), and rapid breathing (13%) were common morbidities. Successful follow-up visits were possible in 180 (95.2%) and 56 (90.3%) of the children with severe and very severe pneumonia respectively. Eleven (4.4%) needed hospitalization, and four (1.6%) died. Majority (approximately 90%) of the children could be successfully followed up; some failed to attend their scheduled follow-up visits due to hospitalization and death. The common morbidities indicate the importance of follow-up for detecting medical problems and early treatment, thus reducing risk of death.

Prevalence, clinical predictors, and outcome of hypocalcaemia in severely-malnourished under-five children admitted to an urban hospital in Bangladesh: a case-control study.

Hypocalcaemia is common in severely-malnourished children and is often associated with fatal outcome. There is very limited information on the clinical predicting factors of hypocalcaemia in hospitalized severely-malnourished under-five children. Our objective was to evaluate the prevalence, clinical predicting factors, and outcome of hypocalcaemia in such children. In this case-control study, all severely-malnourished under-five children (n=333) admitted to the Longer Stay Ward (LSW), High Dependency Unit (HDU), and Intensive Care Unit (ICU) of the Dhaka Hospital of icddr,b between April 2011 and April 2012, who also had their total serum calcium estimated, were enrolled. Those who presented with hypocalcaemia (serum calcium <2.12 mmol/L) constituted the cases (n=87), and those admitted without hypocalcaemia (n=246) constituted the control group in our analysis. The prevalence of hypocalcaemia among severely-malnourished under-five children was 26% (87/333). The fatality rate among cases was significantly higher than that in the controls (17% vs 5%; p < 0.001). Using logistic regression analysis, after adjusting for potential confounders, such as vomiting, abdominal distension, and diastolic hypotension, we identified acute watery diarrhoea (AWD) (OR 2.19, 95% CI 1.08-4.43, p = 0.030), convulsion on admission (OR 21.86, 95% CI 2.57-185.86, p = 0.005), and lethargy (OR 2.70, 95% CI 1.633-5.46, p = 0.006) as independent predictors of hypocalcaemia in severely-malnourished children. It is concluded, severely-malnourished children presenting with hypocalcaemia have an increased risk of death than those without hypocalcaemia. AWD, convulsion, and lethargy assessed on admission to hospital are the clinical predictors of hypocalcaemia in such children. Presence of these features in hospitalized children with severe acute malnutrition (SAM) should alert clinicians about the possibility of hypocalcaemia and may help undertake potential preventive measures, such as calcium supplementation, in addition to other aspects of management of such children, especially in the resource-poor settings.

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.

Interstitial lung disease and profound hypoxaemia in a severely-malnourished child with very severe pneumonia and potential lymph-node tuberculosis: an uncommon but serious co-morbidity.

A nine-month old boy was initially admitted at the Acute Respiratory Infection Unit of Dhaka Hospital of icddr,b and soon after transferred to the Intensive Care Unit of the same hospital. The boy had problems of very severe pneumonia (confirmed by radiology), severe hypoxaemia, severe malnutrition, and Down's syndrome. The patient was treated according to the hospital protocol for the management of pneumonia and malnutrition. During the hospital stay, hypoxaemia was persistent with very little improvement of pneumonia; a number of differentials, such as pneumocystis jirovecii pneumonia, lymph-node tuberculosis, were added to the problems. Subsequently, the patient's hypoxaemia improved with the empirical use of antitubercular drugs. However, the patient again developed persistent hypoxaemia and, after unsuccessful treatment for a hospital-acquired pneumonia, the problems further expanded to include interstitial lung disease (ILD). This was confirmed by high-resolution computed tomography, and the patient was treated with prednisolone for 6 months, along with antitubercular drugs. He fully recovered from ILD, hypoxaemia, and pneumonia both clinically and radiologically. Therefore, severely-malnourished children having wet cough and pneumonia with persistent hypoxaemia should be assessed for the possible existence of interstitial lung disease. This may help provide a prompt and appropriate management to reduce morbidity and deaths in such patients.

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.

Clinical predictors and outcome of hypoxaemia among under-five diarrhoeal children with or without pneumonia in an urban hospital, Dhaka, Bangladesh.

OBJECTIVE: To explore the predictors and outcome of hypoxaemia in children under 5 years of age who were hospitalized for the management of diarrhoea in Dhaka, where comorbidities are common. METHODS: In a prospective cohort study, we enrolled all children <5 years of age admitted to the special care ward (SCW) of the Dhaka Hospital of ICDDR,B from September to December 2007. Those who presented with hypoxaemia (SpO(2) < 90%) constituted the study group, and those without hypoxaemia formed the comparison group. RESULTS: A total of 258 children were enrolled, all had diarrhoea. Of the total, 198 (77%) had pneumonia and 106 (41%) had severe malnutrition (<-3 Z-score of weight for age of the median of the National Centre for Health Statistics), 119 (46%) had hypoxaemia and 138 children did not have hypoxaemia at the time of admission. Children with hypoxaemia had a higher probability of a fatal outcome (21%vs. 4%; P < 0.001). Using logistic regression analysis, the independent predictors of hypoxaemia at the time of presentation were lower chest wall indrawing [OR 6.91, 95% confidence intervals (CI) 3.66-13.08, P < 0.001], nasal flaring (OR 3.22, 95% CI 1.45-7.17, P = 0.004) and severe sepsis (OR 4.48, 95% CI 1.62-12.42, P = 0.004). CONCLUSION: In this seriously ill population of children with diarrhoea and comorbidities, hypoxaemia was associated with high case-fatality rates. Independent clinical predictors of hypoxaemia in this population, identifiable at the time of admission, were lower chest wall indrawing, nasal flaring and the clinical syndrome of severe sepsis.

Use of only oral rehydration salt solution for successful management of a young infant with serum sodium of 201 mmol/L in an urban diarrhoeal diseases hospital, Bangladesh.

A boy aged 4 months 7 days was admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of icddr,b, Dhaka, Bangladesh, with the problems of acute watery diarrhoea with some dehydration, pneumonia, lethargy, and hypernatraemia (serum sodium of 201 mmol/L). Correction for hypernatraemia was tried by using only oral rehydration salt (ORS) solution. Seizures occurred during correction of the hypernatraemia. These were difficult to control and required three doses of injection lorazepam, a loading dose of injection phenobarbitone, followed by injection phenytoin and finally two doses of injection mannitol (even though there was no clinical or imaging evidence by ultrasonography or computed tomography of cerebral oedema). The correction was continued with ORS, and all the anticonvulsants were successfully weaned without any further seizures, and the patient recovered without any overt neurological sequelae. We present a case report of extreme hypernatraemia, which was successfully managed using only ORS.

A follow-up experience of 6 months after treatment of children with severe acute malnutrition in Dhaka, Bangladesh.

AIM: As there is lack of information about what happens to children after recovery from severe acute malnutrition (SAM), we report their relapse, morbidity, mortality and referral during follow-up period. METHODS: From February 2001 to November 2003, 180 children completing acute and nutrition rehabilitation (NR) phases of protocolized management were advised for 6-months follow-up. The mean (SD) age was 12 (5) months, 55% were infants, 53% were male and 68% were breast-fed. RESULTS: The follow-up compliance rate dropped from 91% at first to 49% at tenth visit. The common morbidities following discharge included fever (26%), cough (24%) and diarrhoea (20%). Successful follow-up done in 124 children [68.9% (95% CI 61.8-75.2%)], partial follow-up in 45 [25% (95% CI 19.2-31.8%)], relapse in 32 [17.8% (95% CI 12.9-24%)] and 5 [2.8% (95% CI 1.2-6.3%)] died. CONCLUSION: Our findings highlight need for follow-up as part of overall management of SAM and recommend an effective community follow-up.

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.