Open-label, randomised controlled trial found that a green banana mixed rice suji diet was most effective for persistent diarrhoea in children in Bangladesh.

AIM: Persistent diarrhoea continues for at least 14 days and kills more children than acute diarrhoea. We assessed whether rice suji, green banana mixed rice suji or 75% rice suji improved persistent diarrhoea in young children. METHODS: This open-labelled randomised controlled trial was carried out between December 2017 and August 2019 at the Dhaka Hospital of icddr,b, Bangladesh, with 135 children aged 6-35 months with persistent diarrhoea. The children were randomly assigned to green banana mixed rice suji, rice suji or 75% rice suji, with 45 in each group. The primary outcome was the percentage who recovered from diarrhoea by day 5 using an intention-to-treat analysis. RESULTS: The children's median age was 8 months (interquartile range: 7-10 months). By day 5, the recovery rate was 58%, 31% and 58% for children in the green banana mixed rice suji, rice suji and 75% rice suji groups, respectively. The green banana mixed rice suji group had fewer relapses (7%) than the 75% rice suji group (24%). Enteroaggregative Escherichia coli, rotavirus, norovirus, Enteropathogenic Escherichia coli, astrovirus and Campylobacter were the major pathogens for persistent diarrhoea. CONCLUSION: Green banana mixed rice suji was the most effective option for managing persistent diarrhoea in young children.

The influence of demographic and meteorological factors on temporal patterns of rotavirus infection in Dhaka, Bangladesh.

To quantify the potential impact of rotavirus vaccines and identify strategies to improve vaccine performance in Bangladesh, a better understanding of the drivers of pre-vaccination rotavirus patterns is required. We developed and fitted mathematical models to 23 years (1990-2012) of weekly rotavirus surveillance data from Dhaka with and without incorporating long-term and seasonal variation in the birth rate and meteorological factors. We performed external model validation using data between 2013 and 2019 from the regions of Dhaka and Matlab. The models showed good agreement with the observed age distribution of rotavirus cases and captured the observed shift in seasonal patterns of rotavirus hospitalizations from biannual to annual peaks. The declining long-term trend in the birth rate in Bangladesh was the key driver of the observed shift from biannual to annual winter rotavirus patterns. Meteorological indices were also important: a 1°C, 1% and 1 mm increase in diurnal temperature range, surface water presence and degree of wetness were associated with a 19%, 3.9% and 0.6% increase in the transmission rate, respectively. The model demonstrated reasonable predictions for both Dhaka and Matlab, and can be used to evaluate the impact of rotavirus vaccination in Bangladesh against changing patterns of disease incidence.

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.

Pathogen-specific risk of seizure in children with moderate-to-severe diarrhoea: Case control study with follow-up.

OBJECTIVE: To determine the pathogen-specific risk of seizure in under-five children hospitalised with moderate-to-severe diarrhoea (MSD) in rural settings. METHOD: This was a prospective case-control study with follow-up, conducted in a sentinel facility of Global Enteric Multicenter Study in Mirzapur, a rural community of Bangladesh between 2007 and 2010. Children aged 0-59 months who presented with MSD and seizure constituted the cases whereas those who did not have seizure comprised the controls. MSD was defined if the episodes were associated with dehydration or dysentery or required hospitalisation with diarrhoea or dysentery. All enrolled children were followed up at home within 50-90 days of enrolment. A total of 64 cases and 128 randomly selected controls formed the analysable dataset. RESULTS: The result of logistic regression analysis after adjusting for potential confounders revealed that shigellosis (Shigella species, OR = 5.34, 95% CI = 2.37-12.04) particularly S. flexneri (OR = 3.34, 95% CI = 1.48-7.57), S. flexneri 6 (OR = 23.24, 95% CI = 2.79-193.85), S. sonnei (OR = 6.90, 95% CI = 2.34-19.85); norovirus (OR = 6.77, 95% CI = 1.69-27.11), fever (OR = 16.75, 95% CI = 1.81-154.70) and loss of consciousness (OR = 35.25, 95% CI = 1.71-726.20) were the independent risk factors for seizure in MSD children. At enrolment, cases had lower WHZ (P = 0.006) compared to their peers, follow-up anthropometrics showed significant improvement in WHZ (P < 0.001) and WAZ (P < 0.05), whereas deterioration in HAZ (P < 0.001) in both cases and controls. CONCLUSION: Childhood MSD episodes particularly due to Shigella and norovirus are often associated with seizure. Prompt identification and appropriate management of children with shigellosis may reduce occurrence and adverse consequences of seizure linked with MSD.

OBJECTIF: Déterminer le risque spécifique de convulsions chez les enfants de moins de cinq ans hospitalisés pour une diarrhée modérée à sévère (DMS) en milieu rural. MÉTHODE: Il s'agissait d'une étude prospective cas-témoins avec suivi, menée dans un établissement sentinelle de l'Etude Globale Multicentrique Entérique à Mirzapur, une communauté rurale du Bangladesh entre 2007 et 2010. Les enfants âgés de 0 à 59 mois qui se sont présentés avec une DMS et des convulsions constituaient les cas, tandis que ceux qui n'avaient pas des convulsions constituaient les témoins. La DMS a été définie si les épisodes étaient associés à une déshydratation ou à une dysenterie ou nécessitaient une hospitalisation pour diarrhée ou dysenterie. Tous les enfants recrutés ont été suivis à domicile dans les 50 à 90 jours suivant le recrutement. Un total de 64 cas et 128 témoins sélectionnés au hasard ont constitué l'ensemble de données analysables. RÉSULTATS: Le résultat de l'analyse de régression logistique après ajustement des facteurs de confusion potentiels a révélé que la shigellose (espèce Shigella, OR = 5,34 ; IC95%: 2,37-12,04) en particulier S. flexneri (OR = 3,34 ; IC95%: 1,48-7,57), S. flexneri 6 (OR = 23,24 ; IC95%: 2.79-193,85), S. sonnei (OR = 6,90 ; IC95%: 2,34-19,85) ; les norovirus (OR = 6,77 ; IC95%: 1,69-27,11), la fièvre (OR = 16,75 ; IC95%: 1,81-154,70) et la perte de conscience (OR = 35,25 ; IC95%: 1,71-726,20) étaient les facteurs de risque indépendants de convulsions chez les enfants souffrant de DMS. Lors du recrutement, les cas avaient un score Z poids pour la taille (ZPT) plus faible (P = 0,006) que leurs pairs, les anthropométries de suivi ont montré une amélioration significative du ZPT (P < 0,001) et du score Z poids pour l'âge (P < 0,05); tandis que le score Z taille pour l'âge (p < 0,001) s'est détérioré chez cas et chez les témoins. CONCLUSION: Les épisodes de DMS de l'enfance, notamment due à Shigella et aux norovirus, sont souvent associés à des convulsions. L'identification rapide et la prise en charge appropriée des enfants atteints de shigellose peuvent réduire la survenue et les conséquences négatives des crises liées aux DMS.

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.

Prognostic accuracy of early warning scores for predicting serious illness and in-hospital mortality in patients with COVID-19.

A simple bedside triage tool is essential to stratify COVID-19 patients in the emergency department (ED). This study aimed to identify an early warning score (EWS) that could best predict the clinical outcomes in COVID-19 patients. Data were obtained from medical records of 219 laboratory-confirmed COVID-19 positive patients. We calculated 13 EWSs based on the admission characteristics of the patients. Receiver operating characteristic (ROC) curve analysis was used to assess the performance of the scores in predicting serious illness and in-hospital mortality. The median patient age was 51 (38, 60) years, and 25 (11.4%) patients died. Among patients admitted with mild to moderate illness (n = 175), 61 (34.9%) developed serious illness. Modified National Early Warning Score (m-NEWS) (AUROC 0.766; 95% CI: 0.693, 0.839) and Rapid Emergency Medicine Score (REMS) (AUROC 0.890; 95% CI: 0.818, 0.962) demonstrated the highest AUROC point estimates in predicting serious illness and in-hospital mortality, respectively. Both m-NEWS and REMS demonstrated good accuracy in predicting both the outcomes. However, no significant difference was found between m-NEWS (p = 0.983) and REMS (p = 0.428) as well as some other EWSs regarding the AUROCs in predicting serious illness and in-hospital mortality. We propose m-NEWS could be used as a triage score to identify COVID-19 patients at risk of disease progression and death especially in resource-poor settings because it has been explicitly developed for risk stratification of COVID-19 patients in some countries like China and Italy. However, this tool needs to be validated by further large-scale prospective studies.

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.

Performance of chest X-ray scoring in predicting disease severity and outcomes of patients hospitalised with COVID-19 in Bangladesh.

Introduction: Evaluation of potential outcomes of COVID-19-affected pneumonia patients using computed tomography scans may not be conceivable in low-resource settings. Thus, we aimed to evaluate the performance of chest X-ray scoring in predicting the disease severity and outcomes of adults hospitalised with COVID-19. Methods: This was a retrospective chart analysis consuming data from COVID-19-positive adults who had chest X-ray availability and were admitted to a temporary COVID unit, in Bangladesh from 23rd April 2020 to 15th November 2021. At least one clinical intensivist and one radiologist combinedly reviewed each admission chest X-ray for the different lung findings. Chest X-ray scoring varied from 0 to 8, depending on the area of lung involvement with 0 indicating no involvement and 8 indicating ⩾75% involvement of both lungs. The receiver operating characteristic curve was used to determine the optimum chest X-ray cut-off score for predicting the fatal outcomes. Result: A total of 218 (82.9%) out of 263 COVID-19-affected adults were included in the study. The receiver operating characteristic curve demonstrated the optimum cut-off as ⩾3 and ⩾5 for disease severity and death, respectively. In multivariate logistic regression analysis, a chest X-ray score of ⩾3 was found to be independently associated with disease severity (aOR: 8.70; 95% CI: 3.82, 19.58, p < 0.001) and a score of ⩾5 with death (aOR: 16.53; 95% CI: 4.74, 57.60, p < 0.001) after adjusting age, sex, antibiotic usage before admission, history of fever, cough, diabetes mellitus, hypertension, total leukocytes count and C-reactive protein. Conclusion: Using chest X-ray scoring derived cut-off at admission might help to identify the COVID-19-affected adults who are at risk of severe disease and mortality. This may help to initiate early and aggressive management of such patients, thereby reducing their fatal outcomes.

COVID-19 and diarrhea: putative mechanisms and management.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), has recently posed a threat to global health by spreading at a high rate and taking millions of lives worldwide. Along with the respiratory symptoms, there are gastrointestinal manifestations and one of the most common gastrointestinal symptoms is diarrhea which is seen in a significant percentage of COVID-19 patients. LITERATURE REVIEW: Several studies have shown the plausible correlation between overexpressed angiotensin converting enzyme 2 (ACE2) in enterocytes and SARS-CoV-2, as ACE2 is the only known receptor for the virus entry. Along with the dysregulated ACE2, there are other contributing factors such as gut microbiome dysbiosis, adverse effects of antiviral and antibiotics for treating infections and inflammatory response to SARS-CoV-2 which bring about increased permeability of gut cells and subsequent occurrence of diarrhea. Few studies found that the SARS-CoV-2 is capable of damaging liver cells too. No single effective treatment option is available. LIMITATIONS: Confirmed pathophysiology is still unavailable. Studies regarding global population are also insufficient. CONCLUSION: In this review, based on the previous works and literature, we summarized the putative molecular pathophysiology of COVID-19 associated diarrhea, concomitant complications and the standard practices of management of diarrhea and hepatic manifestations in international setups.

Derivation and validation of a clinical prediction model for risk-stratification of children hospitalized with severe pneumonia in Bangladesh.

Children with severe pneumonia in low- and middle-income countries (LMICs) suffer from high rates of treatment failure despite appropriate World Health Organization (WHO)-directed antibiotic treatment. Developing a clinical prediction rule for treatment failure may allow early identification of high-risk patients and timely intervention to decrease mortality. We used data from two separate studies conducted at the Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) to derive and externally validate a clinical prediction rule for treatment failure of children hospitalized with severe pneumonia. The derivation dataset was from a randomized clinical trial conducted from 2018 to 2019, studying children aged 2 to 59 months hospitalized with severe pneumonia as defined by WHO. Treatment failure was defined by the persistence of danger signs at the end of 48 hours of antibiotic treatment or the appearance of any new danger signs within 24 hours of enrollment. We built a random forest model to identify the top predictors. The top six predictors were the presence of grunting, room air saturation, temperature, the presence of lower chest wall indrawing, the presence of respiratory distress, and central cyanosis. Using these six predictors, we created a parsimonious model with a discriminatory performance of 0.691, as measured by area under the receiving operating curve (AUC). We performed external validation using a temporally distinct dataset from a cohort study of 191 similarly aged children with severe acute malnutrition and pneumonia. In external validation, discriminatory performance was maintained with an improved AUC of 0.718. In conclusion, we developed and externally validated a parsimonious six-predictor model using random forest methods to predict treatment failure in young children with severe pneumonia in Bangladesh. These findings can be used to further develop and validate parsimonious and pragmatic prognostic clinical prediction rules for pediatric pneumonia, particularly in LMICs.

Burden, predictors, and outcome of unconsciousness among under-five children hospitalized for community-acquired pneumonia: A retrospective study from a developing country.

Despite the reduction of death from pneumonia over recent years, pneumonia has still been the leading infectious cause of death in under-five children for the last several decades. Unconsciousness is a critical condition in any child resulting from any illness. Once it occurs during a pneumonia episode, the outcome is perceived to be fatal. However, data on children under five with pneumonia having unconsciousness are scarce. We've retrospectively analyzed the data of under-five children admitted at the in-patient ward of Dhaka Hospital of icddr,b during 1 January 2014 and 31 December 2017 with World Health Organization classified pneumonia or severe pneumonia. Children presented with or without unconsciousness were considered as cases and controls respectively. Among a total of 3,876 children fulfilling the inclusion criteria, 325 and 3,551 were the cases and the controls respectively. A multivariable logistic regression analysis revealed older children (8 months vs. 7.9 months) (adjusted odds ratio, aOR 1.02, 95% CI: 1.004-1.04, p = 0.015), hypoxemia (aOR 3.22, 95% CI: 2.39-4.34, p<0.001), severe sepsis (aOR 4.46, 95% CI: 3.28-6.06, p<0.001), convulsion (aOR 8.90, 95% CI: 6.72-11.79, p<0.001), and dehydration (aOR 2.08, 95% CI: 1.56-2.76, p<0.001) were found to be independently associated with the cases. The cases more often had a fatal outcome than the controls (23% vs. 3%, OR 9.56, 95% CI: 6.95-13.19, p<0.001). If the simple predicting factors of unconsciousness in children under five hospitalized for pneumonia with different severity can be initially identified and adequately treated with prompt response, pneumonia-related deaths can be reduced more effectively, especially in resource-limited settings.

Prevalence and predictors of magnesium imbalance among critically ill diarrheal children and their outcome in a developing country.

Despite having essential roles in maintaining human body physiology, magnesium has gained little attention. We sought to evaluate the prevalence and predictors of magnesium imbalance in diarrheal children admitted to an intensive care unit. This retrospective data analysis was conducted among children admitted between January 2019 and December 2019. Eligible children were categorized by serum magnesium levels that were extracted from the hospital database. Among 557 participants, 29 (5.2%) had hypomagnesemia, 344 (61.8%) had normomagnesemia and 184 (33.0%) had hypermagnesemia. By multivariable multinomial logistic regression, we have identified older children (adjusted multinomial odds ratio, mOR 1.01, 95% CI: 1.004-1.018, p = 0.002) as a predictor of hypomagnesemia. Conversely, younger children (adjusted mOR 0.99, 95% CI: 0.982-0.998, p = 0.02), shorter duration of fever (adjusted mOR 0.92, 95% CI: 0.857-0.996, p = 0.04), convulsion (adjusted mOR 1.55, 95% CI: 1.005-2.380, p = 0.047), dehydration (adjusted mOR 3.27, 95% CI: 2.100-5.087, p<0.001), pneumonia (adjusted mOR 2.65, 95% CI: 1.660-4.240, p<0.001) and acute kidney injury (adjusted mOR 2.70, 95% CI: 1.735-4.200, p<0.001) as the independent predictors of hypermagnesemia. The mortality was higher among children with hypermagnesemia (adjusted mOR 2.31, 95% CI: 1.26-4.25, p = 0.007). Prompt identification and management of the magnesium imbalance among critically ill diarrheal children might have survival benefits, especially in resource-limited settings.

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.

Efficacy of dopamine, epinephrine and blood transfusion for treatment of fluid refractory shock in children with severe acute malnutrition or severe underweight and cholera or other dehydrating diarrhoeas: protocol for a randomised controlled clinical trial.

INTRODUCTION: Diarrhoea is one of the leading causes of under-5 childhood mortality and accounts for 8% of 5.4 million global under-5 deaths. In severely malnourished children, diarrhoea progresses to shock, where the risk of mortality is even higher. At icddr,b Dhaka Hospital, the fatality rate is as high as 69% in children with severe malnutrition and fluid refractory septic shock. To date, no study has evaluated systematically the effects of inotrope or vasopressor or blood transfusion in children with dehydrating diarrhoea (eg, in cholera) and severe acute malnutrition (SAM) or severe underweight who are in shock and unresponsive to WHO-recommended fluid therapy. To reduce the mortality of severely malnourished children presenting with diarrhoea and fluid refractory shock, we aim to compare the efficacy of blood transfusion, dopamine and epinephrine in fluid refractory shock in children who do not respond to WHO-recommended fluid resuscitation. METHODS AND ANALYSIS: In this randomised, three-arm, controlled, non-masked clinical trial in children 1-59 months old with SAM or severe underweight and fluid refractory shock, we will compare the efficacy of dopamine or epinephrine administration versus blood transfusion in children who failed to respond to WHO-recommended fluid resuscitation. The primary outcome variable is the case fatality rate. The effect of the intervention will be assessed by performing an intention-to-treat analysis. Recruitment and data collection began in July 2021 and are now ongoing. Results are expected by May 2023. ETHICS AND DISSEMINATION: This study has been approved by the icddr,b Institutional Review Board. We adhere to the 'Declaration of Helsinki' (2000), guidelines for Good Clinical Practice. Before enrolment, we collect signed informed consent from the parents or caregivers of the children. We will publish the results in a peer-reviewed journal and will arrange a dissemination seminar. TRIAL REGISTRATION NUMBER: NCT04750070.

Evaluation of feasibility phase of adaptive version of locally made bubble continuous positive airway pressure oxygen therapy for the treatment of COVID-19 positive and negative adults with severe pneumonia and hypoxaemia.

Background: Bubble continuous positive airway pressure (bCPAP) oxygen therapy has been shown to be safe and effective in treating children with severe pneumonia and hypoxaemia in Bangladesh. Due to lack of adequate non-invasive ventilatory support during coronavirus disease 2019 (COVID-19) crisis, we aimed to evaluate whether bCPAP was safe and feasible when adapted for use in adults with similar indications. Methods: Adults (18-64 years) with severe pneumonia and moderate hypoxaemia (80 to <90% oxygen saturation (SpO2) in room air) were provided bCPAP via nasal cannula at a flow rate of 10 litres per minute (l/min) oxygen at 10 centimetres (cm) H2O pressure, in two tertiary hospitals in Dhaka, Bangladesh. Qualitative interviews and focus group discussions, using a descriptive phenomenological approach, were performed with patients and staff (n = 39) prior to and after the introduction (n = 12 and n = 27 respectively) to understand the operational challenges to the introduction of bCPAP. Results: We enrolled 30 adults (median age 52, interquartile range (IQR) 40-60 years) with severe pneumonia and hypoxaemia and/or acute respiratory distress syndrome (ARDS) irrespective of coronavirus disease 2019 (COVID-19) test results to receive bCPAP. At baseline mean SpO2 on room air was 87% (±2) which increased to 98% (±2), after initiation of bCPAP. The mean duration of bCPAP oxygen therapy was 14.4 ± 24.8 hours. There were no adverse events of note, and no treatment failure or deaths. Operational challenges to the clinical introduction of bCPAP were lack of functioning pulse oximeters, difficult nasal interface fixation among those wearing nose pin, occasional auto bubbling or lack of bubbling in water-filled plastic bottle, lack of holder for water-filled plastic bottle, rapid turnover of trained clinicians at the hospitals, and limited routine care of patients by hospital clinicians particularly after official hours. Discussion: If the tertiary hospitals in Bangladesh are supplied with well-functioning good quality pulse oximeters and enhanced training of the doctors and nurses on proper use of adapted version of bCPAP, in treating adults with severe pneumonia and hypoxaemia with or without ARDS, the bCPAP was found to be safe, well tolerated and not associated with treatment failure across all study participants. These observations increase the confidence level of the investigators to consider a future efficacy trial of adaptive bCPAP oxygen therapy compared to WHO standard low flow oxygen therapy in such patients. Conclusion: s Although bCPAP oxygen therapy was found to be safe and feasible in this pilot study, several challenges were identified that need to be taken into account when planning a definitive clinical trial.

Prolonged diarrhea among under-five children in Bangladesh: Burden and risk factors.

INTRODUCTION & BACKGROUND: Prolonged (duration >7 to 13 days) diarrhea (ProD) in under-five children is a universal health problem including Bangladesh. Data on epidemiology and associated or risk factors of ProD are limited, particularly in Bangladesh where a high burden of ProD is reported. This study intended to assess the case load of ProD and its associated or risk factors compared to acute diarrhea (AD, duration ≤7 days). METHODS: We analyzed the data collected between 1996-2014 from a hospital-based Diarrheal-Disease-Surveillance-System (DDSS) in the 'Dhaka Hospital' of International Centre for Diarrhoeal Diseases, Bangladesh (icddr,b). The DDSS enrolled a 2% systematic sample, regardless of age, sex, and diarrhea severity. The data included information on socio-demographic factors, environmental history, clinical characteristics, nutritional status, and diarrhea-pathogens. After cleaning of data, relevant information of 21,566 under-five children were available who reported with ≤13 days diarrhea (including AD and ProD), and their data were analyzed. Variables found significantly associated with ProD compared to AD in bi-variate analysis were used in logistic regression model after checking the multicollinearity between independent variables. RESULTS: The mean±SD age of the children was 14.9±11.7 months and 40.4% were female; 7.6% had ProD and 92.4% had AD. Age <12 months, mucoid- or bloody-stool, warmer months (April-September), drug used at home before seeking care from hospital, and history of diarrhea within last one month were found associated with ProD (p<0.05); however, rotavirus infection was less common in children with ProD (p<0.05). ProD children more often needed inpatient admission than AD children (14.4 vs. 6.3, p<0.001). Case fatality rate of ProD vs. AD was 0.3% (n = 5) vs. 0.1% (n- = 22) respectively (p = 0.051). CONCLUSION: A considerable proportion (7.6%) of under-five children reporting to icddr,b hospital suffered from ProD. Understanding the above-mentioned associated or risk factors is likely to help policy makers formulating appropriate strategies for alleviating the burden and effectively managing ProD in under-five children.

Factors associated with mortality in severely malnourished hospitalized children who developed septic shock.

INTRODUCTION: Septic shock can often lead to death, even in resourceful settings, if not handled carefully. Therefore, we sought to evaluate the factors associated with deaths in the context of severe malnutrition and also the effects of early, i.e., within 3 hours of diagnosing septic shock vs. late blood transfusion. METHODOLOGY: Here, all under-five severely malnourished septic shock children were admitted to ICU during 2013-2017. Children who died constituted cases (n = 54), and the survived (n = 39) represented controls. We excluded children who received the blood transfusion for other causes and who left against medical advice. RESULTS: In both descriptive and multivariate analysis, we found that death was significantly associated with the use of fourth-line antibiotics, corticosteroids, and the addition of vasopressors on top of dopamine (all p < 0.05). However, the decrease of serum calcium level was found significantly associated with death only after adjusting (p < 0.05). Even though the cases more often received early blood transfusion than the controls, the difference was insignificant (p = 0.134). CONCLUSIONS: When a severely malnourished under-five child develops septic shock, requiring vasopressors, fourth-line antibiotic, and corticosteroid, with reduced serum calcium, the probability of death increases significantly. Our findings underscore the gravity of close monitoring at these points and the niches for early interventions.

COVID-19 among staff and their family members of a healthcare research institution in Bangladesh between March 2020 and April 2021: a test-negative case-control study.

OBJECTIVE: To identify factors associated with COVID-19 positivity among staff and their family members of icddr,b, a health research institute located in Bangladesh. SETTING: Dhaka, Bangladesh. PARTICIPANTS: A total of 4295 symptomatic people were tested for SARS-CoV-2 by reverse-transcription PCR between 19 March 2020 and 15 April 2021. Multivariable logistic regression was done to identify the factors associated with COVID-19 positivity by contrasting test positives with test negatives. RESULT: Forty-three per cent of the participants were tested positive for SARS-CoV-2. The median age was high in positive cases (37 years vs 34 years). Among the positive cases, 97% were recovered, 2.1% had reinfections, 24 died and 41 were active cases as of 15 April 2021. Multivariable regression analysis showed that age more than 60 years (adjusted OR (aOR)=2.1, 95% CI 1.3 to 3.3; p<0.05), blood group AB (aOR=1.5, 95% CI 1.1 to 2; p<0.05), fever (aOR=3.1, 95% CI 2.6 to 3.7; p<0.05), cough (aOR=1.3, 95% CI 1.1 to 1.6; p<0.05) and anosmia (aOR=2.7, 95% CI 1.3 to 5.7; p<0.05) were significantly associated with higher odds of being COVID-19 positive when compared with participants who were tested negative. CONCLUSIONS: The study findings suggest that older age, fever, cough and anosmia were associated with COVID-19 among the study participants.

Comparative Clinical Characteristics, Laboratory Findings, and Outcomes of Hypoxemic and Non-Hypoxemic Patients Treated at a Makeshift COVID-19 Unit in Bangladesh: A Retrospective Chart Analysis.

Background: Starting on 31 December 2019, from Wuhan City, China, Coronavirus disease 2019 (COVID-19) caused a global pandemic by 11 March 2020. Bangladesh detected its first case on 8 March 2020, only 66 days later the detection of the first case in China. We aimed to describe the epidemiology, clinical features, laboratory characteristics, and outcomes of Bangladeshi COVID-19 patients. Methods: This retrospective chart analysis compared Bangladeshi COVID-19 patients with hypoxemia compared to those without hypoxemia treated in a makeshift COVID-19 unit of icddr,b. Results: By March 2021, 207 remained in-patient. Nineteen patients (9.2%) died, whereas 10 (4.8%) were referred to different facilities for definitive care. Out of 207 in-patients, 88 patients required oxygen therapy. Multivariable logistic regression identified age (1.07 (1.02−1.13)), dyspnea (3.56 (1.06−11.96)), high CRP (1.13 (1.03−1.25)), and lymphopenia (6.18 (1.81−21.10)) as the independent predictors for hypoxemia in patients hospitalized for COVID 19 (for all, p < 0.05). Conclusion: Older age, dyspnea, high CRP, and lymphopenia are simple, but important, clinical and laboratory parameters. These may help clinicians to identify COVID-19 patients early who are at risk of fatal hypoxemia. Close monitoring, and prompt and aggressive treatment of these patients would curb their morbidity and mortality, especially in resource-limited settings.