The role of healthcare providers and caregivers in monitoring critically ill children: a qualitative study in a tertiary hospital, southern Malawi.

BACKGROUND: Critically ill children require close monitoring to facilitate timely interventions throughout their hospitalisation. In low- and middle-income countries with a high disease burden, scarce paediatric critical care resources complicates effective monitoring. This study describes the monitoring practices for critically ill children in a paediatric high-dependency unit (HDU) in Malawi and examines factors affecting this vital process. METHODS: A formative qualitative study based on 21 in-depth interviews of healthcare providers (n = 12) and caregivers of critically ill children (n = 9) in the HDU along with structured observations of the monitoring process. Interviews were transcribed and translated for thematic content analysis. RESULTS: The monitoring of critically ill children admitted to the HDU was intermittent, using devices and through clinical observations. Healthcare providers prioritised the most critically ill children for more frequent monitoring. The ward layout, power outages, lack of human resources and limited familiarity with available monitoring devices, affected monitoring. Caregivers, who were present throughout admission, were involved informally in monitoring and flagging possible deterioration of their child to the healthcare staff. CONCLUSION: Barriers to the monitoring of critically ill children in the HDU were related to ward layout and infrastructure, availability of accurate monitoring devices and limited human resources. Potential interventions include training healthcare providers to prioritise the most critically ill children, allocate and effectively employ available devices, and supporting caregivers to play a more formal role in escalation.

Identifying critically ill children in Malawi: A modified qSOFA score for low-resource settings.

In low-resource settings, a reliable bedside score for timely identification of children at risk of dying, could help focus resources and improve survival. The rapid bedside Liverpool quick Sequential Organ Failure Assessment (LqSOFA) uses clinical parameters only and performed well in United Kingdom cohorts. A similarly quick clinical assessment-only score has however not yet been developed for paediatric populations in sub-Saharan Africa. In a development cohort of critically ill children in Malawi, we calculated the LqSOFA scores using age-adjusted heart rate and respiratory rate, capillary refill time and Blantyre Coma Scale, and evaluated its prognostic performance for mortality. An improved score, the Blantyre qSOFA (BqSOFA), was developed (omitting heart rate, adjusting respiratory rate cut-off values and adding pallor), subsequently validated in a second cohort of Malawian children, and compared with an existing score (FEAST-PET). Prognostic performance for mortality was evaluated using area under the receiver operating characteristic curve (AUC). Mortality was 15.4% in the development (N = 493) and 22.0% in the validation cohort (N = 377). In the development cohort, discriminative ability (AUC) of the LqSOFA to predict mortality was 0.68 (95%-CI: 0.60-0.76). The BqSOFA and FEAST-PET yielded AUCs of 0.84 (95%-CI:0.79-0.89) and 0.83 (95%-CI:0.77-0.89) in the development cohort, and 0.74 (95%-CI:0.68-0.79) and 0.76 (95%-CI:0.70-0.82) in the validation cohort, respectively. We developed a simple prognostic score for Malawian children based on four clinical parameters which performed as well as a more complex score. The BqSOFA might be used to promptly identify critically ill children at risk of dying and prioritize hospital care in low-resource settings.

Prevalence, mortality, and aetiology of paediatric shock in a tertiary hospital in Malawi: A cohort study.

Shock is considered one of the most important mechanisms of critical illness in children. However, data on paediatric shock in sub-Saharan Africa is limited, which constrains development of effective treatment strategies. We aimed to describe the prevalence, mortality, and aetiology of paediatric shock in a tertiary hospital in Malawi. Children aged two months to 16 years presenting with shock (FEAST criteria; respiratory distress and/or impaired consciousness, and at least one sign of impaired circulation; capillary refill>3 seconds, cold extremities, weak pulse, or severe tachycardia) to the emergency department were included and followed-up prospectively using routinely collected data between February 2019 and January 2020. Prevalence, mortality and aetiology of shock were reported for both the FEAST criteria and World Health Organization (WHO) definition. The association between aetiology and mortality was assessed with univariable analysis. Of all screened admissions (N = 12,840), 679 (5.3%) children presented with shock using FEAST criteria and the mortality was 79/663 (11.9%). WHO-defined shock applied to 16/12,840 (0.1%) and the mortality was 9/15 (60.0%). Main diagnoses were viral/reactive airway diseases (40.4%), severe pneumonia (14.3%), gastroenteritis (11.3%) and presumed sepsis (5.7%). Children diagnosed with presumed sepsis and gastroenteritis had the highest odds of dying (OR 11.3; 95%-CI:4.9-25.8 and OR 4.4; 95%-CI:2.4-8.2). Considering the high mortality, prevalence of paediatric shock (FEAST and WHO definitions) in Malawi is high. Sepsis and gastroenteritis are diagnoses associated with poor outcome in these children. Consensus on a clinical meaningful definition for paediatric shock is essential to boost future studies.

Using interprofessional education to build dynamic teams to help drive collaborative, coordinated and effective newborn care.

BACKGROUND: As countries strive to achieve sustainable development goal 3.2, high-quality medical education is crucial for high-quality neonatal care. Women are encouraged to deliver in health units attended by a skilled team. Traditionally, the team is doctors and nurses, but they are members of a large group of interdependent experts from other disciplines. Each discipline trains separately, yet the goal of good neonatal care is common to all. The use of interprofessional education breaks down these professional silos improving collaborative practice and promoting excellent clinical care. Introduction of new educational materials and training requires a rigorous approach to ensure sustainability. METHODS: An extensive needs assessment identified gaps in neonatal training. Specifically, there was a lack of inclusion of medical devices used in clinical care. In each country, national key stakeholders came together to develop and revise their own neonatal curricula, trainings or guidelines. A core writing education team were tasked to develop evidence-based materials on pertinent medical devices to include in these national materials. These then underwent internal and external review. A provider course for biomedical engineers and technicians was introduced. Skills labs were established to improve practical skills teaching. To improve the quality of teaching, a NEST360 generic instructors course (GIC) was developed. RESULTS: Twenty modules, 14 scenarios, 17 job aids and 34 videos have been published to date. Materials have been embedded into neonatal curricula and national trainings. Forty-one skills labs were installed in pre-service learning institutions and, up to June 2022, have been used by 7281 students. Pre- and in-service interprofessional training was implemented at all NEST360 institutions (clinical and biomedical). GIC courses were conducted at least twice a year in all countries. Three hundred seventeen nurses, biomedical and clinical staff have undertaken the GIC in all four countries. GIC participants report that the course has very positively influenced their teaching practice. CONCLUSIONS: Inclusion of key stakeholders throughout has ensured training is embedded within the four countries. Use of interprofessional education and inclusion of biomedical engineers and technicians has been very successful. Introduction of the GIC has developed a pool of high-quality educators for neonatal care. This approach has ensured that high-quality interprofessional neonatal training is included within national agendas for neonatal care and beyond.

Outcome in Children Admitted to the First PICU in Malawi.

OBJECTIVES: Dedicated PICUs are slowly starting to emerge in sub-Saharan Africa. Establishing these units can be challenging as there is little data from this region to inform which populations and approaches should be prioritized. This study describes the characteristics and outcome of patients admitted to the first PICU in Malawi, with the aim to identify factors associated with increased mortality. DESIGN: Review of a prospectively constructed PICU database. Univariate analysis was used to assess associations between demographic, clinical and laboratory factors, and mortality. Univariate associations ( p < 0.1) for mortality were entered in two multivariable models. SETTING: A recently opened PICU in a public tertiary government hospital in Blantyre, Malawi. PATIENTS: Children admitted to PICU between August 1, 2017, and July 31, 2019. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of 531 included PICU admissions, 149 children died (28.1%). Mortality was higher in neonates (88/167; 52.7%) than older children (61/364; 16.8%; p ≤ 0.001). On univariate analysis, gastroschisis, trachea-esophageal fistula, and sepsis had higher PICU mortality, while Wilms tumor, other neoplasms, vocal cord papilloma, and foreign body aspiration had higher survival rates compared with other conditions. On multivariable analysis, neonatal age (adjusted odds ratio [AOR], 4.0; 95% CI, 2.0-8.3), decreased mental state (AOR, 5.8; 95 CI, 2.4-13.8), post-cardiac arrest (AOR, 2.0; 95% CI, 1.0-8.0), severe hypotension (AOR, 6.3; 95% CI, 2.0-19.1), lactate greater than 5 mmol/L (AOR, 4.2; 95% CI, 1.5-11.2), pH less than 7.2 (AOR, 3.1; 95% CI, 1.2-8.0), and platelets less than 150 × 10 9 /L (AOR, 2.4; 95% CI, 1.1-5.2) were associated with increased mortality. CONCLUSIONS: In the first PICU in Malawi, mortality was relatively high, especially in neonates. Surgical neonates and septic patients were identified as highly vulnerable, which stresses the importance of improvement of PICU care bundles for these groups. Several clinical and laboratory variables were associated with mortality in older children. In neonates, severe hypotension was the only clinical variable associated with increased mortality besides blood gas parameters. This stresses the importance of basic laboratory tests, especially in neonates. These data contribute to evidence-based approaches establishing and improving future PICUs in sub-Saharan Africa.

Effect of resistance to third-generation cephalosporins on morbidity and mortality from bloodstream infections in Blantyre, Malawi: a prospective cohort study.

BACKGROUND: The burden of antimicrobial resistance is a major threat to global health; however, prospective clinical outcome data from Africa are scarce. In Malawi, third-generation cephalosporins are the antibiotics of choice in patients admitted to hospital despite a rapid proliferation of resistance to these drugs. We aimed to quantify the effect of resistance to third-generation cephalosporins on mortality and length of hospital stay among patients with bloodstream infections. METHODS: We did a prospective cohort study of patients admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi. Patients of all ages who had positive blood cultures for Enterobacterales were included, with the exception of those from the genus Salmonella, and were followed up for 180 days. We characterised blood culture isolates using whole-genome sequencing and used Cox regression models to estimate the effect of resistance to third-generation cephalosporins on length of hospital stay, in-hospital mortality, and survival. FINDINGS: Between Jan 31, 2018, and Jan 13, 2020, we recruited 326 patients, from whom 220 (68%) of 326 isolates were resistant to third-generation cephalosporins. The case fatality proportion was 45% (99 of 220) in patients with bloodstream infections that were resistant to third-generation cephalosporins, and 34% (36 of 106) in patients with bloodstream infections that were sensitive to third-generation cephalosporins. Resistance to third-generation cephalosporins was associated with an increased probability of in-hospital mortality (hazard ratio [HR] 1·44, 95% CI 1·02-2·04), longer hospital stays (1·5 days, 1·0-2·0) and decreased probability of discharge alive (HR 0·31, 0·22-0·45). Whole-genome sequencing showed a high diversity of sequence types of both Escherichia coli and Klebsiella pneumoniae. Although isolates associated with death were distributed across clades, we identified three E coli clades (ST410, ST617, and ST648) that were isolated from 14 patients who all died. INTERPRETATION: Resistance to third-generation cephalosporins is associated with increased mortality and longer hospital stays in patients with bloodstream infections in Malawi. These data show the urgent need for allocation of resources towards antimicrobial resistance mitigation strategies in Africa. FUNDING: Wellcome Trust and Wellcome Asia and Africa Programme.

A U - Net Deep Learning Model for Infant Heart Rate Estimation from Ballistography.

Ballistography(BSG) is a non-intrusive and low- cost alternative to electrocardiography (ECG) for heart rate (HR) monitoring in infants. Due to the inter-patient variance and susceptibility to noise, heartbeat detection in the BSG waveform remains a challenge. The aim of this study was to estimate HR from a bed-based pressure mat BSG signal using a deep learning approach. We trained a U-Net deep neural network through supervised learning by deriving ground truth as the location of the heartbeats from simultaneously recorded ECG signals after peak matching. For improved generalization, we modified an existing U - Net to include an IC-layer. A predictive performance of 80% was achieved using the U-Net without the IC-layer. The inclusion of the IC-layer, while improving the generalization ability of the model to detect heartbeats, did not improve the HR estimation performance.

Etiology, Pathophysiology and Mortality of Shock in Children in Low (Middle) Income Countries: A Systematic Review.

OBJECTIVES: Shock is a life-threatening condition in children in low- and middle-income countries (LMIC), with several controversies. This systematic review summarizes the etiology, pathophysiology and mortality of shock in children in LMIC. METHODS: We searched for studies reporting on children with shock in LMIC in PubMed, Embase and through snowballing (up to 1 October 2019). Studies conducted in LMIC that reported on shock in children (1 month-18 years) were included. We excluded studies only containing data on neonates, cardiac surgery patients or iatrogenic causes. We presented prevalence data, pooled mortality estimates and conducted subgroup analyses per definition, region and disease. Etiology and pathophysiology data were systematically collected. RESULTS: We identified 959 studies and included 59 studies of which six primarily studied shock. Definitions used for shock were classified into five groups. Prevalence of shock ranged from 1.5% in a pediatric hospital population to 44.3% in critically ill children. Pooled mortality estimates ranged between 3.9-33.3% for the five definition groups. Important etiologies included gastroenteritis, sepsis, malaria and severe anemia, which often coincided. The pathophysiology was poorly studied but suggests that in addition to hypovolemia, dissociative and cardiogenic shock are common in LMIC. CONCLUSIONS: Shock is associated with high mortality in hospitalized children in LMIC. Despite the importance few studies investigated shock and as a consequence limited data on etiology and pathophysiology of shock is available. A uniform bedside definition may help boost future studies unravelling shock etiology and pathophysiology in LMIC.

Prospective cohort study of referred Malawian children and their survival by hypoxaemia and hypoglycaemia status.

Objective: To investigate survival in children referred from primary care in Malawi, with a focus on hypoglycaemia and hypoxaemia progression. Methods: The study involved a prospective cohort of children aged 12 years or under referred from primary health-care facilities in Mchinji district, Malawi in 2019 and 2020. Peripheral blood oxygen saturation (SpO2) and blood glucose were measured at recruitment and on arrival at a subsequent health-care facility (i.e. four hospitals and 14 primary health-care facilities). Children were followed up 2 weeks after discharge or their last clinical visit. The primary study outcome was the case fatality ratio at 2 weeks. Associations between SpO2 and blood glucose levels and death were evaluated using Cox proportional hazards models and the treatment effect of hospitalization was assessed using propensity score matching. Findings: Of 826 children recruited, 784 (94.9%) completed follow-up. At presentation, hypoxaemia was moderate (SpO2: 90-93%) in 13.1% (108/826) and severe (SpO2: < 90%) in 8.6% (71/826) and hypoglycaemia was moderate (blood glucose: 2.5-4.0 mmol/L) in 9.0% (74/826) and severe (blood glucose: < 2.5 mmol/L) in 2.3% (19/826). The case fatality ratio was 3.7% (29/784) overall but 26.3% (5/19) in severely hypoglycaemic children and 12.7% (9/71) in severely hypoxaemic children. Neither moderate hypoglycaemia nor moderate hypoxaemia was associated with mortality. Conclusion: Presumptive pre-referral glucose treatment and better management of hypoglycaemia could reduce the high case fatality ratio observed in children with severe hypoglycaemia. The morbidity and mortality burden of severe hypoxaemia was high; ways of improving hypoxaemia identification and management are needed.

Hypoxemia, hypoglycemia and IMCI danger signs in pediatric outpatients in Malawi.

Hypoxemia and hypoglycemia are known risks for mortality in children in low-income settings. Routine screening with pulse oximetry and blood glucose assessments for outpatients could assist in early identification of high-risk children. We assessed the prevalence of hypoglycemia and hypoxemia, and the overlap with Integrated Management of Childhood Illness (IMCI) general danger signs, among children seeking outpatient care in Malawi. A cross-sectional study was conducted at 14 government primary care facilities, four rural hospitals and one district referral hospital in Mchinji district, Malawi from August 2019-April 2020. All children aged 0-12 years seeking care with an acute illness were assessed on one day per month in each facility. Study research assistants measured oxygen saturation using Lifebox LB-01 pulse oximeter and blood glucose was assessed with AccuCheck Aviva glucometers. World Health Organization definitions were used for severe hypoglycemia (<2.5mmol/l) and hypoxemia (SpO2 <90%). Moderate hypoglycemia (2.5-4.0mmol/l) and hypoxemia (SpO2 90-93%) were also calculated and prevalence levels compared between those with and without IMCI danger signs using chi2 tests. In total 2,943 children were enrolled, with a median age of 41 (range: 0-144) months. The prevalence of severe hypoxemia was 0.6% and moderate hypoxemia 5.4%. Severe hypoglycemia was present in 0.1% of children and moderate hypoglycemia in 11.1%. IMCI general danger signs were present in 29.3% of children. All severely hypoglycemic children presented with an IMCI danger sign (p <0.001), but only 23.5% of the severely hypoxemic and 31.7% of the moderately hypoxemic children. We conclude that while the prevalence of severe hypoxemia and hypoglycemia were low, moderate levels were not uncommon and could potentially be useful as an objective tool to determine referral needs. IMCI danger signs identified hypoglycemic children, but results highlight the challenge to detect hypoxemia. Future studies should explore case management strategies for moderate hypoxemia and hypoglycemia.

Paediatric Emergency Triage, Assessment and Treatment (ETAT) - preparedness for implementation at primary care facilities in Malawi.

BACKGROUND: The majority of deaths amongst children under 5 years are still due to preventable infectious causes. Emergency care has been identified as a key health system weakness, and referrals are often challenging. OBJECTIVE: We aimed to establish how prepared frontline facilities in Malawi are to implement WHO Emergency Triage Assessment and Treatment (ETAT) guidelines, to support policy and planning decisions. METHODS: We conducted a concurrent mixed-methods study, including facility audit; healthcare provider survey; focus group discussions (FGD) and semi-structured interviews with facility staff. The study was conducted in two districts in Malawi, Zomba and Mchinji, between January and May 2019. We included all frontline facilities, including dispensaries, primary health centres, rural and community hospitals. Quantitative data were described using proportions, means and linear regression. Qualitative data was analysed using a framework approach. Data were analysed separately and then triangulated into common themes. RESULTS: Forty-seven facilities and 531 healthcare providers were included in the audit and survey; 6 FGDs and 5 interviews were completed. Four common themes emerged: (1) current emergency case management; (2) referral practices; (3) trained staff capacity; (4) opportunities and barriers for ETAT. Triage was conducted in most facilities with various methods described, and 53% reporting all staff are responsible. Referrals were common, but challenging due to issues in transportation. Twelve percent of survey respondents had ETAT training, with clinical officers (41%) reporting this more frequently than other cadres. Training was associated with increased knowledge, independent of cadre. The main barriers to ETAT implementation were the lack of resources, but opportunities to improve quality of care were reported. CONCLUSIONS: Malawian frontline facilities are already providing a level of emergency paediatric care, but issues in training, drug supplies and equipment were present. To effectively scale-up ETAT, policies need to include supply chain management, maintenance and strengthening referral communication.

The Association of Low Blood Glucose and Low Serum Cortisol Levels in Severely Ill Children Admitted to Tertiary Referral Hospitals in Malawi: A Case-Control Study.

Low blood glucose concentrations < 5 mmol/L in severely ill children presenting to hospitals in low-income countries are associated with mortality. Adrenal insufficiency with low cortisol levels may contribute to low blood glucose concentrations. Understanding the association between low cortisol and low blood glucose may assist in improving guidelines for management of severely ill children. The study aimed to determine the association between low serum cortisol and low blood glucose in severely ill children. A matched case-control study of children aged 1 month to 15 years was conducted at two tertiary hospitals in Malawi. Cases were children with blood glucose < 5 mmol/L. Two age-matched controls with blood glucose of ≥ 5-15 mmol/L were enrolled per case. Low cortisol was defined as serum cortisol of < 25 µg/dL (690 nmol/L) and adrenal insufficiency as serum cortisol of < 10 µg/dL (276 nmol/L). A total of 54 cases and 108 controls were enrolled with, median age of 2.8 years (interquartile range [IQR]: 1.7-4.4). The median cortisol level was 58.7 µg/dL (IQR: 42.3-61.8) in cases and 40.9 µg/dL (IQR: 33.7-51.2) in controls (P = 0.911). The proportion of low cortisol was 4/54 (7.4%) in cases and 9/108 (8.3%) in controls. Logistic regression shows no association between low cortisol and low blood glucose (adjusted odds ratio: 0.33; 95% confidence interval, 0.04-3.02). Results suggest that there is no association between low cortisol and low blood glucose among severely ill children presenting to hospitals in Malawi. The reason for low blood glucose needs further investigation.

Integrated Management of Childhood Illnesses (IMCI): a mixed-methods study on implementation, knowledge and resource availability in Malawi.

Background: The introduction of the WHO's Integrated Management of Childhood Illnesses (IMCI) guidelines in the mid-1990s contributed to global reductions in under-five mortality. However, issues in quality of care have been reported. We aimed to determine resource availability and healthcare worker knowledge of IMCI guidelines in two districts in Malawi. Methods: We conducted a mixed-methods study, including health facility audits to record availability and functionality of essential IMCI equipment and availability of IMCI drugs, healthcare provider survey and focus group discussions (FGDs) with facility staff. The study was conducted between January and April 2019 in Mchinji (central region) and Zomba (southern region) districts. Quantitative data were described using proportions and χ2 tests; linear regression was conducted to explore factors associated with IMCI knowledge. Qualitative data were analysed using a pragmatic framework approach. Qualitative and quantitative data were analysed and presented separately. Results: Forty-seven health facilities and 531 healthcare workers were included. Lumefantrine-Artemether and cotrimoxazole were the most available drugs (98% and 96%); while amoxicillin tablets and salbutamol nebuliser solution were the least available (28% and 36%). Respiratory rate timers were the least available piece of equipment, with only 8 (17%) facilities having a functional device. The mean IMCI knowledge score was 3.96 out of 10, and there was a statistically significant association between knowledge and having received refresher training (coeff: 0.42; 95% CI 0.01 to 0.82). Four themes were identified in the FGDs: IMCI implementation and practice, barriers to IMCI, benefits of IMCI and sustainability. Conclusion: We found key gaps in IMCI implementation; however, these were not homogenous across facilities, suggesting opportunities to learn from locally adapted IMCI best practices. Improving on-going mentorship, training and supervision should be explored to improve quality of care, and programming which moves away from vertical financing with short-term support, to a more holistic approach with embedded sustainability may address the balance of resources for different conditions.

Application of systems dynamics and group model building to identify barriers and facilitators to acute care delivery in a resource limited setting.

BACKGROUND: Group model building (GMB) is a method to facilitate shared understanding of structures and relationships that determine system behaviors. This project aimed to determine the feasibility of GMB in a resource-limited setting and to use GMB to describe key barriers and facilitators to effective acute care delivery at a tertiary care hospital in Malawi. METHODS: Over 1 week, trained facilitators led three GMB sessions with two groups of healthcare providers to facilitate shared understanding of structures and relationships that determine system behaviors. One group aimed to identify factors that impact patient flow in the paediatric special care ward. The other aimed to identify factors impacting delivery of high-quality care in the paediatric accident and emergency room. Synthesized causal maps of factors influencing patient care were generated, revised, and qualitatively analyzed. RESULTS: Causal maps identified patient condition as the central modifier of acute care delivery. Severe illness and high volume of patients were identified as creating system strain in several domains: (1) physical space, (2) resource needs and utilization, (3) staff capabilities and (4) quality improvement. Stress in these domains results in worsening patient condition and perpetuating negative reinforcing feedback loops. Balancing factors inherent to the current system included (1) parental engagement, (2) provider resilience, (3) ease of communication and (4) patient death. Perceived strengths of the GMB process were representation of diverse stakeholder viewpoints and complex system synthesis in a visual causal pathway, the process inclusivity, development of shared understanding, new idea generation and momentum building. Challenges identified included time required for completion and potential for participant selection bias. CONCLUSIONS: GMB facilitated creation of a shared mental model, as a first step in optimizing acute care delivery in a paediatric facility in this resource-limited setting.

Effect on mortality of increasing the cutoff blood glucose concentration for initiating hypoglycaemia treatment in severely sick children aged 1 month to 5 years in Malawi (SugarFACT): a pragmatic, randomised controlled trial.

BACKGROUND: Low blood glucose concentrations are common in sick children who present to hospital in low-resource settings and are associated with increased mortality. The cutoff blood glucose concentration for the diagnosis and treatment of hypoglycaemia currently recommended by WHO (2·5 mmol/L) is not evidence-based. We aimed to assess whether increasing the cutoff blood glucose concentration for hypoglycaemia treatment in severely ill children at presentation to hospital improves mortality outcomes. METHODS: We did a pragmatic, randomised controlled trial at two referral hospitals in Malawi. Severely ill children aged 1 month to 5 years presenting to the emergency department with a capillary blood glucose concentration of between 2·5 mmol/L (3·0 mmol/L in severely malnourished children) and 5·0 mmol/L were randomly assigned (1:1) by a computer-generated randomisation sequence, stratified by study site and severe malnutrition, to receive either an immediate intravenous bolus of 10% dextrose at 5 mL/kg followed by a 24-h maintenance infusion of 10% dextrose at 100 mL/kg for the first 10 kg of bodyweight, 50 mL/kg for the next 10 kg, and 20 mL/kg for each subsequent kg of bodyweight (intervention group) or observation for a minimum of 60 min and standard care (control group). Participants and study personnel were not masked to treatment allocation. The primary outcome was all-cause in-hospital mortality, assessed on an intention-to-treat basis. Safety was also assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02989675. FINDINGS: Between Dec 5, 2016, and Jan 22, 2019, 10 947 children were screened, of whom 332 were randomly assigned, and 322 were included in the final analysis (n=162 in the control group and n=160 in the intervention group). The study was terminated after an interim analysis at 24% enrolment indicated futility. The median age of participants was 2·3 years (IQR 1·4-3·2), 65 (45%) were female, and the baseline characteristics of participants were similar between the two groups. The number of in-hospital deaths from any cause was 26 (16%) in the control group and 24 (15%) in the intervention group, with an absolute mortality difference of 1·0% (95% CI -6·9 to 9·0). Serious adverse events, including hypoglycaemia, hyperglycaemia, convulsions, reduced consciousness, and death, were reported in 47 (29%) children in the control group and 39 (24%) children in the intervention group. INTERPRETATION: Increasing the cutoff blood glucose concentration for hypoglycaemia treatment in severely sick children in Malawi from 2·5 mmol/L to 5·0 mmol/L did not reduce all-cause in-hospital mortality. Our findings do not support changing the cutoff for dextrose administration, and further research on the optimal management of severely ill children who present to the emergency department with low blood glucose concentrations is warranted. FUNDING: Swedish Research Council and Stockholm Country Council.

Feeding practices and association of fasting and low or hypo glycaemia in severe paediatric illnesses in Malawi - a mixed method study.

BACKGROUND: The presence of low or hypo glycaemia in children upon admission to hospital in low income countries is a marker for poor outcome. Fasting during illness may contribute to low blood glucose and caretakers' feeding practices during childhood illnesses may thus play a role in the development of low or hypo glycaemia. This study aims to describe the caretaker's feeding practices and association of fasting with low or hypo glycaemia in sick children in Malawi. METHODS: A mixed method approach was used combining quantitative cross-sectional data for children aged 0-17 years admitted to Queen Elizabeth Central Hospital (QECH), a tertiary hospital in Malawi, with qualitative focus group discussions conducted with caretakers of young children who were previously referred to QECH from the five health centres around QECH. Logistic regression was used to analyse the quantitative data and thematic content analysis was conducted for qualitative data analysis. RESULTS: Data for 5131 children who were admitted through the hospital's Paediatric Accident and Emergency Department (A&E) were analysed whereof 2.1% presented with hypoglycaemia (< 2.5 mmol/l) and 6.6% with low glycaemia (≥2.5mmoll/l - < 5 mmol/l). Fasting for more than eight hours was associated with low glycaemia as well as hypoglycaemia with Adjusted Odds Ratios (AOR) of 2.9 (95% Confidence Interval (CI) of 2.3-3.7) and 4.6, (95% CI 3.0-7.0), respectively. Caretakers demonstrated awareness of the importance of feeding during childhood illness and reported intensified feeding attention to sick children but face feeding challenges when illness becomes severe causing them to seek care at a health facility. CONCLUSION: Results suggests that caretakers understand the importance of feeding during illness and make efforts to intensify feeding a sick child but challenges occur when illness is severe leading to fasting. Fasting among children admitted to hospitals may serve as a marker of severe illness and determine those at risk of low and hypoglycaemia.

Association of Neonatal Hypothermia with Morbidity and Mortality in a Tertiary Hospital in Malawi.

OBJECTIVES: To evaluate associations with neonatal hypothermia in a tertiary-level neonatal unit (NU) in Malawi. METHODS: Neonates with a birth weight >1000 g were recruited and temperatures were recorded 5 min after birth, on admission and 4 h thereafter. Clinical course and outcome were reviewed. Data were analysed using Stata v.15 and p < 0.05 was considered statistically significant. RESULTS: Between August 2018 to March 2019, 120 neonates were enrolled, and 112 were included in the data analysis. Hypothermia at 5 min after birth was noted in 74%, 77% on admission to the NU and 38% at 24 h. Neonates who had hypothermia 5 min after birth were more likely to have hypothermia on admission to the NU compared with normothermic subjects (p < 0.01). All neonates with hypothermia on admission to the NU died (100 vs.72%, p = 0.02), but hypothermia at 5 min nor at 24 h were not associated with mortality. After adjusting for potential confounders, the odds ratio of hypothermia at 5 min for hypothermia on admission to NU was 13.31 (95% CI 4.17-42.54). DISCUSSION: A large proportion of hospitalized neonates is hypothermic on admission and has associated morbidity and mortality. Our findings suggest that a strong predictor of mortality is neonatal hypothermia on admission to the NU, and that early intervention in the immediate period after delivery could decrease the incidence of hypothermia and reduce associated morbidity and mortality.

The introduction of a paediatric nutrition support program led by a clinical dietitian at a low-resource hospital setting in Malawi.

In low- and middle-income countries, nutrition support strategies are often suboptimal or non-existent in hospital settings. This is further compounded by high rates of malnutrition in these countries. The first four dietitians graduated in Malawi in 2017 providing a new opportunity to build capacity to introduce nutrition support in an acute care setting. A paediatric nutrition support program was implemented at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi including the hiring of a local dietitian. This capacity building paper explains the development and introduction of the nutrition support program including a description of perceptions of health professionals at QECH working alongside the dietitian. In the first four months of the program at QECH, the dietitian provided nutrition support to 183 different patients across paediatric wards. Nutritional interventions predominantly included infant formula and breastmilk fortification, provision of therapeutic feeds orally or via nasogastric tubes, increased dietary protein intake for children identified to be at high risk, and nutritional counselling to caregivers. More complex nutritional interventions were also given such as the insertion of gastrostomy tubes to deliver nutrition directly to the stomach. Following the introduction of the program, qualitative interviews were done with health professionals at QECH including nurses (n = 5) and physicians (n = 11). All participants emphasized the importance and impact of the nutrition support program in enhancing the care of hospitalized children, therefore improving outcomes such as tolerability of clinical interventions, decreased duration of stay, and reduced risk of hospital readmission. In conclusion, there is a need for nutrition support provided by a dietitian for different paediatric patients which was corroborated by positive feedback from health professionals at QECH. Integration of dietitians into the healthcare system by respective Ministries of Health will require advocacy around the potential for nutrition support to strengthen the quality of care of vulnerable children. A Chichewa abstract for this paper is available in a supplementary file.

Risk Factors for Mortality in Severely Ill Children Admitted to a Tertiary Referral Hospital in Malawi.

In low-resource settings, many children are severely ill at arrival to hospital. The risk factors for mortality among such ill children are not well-known. Understanding which of these patients are at the highest risk could assist in the allocation of limited resources to where they are most needed. A cohort study of severely ill children treated in the resuscitation room of the pediatric emergency department at Queen Elizabeth Central Hospital in Malawi was conducted over a 6-month period in 2017. Data on signs and symptoms, vital signs, blood glucose levels, and nutritional status were collected and linked with in-hospital mortality data. The factors associated with in-hospital mortality were analyzed using multivariable logistic regression. Data for 1,359 patients were analyzed and 118 (8.7%) patients died. The following factors were associated with mortality: presence of any severely deranged vital sign, unadjusted odds ratio (UOR) 2.6 (95% CI 1.7-4.0) and adjusted odds ratio (AOR) 3.2 (95% CI 2.0-5.0); severe dehydration, UOR 2.6 (1.4-5.1) and AOR 2.8 (1.3-6.0); hypoglycemia glycemia (< 5 mmol/L), UOR 3.6 (2.2-5.8) and AOR 2.7 (1.6-4.7); and severe acute malnutrition, UOR 5.8 (3.5-9.6) and AOR 5.7 (3.3-10.0). This study suggests that among severely sick children, increased attention should be given to those with hypo/low glycemia, deranged vital signs, malnutrition, and severe dehydration to avert mortality among these high-risk patients.