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

Introduction: Accelerating progress in reducing child deaths is needed in order to achieve the Sustainable Development Goal child mortality target. This will require a focus on vulnerable children-including young children, those who are undernourished or with acute illnesses requiring hospitalization. Improving adherence to inpatient guidelines may be an important strategy to reduce child mortality, including among the most vulnerable. The aim of our assessment of nine sub-Saharan African and South Asian hospitals was to determine adherence to pediatric inpatient care recommendations, in addition to capacity for and barriers to implementation of guideline-adherent care prior to commencing the Childhood Acute Illness and Nutrition (CHAIN) Cohort study. The CHAIN Cohort study aims to identify modifiable risk factors for poor inpatient and post discharge outcomes above and beyond implementation of guidelines.Methods: Hospital infrastructure, staffing, durable equipment, and consumable supplies such as medicines and laboratory reagents, were evaluated through observation and key informant interviews. Inpatient medical records of 2-23 month old children were assessed for adherence to national and international guidelines. The records of children with severe acute malnutrition (SAM) were oversampled to reflect the CHAIN study population. Seven core adherence indicators were examined: oximetry and oxygen therapy, fluids, anemia diagnosis and transfusion, antibiotics, malaria testing and antimalarials, nutritional assessment and management, and HIV testing.Results: All sites had facilities and equipment necessary to implement care consistent with World Health Organization and national guidelines. However, stockouts of essential medicines and laboratory reagents were reported to be common at some sites, even though they were mostly present during the assessment visits. Doctor and nurse to patient ratios varied widely. We reviewed the notes of 261 children with admission diagnoses of sepsis (17), malaria (47), pneumonia (70), diarrhea (106), and SAM (119); 115 had multiple diagnoses. Adherence to oxygen therapy, antimalarial, and malnutrition refeeding guidelines was \u3e75%. Appropriate antimicrobials were prescribed for 75% of antibiotic-indicative conditions. However, 20/23 (87%) diarrhea and 20/27 (74%) malaria cases without a documented indication were prescribed antibiotics. Only 23/122 (19%) with hemoglobin levels meeting anemia criteria had recorded anemia diagnoses. HIV test results were infrequently documented even at hospitals with universal screening policies (66/173, 38%). Informants at all sites attributed inconsistent guideline implementation to inadequate staffing.Conclusion: Assessed hospitals had the infrastructure and equipment to implement guideline-consistent care. While fluids, appropriate antimalarials and antibiotics, and malnutrition refeeding adherence was comparable to published estimates from low- and high-resource settings, there were inconsistencies in implementation of some other recommendations. Stockouts of essential therapeutics and laboratory reagents were a noted barrier, but facility staff perceived inadequate human resources as the primary constraint to consistent guideline implementation

Minimally invasive postmortem intestinal tissue sampling in malnourished and acutely ill children is feasible and informative

BACKGROUND: Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies\u27 utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition. METHODS: Transabdominal needle and endoscopic forceps upper and lower intestinal sampling were conducted among children aged 1 week to 59 months who died while hospitalized in Blantyre, Malawi. Autolysis ratings were determined for each hematoxylin and eosin slide, and upper and lower intestinal scoring systems were adapted to assess histopathologic features and their severity. RESULTS: Endoscopic and transabdominal sampling procedures were attempted in 28 and 14 cases, respectively, with \u3e90% success obtaining targeted tissue. Varying degrees of autolysis were present in all samples and precluded histopathologic scoring of 6% of 122 biopsies. Greater autolysis in duodenal samples was seen with longer postmortem interval (Beta = 0.06, 95% confidence interval, 0.02-0.11). Histopathologic features identified included duodenal Paneth and goblet cell depletion. Acute inflammation was absent but chronic inflammation was prevalent in both upper and lower enteric samples. Severe chronic rectal inflammation was identified in children as young as 5.5 weeks. CONCLUSIONS: Minimally invasive postmortem intestinal sampling is feasible and identifies histopathology that can inform mortality contributors

Minimally invasive postmortem intestinal tissue sampling in malnourished and acutely ill children is feasible and informative

BACKGROUND: Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies\u27 utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition. METHODS: Transabdominal needle and endoscopic forceps upper and lower intestinal sampling were conducted among children aged 1 week to 59 months who died while hospitalized in Blantyre, Malawi. Autolysis ratings were determined for each hematoxylin and eosin slide, and upper and lower intestinal scoring systems were adapted to assess histopathologic features and their severity. RESULTS: Endoscopic and transabdominal sampling procedures were attempted in 28 and 14 cases, respectively, with \u3e90% success obtaining targeted tissue. Varying degrees of autolysis were present in all samples and precluded histopathologic scoring of 6% of 122 biopsies. Greater autolysis in duodenal samples was seen with longer postmortem interval (Beta = 0.06, 95% confidence interval, 0.02-0.11). Histopathologic features identified included duodenal Paneth and goblet cell depletion. Acute inflammation was absent but chronic inflammation was prevalent in both upper and lower enteric samples. Severe chronic rectal inflammation was identified in children as young as 5.5 weeks. CONCLUSIONS: Minimally invasive postmortem intestinal sampling is feasible and identifies histopathology that can inform mortality contributors

Enteric Permeability, Systemic Inflammation, and Post-Discharge Growth among a Cohort of Hospitalized Children in Kenya and Pakistan

Funding Information: Sources of Funding: The CHAIN Network is supported by the Bill & Melinda Gates Foundation [OPP1131320]. For the purpose of Open Access, the authors have applied a CC-BY public copyright license to any author accepted manuscript version arising from this submission. The lactulose-rhamnose testing was funded by an Early Career Award from the Thrasher Research Foundation. The funders had no role in conduct of the study, interpretation, writing the manuscript or decision to submit. No authors were paid to write this article by any company, organization or agency. Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.Objectives: To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries. Methods: Children aged 2-23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups. Results: One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15-0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00-0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα (P = 0.017), CD14 (P = 0.078), and IL-6 (P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα (P = 0.004) and approached significance with CD14 (P = 0.078) and IL-6 (P = 0.062) in community children, but there was no evidence of these associations among hospitalized children. Conclusions: Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children.Peer reviewe

Data Management in Multicountry Consortium Studies: The Enterics For Global Health (EFGH) Shigella Surveillance Study Example

Background: Rigorous data management systems and planning are essential to successful research projects, especially for large, multicountry consortium studies involving partnerships across multiple institutions. Here we describe the development and implementation of data management systems and procedures for the Enterics For Global Health (EFGH) Shigella surveillance study—a 7-country diarrhea surveillance study that will conduct facility-based surveillance concurrent with population-based enumeration and a health care utilization survey to estimate the incidence of Shigella­-associated diarrhea in children 6 to 35 months old. Methods: The goals of EFGH data management are to utilize the knowledge and experience of consortium members to collect high-quality data and ensure equity in access and decision-making. During the planning phase before study initiation, a working group of representatives from each EFGH country site, the coordination team, and other partners met regularly to develop the data management systems for the study. Results: This resulted in the Data Management Plan, which included selecting REDCap and SurveyCTO as the primary database systems. Consequently, we laid out procedures for data processing and storage, study monitoring and reporting, data quality control and assurance activities, and data access. The data management system and associated real-time visualizations allow for rapid data cleaning activities and progress monitoring and will enable quicker time to analysis. Conclusions: Experiences from this study will contribute toward enriching the sparse landscape of data management methods publications and serve as a case study for future studies seeking to collect and manage data consistently and rigorously while maintaining equitable access to and control of data

Minimizing error in estimates of the effect of interventions by accounting for baseline measurements: A simulation study analyzing effects on child growth

Abstract Interventions to reduce childhood stunting burden require clinical trials with a primary outcome of linear growth. When growth is measured longitudinally, there are several options for including baseline measurements in the analysis. This study compares the performance of several methods. Randomized controlled trials evaluating a hypothetical intervention to improve length‐for‐age z‐score (LAZ) from birth through 24 months of age were simulated. The intervention effect was evaluated using linear regression and five methods for handling baseline measurements: comparing final measurements only (FINAL), comparing final measurement adjusted for baseline (ADJUST), comparing the change in the measurement over time (DELTA), adjusting for baseline when comparing the changes over time (DELTA+ADJUST) and adjusting for baseline in two‐step residuals approach (RESIDUALS). We calculated bias, precision and power of each method for scenarios with and without a baseline imbalance in LAZ. Using a 0.15 effect size at 18 months, FINAL and DELTA required 1200 and 1500 enroled participants, respectively, to reach 80% power, whereas ADJUST, DELTA+ADJUST and RESIDUALS only required 900 participants. The adjusted models also produced unbiased estimates when there was a baseline imbalance, whereas the FINAL and DELTA methods produced biased estimates, as large as 0.07 lower and higher, respectively, than the true effect. Adjusted methods required smaller sample size and produced more precise results than both DELTA and FINAL methods in all test scenarios. If randomization fails, and there is an imbalance in LAZ at baseline, DELTA and FINAL methods can produce biased estimates, but adjusted models remain unbiased. These results warn against using the FINAL or DELTA methods

Lower respiratory tract disorder hospitalizations among children born via elective early-term delivery

<p><i>Objective</i>: We evaluated the hypothesis that elective early-term delivery increases the risk of childhood lower respiratory tract disorder hospitalization.</p> <p><i>Methods</i>: Children born via early-term elective inductions were compared to full- or late-term elective inductions in a retrospective cohort study using Washington State birth certificate and hospital discharge data. Outcomes were the odds of lower respiratory disorder hospitalization before age five and cause specific odds ratios for asthma, bronchiolitis, bronchitis, and pneumonia. In addition, a subgroup analysis excluding infants with perinatal complications was conducted.</p> <p><i>Results</i>: Electively induced early-term children were at significantly increased risk of hospitalization before age five for lower respiratory disorders compared to similar full- or late-term children (adjusted OR: 1.31, 95% CI: 1.11–1.55). Bronchiolitis was the only cause-specific outcome with a statistically significant increase in odds of hospitalization, though comparable increases were found for the less common diagnoses of asthma (adjusted OR: 1.39, 95% CI: 0.93–2.08) and pneumonia (adjusted OR: 1.27, 95% CI: 0.99–1.64). Excluding infants with perinatal complications did not alter the results.</p> <p><i>Conclusions</i>: There was an association between electively induced early-term delivery and hospitalization for lower respiratory tract disorders before age five. This reinforces policies discouraging elective early-term delivery.</p

Depressive symptoms among mothers with hospitalized children in South Asia and sub-Saharan Africa

Background: Poor maternal mental health during childhood hospitalization is associated with post-discharge child mortality. We aimed to establish if maternal PHQ-9 scores during hospitalization are associated with acute stressors or longer trends in mental health status. Method: Mothers of children admitted to nine hospitals in six countries completed a PHQ-9 assessment during hospitalization and 45-days post-discharge. Community participants were recruited from homes near the hospitalized children. The prevalence and correlates of high PHQ-9 scores among hospitalized and community mothers were compared. Outcomes: Among 2762 mothers of hospitalized children, 514 (19 %) had PHQ-9 scores ≥10, significantly more than the 116 (10 %, p < 0·001) of 1159 community participants. Recruitment site and food insecurity were PHQ-9 correlates in both groups. Correlates of higher mean PHQ-9 scores among the hospitalized cohort included maternal illness (mean difference [MD]: 1·27, 95%CI: 0·77, 1·77), pregnancy (MD: 0·77, 95%CI: 0·27, 1·28), child HIV-infection (MD: 2·51. 95%CI: 1·55, 3·52), and lower child weight-for-height (MD: 0·21, 95%CI: 0·32, 0·11). Marriage (MD −0·92, 95%CI: −1·36, −0·48) and a positive malaria test (MD: −0·63, 95%CI: −1·15, −0·10) were associated with lower PHQ-9 scores among mothers of hospitalized children. Among mothers with PHQ-9 ≥10 during admission, 410 had repeat assessments 45-days after their child's discharge, and 108 (26 %) continued to meet the high PHQ-9 criterion. Interpretation: Among mothers of hospitalized children, there are subgroups with transient and persistent depressive symptoms. Interventions tailored to address acute stressors may improve post-discharge pediatric and maternal health outcomes. Funding: Bill & Melinda Gates Foundation OPP1131320

Prevalence and correlates of paediatric guideline non-adherence for initial empirical care in six low and middle-income settings: A hospital-based cross-sectional study

Objectives: This study evaluated the prevalence and correlates of guideline non-adherence for common childhood illnesses in low-resource settings.Design and setting: We used secondary cross-sectional data from eight healthcare facilities in six Asian and African countries.Participants: A total of 2796 children aged 2-23 months hospitalised between November 2016 and January 2019 with pneumonia, diarrhoea or severe malnutrition (SM) and without HIV infection were included in this study.Primary outcome measures: We identified children treated with full, partial or non-adherent initial inpatient care according to site-specific standard-of-care guidelines for pneumonia, diarrhoea and SM within the first 24 hours of admission. Correlates of guideline non-adherence were identified using generalised estimating equations.Results: Fully adherent care was delivered to 32% of children admitted with diarrhoea, 34% of children with pneumonia and 28% of children with SM when a strict definition of adherence was applied. Non-adherence to recommendations was most common for oxygen and antibiotics for pneumonia; fluid, zinc and antibiotics for diarrhoea; and vitamin A and zinc for SM. Non-adherence varied by site. Pneumonia guideline non-adherence was more likely among patients with severe disease (OR 1.82; 95% CI 1.38, 2.34) compared with non-severe disease. Diarrhoea guideline non-adherence was more likely among lower asset quintile groups (OR 1.16; 95% CI 1.01, 1.35), older children (OR 1.10; 95% CI 1.06, 1.13) and children presenting with wasting (OR 6.44; 95% CI 4.33, 9.57) compared with those with higher assets, younger age and not wasted.Conclusions: Non-adherence to paediatric guidelines was common and associated with older age, disease severity, and comorbidities, and lower household economic status. These findings highlight opportunities to improve guidelines by adding clarity to specific recommendations