Prediction models for post-discharge mortality among under-five children with suspected sepsis in Uganda: A multicohort analysis.

In many low-income countries, over five percent of hospitalized children die following hospital discharge. The lack of available tools to identify those at risk of post-discharge mortality has limited the ability to make progress towards improving outcomes. We aimed to develop algorithms designed to predict post-discharge mortality among children admitted with suspected sepsis. Four prospective cohort studies of children in two age groups (0-6 and 6-60 months) were conducted between 2012-2021 in six Ugandan hospitals. Prediction models were derived for six-months post-discharge mortality, based on candidate predictors collected at admission, each with a maximum of eight variables, and internally validated using 10-fold cross-validation. 8,810 children were enrolled: 470 (5.3%) died in hospital; 257 (7.7%) and 233 (4.8%) post-discharge deaths occurred in the 0-6-month and 6-60-month age groups, respectively. The primary models had an area under the receiver operating characteristic curve (AUROC) of 0.77 (95%CI 0.74-0.80) for 0-6-month-olds and 0.75 (95%CI 0.72-0.79) for 6-60-month-olds; mean AUROCs among the 10 cross-validation folds were 0.75 and 0.73, respectively. Calibration across risk strata was good: Brier scores were 0.07 and 0.04, respectively. The most important variables included anthropometry and oxygen saturation. Additional variables included: illness duration, jaundice-age interaction, and a bulging fontanelle among 0-6-month-olds; and prior admissions, coma score, temperature, age-respiratory rate interaction, and HIV status among 6-60-month-olds. Simple prediction models at admission with suspected sepsis can identify children at risk of post-discharge mortality. Further external validation is recommended for different contexts. Models can be digitally integrated into existing processes to improve peri-discharge care as children transition from the hospital to the community.

The effect of activity and face masks on exhaled particles in children.

Importance: Despite the high burden of respiratory infections among children, the production of exhaled particles during common activities and the efficacy of face masks in children have not been sufficiently studied. Objective: To determine the effect of type of activity and mask usage on exhaled particle production in children. Methods: Healthy children were asked to perform activities that ranged in intensity (breathing quietly, speaking, singing, coughing, and sneezing) while wearing no mask, a cloth mask, or a surgical mask. The concentration and size of exhaled particles were assessed during each activity. Results: Twenty-three children were enrolled in the study. Average exhaled particle concentration increased by intensity of activity, with the lowest particle concentration during tidal breathing (1.285 particles/cm3 [95% CI 0.943, 1.627]) and highest particle concentration during sneezing (5.183 particles/cm3 [95% CI 1.911, 8.455]). High-intensity activities were associated with an increase primarily in the respirable size (≤ 5 µm) particle fraction. Surgical and cloth masks were associated with lower average particle concentration compared to no mask (P = 0.026 for sneezing). Surgical masks outperformed cloth masks across all activities, especially within the respirable size fraction. In a multivariable linear regression model, we observed significant effect modification of activity by age and by mask type. Interpretation: Similar to adults, children produce exhaled particles that vary in size and concentration across a range of activities. Production of respirable size fraction particles (≤ 5 µm), the dominant mode of transmission of many respiratory viruses, increases significantly with coughing and sneezing and is most effectively reduced by wearing surgical face masks.

Mortality after hospital discharge among children younger than 5 years admitted with suspected sepsis in Uganda: a prospective, multisite, observational cohort study.

BACKGROUND: Substantial mortality occurs after hospital discharge in children younger than 5 years with suspected sepsis, especially in low-income countries. A better understanding of its epidemiology is needed for effective interventions to reduce child mortality in these countries. We evaluated risk factors for death after discharge in children admitted to hospital for suspected sepsis in Uganda, and assessed how these differed by age, time of death, and location of death. METHODS: In this prospective, multisite, observational cohort study, we recruited and consecutively enrolled children aged 0-60 months admitted with suspected sepsis from the community to the paediatric wards of six Ugandan hospitals. Suspected sepsis was defined as the need for admission due to a suspected or proven infectious illness. At admission, trained study nurses systematically collected data on clinical variables, sociodemographic variables, and baseline characteristics with encrypted study tablets. Participants were followed up for 6 months after discharge by field officers who contacted caregivers at 2 months and 4 months after discharge by telephone and at 6 months after discharge in person to measure vital status, health-care seeking after discharge, and readmission details. We assessed 6-month mortality after hospital discharge among those discharged alive, with verbal autopsies conducted for children who had died after hospital discharge. FINDINGS: Between July 13, 2017, and March 30, 2020, 16 991 children were screened for eligibility. 6545 children (2927 [44·72%] female children and 3618 [55·28%] male children) were enrolled and 6191 were discharged from hospital alive. 6073 children (2687 [44·2%] female children and 3386 [55·8%] male children) completed follow-up. 366 children died in the 6-month period after discharge (weighted mortality rate 5·5%). Median time from discharge to death was 28 days (IQR 9-74). For the 360 children for whom location of death was documented, deaths occurred at home (162 [45·0%]), in transit to care (66 [18·3%]), or in hospital (132 [36·7%]) during a subsequent readmission. Death after hospital discharge was strongly associated with weight-for-age Z scores less than -3 (adjusted risk ratio [aRR] 4·7, 95% CI 3·7-5·8 vs a Z score of >-2), discharge or referral to a higher level of care (7·3, 5·6-9·5), and unplanned discharge (3·2, 2·5-4·0). Hazard ratios (HRs) for severe anaemia (<7g/dL) increased with time since discharge, from 1·7 (95% CI 0·9-3·0) for death occurring in the first time tertile to 5·2 (3·1-8·5) in the third time tertile. HRs for some discharge vulnerabilities decreased significantly with increasing time since discharge, including unplanned discharge (from 4.5 [2·9-6·9] in the first tertile to 2·0 [1·3-3·2] in the third tertile) and poor feeding status (from 7·7 [5·4-11·0] to 1·84 [1·0-3·3]). Age interacted with several variables, including reduced weight-for-age Z score, severe anaemia, and reduced admission temperature. INTERPRETATION: Paediatric mortality following hospital discharge after suspected sepsis is common, with diminishing, although persistent, risk during the first 6 months after discharge. Efforts to improve outcomes after hospital discharge are crucial to achieving Sustainable Development Goal 3.2 (ending preventable childhood deaths under age 5 years). FUNDING: Grand Challenges Canada, Thrasher Research Fund, BC Children's Hospital Foundation, and Mining4Life.

Remote online global health education among U.S. medical students during COVID-19 and beyond.

BACKGROUND: Due to the COVID-19 pandemic, the 2021 Harvard Medical School course Clinical Topics in Global Health was offered for the first time as a remote class. We sought to understand student and faculty perceptions of the elective and evaluate the perceived effectiveness of teaching global health using an online education platform. METHODS: Following the course, students and faculty were invited to complete a combined total of three online surveys, which consisted of closed- and open-response questions assessing the strengths and challenges of online learning. Data analyses included traditional descriptive statistics, Net Promoter Score calculation, and inductive thematic analysis of qualitative data. RESULTS: Thirty-two students and eighteen guest faculty (including four international faculty) participated in the course. Highly-rated course components included guest lecturers, practical skill sessions, polls, and case studies. The Net Promoter Score for the course was excellent at 92, and students reported a greater likelihood of pursuing a career in global health because of the course. While students and faculty highlighted limitations of the remote learning platform (lack of community and interactivity), they also commented on increased accessibility and faculty diversity. Most faculty and students recommended a hybrid model for future versions of the course and suggested strategies to address current limitations. CONCLUSIONS: A remote learning platform can effectively deliver global health education, both in the pandemic setting and beyond.

ARDS With Pneumothorax in a Young Adult.

CASE PRESENTATION: A 19-year-old, previously healthy man presented with 3 days of cough, high-grade fevers (40 °C), and dyspnea. Apart from a resolved history of seizures not requiring medications, he had no medical or surgical history. He had no known drug allergies. He took montelukast for allergies and trimethoprim-sulfamethoxazole (TMP-SMX) for 2 weeks before admission for acne, but no other medications, including over-the-counter medications and supplements. He had animal exposures to a new puppy and a friend's bird. He had no history of smoking, vaping, or recreational drug use. His paternal grandmother had rheumatoid arthritis.

Effect modification by age of the association between obstructive lung diseases, smoking, and COVID-19 severity.

INTRODUCTION: Obstructive lung diseases (asthma and chronic obstructive pulmonary disease (COPD)) and smoking are associated with greater risk of respiratory infections and hospitalisations, but conflicting data exist regarding their association with severity of COVID-19, and few studies have evaluated whether these associations differ by age. OBJECTIVES: To examine the associations between asthma, COPD and smoking on the severity of COVID-19 among a cohort of hospitalised patients, and to test for effect modification by age. METHODS: We performed a retrospective analysis of electronic health record data of patients admitted to Massachusetts General Hospital, assigning the maximal WHO Clinical Progression Scale score for each patient during the first 28 days following hospital admission. Using ordered logistic regression, we measured the association between maximal severity score and asthma, COPD and smoking and their interaction with age. MEASUREMENTS AND MAIN RESULTS: Among 1391 patients hospitalised with COVID-19, we found an increased risk of severe disease among patients with COPD and prior smoking, independent of age. We also found evidence of effect modification by age with asthma and current smoking; in particular, asthma was associated with decreased COVID-19 severity among older adults, and current smoking was associated with decreased severity among younger patients. CONCLUSIONS: This cohort study identifies age as a modifying factor for the association between asthma and smoking on severity of COVID-19. Our findings highlight the complexities of determining risk factors for COVID-19 severity, and suggest that the effect of risk factors may vary across the age spectrum.

Virologic Features of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children.

BACKGROUND: Data on pediatric coronavirus disease 2019 (COVID-19) has lagged behind adults throughout the pandemic. An understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral dynamics in children would enable data-driven public health guidance. METHODS: Respiratory swabs were collected from children with COVID-19. Viral load was quantified by reverse-transcription polymerase chain reaction (RT-PCR); viral culture was assessed by direct observation of cytopathic effects and semiquantitative viral titers. Correlations with age, symptom duration, and disease severity were analyzed. SARS-CoV-2 whole genome sequences were compared with contemporaneous sequences. RESULTS: One hundred ten children with COVID-19 (median age, 10 years [range, 2 weeks-21 years]) were included in this study. Age did not impact SARS-CoV-2 viral load. Children were most infectious within the first 5 days of illness, and severe disease did not correlate with increased viral loads. Pediatric SARS-CoV-2 sequences were representative of those in the community and novel variants were identified. CONCLUSIONS: Symptomatic and asymptomatic children can carry high quantities of live, replicating SARS-CoV-2, creating a potential reservoir for transmission and evolution of genetic variants. As guidance around social distancing and masking evolves following vaccine uptake in older populations, a clear understanding of SARS-CoV-2 infection dynamics in children is critical for rational development of public health policies and vaccination strategies to mitigate the impact of COVID-19.

Antibiotic-Resistant Bacteremia in Young Children Hospitalized With Pneumonia in Bangladesh Is Associated With a High Mortality Rate.

BACKGROUND: Pneumonia is a leading cause of sepsis and mortality in children under 5 years. However, our understanding of the causes of bacteremia in children with pneumonia is limited. METHODS: We characterized risk factors for bacteremia and death in a cohort of children admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) between 2014 and 2017 with radiographically confirmed pneumonia. RESULTS: A total of 4007 young children were hospitalized with pneumonia over the study period. A total of 1814 (45%) had blood cultures obtained. Of those, 108 (6%) were positive. Gram-negative pathogens predominated, accounting for 83 (77%) of positive cultures. These included Pseudomonas (N = 22), Escherichia coli (N = 17), Salmonella enterica (N = 14, including 11 Salmonella Typhi), and Klebsiella pneumoniae (N = 11). Gram-positive pathogens included Pneumococcus (N = 7) and Staphylococcus aureus (N = 6). Resistance to all routinely used empiric antibiotics (ampicillin, gentamicin, ciprofloxacin, and ceftriaxone) for children with pneumonia at the icddr,b was observed in 20 of the 108 isolates. Thirty-one of 108 (29%) children with bacteremia died, compared to 124 of 1706 (7%) who underwent culture without bacteremia (odds ratio [OR], 5.1; 95% confidence interval [CI], 3.3-8.1; P < .001). Children infected with bacteria resistant to all routinely used empiric antibiotics were at greater risk of death compared to children without bacteremia (OR, 17.3; 95% CI, 7.0-43.1; P < .001). CONCLUSIONS: Antibiotic-resistant Gram-negative bacteremia in young children with pneumonia in Dhaka, Bangladesh was associated with a high mortality rate. The pandemic of antibiotic resistance is shortening the lives of young children in Bangladesh, and new approaches to prevent and treat these infections are desperately needed.

Virologic features of SARS-CoV-2 infection in children.

BACKGROUND: Data on pediatric COVID-19 has lagged behind adults throughout the pandemic. An understanding of SARS-CoV-2 viral dynamics in children would enable data-driven public health guidance. METHODS: Respiratory swabs were collected from children with COVID-19. Viral load was quantified by RT-PCR; viral culture was assessed by direct observation of cytopathic effects and semiquantitative viral titers. Correlations with age, symptom duration, and disease severity were analyzed. SARS-CoV-2 whole genome sequences were compared with contemporaneous sequences. RESULTS: 110 children with COVID-19 (median age 10 years, range 2 weeks-21 years) were included in this study. Age did not impact SARS-CoV-2 viral load. Children were most infectious within the first five days of illness, and severe disease did not correlate with increased viral loads. Pediatric SARS-CoV-2 sequences were representative of those in the community and novel variants were identified. CONCLUSIONS: Symptomatic and asymptomatic children can carry high quantities of live, replicating SARS-CoV-2, creating a potential reservoir for transmission and evolution of genetic variants. As guidance around social distancing and masking evolves following vaccine uptake in older populations, a clear understanding of SARS-CoV-2 infection dynamics in children is critical for rational development of public health policies and vaccination strategies to mitigate the impact of COVID-19.

Aerosol transmission of SARS-CoV-2 by children and adults during the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be transmitted via respiratory droplets, aerosols, and to a lesser extent, fomites. Defining the factors driving infectivity and transmission is critical for infection control and containment of this pandemic. We outline the major methods of transmission of SARS-CoV-2, focusing on aerosol transmission. We review principles of aerosol science and discuss their implications for mitigating the spread of SARS-CoV-2 among children and adults.

The diagnosis of respiratory disease in children using a phone-based cough and symptom analysis algorithm: The smartphone recordings of cough sounds 2 (SMARTCOUGH-C 2) trial design.

The diagnosis of acute respiratory diseases in children can be challenging, and no single objective diagnostic test exists for common pediatric respiratory diseases. Previous research has demonstrated that ResAppDx, a cough sound and symptom-based analysis algorithm, can identify common respiratory diseases at the point of care. We present the study protocol for SMARTCOUGH-C 2, a prospective diagnostic accuracy trial of a cough and symptom-based algorithm in a cohort of children presenting with acute respiratory diseases. The objective of the study is to assess the performance characteristics of the ResAppDx algorithm in the diagnosis of common pediatric acute respiratory diseases.

Recognizing genetic disease: A key aspect of pediatric pulmonary care.

Advancement in technology has improved recognition of genetic etiologies of disease, which has impacted diagnosis and management of rare disease patients in the pediatric pulmonary clinic. This review provides an overview of genetic conditions that are likely to present with pulmonary features and require extensive care by the pediatric pulmonologist. Increased familiarity with these conditions allows for improved care of these patients by reducing time to diagnosis, tailoring management, and prompting further investigation into these disorders.

The future is here: Integrating genetics into the pediatric pulmonary clinic.

Recognition of underlying genetic etiologies of disease is increasing at an exponential rate, likely due to greater access to and lower cost of genetic testing. Monogenic causes of disease, or conditions resulting from a mutation or mutations in a single gene, are now well recognized in every subspecialty, including pediatric pulmonary medicine; thus, it is important to consider genetic conditions when evaluating children with respiratory disease. In the pediatric pulmonary clinic, genetic testing should be considered when multiple family members present with similar or related clinical features and when individuals have unusual clinical presentations, such as early-onset disease or complex, syndromic features. This review provides a practical guide for genetic diagnosis in the pediatric pulmonary setting, including a review of genetic concepts, considerations for test selection and results in interpretation, as well as an overview of genetic differential diagnoses for common pediatric pulmonary phenotypes. Genetic conditions that commonly present to the pediatric pulmonary clinic are reviewed in a companion article by Yonker et al.

Very severe anemia and one year mortality outcome after hospitalization in Tanzanian children: A prospective cohort study.

BACKGROUND: Africa has the highest rates of child mortality. Little is known about outcomes after hospitalization for children with very severe anemia. OBJECTIVE: To determine one year mortality and predictors of mortality in Tanzanian children hospitalized with very severe anemia. METHODS: We conducted a prospective cohort study enrolling children 2-12 years hospitalized from August 2014 to November 2014 at two public hospitals in northwestern Tanzania. Children were screened for anemia and followed until 12 months after discharge. The primary outcome measured was mortality. Predictors of mortality were determined using Cox regression analysis. RESULTS: Of the 505 children, 90 (17.8%) had very severe anemia and 415 (82.1%) did not. Mortality was higher for children with very severe anemia compared to children without over a one year period from admission, 27/90 (30.0%) vs. 59/415 (14.2%) respectively (Hazard Ratio (HR) 2.42, 95% Cl 1.53-3.83). In-hospital mortality was 11/90 (12.2%) and post-hospital mortality was 16/79 (20.2%) for children with very severe anemia. The strongest predictors of mortality were age (HR 1.01, 95% Cl 1.00-1.03) and decreased urine output (HR 4.30, 95% Cl 1.04-17.7). CONCLUSIONS: Children up to 12 years of age with very severe anemia have nearly a 30% chance of mortality following admission over a one year period, with over 50% of mortality occurring after discharge. Post-hospital interventions are urgently needed to reduce mortality in children with very severe anemia, and should include older children.

Paediatric postdischarge mortality in developing countries: a systematic review.

OBJECTIVES: To update the current evidence base on paediatric postdischarge mortality (PDM) in developing countries. Secondary objectives included an evaluation of risk factors, timing and location of PDM. DESIGN: Systematic literature review without meta-analysis. DATA SOURCES: Searches of Medline and EMBASE were conducted from October 2012 to July 2017. ELIGIBILITY CRITERIA: Studies were included if they were conducted in developing countries and examined paediatric PDM. 1238 articles were screened, yielding 11 eligible studies. These were added to 13 studies identified in a previous systematic review including studies prior to October 2012. In total, 24 studies were included for analysis. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted and synthesised data using Microsoft Excel. RESULTS: Studies were conducted mostly within African countries (19 of 24) and looked at all admissions or specific subsets of admissions. The primary subpopulations included malnutrition, respiratory infections, diarrhoeal diseases, malaria and anaemia. The anaemia and malaria subpopulations had the lowest PDM rates (typically 1%-2%), while those with malnutrition and respiratory infections had the highest (typically 3%-20%). Although there was significant heterogeneity between study populations and follow-up periods, studies consistently found rates of PDM to be similar, or to exceed, in-hospital mortality. Furthermore, over two-thirds of deaths after discharge occurred at home. Highly significant risk factors for PDM across all infectious admissions included HIV status, young age, pneumonia, malnutrition, anthropometric variables, hypoxia, anaemia, leaving hospital against medical advice and previous hospitalisations. CONCLUSIONS: Postdischarge mortality rates are often as high as in-hospital mortality, yet remain largely unaddressed. Most children who die following discharge do so at home, suggesting that interventions applied prior to discharge are ideal to addressing this neglected cause of mortality. The development, therefore, of evidence-based, risk-guided, interventions must be a focus to achieve the sustainable development goals.

Individual, maternal and household risk factors for anaemia among young children in sub-Saharan Africa: a cross-sectional study.

OBJECTIVE: Anaemia affects the majority of children in sub-Saharan Africa (SSA). Previous studies of risk factors for anaemia have been limited by sample size, geography and the association of many risk factors with poverty. In order to measure the relative impact of individual, maternal and household risk factors for anaemia in young children, we analysed data from all SSA countries that performed haemoglobin (Hb) testing in the Demographic and Health Surveys. DESIGN AND SETTING: This cross-sectional study pooled household-level data from the most recent Demographic and Health Surveys conducted in 27 SSA between 2008 and 2014. PARTICIPANTS: 96 804 children age 6-59 months. RESULTS: The prevalence of childhood anaemia (defined as Hb <11 g/dL) across the region was 59.9%, ranging from 23.7% in Rwanda to 87.9% in Burkina Faso. In multivariable regression models, older age, female sex, greater wealth, fewer household members, greater height-for-age, older maternal age, higher maternal body mass index, current maternal pregnancy and higher maternal Hb, and absence of recent fever were associated with higher Hb in tested children. Demographic, socioeconomic factors, family structure, water/sanitation, growth, maternal health and recent illnesses were significantly associated with the presence of childhood anaemia. These risk factor groups explain a significant fraction of anaemia (ranging from 1.0% to 16.7%) at the population level. CONCLUSIONS: The findings from our analysis of risk factors for anaemia in SSA underscore the importance of family and socioeconomic context in childhood anaemia. These data highlight the need for integrated programmes that address the multifactorial nature of childhood anaemia.