A research definition and framework for acute paediatric critical illness across resource-variable settings: a modified Delphi consensus.

The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness. DEFCRIT was developed following a scoping review of 29 studies and key concepts identified by an interdisciplinary, international core expert panel (n=24). A modified Delphi process was then done with a panel of multidisciplinary health-care global experts (n=109) until consensus was reached on eight essential attributes and 28 statements as the basis of DEFCRIT. Consensus was reached in two Delphi rounds with an expert retention rate of 89%. The final consensus definition for acute paediatric critical illness is: an infant, child, or adolescent with an illness, injury, or post-operative state that increases the risk for or results in acute physiological instability (abnormal physiological parameters or vital organ dysfunction or failure) or a clinical support requirement (such as frequent or continuous monitoring or time-sensitive interventions) to prevent further deterioration or death. The proposed definition and framework provide the conceptual clarity needed for a unified approach for global research across resource-variable settings. Future work will centre on validating DEFCRIT and determining high priority measures and guidelines for data collection and analysis that will promote its use in research.

Pediatric Acute Respiratory Distress Syndrome in South African PICUs: A Multisite Point-Prevalence Study.

OBJECTIVES: To describe the prevalence of pediatric acute respiratory distress syndrome (pARDS) and the characteristics of children with pARDS in South African PICUs. DESIGN: Observational multicenter, cross-sectional point-prevalence study. SETTING: Eight PICUs in four South African provinces. PATIENTS: All children beyond the neonatal period and under 18 years of age admitted to participating PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and demographic data were prospectively collected on a single day of each month, from February to July 2022, using a centralized database. Cases with or at risk of pARDS were identified using the 2015 Pediatric Acute Lung Injury Consensus Conference criteria. Prevalence was calculated as the number of children meeting pARDS criteria/the total number of children admitted to PICU at the same time points. Three hundred ten patients were present in the PICU on study days: 166 (53.5%) male, median (interquartile range [IQR]) age 9.8 (3.1-32.9) months, and 195 (62.9%) invasively mechanically ventilated. Seventy-one (22.9%) patients were classified as being "at risk" of pARDS and 95 patients (prevalence 30.6%; 95% CI, 24.7-37.5%) fulfilled pARDS case criteria, with severity classified as mild (58.2%), moderate (25.3%), and severe (17.6%). Median (IQR) admission Pediatric Index of Mortality 3 risk of mortality in patients with and without pARDS was 5.6 (3.4-12.1) % versus 3.9 (1.0-8.2) % ( p = 0.002). Diagnostic categories differed between pARDS and non-pARDS groups ( p = 0.002), with no difference in age, sex, or presence of comorbidities. On multivariable logistic regression, increasing admission risk of mortality (adjusted odds ratio [aOR] 1.02; 95% CI, 1.00-1.04; p = 0.04) and being admitted with a respiratory condition (aOR 2.64; 95% CI, 1.27-5.48; p = 0.01) were independently associated with an increased likelihood of having pARDS. CONCLUSIONS: The 30.6% prevalence of pARDS in South Africa is substantially higher than reports from other sociogeographical regions, highlighting the need for further research in this setting.

The Reviewer Academy of the Society of Critical Care Medicine: Key Principles and Strategic Plan.

The Society of Critical Care Medicine (SCCM) Reviewer Academy seeks to train and establish a community of trusted, reliable, and skilled peer reviewers with diverse backgrounds and interests to promote high-quality reviews for each of the SCCM journals. Goals of the Academy include building accessible resources to highlight qualities of excellent manuscript reviews; educating and mentoring a diverse group of healthcare professionals; and establishing and upholding standards for insightful and informative reviews. This manuscript will map the mission of the Reviewer Academy with a succinct summary of the importance of peer review, process of reviewing a manuscript, and the expected ethical standards of reviewers. We will equip readers to target concise, thoughtful feedback as peer reviewers, advance their understanding of the editorial process and inspire readers to integrate medical journalism into diverse professional careers.

Prevalence and Incidence of Pediatric Acute Respiratory Distress Syndrome in a Tertiary Academic PICU in South Africa.

OBJECTIVES: To determine the prevalence and incidence of pediatric acute respiratory distress syndrome (pARDS) among infants and children admitted to the PICU. DESIGN: A single-center descriptive point prevalence study with twice weekly data collection over a 6 months (August 2020 to February 12, 2021). SETTING: Red Cross War Memorial Children's Hospital, Cape Town, South Africa. PATIENTS: All infants and children admitted to the PICU on study days were included. INTERVENTIONS: Data were captured electronically on a standardized case record form using a Research Electronic Data Capture electronic database. MEASUREMENTS AND MAIN RESULTS: The Pediatric Acute Lung Injury Consensus Conference criteria were used to define pARDS cases. Prevalence was calculated as the total number of pARDS cases/1,000 PICU bed days. The study included 354 patients (median [interquartile range]) 10.1 months old (1.5-61.3 mo old), with 204 males (57.6%), who occupied 879 bed days. Of these 879 bed days, 266 (30.3%; 95% CI, 27.2-33.3%) were occupied by pARDS cases, with a calculated prevalence and incidence of 302.6 of 1,000 bed days (30.3%) and 29.7% (95% CI, 26.7-32.7%), respectively. Three cases from the cohort were defined using the oxygen saturation index calculation. In cases receiving invasive ventilation ( n = 494; 56.2%), pARDS severity was classified as mild ( n = 143; 16.3%), moderate ( n = 44; 5.0%), and severe ( n = 29, 3.3%). A further 205 beds (23.3%) were occupied by patients classified as being at risk of pARDS. CONCLUSIONS: The prevalence and incidence of pARDS in a South African PICU appears substantially higher than findings described in international reports. Further investigation of risk factors and outcomes is warranted.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

Nonpulmonary Treatments for Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: To provide an updated review of the literature on nonpulmonary treatments for pediatric acute respiratory distress syndrome (PARDS) from the Second Pediatric Acute Lung Injury Consensus Conference. DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: Searches were limited to children with PARDS or hypoxic respiratory failure focused on nonpulmonary adjunctive therapies (sedation, delirium management, neuromuscular blockade, nutrition, fluid management, transfusion, sleep management, and rehabilitation). DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. Twenty-five studies were identified for full-text extraction. Five clinical practice recommendations were generated, related to neuromuscular blockade, nutrition, fluid management, and transfusion. Thirteen good practice statements were generated on the use of sedation, iatrogenic withdrawal syndrome, delirium, sleep management, rehabilitation, and additional information on neuromuscular blockade and nutrition. Three research statements were generated to promote further investigation in nonpulmonary therapies for PARDS. CONCLUSIONS: These recommendations and statements about nonpulmonary treatments in PARDS are intended to promote optimization and consistency of care for patients with PARDS and identify areas of uncertainty requiring further investigation.

Diagnostic, Management, and Research Considerations for Pediatric Acute Respiratory Distress Syndrome in Resource-Limited Settings: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: Diagnosis of pediatric acute respiratory distress syndrome (PARDS) in resource-limited settings (RLS) is challenging and remains poorly described. We conducted a review of the literature to optimize recognition of PARDS in RLS and to provide recommendations/statements for clinical practice and future research in these settings as part of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2). DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included studies related to precipitating factors for PARDS, mechanical ventilation (MV), pulmonary and nonpulmonary ancillary treatments, and long-term outcomes in children who survive PARDS in RLS. DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. Seventy-seven studies were identified for full-text extraction. We were unable to identify any literature on which to base recommendations. We gained consensus on six clinical statements (good practice, definition, and policy) and five research statements. Clinicians should be aware of diseases and comorbidities, uncommon in most high-income settings, that predispose to the development of PARDS in RLS. Because of difficulties in recognizing PARDS and to avoid underdiagnosis, the PALICC-2 possible PARDS definition allows exclusion of imaging criteria when all other criteria are met, including noninvasive metrics of hypoxemia. The availability of MV support, regular MV training and education, as well as accessibility and costs of pulmonary and nonpulmonary ancillary therapies are other concerns related to management of PARDS in RLS. Data on long-term outcomes and feasibility of follow-up in PARDS survivors from RLS are also lacking. CONCLUSIONS: To date, PARDS remains poorly described in RLS. Clinicians working in these settings should be aware of common precipitating factors for PARDS in their patients. Future studies utilizing the PALICC-2 definitions are urgently needed to describe the epidemiology, management, and outcomes of PARDS in RLS.

ß-adrenergic sweat test in children with inconclusive cystic fibrosis diagnosis: Do we need new reference ranges?

BACKGROUND: Investigating inconclusive cystic fibrosis (CF) diagnosis in children is difficult without advanced cystic fibrosis transmembrane conductance regulator (CFTR) function tests. This study investigated the utility of beta (ß)-adrenergic sweat test to exclude CF in participants with inconclusive diagnosis (CF suspects) in South Africa. METHODS: ß-adrenergic sweat test and sweat chloride tests (SCT) were performed simultaneously in CF suspects and adult controls (healthy, CFTR heterozygotes and CF). Cholinergic and ß-adrenergic induced sweat rate was measured by evaporimetry (transepithelial water loss [TEWL]: g H2 O/m2 /h) following intradermal injections. Next-generation sequencing of CFTR was performed in CF suspects. CF diagnosis was defined by genotype. RESULTS: Thirty-seven controls (10 healthy, 14 CF, 13 CFTR heterozygotes) and 32 CF suspects (26 children; 6 adults) were enrolled. Six were excluded from formal analyses due to ß-adrenergic sweat test failure. In adults, evaporimetry was superior to SCT for diagnosis of CF with ß-adrenergic:cholinergic ratio TEWL ≤ 0.05 achieving 100% sensitivity and specificity. Twenty-two CF suspect children (age range: 3.4-15.6 years) completed ß-adrenergic sweat testing of which none had CF confirmed by genotyping: ß-adrenergic:cholinergic ratio > 0.05 successfully excluded CF in all but one child who was CFTR heterozygous. Median peak ß-adrenergic TEWL and ß-adrenergic:cholinergic ratio in CFTR negative and CFTR heterozygous children was significantly lower than adult controls. CONCLUSION: ß-adrenergic sweat test is more accurate than SCT for excluding CF in children with inconclusive diagnosis. Established reference ranges for ß-adrenergic sweat test may not be suitable for children due to lower ß-adrenergic sweat secretion compared to adults.

A Core Outcome Measurement Set for Pediatric Critical Care.

OBJECTIVES: To identify a PICU Core Outcome Measurement Set (PICU COMS), a set of measures that can be used to evaluate the PICU Core Outcome Set (PICU COS) domains in PICU patients and their families. DESIGN: A modified Delphi consensus process. SETTING: Four webinars attended by PICU physicians and nurses, pediatric surgeons, rehabilitation physicians, and scientists with expertise in PICU clinical care or research ( n = 35). Attendees were from eight countries and convened from the Pediatric Acute Lung Injury and Sepsis Investigators Pediatric Outcomes STudies after PICU Investigators and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network PICU COS Investigators. SUBJECTS: Measures to assess outcome domains of the PICU COS are as follows: cognitive, emotional, overall (including health-related quality of life), physical, and family health. Measures evaluating social health were also considered. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures were classified as general or additional based on generalizability across PICU populations, feasibility, and relevance to specific COS domains. Measures with high consensus, defined as 80% agreement for inclusion, were selected for the PICU COMS. Among 140 candidate measures, 24 were delineated as general (broadly applicable) and, of these, 10 achieved consensus for inclusion in the COMS (7 patient-oriented and 3 family-oriented). Six of the seven patient measures were applicable to the broadest range of patients, diagnoses, and developmental abilities. All were validated in pediatric populations and have normative pediatric data. Twenty additional measures focusing on specific populations or in-depth evaluation of a COS subdomain also met consensus for inclusion as COMS additional measures. CONCLUSIONS: The PICU COMS delineates measures to evaluate domains in the PICU COS and facilitates comparability across future research studies to characterize PICU survivorship and enable interventional studies to target long-term outcomes after critical illness.

Trends in cystic fibrosis survival over 40 years in South Africa: An observational cohort study.

INTRODUCTION: Temporal trends in cystic fibrosis (CF) survival from low-middle-income settings is poorly reported. We describe changes in CF survival after diagnosis over 40 years from a South African (SA) CF center. METHODS: An observational cohort study of people diagnosed with CF from 1974 to 2019. Changes in age-specific mortality rates from 2000 (vs. before 2000) were estimated using multivariable Poisson regression. Data were stratified by current age < or ≥10 years and models controlled for diagnosis age, sex, ethnicity, genotype, and Pseudomonas aeruginosa (PA) infection. A second analysis explored the association of mortality with weight and forced expiratory volume in 1 s reported as z-scores (FEV1z-scores) at age 5-8 years. RESULTS: A total of 288 people (52% male; 57% Caucasian; 44% p.Phe508del homozygous) were included (median diagnosis age 0.5 years: Q1, Q3: 0.2, 2.5); 100 (35%) died and 30 (10%) lost to follow-up. Among age >10 years, age-specific mortality from 2000 was significantly lower (adjusted hazard ratio [aHR]: 0.14; 95% confidence interval [CI]: 0.06, 0.29; p < 0.001), but not among age <10 years (aHR: 0.67; 95% CI: 0.28, 1.64; p = 0.383). In children <10 years, Caucasian ethnicity was associated with lower mortality (aHR 0.17; 95% CI: 0.05, 0.63), and longer times since first PA infection with higher mortality (aHR: 1.31; 95% CI: 1.01, 1.68). Mortality was sevenfold higher if FEV1z was <-2.0 at age 5-8 years (aHR: 7.64; 95% CI: 2.58, 22.59). CONCLUSION: Overall, CF survival has significantly improved in SA from 2000 in people older than 10 years. However, increased risk of mortality persists in young non-Caucasian children, and with FEV1z <-2.0 at age 5-8 years.

Erratum: The role of physiotherapy in the respiratory management of children with neuromuscular diseases: A South African perspective.

[This corrects the article DOI: 10.4102/sajp.v77i1.1527.].

Building a culture of early mobilization in the pediatric intensive care unit-a nuts and bolts approach.

The culture of sedation and immobilization in the pediatric intensive care unit (PICU) is associated with PICU-acquired weakness, delirium, and poor functional, neurocognitive and psychosocial outcomes. A structured approach to introducing physical activity, as early as possible after PICU admission, may prevent these complications and optimize the holistic outcomes of critically ill children. Changing culture and introducing new clinical practice in PICU is complex, but can be approached systematically, using a "nuts and bolts" approach targeting the basic, practical considerations and essential required elements or components. Extending the construction analogy, this article reviews the relevant literature to describe the essential elements required to build and sustain a successful and safe early mobility program in the PICU. Effective early mobilization requires individual patient assessment and goal setting, using a collaborative inter-disciplinary, patient- and family-centered approach, to ensure mobility goals and physical activities are appropriate for the patient's age, condition/s, premorbid function, strength, endurance and developmental level. Early mobility activities for the pediatric age spectrum include active or active-assisted range of motion exercises, neurodevelopmental play, use of mobility devices, in-bed exercises, transfers, sitting or standing tolerance, crawling, pre-gait activities, ambulation and activities of daily living, with a focus on play as function. Although there are few complete contraindications to early mobilization, appropriate precautions and preparation should be taken to mitigate potential safety concerns. Although there are many perceived barriers to early mobilization in the PICU, at the level of patient, provider, institution and knowledge translation; these are not objectively associated with increased risk during mobilization and can be overcome through an engaged process of practice change by all members of the interprofessional clinical team. Early mobility programs could be initiated in PICU as systematic quality improvement initiatives, with established processes to optimize structural, process and system elements and to provide continual feedback, measurement, benchmarking and collaboration; to ultimately impact on measurable patient outcomes. Early, graded, and individually prescribed mobilization should be considered as part of the standard PICU "package of care" for all critically ill and injured children, in order to improve their functional status and quality of life after PICU discharge.

Inspiratory muscle training in children and adolescents living with neuromuscular diseases: A pre-experimental study.

BACKGROUND: Children with neuromuscular diseases (NMD) are at risk of morbidity and mortality because of progressive respiratory muscle weakness and ineffective cough. Inspiratory muscle training (IMT) aims to preserve or improve respiratory muscle strength, thereby reducing morbidity and improving health-related quality of life (HRQoL). OBJECTIVES: To describe the safety and feasibility of a 6-week IMT programme using an electronic threshold device (Powerbreathe®). Any adverse events and changes in functional ability, spirometry, peak expiratory cough flow (PECF), inspiratory muscle strength and HRQoL (Pediatric Quality of Life [PedsQL]) were recorded. METHODS: A convenience sample of eight participants (n = 4 boys; median [interquartile range {IQR}] age: 12.21 [9.63-16.05] years) with various NMD were included in a pre-experimental, observational pre-test post-test feasibility study. Training consisted of 30 breaths, twice daily, 5 days a week, for 6 weeks. RESULTS: There were significant pre- to post-intervention improvements in upper limb function and coordination (p = 0.03) and inspiratory muscle strength: maximum inspiratory mouth pressure (Pimax) (p = 0.01); strength-index (p = 0.02); peak inspiratory flow (PIF) (p = 0.02), with no evidence of change in spirometry, PECF or HRQoL. No adverse events occurred and participant satisfaction and adherence levels were high. CONCLUSION: Inspiratory muscle training (at an intensity of 30% Pimax) appears safe, feasible and acceptable, in a small sample of children and adolescents with NMD and was associated with improved inspiratory muscle strength, PIF and upper limb function and coordination. CLINICAL IMPLICATIONS: Larger, longer-term randomised controlled trials are warranted to confirm the safety and efficacy of IMT as an adjunct respiratory management strategy in children with NMD.

Cystic fibrosis in South Africa: spectrum of disease and determinants of outcome.

INTRODUCTION: Little is known about cystic fibrosis (CF) in low- to middle-income settings. This study aimed to describe the spectrum and outcomes of CF in South Africa (SA) from the recently established SA CF registry (SACFR). METHODS: Demographic, diagnosis and clinical data were extracted from the SACFR. Cross-sectional univariable and multivariable regression analysis of best forced expiratory volume in 1 s (FEV1; age≥6 years) and nutrition (all ages) in 2018 was conducted to investigate factors associated with severe lung disease (SLD; FEV1 ≤3.0 z-score) and undernutrition. RESULTS: By December 2018, ancestry of 447 individuals included in the SACFR was Caucasian (315; 70%), mixed (87; 19%) and black African (41; 9%). Median diagnosis age was 7.6 months (IQR 2.7-37.1). Genotype was p.Phe508del homozygous (220; 49%); p.Phe508del heterozygous (144; 32%) and neither p.Phe508del or unknown Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) variant in 83 (19%); the second most frequent CFTR variant was 3120+1G>A, common in black Africans. Median age of patients in 2018 was 14.7 years (IQR 7.4-24.4). SLD was independently associated with chronic methicillin-resistant Staphylococcus aureus (MRSA) (adjusted odds ratio( aOR) 16.75; 95% CI 1.74-161.50), undernutrition (aOR 5.20; 95% CI 2.23-12.13) and age (aOR 2.23 per 10 years; 95% CI 1.50-3.31). Undernutrition was associated in univariable analysis with low weight at diagnosis, non-Caucasian ancestry, chronic P. aeruginosa infection and lower socioeconomic status. CONCLUSION: Interventions targeting MRSA infection and nutrition are needed to improve CF outcomes in SA. Most people with CF in SA are eligible for highly effective CFTR modulator therapy.

The role of physiotherapy in the respiratory management of children with neuromuscular diseases: A South African perspective.

BACKGROUND: Respiratory morbidity is common in children with neuromuscular diseases (NMD) owing to chronic hypoventilation and impaired cough. Optimal, cost-effective respiratory management requires implementation of clinical practice guidelines and a coordinated multidisciplinary team approach. OBJECTIVES: To explore South African physiotherapists' knowledge, perception and implementation of respiratory clinical practice guidelines for non-ventilated children with NMD. METHODS: An online survey was conducted amongst members of the South African Society of Physiotherapy's Cardiopulmonary Rehabilitation (CPRG) and Paediatric special interest groups and purposive sampling of non-member South African physiotherapists with respiratory paediatrics expertise (N= 481). RESULTS: Most respondents worked in private healthcare, with 1-10 years' experience treating patients with NMD. For acute and chronic management, most participants recommended nebulisation and 24-h postural management for general respiratory care. Percussions, vibrations, positioning, adapted postural drainage, breathing exercises and manually assisted cough were favoured as airway clearance techniques. In addition, participants supported non-invasive ventilation, oscillatory devices and respiratory muscle training for chronic management. CONCLUSION: Respondents seemed aware of internationally-endorsed NMD clinical practice guidelines and recommendations, but traditional manual airway clearance techniques were favoured. This survey provided novel insight into the knowledge, perspectives and implementation of NMD clinical practice guidelines amongst South African physiotherapists. CLINICAL IMPLICATIONS: There is an urgent need to increase the abilities of South African physiotherapists who manage children with NMD, as well as the establishment of specialised centres with the relevant equipment, ventilatory support and expertise in order to provide safe, cost-effective and individualised patient care.

Decreased Human Leukocyte Antigen DR on Circulating Monocytes Expression After Severe Pediatric Trauma: An Exploratory Report.

OBJECTIVES: Major trauma in adults induces immune dysfunction, with diminished expression of human leukocyte antigen-DR on circulating monocytes. No pediatric data are available. This study described the kinetics of human leukocyte antigen-DR on circulating monocytes following major pediatric trauma and relationships between human leukocyte antigen-DR on circulating monocytes and outcomes. DESIGN: Prospective observational study. SETTING: PICU and trauma unit at a tertiary-care university hospital in South Africa. PATIENTS: Children between 1 month and 13 years hospitalized for severe brain trauma or trauma with an Injury Severity Score greater than or equal to 16, from November 2016 to March 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 36 children. Median (interquartile range) age and Injury Severity Score were 7 years (4.9-10.5 yr) and 25 years (22.7-30 yr), respectively. Blood samples (n = 83) for standardized human leukocyte antigen-DR on circulating monocytes measurement were collected at days 1-2, 3-4, and 8-9 after injury (D1, D3, and D8, respectively). On D1, median (interquartile range) human leukocyte antigen-DR on circulating monocytes was markedly reduced relative to normal values (7,031 [5,204-11,201] antibodies per cell). There was a significant increase in human leukocyte antigen-DR on circulating monocytes from D1 to D8. Although all patients with secondary infections (n = 8; 22%) had human leukocyte antigen-DR on circulating monocytes less than 15,000 antibodies per cell at D3, human leukocyte antigen-DR on circulating monocytes levels were not associated with the occurrence of secondary infections (p = 0.22). At D3, human leukocyte antigen-DR on circulating monocytes was significantly higher in patients discharged home (n = 21) by Day 30 after trauma compared with those who died or were still hospitalized (n = 14) (p = 0.02). CONCLUSIONS: Pediatric severe trauma induced an early and dramatic decrease in human leukocyte antigen-DR on circulating monocytes expression. This alteration of innate immunity was not associated with the occurrence of secondary infection, possibly due to a lack of statistical power. However, human leukocyte antigen-DR on circulating monocytes at Day 3 is a potential indicator of those at high risk of secondary infection and worse outcomes.

Use of airway clearance therapy in children hospitalised with acute lower respiratory tract infections in a South African paediatric hospital.

BACKGROUND: Little is known about the prescription, frequency and nature of airway clearance therapy (ACT) in children hospitalised with lower respiratory tract infections (LRTIs). OBJECTIVES: To describe the characteristics and outcomes of children hospitalised with LRTIs at a tertiary paediatric hospital in South Africa and to investigate the role and impact of ACT in these children. METHOD: A retrospective folder review of children hospitalised with LRTI between January and June 2015 was conducted, extracting data on demographic characteristics, health condition, ACT interventions and patient outcomes. RESULTS: A total of 1208 individual cases (median [IQR] age 7.6 (2.8-19.0) months), in 1440 hospitalisations, were included. The majority of children were hospitalised primarily for the management of bronchiolitis. Comorbidities were present in 52.6% of patients during at least one of their hospitalisations. Airway clearance therapy was administered in 5.9% (n = 85) of admissions, most commonly conventional (manual) ACT. Transient oxyhaemoglobin desaturation was reported in six children, and one child developed lobar collapse an hour post-treatment. No other adverse events were reported. The median (IQR) duration of hospitalisation was 2.3 (1.5-5.0) days, and the overall mortality rate was 0.7%. Children hospitalised for presumed nosocomial infections and pneumonia had the longest length of stay, were more likely to receive ACT and had the highest mortality rate. CONCLUSION: Airway clearance therapy was infrequently used in this population and was more commonly applied in those with nosocomial LRTI and pneumonia. CLINICAL IMPLICATIONS: Although ACT was generally well tolerated, safety has not been ascertained, and oxygen saturation should be carefully monitored during therapy.

Motor Performance in South African Children with Cystic Fibrosis.

Aims: This study aimed to investigate motor performance in children with cystic fibrosis (CF) and the relationship with respiratory and anthropometric outcome measures.Methods: A cross-sectional exploratory study investigated 12 children with CF, mean (SD) age 6.17 (0.67) years, using the Movement Assessment Battery for Children 2nd edition (MABC-2), spirometry, body weight, height, body mass index, and age-related anthropomorphic z-scores.Results: MABC-2 total scores indicated 9/12 (75%) children performed below average (<50th percentile), of which 4/12 children (33.3%) had motor delay and 2/12 (16.7%) were at risk for motor delay. The balance subscale showed the lowest scores, with 5/12 (41.7%) participants performing at or below the 5th percentile and a median (IQR) percentile score of 9.00 (5.00-62.50). A significant negative correlation was found between the manual dexterity subscale and both height and height for age z-scores (p = 0.017 and p = 0.019, respectively), as well as peak expiratory flow in liter (p = 0.027). The balance subscale scores were positively correlated with forced expiratory volume in %predicted (p = 0.048). No other significant correlations were found.Conclusion: Children with CF may be at risk for delayed motor development, particularly their balance skills. Poor lung function might affect motor development but further research is recommended.

Cystic fibrosis in black African children in South Africa: a case control study.

BACKGROUND: Cystic fibrosis (CF) is described more commonly in Caucasian populations in whom p.Phe508del is the most common mutation. There is a paucity of data of CF in black African children. The aim of this study was to describe and compare the presentation and outcomes of black African children with CF to those with p.Phe508del genotype. METHODS: A retrospective case-controlled study was conducted from January 2000 - March 2018 of children with CF attending two CF centres in South Africa. Presentation, genotype, nutrition and pulmonary function outcomes of black African children were compared to matched controls with the p.Phe508del mutation. RESULTS: Thirty-four black African children (cases) with median age of diagnosis (5.5 months, IQR 2.0-15.0) were matched to 34 controls. Among cases, 3120+1G->A CFTR mutation was most commonly identified; homozygous n=22 (64.7%) and heterozygous=7(20.5%). Compared to controls, cases at diagnosis were more malnourished and fewer presented with neonatal bowel obstruction [cases n=2 (5.9%) vs. controls n=10 (29.4%); p = 0.03]. Nutrition and pulmonary function (FEV1 in children ≥ 6 years) outcomes and changes over time from ages 3-16 years were similar in both groups; median FEV1 z-score at age 6,10 and 14 years was -0.9 (±1.5), -1.8 (±2.0) and -1.8 (±1.9) respectively for all patients. Deaths were recorded in three cases (8.8%) and one control (2.9%) (p = 0.6). CONCLUSION: Black African children with CF were more malnourished at diagnosis, and fewer presented with neonatal bowel obstruction. Cases and controls had comparable nutritional, pulmonary function and early mortality outcomes.