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.

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.

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.

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.

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.

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.

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.

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.

Autogenic Drainage in Children With Cystic Fibrosis.

PURPOSE: Airway clearance is an essential part of the management of cystic fibrosis (CF) as it facilitates clearance of viscous pulmonary secretions. This review aimed to determine the effect of autogenic drainage (AD) and assisted autogenic drainage (AAD) compared with no, sham, or other types of airway clearance in children with CF. SUMMARY OF KEY POINTS: Two pediatric randomized cross-over trials were identified on the use of AD in children with CF; no studies were available on the use of AAD. In one study AD had a positive influence on the Huang score, and is preferred over postural drainage in this population. CONCLUSIONS AND RECOMMENDATIONS: We could not determine the efficacy of AD and AAD in children with CF. We recommend the implementation of pediatric-specific randomized controlled trials with adequate sample sizes, appropriate clinical outcome measures, and analysis of adverse effects.

Informed consent in paediatric critical care research--a South African perspective.

BACKGROUND: Medical care of critically ill and injured infants and children globally should be based on best research evidence to ensure safe, efficacious treatment. In South Africa and other low and middle-income countries, research is needed to optimise care and ensure rational, equitable allocation of scare paediatric critical care resources. Ethical oversight is essential for safe, appropriate research conduct. Informed consent by the parent or legal guardian is usually required for child research participation, but obtaining consent may be challenging in paediatric critical care research. Local regulations may also impede important research if overly restrictive. By narratively synthesising and contextualising the results of a comprehensive literature review, this paper describes ethical principles and regulations; potential barriers to obtaining prospective informed consent; and consent options in the context of paediatric critical care research in South Africa. DISCUSSION: Voluntary prospective informed consent from a parent or legal guardian is a statutory requirement for child research participation in South Africa. However, parents of critically ill or injured children might be incapable of or unwilling to provide the level of consent required to uphold the ethical principle of autonomy. In emergency care research it may not be practical to obtain consent when urgent action is required. Therapeutic misconceptions and sociocultural and language issues are also barriers to obtaining valid consent. Alternative consent options for paediatric critical care research include a waiver or deferred consent for minimal risk and/or emergency research, whilst prospective informed consent is appropriate for randomised trials of novel therapies or devices. We propose that parents or legal guardians of critically ill or injured children should only be approached to consent for their child's participation in clinical research when it is ethically justifiable and in the best interests of both child participant and parent. Where appropriate, alternatives to prospective informed consent should be considered to ensure that important paediatric critical care research can be undertaken in South Africa, whilst being cognisant of research risk. This document could provide a basis for debate on consent options in paediatric critical care research and contribute to efforts to advocate for South African law reform.

Acinetobacter baumannii infections in a South African paediatric intensive care unit.

OBJECTIVES: To describe and compare characteristics and outcomes of patients colonized or infected with Acinetobacter baumannii (cases) to a control group. METHODS: A retrospective case-controlled study of patients admitted to a South African paediatric intensive care unit (PICU) between January and December 2010. RESULTS: Acinetobacter baumannii was isolated in 194 patients. Mortality was similar between cases (9.3%) and controls (9.8%). Median duration of PICU stay and mechanical ventilation in cases vs. controls was 10 vs. 2 (p < 0.0001) and 9 vs. 1 days (p < 0.0001), respectively. Admission diagnosis of traumatic brain injury [adjusted odds ratio (OR): 5.6, 95% CI: 1.2-27.0; p = 0.03] and duration of mechanical ventilation (adjusted OR: 1.4, 95% CI: 1.3-1.5; p < 0.0001) were independently associated with A. baumannii aquisition. CONCLUSION: Acinetobacter baumannii acquisition was common and associated with increased morbidity, but not increased mortality.

Pediatric intensive care in South Africa: an account of making optimum use of limited resources at the Red Cross War Memorial Children's Hospital*.

OBJECTIVE: To develop explicit criteria for patient admission in order to optimize utilization of PICU facilities in the face of increasing demand outstripping resources. SETTING: Multidisciplinary PICU in a university-affiliated referral hospital in Cape Town, South Africa. DESIGN: Retrospective description of policy development and implementation PATIENTS: All patients referred to the Paediatric Intensive Care Unit of the Red Cross War Memorial Children's Hospital. INTERVENTIONS: Development and application of admission policy. MEASUREMENTS AND MAIN RESULTS: In consultation with clinicians at the hospital, principles for utilization of PICU resources were established and then translated into specific policies for prioritization of admission of particular groups of patients. The hospital team developed and implemented: criteria for intensive care admission; prioritization for certain categories of patients (including those scheduled for elective surgery); processes for refusing intensive care admission to other categories of patients; and processes to review implementation. These criteria and procedures were made explicit to clinicians, administrators, and managers and eventually agreed to by them. It was challenging to obtain "buy-in" from all potential stakeholders in the process and also to implement such policies under conditions of high stress. CONCLUSION: Development and implementation of explicit policies for utilization of PICU resources provide a "reasonable" process for fair and equitable utilization of scarce resources. The factors that have to be considered while developing these policies may extend beyond the priorities of individual patients. Implementation is still fraught with problems. Development of explicit admission policies that consider the needs of individual patients and also the longer term development of healthcare services may enable the retention of small but essential services.

Measles in a South African paediatric intensive care unit: again!

AIM: The aim of this study is to evaluate the outcomes of children with measles-related disease (MRD) admitted to a paediatric intensive care unit (PICU) and the effect on PICU resources and elective surgery of a recent measles epidemic. METHODS: This was a retrospective observational study of all patients admitted to the PICU of Red Cross War Memorial Children's Hospital, Cape Town, South Africa, with MRD from January to December 2010. Patient admission characteristics, duration of PICU admission and mortality were recorded. Costs were calculated using bed days utilised and estimated daily PICU admission cost. RESULTS: A total of 1274 children were admitted over the study period, 58 (4.6%) with MRD (median (interquartile range) age 7 (5-9) months). Pneumonia was the most common reason for admission (81%) and the main cause of mortality. Non-MRD mortality was 8.8% compared with MRD mortality of 31% (P < 0.0001). Standardised mortality for non-MRD was 0.7 versus 1.7 in MRD (P = 0.002). HIV comorbidity and being underweight for age were associated with increased mortality. Patients with MRD occupied 379 bed days with a median (interquartile range) duration of stay of 5.5 (3.0-9.0) days at an estimated overall cost of R4,813,300 (approximately $543,900). During the study period, 67 children booked for elective surgery, and 87 other referrals were refused PICU admission. CONCLUSIONS: MRD was associated with significant morbidity and mortality, and substantial strain on scarce PICU resources.

North-South divide: distribution and outcome of respiratory viral infections in paediatric intensive care units in Cape Town (South Africa) and Nottingham (United Kingdom).

AIM: This study aims to describe and compare the spectrum, course, seasonality and outcome of children with virus-associated respiratory symptoms (VARS) admitted to two paediatric intensive care units (PICUs) in the United Kingdom (UK) and South Africa (SA). METHODS: Cross-sectional study of routinely collected data on subjects admitted to PICU with respiratory symptoms and positive respiratory viral polymerase chain reaction between July 2009 and July 2011. RESULTS: Six hundred forty-six samples yielding 765 viral isolates (74% from SA) from 599 patients (53% male; median (interquartile range) age 6.0 (2.3-16.5) months) were included. Rhinovirus, respiratory syncytial virus and adenovirus were most commonly isolated. Adenovirus was more prevalent in SA (24.3% vs. 16.8%, P = 0.03). Possible or likely nosocomial viral acquisition occurred in 78% of isolates in SA versus 48% in the UK (P < 0.0001).Total mortality was 13.5%; 17% in SA versus 4% in the UK (P < 0.0001). Mortality for community acquired VARS was 8.4% versus 16.1% in those with possible nosocomial viral acquisition (P = 0.009). Factors independently associated with mortality were: SA study site (adjusted odds ratio (OR) 3.4, 95% confidence interval (CI) 1.4-8.5; P = 0.008); age (months) (OR 1.0, 95% CI 1.0-1.02; P = 0.001); Paediatric Index of Mortality 2 score (%) (OR 1.0, 95% CI 1.01-1.03; P = 0.0002) and isolation of adenovirus (OR 3.0, 95% CI 1.8-5.0; P < 0.0001). CONCLUSIONS: The outcome of children with VARS was worse in SA compared with the UK PICU. Nosocomial VARS was highlighted as an important concern and requires further investigation.

Fluid overload in a South African pediatric intensive care unit.

OBJECTIVE: Fluid resuscitation is integral to resuscitation guidelines and critical care. However, fluid overload (FO) yields increased morbidity. METHODS: Prospective observational study of Red Cross War Memorial Children's Hospital pediatric intensive care unit admissions (February to March 2013). FO % = (fluid in minus fluid out) [liters]/weight [kg] × 100%. PRIMARY OUTCOMES: FO ≥ 10%, 28 day mortality. RESULTS: Median [interquartile range (IQR)] age: 9.5 (2.0-39.0) months, median (IQR) admission weight: 7.9 (3.6-13.7) kg. Median (IQR) FO with admission weight: 3.5 (2.1-4.9)%; three patients had FO ≥ 10%. The 28 day mortality was 10% (n = 10). Patients who died had higher mean (IQR) FO using admission weight [4.9 (2.9-9.3)% vs. 3.4 (1.9-4.8)%; p = 0.04]. CONCLUSIONS: Low FO ≥ 10% prevalence with 28 day mortality 10%. Higher FO% with admission weight associated with mortality (p = 0.04). We advocate further investigation of FO% as a simple bedside tool.

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.

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.