The Infant KIdney Dialysis and Utrafiltration (I-KID) Study: A Stepped-Wedge Cluster-Randomized Study in Infants, Comparing Peritoneal Dialysis, Continuous Venovenous Hemofiltration, and Newcastle Infant Dialysis Ultrafiltration System, a Novel Infant Hemodialysis Device.

OBJECTIVES: Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformité Européenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH). DESIGN: Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence. SETTING: Clusters were six U.K. PICUs. PATIENTS: Babies less than 8 kg requiring RRT for fluid overload or biochemical disturbance. INTERVENTIONS: In controls, RRT was delivered by PD or CVVH, and in interventions, NIDUS was used. The primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances. MEASUREMENTS AND MAIN RESULTS: At closure, 97 participants were recruited from the six PICUs (62 control and 35 intervention). The primary outcome, obtained from 62 control and 21 intervention patients, showed that ultrafiltration with NIDUS was closer to that prescribed than with control: sd controls, 18.75, intervention, 2.95 (mL/hr); adjusted ratio, 0.13; 95% CI, 0.03-0.71; p = 0.018. Creatinine clearance was smallest and least variable for PD (mean, sd ) = (0.08, 0.03) mL/min/kg, larger for NIDUS (0.46, 0.30), and largest for CVVH (1.20, 0.72). Adverse events were reported in all groups. In this critically ill population with multiple organ failure, mortality was lowest for PD and highest for CVVH, with NIDUS in between. CONCLUSIONS: NIDUS delivers accurate, controllable fluid removal and adequate clearances, indicating that it has important potential alongside other modalities for infant RRT.

In the eye of the storm: impact of COVID-19 pandemic on admission patterns to paediatric intensive care units in the UK and Eire.

BACKGROUND: The coronavirus disease-19 (COVID-19) pandemic had a relatively minimal direct impact on critical illness in children compared to adults. However, children and paediatric intensive care units (PICUs) were affected indirectly. We analysed the impact of the pandemic on PICU admission patterns and patient characteristics in the UK and Ireland. METHODS: We performed a retrospective cohort study of all admissions to PICUs in children < 18 years during Jan-Dec 2020, using data collected from 32 PICUs via a central database (PICANet). Admission patterns, case-mix, resource use, and outcomes were compared with the four preceding years (2016-2019) based on the date of admission. RESULTS: There were 16,941 admissions in 2020 compared to an annual average of 20,643 (range 20,340-20,868) from 2016 to 2019. During 2020, there was a reduction in all PICU admissions (18%), unplanned admissions (20%), planned admissions (15%), and bed days (25%). There was a 41% reduction in respiratory admissions, and a 60% reduction in children admitted with bronchiolitis but an 84% increase in admissions for diabetic ketoacidosis during 2020 compared to the previous years. There were 420 admissions (2.4%) with either PIMS-TS or COVID-19 during 2020. Age and sex adjusted prevalence of unplanned PICU admission reduced from 79.7 (2016-2019) to 63.1 per 100,000 in 2020. Median probability of death [1.2 (0.5-3.4) vs. 1.2 (0.5-3.4) %], length of stay [2.3 (1.0-5.5) vs. 2.4 (1.0-5.7) days] and mortality rates [3.4 vs. 3.6%, (risk-adjusted OR 1.00 [0.91-1.11, p = 0.93])] were similar between 2016-2019 and 2020. There were 106 fewer in-PICU deaths in 2020 (n = 605) compared with 2016-2019 (n = 711). CONCLUSIONS: The use of a high-quality international database allowed robust comparisons between admission data prior to and during the COVID-19 pandemic. A significant reduction in prevalence of unplanned admissions, respiratory diseases, and fewer child deaths in PICU observed may be related to the targeted COVID-19 public health interventions during the pandemic. However, analysis of wider and longer-term societal impact of the pandemic and public health interventions on physical and mental health of children is required.

Linkage of National Congenital Heart Disease Audit data to hospital, critical care and mortality national data sets to enable research focused on quality improvement.

OBJECTIVES: To link five national data sets (three registries, two administrative) and create longitudinal healthcare trajectories for patients with congenital heart disease (CHD), describing the quality and the summary statistics of the linked data set. DESIGN: Bespoke linkage of record-level patient identifiers across five national data sets. Generation of spells of care defined as periods of time-overlapping events across the data sets. SETTING: National Congenital Heart Disease Audit (NCHDA) procedures in public (National Health Service; NHS) hospitals in England and Wales, paediatric and adult intensive care data sets (Paediatric Intensive Care Audit Network; PICANet and the Case Mix Programme from the Intensive Care National Audit & Research Centre; ICNARC-CMP), administrative hospital episodes (hospital episode statistics; HES inpatient, outpatient, accident and emergency; A&E) and mortality registry data. PARTICIPANTS: Patients with any CHD procedure recorded in NCHDA between April 2000 and March 2017 from public hospitals. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary: number of linked records, number of unique patients and number of generated spells of care. Secondary: quality and completeness of linkage. RESULTS: There were 143 862 records in NCHDA relating to 96 041 unique patients. We identified 65 797 linked PICANet patient admissions, 4664 linked ICNARC-CMP admissions and over 6 million linked HES episodes of care (1.1M inpatient, 4.7M outpatient). The linked data set had 4 908 153 spells of care after quality checks, with a median (IQR) of 3.4 (1.8-6.3) spells per patient-year. Where linkage was feasible (in terms of year and centre), 95.6% surgical procedure records were linked to a corresponding HES record, 93.9% paediatric (cardiac) surgery procedure records to a corresponding PICANet admission and 76.8% adult surgery procedure records to a corresponding ICNARC-CMP record. CONCLUSIONS: We successfully linked four national data sets to the core data set of all CHD procedures performed between 2000 and 2017. This will enable a much richer analysis of longitudinal patient journeys and outcomes. We hope that our detailed description of the linkage process will be useful to others looking to link national data sets to address important research priorities.

The road to hell is paved with good intentions: the experience of applying for national data for linkage and suggestions for improvement.

BACKGROUND: We can improve healthcare services by better understanding current provision. One way to understand this is by linking data sets from clinical and national audits, national registries and other National Health Service (NHS) encounter data. However, getting to the point of having linked national data sets is challenging. OBJECTIVE: We describe our experience of the data application and linkage process for our study 'LAUNCHES QI', and the time, processes and resource requirements involved. To help others planning similar projects, we highlight challenges encountered and advice for applications in the current system as well as suggestions for system improvements. FINDINGS: The study set up for LAUNCHES QI began in March 2018, and the process through to data acquisition took 2.5 years. Several challenges were encountered, including the amount of information required (often duplicate information in different formats across applications), lack of clarity on processes, resource constraints that limit an audit's capacity to fulfil requests and the unexpected amount of time required from the study team. It is incredibly difficult to estimate the resources needed ahead of time, and yet necessary to do so as early on as funding applications. Early decisions can have a significant impact during latter stages and be hard to change, yet it is difficult to get specific information at the beginning of the process. CONCLUSIONS: The current system is incredibly complex, arduous and slow, stifling innovation and delaying scientific progress. NHS data can inform and improve health services and we believe there is an ethical responsibility to use it to do so. Streamlining the number of applications required for accessing data for health services research and providing clarity to data controllers could facilitate the maintenance of stringent governance, while accelerating scientific studies and progress, leading to swifter application of findings and improvements in healthcare.

Impact of the introduction of a universal childhood influenza vaccination programme on influenza-related admissions to paediatric intensive care units in England.

INTRODUCTION: A universal childhood influenza vaccination programme was introduced in the UK in September 2013. We examine the impact of the gradual introduction of this programme on influenza-related paediatric intensive care unit (PICU) admission rates in England. METHODS: We extracted data on all influenza-related admissions to PICUs in England in resident children aged 0-15 years old between October 2003 and March 2017 from the Paediatric Intensive Care Audit Network (PICANet) database. We estimated influenza-associated PICU admission rates per 100 000 children by age group, sex and winter season (October to March), and used Poisson regression models to estimate incidence rate ratios (IRRs) in the winter seasons since the introduction of universal childhood vaccination compared with the two winters before the introduction of the programme (2011-2013). RESULTS: We identified 929 influenza-related PICU admissions among 873 children. 48.3% of admissions were among children aged less than 2 years old. The influenza-associated PICU admission rate was 1.32 per 100 000 children (95% CI 1.23 to 1.40). We identified a significant increase in influenza PICU admissions in the winters following the introduction of the universal childhood vaccination programme compared with the winters of 2010/2011-2012/2013 among children aged <5 years old: IRR 1.58 (1.05, 2.37) in children <1 year, 2.71 (1.43, 5.17) in 1 year-olds and 1.98 (1.18, 3.31) in children 2-4 years old. No significant difference was found among children aged 5-15 years. CONCLUSION: The universal childhood influenza vaccination has not yet reduced the influenza-associated burden on PICUs in England during its early phase of introduction. Monitoring of influenza PICU admission rates needs to continue in England to assess the long-term impact of universal paediatric influenza vaccination. Linkage between PICANet and national infection surveillance databases would better enable such monitoring.

Characteristics and mortality risk of children with life-threatening influenza infection admitted to paediatric intensive care in England 2003-2015.

BACKGROUND: Information is lacking about the severity of complications in children with influenza admitted to paediatric intensive care units (PICU) in the UK. In this study, we report risk factors for mortality, invasive ventilation and use of vasoactive drugs for children admitted to PICU with influenza. METHODS: We evaluated all admissions to PICUs in England for resident children with a recorded influenza diagnosis between September 2003 and March 2015. We used the Paediatric Intensive Care Audit Network (PICANet) database linked to hospital admission records to identify influenza cases, and high-risk comorbidities among admitted children. We used mixed effects logistic regression models to determine risk factors for mortality, use of invasive ventilation and vasoactive drugs. RESULTS: We identified 1961 influenza-related PICU admissions in 1778 children. Children with high-risk conditions accounted for 1540 admissions (78.5%). The odds of mortality were significantly higher for girls than boys (adjusted odds ratio 1.91; 95% confidence interval 1.31, 2.79), children from Asian/Asian British (2.70; 1.74, 4.20) or other minority ethnic groups (3.95; 1.65, 9.42) compared to white British children, and significantly increased before and during the A(H1N1)pdm 2009 pandemic compared to the post-pandemic period. Children required invasive ventilation in 1588 admissions (81.0%), and received vasoactive drugs in 586 admissions (29.9%). CONCLUSIONS: Nearly four fifths of influenza-related PICU admissions occurred in children with high-risk conditions, highlighting the burden of severe influenza in this vulnerable population Further research is required to explain sex and ethnic group differences in PICU mortality among children admitted with influenza.

Diet-induced obese mice retain endogenous leptin action.

Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. The antagonist increased feeding and body weight (BW) in lean mice, but not in obese models of leptin, leptin receptor, or melanocortin-4 receptor deficiency. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese (DIO) mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. These findings demonstrate that hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean mice and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice.