Methylprednisolone versus intravenous immunoglobulins in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): an open-label, multicentre, randomised trial.

BACKGROUND: The emergence of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) led to the widespread use of anti-inflammatory treatments in the absence of evidence from randomised controlled trials (RCTs). We aimed to assess the effectiveness of intravenous methylprednisolone compared with intravenous immunoglobulins. METHODS: This is an open-label, multicentre, two-arm RCT done at ten hospitals in Switzerland in children younger than 18 years hospitalised with PIMS-TS (defined as age <18 years; fever and biochemical evidence of inflammation, and single or multiorgan dysfunction; microbiologically proven or putative contact with SARS-CoV-2; and exclusion of any other probable disease). Patients were randomly assigned 1:1 to intravenous methylprednisolone (10 mg/kg per day for 3 days) or intravenous immunoglobulins (2 g/kg as a single dose). The primary outcome was length of hospital stay censored at day 28, death, or discharge. Secondary outcomes included proportion and duration of organ support. Analyses were done by intention-to-treat. The study was registered with Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). FINDINGS: Between May 21, 2021, and April 15, 2022, 75 patients with a median age of 9·1 years (IQR 6·2-12·2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulins group). The median length of hospital stay was 6·0 days (IQR 4·0-8·0) in the methylprednisolone group and 6·0 days (IQR 5·0-8·8) in the intravenous immunoglobulins group (estimated effect size -0·037 of the log10 transformed times, 95% CI -0·13 to 0·065, p=0·42). Fewer patients in the methylprednisolone group (ten [27%] of 37) required respiratory support compared with the intravenous immunoglobulin group (21 [55%] of 38, p=0·025). Need and duration of inotropes, admission to intensive care units, cardiac events after baseline, and major bleeding and thrombotic events were not significantly different between the study groups. INTERPRETATION: In this RCT, treatment with methylprednisolone in children with PIMS-TS did not significantly affect the length of hospital stay compared with intravenous immunoglobulins. Intravenous methylprednisolone could be an acceptable first-line treatment in children with PIMS-TS. FUNDING: NOMIS Foundation, Vontobel Foundation, and Gaydoul Foundation.

Trends and outcomes of children, adolescents, and adults hospitalized with inherited metabolic disorders: A population-based cohort study.

Inherited metabolic disorders (IMDs) comprise a heterogeneous class of genetic disorders characterized by impaired biochemical functions in metabolism. However, incidences and outcomes of patients hospitalized with IMDs are largely unknown. We conducted a population-based cohort study using nationwide in-hospital claims data in Switzerland from 2012 to 2020. We assessed incidence rates of hospitalizations and hospital-associated outcomes, stratified in five age groups (0-9, 10-19, 20-39, 40-59, and 60-90 years) and three types of IMDs (peptide, amine and amino acid metabolism disorders [AD], carbohydrate metabolism disorders [CD], fatty acid, and ketone body metabolism disorders [FD]). A total of 7293 hospitalizations with IMD were identified, of which 3638 had AD, 3153 CD, and 502 FD. Incidence rates for hospitalizations per 100 000 person-years were highest under the age of 10 years across all types of IMDs (8.69 for AD, 5.73 for CD, 3.71 for FD) and decreased thereafter. In patients with AD and CD, hospitalization rates increased again in adults aged 60-90 years (7.28 for AD, 7.25 for CD), while they remained low in patients with FD (0.31). Compared to inpatients without IMD, adult IMD patients had a higher burden of hospital-associated adverse outcomes including an increased risk of in-hospital mortality, intensive care unit admission, mechanical ventilation, and longer length of hospital or intensive care unit stay. Incremental risk of 30-day, 1-year, and 2-year hospital readmission was highest among children and adolescents with IMD.

Multicenter Randomized Trial of Methylprednisolone vs. Intravenous Immunoglobulins to Treat the Pediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS): Protocol of the Swissped RECOVERY Trial.

Introduction: In 2020, a new disease entitled Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C), emerged, with thousands of children affected globally. There is no available evidence based on randomized controlled trials (RCT) to date on the two most commonly used immunomodulatory treatments, intravenous immunoglobulins (IVIG) and corticosteroids. Therefore, the Swissped RECOVERY trial was conducted to assess whether intravenous (IV) methylprednisolone shortens hospital length of stay compared with IVIG. Methods and Analysis: Swissped RECOVERY is an ongoing investigator-initiated, open-label, multicenter two-arm RCT in children and adolescents <18 years hospitalized with a diagnosis of PIMS-TS. The trial is recruiting at 10 sites across Switzerland. Patients diagnosed with PIMS-TS are randomized 1:1 to methylprednisolone IV (10 mg/kg/day for 3 days) or IVIG (2 g/kg as a single dose). The primary outcome is hospital length of stay censored at day 28, death, or discharge (whichever is first). The target total sample size is ~80 patients 1:1 randomized to each study arm. Ancillary and exploratory studies on inflammation, vaccination acceptance and coverage, long-term outcomes, and healthcare costs are pre-planned. Significance: Currently, robust trial evidence for the treatment of PIMS-TS is lacking, with a controversy surrounding the use of corticosteroids vs. IVIG. This trial will provide evidence for the effectiveness and safety of these two treatments. Ethics and Dissemination: The study protocol, which was designed based on the U.K. RECOVERY trial, the patient information and consent forms, and other study-specific study documents were approved by the local ethics committees (Project ID: 2021-00362). Registration Details: The study is registered on the Swiss National Clinical Trials Portal (SNCTP000004720) and Clinicaltrials.gov (NCT04826588).

Pediatric Buried Bumper Syndrome: Diagnostic Validity of Transabdominal Ultrasound and Artificial Intelligence.

PURPOSE: Buried bumper syndrome (BBS) is a severe complication of percutaneous endoscopic gastrostomy (PEG) resulting from overgrowth of gastric mucosa and penetration of the inner holding plate into the gastric wall. The aim of this study was to evaluate the diagnostic value of transabdominal ultrasound (US) in comparison to an artificial intelligence (AI) model for the diagnosis of BBS in children. MATERIALS AND METHODS: In this monocentric retrospective study, pediatric US data concerning BBS from a ten-year period (2009-2019) were analyzed. US findings were compared to a clinical multiparameter-based AI model and reference standard endoscopy. Clinical risk factors for the occurrence of pediatric BBS were determined. RESULTS: In n = 121 independent examinations of n = 82 patients, the placement of the inner holding plate of the PEG was assessed by US. In n = 18 cases BBS was confirmed. Recall and precision rates were 100 % for US and 88 % for the AI-based assessment. Risk factors for the occurrence of BBS were mobilization problems of the PEG (rs = 0.66, p < 0.001), secretion/exudation (rs = 0.29, p = 0.002), time between 1st PEG placement and US (rs = 0.38, p < 0.001), and elevated leukocyte count (rs = 0.24, p = 0.016). CONCLUSION: Transabdominal US enables correct, rapid, and noninvasive diagnosis of BBS in pediatric patients. Preceding AI models could aid during diagnostic workup. To avoid unnecessary invasive procedures, US could be considered as a primary diagnostic procedure in suspected BBS. .

Determining transition readiness in Swiss childhood cancer survivors - a feasibility study.

BACKGROUND: The successful transition of childhood cancer survivors (CCSs) from pediatric to adult long-term follow-up care is a critical phase, and determining the right time point can be challenging. We assessed the feasibility of the use of existing transition readiness tools in the context of the Swiss health care system, assessed partly transition readiness in Swiss CCSs, and compared our findings with Canadian CCSs for which these tools were originally developed. METHODS: We officially translated the Cancer Worry Scale (CWS) and Self-Management Skill Scale (SMSS) into German and integrated them into this cross-sectional study. We included CCSs attending the long-term follow-up (LTFU) clinic in the Division of Oncology-Hematology, Department of Pediatrics, Kantonsspital Aarau. We used descriptive statistics to describe transition readiness. RESULTS: We randomly recruited 50 CCSs aged ≥18 years at participation. The CCSs had a median CWS score of 62 (interquartile range 55-71), indicating a moderate level of cancer-related worry. Despite high self-management skills, some answers showed a dependency of CCSs on their parents. Our experience shows that the CWS and SMSS are easy for Swiss CCSs to use, understand, and complete. The interpretation of the results must take differences in health care systems between countries into account. CONCLUSIONS: The translated CWS and SMSS are appropriate additional measures to assess transition readiness in CCSs. These scales can be used longitudinally to find the individual time point for transition and the completion by CCSs enables the health care team to individualize the transition process and to support the CCSs according to their individual needs.

Transition from pediatric to adult follow-up care in childhood cancer survivors-a systematic review.

PURPOSE: The successful transition of childhood cancer survivors from pediatric- to adult-focused long-term follow-up care is crucial and can be a critical period. Knowledge of current transition practices, especially regarding barriers and facilitators perceived by survivors and health care professionals, is important to develop sustainable transition processes and implement them into daily clinical practice. We performed a systematic review with the aim of assessing transition practices, readiness tools, and barriers and facilitators. METHODS: We searched three databases (PubMed, Embase/Ovid, CINAHL) and included studies published between January 2000 and January 2020. We performed this review according to the PRISMA guidelines and registered the study protocol on PROSPERO; two reviewers independently extracted the content of the included studies. RESULTS: We included 26 studies: six studies described current transition practices, six assessed transition readiness tools, and 15 assessed barriers and facilitators to transition. CONCLUSION: The current literature describing transition practices is limited and overlooks adherence to follow-up care as a surrogate marker of transition success. However, the literature provides deep insight into barriers and facilitators to transition and theoretical considerations for the assessment of transition readiness. We showed that knowledge and education are key facilitators to transition that should be integrated into transition practices tailored to the individual needs of each survivor and the possibilities and limitations of each country's health care system. IMPLICATIONS FOR CANCER SURVIVORS: The current knowledge on barriers and facilitators on transition should be implemented in clinical practice to support sustainable transition processes.