Children with palliative care needs - the landscape of the nordic countries.

BACKGROUND: To strengthen palliative care for children in the Nordic countries, an updated status of current needs, resources, clinical services, education, and research is necessary to align and consolidate future research. A Nordic research collaboration initiative for children with palliative care needs was assembled in 2023. Building on this initiative, this paper presents an overview of pediatric palliative care (PPC) in the Nordic countries' (a) population characteristics, (b) care models and setting of care, (c) education and training, and (d) research. METHODS: The Nordic initiative researchers collaboratively gathered and assessed available data on the characteristics of PPC within Denmark, Finland, Greenland, Iceland, Norway, the Faroe Islands, Sweden, and Åland. Data were compiled in a matrix with population characteristics, models- and setting of care, education and training, and areas of research in a Nordic context. The findings are narratively and descriptively presented, providing an overview of Nordic PPC. RESULTS: In total, the Nordic child population comprises around six million children (0-19 years), of which about 41.200 are estimated to be living with a life-limiting and/or life-threatening condition. Healthcare services are provided through various care models, ranging from specialized care to homecare settings. Overall, there remain few opportunities for education and training with some exceptions. Also, Nordic research within PPC has been shown to be a growing field although much remains to be done. CONCLUSION: This overview is the first outline of the current PPC in Nordic countries. Although some differences remain important to acknowledge, overall, the strengths and challenges faced within PPC in the Nordic countries are comparable and call for joint action to increase evidence, services, and education to better serve the children, families, and healthcare personnel within PPC. Despite the varying structural premises for PPC, research endeavors aiming to provide evidence in this field seem increasing, timely and relevant for the Nordic countries, as well as the international context.

Advances in pediatric perioperative care using artificial intelligence.

PURPOSE OF THIS REVIEW: This article explores how artificial intelligence (AI) can be used to evaluate risks in pediatric perioperative care. It will also describe potential future applications of AI, such as models for airway device selection, controlling anesthetic depth and nociception during surgery, and contributing to the training of pediatric anesthesia providers. RECENT FINDINGS: The use of AI in healthcare has increased in recent years, largely due to the accessibility of large datasets, such as those gathered from electronic health records. Although there has been less focus on pediatric anesthesia compared to adult anesthesia, research is on- going, especially for applications focused on risk factor identification for adverse perioperative events. Despite these advances, the lack of formal external validation or feasibility testing results in uncertainty surrounding the clinical applicability of these tools. SUMMARY: The goal of using AI in pediatric anesthesia is to assist clinicians in providing safe and efficient care. Given that children are a vulnerable population, it is crucial to ensure that both clinicians and families have confidence in the clinical tools used to inform medical decision- making. While not yet a reality, the eventual incorporation of AI-based tools holds great potential to contribute to the safe and efficient care of our patients.

The impact of the COVID-19 pandemic on outpatients of internal medicine and pediatrics: A descriptive study.

ABSTRACT: This study analyzed the changes in the number of outpatients and disease presentation during the entirety of 2020, the period of COVID-19 pandemic.The average annual number of outpatient visits between 2017 and 2019 (before COVID-19) and the total number of outpatient visits in 2020 (COVID-19 period) were compared. Diagnostic codes were identified during 2 periods to analyze changes in the number of outpatient visits according to disease and month.The average annual number of outpatient visits was 47,105 before, and 40,786 during the COVID-19 pandemic, with a decrease of 13.4%. The number of outpatient visits in internal medicine decreased by 10.2% during the COVID-19 pandemic and tended to rebound during the second half of the year. However, the number of outpatient visits in the pediatric department decreased by 37.5% overall throughout the COVID-19 period and continued to decline in the second half of the year. The number of outpatients with infectious diseases decreased significantly (35.9%) compared to noninfectious diseases (cancer, 5.0%; circulatory disease, 4.1%). In addition, the number of outpatient visits due to viral diseases continued to decline, while the incidence of bacterial diseases increased rapidly in the second half of the year.This study confirmed that the number of outpatient visits due to bacterial or viral infections decreased throughout the COVID-19 crisis. Therefore, expanding public health and telemedicine services is necessary to prevent secondary health problems caused by essential medical use restrictions.

The Practice of Pediatric Cardiac Anesthesiology in the United States.

BACKGROUND: With advances in surgical and catheter-based interventions and technologies in patients with congenital heart disease (CHD), the practice of pediatric cardiac anesthesiology has evolved in parallel with pediatric cardiac surgery and pediatric cardiology as a distinct subspecialty over the past 80 years. To date, there has not been an analysis of the distribution of pediatric cardiac anesthesiologists relative to cardiac and noncardiac procedures in the pediatric population. The primary aim is to report the results of a survey and its subsequent analysis to describe the distribution of pediatric cardiac anesthesiologists relative to pediatric cardiac procedures that include surgical interventions, cardiac catheterization procedures, imaging studies (echocardiography, magnetic resonance, computed tomography, positron emission tomography), and noncardiac procedures. METHODS: A survey developed in Research Electronic Data Capture (REDcap) was sent to the identifiable division chiefs/cardiac directors of 113 pediatric cardiac anesthesia programs in the United States. Data regarding cardiac surgical patients and procedures were collected from the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHD). RESULTS: This analysis reveals that only 38% (117 of 307) of pediatric cardiac anesthesiologists caring for patients with CHD pursued additional training in pediatric cardiac anesthesiology, while 44% (136 of 307) have gained experience during their clinical practice. Other providers have pursued different training pathways such as adult cardiac anesthesiology or pediatric critical care. Based on this survey, pediatric cardiac anesthesiologists devote 35% (interquartile range [IQR], 20%-50%) of clinical time to the care of patients in the cardiac operating room, 25% (20%-35%) of time to the care of patients in the cardiac catheterization laboratory, 10% (5%-10%) to patient care in imaging locations, and 15% covering general pediatric, adult, or cardiac patients undergoing noncardiac procedures. Attempts to actively recruit pediatric cardiac anesthesiologists were reported by 49.2% (29 of 59) of the institutions surveyed. Impending retirement of staff was anticipated in 17% (10 of 59) of the institutions, while loss of staff to relocation was anticipated in 3.4% (2 of 59) of institutions. Thirty-seven percent of institutions reported that they anticipated no immediate changes in current staffing levels. CONCLUSIONS: The majority of currently practicing pediatric cardiac anesthesiologists have not completed a fellowship training in the subspecialty. There is, and will continue to be, a need for subspecialty training to meet increasing demand for services especially with increase survival of this patient population and to replace retiring members of the workforce.

Patient and family experience of telehealth care delivery as part of the CF chronic care model early in the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, CF centers shifted to a telehealth delivery model. Our study aimed to determine how people with CF (PwCF) and their families experienced telehealth and assessed its quality and acceptability for future CF care. METHODS: The CF Patient and Family State of Care Survey (PFSoC) was fielded from August 31-October 30, 2020. The PFSoC explored themes of overall telehealth quality, ease of use, desirability, and preference for a future mix of in-person and telehealth care. Demographic covariates considered included: gender, age, CFTR modulator status, and region of residence. RESULTS: 424 PwCF and parents of PwCF responded (47% parents). Most (81%) reported a telehealth visit which included a MD/APP and nurse team members. 91% found telehealth easy to use, and 66% reported similar/higher quality than in-person care. One-third (34%) reported the highest desire for future telehealth care, with 45% (n =212) desiring 50% or more of visits conducted via telehealth. Adults were more likely than parents to report highest desire for future telehealth (64% vs. 36%). Respondents who perceived telehealth as similar/higher quality were more likely to desire future telehealth compared to those who perceived telehealth as lower quality (96% vs. 50%). Mixed methods analysis revealed themes affecting perceptions of telehealth. CONCLUSIONS: PwCF desire for future telehealth was influenced by perception of quality and age. Several themes emerged that need to be explored as telehealth is adapted into the CF chronic care model, especially when thinking about integration into pediatric care.

Novel Circulating Hypermethylated RASSF1A ddPCR for Liquid Biopsies in Patients With Pediatric Solid Tumors.

Liquid biopsies can be used to investigate tumor-derived DNA, circulating in the cell-free DNA (cfDNA) pool in blood. We aimed to develop a droplet digital polymerase chain reaction (ddPCR) assay detecting hypermethylation of tumor suppressor gene RASSF1A as a simple standard test to detect various pediatric tumor types in small volume blood samples and to evaluate this test for monitoring treatment response of patients with high-risk neuroblastoma. METHODS: We developed a ddPCR assay to sensitively detect tumor-derived hypermethylated RASSF1A DNA in liquid biopsies. We tested this assay in plasma of 96 patients with neuroblastoma, renal tumors, rhabdomyosarcoma, or Hodgkin lymphoma at diagnosis and in cerebrospinal fluid of four patients with brain tumors. We evaluated the presence of hypermethylated RASSF1A in plasma samples during treatment and follow-up in 47 patients with neuroblastoma treated according to high-risk protocol and correlated results with blood mRNA-based and bone marrow mRNA-based minimal residual disease detection and clinical outcomes. RESULTS: The total cfDNA level was significantly higher in patients with metastatic neuroblastoma and nephroblastoma compared with healthy adult and pediatric controls. Hypermethylated RASSF1A was present in 41 of 42 patients with metastatic neuroblastoma and in all patients with nephroblastoma, with the median percentage of 69% and 21% of total RASSF1A, respectively. Hypermethylated RASSF1A levels decreased during therapy and recurred at relapse. CONCLUSION: Our findings demonstrate the value of ddPCR-based detection of hypermethylated RASSF1A as a circulating molecular tumor marker in neuroblastoma. Our preliminary investigation of RASSF1A hypermethylation detection in circulating cfDNA of other pediatric tumor entities demonstrates potential as a pan-tumor marker, but requires investigation in larger cohorts to evaluate its use and limitations.

Cervical lymphatic malformations amenable to transhairline robotic surgical excision in children: A case series.

ABSTRACT: Lymphatic malformations are rare benign malformations that predominantly occur in the head and neck region. The advent of surgical robots in head and neck surgery may provide beneficial outcomes for pediatric patients. Here, we describe our experiences with transhairline incisions for robot-assisted surgical resection of cervical lymphatic malformations in pediatric patients.In this prospective longitudinal cohort study, we recruited consecutive patients under 18 years of age who were diagnosed with congenital cervical lymphatic malformations and scheduled for transhairline approach robotic surgery at a single medical center. We documented the docking times, console times, surgical results, complications, and postoperative follow-up outcomes.The studied patients included 2 with mixed-type lymphatic malformations and 2 with macrocystic-type lymphatic malformations. In all 4 patients, the incision was hidden in the hairline; the incision length was <5 cm in 3 patients but was extended to 6 cm in 1 patient. Elevating the skin flap and securely positioning it with Yang retractor took <1 hour in all cases. The mean docking time was 5.5 minutes, and the mean console time was 1 hour and 46 minutes. All 4 surgeries were completed endoscopically with the robot. The average total drainage volume in the postoperative period was 21.75 mL. No patients required tracheotomy or nasogastric feeding tubes. Neither were adverse surgery-associated neurovascular sequelae observed. All 4 patients were successfully treated for their lymphatic malformations, primarily with robotic surgical excisions.Cervical lymphatic malformations in pediatric patients could be accessed, properly visualized, and safely resected with transhairline-approach robotic surgery. Transhairline-approach robotic surgery is an innovative method for meeting clinical needs and addressing esthetic concerns.

Hospital Volumes of Inpatient Pediatric Surgery in the United States.

BACKGROUND: Perioperative outcomes of children depend on the skill and expertise in managing pediatric patients, as well as integration of surgical, anesthesiology, and medical teams. We compared the types of pediatric patients and inpatient surgical procedures performed in low- versus higher-volume hospitals throughout the United States. METHODS: Retrospective analysis of 323,258 hospitalizations with an operation for children age 0 to 17 years in 2857 hospitals included in the Agency for Healthcare Research and Quality (AHRQ) Kids' Inpatient Database (KID) 2016. Hospitals were categorized by their volume of annual inpatient surgical procedures. Specific surgeries were distinguished with the AHRQ Clinical Classification System. We assessed complex chronic conditions (CCCs) using Feudtner and Colleagues' system. RESULTS: The median annual volume of pediatric inpatient surgeries across US hospitals was 8 (interquartile range [IQR], 3-29). The median volume of inpatient surgeries for children with a CCC was 4 (IQR, 1-13). Low-volume hospitals performed significantly fewer types of surgeries (median 2 vs 131 types of surgeries in hospitals with 1-24 vs ≥2000 volumes). Appendectomy and fixation of bone fracture were among the most common surgeries in low-volume hospitals. As the volume of surgical procedures increased from 1 to 24 to ≥2000, the percentage of older children ages 11 to 17 years decreased (70.9%-32.0% [P < .001]) and the percentage of children with a CCC increased (11.2%-60.0% [P < .001]). CONCLUSIONS: Thousands of US hospitals performed inpatient surgeries on few pediatric patients, including those with CCCs who have the highest risk of perioperative morbidity and mortality. Evaluation of perioperative decision making, workflows, and pediatric clinicians in low- and higher-volume hospitals is warranted.

Pediatric cancer care in Africa: SIOP Global Mapping Program report on economic and population indicators.

INTRODUCTION: Inalignment with the World Health Organization (WHO) Global Initiative for Childhood Cancer (GICC), the International Society of Pediatric Oncology initiated a program to map global pediatric oncology services. As survival rates in Africa are low and data are scant, this continent was mapped first to identify areas with greatest need. METHODS: Beginning November 2018, an electronic survey was sent to all known stakeholders, followed by email communications and internet searches to verify data. Availability of pediatric oncologists, chemotherapy, surgical expertise, and radiotherapy was correlated with geographic region, World Bank income status, Universal Health Coverage, population < 15 and < 24 years, percentage of gross domestic product spent on healthcare, and Human Development Index (HDI). RESULTS: Responses were received from 48/54 African countries. All three treatment modalities were reportedly available in 9/48 countries, whereas seven countries reported no pediatric oncology services. Negative correlations were detected between provision of all three services and geographic region (P = 0.01), younger median population age (P = 0.002), low-income country status (P = 0.045), and lower HDI (P < 0.001). CONCLUSION: This study provides a comprehensive overview of pediatric oncology care in Africa, emphasizing marked disparities between countries: some have highly specialized services, whereas others have no services. A long-term strategy to eliminate disparities in African pediatric cancer care should be aligned with the WHO GICC aims and facilitated by SIOP Africa. MEETING ABSTRACTS: SIOP maps pediatric oncology services in Africa to address inequalities in childhood cancer services. Geel J, Ranasinghe N, Davidson A, Challinor J, Howard S, Wollaert S, Myezo K, Renner L, Hessissen L, Bouffet E. 51st Annual Congress of the International Society of Paediatric Oncology (SIOP), Lyon, France, October 2019. Pediatric Blood and Cancer Vol 66 S219-S219. Pediatric cancer care in Africa: SIOP Global Mapping Program report on economic and population indicators.

Pharmacogenetics in Neuroblastoma: What Can Already Be Clinically Implemented and What Is Coming Next?

Pharmacogenetics is one of the cornerstones of Personalized Precision Medicine that needs to be implemented in the routine of our patients' clinical management in order to tailor their therapies as much as possible, with the aim of maximizing efficacy and minimizing toxicity. This is of great importance, especially in pediatric cancer and even more in complex malignancies such as neuroblastoma, where the rates of therapeutic success are still below those of many other types of tumors. The studies are mainly focused on germline genetic variants and in the present review, state of the art is presented: which are the variants that have a level of evidence high enough to be implemented in the clinic, and how to distinguish them from the ones that still need validation to confirm their utility. Further aspects as relevant characteristics regarding ontogeny and future directions in the research will also be discussed.

Pediatric cancer care in Africa: SIOP Global Mapping process.

In November 2018, theInternational Society of Paediatric Oncology (SIOP) launched a project to map African facilities providing pediatric oncology treatment. A 55-item digital survey was created in English, piloted in India, translated to French and Portuguese, and distributed by email, social media, or personal contacts. December 2019, 48/54 African countries responded (72% surveys completed and analyzed). Issues included incomplete responses, multiple entries for one facility with conflicting data for key services, and repeated entries with varied answers by the same respondent. The facility mapping project, now on-going program will serve as a global registry of global pediatric cancer centers.

Non-alcoholic fatty liver disease in children and young adults is associated with increased long-term mortality.

BACKGROUND & AIMS: Longitudinal data are scarce regarding the natural history and long-term risk of mortality in children and young adults with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD). METHODS: This nationwide, matched cohort study included all Swedish children and young adults (≤25 years) with biopsy-confirmed NAFLD (1966-2017; n = 718). NAFLD was confirmed histologically from all liver biopsies submitted to Sweden's 28 pathology departments, and further categorized as simple steatosis or steatohepatitis (NASH). Patients with NAFLD were matched to ≤5 general population controls by age, sex, calendar year and county (n = 3,457). To account for shared genetic and early-life factors, we also matched patients with NAFLD to full-sibling comparators. Using Cox regression, we estimated multivariable-adjusted hazard ratios (aHRs) and 95% CIs. RESULTS: Over a median of 15.8 years, 59 patients with NAFLD died (5.5/1,000 person-years [PY]) compared to 36 population controls (0.7/1,000 PY; difference = 4.8/1,000 PY; multivariable aHR 5.88; 95% CI 3.77-9.17), corresponding to 1 additional death per 15 patients with NAFLD, followed for 20 years. The 20-year absolute risk of overall mortality was 7.7% among patients with NAFLD, and 1.1% among controls (difference = 6.6%; 95% CI 4.0-9.2). Findings persisted after excluding those who died within the first 6 months (aHR 4.65; 95% CI 2.92-7.42), and after using full-sibling comparators (aHR 11.72; 95% CI 3.18-43.23). Simple steatosis was associated with a 5.26-fold higher adjusted rate of mortality compared to controls (95% CI 3.05-9.07), and this was amplified with NASH (aHR 11.51, 95% CI 4.77-27.79). Most of the excess mortality was from cancer (1.67 vs. 0.07/1,000PY; aHR 15.60; 95% CI 4.97-48.93), liver disease (0.93 vs. 0.04/1,000PY; aHR 16.46; 95% CI 2.75-98.43) and cardiometabolic disease (1.12 vs. 0.14/1,000PY; aHR 4.32, 95% CI 1.73-10.79). CONCLUSIONS: Swedish children and young adults with biopsy-confirmed NAFLD have significantly higher rates of overall, cancer-, liver- and cardiometabolic-specific mortality compared to matched general population controls. LAY SUMMARY: Currently, the natural history and long-term risk of mortality in children and young adults with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) is unknown. This nationwide cohort study compared the risk of all-cause and cause-specific mortality in pediatric and young adult patients in Sweden with biopsy-confirmed NAFLD to matched general population controls. We found that compared to controls, children and young adults with biopsy-confirmed NAFLD and NASH have significantly higher rates of overall, cancer-, liver- and cardiometabolic-specific mortality.

The paediatric cancer clinical research landscape in Spain: a 13-year multicentre experience of the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

PURPOSE: Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. METHODS: Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007-2013 and 2014-2020. RESULTS: Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2 months (IQR 0-6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. CONCLUSIONS: The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barriers to accessing new drugs for all ranges of age and cancer diseases remain. Additionally, opportunities to improve academic research are still required in Spain.

Ustekinumab in Paediatric Patients with Moderately to Severely Active Crohn's Disease: Pharmacokinetics, Safety, and Efficacy Results from UniStar, a Phase 1 Study.

BACKGROUND AND AIMS: The objective was to evaluate the pharmacokinetics, safety/tolerability, and efficacy of ustekinumab in children with moderately to severely active Crohn's disease. METHODS: In this Phase 1, multicentre, 16-week, double-blind, induction dose-ranging study [NCT02968108], patients aged 2-<18 years [body weight ≥10 kg] were randomised [1:1] to one of two weight range-based intravenous induction doses: 130 mg vs 390 mg in patients ≥40kg and 3 mg/kg vs 9 mg/kg in patients <40kg. At Week 8, all patients received a single subcutaneous ustekinumab maintenance dose of 90 mg in patients ≥40kg or 2 mg/kg in patients <40kg. RESULTS: A total of 44 patients were randomised and treated with ustekinumab [n = 23 lower dose; n = 21 higher dose]; median [interquartile range] age was 13.0 [12-16] years. Pharmacokinetics were similar to those in adults with Crohn's disease. However, serum ustekinumab concentrations were lower among those with body weight <40 kg compared with patients ≥40 kg and the reference Phase 3 adult population. Through Week 16, 73% of patients reported ≥1 adverse event [82.6% lower vs 62% higher dose]; two discontinued due to adverse events [one in each group]. Serious adverse events occurred in 16% [26% lower, 5% higher dose], with Crohn's disease exacerbation being the most frequent. At Week 16, 22%/29% [lower/higher dose] achieved clinical remission [Paediatric Crohn's Disease Activity Index ≤10]. CONCLUSIONS: The pharmacokinetics/safety profiles were generally consistent with those observed in adults with Crohn's disease. These results suggest a different dosing regimen may be required for patients <40 kg from that employed in this study; additional pharmacokinetic analyses may be needed in this population.

8th European Conference on Infections in Leukaemia: 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or post-haematopoietic cell transplantation.

Paediatric patients with cancer and those undergoing allogeneic haematopoietic cell transplantation have an increased susceptibility to invasive fungal diseases. In addition to differences in underlying conditions and comorbidities relative to adults, invasive fungal diseases in infants, children, and adolescents are unique in terms of their epidemiology, the validity of current diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of phase 3 clinical trials to provide data to guide evidence-based interventions. To re-examine the state of knowledge and to further improve invasive fungal disease diagnosis, prevention, and management, the 8th European Conference on Infections in Leukaemia (ECIL-8) reconvened a Paediatric Group to review the literature and to formulate updated recommendations according to the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and European Confederation of Medical Mycology (ECMM) grading system, which are summarised in this Review.

8th European Conference on Infections in Leukaemia: 2020 guidelines for the use of antibiotics in paediatric patients with cancer or post-haematopoietic cell transplantation.

Paediatric patients with cancer and those undergoing haematopoietic cell transplantation are at high risk of bacterial infections. The 8th European Conference on Infections in Leukaemia (ECIL-8) convened a Paediatric Group to review the literature and to formulate recommendations for the use of antibiotics according to the European Society of Clinical Microbiology and Infectious Diseases grading system. The evaluation of antibacterial prophylaxis included mortality, bloodstream infection, febrile neutropenia, emergence of resistance, and adverse effects as endpoints. Initial antibacterial therapy and antibiotic de-escalation or discontinuation focused on patients with a clinically stable condition and without previous infection or colonisation by resistant bacteria, and on patients with a clinically unstable condition or with previous infection or colonisation by resistant bacteria. The final considerations and recommendations of the ECIL-8 Paediatric Group on antibacterial prophylaxis, initial therapy, and de-escalation strategies are summarised in this Policy Review.