Population-Level Analysis of Appropriateness of End-of-Life Care for Children with Neurologic Conditions.

OBJECTIVE: The objective of this study was to measure the appropriateness of end-of-life care for children who died with neurologic conditions. STUDY DESIGN: Based on linked routinely collected databases, we conducted a population-level decedent retrospective cohort study of children with neurologic conditions who died in Belgium between 2010 and 2017. We measured a set of 22 face-validated quality indicators. The set concerns 12 indicators of potentially appropriate end-of-life care (eg, specialized comfort medication, physician contact, continuous care) and 10 indicators of potentially inappropriate end-of-life care (eg, diagnostic tests, phlebotomy). We performed ANOVA for predictors (age, sex, disease category, nationality, having siblings, year of death) for scales of appropriate and inappropriate care. RESULTS: Between 2010 and 2017, 139 children with neurologic conditions died in Belgium. For potentially appropriate care, in the last 30 days, 76% of children received clinical care, 55% had continuous care relationships, 17% had contact with a general physician, 8% of children received specialized comfort medication, and 14% received care from a palliative care team. For potentially inappropriate care, in the last 14 days, 45% had blood drawn and 27% were admitted to intensive care unit. CONCLUSIONS: Our study found indications of appropriate as well as inappropriate end-of-life care for children who died with neurologic conditions. These findings reveal a substantial margin for potential quality improvement, in regard to palliative care provision, multidisciplinary care, financial support, specialized comfort medication, clinical follow-up, general physician contact, diagnostics, and blood drawing.

Outcome of 10 years of ear and hearing screening in people with intellectual disability in Europe: A multicentre study.

BACKGROUND: Undetected ear and hearing problems negatively impact the quality of life of people with intellectual disability. METHODS: This multicentre retrospective study describes the outcome of 10 years of ear and hearing screening in athletes with intellectual disability in seven European countries. The screening was conducted by a trained team using a strictly standardised protocol. RESULTS: Of 15,363 screened athletes with intellectual disability, more than half (58.7%) needed referral for ear and/or hearing problems, ranging from 51.7% (<20 years old) to 81.4% (≥60 years old). The most commonly detected conditions were excessive/impacted earwax (40.3%), middle ear problems (30.1%) and hearing loss (27.0%), with significant differences between age groups and countries. DISCUSSION: This study demonstrates an increased risk of ear and hearing problems in people with intellectual disability as compared to the general population. Considering the unawareness and impact of these problems, it is highly recommended to organise systematic screening. Follow-up for diagnostic elaboration, therapeutic management and long-term guidance should be provided.

Diagnosing enterovirus meningitis via blood transcriptomics: an alternative for lumbar puncture?

BACKGROUND: Meningitis can be caused by several viruses and bacteria. Identifying the causative pathogen as quickly as possible is crucial to initiate the most optimal therapy, as acute bacterial meningitis is associated with a significant morbidity and mortality. Bacterial meningitis requires antibiotics, as opposed to enteroviral meningitis, which only requires supportive therapy. Clinical presentation is usually not sufficient to differentiate between viral and bacterial meningitis, thereby necessitating cerebrospinal fluid (CSF) analysis by PCR and/or time-consuming bacterial cultures. However, collecting CSF in children is not always feasible and a rather invasive procedure. METHODS: In 12 Belgian hospitals, we obtained acute blood samples from children with signs of meningitis (49 viral and 7 bacterial cases) (aged between 3 months and 16 years). After pathogen confirmation on CSF, the patient was asked to give a convalescent sample after recovery. 3' mRNA sequencing was performed to determine differentially expressed genes (DEGs) to create a host transcriptomic profile. RESULTS: Enteroviral meningitis cases displayed the largest upregulated fold change enrichment in type I interferon production, response and signaling pathways. Patients with bacterial meningitis showed a significant upregulation of genes related to macrophage and neutrophil activation. We found several significantly DEGs between enteroviral and bacterial meningitis. Random forest classification showed that we were able to differentiate enteroviral from bacterial meningitis with an AUC of 0.982 on held-out samples. CONCLUSIONS: Enteroviral meningitis has an innate immunity signature with type 1 interferons as key players. Our classifier, based on blood host transcriptomic profiles of different meningitis cases, is a possible strong alternative for diagnosing enteroviral meningitis.

Evaluation of late cardiac effects after multisystem inflammatory syndrome in children.

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is associated with important cardiovascular morbidity during the acute phase. Follow-up shows a swift recovery of cardiac abnormalities in most patients. However, a small portion of patients has persistent cardiac sequelae at mid-term. The goal of our study was to assess late cardiac outcomes of MIS-C. Methods: A prospective observational multicenter study was performed in children admitted with MIS-C and cardiac involvement between April 2020 and March 2022. A follow-up by NT-proBNP measurement, echocardiography, 24-h Holter monitoring, and cardiac MRI (CMR) was performed at least 6 months after MIS-C diagnosis. Results: We included 36 children with a median age of 10 (8.0-11.0) years, and among them, 21 (58%) were girls. At diagnosis, all patients had an elevated NT-proBNP, and 39% had a decreased left ventricular ejection fraction (LVEF) (<55%). ECG abnormalities were present in 13 (36%) patients, but none presented with arrhythmia. Almost two-thirds of patients (58%) had echocardiographic abnormalities such as coronary artery dilation (20%), pericardial effusion (17%), and mitral valve insufficiency (14%). A decreased echocardiographic systolic left ventricular (LV) function was detected in 14 (39%) patients. A follow-up visit was done at a mean time of 12.1 (±5.8) months (range 6-28 months). The ECG normalized in all except one, and no arrhythmias were detected on 24-h Holter monitoring. None had persistent coronary artery dilation or pericardial effusion. The NT-proBNP level and echocardiographic systolic LV function normalized in all patients, except for one, who had a severely reduced EF. The LV global longitudinal strain (GLS), as a marker of subclinical myocardial dysfunction, decreased (z < -2) in 35%. CMR identified one patient with severely reduced EF and extensive myocardial fibrosis requiring heart transplantation. None of the other patients had signs of myocardial scarring on CMR. Conclusion: Late cardiac outcomes after MIS-C, if treated according to the current guidelines, are excellent. CMR does not show any myocardial scarring in children with normal systolic LV function. However, a subgroup had a decreased GLS at follow-up, possibly as a reflection of persistent subclinical myocardial dysfunction.

Factors influencing the occurrence of infectious disease outbreaks in Lebanon since the Syrian crisis.

Since the beginning of the Syrian crisis in 2011, the region has witnessed a major population displacement. Lebanon, a country with a population of 4.2 million, has welcomed around one million refugees. A rise in the incidence of Measles, Hepatitis A and Leishmaniosis was noted. This paper aims to document the incidence of outbreaks along with the factors that contributed to their emergence in Lebanon. A comprehensive literature review was conducted using electronic databases and (non) governmental reports, including studies reporting the state of Syrian refugees in Lebanon and those reporting on infectious outbreaks in Lebanon and Syria. Primary outcomes were defined as incidence or prevalence of Measles, Hepatitis A, and Leishmaniosis in both populations. Secondary outcomes were set to be the risk factors for the outbreaks. As of February 2016, Lebanon registered a total of 1.067.785 refugees. Infectious outbreaks were reported in Lebanon just after initiation of Syrian migration, with 1760 new measles cases, 1551 hepatitis A cases, and 1033 Leishmania cases in 2013. Local factors probably contributing to the emergence and dissemination of the outbreaks include living conditions, water and sanitation, nutritional state, and immunization. The outbreaks were not only reported in regions with higher refugee concentration, but also within other Lebanese regions. This was attributed to deficiencies in immunization of measles, low socioeconomic status and poor living conditions. The Syrian crisis has led to considerable impact on the demographic, economic, and political systems in Lebanon, next to an important burden on the healthcare system.

Acute Health Effects and Outcome Following Sarin Gas Attacks in Khan Shaykhun, Syria.

Background In 2017, Idlib, Syria, was exposed to a chemical attack with sarin gas. Many patients of the attack were presented to the Al Rahman Charity Hospital in northern Syria. The aim of this study is to describe the clinical manifestations of sarin gas exposure, as well as the management and outcome of these manifestations in areas with poor healthcare infrastructure. Methods In a case series study design, medical records of suspected sarin exposed patients were reviewed in terms of age, gender, initial clinical presentation, management, and outcome. Results Seventeen patients with signs of sarin gas exposure had detailed medical records. The mean age was 29.1 years with a range of 4-70 years. Six patients were male (35.3%), and four (23.5%) were children under 18 years. At initial presentation, all victims suffered from respiratory distress because of severe airway inflammation, chest pain, and ophthalmological symptoms. All patients featured varying degrees of intestinal, neurologic, and dermatological signs and symptoms. Acute symptom management consisted of oxygen (100% of patients), atropine (100%), bronchodilators (82.4%), dexamethasone (82.4%), anti-emetics (82.4%), paracetamol (47.1%), and ranitidine (41.2%). Rapid symptomatic recovery was observed in 13 patients (76.5%) who stayed in the hospital for less than 24 hours, but four patients (23.5%) had to be admitted for more than 24 hours. The median length of stay was 22.2 hours (with a range of eight to 48 hours). Two patients required intensive care. Of the studied sample, all patients survived. Interpretation This study demonstrates that even in austere healthcare settings, survival rate and prognosis of sarin gas contaminated patients are fair if basic measures and symptomatic treatment are performed. The study provides insight into the clinical presentation, management, and hospital course likely to result from future sarin gas releases.

Blood transcriptomics to facilitate diagnosis and stratification in pediatric rheumatic diseases - a proof of concept study.

BACKGROUND: Transcriptome profiling of blood cells is an efficient tool to study the gene expression signatures of rheumatic diseases. This study aims to improve the early diagnosis of pediatric rheumatic diseases by investigating patients' blood gene expression and applying machine learning on the transcriptome data to develop predictive models. METHODS: RNA sequencing was performed on whole blood collected from children with rheumatic diseases. Random Forest classification models were developed based on the transcriptome data of 48 rheumatic patients, 46 children with viral infection, and 35 controls to classify different disease groups. The performance of these classifiers was evaluated by leave-one-out cross-validation. Analyses of differentially expressed genes (DEG), gene ontology (GO), and interferon-stimulated gene (ISG) score were also conducted. RESULTS: Our first classifier could differentiate pediatric rheumatic patients from controls and infection cases with high area-under-the-curve (AUC) values (AUC = 0.8 ± 0.1 and 0.7 ± 0.1, respectively). Three other classifiers could distinguish chronic recurrent multifocal osteomyelitis (CRMO), juvenile idiopathic arthritis (JIA), and interferonopathies (IFN) from control and infection cases with AUC ≥ 0.8. DEG and GO analyses reveal that the pathophysiology of CRMO, IFN, and JIA involves innate immune responses including myeloid leukocyte and granulocyte activation, neutrophil activation and degranulation. IFN is specifically mediated by antibacterial and antifungal defense responses, CRMO by cellular response to cytokine, and JIA by cellular response to chemical stimulus. IFN patients particularly had the highest mean ISG score among all disease groups. CONCLUSION: Our data show that blood transcriptomics combined with machine learning is a promising diagnostic tool for pediatric rheumatic diseases and may assist physicians in making data-driven and patient-specific decisions in clinical practice.

Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey.

BACKGROUND: During the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group. We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium. METHODS: From July 1, 2009, to January 31, 2010, we collected epidemiological and clinical data of all proven (positive H1N1v PCR) and probable (positive influenza A antigen or culture) pediatric cases of influenza A/H1N1v infections, hospitalized in four tertiary centers. RESULTS: During the epidemic period, an excess of 18% of pediatric outpatients and emergency department visits was registered. 215 children were hospitalized with proven/probable influenza A/H1N1v infection. Median age was 31 months. 47% had ≥ 1 comorbid conditions. Febrile respiratory illness was the most common presentation. 36% presented with initial gastrointestinal symptoms and 10% with neurological manifestations. 34% had pneumonia. Only 24% of the patients received oseltamivir but 57% received antibiotics. 10% of children were admitted to PICU, seven of whom with ARDS. Case fatality-rate was 5/215 (2%), concerning only children suffering from chronic neurological disorders. Children over 2 years of age showed a higher propensity to be admitted to PICU (16% vs 1%, p = 0.002) and a higher mortality rate (4% vs 0%, p = 0.06). Infants less than 3 months old showed a milder course of infection, with few respiratory and neurological complications. CONCLUSION: Although influenza A/H1N1v infections were generally self-limited, pediatric burden of disease was significant. Compared to other countries experiencing different health care systems, our Belgian cohort was younger and received less frequently antiviral therapy; disease course and mortality were however similar.

Effects of Two Chlorine Gas Attacks on Hospital Admission and Clinical Outcomes in Kafr Zita, Syria.

Background In 2014, Hama Governorate was exposed twice to chlorine gas, with 15 patients presenting to Kafr Zita Hospital in Northwest Syria. This study aimed to describe clinical manifestations of chlorine gas exposure to identify factors leading to facility admission and the need for ICU/intubation in conflict-affected areas with limited healthcare infrastructure. Methods We conducted a case-series study, using medical records of suspected chlorine-exposed patients presenting at Kafr Zita Hospital on either 11 April or 22 May 2014. Data on age, sex, initial clinical presentation, therapeutic management, and outcome were compared by hospital admission/non-admission and attack date. All patients provided verbal informed consent. Results Fifteen patients with signs of chlorine gas exposure had detailed medical records. The mean age was 25.7 years (range 2-59), eight were male (53%), and three (20%) were under age 16. At initial presentation, all experienced respiratory distress, due to severe airway inflammation confirmed by nonspecific pulmonary infiltrates on chest x-ray, and similar intestinal, neurological, dermatological, ophthalmological, and psychological signs and symptoms. Acute management consisted of oxygen and bronchodilators for all patients, hydrocortisone (93%), antiemetics (80%), and dexamethasone (13%). Seven (47%) made a rapid symptomatic recovery and were discharged the same day and eight (53%) were admitted for a median of two days (range 1-6 days), one of whom required intubation and later died. The only significant associations found were higher mean pulse rate (i.e. 138 versus 124; p=0.043) and body temperature (37.0 versus 36.5; p=0.019) among admitted patients compared to non-admitted. Conclusion Our results demonstrated that even in low-resource humanitarian settings the survival rate for chlorine gas exposed patients is fair. Despite the small sample, this study provides insight into the clinical presentation, management, and outcomes of weaponized chlorine gas exposure, though further research is required to understand any chronic consequences.

Varying Presentations of Multisystem Inflammatory Syndrome Temporarily Associated with COVID-19.

Background. A novel coronavirus identified in 2019 leads to a pandemic of severe acute respiratory distress syndrome with important morbidity and mortality. Initially, children seemed minimally affected, but there were reports of cases similar to (atypical) Kawasaki disease or toxic shock syndrome, and evidence emerges about a complication named paediatric inflammatory multisystem syndrome temporarily associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C). Case Presentations. Two cases were compared and discussed demonstrating varying presentations, management, and evolution of MIS-C. These cases are presented to increase awareness and familiarity among paediatricians and emergency physicians with the different clinical manifestations of this syndrome. Discussion. MIS-C may occur with possible diverse clinical presentations. Early recognition and treatment are paramount for a beneficial outcome.