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Retrospective study of haemophagocytic syndrome hospitalisations in children in the USA.

ABSTRACT: Introduction:The haemophagocytic syndrome (HS) is a rare condition that presents with uncontrolled inflammation leading to multiorgan failure and is associated with significant morbidity and mortality. Current national estimates of children hospitalised due to HS are unknown. Characterising and understanding the burden of HS-related hospitalisations at a national level is the initial step in optimising the overall care. Methods:We performed a retrospective analysis of the Nationwide Inpatient Sample (NIS) from 2012 to 2014. The NIS is the largest all-payer inpatient care dataset in the USA that contains more than seven million hospital stays and its large sample size is ideal for developing national estimates of rare conditions. All patients aged up to 18 years who were primarily hospitalised due to HS were selected for our study. Descriptive statistics were used. A multitude of patient-level and hospital-level variables were assessed. Outcome variables included overall in-hospital mortality, hospital charges and the length of stay. Results:A total of 840 patients aged up to 18 years were hospitalised primarily due to HS in the USA. Mean age was 5.7 years. 57.4% were males. Whites comprised 45%. 6.5% died in hospital. A vast majority (78%) were admitted on an emergency/urgent basis. The most frequent payers included Medicaid (50%) and private insurance (36.9%). Almost 80% of children had at least one comorbid condition. 96.3% of patients were treated in urban teaching hospitals. Southern regions accounted for 42.6% of all hospitalisations. The median length of stay in hospital was 9.6 days and the median hospitalisation charge was US$100 426. Conclusion:Nearly 1 in 15 children who were hospitalised due to HS died. The resource utilisation associated with HS-related hospitalisations is considerable. The majority of hospitalised children with HS had comorbid conditions.

SUBMITTER: Badheka A

PROVIDER: S-EPMC6242022 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Retrospective study of haemophagocytic syndrome hospitalisations in children in the USA.

Badheka Aditya A Bangalore Prakash Pradeep P Allareddy Veerasathpurush V Allareddy Veerajalandhar V

BMJ paediatrics open 20181109 1

<h4>Introduction</h4>The haemophagocytic syndrome (HS) is a rare condition that presents with uncontrolled inflammation leading to multiorgan failure and is associated with significant morbidity and mortality. Current national estimates of children hospitalised due to HS are unknown. Characterising and understanding the burden of HS-related hospitalisations at a national level is the initial step in optimising the overall care.<h4>Methods</h4>We performed a retrospective analysis of the Nationwi ...[more]

PMID: 30498794

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Project description:Background: Most children and adolescents infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop a mild coronavirus disease 2019 (COVID-19) that usually does not require medical intervention. However, a small proportion of pediatric patients develop a severe clinical condition, Multisystem Inflammatory Syndrome in Children (MIS-C). The involvement of epigenetics in the control of the immune response and viral activity prompted us to carry out an epigenomic study to uncover target loci regulated by DNA methylation that could be altered upon the appearance of MIS-C. Methods: Peripheral blood samples were recruited from 43 confirmed MIS-C patients with a median age of 7.7 years, most of whom were of West-Eurasian origin. Four or more organ systems were involved in the majority of patients. 69 non-COVID-19 pediatric samples and 15 COVID-19 pediatric samples without MIS-C were used as controls. The cases in the two groups were mixed and divided into discovery (MIS-C = 29 and non-MIS-C = 56) and validation (MIS-C = 14 and non-MIS-C = 28) cohorts, and balanced for age, gender and ethnic background. We interrogated 850,000 CpG sites of the human genome for DNA methylation variants. Findings: The DNA methylation content of 33 CpG loci was linked with the presence of MIS-C. Of these sites, 18 (54.5%) were located in described genes. The top candidate gene was the immune T-cell mediator ZEB2; and others highly ranked candidates included the regulator of natural killer cell functional competence SH2D1B; VWA8, which contains a domain of the Von Willebrand factor A involved in the pediatric hemostasis disease; and human leukocyte antigen complex member HLA-DRB1; in addition to pro-inflammatory genes such as CUL2 and AIM2. The identified loci were used to construct a DNA methylation profile (EPIMISC) that was associated with MIS-C in both cohorts. The EPIMISC signature was also overrepresented in Kawasaki disease patients, a childhood pathology with also a possible viral trigger, that shares many of the clinical features of MIS-C. Interpretation: We have characterized DNA methylation loci that are associated with the onset of MIS-C. The identified genes are likely contributors to the characteristic exaggerated host inflammatory response observed in these patients. The described epigenetic signature could also provide new targets for more specific therapies for the disorder.

Project description:ObjectiveTo describe the epidemiology and risk factors for hospitalisation and death in Mexican children under 18 years of age with COVID-19.DesignRetrospective, cross-sectional and analytical study.SettingMexican Ministry of Health open databases with COVID-19 cases occurred from 7 March 2020 to 30 September 2021.ParticipantsMexican children under 18 years of age with COVID-19.Main outcome measuresCOVID-19 hospitalisations and deaths were characterised by age group, sex, presence of pneumonia and comorbidities, intubation and intensive care unit admission, and institution that provided medical care. Cumulative incidence, mortality, case fatality rates and ORs for hospitalisation and death were estimated by age group.Results5.5% (204 641) of national COVID-19 cases were children under 18 years of age: 2.9% under 1 year, 12.5% from 1 to 5 years, 15% from 6 to 9 years and 69.4% from 10 to 17 years. 4.6% of all cases were hospitalised, from which 54.6% were male, 35.3% were children under 1 year old, 39.6% were adolescents and 34% had pneumonia. Pneumonia developed in 2.3% of cases, from which 50% were adolescents. Case fatality rate was higher in children less than 1 year old (4.2%). Risk analyses showed that male sex (OR 1.16-1.28), history of pneumonia (OR 29.7-65.4), immunosuppression (OR 5.3-42.9), cardiovascular disease (OR 4.4-14.6) and other comorbidities (OR 5.4-19.1), as well as age less than 1 year (OR 20.1, 95% CI 18.8 to 21.4), confer a greater risk of hospitalisation; in addition to comorbidities, age less than 1 year (OR 16.6, 95% CI 14.1 to 19.6), history of pneumonia (OR 14.1-135.1) and being an adolescent from an indigenous community (OR 2.6, 95% CI 1.23 to 5.54, p=0.012) increase the risk of death.ConclusionsIn Mexico, children less than 1 year old with COVID-19 have higher risk of hospitalisation and death than older children. Adolescents with COVID-19 in association with comorbidities develop adverse outcomes more frequently.

Project description:BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a newly identified and serious health condition associated with SARS-CoV-2 infection. Clinical manifestations vary widely among patients with MIS-C, and the aim of this study was to investigate factors associated with severe outcomes.MethodsIn this retrospective surveillance study, patients who met the US Centers for Disease Control and Prevention (CDC) case definition for MIS-C (younger than 21 years, fever, laboratory evidence of inflammation, admitted to hospital, multisystem [≥2] organ involvement [cardiac, renal, respiratory, haematological, gastrointestinal, dermatological, or neurological], no alternative plausible diagnosis, and either laboratory confirmation of SARS-CoV-2 infection by RT-PCR, serology, or antigen test, or known COVID-19 exposure within 4 weeks before symptom onset) were reported from state and local health departments to the CDC using standard case-report forms. Factors assessed for potential links to severe outcomes included pre-existing patient factors (sex, age, race or ethnicity, obesity, and MIS-C symptom onset date before June 1, 2020) and clinical findings (signs or symptoms and laboratory markers). Logistic regression models, adjusted for all pre-existing factors, were used to estimate odds ratios between potential explanatory factors and the following outcomes: intensive care unit (ICU) admission, shock, decreased cardiac function, myocarditis, and coronary artery abnormalities.Findings1080 patients met the CDC case definition for MIS-C and had symptom onset between March 11 and Oct 10, 2020. ICU admission was more likely in patients aged 6-12 years (adjusted odds ratio 1·9 [95% CI 1·4-2·6) and patients aged 13-20 years (2·6 [1·8-3·8]), compared with patients aged 0-5 years, and more likely in non-Hispanic Black patients, compared with non-Hispanic White patients (1·6 [1·0-2·4]). ICU admission was more likely for patients with shortness of breath (1·9 [1·2-2·9]), abdominal pain (1·7 [1·2-2·7]), and patients with increased concentrations of C-reactive protein, troponin, ferritin, D-dimer, brain natriuretic peptide (BNP), N-terminal pro B-type BNP, or interleukin-6, or reduced platelet or lymphocyte counts. We found similar associations for decreased cardiac function, shock, and myocarditis. Coronary artery abnormalities were more common in male patients (1·5 [1·1-2·1]) than in female patients and patients with mucocutaneous lesions (2·2 [1·3-3·5]) or conjunctival injection (2·3 [1·4-3·7]).InterpretationIdentification of important demographic and clinical characteristics could aid in early recognition and prompt management of severe outcomes for patients with MIS-C.FundingNone.

Project description:The difficulties and challenges of applying the HLH-2004 diagnostic criteria to early identification and diagnosis of haemophagocytic lymphohistiocytosis have been fully addressed in previous studies. However, the distribution of the diagnostic time lag of haemophagocytic lymphohistiocytosis and related patient characteristics remain unclear. This study investigated the time lags between symptom onset and diagnosis and between hospital admission and diagnosis among pediatric patients with haemophagocytic lymphohistiocytosis, and identified factors that associated with a shorter or longer diagnostic time lag. The cohort of patients with haemophagocytic lymphohistiocytosis was drawn from a tertiary children's hospital and consisted of 122 pediatric patients. The distributions of symptom-to-diagnosis and admission-to-diagnosis time lags were assessed. Clinical characteristics within 48 h of admission and the fulfillment of HLH-2004 diagnostic criteria were compared among admission-to-diagnosis time lag categories. Logistic regression analyses were conducted to identify factors associated with an admission-to-diagnosis time lag >3 days. The median interval from first symptom onset to HLH diagnosis was 12 days (range 4-71 days) and the median interval from hospital admission to HLH diagnosis was 2 days (range 0-23 days). The following factors were negatively associated with admission-to-diagnosis > 3 days: Epstein-Barr virus infection; admission through pediatric intensive care unit; diagnosis established without NK-cell activity and soluble CD25 tests; the performance of all readily available diagnostic tests for HLH (within 48 and 72 h); concurrent fever, splenomegaly, and cytopenias within 48 h; hemophagocytosis, hypertriglyceridemia and/or hypofibrinogenemia within 48 h; and elevated ferritin, total bilirubin, alanine aminotransferase, and prothrombin time within 48 h. Our findings suggest that performance of adequate diagnostic tests for HLH is essential for early diagnosis of HLH. Once suspected, immediate and adequate diagnostic tests for HLH should be arranged for PICU patients. Improvements in diagnostic procedures and monitoring plans are needed to promote early diagnosis of HLH.

Project description:ObjectiveTo investigate current Down syndrome live birth and death rates, and childhood hospitalisations, compared with peers.SettingGeneral community.ParticipantsAll live births with Down syndrome, 1990-2015, identified via Scottish regional cytogenetic laboratories, each age-sex-neighbourhood deprivation matched with five non-Down syndrome controls. Record linkage to Scotland's hospital admissions and death data.Primary outcomeHRs comparing risk of first hospitalisation (any and emergency), readmission for children with Down syndrome and matched controls were calculated using stratified Cox proportional hazards (PH) model, and length of hospital stay was calculated using a conditional log-linear regression model.Results689/1479 (46.6%) female and 769/1479 (51.9%) male children/young people with Down syndrome were identified (1.0/1000 births, with no reduction over time); 1235 were matched. 92/1235 (7.4%) died during the period, 18.5 times more than controls. More of the Down syndrome group had at least one admission (incidence rate ratio(IRR) 72.89 (68.72-77.32) vs 40.51 (39.15-41.92); adjusted HR=1.84 (1.68, 2.01)) and readmissions (IRR 54.85 (51.46-58.46) vs 15.06 (14.36-15.80); adjusted HR=2.56 (2.08, 3.14)). More of their admissions were emergencies (IRR 56.78 (53.13-60.72) vs 28.88 (27.73-30.07); first emergency admission adjusted HR=2.87 (2.61, 3.15)). Children with Down syndrome had 28% longer first admission after birth. Admission rate increased from 1990-2003 to 2004-2014 for the Down syndrome group (from 90.7% to 92.2%) and decreased for controls (from 63.3% to 44.8%).ConclusionsWe provide contemporaneous statistics on the live birth rate of babies with Down syndrome, and their childhood death rate. They require more hospital admissions, readmissions emergency admissions and longer lengths of stays than their peers, which has received scant research attention in the past. This demonstrates the importance of statutory planning as well as informal support to families to avoid added problems in child development and family bonding over and above that brought by the intellectual disabilities associated with Down syndrome.

Dataset Information

Retrospective study of haemophagocytic syndrome hospitalisations in children in the USA.

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Retrospective study of haemophagocytic syndrome hospitalisations in children in the USA.

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