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Clinical trials investigating the potential of mesenchymal stromal cells (MSCs) for the treatment of inflammatory diseases, such as acute respiratory distress syndrome (ARDS), have been disappointing, with less than 50% of patients responding to treatment. Licensed MSCs show enhanced therapeutic efficacy in response to cytokine-mediated activation signals. There are two distinct sub-phenotypes of ARDS: hypo- and hyper-inflammatory. We hypothesized that pre-licensing MSCs in a hyper-inflammatory ARDS environment would enhance their therapeutic efficacy in acute lung inflammation (ALI). Serum samples from patients with ARDS were segregated into hypo- and hyper-inflammatory categories based on interleukin (IL)-6 levels. MSCs were licensed with pooled serum from patients with hypo- or hyper-inflammatory ARDS or healthy serum controls. Our findings show that hyper-inflammatory ARDS pre-licensed MSC conditioned medium (MSC-CMHyper) led to a significant enrichment in tight junction expression and enhanced barrier integrity in lung epithelial cells in vitro and in vivo in a vascular endothelial growth factor (VEGF)-dependent manner. Importantly, while both MSC-CMHypo and MSC-CMHyper significantly reduced IL-6 and tumor necrosis factor alpha (TNF-α) levels in the bronchoalveolar lavage fluid (BALF) of lipopolysaccharide (LPS)-induced ALI mice, only MSC-CMHyper significantly reduced lung permeability and overall clinical outcomes including weight loss and clinical score. Thus, the hypo- and hyper-inflammatory ARDS environments may differentially influence MSC cytoprotective and immunomodulatory functions.
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BACKGROUND: Investigating the contributory role that epithelial cell metabolism plays in allergic inflammation is a key factor to understanding what influences dysfunction and the pathogenesis of the allergic disease eosinophilic esophagitis (EoE). We previously highlighted the absence of hypoxia signaling through HIF-1α in EoE contributes to esophageal epithelial dysfunction. However, metabolic regulation by HIF-1α has not been explored in esophageal allergy. OBJECTIVES: Herein, we sought to define the role of HIF-1α-mediated metabolic dysfunction in esophageal epithelial differentiation processes and barrier function in EoE. METHODS: In RNA-sequencing derived from EoE patient biopsies, we observed the expression pattern of key genes involved in mitochondrial metabolism/oxidative phosphorylation (OXPHOS) and glycolysis. Bioenergetics analysis using Seahorse was performed on EPC2-hTERT cells to decipher the metabolic processes involved in epithelial differentiation processes. In addition, air-liquid interface cultures were employed to delineate metabolic dependency mechanisms required for epithelial differentiation. RESULTS: Transcriptomic analysis identified an increase in genes associated with OXPHOS in patients with EoE. Epithelial origin of this signature was confirmed by complex V immunofluorescence of patient biopsies. Bioenergetic analysis in vitro revealed that differentiated epithelium was less reliant on OXPHOS compared with undifferentiated epithelium. Increased OXPHOS potential and reduced glycolytic capacity was mirrored in HIF1A-knockdown EPC2-hTERT cells which portray a significant absence of terminal markers of epithelial differentiation, including involucrin. Pharmacological glucose transport inhibition phenocopied this, while rescue of the HIF-1α-deficient phenotype using the pan-prolyl hydroxylase inhibitor DMOG resulted in restored expression of epithelial differentiation markers. CONCLUSIONS: An OXPHOS-dominated metabolic pattern in EoE patients, brought about largely by the absence of HIF-1α-mediated glycolysis, is linked with the deficit in esophageal epithelial differentiation.
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OBJECTIVE: To investigate if preschool children differ to school age children with mild traumatic brain injury (TBI) with respect to injury causes, clinical presentation, and medical management. DESIGN: A secondary analysis of a dataset from a large, prospective and multisite cohort study on TBI in children aged 0-18 years, the Australian Paediatric Head Injury Rules Study. SETTING: Nine pediatric emergency departments (ED) and 1 combined adult and pediatric ED located across Australia and New Zealand. PARTICIPANTS: 7080 preschool aged children (2-5 years) were compared with 5251 school-age children (6-12 years) with mild TBI (N= (N=12,331) MAIN OUTCOME MEASURES: Clinical report form on medical symptoms, injury causes, and management. RESULTS: Preschool children were less likely to be injured with a projectile than school age children (P<.001). Preschool children presented with less: loss of consciousness (P<.001), vomiting (P<.001), drowsiness (P=.002), and headache (P<.001), and more irritability and agitation (P=.003), than school-age children in the acute period after mild TBI. Preschool children were less likely to have neuroimaging of any kind (P<.001) or to be admitted for observation than school age children (P<.001). CONCLUSIONS: Our large prospective study has demonstrated that preschool children with mild TBI experience a different acute symptom profile to older children. There are significant clinical implications with symptoms post-TBI used in medical management to aid decisions on neuroimaging and post-acute intervention.
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Concussão Encefálica , Lesões Encefálicas Traumáticas , Adulto , Criança , Pré-Escolar , Humanos , Austrália , Estudos de Coortes , Serviço Hospitalar de Emergência , Estudos ProspectivosRESUMO
CO2 is produced during aerobic respiration. Normally, levels of CO2 in the blood are tightly regulated but pCO2 can rise (hypercapnia, pCO2 > 45 mmHg) in patients with lung diseases, for example, chronic obstructive pulmonary disease (COPD). Hypercapnia is a risk factor in COPD but may be of benefit in the context of destructive inflammation. The effects of CO2 per se, on transcription, independent of pH change are poorly understood and warrant further investigation. Here we elucidate the influence of hypercapnia on monocytes and macrophages through integration of state-of-the-art RNA-sequencing, metabolic and metabolomic approaches. THP-1 monocytes and interleukin 4-polarized primary murine macrophages were exposed to 5% CO2 versus 10% CO2 for up to 24 h in pH-buffered conditions. In hypercapnia, we identified around 370 differentially expressed genes (DEGs) under basal and about 1889 DEGs under lipopolysaccharide-stimulated conditions in monocytes. Transcripts relating to both mitochondrial and nuclear-encoded gene expression were enhanced in hypercapnia in basal and lipopolysaccharide-stimulated cells. Mitochondrial DNA content was not enhanced, but acylcarnitine species and genes associated with fatty acid metabolism were increased in hypercapnia. Primary macrophages exposed to hypercapnia also increased activation of genes associated with fatty acid metabolism and reduced activation of genes associated with glycolysis. Thus, hypercapnia elicits metabolic shifts in lipid metabolism in monocytes and macrophages under pH-buffered conditions. These data indicate that CO2 is an important modulator of monocyte transcription that can influence immunometabolic signaling in immune cells in hypercapnia. These immunometabolic insights may be of benefit in the treatment of patients experiencing hypercapnia.
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Hipercapnia , Doença Pulmonar Obstrutiva Crônica , Humanos , Animais , Camundongos , Hipercapnia/etiologia , Hipercapnia/metabolismo , Dióxido de Carbono , Monócitos/metabolismo , Genes Mitocondriais , Lipopolissacarídeos , Doença Pulmonar Obstrutiva Crônica/complicações , Expressão Gênica , Ácidos GraxosRESUMO
Mild traumatic brain injury (mTBI) is common in children aged < 5 years, however, less is known about their experience of post-concussive signs and symptoms. This systematic review aims to identify post-concussive signs and symptoms experienced by preschool children up to 12 months post-injury, and to review the methods used to report this data. Relevant findings, including rates, progression, and possible predictors of post-concussive signs and symptoms were also identified. Databases (Ovid MEDLINE, EMBASE, PsycInfo, PubMed, Scopus) and reference lists were searched for relevant articles, which were screened based on specified criteria. Eleven articles met the inclusion criteria, being original studies published in English and presenting data on post-concussive signs and symptoms specific to preschool children with mTBI. Most reviewed studies investigated acute presentations of mTBI, and identified that preschool children demonstrate post-concussive symptoms (PCS) similar to other age groups. Post-traumatic amnesia duration of approximately one day was reported in preschool children following mTBI, as were changes in mood and behavior during the recovery period. Parents were the main informants, with data obtained through either interview or questionnaire. Review findings highlight the lack of empirical data regarding the presentation and progression of PCS in preschoolers following mTBI and evidence on how to best manage this group during recovery.
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Concussão Encefálica , Síndrome Pós-Concussão , Concussão Encefálica/complicações , Pré-Escolar , Humanos , Pais , Síndrome Pós-Concussão/diagnósticoRESUMO
Acquired brain injury (ABI) occurs commonly in young children. Despite this, the psychosocial implications of ABI in young children are not established, with little understood about the impacts on self-perception and self-esteem. In this study we investigated self-perception, self-esteem and behaviour of children with early ABI. Children with an ABI (n = 47) before six years were compared to 17 typically developing controls (TDCs) matched on demographics. Children were aged 6-12 years and completed the Harter Self-Perception Profile. One parent completed the Child Behavior Checklist. No differences for self-perception and self-esteem were found between the groups. Parents of children with an early ABI reported more internalizing and externalizing behaviours. Children with more externalizing behaviour and social skill problems had more negative self-perceptions. Interaction effects were seen between socioeconomic status (SES) and child self-perception and behaviour. Specifically, children from families of higher SES had a more positive perception of their appearance and children from lower SES backgrounds had more externalizing behaviours and social problems. The study suggests that the relationship between ABI and self-perception and self-esteem is complicated and that children with behavioural problems have lowered feelings of competence. SES has an important role in self-perception and behavioural outcomes.
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Lesões Encefálicas , Comportamento Problema , Lesões Encefálicas/psicologia , Criança , Pré-Escolar , Humanos , Pais , Autoimagem , Classe SocialRESUMO
OBJECTIVES: A systematic review and meta-analysis were conducted to determine if children born with cleft lip and/or palate are at increased risk of psychological and peer difficulties, and if so, which difficulties they develop. METHODS: EMBASE, MEDLINE, and PsycINFO were searched for English language studies published between January 2005 and January 2022 which investigated the psychological outcomes and peer function of children with nonsyndromic cleft lip and palate. Outcomes included internalizing problems, such as anxiety and depression, externalizing problems, such as hyperactivity, conduct disorders, self-concept including self-image and self-esteem, peer problems, resilience, coping, and overall psychological function. A risk of bias assessment was performed using the Newcastle-Ottawa Scale. Random effects models were used in the meta-analysis to compare the outcomes for children born with a cleft and those without. RESULTS: In total 41 studies met inclusion criteria, with 9 included in the meta-analysis. Children born with a cleft appear to have similar psychological outcomes compared to normative controls when using the strengths and difficulties questionnaire. There are some minor differences between self-report and parent report, with parents generally reporting that their child with a cleft has increased emotional, conduct, and hyperactivity problems. The small differences between the study cohort and control cohorts are unlikely to imply any differences on a clinical level. CONCLUSIONS: Overall psychological outcomes appear to be similar between children born with a cleft and the nonaffected population, however, some symptoms such as anxiety and depression appear higher in children with cleft lip and/or palate.
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Background and Purpose: Childhood and adolescence coincide with rapid maturation of distributed brain networks supporting social cognition; however, little is known about the impact of early ischemic brain insult on the acquisition of these skills. This study aimed to examine the influence of arterial ischemic stroke (AIS) on facial emotion recognition and theory of mind (ToM) abilities of children and adolescents initially recruited to a single-center, prospective longitudinal study of recovery following AIS. Methods: The study involved 67 participants, including 30 children with AIS (mean time since stroke=5 years) and 37 age-matched typically developing controls who were assessed on measures of cognitive ToM, facial emotion recognition, and affective ToM. Acute clinical magnetic resonance imaging, including diffusion-weighted imaging sequences, were used to evaluate prospective structure-function relationships between acute lesion characteristics (size, location, and arterial territories affected) and long-term social cognitive abilities. Results: Relative to age-matched typically developing controls, children with AIS showed significantly worse performance on measures of basic facial emotion processing, cognitive ToM, and affective ToM. In univariate models, poorer ToM was associated with larger infarcts, combined cortical-subcortical pathology, and involvement of multiple arterial territories. In multivariate analyses, larger lesions and multiterritory infants were predictive of ToM processing but not facial emotion recognition. Poorer cognitive ToM predicted less frequent prosocial behavior and increased peer problems. Conclusions: Social cognitive skills appear vulnerable to disruption from early ischemic brain insult. In the first study to examine social cognition in a prospective cohort of children with AIS, our findings suggest that acute magnetic resonance imaging-based lesion characteristics may have predictive value for long-term social cognitive outcomes and may assist to identify children at elevated risk for social cognitive dysfunction.
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Disfunção Cognitiva , AVC Isquêmico , Comportamento Social , Adolescente , Criança , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Feminino , Seguimentos , Humanos , AVC Isquêmico/complicações , AVC Isquêmico/fisiopatologia , AVC Isquêmico/psicologia , Masculino , Estudos ProspectivosRESUMO
OBJECTIVE: To investigate long-term intellectual function following a traumatic brain injury (TBI) in early childhood and to identify the contribution of injury and environment to outcome. PARTICIPANTS: Fifty children younger than 3 years with a diagnosis of accidental TBI were recruited through a pediatric hospital emergency department. Children with TBI were compared with a group (n = 33) of typically developing children (TDC) matched on demographics. DESIGN: Longitudinal, single-site, case-control study. MEASURES: Children completed intellectual assessments (IQ) at 4.5 to 5.5 years of age (average 3.5 years after TBI) and at 7.5 to 9 years of age (average 6.5 years after TBI). Information on injury and environmental predictors of outcome was collected. RESULTS: IQ scores for all groups were in the average range; however, children with TBI of any severity had lower scores than TDC at both time points. There was some suggestion of children with TBI achieving lower verbal IQ scores over time than TDC. IQ scores were predicted by family environment, not injury characteristics. CONCLUSIONS: A TBI in early childhood is associated with lower IQ scores that persist several years postinjury. Socioeconomic status is an influential factor on IQ at 6.5 years post-TBI.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Humanos , Relações Interpessoais , Estudos LongitudinaisRESUMO
BACKGROUND: The Pediatric Emergency Care Applied Research Network (PECARN) decision rule demonstrates high sensitivity for identifying children at low risk for clinically important traumatic brain injury (ciTBI). As with the PECARN rule, the Israeli Decision Algorithm for Identifying TBI in Children (IDITBIC) recommends proceeding directly to computed tomography (CT) in children with Glasgow Coma Score (GCS) <15. The aim was to assess the diagnostic accuracy of two clinical rules that assign children with GCS <15 at presentation directly to CT. MATERIALS AND METHODS: Accuracy analysis for detecting ciTBI was performed on a multicenter cohort of children used in the Australasian Pediatric Head Injury Rules Study. RESULTS: The external cohort included 18,913 children; 1691 (8.9%) had CT scan, 160 had ciTBI, and 24 (0.13%) had neurosurgery. Applying IDITBIC and PECARN rules would have missed 11 and 1 ciTBI patients; respectively. All patients with missed injuries were classified as such based on a hospital stay of >2 d. None of these patients died, needed neurosurgery, or required ventilatory support. In children aged <2 y, sensitivity, specificity, positive predictive value and negative predictive value of IDITBIC and PECARN rule were 95.2%, 79.5%, 3.8%, and 99.9% and 100.0%, 59.1%, 2.0%, and 100.0%, respectively. In children ≥2 y, sensitivity, specificity, positive predictive value and negative predictive value of IDITBIC and PECARN rule were 92.4%, 75.3%, 3.1%, and 99.9% and 99.2%, 52.9%, 1.7%, and 100.0%, respectively. CONCLUSIONS: The two decision rules demonstrated high accuracy in identifying ciTBI. As a screening tool, the PECARN rule outperformed IDITBIC. The findings suggest that clinicians should strongly consider directing children with GCS <15 at presentation to CT scan.
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Lesões Encefálicas Traumáticas/diagnóstico , Regras de Decisão Clínica , Adolescente , Algoritmos , Criança , Pré-Escolar , Estudos de Coortes , Traumatismos Craniocerebrais , Humanos , Lactente , Tomografia Computadorizada por Raios XRESUMO
AIM: To characterise the causes, clinical characteristics and short-term outcomes of neonates who presented to paediatric emergency departments with a head injury. METHODS: Secondary analysis of a prospective data set of paediatric head injuries at 10 emergency departments in Australia and New Zealand. Patients without neuroimaging were followed up by telephone call. We extracted epidemiological information, clinical findings and outcomes in neonates (≤28 days). RESULTS: Of 20 137 children with head injuries, 93 (0.5%) occurred in neonates. These were mostly fall-related (75.2%), commonly from a care giver's arms, or due to being accidentally struck by a person/object (20.4%). There were three cases of non-accidental head injuries (3.2%). Most neonates were asymptomatic (67.7%) and many had no findings on examination (47.3%). Most neonates had a Glasgow Coma Scale 15 (89.2%) or 14 (7.5%). A total of 15.1% presented with vomiting and 5.4% were abnormally drowsy. None had experienced a loss of consciousness. The most common findings on examination were scalp haematoma (28.0%) and possible palpable skull fracture (6.5%); 8.6% underwent computed tomography brain scan and 4.3% received an ultrasound. Five of eight computed tomography scan (5.4% of neonates overall) showed traumatic brain injury and two of four (2.2% overall) had traumatic brain injury on ultrasound. Thirty-seven percent were admitted, one patient was intubated and none had neurosurgery or died. CONCLUSIONS: Neonatal head injuries are rare with a mostly benign short-term outcome and are appropriate for observation. However, non-accidental injuries need to be considered.
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Traumatismos Craniocerebrais , Austrália/epidemiologia , Criança , Estudos de Coortes , Traumatismos Craniocerebrais/diagnóstico por imagem , Traumatismos Craniocerebrais/epidemiologia , Serviço Hospitalar de Emergência , Humanos , Recém-Nascido , Nova Zelândia , Estudos ProspectivosRESUMO
AIM: Abusive head trauma (AHT) is associated with high morbidity and mortality. We aimed to describe characteristics of cases where clinicians suspected AHT and confirmed AHT cases and describe how they differed. METHODS: This was a planned secondary analysis of a prospective multicentre cohort study of head injured children aged <18 years across five centres in Australia and New Zealand. We identified cases of suspected AHT when emergency department clinicians raised suspicion on a clinical report form or based on research assistant-assigned epidemiology codes. Cases were categorised as AHT positive, negative and indeterminate after multidisciplinary review. Suspected and confirmed AHT and non-AHT cases were compared using odds ratios with 95% confidence intervals. RESULTS: AHT was suspected in 70 of 13 371 (0.5%) head-injured children. Of these, 23 (32.9%) were categorised AHT positive, 18 (25.7%) AHT indeterminate and 29 (27.1%) AHT negative. Median age was 0.8 years in suspected, 1.4 years in confirmed AHT and 4.1 years in non-AHT cases. Odds ratios (95% confidence interval) for presenting features and outcomes in confirmed AHT versus non-AHT were: loss of consciousness 2.8 (1.2-6.9), scalp haematoma 3.9 (1.7-9.0), seizures 12.0 (4.0-35.5), Glasgow coma scale ≤12 30.3 (11.8-78.0), abnormal neuroimaging 38.3 (16.8-87.5), intensive care admission 53.4 (21.6-132.5) and mortality 105.5 (22.2-500.4). CONCLUSIONS: Emergency department presentations of children with suspected and confirmed AHT had higher rates of loss of consciousness, scalp haematomas, seizures and low Glasgow coma scale. These cases were at increased risk of abnormal computed tomography scans, need for intensive care and death.
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Maus-Tratos Infantis , Traumatismos Craniocerebrais , Adolescente , Austrália/epidemiologia , Criança , Maus-Tratos Infantis/diagnóstico , Estudos de Coortes , Traumatismos Craniocerebrais/diagnóstico , Traumatismos Craniocerebrais/epidemiologia , Traumatismos Craniocerebrais/etiologia , Serviço Hospitalar de Emergência , Humanos , Lactente , Nova Zelândia/epidemiologia , Estudos ProspectivosRESUMO
OBJECTIVE: The validated Predicting Abusive Head Trauma (PredAHT) clinical prediction tool calculates the probability of abusive head trauma (AHT) in children <3 years of age who have sustained intracranial injuries (ICIs) identified on neuroimaging, based on combinations of six clinical features: head/neck bruising, seizures, apnoea, rib fracture, long bone fracture and retinal haemorrhages. PredAHT version 2 enables a probability calculation when information regarding any of the six features is absent. We aimed to externally validate PredAHT-2 in an Australian/New Zealand population. METHODS: This is a secondary analysis of a prospective multicentre study of paediatric head injuries conducted between April 2011 and November 2014. We extracted data on patients with possible AHT at five tertiary paediatric centres and included all children <3 years of age admitted to hospital who had sustained ICI identified on neuroimaging. We assigned cases as positive for AHT, negative for AHT or having indeterminate outcome following multidisciplinary review. The estimated probability of AHT for each case was calculated using PredAHT-2, blinded to outcome. Tool performance measures were calculated, with 95% CIs. RESULTS: Of 87 ICI cases, 27 (31%) were positive for AHT; 45 (52%) were negative for AHT and 15 (17%) had indeterminate outcome. Using a probability cut-off of 50%, excluding indeterminate cases, PredAHT-2 had a sensitivity of 74% (95% CI 54% t o89%) and a specificity of 87% (95% CI 73% to 95%) for AHT. Positive predictive value was 77% (95% CI 56% to 91%), negative predictive value was 85% (95% CI 71% to 94%) and the area under the curve was 0.80 (95% CI 0.68 to 0.92). CONCLUSION: PredAHT-2 demonstrated reasonably high point sensitivity and specificity when externally validated in an Australian/New Zealand population. Performance was similar to that in the original validation study. TRIAL REGISTRATION NUMBER: ACTRN12614000463673.
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Maus-Tratos Infantis/estatística & dados numéricos , Traumatismos Craniocerebrais/diagnóstico , Valor Preditivo dos Testes , Área Sob a Curva , Pré-Escolar , Traumatismos Craniocerebrais/epidemiologia , Feminino , Humanos , Lactente , Masculino , Análise Multivariada , Estudos Prospectivos , Curva ROCRESUMO
OBJECTIVE: The National Emergency X-Radiography Utilisation Study II (NEXUS II) clinical decision rule (CDR) can be used to optimise the use of CT in children with head trauma. We set out to externally validate this CDR in a large cohort. METHODS: We performed a prospective observational study of patients aged <18 years presenting with head trauma of any severity to 10 Australian/New Zealand EDs. In a planned secondary analysis, we assessed the accuracy of the NEXUS II CDR (with 95% CI) to detect clinically important intracranial injury (ICI). We also assessed clinician accuracy without the rule. RESULTS: Of 20 137 total patients, we excluded 28 with suspected penetrating injury. Median age was 4.2 years. CTs were obtained in ED for 1962 (9.8%), of whom 377 (19.2%) had ICI as defined by NEXUS II. 74 (19.6% of ICI) patients underwent neurosurgery.Sensitivity for ICI based on the NEXUS II CDR was 379/383 (99.0 (95% CI 97.3% to 99.7%)) and specificity was 9320/19 726 (47.2% (95% CI 46.5% to 47.9%)) for the total cohort. Sensitivity in the CT-only cohort was similar. Of the 18 022 children without CT in ED, 49.4% had at least one NEXUS II risk criterion. Sensitivity for ICI by the clinicians without the rule was 377/377 (100.0% (95% CI 99.0% to 100.0%)) and specificity was 18 147/19 732 (92.0% (95% CI 91.6% to 92.3%)). CONCLUSIONS: NEXUS II had high sensitivity, similar to the derivation study. However, approximately half of unimaged patients were positive for NEXUS II risk criteria; this may result in an increased CT rate in a setting with high clinician accuracy.
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Técnicas de Apoio para a Decisão , Adolescente , Austrália , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Nova Zelândia , Pediatria/métodos , Pediatria/normas , Estudos Prospectivos , Radiografia/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Clinical decision rules can help to determine the need for CT imaging in children with head injuries. We aimed to validate three clinical decision rules (PECARN, CATCH, and CHALICE) in a large sample of children. METHODS: In this prospective observational study, we included children and adolescents (aged <18 years) with head injuries of any severity who presented to the emergency departments of ten Australian and New Zealand hospitals. We assessed the diagnostic accuracy of PECARN (stratified into children aged <2 years and ≥2 years), CATCH, and CHALICE in predicting each rule-specific outcome measure (clinically important traumatic brain injury [TBI], need for neurological intervention, and clinically significant intracranial injury, respectively). For each calculation we used rule-specific predictor variables in populations that satisfied inclusion and exclusion criteria for each rule (validation cohort). In a secondary analysis, we compiled a comparison cohort of patients with mild head injuries (Glasgow Coma Scale score 13-15) and calculated accuracy using rule-specific predictor variables for the standardised outcome of clinically important TBI. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614000463673. FINDINGS: Between April 11, 2011, and Nov 30, 2014, we analysed 20â137 children and adolescents attending with head injuries. CTs were obtained for 2106 (10%) patients, 4544 (23%) were admitted, 83 (<1%) underwent neurosurgery, and 15 (<1%) died. PECARN was applicable for 4011 (75%) of 5374 patients younger than 2 years and 11â152 (76%) of 14â763 patients aged 2 years and older. CATCH was applicable for 4957 (25%) patients and CHALICE for 20â029 (99%). The highest point validation sensitivities were shown for PECARN in children younger than 2 years (100·0%, 95% CI 90·7-100·0; 38 patients identified of 38 with outcome [38/38]) and PECARN in children 2 years and older (99·0%, 94·4-100·0; 97/98), followed by CATCH (high-risk predictors only; 95·2%; 76·2-99·9; 20/21; medium-risk and high-risk predictors 88·7%; 82·2-93·4; 125/141) and CHALICE (92·3%, 89·2-94·7; 370/401). In the comparison cohort of 18â913 patients with mild injuries, sensitivities for clinically important TBI were similar. Negative predictive values in both analyses were higher than 99% for all rules. INTERPRETATION: The sensitivities of three clinical decision rules for head injuries in children were high when used as designed. The findings are an important starting point for clinicians considering the introduction of one of the rules. FUNDING: National Health and Medical Research Council, Emergency Medicine Foundation, Perpetual Philanthropic Services, WA Health Targeted Research Funds, Townsville Hospital Private Practice Fund, Auckland Medical Research Foundation, Aâ+âTrust.
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Traumatismos Craniocerebrais/diagnóstico , Técnicas de Apoio para a Decisão , Triagem/métodos , Adolescente , Fatores Etários , Austrália , Criança , Pré-Escolar , Tomada de Decisão Clínica/métodos , Traumatismos Craniocerebrais/etiologia , Serviço Hospitalar de Emergência , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Masculino , Nova Zelândia , Estudos Prospectivos , Tomografia Computadorizada por Raios XRESUMO
STUDY OBJECTIVE: Three clinical decision rules for head injuries in children (Pediatric Emergency Care Applied Research Network [PECARN], Canadian Assessment of Tomography for Childhood Head Injury [CATCH], and Children's Head Injury Algorithm for the Prediction of Important Clinical Events [CHALICE]) have been shown to have high performance accuracy. The utility of any of these in a particular setting depends on preexisting clinician accuracy. We therefore assess the accuracy of clinician practice in detecting clinically important traumatic brain injury. METHODS: This was a planned secondary analysis of a prospective observational study of children younger than 18 years with head injuries at 10 Australian and New Zealand centers. In a cohort of children with mild head injuries (Glasgow Coma Scale score 13 to 15, presenting in <24 hours) we assessed physician accuracy (computed tomography [CT] obtained in emergency departments [EDs]) for the standardized outcome of clinically important traumatic brain injury and compared this with the accuracy of PECARN, CATCH, and CHALICE. RESULTS: Of 20,137 children, 18,913 had a mild head injury. Of these patients, 1,579 (8.3%) received a CT scan during the ED visit, 160 (0.8%) had clinically important traumatic brain injury, and 24 (0.1%) underwent neurosurgery. Clinician identification of clinically important traumatic brain injury based on CT performed had a sensitivity of 158 of 160, or 98.8% (95% confidence interval [CI] 95.6% to 99.8%) and a specificity of 17,332 of 18,753, or 92.4% (95% CI 92.0% to 92.8%). Sensitivity of PECARN for children younger than 2 years was 42 of 42 (100.0%; 95% CI 91.6% to 100.0%), and for those 2 years and older, it was 117 of 118 (99.2%; 95% CI 95.4% to 100.0%); for CATCH (high/medium risk), it was 147 of 160 (91.9%; 95% CI 86.5% to 95.6%); and for CHALICE, 148 of 160 (92.5%; 95% CI 87.3% to 96.1%). CONCLUSION: In a setting with high clinician accuracy and a low CT rate, PECARN, CATCH, or CHALICE clinical decision rules have limited potential to increase the accuracy of detecting clinically important traumatic brain injury and may increase the CT rate.
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Lesões Encefálicas Traumáticas/diagnóstico , Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Serviço Hospitalar de Emergência , Austrália , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Uso Excessivo dos Serviços de Saúde , Nova Zelândia , Estudos Prospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To prospectively compare the proportion of traumatic brain injuries (TBIs) that would be classified as mild by applying different published definitions of mild TBI to a large prospectively collected dataset, and to examine the variability in the proportions included by various definitions. DESIGN: Prospective observational study. SETTING: Hospital emergency departments. PARTICIPANTS: Children (N=11,907) aged 3 to 16 years (mean age, 8.2±3.9y). Of the participants, 3868 (32.5%) were girls, and 7374 (61.9%) of the TBIs were the result of a fall. Median Glasgow Coma Scale score was 15. MAIN OUTCOME MEASURES: We applied 17 different definitions of mild TBI, identified through a published systematic review, to children aged 3 to 16 years. Adjustments and clarifications were made to some definitions. The number and percentage identified for each definition is presented. RESULTS: Adjustments had to be made to the 17 definitions to apply to the dataset: none in 7, minor to substantial in 10. The percentage classified as mild TBI across definitions varied from 7.1% (n=841) to 98.7% (n=11,756) and varied by age group. CONCLUSIONS: When applying the 17 definitions of mild TBI to a large prospective multicenter dataset of TBI, there was wide variability in the number of cases classified. Clinicians and researchers need to be aware of this variability when examining literature concerning children with mild TBI.
Assuntos
Concussão Encefálica/classificação , Serviço Hospitalar de Emergência/estatística & dados numéricos , Escala de Coma de Glasgow/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Conjuntos de Dados como Assunto , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
AIM: Penetrating head injuries (pHIs) are associated with high morbidity and mortality. Data on pHIs in children outside North America are limited. We describe the mechanism of injuries, neuroimaging findings, neurosurgery and mortality for pHIs in Australia and New Zealand. METHODS: This was a planned secondary analysis of a prospective observational study of children <18 years who presented with a head injury of any severity at any of 10 predominantly paediatric Australian/New Zealand emergency departments (EDs) between 2011 and 2014. We reviewed all cases where clinicians had clinically suspected pHI as well as all cases of clinically important traumatic brain injuries (death, neurosurgery, intubation >24 h, admission >2 days and abnormal computed tomography). RESULTS: Of 20 137 evaluable patients with a head injury, 21 (0.1%) were identified to have sustained a pHI. All injuries were of non-intentional nature, and there were no gunshot wounds. The mechanisms of injuries varied from falls, animal attack, motor vehicle crashes and impact with objects. Mean Glasgow Coma Scale on ED arrival was 10; 10 (48%) had a history of loss of consciousness, and 7 (33%) children were intubated pre-hospital or in the ED. Fourteen (67%) children underwent neurosurgery, two (10%) craniofacial surgery, and five (24%) were treated conservatively; four (19%) patients died. CONCLUSIONS: Paediatric pHIs are very rare in EDs in Australia and New Zealand but are associated with high morbidity and mortality. The absence of firearm-related injuries compared to North America is striking and may reflect Australian and New Zealand firearm regulations.
Assuntos
Causas de Morte , Traumatismos Cranianos Penetrantes/diagnóstico por imagem , Traumatismos Cranianos Penetrantes/epidemiologia , Procedimentos Neurocirúrgicos/métodos , Austrália , Pré-Escolar , Estudos de Coortes , Tratamento Conservador , Bases de Dados Factuais , Serviço Hospitalar de Emergência , Escala de Coma de Glasgow , Traumatismos Cranianos Penetrantes/terapia , Mortalidade Hospitalar/tendências , Humanos , Escala de Gravidade do Ferimento , Neuroimagem/métodos , Procedimentos Neurocirúrgicos/mortalidade , Nova Zelândia , Estudos Prospectivos , Medição de Risco , Análise de SobrevidaRESUMO
Mucopolysaccharidosis Type II (MPS II) or Hunter Syndrome is a rare X-linked condition, due to a defect in a lysosomal enzyme involved in the breakdown of glycosaminoglycans. It is a progressive condition with worsening over time; however, symptom severity and progression rates vary. Normal intellectual function has been reported in males with mild MPS II but few studies are available that provide comprehensive cognitive profiles. Enzyme replacement therapy (ERT) can stabilize physical symptoms and has become standard treatment. Whether ERT can influence cognition is currently unknown. Considering this, we conducted cognitive, fine motor, and behavioural assessments with three males (7;6-12;1 years) with mild MPS II before and after ERT. Generally, cognition, fine motor skills, and behaviour were in the normal range; however, specific deficits in attention and executive function were identified. Following ERT, some memory improvements were seen. Executive deficits remained, and processing speed declined over time.
Assuntos
Atenção , Cognição , Função Executiva , Mucopolissacaridose II/psicologia , Criança , Progressão da Doença , Terapia de Reposição de Enzimas , Humanos , Iduronato Sulfatase/metabolismo , Lactente , Masculino , Memória , Mucopolissacaridose II/enzimologia , Mucopolissacaridose II/terapiaRESUMO
BACKGROUND: Recovery from concussion sustained in childhood and adolescence is poorly understood. We explored patterns of recovery for neurocognition and postconcussive symptoms following concussion in children and adolescents. METHODS: Using a prospective, longitudinal design, we collected baseline data on 728 children and adolescents aged 10-17â years. 10 participants sustained a concussive injury (n=10) in the 12â months following baseline testing and they were reviewed at day 5, 10 and 30 postconcussion. Assessments included the CogSport for Kids computerised test battery to evaluate neurocognitive function and self-report, and parent measures of postconcussive symptoms. At day 30, parents also completed measures rating their child's quality of life and executive functions. RESULTS: Children and adolescents displayed a gradual reduction in postconcussive symptoms over the 30â days following injury. At day 5, 87% of participants were reporting physical and cognitive symptoms, with a generalised reduction in all symptoms by day 10 (40% of participants). On the computerised measure, reaction time was slower after concussion, but returned to baseline levels by day 30. At day 30, 10% of participants demonstrated ongoing postconcussive symptoms. Number of previous concussions was related to speed of symptom resolution. CONCLUSIONS: At 5â days postconcussion, the majority of children and adolescents experienced debilitating postconcussive symptoms. However, by 30â days postinjury, 90% demonstrated recovery to normal for both neurocognition and postconcussive symptoms.