AKT Hyperphosphorylation and T Cell Exhaustion in Down Syndrome.

Down syndrome (DS) is associated with increased susceptibility to infections, auto-immunity, immunodeficiency and haematological malignancies. The exact underlying immunological pathophysiology is still unclear. The immunophenotype and clinical characteristics of DS resemble those of Activated PI3K Delta Syndrome (APDS), in which the PI3K/AKT/mTOR pathway is overactivated. We hypothesized that T cell exhaustion and the hyperactivation of the AKT signalling pathway is also present in immune cells of children with DS. In this observational non-interventional cohort study we collected blood samples of children with DS (n=22) and healthy age-matched controls (n=21) for flowcytometric immunophenotyping, phospho-flow AKT analysis and exhaustion analysis of T cells. The median age was 5 years (range 1-12y). Total T and NK cells were similar for both groups, but absolute values and transitional B cells, naive memory B cells and naive CD4+ and CD8+ T cells were lower in DS. pAKT and AKT were increased for CD3+ and CD4+ T cells and CD20+ B cells in children with DS. Total AKT was also increased in CD8+ T cells. Children with DS showed increased expression of inhibitory markers Programmed cell dealth-1 (PD-1), CD244 and CD160 on CD8+ T cells and increased PD-1 and CD244+ expression on CD4+ T cells, suggesting T cell exhaustion. Children with DS show increased pAKT and AKT and increased T cell exhaustion, which might contribute to their increased susceptibility to infections, auto immunity and haematological malignancies.

Accuracy of a screening instrument to identify potential child abuse in emergency departments.

Although screening for child abuse at emergency departments (EDs) increases the detection rate of potential child abuse, an accurate instrument is lacking. This study was designed to measure the accuracy of a screening instrument for detection of potential child abuse used in EDs. In a prospective cohort study at three Dutch EDs, a 6-item screening instrument for child abuse, Escape, was completed for each child visiting the ED. The data from the completed Escape instrument was used to calculate sensitivity, specificity, and the positive/negative predictive value per item. The clinical notes and conclusions of the screen instruments of all potentially abused children reported to the hospitals' Child Abuse Teams were collected and reviewed by an expert panel. A logistic regression model was used to evaluate the predictors of potential abuse. Completed Escape instruments were available for 18,275 ED visits. Forty-four of the 420 children with a positive screening result, and 11 of the 17,855 children with a negative result were identified as potentially abused. Sensitivity of the Escape instrument was 0.80 and specificity was 0.98. Univariate logistic regression showed that potentially abused children were significantly more likely to have had an aberrant answer to at least one of the items, OR=189.8, 95% CI [97.3, 370.4]. Most of the children at high risk for child abuse were detected through screening. The Escape instrument is a useful tool for ED staff to support the identification of those at high risk for child abuse.

Effects of systematic screening and detection of child abuse in emergency departments.

OBJECTIVE: Although systematic screening for child abuse of children presenting at emergency departments might increase the detection rate, studies to support this are scarce. This study investigates whether introducing screening, and training of emergency department nurses, increases the detection rate of child abuse. METHODS: In an intervention cohort study, children aged 0 to 18 years visiting the emergency departments of 7 hospitals between February 2008 and December 2009 were enrolled. We developed a screening checklist for child abuse (the "Escape Form") and training sessions for nurses; these were implemented by using an interrupted time-series design. Cases of suspected child abuse were determined by an expert panel using predefined criteria. The effect of the interventions on the screening rate for child abuse was calculated by interrupted time-series analyses and by the odds ratios for detection of child abuse in screened children. RESULTS: A total of 104028 children aged 18 years or younger were included. The screening rate increased from 20% in February 2008 to 67% in December 2009. Significant trend changes were observed after training the nurses and after the legal requirement of screening by the Dutch Health Care Inspectorate in 2009. The detection rate in children screened for child abuse was 5 times higher than that in children not screened (0.5% vs 0.1%, P < .001). CONCLUSIONS: These results indicate that systematic screening for child abuse in emergency departments is effective in increasing the detection of suspected child abuse. Both a legal requirement and staff training are recommended to significantly increase the extent of screening.

Self-referral and serious illness in children with fever.

OBJECTIVE: The goal of this study was to evaluate parents' capability to assess their febrile child's severity of illness and decision to present to the emergency department. We compared children referred by a general practitioner (GP) with those self-referred on the basis of illness-severity markers. METHODS: This was a cross-sectional observational study conducted at the emergency departments of a university and a teaching hospital. GP-referred or self-referred children with fever (aged <16 years) who presented to the emergency department (2006-2008) were included. Markers for severity of illness were urgency according to the Manchester Triage System, diagnostic interventions, therapeutic interventions, and follow-up. Associations between markers and referral type were assessed by using logistic regression analysis. Subgroup analyses were performed for patients with the most common presenting problems that accompanied the fever (ie, dyspnea, gastrointestinal complaints, neurologic symptoms, fever without specific symptoms). RESULTS: Thirty-eight percent of 4609 children were referred by their GP and 62% were self-referred. GP-referred children were classified as high urgency (immediate/very urgent categories) in 46% of the cases and self-referrals in 45%. Forty-three percent of GP referrals versus 27% of self-referrals needed extensive diagnostic intervention, intravenous medication/aerosol treatment, hospitalization, or a combination of these (odds ratio: 2.0 [95% confidence interval: 1.75-2.27]). In all subgroups, high urgency was not associated with referral type. GP-referred and self-referred children with dyspnea had similar frequencies of illness-severity markers. CONCLUSIONS: Although febrile self-referred children were less severely ill than GP-referred children, many parents properly judged and acted on the severity of their child's illness. To avoid delayed or missed diagnoses, recommendations regarding interventions that would discourage self-referral to the emergency department should be reconsidered.

The Manchester triage system: improvements for paediatric emergency care.

OBJECTIVE: To improve the Manchester Triage System (MTS) in paediatric emergency care. METHODS: The authors performed a prospective observational study at the emergency departments of a university and teaching hospital in The Netherlands and included children attending in 2007 and 2008. The authors developed and implemented specific age-dependent modifications for the MTS, based on patient groups where the system's performance was low. Nurses applied the modified system in 11,481 (84%) patients. The reference standard for urgency defined five levels based on a combination of vital signs at presentation, potentially life-threatening conditions, diagnostic resources, therapeutic interventions and follow-up. The reference standard for urgency was previously defined and available in 11,260/11,481 (96%) patients. RESULTS: Compared with the original MTS specificity improved from 79% (95% CI 79% to 80%) to 87% (95% CI 86% to 87%) while sensitivity remained similar ((63%, 95% CI 59% to 66%) vs (64%, 95% CI 60% to 68%)). The diagnostic OR increased (4.1 vs 11). CONCLUSIONS: Modifications of the MTS for paediatric emergency care resulted in an improved specificity while sensitivity remained unchanged. Further research should focus on the improvement of sensitivity.

Referral of nonurgent children from the emergency department to general practice: compliance and cost savings.

OBJECTIVE: To evaluate compliance and costs of referral of nonurgent children, who present at the emergency department, to the general practitioner cooperative (GPC). MATERIALS AND METHODS: In a prospective observational before-after study, during 6 months in 2008, the triage nurse discussed referral to the GPC with parents, when self-referred children with a nontraumatic problem, aged 3 months-16 years were triaged as nonurgent (levels 4 and 5) according to the Manchester Triage System. A telephone follow-up was performed 2-4 days after referral. Real costs were calculated for emergency department consultation (preintervention period) and GPC referral (postintervention period). Compliance of referral was studied for 4 days a week. RESULTS: One hundred and forty patients were referred to the GPC, of which 101 out of 140 patients (72%) attended a follow-up. After discharge seven patients (7%) had an unscheduled revisit. No patients were subsequently hospitalized. In total 275 patients were included to study compliance, with 28 (10%) reported missing. Ninety-five out of 247 (38%) patients were referred to the general practitioner and 46 out of 247 parents (19%) refused referral. For 106 out of 247 patients (43%) referral was not initiated by the nurse mainly because of comorbidity. Mean costs per patient were €106 for the preintervention period and €101 for the postintervention period. CONCLUSION: Compliance of referring low urgent patients is low, mainly because it was difficult for nursing staff to refer. Total overall cost benefit is minimal. Cost savings may be achieved in different settings, where general practitioner services are colocated and where large numbers can be referred.

Safety of the Manchester Triage System to identify less urgent patients in paediatric emergence care: a prospective observational study.

OBJECTIVE: To assess hospitalisation rate as a proxy for the ability of the Manchester Triage System (MTS) to identify less urgent paediatric patients. We also evaluated general practitioner (GP) services to determine if they met patients' needs compared to emergency department care. METHODS: Self-referred children triaged as less urgent by the MTS in two emergency departments in the Netherlands were included in a prospective observational study. Therapeutic interventions during emergency department consultation, hospitalisation after consultation and determinants for hospitalisation were assessed using logistic regression analysis. RESULTS: During emergency department consultation, extensive therapeutic interventions were performed more often in patients with extremity problems (n=175, 19%) and dyspnoea (n=30, 15%). 191 (3.5%) of 5425 patients were hospitalised. Age and presenting problem remained statistically significant in multivariable logistic analysis, predicting hospitalisation with ORs of 3.0 (95% CI 2.2 to 4.1) for age <1 year, 2.5 (1.5 to 4.1) for dyspnoea, 3.5 (2.5 to 4.9) for gastrointestinal problems and 2.8 (1.1 to 7.2) for patients with fever without identified source compared to all other patients. 3975 (76%) of 5234 patients were contacted for follow-up after discharge. Six (0.15%) patients were hospitalised after emergency department discharge. CONCLUSION: In the MTS less urgent categories, overall hospitalisation is low, although children <1 year of age or with dyspnoea, gastrointestinal problems or fever without identified source have an increased risk for hospitalisation. Except for these patient groups, the MTS identifies less urgent patients safely. It may not be optimal for GP services to treat patients with extremity problems.

Detection of child abuse in emergency departments: a multi-centre study.

OBJECTIVE: This study examines the detection rates of suspected child abuse in the emergency departments of seven Dutch hospitals complying and not complying with screening guidelines for child abuse. DESIGN: Data on demographics, diagnosis and suspected child abuse were collected for all children aged ≤18 years who visited the emergency departments over a 6-month period. The completion of a checklist of warning signs of child abuse in at least 10% of the emergency department visits was considered to be compliance with screening guidelines. RESULTS: A total of 24 472 visits were analysed, 54% of which took place in an emergency department complying with screening guidelines. Child abuse was suspected in 52 children (0.2%). In 40 (77%) of these 52 cases, a checklist of warning signs had been completed compared with a completion rate of 19% in the total sample. In hospitals complying with screening guidelines for child abuse, the detection rate was higher (0.3%) than in those not complying (0.1%, p<0.001). CONCLUSION: During a 6-month period, emergency department staff suspected child abuse in 0.2% of all children visiting the emergency department of seven Dutch hospitals. The numbers of suspected abuse cases detected were low, but an increase is likely if uniform screening guidelines are widely implemented.

Manchester triage system in paediatric emergency care: prospective observational study.

OBJECTIVE: To validate use of the Manchester triage system in paediatric emergency care. DESIGN: Prospective observational study. SETTING: Emergency departments of a university hospital and a teaching hospital in the Netherlands, 2006-7. PARTICIPANTS: 17,600 children (aged <16) visiting an emergency department over 13 months (university hospital) and seven months (teaching hospital). INTERVENTION: Nurses triaged 16,735/17,600 patients (95%) using a computerised Manchester triage system, which calculated urgency levels from the selection of discriminators embedded in flowcharts for presenting problems. Nurses over-ruled the urgency level in 1714 (10%) children, who were excluded from analysis. Complete data for the reference standard were unavailable in 1467 (9%) children leaving 13,554 patients for analysis. MAIN OUTCOME MEASURES: Urgency according to the Manchester triage system compared with a predefined and independently assessed reference standard for five urgency levels. This reference standard was based on a combination of vital signs at presentation, potentially life threatening conditions, diagnostic resources, therapeutic interventions, and follow-up. Sensitivity, specificity, and likelihood ratios for high urgency (immediate and very urgent) and 95% confidence intervals for subgroups based on age, use of flowcharts, and discriminators. RESULTS: The Manchester urgency level agreed with the reference standard in 4582 of 13,554 (34%) children; 7311 (54%) were over-triaged and 1661 (12%) under-triaged. The likelihood ratio was 3.0 (95% confidence interval 2.8 to 3.2) for high urgency and 0.5 (0.4 to 0.5) for low urgency; though the likelihood ratios were lower for those presenting with a medical problem (2.3 (2.2 to 2.5) v 12.0 (7.8 to 18.0) for trauma) and in younger children (2.4 (1.9 to 2.9) at 0-2 months [corrected] v 5.4 (4.5 to 6.5) at 8-16 years). CONCLUSIONS: The Manchester triage system has moderate validity in paediatric emergency care. It errs on the safe side, with much more over-triage than under-triage compared with an independent reference standard for urgency. Triage of patients with a medical problem or in younger children is particularly difficult.