Characteristics of revisits of children at risk for serious infections in pediatric emergency care

In this study, we aimed to identify characteristics of (unscheduled) revisits and its optimal time frame after Emergency Department (ED) discharge. Children with fever, dyspnea, or vomiting/diarrhea (1 month–16 years) who attended the ED of Erasmus MC-Sophia, Rotterdam (2010–2013), the Netherlands, were prospectively included. Three days after ED discharge, we applied standardized telephonic questionnaires on disease course and revisits. Multivariable logistic regression analysis was used to identify independent characteristics of revisits. Young age, parental concern, and alarming signs and symptoms (chest wall retractions, ill appearance, clinical signs of dehydration, and tachypnea) were associated with revisits (n = 527) in children at risk for serious infections discharged from the ED (n = 1765). Children revisited the ED within a median of 2 days (IQR 1.0–3.0), but this was proven to be shorter in children with vomiting/diarrhea (1.0 day (IQR 1.0–2.0)) compared to children with fever or dyspnea (2.0 (IQR 1.0–3.0)). Conclusion: Young age, parental concern, and alarming signs and symptoms (chest wall retractions, ill appearance, clinical signs of dehydration, and tachypnea) were associated with emergency health care revisits in children with fever, dyspnea, and vomiting/diarrhea. These characteristics could help to define targeted review of children during post-discharge period. We observed a disease specific and differential timing of control revisits after ED discharge.(Table presented.

Tools for 'safety netting' in common paediatric illnesses: A systematic review in emergency care

Context Follow-up strategies after emergency department (ED) discharge, alias safety netting, is often based on the gut feeling of the attending physician. Objective To systematically identify evaluated safetynetting strategies after ED discharge and to describe determinants of paediatric ED revisits. Data sources MEDLINE, Embase, CINAHL, Cochrane central, OvidSP, Web of Science, Google Scholar, PubMed. Study selection Studies of any design reporting on safety netting/follow-up after ED discharge and/or determinants of ED revisits for the total paediatric population or specifically for children with fever, dyspnoea and/or gastroenteritis. Outcomes included complicated course of disease after initial ED visit (eg, revisits, hospitalisation). Data extraction Two reviewers independently assessed studies for eligibility and study quality. As meta-analysis was not possible due to heterogeneity of studies, we performed a narrative synthesis of study results. A best-evidence synthesis was used to identify the level of evidence. Results We summarised 58 studies, 36% (21/58) were assessed as having low risk of bias. Limited evidence was observed for different strategies of safety netting, with educational interventions being mostly studied. Young children, a relevant medical history, infectious/ respiratory symptoms or seizures and progression/ persistence of symptoms were strongly associated with ED revisits. Gender, emergency crowding, physicians' characteristics and diagnostic tests and/or therapeutic interventions at the index visit were not associated with revisits. Conclusions Within the heterogeneous available evidence, we identified a set of strong determinants of revisits that identify high-risk groups in need for safety netting in paediatric emergency care being related to age and clinical symptoms. Gaps remain on intervention studies concerning specific application of a uniform safety-netting strategy and its included time frame

Clinicians’ overestimation of febrile child risk assessment

We aimed to estimate clinicians’ based risk thresholds at which febrile children would be managed as serious bacterial infections (SBI) to determine influencing characteristics and to compare thresholds with prediction model (Feverkidstool) risk estimates. Twenty-one video vignettes of febrile children visiting the emergency department (ED) were assessed by 42 (40.4 %) international paediatricians/paediatric emergency clinicians. Questions were related to clinical risk scores of the child having SBI and SBI management decisions on visual analogue scales. Feverkidstool risk scores were based on clinical signs/symptoms and C-reactive protein. Amongst vignettes assigned to SBI management, the median risk was 60 % (interquartile range (IQR) 30.0–80.5) and 16.0 % (IQR 5.0–32.0) when vignettes were not managed as SBI. Ill appearance and aberrant circulatory signs were the most influencing factors, as age and duration of fever were the least influencing factors on SBI management decisions. Feverkidstool risk scores varied from 13 % (IQR 7.7–28.1) for SBI management to 7.3 % (IQR 5.7–16.3) for no SBI management. Conclusion: Clinicians assigned high risk scores to children who they would have managed as SBI, mostly influenced by ill appearance and aberrant circulation. In contrast to SBI risk assessment of the Feverkidstool, clinicians’ appeared to apply a more stepwise assessment of the risk of presence/absence of SBI at different steps in the diagnostic and therapeutic process. Uniform risk thresholds at which one should start SBI management in febrile children remains unclear; risk thresholds at which we refrained from SBI management were more consistent

A Population Pharmacokinetic Modelling Approach to Unravel the Complex Pharmacokinetics of Vincristine in Children

Background Vincristine, a chemotherapeutic agent that extensively binds to beta-tubulin, is commonly dosed at 1.4-2.0 mg/m(2) capped at 2 mg. For infants, doses vary from 0.025-0.05 mg/kg or 50-80% of the mg/m(2) dose. However, evidence for lower doses in infants compared to older children is lacking. This study was conducted to unravel the complex pharmacokinetics of vincristine, including the effects of age, to assist optimal dosing in this population. Methods 206 patients (0.04-33.9 years; 25 patients < 1 years), receiving vincristine, with 1297 plasma concentrations were included. Semi-mechanistic population pharmacokinetic analyses were performed using non-linear mixed effects modelling. Results A three-compartment model, with one saturable compartment resembling saturable binding to beta-tubulin and thus, saturable distribution, best described vincristine pharmacokinetics. Body weight and age were covariates significantly influencing the maximal binding capacity to beta-tubulin, which increased with increasing body weight and decreased with increasing age. Vincristine clearance (CL) was estimated as 30.6 L/h (95% confidence interval (CI) 27.6-33.0), intercompartmental CL (Q) as 63.2 L/h (95%CI 57.2-70.1), volume of distribution of the central compartment as 5.39 L (95%CI 4.23-6.46) and of the peripheral compartment as 400 L (95%CI 357-463) (all parameters correspond to a patient of 70 kg). The maximal binding capacity was 0.525 mg (95%CI 0.479-0.602) (for an 18 year old patient of 70 kg), with a high association rate constant, fixed at 1300 /h and a dissociation constant of 11.5 /h. Interpretation A decrease of vincristine beta-tubulin binding capacity with increasing age suggests that young children tolerate higher doses of vincristine

Ophthalmological Findings in Youths with a Newly Diagnosed Brain Tumor

Importance: Visual impairment is an irreversible adverse effect in individuals who experienced a childhood brain tumor. Ophthalmological evaluation at diagnosis enables early detection of vision loss, decision-making about treatment, and when applicable, the timely use of visual interventions. However, awareness of visual impairment in clinical practice is suboptimal, and adherence to ophthalmological evaluation needs to be improved. Objective: To assess the prevalence and types of abnormal ophthalmological findings in youths with a newly diagnosed brain tumor. Design, Setting, and Participants: In this nationwide, prospective cohort study, youths aged 0 to 18 years with a newly diagnosed brain tumor between May 15, 2019, and August 11, 2021, were consecutively enrolled in 4 hospitals in the Netherlands, including the dedicated tertiary referral center for pediatric oncology care. Exposures: A standardized and comprehensive ophthalmological examination, including orthoptic evaluation, visual acuity testing, visual field examination, and ophthalmoscopy, was performed within 4 weeks from brain tumor diagnosis. Main Outcomes and Measures: The main outcomes were prevalence and types of visual symptoms and abnormal ophthalmological findings at brain tumor diagnosis. Results: Of 170 youths included in the study (96 [56.5%] male; median age, 8.3 years [range, 0.2-17.8 years]), 82 (48.2%) had infratentorial tumors; 53 (31.2%), supratentorial midline tumors; and 35 (20.6%), cerebral hemisphere tumors. A total of 161 patients (94.7%) underwent orthoptic evaluation (67 [41.6%] preoperatively; 94 [58.4%] postoperatively); 152 (89.4%), visual acuity testing (63 [41.4%] preoperatively; 89 [58.6%] postoperatively); 121 (71.2%), visual field examination (49 [40.4%] preoperatively; 72 [59.6%] postoperatively); and 164 (96.5%), ophthalmoscopy (82 [50.0%] preoperatively; 82 [50.0%] postoperatively). Overall, 101 youths (59.4%) presented with visual symptoms at diagnosis. Abnormal findings were found in 134 patients (78.8%) during ophthalmological examination. The most common abnormal findings were papilledema in 86 of 164 patients (52.4%) who underwent ophthalmoscopy, gaze deficits in 54 of 161 (33.5%) who underwent orthoptic evaluation, visual field defects in 32 of 114 (28.1%) with reliable visual field examination, nystagmus in 40 (24.8%) and strabismus in 32 (19.9%) of 161 who underwent orthoptic evaluation, and decreased visual acuity in 13 of 152 (8.6%) with reliable visual acuity testing. Forty-five of 69 youths (65.2%) without visual symptoms at diagnosis had ophthalmological abnormalities on examination. Conclusions and Relevance: The results of this study suggest that there is a high prevalence of abnormal ophthalmological findings in youths at brain tumor diagnosis regardless of the presence of visual symptoms. These findings support the need of standardized ophthalmological examination and the awareness of ophthalmologists and referring oncologists, neurologists, and neurosurgeons for ophthalmological abnormalities in this patient group

Ophthalmological Findings in Youths with a Newly Diagnosed Brain Tumor

Importance: Visual impairment is an irreversible adverse effect in individuals who experienced a childhood brain tumor. Ophthalmological evaluation at diagnosis enables early detection of vision loss, decision-making about treatment, and when applicable, the timely use of visual interventions. However, awareness of visual impairment in clinical practice is suboptimal, and adherence to ophthalmological evaluation needs to be improved. Objective: To assess the prevalence and types of abnormal ophthalmological findings in youths with a newly diagnosed brain tumor. Design, Setting, and Participants: In this nationwide, prospective cohort study, youths aged 0 to 18 years with a newly diagnosed brain tumor between May 15, 2019, and August 11, 2021, were consecutively enrolled in 4 hospitals in the Netherlands, including the dedicated tertiary referral center for pediatric oncology care. Exposures: A standardized and comprehensive ophthalmological examination, including orthoptic evaluation, visual acuity testing, visual field examination, and ophthalmoscopy, was performed within 4 weeks from brain tumor diagnosis. Main Outcomes and Measures: The main outcomes were prevalence and types of visual symptoms and abnormal ophthalmological findings at brain tumor diagnosis. Results: Of 170 youths included in the study (96 [56.5%] male; median age, 8.3 years [range, 0.2-17.8 years]), 82 (48.2%) had infratentorial tumors; 53 (31.2%), supratentorial midline tumors; and 35 (20.6%), cerebral hemisphere tumors. A total of 161 patients (94.7%) underwent orthoptic evaluation (67 [41.6%] preoperatively; 94 [58.4%] postoperatively); 152 (89.4%), visual acuity testing (63 [41.4%] preoperatively; 89 [58.6%] postoperatively); 121 (71.2%), visual field examination (49 [40.4%] preoperatively; 72 [59.6%] postoperatively); and 164 (96.5%), ophthalmoscopy (82 [50.0%] preoperatively; 82 [50.0%] postoperatively). Overall, 101 youths (59.4%) presented with visual symptoms at diagnosis. Abnormal findings were found in 134 patients (78.8%) during ophthalmological examination. The most common abnormal findings were papilledema in 86 of 164 patients (52.4%) who underwent ophthalmoscopy, gaze deficits in 54 of 161 (33.5%) who underwent orthoptic evaluation, visual field defects in 32 of 114 (28.1%) with reliable visual field examination, nystagmus in 40 (24.8%) and strabismus in 32 (19.9%) of 161 who underwent orthoptic evaluation, and decreased visual acuity in 13 of 152 (8.6%) with reliable visual acuity testing. Forty-five of 69 youths (65.2%) without visual symptoms at diagnosis had ophthalmological abnormalities on examination. Conclusions and Relevance: The results of this study suggest that there is a high prevalence of abnormal ophthalmological findings in youths at brain tumor diagnosis regardless of the presence of visual symptoms. These findings support the need of standardized ophthalmological examination and the awareness of ophthalmologists and referring oncologists, neurologists, and neurosurgeons for ophthalmological abnormalities in this patient group

Assessment of Cancer Predisposition Syndromes in a National Cohort of Children With a Neoplasm

Importance: To improve diagnostics of cancer predisposition syndromes (CPSs) in children with cancer, it is essential to evaluate the effect of CPS gene sequencing among all children with cancer and compare it with genetic testing based on clinical selection. However, a reliable comparison is difficult because recent reports on a phenotype-first approach in large, unselected childhood cancer cohorts are lacking. Objective: To describe a national children's cancer center's experience in diagnosing CPSs before introducing routine next-generation sequencing. Design, Setting, and Participants: This retrospective cohort study was conducted at the National Retinoblastoma Treatment Center (Amsterdam, the Netherlands) and the Princess Máxima Center for Pediatric Oncology (Utrecht, Netherlands) and included Dutch pediatric patients with a new diagnosis of neoplasm between June 1, 2018, and December 31, 2019. Follow-up was at least 18 months after neoplasm diagnosis. Data analysis was conducted from July 2021 to February 2022. Exposures: As part of routine diagnostics, pediatric oncologists and ophthalmologists checked for characteristics of CPSs and selected children for referral to clinical geneticists and genetic testing. Main Outcomes and Measures: Detected cancer predisposition syndromes. Results: A total of 824 patients (median [range] age at diagnosis 7.5 [0-18.9] years; 361 girls [44%]) were assessed, including 335 children with a hematological neoplasm (41%) and 489 (59%) with a solid tumor. In 71 of 824 children (8.6%), a CPS was identified, of which most (96%) were identified by a phenotype-driven approach. Down syndrome and neurofibromatosis type 1 were the most common CPSs diagnosed. In 42 of 71 patients (59%), a CPS was identified after these children developed a neoplasm. The specific type of neoplasm was the most frequent indicator for genetic testing, whereas family history played a minor role. Conclusions and Relevance: In this cohort study of children with a neoplasm, the prevalence of CPSs identified by a phenotype-driven approach was 8.6%. The diagnostic approach for identifying CPSs is currently shifting toward a genotype-first approach. Future studies are needed to determine the diagnostic value, as well as possible disadvantages of CPS gene sequencing among all children with cancer compared with the phenotype-driven approach