Johanna H. van der Lee

Prognostic Tests in Term Neonates With Hypoxic-Ischemic Encephalopathy: A Systematic Review

BACKGROUND AND OBJECTIVE: Hypoxic-ischemic encephalopathy (HIE) after perinatal asphyxia in term neonates causes long-term neurologic sequelae or death. A reliable evidence-based prognosis is essential. The study goal was to investigate the prognostic value of currently used clinical tests in neonatal patients with perinatal asphyxia and HIE. METHODS: Searches were made on MEDLINE, Embase, Central, and CINAHL for studies occurring between January 1980 and November 2011. Studies were included if they (1) evaluated outcome in term infants with perinatal asphyxia and HIE, (2) evaluated prognostic tests, and (3) reported outcome at a minimal follow-up age of 18 months. Study selection, assessment of methodologic quality, and data extraction were performed by 3 independent reviewers. Pooled sensitivities and specificities of investigated tests were calculated when possible. RESULTS: Of the 259 relevant studies, 29 were included describing 13 prognostic tests conducted 1631 times in 1306 term neonates. A considerable heterogeneity was noted in test performance, cut-off values, and outcome measures. The most promising tests were amplitude-integrated electroencephalography (sensitivity 0.93, [95% confidence interval 0.78–0.98]; specificity 0.90 [0.60–0.98]), EEG (sensitivity 0.92 [0.66–0.99]; specificity 0.83 [0.64–0.93]), and visual evoked potentials (sensitivity 0.90 [0.74–0.97]; specificity 0.92 [0.68–0.98]). In imaging, diffusion weighted MRI performed best on specificity (0.89 [0.62–0.98]) and T1/T2-weighted MRI performed best on sensitivity (0.98 [0.80–1.00]). Magnetic resonance spectroscopy demonstrated a sensitivity of 0.75 (0.26–0.96) with poor specificity (0.58 [0.23–0.87]). CONCLUSIONS: This evidence suggests an important role for amplitude-integrated electroencephalography, EEG, visual evoked potentials, and diffusion weighted and conventional MRI. Given the heterogeneity in the tests’ performance and outcomes studied, well-designed large prospective studies are needed.

Quality of life of female caregivers of children with sickle cell disease: a survey

This Dutch survey demonstrates a lower quality of life in female caregivers of children with sickle cell disease than in the healthy female population and caregivers of healthy children with the same socioeconomic status. Therefore, better support is needed to improve the quality of life of both children with sickle cell disease and their caregivers. Caring for a child with sickle cell disease poses extra demands on parents, both practically and psychologically, which may influence their quality of life. Since families of children with sickle cell disease in the Netherlands usually belong to immigrant communities with a low socio-economic status, there may be an additional strain on caregivers. The aim of the present study was to evaluate the quality of life of caregivers of children with sickle cell disease. The quality of life of female caregivers of sickle cell disease patients, measured with the TNO-AZL Adult Quality of Life questionnaire, was compared to the norm data of healthy Dutch females (n=700) and female caregivers of healthy children with the same socio-economic status and ethnic background (socio-economic status control group). Groups were compared by the Mann-Whitney U test. Point estimates and 95% confidence intervals of the median difference are presented. The results of questionnaires of 54 caregivers of children with sickle cell disease and 28 caregivers of a control group of the same socio-economic status were analyzed. Caregivers of patients with sickle cell disease had a significantly lower quality of life on all subscales compared to the Dutch norm population. Compared to the control group of the same socio-economic status, the quality of life of caregivers of patients with sickle cell disease was significantly lower on the subscales depressive moods, daily activities and vitality. In this first study reporting on the quality of life of caregivers of children with sickle cell disease, we demonstrate a reduced quality of life in these caregivers compared to the healthy Dutch female population and caregivers of healthy children with the same socio-economic status.

Initial antibiotic treatment for acute simple appendicitis in children is safe: Short-term results from a multicenter, prospective cohort study

BACKGROUND Initial antibiotic treatment for acute appendicitis has been shown to be safe in adults; so far, not much is known about the safety and efficacy of this treatment in children. The aims of this study were to investigate the feasibility of a randomized controlled trial (RCT) evaluating initial antibiotic treatment for acute appendectomy in children with acute simple appendicitis and to evaluate the safety of this approach. METHODS In a multicenter, prospective cohort study patients aged 7-17 years with a radiologically confirmed simple appendicitis were eligible. Intravenous antibiotics (amoxicillin/clavulanic acid 250/25 mg/kg 4 times daily; maximum 6,000/600 mg/d and gentamicin 7 mg/kg once daily) were administered for 48-72 hours. Clinical reevaluation every 6 hours, daily blood samples, and ultrasound follow-up after 48 hours was performed. In case of improvement after 48 hours, oral antibiotics were given for a total of 7 days. At any time, in case of clinical deterioration or non-improvement after 72 hours, an appendectomy could be performed. Follow-up continued until 8 weeks after discharge. Adverse events were defined as major complications of antibiotic treatment, such as allergic reactions, perforated appendicitis, and recurrent appendicitis. RESULTS Of 44 eligible patients, 25 participated (inclusion rate, 57%; 95% CI, 42%-70%). Delayed appendectomy was performed in 2, and the other 23 were without symptoms at the 8 weeks follow-up. Minor complications occurred in three patients. None of the patients suffered from an adverse event or a recurrent appendicitis. CONCLUSION Our study shows that an RCT comparing initial antibiotic treatment strategy with urgent appendectomy is feasible in children; the intervention seems to be safe.

Comparison of two instruments measuring carotid-femoral pulse wave velocity: Vicorder versus SphygmoCor

Background The carotid-femoral pulse wave velocity (PWVcf) is used as an indicator of arterial stiffness. It is often measured using applanation tonometry, for instance with the SphygmoCor. In young children, this method is difficult to perform. Therefore, techniques are needed that are less dependent on patient compliance. The Vicorder device uses the oscillometric technique to measure the PWVcf and is thought to be less time consuming and less dependent on operator skills. Objective To compare the PWVcf measured by an extensively used device (SphygmoCor) and the Vicorder in adults initially. Methods Thirty-eight healthy volunteers (20 men, mean age 48 ± 13.1 years) participated in this cross-sectional study. The PWVcf was assessed twice using the SphygmoCor and the Vicorder by a single investigator during one visit. Intra-rater reproducibility of each instrument and comparison between the two instruments were assessed by the Bland–Altman method. Results The mean difference (95% confidence interval) between repeated measurements was 0.09 (−0.20 to 0.38) m/s and 0.24 (−0.55 to 1.03) m/s, for the SphygmoCor and Vicorder, respectively. The Limits of Agreement (LoA) were −1.53 to 1.71 m/s and −4.24 to 4.72 m/s, for the SphygmoCor and Vicorder, respectively. The mean PWVcf measured by the Vicorder was 0.58 (−0.20 to 1.35) m/s higher than the PWVcf measured by the SphygmoCor. The LoA between the two instruments were −3.50 to 4.66 m/s. Conclusion The LoA of both instruments exceed a value of 1.5 m/s. The LoA of the Vicorder PWVcf measurements are considered too wide for using this technique reliably in adults or in children.

Transition to the adult nephrologist does not induce acute renal transplant rejection

BACKGROUND In spite of the overall increased renal graft survival, long-term allograft survival has remained least successful in adolescent recipients. A major change in their care is the transition from the paediatric to the adult nephrology unit. METHODS To analyse the effect of transition on the acute rejection frequency and graft survival, we performed a historical cohort study in all patients transplanted at the paediatric unit between 1980 and 2004. Data were obtained by reviewing medical charts in two of the four Dutch pediatric renal transplantation centers from time of transplantation until 3 years after transition. For analysis, we used a Cox proportional hazards model. RESULTS The cohort consisted of 162 patients: 133 native Dutch and 29 immigrant patients. Transition occurred at a mean age of 18 years (range 14-22). At transition, 72% had a functioning allograft. Acute rejections occurred in 92/162 patients before (median follow-up 4.8 years, range 0.2-12.8) and in 15/116 patients after transition (median follow-up 3.0 years, range 1.6-3.0). Most rejections (62%) occurred within the first year after transplantation. The relative risk of acute rejections after transition in comparison to before transition was 0.10 [95% confidence interval (95% CI) 0.04-0.28] in Dutch patients and 0.69 (95% CI 0.33-1.40) in immigrant patients. In the 3 years before transition, 28/154 patients (18%) experienced graft failure compared to 19/116 patients (16%) in the 3 years after transition. CONCLUSIONS The risk for acute rejection decreases after transition to the adult unit. There is less risk reduction in immigrant patients. Nephrologists should pay special attention to these patients.

Early prediction of nasal continuous positive airway pressure failure in preterm infants less than 30 weeks gestation

Aim:  To predict early nasal continuous positive airway pressure failure within the first 2 h after birth in preterm infants.

State of the Evidence on Acute Asthma Management in Children: A Critical Appraisal of Systematic Reviews

OBJECTIVE. Our goal was to evaluate clinical, methodologic, and reporting aspects of systematic reviews on the management of acute asthma in children. METHODS. We undertook a systematic review of systematic reviews on acute asthma management in children. We identified eligible reviews by searching the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Medline, and Embase 1990 to March 2006. Data were extracted on clinical issues, methodologic characteristics, and results of the reviews. Methodologic quality was assessed with the Overview Quality Assessment Questionnaire and with additional questions on heterogeneity. Separate reporting on children in mixed adult-pediatric population reviews was assessed. Methodologic quality of systematic reviews published in peer-reviewed journals was compared with Cochrane reviews. RESULTS. A total of 23 systematic reviews were included: 14 were published in the Cochrane Library, and 9 were published in peer-reviewed journals. Eight reviews included children only, and 15 were mixed-population reviews. The majority of reviews defined the study population as having “acute asthma” without a more precise definition, and 16 different health outcomes were reported. The overall quality according to the Overview Quality Assessment Questionnaire was good, with Cochrane reviews showing minimal flaws and journal reviews showing minor flaws (median scores: 7 vs 5). Results on children were reported separately in 8 of 15 mixed-population reviews. Clinical heterogeneity was explored in only 2 of 23 reviews, and the methods used to identify and address heterogeneity were diverse. CONCLUSIONS. The methodologic quality of both the Cochrane and journal reviews on the management of acute asthma in children seems good, with Cochrane reviews being more rigorous. However, their usefulness for clinical practice is hampered by a lack of clear definitions of included populations, clinically important health outcomes, and separate reporting on children in mixed reviews. A major threat to these reviews’ validity is the insufficient identification and handling of heterogeneity.

A systematic review of the reporting of Data Monitoring Committees' roles, interim analysis and early termination in pediatric clinical trials

BackgroundDecisions about interim analysis and early stopping of clinical trials, as based on recommendations of Data Monitoring Committees (DMCs), have far reaching consequences for the scientific validity and clinical impact of a trial. Our aim was to evaluate the frequency and quality of the reporting on DMC composition and roles, interim analysis and early termination in pediatric trials.MethodsWe conducted a systematic review of randomized controlled clinical trials published from 2005 to 2007 in a sample of four general and four pediatric journals. We used full-text databases to identify trials which reported on DMCs, interim analysis or early termination, and included children or adolescents. Information was extracted on general trial characteristics, risk of bias, and a set of parameters regarding DMC composition and roles, interim analysis and early termination.Results110 of the 648 pediatric trials in this sample (17%) reported on DMC or interim analysis or early stopping, and were included; 68 from general and 42 from pediatric journals. The presence of DMCs was reported in 89 of the 110 included trials (81%); 62 papers, including 46 of the 89 that reported on DMCs (52%), also presented information about interim analysis. No paper adequately reported all DMC parameters, and nine (15%) reported all interim analysis details. Of 32 trials which terminated early, 22 (69%) did not report predefined stopping guidelines and 15 (47%) did not provide information on statistical monitoring methods.ConclusionsReporting on DMC composition and roles, on interim analysis results and on early termination of pediatric trials is incomplete and heterogeneous. We propose a minimal set of reporting parameters that will allow the reader to assess the validity of trial results.

Data monitoring committees, interim analysis and early termination in paediatric trials

Aim:  To evaluate whether paediatric randomized clinical trials (RCTs) adopt recent guidance on Data Monitoring Committees (DMCs), interim analysis and early termination.

Clinical Trial Decisions in Difficult Circumstances: Parental Consent Under Time Pressure

Treatments and interventions used to care for children in emergencies should be based on strong evidence. Well-designed clinical trials investigating these interventions for children are therefore indispensable. Parental informed consent is a key ethical requirement for the enrollment of children in such studies. However, if time is limited because of an urgent need for intervention, there are additional ethical challenges to adequately support the informed consent process. The acute situation and associated psychological impact may compromise the ability of parents to give informed consent. Little evidence exists to guide the process of consent seeking for a child’s research participation when time is limited. It is also unclear in what circumstances alternatives to prospective informed consent could be applied. This article describes possible options to manage the informed consent process in an appropriate, practical, and, we believe, ethical way when time is limited.