Virtual Reality for Pediatric Needle Procedural Pain: Two Randomized Clinical Trials.

OBJECTIVE: To assess the efficacy and safety of a virtual reality distraction for needle pain in 2 common hospital settings: the emergency department (ED) and outpatient pathology (ie, outpatient laboratory). The control was standard of care (SOC) practice. STUDY DESIGN: In 2 clinical trials, we randomized children aged 4-11 years undergoing venous needle procedures to virtual reality or SOC at 2 tertiary Australian hospitals. In the first study, we enrolled children in the ED requiring intravenous cannulation or venipuncture. In the second, we enrolled children in outpatient pathology requiring venipuncture. In the ED, 64 children were assigned to virtual reality and 59 to SOC. In pathology, 63 children were assigned to virtual reality and 68 to SOC; 2 children withdrew assent in the SOC arm, leaving 66. The primary endpoint was change from baseline pain between virtual reality and SOC on child-rated Faces Pain Scale-Revised. RESULTS: In the ED, there was no change in pain from baseline with SOC, whereas virtual reality produced a significant reduction in pain (between-group difference, -1.78; 95% CI, -3.24 to -0.317; P = .018). In pathology, both groups experienced an increase in pain from baseline, but this was significantly less in the virtual reality group (between-group difference, -1.39; 95% CI, -2.68 to -0.11; P = .034). Across both studies, 10 participants experienced minor adverse events, equally distributed between virtual reality/SOC; none required pharmacotherapy. CONCLUSIONS: In children aged 4-11 years of age undergoing intravenous cannulation or venipuncture, virtual reality was efficacious in decreasing pain and was safe. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry: ACTRN12617000285358p.

Sources of error in measurement of minimal residual disease in childhood acute lymphoblastic leukemia.

INTRODUCTION: The level of minimal residual disease (MRD) in marrow predicts outcome and guides treatment in childhood acute lymphoblastic leukemia (ALL) but accurate prediction depends on accurate measurement. METHODS: Forty-one children with ALL were studied at the end of induction. Two samples were obtained from each iliac spine and each sample was assayed twice. Assay, sample and side-to-side variation were quantified by analysis of variance and presumptively incorrect decisions related to high-risk disease were determined using the result from each MRD assay, the mean MRD in the patient as the measure of the true value, and each of 3 different MRD cut-off levels which have been used for making decisions on treatment. RESULTS: Variation between assays, samples and sides each differed significantly from zero and the overall standard deviation for a single MRD estimation was 0.60 logs. Multifocal residual disease seemed to be at least partly responsible for the variation between samples. Decision errors occurred at a frequency of 13-14% when the mean patient MRD was between 10-2 and 10-5. Decision errors were observed only for an MRD result within 1 log of the cut-off value used for assessing high risk. Depending on the cut-off used, 31-40% of MRD results were within 1 log of the cut-off value and 21-16% of such results would have resulted in a decision error. CONCLUSION: When the result obtained for the level of MRD is within 1 log of the cut-off value used for making decisions, variation in the assay and/or sampling may result in a misleading assessment of the true level of marrow MRD. This may lead to an incorrect decision on treatment.

Infantile haemangiomas that failed treatment with propranolol: clinical and histopathological features.

AIM: To describe the clinical and histopathological characteristics of infantile haemangiomas that failed treatment with oral propranolol . DESIGN: This study is a case series from the vascular birthmarks clinic at Royal Children's Hospital, Melbourne. PATIENTS: The patients for this study were infants who commenced treatment with oral propranolol before 6 months of age and who were treated for at least 4 months without a satisfactory result. For histology and immunohistochemistry, tissue from the four non-responding patients who subsequently underwent surgical excision was matched with four historical controls. OUTCOME MEASURES: Based on medical record review and photographic assessments, infants were defined as having failed treatment with oral propranolol if the infantile haemangioma either continued to grow or showed 20% improvement or less. Tissue sections were examined for tissue structure, mast cells, sympathetic innervations and beta-2 adrenergic receptor expression, and the number of mast cells and beta-2 adrenergic positive cells. RESULTS: From a group of 135 infants who met the inclusion criteria, 14 infants failed propranolol treatment. Eleven of these infants had focal facial haemangiomas. No difference was seen in tissue morphology, tissue innervations, beta-2 adrenergic receptor expression, cell number or mast cell distribution, and number between non-responding and control haemangiomas. CONCLUSION: We report a treatment failure rate of 10%, which is higher than previously reported. Focal facial lesions failed to respond twice as frequently as other types of haemangioma. No histopathological reason was identified to indicate why some haemangiomas failed to respond.

Headache after lumbar puncture: randomised crossover trial of 22-gauge versus 25-gauge needles.

OBJECTIVES: To compare the frequency of headache and the procedure time following lumbar puncture (LP) using a 25-gauge needle compared to a 22-gauge needle. DESIGN: 4-period crossover blinded randomised controlled trial. SETTING: Oncology unit, Royal Children's Hospital, Melbourne. PATIENTS: Children aged 4-15 years at enrolment having LPs as part of their treatment for leukaemia. INTERVENTIONS: Each child was allocated a random sequence of four LPs, two with a 22-gauge and two with a 25-gauge needle. OUTCOME MEASURES: The presence of post-LP headache. Secondary outcomes included the presence of any headache, procedure time and impact of headache on the family. RESULTS: Data on 341 procedures in 93 randomised children were analysed. There was little difference in the incidence of post-LP headache between the two needle sizes (22-gauge 7.2%, 95% CI 3.8 to 12.2; 25-gauge 4.6%, 95% CI 2.0 to 8.9, p=0.3) or in the incidence of any headache (22-gauge 18% 95% CI 12.5 to 24.6; 25-gauge 15%, 95% CI 10.0 to 21.1, p=0.4). Use of the 25-gauge needle was associated with longer procedure times. The incidence of post-LP headache showed little evidence of an age effect (OR =1.1, 95% CI 0.98 to 1.3) and was higher in girls than in boys (11% vs 3%, respectively, OR=3.3, 95% CI 1.3 to 8.4, p=0.014). Fifty-five per cent of families with a child with a post-LP headache assessed the overall functional impact as moderate or severe. CONCLUSIONS: There was little difference in the occurrence of post-LP headache or any headache between procedures carried out using the 22-gauge or 25-gauge needles. Depending on the circumstances of the procedure and the experience of the operator, either gauge may be appropriate for an LP in a child.

Use of propranolol for treatment of infantile haemangiomas in an outpatient setting.

INTRODUCTION: Propranolol has recently emerged as an effective drug treatment for infantile haemangiomas. The side effect profile of the drug and the safety of administering propranolol in outpatient settings in this age group remain uncertain. We report our experience with 200 infants and children prescribed propranolol to treat infantile haemangiomas, including 37 patients considered to have a poor response to treatment. METHOD: Patients were prescribed propranolol (1 mg/kg/dose bd) as outpatients at the Vascular Anomalies Service at the Royal Children's Hospital, Melbourne. RESULTS: The median age at commencement was 4 months (range 5 days-7 years). Twenty patients were older than 12 months at commencement. The median duration of treatment was 8 months. About 80% of treated haemangiomas were on the face. Approximately 50% of patients were considered to have an excellent response, 30% to have a good response and 20% to have a poor response. All segmental facial haemangiomas responded well. In contrast, 25% of focal facial haemangiomas responded poorly. Sleep disturbance was the most common side effect. Gross motor abnormalities including delayed walking were observed in 13 patients. CONCLUSION: Propranolol appears to be an effective treatment for infantile haemangiomas, particularly large segmental facial lesions. A poor response was seen in 20% of patients. Treatment has been provided in an outpatient setting without major complications and with excellent parental compliance. The side effect profile appears to be favourable, but further follow-up is required to identify unexpected long-term side effects.

Sensitive and specific measurement of minimal residual disease in acute lymphoblastic leukemia.

A sensitive and specific quantitative real-time polymerase chain reaction method, involving three rounds of amplification with two allele-specific oligonucleotide primers directed against an rearrangement, was developed to quantify minimal residual disease (MRD) in B-lineage acute lymphoblastic leukemia (ALL). For a single sample containing 10 microg of good quality DNA, MRD was quantifiable down to approximately 10(-6), which is at least 1 log more sensitive than current methods. Nonspecific amplification was rarely observed. The standard deviation of laboratory estimations was 0.32 log units at moderate or high levels of MRD, but increased markedly as the level of MRD and the number of intact marker gene rearrangements in the sample fell. In 23 children with ALL studied after induction therapy, the mean MRD level was 1.6 x 10(-5) and levels ranged from 1.5 x 10(-2) to less than 10(-7). Comparisons with the conventional one-round quantitative polymerase chain reaction method on 29 samples from another 24 children who received treatment resulted in concordant results for 22 samples and discordant results for seven samples. The sensitivity and specificity of the method are due to the use of nested polymerase chain reaction, one segment-specific and two allele-specific oligonucleotide primers, and the use of a large amount of good quality DNA. This method may improve MRD-based decisions on treatment for ALL patients, and the principles should be applicable to DNA-based MRD measurements in other disorders.

Arterial thromboembolic disease: a single-centre case series study.

AIM: Paediatric venous thromboembolic disease has been reported with increased frequency during the last decade. In contrast, the pathophysiology of arterial thromboembolic disease in infants and children has not been adequately explored. The aim of this study was to determine the prevalence, aetiology, diagnostic criteria, management and outcome of arterial thromboembolism (TE) in a tertiary paediatric centre. METHODS: A prospective, single-centre registry was established at an Australian tertiary paediatric centre in order to address the aim of this study. RESULTS: One-hundred-and-two arterial thrombotic events occurred in 98 patients during 48 months. Infants were most likely to have a lower limb arterial TE (n = 22) whilst children were most likely to have a central nervous system arterial TE (n = 26). Surgery was a frequent predisposing factor in both infants and children. Doppler ultrasonography, computerized tomography and magnetic resonance imaging were the most commonly used diagnostic modalities. Unfractionated heparin was the most frequently used treatment in both age groups. At discharge, 25 infants and twelve children had complete resolution of their arterial TE. Direct thrombosis-related mortality was 4% in infants and 9% in children. Duration of follow-up ranged from 1 to 900 days, with thirteen infants and 32 children never achieving complete resolution. Forty-nine percent of post-discharge survivors had significant long term sequelae directly attributable to their arterial TE. CONCLUSION: Arterial TE occurred as frequently as venous TE in our tertiary paediatric population. The clinical outcome and long term sequelae of such events are significant.

Venous thromboembolic disease: a single-centre case series study.

AIM: The epidemiology of venous thromboembolism in children has likely changed since first being described a decade ago because of evolving management strategies and a greater awareness of predisposing factors for thrombosis in children. The Royal Children's Hospital commenced a 4-year prospective registry of venous thrombosis in 1999 to determine the current Australian epidemiology of venous thrombosis in infants and children. METHODS: A prospective, single-centre registry was established to determine the prevalence, aetiology, diagnostic criteria, management and outcome of venous thromboembolism in an Australian tertiary paediatric centre. RESULTS: The incidence of venous thrombosis was 8.0/10 000 hospital admissions. Fifty-eight per cent of infants and 49% of children were male. Seventy-seven per cent of venous thromboses in infants were associated with central venous cannulation compared with 47% in children. Doppler ultrasonography was the most frequently used diagnostic tool. Treatment strategies varied between age groups. The all-cause mortality rate for infants and children in this study was 8.4% (direct thrombus-related mortality 0%). Fifteen per cent of all patients demonstrated complete resolution of their venous thrombosis at discharge, with 48% demonstrating complete resolution at follow-up assessment. Fifteen per cent of patients experienced significant thrombosis-related morbidity at follow-up assessment. CONCLUSION: In this single-centre registry, venous thrombosis in infants and children occurred with greater frequency than has previously been reported and its epidemiology varied. Central venous catheterisation continues to be a common precipitant to venous thrombosis. Optimal diagnostic and treatment interventions for venous thromboembolism have not yet been determined for infants and children, despite the significant incidence of long-term sequelae.