Magnetic toys: forbidden for pediatric patients with certain programmable shunt valves?

Background: Inadvertent adjustments and malfunctions of programmable valves have been reported in cases in which patients have encountered powerful electromagnetic fields such as those involved in magnetic resonance imaging, but the potential effects of magnetic toys on programmable valves are not well known. Materials and methods: The magnetic properties of nine toy magnets were examined. To calculate the effect of a single magnet over a distance, the magnetic flux density was directly measured using a calibrated Hall probe at seven different positions between 0 and 120mm from the magnet. Strata II small (Medtronic Inc.), Codman Hakim (Codman & Shurtleff), and Polaris (Sophysa) programmable valves were then tested to determine the effects of the toy magnets on each valve type. Results: The maximal flux density of different magnetic toys differed between 17 and 540mT, inversely proportional to the distance between toy and measurement instrument. Alterations to Strata and Codman valve settings could be effected with all the magnetic toys. The distances that still led to an alteration of the valve settings differed from 10 to 50mm (Strata), compared with 5 to 30mm (Codman). Valve settings of Polaris could not be altered by any toy at any distance due to its architecture with two magnets adjusted in opposite directions. Conclusion: This is the first report describing changes in the pressure setting of some adjustable valves caused by magnetic toys in close contact. Parents, surgeons, neurologists, pediatric oncologists, and paramedics should be informed about the potential dangers of magnetic toys to prevent unwanted changes to pressure setting

Description of a clinical decision support tool with integrated dose calculator for paediatrics

Medication errors, especially dosing errors are a leading cause of preventable harm in paediatric patients. The paediatric patient population is particularly vulnerable to dosing errors due to immaturity of metabolising organs and developmental changes. Moreover, the lack of clinical trial data or suitable drug forms, and the need for weight-based dosing, does not simplify drug dosing in paediatric or neonatal patients. Consequently, paediatric pharmacotherapy often requires unlicensed and off-label use including manipulation of adult dosage forms. In practice, this results in the need to calculate individual dosages which in turn increases the likelihood of dosing errors. In the age of digitalisation, clinical decision support (CDS) tools can support healthcare professionals in their daily work. CDS tools are currently amongst the gold standards in reducing preventable errors. In this publication, we describe the development and core functionalities of the CDS tool PEDeDose, a Class IIa medical device software certified according to the European Medical Device Regulation. The CDS tool provides a drug dosing formulary with an integrated calculator to determine individual dosages for paediatric, neonatal, and preterm patients. Even a technical interface is part of the CDS tool to facilitate integration into primary systems. This enables the support of the paediatrician directly during the prescribing process without changing the user interface. Conclusion: PEDeDose is a state-of-the-art CDS tool for individualised paediatric drug dosing that includes a certified calculator

Surgical resection of pediatric skull base meningiomas

Purpose: Meningiomas in children are rare, especially those located at the skull base. In this study, we report our experience of meningioma surgery in the pediatric population and compare our findings of skull base (SB) versus non-skull base (NSB) meningiomas. Methods: From our database of 724 surgically treated meningioma patients at the University Hospital, Zurich between 1995 and 2010, 12 patients under 18years of age were identified. Data for those patients was retrospectively collected through chart review. A descriptive comparison between SB and NSB meningiomas was undertaken to determine statistical significance. Results: In all 12 children (seven males, five females; mean age 12.2 ± 4.3years), surgical removal of the meningioma was performed microsurgically with a mean follow-up of 53months (range 12-137months). Of the 12 tumors, six were located in the SB and six in the NSB. Comparing SB to NSB lesions, the mean age was 11 ± 3.8 versus 14 ± 4.6years, male/female gender distribution was 5:1 compared to 1:5, mean tumor size was 7.5 ± 6.2 versus 26 ± 15.8cm2 (p = 0.03), and mean surgery time was 347 versus 214min. While WHO grade was similar for both groups, the Simpson grade revealed more extensive resection for NSB meningiomas. The Glasgow Outcome Scale at last follow-up was favorable for both groups. Conclusions: Meningioma surgery was safe with favorable outcomes. SB meningiomas were significantly smaller in size, were less likely to undergo complete resection, and had a predilection for younger, male patient

Does diagnostic delay result in decreased survival in paediatric brain tumours?

To study the hypothesis that a delay in the diagnosis of paediatric brain tumours results in decreased survival outcome probability, we compared the prediagnostic period of 315 brain tumour patients (median age 6.7years, range, 0 to 16years) with progression-free and overall survival. The median prediagnostic symptomatic interval was 60days (range, 0 to 3,480days), with a median parental delay of 14days (range, 0 to 1,835days) and a median doctor's delay of 14days (range, 0 to 3,480days). The prediagnostic symptomatic interval correlated significantly with the patient age, tumour histology, tumour location and year of diagnosis, but not with gender. We then grouped the patients according to histology (low-grade glioma [n=77], medulloblastoma [n=57], high-grade glioma [n=40], craniopharyngioma [n=27], ependymoma [n=20] and germ cell tumours [n=18]). Contrary to common belief, long prediagnostic symptomatic interval or long doctor's delay did not result in decreased survival outcome probability in any of these groups. The effect of tumour biology on survival seems to be dominant and overwhelms any possible opposing effect on survival of a delay in diagnosi

Cooperation of Striatin 3 and MAP4K4 promotes growth and tissue invasion

MAP4K4 is associated with increased motility and reduced proliferation in tumor cells, but the regulation of this dichotomous functionality remained elusive. We find that MAP4K4 interacts with striatin 3 and 4 (STRN3/4) and that STRN3 and MAP4K4 exert opposing functions in Hippo signaling and clonal growth. However, depletion of either STRN3 or MAP4K4 in medulloblastoma cells reduces invasion, and loss of both proteins abrogates tumor cell growth in the cerebellar tissue. Mechanistically, STRN3 couples MAP4K4 to the protein phosphatase 2A, which inactivates growth repressing activities of MAP4K4. In parallel, STRN3 enables growth factor-induced PKCθ activation and direct phosphorylation of VASPS157 by MAP4K4, which both are necessary for efficient cell invasion. VASPS157 directed activity of MAP4K4 and STRN3 requires the CNH domain of MAP4K4, which mediates its interaction with striatins. Thus, STRN3 is a master regulator of MAP4K4 function, and disruption of its cooperation with MAP4K4 reactivates Hippo signaling and represses tissue invasion in medulloblastoma

Author Correction: Cooperation of Striatin 3 and MAP4K4 promotes growth and tissue invasion

MAP4K4 is associated with increased motility and reduced proliferation in tumor cells, but the regulation of this dichotomous functionality remained elusive. We find that MAP4K4 interacts with striatin 3 and 4 (STRN3/4) and that STRN3 and MAP4K4 exert opposing functions in Hippo signaling and clonal growth. However, depletion of either STRN3 or MAP4K4 in medulloblastoma cells reduces invasion, and loss of both proteins abrogates tumor cell growth in the cerebellar tissue. Mechanistically, STRN3 couples MAP4K4 to the protein phosphatase 2A, which inactivates growth repressing activities of MAP4K4. In parallel, STRN3 enables growth factor-induced PKCθ activation and direct phosphorylation of VASPS157 by MAP4K4, which both are necessary for efficient cell invasion. VASPS157 directed activity of MAP4K4 and STRN3 requires the CNH domain of MAP4K4, which mediates its interaction with striatins. Thus, STRN3 is a master regulator of MAP4K4 function, and disruption of its cooperation with MAP4K4 reactivates Hippo signaling and represses tissue invasion in medulloblastoma

Outcome of children with low-grade cerebellar astrocytoma: long-term complications and quality of life

Objects: To study the long-term outcome of surgically treated low-grade cerebellar astrocytomas in children. Materials and methods: We followed 31 consecutive patients under 16years of age who were diagnosed between 1980 and 2005 in a single institution. In 21 of 31 survivors (median follow-up time 7.9years; range 5.6-27.4years) who agreed to participate, tumor control, neurological and cognitive complications, and their impact on behavioral and emotional adjustment and health-related quality of life (HRQoL) were comprehensively assessed qualitatively and quantitatively. Results: Neurological sequelae were found in 43%. However, age-appropriate ability to perform daily life activities was normal in all patients. Remarkably, cognitive deficits leading to significant school problems occurred in 19% and behavioral and emotional adjustment disturbances in 27%. In comparison with healthy controls, the survivors rated their HRQoL similarly or even higher. Conclusion: Childhood low-grade cerebellar astrocytomas have an excellent cure rate by tumor surgery alone. When compared with other pediatric brain tumors, the risk of neurological, cognitive, emotional, and behavioral complications is relatively small. HRQoL is similar to that of healthy control

Impact of a clinical decision support system on paediatric drug dose prescribing: a randomised within-subject simulation trial

BACKGROUND Drug dosing errors are among the most frequent causes of preventable harm in paediatrics. Due to the complexity of paediatric pharmacotherapy and the working conditions in healthcare, it is not surprising that human factor is a well-described source of error. Thus, a clinical decision support system (CDSS) that supports healthcare professionals (HCP) during the dose prescribing step provides a promising strategy for error prevention. METHODS The aim of the trial was to simulate the dose derivation step during the prescribing process. HCPs were asked to derive dosages for 18 hypothetical patient cases. We compared the CDSS PEDeDose, which provides a built-in dose calculator to the Summary of Product Characteristics (SmPC) used together with a pocket calculator in a randomised within-subject trial. We assessed the number of dose calculation errors and the time needed for calculation. Additionally, the effect of PEDeDose without using the built-in calculator but with a pocket calculator instead was assessed. RESULTS A total of 52 HCPs participated in the trial. The OR for an erroneous dosage using the CDSS as compared with the SmPC with pocket calculator was 0.08 (95% CI 0.02 to 0.36, p<0.001). Thus, the odds of an error were 12 times higher while using the SmPC. Furthermore, there was a 45% (95% CI 39% to 51%, p<0.001) time reduction when the dosage was derived using the CDSS. The exploratory analysis revealed that using only PEDeDose but without the built-in calculator did not substantially reduce errors. CONCLUSION Our results provide robust evidence that the use of the CDSS is safer and more efficient than manual dose derivation in paediatrics. Interestingly, only consulting a dosing database was not sufficient to substantially reduce errors. We are confident the CDSS PEDeDose ensures a higher safety and speeds up the prescribing process in practice

Pediatric papillary tumors of the pineal region: to observe or to treat following gross total resection?

Introduction: Papillary tumors of the pineal region (PTPR) are rare brain tumors characterized by frequent local recurrences. Standardized treatment strategies are not yet defined. Case report: We present the case of a 3-year-old girl diagnosed with PTPR. Due to her young age, adjuvant radiotherapy was omitted after gross total tumor resection. Thirty-six months later, local tumor recurrence occurred. Considering the possible risks of secondary surgery, the recurrent tumor was irradiated with proton radiotherapy. Three months later, the tumor showed near-complete remission. Discussion: Based on this experience and other pediatric case reports from the literature, local radiotherapy might be suggested also after complete tumor resectio

Natural history of a medulloblastoma: 30months of wait and see in a child with a cerebellar incidentaloma

Introduction: With the increasing use of neuroimaging studies, the discovery of incidental neoplastic lesions is becoming more frequent. However, standard procedures are lacking, and little is known about their optimal management. Case Report: We here present the case of a boy with a cerebellar mass incidentally discovered on a CT scan performed after head trauma. In another scan performed after another incident of head trauma 14months earlier, the lesion could be seen after retrospective examination. In view of the asymptomatic clinical and stable radiological status and the presumed diagnosis of a low-grade glioma, a watch-and-wait strategy was elected. After clinical and radiological progression was observed, the tumour was resected, 2½ years after the initial imaging study. Histological evaluation revealed a WNT pathway-activated classical medulloblastoma. Discussion: To our knowledge, this is the first description of such a long natural history and pre-symptomatic period of a medulloblastoma. The long period of stability followed by a period of accelerated tumour growth is compatible with increasing biological aggressiveness, possibly related to the stepwise accumulation of genetic change