The association of age and adverse events of PEG-asparaginase in a pediatric tertiary care hospital; a retrospective review.

BACKGROUND: Pediatric patients have a better survival rate for lymphoid malignancies than adolescents and young adult patients (AYA) and current evidence suggests that asparaginase plays a role in improved response to treatment. This study aimed to evaluate if increasing age as a continuous variable demonstrated increasing toxicities to PEG-asparaginase (PEG-ASP) for those patients treated at a tertiary care pediatric hospital. METHODS: A retrospective chart review from 2007 to 2017 was conducted in the pediatric population at the Children's Hospital of Eastern Ontario (CHEO). Patients having received PEG-ASP were included. Event incidence and risk related to age at diagnosis were assessed through parameter estimates and Wald chi-square analysis. RESULTS: In total, 75 adverse events were observed: 34/186 (18.3%) experienced allergic reactions, 8/186 (4.3%) pancreatitis, 31/186 (16.7%) thrombosis, and 2/186 (1.1%) hemorrhage. One hundred and eighty two patients had complete information for inclusion in our model. A correlation between age at diagnosis and higher risk of allergic reaction (p < .001) and pancreatitis (p < .035) was observed. CONCLUSION: Allergic reaction and pancreatitis following administration of PEG-ASP have a higher risk of occurrence as age of diagnosis increases up to 18 years of age. This includes the lower limit of traditionally defined AYA population of 15-39 and warrants precaution as PEG-ASP is included in older populations treatment regimens at pediatric centers.

The relationship between acoustic and musical pitch processing in adolescents.

Amusia is defined as a difficulty processing the tonal pitch structure of music such that an individual cannot tell the difference between notes that are in-key and out-of-key. A fine-grained pitch discrimination deficit is often observed in people with amusia. It is possible that an intervention, early in development, could mitigate amusia; however, one challenge identifying amusia early in development is that identifying in- and out-of-key notes is a metacognitive task. Given the common co-occurrence of difficulties with pitch discrimination, it would be easier to identify amusia in developing children by using a pitch change detection task. The goal of this study was to explore the behavioural and neurophysiological profiles of adolescents with poor pitch processing (Poor PP) abilities compared with those with normal pitch processing (Normal PP) abilities. Neurophysiologically, the Poor PPs exhibited a similar event-related potential (ERP) profile to adult amusics during both acoustic and musical pitch discrimination tasks. That is, early ERPs (ERAN, MMN) were similar in Poor PPs compared with Normal PPs, whereas late positivities (P300, P600) were absent in Poor PPs, but present in Normal PPs. At the same time, behavioural data revealed a double dissociation between the abilities to detect a pitch deviant in acoustic and musical context, suggesting that about a third of the children would be missed by selecting a fine-grained acoustic pitch discrimination task to identify the presence of amusia in early childhood.

Occupational exposure to chemotherapy of pharmacy personnel at a single centre.

BACKGROUND: Cyclophosphamide is one of the most commonly used chemotherapy drugs worldwide. Data concerning environmental contamination and biological exposure of pharmacy personnel to this and other chemotherapy drugs are limited. OBJECTIVES: To determine whether pharmacy personnel involved in preparing and checking cyclophosphamide doses were more likely to have detectable levels of this drug in their urine than non-oncology pharmacy personnel with no known contact with the drug, and to compare the degree of surface contamination with cyclophosphamide, methotrexate, and ifosfamide in the oncology pharmacy of a tertiary care pediatric hospital, where chemotherapy doses were prepared, and the main (control) pharmacy in the same institution, where no chemotherapy was prepared. METHODS: Biological exposure to cyclophosphamide was compared between pharmacy personnel who did and did not handle this drug by determining whether participants had detectable amounts of cyclophosphamide in their urine. Environmental exposure to chemotherapy drugs was assessed by using surface wipes to determine the degree of surface contamination with various chemotherapy agents in the oncology pharmacy and the main (control) pharmacy. RESULTS: On initial testing, cyclophosphamide was detected in the urine of all pharmacy personnel (n = 7 oncology personnel, n = 5 control personnel). However, it was determined that all control personnel had been exposed to the oncology pharmacy on the day of testing. Repeat testing of these individuals revealed no positive samples among those not exposed to the oncology pharmacy on the day of repeat testing. The sole positive result on retesting of control personnel was for a participant who had been exposed to the oncology pharmacy on the retest day. Surface wipe testing revealed contamination of the oncology pharmacy with cyclophosphamide and methotrexate before and after cleaning, as well as contamination with ifosfamide after cleaning. The main (control) pharmacy showed no evidence of contamination with cyclophosphamide, methotrexate, or ifosfamide. CONCLUSIONS: The findings suggest that environmental contamination plays a role in biological exposure to cyclophosphamide. Measures to reduce environmental contamination from chemotherapy and biological exposure of pharmacy personnel when handling chemotherapy agents should be identified and implemented as a priority.

CONTEXTE: La cyclophosphamide est l'un des médicaments de chimiothérapie les plus couramment utilisés dans le monde. Or, il n'y a que très peu de données sur la contamination environnementale et l'exposition biologique du personnel de pharmacie à ces produits. OBJECTIFS: Déterminer si le personnel de pharmacie s'occupant de la préparation et de la vérification des doses de cyclophosphamide est plus susceptible de présenter des concentrations détectables de ce médicament dans leurs urines que le personnel de pharmacie ne travaillant pas en oncologie, donc sans contact connu avec ce médicament, et comparer le niveau de contamination de surface par la cyclophosphamide, le méthotrexate et l'ifosfamide dans la pharmacie d'oncologie d'un hôpital pédiatrique de soins tertiaires, où sont préparées les doses de chimiothérapie, à celui dans la pharmacie principale (témoin) du même établissement, où n'est préparée aucune chimiothérapie. MÉTHODES: L'on a comparé l'exposition biologique à la cyclophosphamide du personnel de pharmacie ayant manipulé ce médicament à celle de personnel ne l'ayant pas manipulé en examinant si les participants présentaient des concentrations détectables de cyclophosphamide dans leurs urines. L'exposition environnementale aux produits de chimiothérapie a été évaluée à l'aide de lingettes utilisées pour essuyer les surfaces de la pharmacie d'oncologie et de la pharmacie principale (témoin) afin d'en déterminer les niveaux de contamination par différents agents de chimiothérapie. RÉSULTATS: Lors de l'analyse initiale, des concentrations de cyclophosphamide ont été détectées dans les urines de l'ensemble du personnel de pharmacie (n = 7 dans l'équipe en oncologie et n = 5 dans le groupe témoin). Mais l'on a constaté que tout le personnel du groupe témoin avait été exposé à la pharmacie d'oncologie le jour de l'analyse. Une seconde analyse chez ces personnes s'est montrée négative pour celles n'ayant pas été exposées à la pharmacie d'oncologie le jour de cette seconde analyse. Le seul résultat positif observé au cours de la seconde analyse chez le personnel du groupe témoin concernait un participant ayant été exposé à la pharmacie d'oncologie le jour de la seconde analyse. L'analyse des lingettes a révélé une contamination des surfaces de la pharmacie d'oncologie par la cyclophosphamide et le méthotrexate avant et après nettoyage ainsi qu'une contamination par l'ifosfamide après nettoyage. La pharmacie principale (témoin) ne présentait quant à elle aucun signe de contamination par l'un ou l'autre des trois produits. CONCLUSIONS: D'après ces résultats, la contamination environnementale joue un rôle dans l'exposition biologique à la cyclophosphamide. Ainsi, trouver et mettre en place des mesures visant à réduire la contamination environnementale par les produits de chimiothérapie et l'exposition biologique du personnel de pharmacie lors de la manipulation de ces produits doit représenter une priorité.

Congenital amusia persists in the developing brain after daily music listening.

Congenital amusia is a neurodevelopmental disorder that affects about 3% of the adult population. Adults experiencing this musical disorder in the absence of macroscopically visible brain injury are described as cases of congenital amusia under the assumption that the musical deficits have been present from birth. Here, we show that this disorder can be expressed in the developing brain. We found that (10-13 year-old) children exhibit a marked deficit in the detection of fine-grained pitch differences in both musical and acoustical context in comparison to their normally developing peers comparable in age and general intelligence. This behavioral deficit could be traced down to their abnormal P300 brain responses to the detection of subtle pitch changes. The altered pattern of electrical activity does not seem to arise from an anomalous functioning of the auditory cortex, because all early components of the brain potentials, the N100, the MMN, and the P200 appear normal. Rather, the brain and behavioral measures point to disrupted information propagation from the auditory cortex to other cortical regions. Furthermore, the behavioral and neural manifestations of the disorder remained unchanged after 4 weeks of daily musical listening. These results show that congenital amusia can be detected in childhood despite regular musical exposure and normal intellectual functioning.

Congenital amusia in childhood: a case study.

Here we describe the first documented case of congenital amusia in childhood. AS is a 10-year-old girl who was referred to us by her choir director for persisting difficulties in singing. We tested her with the child version of the Montreal Battery for the Evaluation of Amusia (MBEA) which confirmed AS's severe problems with melodic and rhythmic discrimination and memory for melodies. The disorder appears to be limited to music since her audiometry as well as her intellectual and language skills are normal. Furthermore, the musical disorder is associated to a severe deficit in detecting small pitch changes. The electrical brain responses point to an anomaly in the early stages of auditory processing, such as reflected by an abnormal mismatch negativity (MMN) response to small pitch changes. In singing, AS makes more pitch than time errors. Thus, despite frequent and regular musical practice, AS's profile is similar to the adult form of congenital amusia.

Daily light exposure in morning-type and evening-type individuals.

Morning-type individuals (M-types) have earlier sleep schedules than do evening types (E-types) and therefore differ in their exposure to the external light-dark cycle. M-types and E-types usually differ in their endogenous circadian phase as well, but whether this is the cause or the consequence of the difference in light exposure remains controversial. In this study, ambulatory monitoring was used to measure 24-h light exposure in M-type and E-type subjects for 7 consecutive days. The circadian phase of each subject was then estimated in the laboratory using the dim-light melatonin onset in saliva (DLMO) and the core body temperature minimum (Tmin). On average, M-types had earlier sleep schedules and earlier circadian phases than E-types. They also showed more minutes of daily bright light exposure (> 1000 lux) than E-types. As expected, the 24-h patterns of light exposure analyzed in relation to clock time indicated that M-types were exposed to more light in the morning than E-types and that the reverse was true in the late evening. However, there was no significant difference when the light profiles were analyzed in relation to circadian phase, suggesting that, on average, the circadian pacemaker of both M-types and E-types was similarly entrained to the light-dark cycle they usually experience. Some M-types and E-types had different sleep schedules but similar circadian phases. These subjects also had identical light profiles in relation to their circadian phase. By contrast, M-types and E-types with very early or very late circadian phases showed large differences in their profiles of light exposure in relation to their circadian phase. This observation suggests that in these individuals, early or late circadian phases are related to relatively short and long circadian periods and that a phase-delaying profile of light exposure in M-types and a phase-advancing profile in E-types are necessary to ensure a stable entrainment to the 24-h day.