Quantification of healthcare workers' exposure to cyclophosphamide, ifosfamide, methotrexate, and 5-fluorouracil by 24-h urine assay: A descriptive pilot study.

PURPOSE: The objective of this pilot study was to determine the frequency of urination and the concentration of four hazardous drugs (cyclophosphamide, ifosfamide, methotrexate, and fluorouracil) in workers' 24-h urine samples in relation to exposure to traces with hazardous drugs. METHODS: The study was conducted in three healthcare centers in the region of Montréal, Quebec, Canada. We recruited healthcare workers (nurses and pharmacy technicians) assigned to the hematology-oncology department. Each participant was asked to collect all urine voided during a 24-h period, to fill out an activity journal documenting tasks performed and to document the use of personal protective equipment. Samples were analyzed for cyclophosphamide, ifosfamide, methotrexate, and alpha-fluoro-beta-alanine (FBAL, the main urinary metabolite of 5-fluorouracil). Drugs were quantified by ultra-performance liquid chromatography-tandem mass spectrometry (positive electrospray MRM mode). RESULTS: Eighteen healthcare workers (10 nurses and 8 technicians) were recruited and provided consent to participate. Urine samples were obtained between 1 September and 30 September 2019. The number of urinations over the 24-h collection period ranged from 3 to 11 per participant. A total of 128 urine samples were analyzed for the 18 workers. All urine samples were negative for the four antineoplastics tested. CONCLUSION: No traces of cyclophosphamide, ifosfamide, methotrexate, or FBAL were found in the 24-h urine samples of 18 healthcare workers practicing in three healthcare facilities in Quebec. Although it was feasible to collect 24-h urine samples in this research project, it appears unrealistic to do so recurrently as part of a large-scale surveillance program.

Carboplatin and vincristine neurotoxicity in the treatment of pediatric low-grade gliomas.

BACKGROUND: Pediatric low-grade gliomas (LGG) represent 30-50% of central nervous system pediatric tumors. Over the last decades, the combination of carboplatin and vincristine (CV) has become the first line of treatment in most centers. In a large clinical trial where the efficacy of CV was compared to another regimen, 19% presented grade III neurotoxicity. Despite the fact that CV therapy is widely used for pediatric patients with LGG, no study has reported detailed neurological adverse events and outcome with this treatment regimen. The purpose of this retrospective study is to better understand neurotoxicity associated with CV. PROCEDURE: We conducted a retrospective study to better evaluate the incidence and evolution of neurotoxicity associated with CV in patients with LGG. RESULTS: Twenty-one pediatric patients were treated with CV at our single institution over 16 years. Most patients had optic glioma. Peripheral neuropathy was present in most patients (86%). Eight patients (38%) had a dose reduction of vincristine due to grade III toxicity (three motor neuropathies, three sensory neuropathies, one constipation, and one dysphagia). Most neurotoxicity occurred during induction or the first maintenance cycle. No ototoxicity was observed during treatment or follow-up. CONCLUSIONS: In our study, neurotoxicity with vincristine occurred two times more frequently than in previously published literature. Careful neurological assessment is important to detect neurotoxicity, especially during induction. The high incidence of neurotoxicity should be considered when selecting a chemotherapy regimen for pediatric LGG.

Effectiveness of pamidronate as treatment of symptomatic osteonecrosis occurring in children treated for acute lymphoblastic leukemia.

BACKGROUND: Osteonecrosis (ON) is a severe complication of acute lymphoblastic leukemia (ALL) treatments. Recent studies suggest that bisphosphonates might reduce pain and loss of motor function in patients with ON. We assessed the effects of pamidronate compared to standard care in patients with symptomatic ON (sON) and studied whether steroids might be continued after diagnosis of ON in some patients. METHODS: We evaluated 17 patients with sON as complication of primary ALL treatment between 2000 and 2008. Fourteen patients were treated with pamidronate. Mobility and pain control were monitored in all patients. Affected joints were classified by magnetic resonance imaging (MRI) at ON diagnosis and after 6-72 months. RESULTS: Out of 220 patients with ALL, 17 (7.7%) patients developed sON. The median age at ALL diagnosis was 11 years (range: 2.7-16.6 years) and sON occurred a median of 13.4 months (range: 2.5-34 months) after ALL diagnosis. Affected joints were hip, knee and ankle. MRI scans showed 7 severe, 4 moderate, and 6 mild ON lesions. Fourteen patients showed improvement in pain (77% of patients) and motor function (59% of patients), even though corticoids were reintroduced in 4 patients. MRI demonstrated improvement, stability or worsening in 6, 3, and 5 cases, respectively. CONCLUSIONS: Pamidronate seems to be effective in the management of pain and motor function recovery in sON. Further studies are needed to provide evidence as to whether bisphosphonates can be recommended for the treatment or the prevention of ON in childhood ALL patients.

The Three W's of Acetaminophen In Children: Who, Why, and Which Administration Mode.

Acetaminophen is one of the oldest medications commonly administered in children. Its efficacy in treating fever and pain is well accepted among clinicians. However, the available evidence supporting the use of acetaminophen's different modes of administration remains relatively scarce and poorly known. This short report summarizes the available evidence and provides a framework to guide clinicians regarding a rational use of acetaminophen in children.

Risk perception and reasons for noncompliance in pharmacovigilance: a qualitative study conducted in Canada.

BACKGROUND: The postmarketing safety evaluation of drugs relies on the spontaneous reporting of adverse reactions to authorities. Under-reporting is a known issue, with only 3% of all adverse reactions that occur actually being reported. Therefore, the postmarketing safety evaluation of medications is compromised. OBJECTIVE: This investigation aimed to identify determining factors that influence reporting as well as corrective actions. We specifically wanted to define the perceptions physicians and pharmacists have of pharmacovigilance, of the local and national reporting systems, of their role and that of other players in reporting adverse reactions, and of its consequences in their clinical practice. METHODS: Three focus groups with pharmacists and 16 semi-structured interviews with physicians from four different clinical services were conducted. RESULTS: Four major obstacles to reporting adverse reactions were identified: (i) pharmacovigilance is seen as an unrealistic ideal; (ii) the reporting authority is perceived as a virtual and remote entity; (iii) healthcare professionals do not feel concerned by the risks associated with the medications used in their practice; and (iv) healthcare professionals are uncertain about the scope of their role in reporting adverse effects. CONCLUSION: In order to promote reporting and a greater awareness of the system, a redefinition of its expectations and targeted feedback seem to be essential. Increased reporting can also be achieved by the presence of an onsite professional dedicated to reporting and educating others. Several definite measures are proposed in order to achieve this goal.