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.

A Retrospective Study on Infusion-Related Reactions to Rituximab in a Heterogeneous Pediatric Population.

OBJECTIVES: To assess risks and outcomes of infusion-related reactions to rituximab in a heterogeneous pediatric population. METHODS: All patients who received rituximab between July 2010 and July 2012 were retrieved from the pharmacy software and included for analysis. Data were collected according to 4 categories: demographic data, infusion data, infusion-related reactions, and biological data considered as risk factors (i.e., absolute lymphocyte count, lactate dehydrogenase levels). RESULTS: Sixty-seven patients treated for a total of 17 different indications were included. A total of 282 rituximab infusions were administered. Forty-three, mostly grade 1 or 2, infusion-related reactions occurred in 30 patients. Reactions occurred in 39.2% "first-dose" infusions, but this rate dropped drastically to 2.7% in subsequent doses. In multivariate analysis, high absolute lymphocyte count was the only risk factor for infusion-related reaction (OR = 1.03; 95% CI: 1.01-1.06; p = 0.014). CONCLUSIONS: Rituximab infusion-related reactions in a heterogeneous pediatric population were frequent on first infusion, but rare in subsequent ones. Overall, these reactions were mild and manageable through pharmacological treatment. Patients with an elevated absolute lymphocyte count before infusion were at greater risk for an infusion-related reaction.

Calcineurin inhibitor-free graft-versus-host disease prophylaxis with sirolimus and mycophenolate mofetil in a second allogeneic stem cell transplantation for engraftment failure and rituximab-refractory Epstein-Barr virus-induced posttransplant lymphoproliferative disease.

Posttransplant lymphoproliferative disease (PTLD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. We describe here the case of a boy with history of induction failure of a T-cell acute lymphoblastic leukemia, who presented a life-threatening situation of nonengraftment and rituximab-refractory PTLD after the first hematopoietic stem cell transplantation. We decided to use an unusual strategy of combining a nonmyeloablative conditioning (fludarabine and cyclophosphamide) with a calcineurin inhibitor-free GvHD prophylaxis (sirolimus and mycophenolate mofetil). This strategy had permitted the control of an Epstein-Barr virus PLTD in umbilical cord blood transplantation without further reactivation.

Impact and appreciation of two methods aiming at reducing hazardous drug environmental contamination: The centralization of the priming of IV tubing in the pharmacy and use of a closed-system transfer device.

OBJECTIVES: The main objective was to evaluate the impact of two methods aiming at reducing hazardous drug environmental contamination: the centralization of the priming of IV tubing in the pharmacy and the use of a closed-system transfer device. The secondary objective was to evaluate the satisfaction of pharmacy technicians using a survey. METHODS: Sites in the hematology-oncology satellite pharmacy and care unit were analyzed for the presence of cyclophosphamide, ifosfamide and methotrexate before and after the centralization of the priming of IV tubing in the pharmacy and before and after using a closed-system transfer device. The limits of detection for cyclophosphamide, ifosfamide and methotrexate were, respectively, of 0.0015 ng/cm(2), 0.0012 ng/cm(2) and 0.0060 ng/cm(2). The pharmacy technician satisfaction was evaluated using a questionnaire. RESULTS: A total of 225 samples was quantified. After the centralization of priming in the pharmacy, no significant difference was found in the proportion of positive samples for cyclophosphamide, ifosfamide and methotrexate. Traces of cyclophosphamide found on the floor in patient care areas was significantly reduced (median[min-max] 0.08[0.06-0.09]ng/cm(2) vs. 0.03[0.02-0.05], p < 0.0001). After using a closed-system transfer device, a significant difference was found for the proportion of cyclophosphamide positive samples (15/45(33%) vs. 0/45(0%), p < 0.0001), but no significant difference was found for ifosfamide (12/45(27%) vs. 5/45(11%), p = 0.059) and methotrexate (1/45(2%) vs. 2/45(4%), p = 0.557). Pharmacy technicians raised issues following the centralization of priming (e.g. workload) and the use of closed-system transfer devices (e.g. spills, particles, workload and handling difficulties). CONCLUSION: The centralization of the priming of IV tubing in the pharmacy reduced floor contamination in patient care areas without increasing surface contamination in the pharmacy. Closed-system transfer devices reduced contamination in pharmacy, but handling issues were raised by pharmacy technicians.

Pilot Study on the Impact of Evidence-Based Data on Oncology Pharmacists' Perceptions.

OBJECTIVES: The main objective was to evaluate whether the level of agreement of oncology hospital pharmacists with statements on their impact is influenced by the presence or absence of evidence-based data. The secondary objective was to evaluate the relative importance of evidence-based data among factors that may have contributed to oncology pharmacy practice evolution. METHODS: Oncology pharmacists' answered a Web questionnaire to measure their level of agreement with statements regarding their impact. Respondents answered the questionnaire before (pre) and after (post) being informed whether supporting evidence was available for each statement. Respondents were also asked to rank all of the factors in order of their perceived contribution to oncology pharmacy practice evolution. RESULTS: A total of 64 questionnaires were obtained. Respondents reported a high level of agreement with statements regarding their impact on oncology pharmacy practice (mean agreement of 95.9% pre vs 93.8% post). A statistically significant diminution in the level of agreement was observed for 3 statements after respondents were informed that no supporting evidence was available for these statements. Respondents assigned a high importance to factors related to the perception of positive outcomes of pharmaceutical activities on patient safety, health care costs, and clinical results but a low importance to the use of evidence-based data.

[Not Available]. / Démarche pour la mise à niveau d'un secteur de soins pharmaceutiques : le cas de l'hémato-oncologie pédiatrique.

BACKGROUND: Although the concept of clinical pharmacy was originally developed some time ago, in the 1960s, there is a wide variety of programs in existence, as well as great disparity between programs where the presence of a pharmacist is provided in outpatient and inpatient settings. OBJECTIVE: To test a method for upgrading pharmaceutical care areas in a hospital setting. METHOD: This descriptive study was conducted at the Sainte-Justine university health centre, a 500-bed mother-and-child hospital. The pharmaceutical care area that was used to exemplify the upgrading method was pediatric hematology-oncology. A 3-step method was used: review of the scientific literature, creation of a profile of the targeted area, and upgrading of the practice level according to the pre- and post-upgrading profile of the pharmaceutical activities in the area. RESULTS: A total of 108 articles were identified in a search of the PubMed database, of which 22 were retained. After a complementary manual search, a total of 36 articles were evaluated. The articles retained included 3 guidelines, 11 development studies, 1 review of scientific literature, 6 pre- and post-intervention studies, and 15 quasi-experimental studies. Although patients in the pediatric hematology-oncology area account for only 5% of admissions to this hospital, the cases are highly complex, in terms of both the codification of the care phase and the potential for pharmaceutical intervention per admission. CONCLUSION: There are few data to illustrate a method for upgrading practice in a pharmaceutical care area. This study tested a method for upgrading pharmaceutical care in a pediatric hematology-oncology service, with a review of the scientific literature, a profile of the area, and the pharmacists' pre- and post-upgrading job description in this area. [Publisher's translation].

Retrospective cohort study of 163 pediatric glaucoma patients.

OBJECTIVE: The aim of our study was to describe a cohort of pediatric glaucoma patients in Quebec. DESIGN: This study was a retrospective medical record review. PARTICIPANTS: The study included patients younger than 18 years who were diagnosed with glaucoma between 1980 and 2000 and monitored at the Ophthalmology Clinic of the Sainte-Justine University Hospital Centre (Centre Hospitalier Universitaire Sainte-Justine) and had ocular hypertension or glaucoma in at least 1 eye. METHODS: The data gathered concerned patients' information, the surgical procedures performed post diagnosis associated with the glaucoma diagnosis, and the drugs prescribed. RESULTS: The study included 163 patients (254 eyes), a total of 374 surgical procedures, and the use of 2885 antiglaucoma drug therapies. For the 4 most frequent pathologies, patients were monitored for 8.4 (SD 4.2) years for aphakic glaucoma/pseudophakic glaucoma, 10.0 (SD 5.5) years for congenital glaucoma, 9.0 (SD 5.2) years for Axenfeld-Rieger syndrome, and 7.5 (SD 3.4) years for uveitic glaucoma. In total, 113 patients had at least 1 surgical procedure (69.3%). Before 1985, only timolol, pilocarpine, epinephrine, acetazolamide, and dipivefrin were used. Other beta blockers then appeared (betaxolol, levobunolol between 1985 and 1990, and the timolol-pilocarpine association between 1990 and 1995). After 1995, we saw the arrival of a new class of prostaglandin F2 alpha analogues, with latanoprost and other carbonic acid anhydrase inhibitors such as dorzolamide and brinzolamide. CONCLUSIONS: This study illustrates the great variety of glaucoma diagnostic subgroups and the use of surgery and drug therapies.

Enzyme replacement therapy in pediatric patients with Gaucher disease: what should we use as maintenance dosage?

INTRODUCTION: No consensus exists on the minimal dose of enzyme replacement therapy (ERT) effective to maintain therapeutic goals in pediatric Gaucher patients. OBJECTIVE: Evaluate the efficacy of low dosage ERT to maintain treatment goals. RESULTS: Six patients had a maintenance dose of 30-35U/kg/month. All patients, with the exception of one L444P/L444P homozygote, maintained therapeutic goals. DISCUSSION: A low maintenance dose may be adequate in most pediatric patients. L444P homozygotes may require a higher maintenance dosage.

Pharmaceutical care in an inpatient pediatric hematopoietic stem cell transplant service.

INTRODUCTION: Hematopoietic stem cell transplant patients represent a population at high risk for drug-related problems. Our objective is to describe pharmacist interventions in a hematopoietic stem cell transplant pediatric unit. METHODS AND PATIENTS. The Hematopoietic Stem Cell Transplant Unit of the Centre Hospitalier Universitaire Sainte-Justine performs around 50 hematopoietic stem cell transplants per year. During a pharmaceutical care specialized residency program, a French pharmacist participated in certain clinical activities. Drug-related problems and clinical interventions were compiled over 31 nonconsecutive days using a tool developed by the Société Française de Pharmacie Clinique. Data concerning patients, drugs, intervention, documentation, approval (if needed), and estimated impact were compiled. RESULTS: During the 31-day period, 525 interventions were collected (16.9 +/- 3.7 per day), targeting 29 patients. The main drug-related problems were adverse drug reactions (N = 125, 23.8%), untreated indication (N = 92, 17.5%) and failure to receive drug (N = 89, 17.0%). The pharmacist's interventions concerned mainly dose adjustment (N = 174, 33.1%) and drug monitoring (N = 132, 25.1%). Among the 324 (61.7%) interventions requiring a physician's approval, 302 (93.2%) were accepted without any change. CONCLUSION: A pharmacist is able to perform clinically relevant interventions in a hematopoietic stem cell transplant unit, given the complexity of the pharmacotherapy. Our description of drug-related problems and interventions may help other pharmacists already working or developing pharmaceutical care in a hematopoietic stem cell transplant unit to compare their practice and it is one of the few reported in the literature.

Possible trimethoprim/sulfamethoxazole-induced aseptic meningitis.

OBJECTIVE: To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced aseptic meningitis. CASE SUMMARY: An 18-year-old woman diagnosed with acute myeloid leukemia was admitted for a bone marrow transplant. She had already attained remission with daunorubicin, thioguanine, and high-dose cytarabine. A routine lumbar puncture performed on admission revealed an abnormally elevated leukocyte count, and meningitis was suspected. The patient had been taking TMP/SMX (trimethoprim 120 mg) twice daily on Monday, Tuesday, and Wednesday for the past 3 months; no other medication was being used. Upon examination, the patient mentioned having had headaches for the past few weeks. Since viral, bacterial, and fungal cultures were negative, a diagnosis of aseptic meningitis was made. According to the Naranjo probability scale, TMP/SMX was a possible cause of the aseptic meningitis. Eleven days after discontinuation of TMP/SMX, lumbar puncture results had returned to normal. DISCUSSION: Many drugs have been associated with aseptic meningitis. Antibiotics are often linked with aseptic meningitis, with TMP/SMX being the most frequently associated antibiotic. Many cases of TMP/SMX-induced aseptic meningitis have been reported, while few cases have been reported with trimethoprim and sulfamethoxazole given separately. CONCLUSIONS: Despite the widespread use of TMP/SMX and the years of experience we have had with the drug, it is important to remain vigilant regarding possible adverse effects, particularly aseptic meningitis.