Environmental contamination with hazardous drugs in quebec hospitals.

BACKGROUND: Since publication of the US National Institute for Occupational Safety and Health alert on hazardous drugs in 2004, many health care organizations have reviewed their procedures for handling hazardous drugs. Occupational exposure may occur when handling, compounding, or administering a drug considered to be hazardous, at any stage from storage to waste management. OBJECTIVES: To describe environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in pharmacy and patient care areas of Quebec hospitals. METHODS: Sixty-eight hospitals were invited to participate. At each hospital, 12 prespecified measurement sites (6 each within pharmacy and patient care areas) were sampled once (midweek, end of day). The samples were analyzed by ultra-performance liquid chromatography tandem mass spectrometry to determine the presence of the 3 drugs. The limits of detection (LODs) were 0.0015 ng/cm(2) for cyclophosphamide, 0.0012 ng/cm(2) for ifosfamide, and 0.0060 ng/cm(2) for methotrexate. RESULTS: Twenty-five (37%) of the hospitals agreed to participate. Samples from sites other than the 12 prespecified sites were excluded. Overall, 259 valid samples were collected between April 2008 and January 2010 (147 samples from pharmacy areas in 25 hospitals and 112 samples from patient care areas in 24 hospitals). No hospital was using a closed-system drug transfer device at the time of the study. The median (minimum, maximum) number of sites per hospital with at least 1 positive sample for at least 1 of the 3 hazardous drugs was 6 (1, 12). A total of 135 (52%) samples were positive for cyclophosphamide, 53 (20%) for ifosfamide, and 7 (3%) for methotrexate. The median (minimum, maximum) concentration in positive samples was 0.0035 ng/cm(2) (below LOD, 28 ng/cm(2)) for cyclophosphamide, below LOD (below LOD, 8.6 ng/cm(2)) for ifosfamide, and below LOD (below LOD, 0.58 ng/cm(2)) for methotrexate. CONCLUSIONS: The levels of environmental contamination with 3 hazardous drugs in this multicentre study were similar to or below those in most published studies. Periodic measurement of surface contamination is necessary to ensure that current practices limit occupational exposure to hazardous drugs.

An assessment of drug administration compliance in a university hospital centre.

RATIONALE, AIMS AND OBJECTIVES: Ensuring the safety of the medication process is a major world health concern. Within this framework, a field study of compliance at various stages of the medication process in health care units was conducted. The objective of our study was to compare compliance at the moment of drug administration at the patient's bedside before and after implementing certain measures (self-study activities for the nursing staff, publication of the findings of the preliminary study and identification of priorities for action, among others). METHODS: This is an observational study aimed at comparing compliance at various stages of the medication process in terms of dose verification, preparation and administration, on ward, before and after the implementation of corrective measures. Compliance was evaluated using an observational checklist that included 36 criteria. The evaluation was conducted on inpatients in nine health care units and the Emergency Care Unit of a university hospital centre. Compliance rates were calculated for each evaluated criterion separately and by category. The degree of significance and corresponding changes between 2007 and 2008 were also measured. RESULTS: The compliance rate for all the applicable criteria used on the checklist showed a significant increase from 16% in 2007 to 28% in 2008. A significant increase was also observed in the compliance rates for drug verification (91% vs. 76%) and drug preparation on wards (50% vs. 23%), particularly with regard to entering drug names and a second identifier on the label. CONCLUSIONS: Compliance rates at various separately evaluated stages in 2008 were relatively satisfactory. There is, however, room for improvement in total compliance. The introduction of simple tools and adapted communication strategies led to a sizeable improvement in the medication process at our facility.

Pilot study comparing the efficacy of two cleaning techniques in reducing environmental contamination with cyclophosphamide.

OBJECTIVE: Compare the efficacy of the cleaning technique usually employed in our healthcare facility to eliminate environmental contamination with cyclophosphamide with that of the Surface Safe commercial kit. METHODS: This is a three-step evaluative and comparative study involving: (i) the voluntary contamination of the surface of a hood with a pre-established quantity of cyclophosphamide (20,000,000 ng), (ii) the cleaning of the work surface of the hood using a cleaning technique usually employed in our healthcare facility or that of the product Surface Safe, and (iii) the quantification of cyclophosphamide detected on the work surface. The usual cleaning technique involves the use of a mixture of 0.05% chlorhexidine and 70% ethyl alcohol to clean surfaces, whereas the product Surface Safe involves a combined two-step sodium hypochlorite and sodium thiosulfate wash. RESULTS: The median concentrations of cyclophosphamide detected after the use of the usual technique and the product Surface Safe came to 165 ng cm(-2) (40-570) and 65 ng cm(-2) (57-110), respectively. The results obtained showed an average 99.5% efficacy in reducing the quantity of cyclophosphamide (ng) detected on the work surface for each of the two techniques that were evaluated. CONCLUSION: The study demonstrates that reducing the residual concentration of cyclophosphamide on work surfaces to levels lower than 1 ng cm(-2) remains difficult despite the use of cleaning techniques with a high percentage of efficacy. It stressed the importance of combining two successive cleaning techniques to maximally restrict the residual concentration of hazardous drugs and suggests the use of a combination of sodium hypochlorite and sodium thiosulfate to best reduce environmental contamination levels.

[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].

Evaluation of surface contamination in a hospital hematology--oncology pharmacy.

OBJECTIVE: To describe environmental contamination with hazardous drugs in a hospital pharmacy setting before and after reorganizing a hematology- oncology satellite pharmacy. METHODS: This is a descriptive study of surface contamination with cyclophosphamide, ifosfamide, and methotrexate in two hematology-oncology satellite pharmacies. In order to measure surface contamination with hazardous drugs, samples from four distinct measurement sites within the pharmacy were taken in each of the two phases (pre-and postphases) using a sampling procedure and an analytical method modified from Larson et al. RESULTS: A total of 133 samples from four measurement sites were taken and analyzed over the course of the study (specifically 60 prephase samples and 73 postphase samples). The study showed a significant increase in the number of positive samples (from 66.7% to 90.4%, p<0.001) from the pre- to the postphase. The increase, however, is only significant in terms of the location where completed preparations were placed after they had come out from under the hood (from 0/15 to 21/28, p<0.001) and the work surface (from 8/15 to 15/15, p=0.006) and only in terms of ifosfamide. Furthermore, for the other sites studied, the number of positive samples remained unchanged between the pre- and postphase. A statistically significant difference between the pre- and postphase was observed in terms of ifosfamide for three of the four measurement sites studied and methotrexate for one of the four sites. Average concentrations were higher in the post phase in three of the four cases. CONCLUSION: This study describes environmental contamination with hazardous drugs in a hospital pharmacy setting before and after reorganizing a hematology-oncology satellite pharmacy. The study showed that a refitting of the hemato-oncology pharmacy is not a sufficient strategy to reduce the environmental contamination by ifosfamide because a significant increase in the number of positive samples from the pre- to the postphase have been observed. Many factors can contribute to influence the contamination of hazardous drugs such as the workflow and the training of the personal. Continuous environmental surveillance of hazardous drugs is required to document traces and help reduce risks.

Cyclophosphamide contamination observed on the external surfaces of drug vials and the efficacy of cleaning on vial contamination.

OBJECTIVE: Evaluate contamination on the external surfaces of cyclophosphamide vials available on the Canadian market during storage in pharmacy departments and the efficacy of decontaminating the external surfaces of vials using various cleaning techniques. METHODS: The study consisted of three phases: the quantification of cyclophosphamide on the external surfaces of 10 vials of Procytox and 10 vials of Cytoxan available on the Canadian market with or without prewashing (Phases I and II) and the quantification of cyclophosphamide on the surfaces of 30 deliberately contaminated empty sterile vials cleaned using three different washing techniques (Phase III). The quantification of cyclophosphamide was conducted using ultra performance liquid chromatography with tandem mass spectrometry. RESULTS: In Phase I, we observed that 9 of 10 vials of Procytox and 4 of 10 vials of Cytoxan had traces of cyclophosphamide. The average concentration of cyclophosphamide measured on the vials was higher for Procytox than it was for Cytoxan. In Phase II, we observed that simply by washing vials with water we could effectively eliminate the presence of contamination on 6 of 10 Procytox vials and on 10 of 10 Cytoxan vials. Phase III demonstrated the efficacy of using a cloth soaked in soapy water to clean the contaminated vials. CONCLUSION: This pilot study demonstrates the presence of contamination on the external surfaces of cyclophosphamide vials from two manufacturers on the Canadian market. It suggests that cleaning vials from manufacturers and wholesalers may help to reduce the risk of occupational exposure. There is a need for a pilot study to establish guidelines on decontamination agents and cleaning process to eliminate the presence of contamination on vial surfaces.

Cardiovascular expression of inflammatory signaling molecules, the kinin B1 receptor and COX2, in the rabbit: effects of LPS, anti-inflammatory and anti-hypertensive drugs.

We first aimed to test the effect of anti-inflammatory drugs, etanercept and dexamethasone sodium phosphate (DSP), on the expression of inducible inflammatory signaling molecules (the bradykinin [BK] B(1) receptor [B(1)R], cyclooxygenase [COX]-2) in lipopolysaccharide (LPS)-treated rabbits. Preliminary experiments mostly based on a novel cellular model, rabbit dermis fibroblasts, showed that etanercept inhibited TNF-alpha-induced B(1)R expression ([(3)H]Lys-des-Arg(9)-BK binding), but that DSP also inhibited cytokine-induced B(1)R upregulation with less selectivity. LPS (100 microg/kg i.v.) induced the expression of the B(1)R (aortic contractility ex vivo, mRNA in hearts) and COX2 (immunoblots, heart extracts). However, the function of the BK B(2) receptor was unchanged (jugular vein contractility ex vivo). DSP pre-treatment profoundly reduced the induction of the B(1)R and COX2 whereas etanercept significantly inhibited only COX2 expression. The second aim was to verify whether chronic angiotensin converting enzyme (ACE) blockade in rabbits would induce B(1)R expression, as reported in other species. 14-Day enalapril oral dosing, but not treatment with the angiotensin receptor antagonist losartan, significantly increased aortic contractions mediated by B(1)Rs, however much less than LPS. Enalapril treatment did not increase COX2 expression but increased the ex vivo relaxation of the mesenteric artery mediated by endogenous prostaglandins. Chronic ACE inhibition recruits inflammatory signaling systems.

Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema.

Angioedema is a potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors. Bradykinin and substance P, substrates of angiotensin-converting enzyme, increase vascular permeability and cause tissue edema in animals. Studies indicate that amino-terminal degradation of these peptides, by aminopeptidase P and dipeptidyl peptidase IV, may be impaired in individuals with angiotensin-converting enzyme inhibitor-associated angioedema. This case-control study tested the hypothesis that dipeptidyl peptidase IV activity and antigen are decreased in sera of patients with a history of angiotensin-converting enzyme inhibitor-associated angioedema. Fifty subjects with a history of angiotensin-converting enzyme inhibitor-associated angioedema and 176 angiotensin-converting enzyme inhibitor-exposed control subjects were ascertained. Sera were assayed for angiotensin-converting enzyme activity, aminopeptidase P activity, aminopeptidase N activity, dipeptidyl peptidase IV activity, and antigen and the ex vivo degradation half-lives of bradykinin, des-Arg(9)-bradykinin, and substance P in a subset. The prevalence of smoking was increased and of diabetes decreased in case versus control subjects. Overall, dipeptidyl peptidase IV activity (26.6+/-7.8 versus 29.6+/-7.3 nmol/mL per minute; P=0.026) and antigen (465.8+/-260.8 versus 563.1+/-208.6 ng/mL; P=0.017) were decreased in sera from individuals with angiotensin-converting enzyme inhibitor-associated angioedema compared with angiotensin-converting enzyme inhibitor-exposed control subjects without angioedema. Dipeptidyl peptidase IV activity (21.5+/-4.9 versus 29.8+/-6.7 nmol/mL per minute; P=0.001) and antigen (354.4+/-124.7 versus 559.8+/-163.2 ng/mL; P=0.003) were decreased in sera from cases collected during angiotensin-converting enzyme inhibition but not in the absence of angiotensin-converting enzyme inhibition. The degradation half-life of substance P correlated inversely with dipeptidyl peptidase IV antigen during angiotensin-converting enzyme inhibition. Environmental or genetic factors that reduce dipeptidyl peptidase IV activity may predispose individuals to angioedema.