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Purpose: The aim of this study was to monitor environmental contamination by 10 antineoplastic drugs in Canadian oncology pharmacy and patient care areas. The secondary objective was to explore the impact of factors that may explain contamination. Methods: Twelve standardized sites were sampled in each center (six in the pharmacy and six in patient care areas). Each sample was prepared to allow quantification of seven antineoplastic drugs (cyclophosphamide, ifosfamide, methotrexate, cytarabine, gemcitabine, 5-fluorouracil, irinotecan) by UPLC-MS-MS. Docetaxel, paclitaxel and vinorelbine were also detected, but not quantified due to sensibility limitations. The impact of some factors was evaluated compared with a Kolmogorov–Smirnov test for independent samples. Results: Eighty-three Canadian centers were recruited in 2017. A total of 953 surfaces were sampled, 495 in pharmacy and 458 in patient care areas. Cyclophosphamide was most often found on surfaces (36% of samples positive, 75th percentile 0.0040 ng/cm2). The arm rest (81.7% of samples positive for at least one antineoplastic drug), the front grille inside the hood (78.3%) and the floor in front of the hood (61.4%) were more frequently contaminated. Centers who prepared more antineoplastic drugs per year had higher concentration on different surfaces (p < 0.0001). Conclusion: Despite growing awareness and implementation of new safe handling guidelines, healthcare centers' surfaces remain contaminated with traces of many antineoplastic drugs. The use of personal protective equipment remains indisputable. Performing an annual monitoring remains a good indicator to monitor trends over time and to compare with similar centers. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of two decontamination protocols on cyclophosphamide surface contamination and to explore its lasting effect 30 days later.

No occupational exposure limit exists for antineoplastic drugs. The main objective of this study was to describe environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in pharmacy and patient care areas of Canadian hospitals in 2013. The secondary objective was to compare the 2013 environmental monitoring results with previous studies. Six standardized sites in the pharmacy and six sites on patient care areas were sampled in each participating center. Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by UPLC-MSMS. The limit of detection (LOD) in pg/cm2was 1.8 for cyclophosphamide, 2.2 for ifosfamide, and 7.5 for methotrexate. The 75th percentile of cyclophosphamide concentration was compared between the 2013, 2008–2010, and 2012 studies. Thirty-six hospitals participated in the study and 422 samples were collected. Overall, 47% (198/422) of the samples were positive for cyclophosphamide, 18% (75/422) were positive for ifosfamide, and 3% (11/422) were positive for methotrexate. In 2013, the 75th percentile value of cyclophosphamide surface concentration was reduced to 8.4pg/cm2(n = 36), compared with 9.4pg/cm2in 2012 (n = 33) and 40pg/cm2(n = 25) in 2008–2010. The 75th percentile for ifosfamide and methotrexate concentration remained lower than the LOD. The 2013 study shows an improvement in the surface contamination level, and a plateau effect in the proportion of positive samples. [ABSTRACT FROM AUTHOR]

The present study explored how patterns of sociocultural appearance pressures were linked to positive and negative facets of body image and eating behaviors in an adolescent sample (N = 438). Latent profile analyses indicated three distinct subgroups of perceived sociocultural appearance-related pressures: a Generalized-Pressure profile (28.8%) (moderate pressure from mother, father, and peers, and relatively high pressure from the media), a High-Media-Pressure profile (38.8%) (low pressure from mother, father, peers, and relatively high pressure from the media), and a Low-Pressure profile (32.4%) (low pressure from all sources). Overall, adolescents in the Generalized-Pressure profile reported a less positive relationship with food and their bodies (i.e., higher internalization of the thin ideal, body dissatisfaction, and bulimia symptoms, and lower body esteem and intuitive eating) than adolescents in the High-Media-Pressure profile, who exhibited poorer outcomes than those in the Low-Pressure profile. These findings highlight the importance of exploring how sociocultural appearance pressures from various sources combine in distinct ways, and how these configurations relate to different aspects of body image and eating behaviors in adolescents., Competing Interests: Declaration of competing interest Declarations of interest: none. All authors have no interest to declare., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Workers can reduce their risk of exposure to hazardous drugs by following safe handling guidelines. Healthcare centers need to dedicate time and resources in order to implement new safety recommendations. The objective was to present the results of a national survey about the safe handling of hazardous drugs in healthcare centers., Methods: Quebec healthcare centers performed an auto-evaluation to the newly updated safe handling guidelines in 2021. Centers rated each criterion as compliant or non-compliant. The guidelines tailored recommendations according to three categories of hazards: G1, consisting mostly of carcinogenic drugs; G2, other hazardous drugs; and G3, those with reproductive toxicity. The questionnaire prompted participants to document their planned corrective measures for non-compliant criteria., Results: Most centers participated (28/29, 97%). The overall compliance was 58% (8761/15,216 criteria). The conformity per theme was hygiene and sanitation (1290/1,878, 69%), laundry (221/367, 60%), pharmacy (2658/4,474, 59%), nursing (3436/6,017, 57%), spills and accidental exposure (353/649, 54%), and general measures (803/1,831, 44%). It was higher for recommendations regarding G1s (4226/6,115, 69%) than for G2s (1626/3557, 46%) and G3s (372/916, 41%)., Conclusions: This project successfully used an innovative approach that combined a national auto-evaluation survey, an actionable report, and the involvement of a community of practice. Centers were able to benchmark their implementation of safe handling guidelines, and community of practices may help in sharing the best practices. The design of the questionnaire helped in targeting corrective measures. More work is needed for safe handling practices that relate to G2 and G3 drugs., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pharmacists are increasingly involved in patient care. Pharmacy practice research helps them identify the most clinically meaningful interventions. However, the lack of a widely accepted controlled vocabulary in this field hinders the discovery of this literature., Objective: To compare the performance of a machine learning model with manual literature searches in identifying potentially relevant publications on the clinical impact of pharmacist interventions. To describe the dataset that was built., Methods: An automated PubMed search was performed weekly starting in November 2021. Titles and abstracts were retrieved and independently evaluated by two reviewers to select potentially relevant publications on the clinical impact of pharmacists. A Cohen's kappa score was calculated. Data was collected during an 11-month period to train a machine learning model. It was evaluated prospectively during a 5-month period (predictions were collected without being shown to the reviewers). The performance of the model was compared with manual searches (positive predictive value [PPV] and sensitivity)., Results: A transformers-based model was selected. During the prospective evaluation period, 114/1631 (7 %) publications met selection criteria. If the model had been used, 1273/1631 (78 %) would not have needed review. Only 3/114 (3 %) would have been incorrectly excluded. The model showed a PPV of 0.310 and a sensitivity of 0.974. The best manual search showed a PPV of 0.046 and a sensitivity of 0.711. On December 12, 2023, the dataset contained 8607 publications, of which 544 (6 %) met the criteria. The kappa between reviewers was 0.786. The dataset and the model were used to develop a website and a newsletter to share publications (https://impactpharmacy.net)., Conclusion: A machine learning model was developed and performs better than manual PubMed searches to identify potentially relevant publications. It represents a considerable workload reduction. This tool can assist pharmacists and other stakeholders in finding evidence that support pharmacists' interventions., Competing Interests: Declaration of competing interest none., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Occupational exposure to antineoplastic drugs can lead to long-term adverse effects on workers' health. A reproducible Canadian surface monitoring program was established in 2010. The objective was to describe contamination with 11 antineoplastic drugs measured on 12 surfaces among hospitals participating in this annual monitoring program., Methods: Each hospital sampled six standardized sites in oncology pharmacies and six in outpatient clinics. Ultra-performance liquid chromatography coupled with tandem mass spectrometry was used for cyclophosphamide, docetaxel, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, irinotecan, methotrexate, paclitaxel, and vinorelbine. Platinum-based drugs were analyzed by inductively coupled plasma mass spectrometry; this excludes inorganic platinum from the environment. Hospitals filled out an online questionnaire about their practices; a Kolmogorov-Smirnov test was used for some practices., Results: One hundred and twenty-four Canadian hospitals participated. Cyclophosphamide (405/1445, 28%), gemcitabine (347/1445, 24%), and platinum (71/756, 9%) were the most frequent. The 90th percentile of surface concentration was 0.01 ng/cm² for cyclophosphamide and 0.003 ng/cm² for gemcitabine. Centers that prepared 5000 or more antineoplastic per year had higher concentrations of cyclophosphamide and gemcitabine on their surfaces ( p   =  0.0001). Almost half maintained a hazardous drugs committee (46/119, 39%), but this did not influence the cyclophosphamide contamination ( p   =  0.051). Hazardous drugs training was more frequent for oncology pharmacy and nursing staff than for hygiene and sanitation staff., Conclusions: This monitoring program allowed centers to benchmark their contamination with pragmatic contamination thresholds derived from the Canadian 90th percentiles. Regular participation and local hazardous drug committee involvement provide an opportunity to review practices, identify risk areas, and refresh training., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Training represents a considerable portion of research activities and is vastly different for each clinical trial. This variation is partially explained by the lack of detailed regulations surrounding training procedures, which hinders the ability of investigational drug service (IDS) staff to plan their workload. The aim of this study was to quantify the workload associated with trial-specific training of IDS staff. The secondary aim was to identify the factors associated with training complexity., Methods: A retrospective study was carried out in the IDS of a mother and child university hospital. Trial-specific documents on which the pharmacy staff was trained were analyzed. Workload was calculated by measuring reading time. The readability of each document was determined by the Flesch Reading Ease score. The complexity of the trials was established using the scoring method of Calvin-Lamas et al. The influence of the following factors on training was assessed by analysis of variance: sponsor type, research phase, and research focus by medical specialty., Results: A total of 93 clinical trials and 433 documents were included. Investigator's brochures were the longest (a mean [SD] of 107 [46] pages; P < 0.0001) and most difficult documents to read (mean [SD] readability score, 25.5 [4.4]; P < 0.0001). Trials with industry sponsors required a significantly longer overall reading time (mean [SD], 12.26 [6.72] hours; P < 0.0001). On average, a mean (SD) of 9.42 (7.16) hours of reading were necessary to train one employee for a clinical trial., Conclusion: This study is the first to document reading time necessary for training of IDS staff. The training workload varied by sponsor type, while the research phase and medical specialty had little impact. IDS units would benefit from a tool that could identify complex trials., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Traumatic brain injury (TBI) is now recognized as an insult triggering a dynamic process of degeneration and regeneration potentially evolving for years with chronic traumatic encephalopathy (CTE) as one major complication. Neurons are at the center of the clinical manifestations, both in the acute and chronic phases. Yet, in the acute phase, conventional neuropathology detects abnormalities predominantly in the axons, if one excludes contusions and hypoxic ischemic changes. We report the finding of ballooned neurons, predominantly in the anterior cingulum, in three patients who sustained severe TBI and remained comatose until death, 2 ½ weeks to 2 ½ months after the traumatic impact. All three cases showed severe changes of traumatic diffuse axonal injury in line with acceleration/deceleration forces. The immunohistochemical profile of the ballooned neurons was like that described in neurodegenerative disorders like tauopathies which were used as controls. The presence of αB-crystallin positive ballooned neurons in the brain of patients who sustained severe craniocerebral trauma and remained comatose thereafter has never been reported. We postulate that the co-occurrence of diffuse axonal injury in the cerebral white matter and ballooned neurons in the cortex is mechanistically reminiscent of the phenomenon of chromatolysis. Experimental trauma models with neuronal chromatolytic features emphasized the presence of proximal axonal defects. In our three cases, proximal swellings were documented in the cortex and subcortical white matter. This limited retrospective report should trigger further studies in order to better establish, in recent/semi-recent TBI, the frequency of this neuronal finding and its relationship with the proximal axonal defects., (© 2023. The Author(s).)

Introduction: Occupational exposure to antineoplastic drugs can lead to long-term adverse effects on workers' health. Environmental monitoring is conducted once a year, as part of a Canadian monitoring program. The objective was to describe contamination with 11 antineoplastic drugs measured on surfaces., Methods: Six standardized sites in oncology pharmacy and six in outpatient clinic were sampled in each hospital. Samples were analyzed by ultra-performance liquid chromatography coupled with tandem mass spectrometry (non-platinum drugs) and by inductively coupled plasma mass spectrometry (platinum-based drugs). The limits of detection (in ng/cm 2 ) were: 0.0006 for cyclophosphamide; 0.001 for docetaxel; 0.04 for 5-fluorouracil; 0.0004 for gemcitabine; 0.0007 for irinotecan; 0.0009 for methotrexate; 0.004 for paclitaxel, 0.009 for vinorelbine, 0.02 for doxorubicine, 0.0037 for etoposide and 0.004 for the platinum. Sub-analyses were done with a Kolmogorov-Smirnov test., Results: 122 Canadian hospitals participated. Cyclophosphamide (451/1412, 32% of positive samples, 90 th percentile of concentration 0.0160 ng/cm 2 ) and gemcitabine (320/1412, 23%, 0.0036 ng/cm 2 ) were most frequently measured on surfaces. The surfaces most frequently contaminated with at least one drug were the front grille inside the biological safety cabinet (97/121, 80%) and the armrest of patient treatment chair (92/118, 78%).The distribution of cyclophosphamide concentration was higher for centers that prepared ≥ 5000 antineoplastic drug preparations/year (p < 0.0001)., Conclusions: This monitoring program allowed centers to benchmark their contamination with pragmatic contamination thresholds derived from the Canadian 90 th percentiles. Problematic areas need corrective measures such as decontamination. The program helps to increase the workers' awareness.

Introduction: Healthcare workers exposure to antineoplastic drugs can lead to adverse health effects. Guidelines promote the safe handling of antineoplastic drugs, but no safe exposure limit was determined. Regular surface sampling contributes to ensuring workers safety., Methods: A cross-sectional monitoring is conducted once a year with voluntary Canadian centers, since 2010. Twelve standardized sampling sites were sampled. Samples were analyzed by high performance mass coupled liquid chromatography. The limits of detection (in ng/cm 2 ) were: 0.001 for cyclophosphamide and gemcitabine; 0.3 for docetaxel and ifosfamide; 0.04 for 5-fluorouracil and paclitaxel; 0.003 for irinotecan; 0.002 for methotrexate; 0.01 for vinorelbine., Results: The surfaces from 109 centers were sampled between 01/01/2020-18/06/2020. Twenty-six centers delayed their participation because of the COVID-19 pandemic. 1217 samples were analyzed. Surfaces were frequently contaminated with cyclophosphamide (34% positive, 75th percentile 0.00165 ng/cm 2 ) and gemcitabine (16% and <0.001 ng/cm 2 ). The armrest of patient treatment chairs (84% to at least one drug), the front grille inside the biological safety cabinet (BSC) (73%) and the floor in front of the BSC (55%) were frequently contaminated. Centers that prepared ≥5000 antineoplastic drugs annually had higher concentration of cyclophosphamide on their surfaces (p < 0.0001). Contamination measured on the surfaces was reduced from 2010 to 2020., Conclusions: This large-scale study showed reproducible long term follow up of the contamination of standardized sites of Canadian centers and a reduction in surface contamination from 2010 to 2020. Periodic surface sampling help centers meet their continuous improvements goals to reduce exposure as much as possible. The COVID-19 pandemic had a limited impact on the program.

Objectives: The main objective was to identify all studies that present data regarding microbial contamination of vials used for preparation with closed-system drug transfer devices (CSTDs). Our secondary objective was to compare the reported contamination of vials punctured with a CSTD versus no CSTD and to evaluate the quality of data reporting as defined by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria., Methods: A literature review was conducted on 31 December 2018 on PubMed, EMBASE and Cumulative Index to Nursing and Allied Health Literature. A manual search of the archives of relevant pharmaceutical conferences was made. All studies that presented data about microbial contamination of vials punctured with a CSTD or about beyond-use date extension were included. Two researchers independently graded the articles according to the STROBE criteria., Results: Of the 280 articles identified initially, 12 were retained for analysis. Studies evaluated microbial contamination according to different incubation times and different culture media. Nine studies did not use any comparator group. Five studies found no contamination of vials punctured with CSTDs. For the others, the contamination was between 0.3% and 27%. Three studies compared the contamination of vials punctured with a CSTD and with a conventional system and did not show a significant difference between the groups. Seven studies declared a conflict of interest. The mean number of STROBE criteria fulfilled was 12.2±4.1 out of 34 (7 not applicable) for studies, and the mean number was 5±0 out of 12 for abstracts., Conclusions: Vials punctured in ISO5 conditions with a CSTD presented a low frequency of microbial contamination. No study showed a significant difference between vials punctured with a CSTD and with a conventional method. Centre-specific sterility testing is needed to reflect the variability of handling procedures and equipment., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The objectives of this study were to review economic data on the use of closed system drug transfer devices (CSTDs) for preparing and administering hazardous drugs, and to evaluate the quality of data reporting as defined by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS)., Methods: All references from a recent Cochrane review about CSTDs were evaluated for inclusion. A literature review was also conducted. Articles containing economic data about the use of CSTDs were retained for analysis. Two researchers independently graded the articles according to the 24-item CHEERS checklist., Results: Of the 138 articles identified initially, 12 were retained for analysis. Nine of these studies did not report acquisition costs or did not detail acquisition costs. Six studies reported economic benefits associated with the used of CSTDs, all related to extending the beyond-use date. The mean number of CHEERS criteria fulfilled by the included articles was 9.2 (SD 2.4)., Conclusions: CSTDs are costly to acquire. However, few studies have examined the economic impact of these devices, and the existing studies are incomplete. As a result, hospitals planning to implement these devices will be unable to make a sound economic evaluation. Robust economic evaluation of CSTDs is needed., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this study was to review the literature regarding the external contamination of commercial vials by antineoplastic drugs. A PubMed and CINAHL searches from 1 January 1990 to 1 May 2018 was performed with the terms: « antineoplastic agents », « environmental monitoring », « drug packaging », « vials » and « contamination ». Articles that presented results on the external contamination of commercial vials were included. Twenty-four articles were identified from 11 countries. A total of 4248 vials were sampled from 28 manufacturers. Traces were found on 56% (2379/4248) of vials. A maximum of 150 000 ng was measured on a glass vial of fluorouracil. This literature review showed that the exterior of the majority of commercial antineoplastic vials was contaminated. Manufacturers should limit this contamination. Centres are also encouraged to clean the vials on receipt. Personal protection equipment should be worn at all steps of the drug-use process., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The main objective was to determine the efficacy of various types of cleaning equipment and products after deliberate contamination with cyclophosphamide. The secondary objective was to test various cleaning scenarios using these equipment and products., Methods: The study had two phases: testing of cleaning equipment (wipe : woven microfibers - Hygen®, two layers of non-woven microfibres and an inner layer of highly absorbent viscose fibres - MicronSolo®, two layers of non-woven microfibres and an inner layer of highly absorbent viscose fibres - MicroMix®, simili-tissu (low filament production) - Tork® and, mop : woven microfibers - Hygen®, microfibre and viscose - MicroOne®) and products (disinfectant : quaternary ammonium - DR100®, chlorine 0.1% - Zochlor® - Brutab® - PCS® NPH, sodium hypochlorite 2%, cleaner : detergent - Nu- Action 3®, cleaner and disinfectant: sodium hypochlorite 0.6% + detergent - Aliflex® and water) in phase 1 and testing of various cleaning procedures in phase 2. Specific areas of a room with a laminar flow hood (class II/type B2) were contaminated with 10 mcg of cyclophosphamide. Different types of surfaces were cleaned with various scenarios and the remaining cyclophosphamide was measured by the Institut national de santé publique du Québec. All tests were performed in triplicate., Results: A total of 189 samples were obtained: 42 negative controls and positive controls, 54 during phase 1 and 93 during phase 2. All products were more than 96.5% effective. The 0.1% chlorines were the most effective products. Cleaning procedures with two or three products had average cleaning efficacies of 99.94-99.99%. Efficacy increased with the number of successive cleanings. When two products were used, the average cleaning efficacy varied between 99.78% and 99.98%, depending on the surface., Conclusion: All cleaning products tested reduced cyclophosphamide contamination by more than 96.58%. Cleaning efficacy increased with successive cleaning. No scenario was effective in removing 100% of traces. Additional studies with larger samples should be conducted to confirm these results.

Background: Surfaces in health care centres are often contaminated with traces of antineoplastic drugs. Such contamination should be limited as much as possible, to reduce workers' exposure., Objectives: The primary objective was to monitor environmental contamination with 9 antineoplastic drugs in oncology pharmacy and patient care areas of Canadian health care centres. The secondary objective was to explore the use of sodium hypochlorite as a cleaning agent for cyclophosphamide contamination., Methods: This cross-sectional evaluation was conducted from January to April 2018. Twelve standardized sites were sampled at each participating centre: 6 in the oncology pharmacy and 6 in patient care areas. Six of the antineoplastic drugs (cyclophosphamide, ifosfamide, methotrexate, gemcitabine, 5-fluorouracil, and irinotecan) were quantified by ultra-performance liquid chromatography - tandem mass spectrometry. For the other 3 antineoplastic drugs (docetaxel, paclitaxel, and vinorelbine), samples were screened for contamination but not quantified. The effect of using sodium hypochlorite as a cleaning agent was evaluated with a Kolmogorov-Smirnov test for independent samples., Results: Of 202 Canadian centres invited, 79 participated. A total of 887 surface samples were analyzed, 467 from pharmacy areas and 420 from patient care areas. Cyclophosphamide was the drug most often found as a contaminant (32.2% [286/887] of samples positive, 75th percentile of measured contamination 0.0017 ng/cm 2 , 90th percentile 0.021 ng/cm 2 ). The front grille inside the hood (80.8% [63/78] of samples positive for at least one antineoplastic drug), treatment chair armrest (78.9% [60/76]), storage shelf in pharmacy (61.5% [48/78]), and floor in front of the hood (60.3% [47/78]) were the most frequently contaminated surfaces. Cleaning with a sodium hypochlorite solution was highly variable. Among centres that reported using sodium hypochlorite to clean armrests on patient chairs, the concentration of cyclophosphamide was lower (0.00866 versus 0.0300 ng/cm 2 , p = 0.014)., Conclusions: Despite growing awareness and implementation of new safe-handling guidelines, surfaces in health care centres were contaminated with traces of many antineoplastic drugs. Providing centres with attainable goals (e.g., 75th to 90th percentile relative to other similar centres) would help in identifying the sampling sites where improvements are needed and in achieving lower surface contamination., Competing Interests: Competing interests: None declared., (2019 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.)

Background/aims: In comparison with commercial drugs, there are few regulations concerning the labeling of investigational drugs. This leads to variability in their content and layout. This increases the risk of errors during storage, validation, compounding, dispensing and administration. The aim of this study was to evaluate the conformity and variability of investigational drug labels. Additional exploratory aims were to evaluate the use of an automated script to describe the labels and to identify the factors associated with the ease of finding a kit number., Methods: An 87-criterion list was developed to evaluate content, format and readability. It included eight criteria to evaluate the conformity to the Canadian Food and Drugs Regulation. A systematic cross-sectional evaluation of all investigational drug labels in our 500-bed mother-child center was performed. All active protocols during the period of 14-22 February 2018 were included. Labels from drugs that were sourced locally were excluded. Labels affixed to the outside (external) and inside (internal) containers, as well as labels from American and European sponsors, were compared with the chi-square and Student's t tests. A script was developed in Python to automatically determine key information (number of words, main colors and their proportion). A short survey was conducted with a convenience sample of pharmacists to rate the ease of finding the kit number on labels. Correlation was evaluated with different factors., Results: A total of 27 protocols were included (24 internal and 34 external labels). The majority (33/34) of external labels were compliant with the Regulation. Some internal labels did not state the expiry date (9/13), the sponsor address (2/13) or storing conditions (1/13). A total of 10 criteria were different between internal and external labels, for instance, the number of languages was higher on external labels (median 3 (2-14) vs 10 (2-50); p = 0.013). Five criteria were different depending on the sponsors' location, for instance, European sponsors were more prone to use bold characters (25% vs 61%, p = 0.034). There was a mean of 146 ± 111 words and 78.3% ± 7.3% empty space per label. These were positively correlated (p < 0.001). The proportion of free space on a label was also correlated with the ease of finding the kit number (p = 0.002)., Conclusion: We measured a high variability in the labeling of investigational drugs. Key information was missing from labels affixed to internal containers, despite the use of a high number of pages. The automation worked well and further work is needed to identify criteria that may improve readability and reduce error risk. Detailed and harmonized international guidelines are needed.

Competing Interests: Competing interests: None declared.

Background: Occupational exposure to hazardous drugs can decrease fertility and result in miscarriages, stillbirths, and cancers in healthcare staff. Several recommended practices aim to reduce this exposure, including protective clothing, gloves, and biological safety cabinets ('safe handling'). There is significant uncertainty as to whether using closed-system drug-transfer devices (CSTD) in addition to safe handling decreases the contamination and risk of staff exposure to infusional hazardous drugs compared to safe handling alone., Objectives: To assess the effects of closed-system drug-transfer of infusional hazardous drugs plus safe handling versus safe handling alone for reducing staff exposure to infusional hazardous drugs and risk of staff contamination., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, OSH-UPDATE, CINAHL, Science Citation Index Expanded, economic evaluation databases, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to October 2017., Selection Criteria: We included comparative studies of any study design (irrespective of language, blinding, or publication status) that compared CSTD plus safe handling versus safe handling alone for infusional hazardous drugs., Data Collection and Analysis: Two review authors independently identified trials and extracted data. We calculated the risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CI) using both fixed-effect and random-effects models. We assessed risk of bias according to the risk of bias in non-randomised studies of interventions (ROBINS-I) tool, used an intracluster correlation coefficient of 0.10, and we assessed the quality of the evidence using GRADE., Main Results: We included 23 observational cluster studies (358 hospitals) in this review. We did not find any randomised controlled trials or formal economic evaluations. In 21 studies, the people who used the intervention (CSTD plus safe handling) and control (safe handling alone) were pharmacists or pharmacy technicians; in the other two studies, the people who used the intervention and control were nurses, pharmacists, or pharmacy technicians. The CSTD used in the studies were PhaSeal (13 studies), Tevadaptor (1 study), SpikeSwan (1 study), PhaSeal and Tevadaptor (1 study), varied (5 studies), and not stated (2 studies). The studies' descriptions of the control groups were varied. Twenty-one studies provide data on one or more outcomes for this systematic review. All the studies are at serious risk of bias. The quality of evidence is very low for all the outcomes.There is no evidence of differences in the proportion of people with positive urine tests for exposure between the CSTD and control groups for cyclophosphamide alone (RR 0.83, 95% CI 0.46 to 1.52; I² = 12%; 2 studies; 2 hospitals; 20 participants; CSTD: 76.1% versus control: 91.7%); cyclophosphamide or ifosfamide (RR 0.09, 95% CI 0.00 to 2.79; 1 study; 1 hospital; 14 participants; CSTD: 6.4% versus control: 71.4%); and cyclophosphamide, ifosfamide, or gemcitabine (RR not estimable; 1 study; 1 hospital; 36 participants; 0% in both groups).There is no evidence of a difference in the proportion of surface samples contaminated in the pharmacy areas or patient-care areas for any of the drugs except 5-fluorouracil, which was lower in the CSTD group than in the control (RR 0.65, 95% CI 0.43 to 0.97; 3 studies, 106 hospitals, 1008 samples; CSTD: 9% versus control: 13.9%).The amount of cyclophosphamide was lower in pharmacy areas in the CSTD group than in the control group (MD -49.34 pg/cm², 95% CI -84.11 to -14.56, I² = 0%, 7 studies; 282 hospitals, 1793 surface samples). Additionally, one interrupted time-series study (3 hospitals; 342 samples) demonstrated a change in the slope between pre-CSTD and CSTD (3.9439 pg/cm², 95% CI 1.2303 to 6.6576; P = 0.010), but not between CSTD and post-CSTD withdrawal (-1.9331 pg/cm², 95% CI -5.1260 to 1.2598; P = 0.20). There is no evidence of difference in the amount of the other drugs between CSTD and control groups in the pharmacy areas or patient-care areas.None of the studies report on atmospheric contamination, blood tests, or other measures of exposure to infusional hazardous drugs such as urine mutagenicity, chromosomal aberrations, sister chromatid exchanges, or micronuclei induction.None of the studies report short-term health benefits such as reduction in skin rashes, medium-term reproductive health benefits such as fertility and parity, or long-term health benefits related to the development of any type of cancer or adverse events.Five studies (six hospitals) report the potential cost savings through the use of CSTD. The studies used different methods of calculating the costs, and the results were not reported in a format that could be pooled via meta-analysis. There is significant variability between the studies in terms of whether CSTD resulted in cost savings (the point estimates of the average potential cost savings ranged from (2017) USD -642,656 to (2017) USD 221,818)., Authors' Conclusions: There is currently no evidence to support or refute the routine use of closed-system drug transfer devices in addition to safe handling of infusional hazardous drugs, as there is no evidence of differences in exposure or financial benefits between CSTD plus safe handling versus safe handling alone (very low-quality evidence). None of the studies report health benefits.Well-designed multicentre randomised controlled trials may be feasible depending upon the proportion of people with exposure. The next best study design is interrupted time-series. This design is likely to provide a better estimate than uncontrolled before-after studies or cross-sectional studies. Future studies may involve other alternate ways of reducing exposure in addition to safe handling as one intervention group in a multi-arm parallel design or factorial design trial. Future studies should have designs that decrease the risk of bias and enable measurement of direct health benefits in addition to exposure. Studies using exposure should be tested for a relevant selection of hazardous drugs used in the hospital to provide an estimate of the exposure and health benefits of using CSTD. Steps should be undertaken to ensure that there are no other differences between CSTD and control groups, so that one can obtain a reasonable estimate of the health benefits of using CSTD.

Context Oncology workers are occupationally exposed to antineoplastic drugs. This exposure can induce adverse health effects. In order to reduce their exposure, contamination on surfaces should be kept as low as possible. Objectives To monitor environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in oncology pharmacy and patient care areas in Canadian hospitals. To describe the impact of some factors that may limit contamination. Methods This is a descriptive study. Twelve standardized sites were sampled in each participating center (six in the pharmacy and six in patient care areas). Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by ultra-performance liquid chromatography tandem mass spectrometry technology. Descriptive statistical analyses were done and results were compared with a Kolmogorov-Smirnov test for independent samples. Results In 2015, 48 hospitals participated in this study (48/202, 24%). Overall, 34% (181/525) of the samples were positive for cyclophosphamide, 8% (41/525) for ifosfamide, and 6% (31/525) for methotrexate. The 75th percentile value of cyclophosphamide surface concentration was 6.9 pg/cm 2 . For ifosfamide and methotrexate, they were lower than the limit of detection. Centers who prepared more antineoplastic drugs per year and centers who used more cyclophosphamide per year showed significantly higher surface contamination ( p < 0.0001). Over the years, we observed a reduction in surface contamination. Conclusion In comparison with other multicenter studies that were conducted in Canada, the concentration of antineoplastic drugs measured on surfaces is decreasing. Regular environmental monitoring is a good practice in order to maintain contamination as low as reasonably achievable.

Purpose There are health risks to workers occupationally exposed to antineoplastic drugs. We hypothesized that implementing a biological monitoring program would be feasible. The goal was to present the results of our pilot cross-sectional study of biological monitoring of four antineoplastic drugs. Methods We recruited workers from the hematology-oncology department and control workers in a mother-child university health center. This study was preceded by an information period during which we aimed at enhancing the workers' awareness and knowledge of the risks of occupational exposure. Participants filled out a journal containing activities performed and personal protective equipment worn. One urine sample was collected at the end of their shift. Samples were analyzed by UPLC/MS-MS for the presence of cyclophosphamide, ifosfamide, methotrexate, and alpha-fluoro-beta-alanine (5-fluorouracile's main urinary metabolite). Results The participation rate was 85.7% (102/119). No urine sample had detectable concentrations of any of the four drugs evaluated (0/101; 0/74 nurses, 0/11 pharmacists, 0/9 pharmacy technicians, and 0/7 doctors). In the 5 days before sampling, 67/92 (72.8%) hematology-oncology participants performed at least one activity with antineoplastic drugs. Nurses wore all of the recommended protection for technical activities (86.2%), but rarely for non-technical activities (14.9%). Pharmacists and pharmacy technicians wore all of the recommended protection for all activities (100.0%). Conclusions This pilot study had a good participation rate. The absence of positive samples was a good indication that the measures in place ensured workers' safety, even though we found areas where the worker protection can be enhanced.

Background: Research suggests that agitation is a common symptom for hospice patients, but while studies have examined the outcomes of music therapy on the agitated behaviors of patients in other settings, none have addressed this symptom in patients with terminal illnesses., Objective: The study objective was to determine whether a single session of music therapy provided by a board certified music therapist and using the entrainment principle would decrease agitation in hospice patients., Design: This pilot study was a single-blind, pretest/posttest design. Music therapists used the principle of entrainment with live music during the treatment session., Setting/subjects: Subjects included in the study were 77 patients at a large hospice in south Florida with documented agitation., Measurements: Agitation was measured using the Overt Agitation Severity Scale (OASS) for 5 minutes prior to and 5 minutes following a 20 minute music therapy intervention., Results: Results from 73 participants were analyzed with a mean difference of -5.77 points from pretest to posttest. Results indicating a decrease in agitation were statistically significant (p < 0.001) for the entire sample. Age, gender, location, and diagnosis were found to have no significant effects on the results., Conclusions: Results indicate that a single session of music therapy using the entrainment principle may be an effective treatment for hospice patients experiencing agitation.

Background: Occupational exposure to hazardous drugs may lead to adverse reproductive effects. There is no safe exposure limit for health care professionals., Objectives: To monitor levels of cyclophosphamide, ifosfamide, and methotrexate contamination in oncology pharmacy and patient care areas in Canadian health care institutions., Methods: The study was conducted in 2014. Hospitals with at least 50 acute care beds were invited to participate. At each participating centre, 12 standardized sites (6 in pharmacy areas and 6 in patient care areas) were sampled. The samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by ultra-performance liquid chromatography tandem mass spectrometry technology. The limits of detection were 0.36 pg/cm(2) for cyclophosphamide, 0.95 pg/cm(2) for ifosfamide, and 0.97 pg/cm(2) for methotrexate. Descriptive statistical analyses were performed to determine the median, 75th percentile, and maximum levels., Results: Fifty-one hospitals participated in this descriptive study, and a total of 584 samples were quantified. Overall, 294 (50%) of the samples were positive for cyclophosphamide, 125 (21%) for ifosfamide, and 54 (9%) for methotrexate. The most frequently contaminated sampling sites in pharmacy areas were the front grille inside the hood and the floor in front of the hood and, in patient care areas, the armrest and outpatient clinic counter. The 75th percentiles for surface concentration were 10.8 pg/cm(2) for cyclophosphamide, 1.59 pg/cm(2) for ifosfamide, and below the limit of detection for methotrexate., Conclusions: Relative to 3 other multicentre studies conducted in Quebec over the past few years, the proportion of positive samples remained constant. Nonetheless, the 75th percentile surface concentration of antineoplastic drugs has been decreasing and seems to have reached a plateau. Local (country-specific or region-specific) and attainable goals for surface contamination with hazardous drugs should be set annually, so long as no health-based limit is known.

Objectives: To compare pharmacy support for paediatric research services in France and Canada and to describe the perception of pharmacists and rank the paediatric clinical research issues., Methods: This was a cross-sectional descriptive study. All paediatric hospitals from Canada and the main hospitals from France were contacted. A survey was conducted from May-September 2012. Descriptive statistics were performed., Key Findings: Results from 11 paediatric hospitals in Canada (11/12, 92%) and 11 (11/18, 61%) in France were obtained. There was a similar number of ongoing paediatric clinical trials per hospital in France versus Canada (38 (10-81) versus 20 (4-178)). A lower number of pharmacists per hospital was observed in France (17 (11.5-35) versus 45 (18.9-76.8)), but a similar number of pharmacists were assigned to clinical trials (1.5 (1-3) versus 1.9 (0.2-17.4)). Institutional protocols represented the majority of paediatric clinical trials in France (61% (14-100) versus 25% (0-100)). Similar pharmacy support services were offered, but the majority of French respondents also offered help for institutional protocol development (91 versus 50% P = 0.063). The main issues associated with paediatric clinical research were absence of financial interest from the pharmaceutical industry, prohibitive cost versus profit ratio, small patient cohorts and the non-availability of the appropriate drug formulations., Conclusions: Difficulties related to pharmaceutical compounding were identified as the main hindrance to paediatric clinical research; particular attention should be paid to these details when setting up a paediatric trial., (© 2014 Royal Pharmaceutical Society.)

Background: Honorary and ghost authorship, as well as competing interests, are well documented concerns related to the publication of scientific articles. Guidelines for writing and publishing scientific manuscripts are available, including those of the International Committee of Medical Journal Editors (ICMJE)., Objectives: The primary objective of this descriptive cross-sectional study was to identify, in the instructions for authors of pharmacy practice journals, guidance on authorship and competing interests. The secondary objective was to suggest suitable corrective measures for more transparent authorship., Methods: The first step of the project was to identify journals in the area of pharmacy practice. The instructions for authors of each journal were then reviewed to determine recommendations for avoiding problems related to authorship and competing interests. Finally, the members of the research team formulated potential corrective measures for researchers., Results: Of 232 pharmacy journals identified, 33 were deemed to focus on pharmacy practice. A total of 24 (73%) of these journals mentioned that they followed ICMJE policies, 14 (42%) asked authors to complete a competing interests disclosure form at the time of submission, 17 (52%) had a formal definition of authorship, and 5 (15%) asked for details of each author's contribution. A list of 40 criteria was developed to define authorship status., Conclusion: Fewer than half of the journals asked authors to provide a competing interests disclosure form upon submission of an article, and only half had a formal definition of authorship. The scientific publication of papers relevant to pharmacy practice is not free from issues related to publication transparency. Publishing articles online and using a checklist to detail each author's contribution may help to limit the associated risks. [Publisher's translation].

Purpose: No occupational exposure limit exists for antineoplastic drugs. The main objective of this study was to describe environmental contamination with cyclophosphamide, ifosfamide and methotrexate in pharmacy and patient care areas of Canadian hospitals in 2012. The secondary objective was to compare the 2012 environmental monitoring results with the 2008-2010 results., Methods: Six standardized sites in the pharmacy and six sites on patient care areas were sampled in each participating center. Samples were analyzed for the presence of cyclophosphamide, ifosfamide and methotrexate by UPLC-MS-MS. The limit of detection (LOD) was 1.8 pg/cm² for cyclophosphamide, 2.2 pg/cm² for ifosfamide and 8.0 pg/cm² for methotrexate. The comparison of surface contamination between the 2008-2010 and 2012 studies was made with the 75th percentile of cyclophosphamide concentration., Results: A total of 33 hospitals participated in the study and 363 samples were collected. Overall, 40 % (147/363) of the samples were positive for cyclophosphamide, 18 % (68/363) were positive for ifosfamide and 5 % (17/363) were positive for methotrexate. In 2012, the 75th percentile value of cyclophosphamide surface concentration was of 9.4 pg/cm², which is four times lower than the 2008-2010 75th percentile of 40 pg/cm². In both studies, the 75th percentile for ifosfamide and methotrexate concentration was lower than the LOD., Conclusions: Surface contamination by cyclophosphamide, ifosfamide and methotrexate in Canadian hospitals is improving both in terms of the proportions of positive samples and in terms of the surface concentration of antineoplastic drugs. A local 75th percentile value should be use to assess local contamination and interpret local results.