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Background and Aims Over 12 million healthcare professionals in Europe are exposed to hazardous medicinal products, including antineoplastic drugs. Dermal route is recognized as the primary route of exposure to antineoplastic drugs, emphasizing the critical importance of skin protection provided by gloves, which necessitates a careful and specific selection process. This study aims to compare the current European standard EN 16523‐1:2015 + A1:2018 with the ASTM D6978‐05(2023) standard used in the United States. Methods Firstly, the three main performance parameters to consider when selecting gloves are described: standardized breakthrough time, standardized permeation rate, and cumulative permeation. Subsequently, the current European and American standards are compared based on the following criteria: part of the glove tested, substances tested, standardized permeation rate, test duration, test temperature, and the information provided on the glove packaging. Additionally, and with a focus on safety, clear examples of how to interpret graphical symbols and indications available on glove packaging are provided to enhance the transferability of the information contained in this study to healthcare settings. Results There is a significant disparity between the requirements of the two standards. Indeed, the only European standard applicable in the context of glove permeation by antineoplastic drugs requires a standardized permeation rate 100 times less stringent than the American standard and does not include any hazardous drugs in its list of substances to be tested. By proposing a list of 24 antineoplastic drugs to be tested, a test temperature of 35 ± 2°C (compared with 23 ± 1°C in the European standard), and by specifically targeting the thinnest part of the glove, the American standard is closer to real‐world conditions of use compared to its European counterpart. Conclusion This study underscores the limitations of current European standard, advocating for regulatory updates to better protect healthcare professionals, while emphasizing the complexity of selecting appropriate gloves for antineoplastic and hazardous drug exposure. Clinical Trial Registration Not concerned.

ObjectiveThe aim of this study was to assess internal antineoplastic drugs (ADs) contamination in the nursing staff in French hospital centers, using highly sensitive analytical methods.MethodsThis cross-sectional study included nurses practicing in care departments where at least one of the five ADs studied was handled (5-fluorouracil, cyclophosphamide, doxorubicin, ifosfamide, methotrexate). The nurses study participation lasted 24 h including collection of three urine samples and one self-questionnaire. All urine samples were assayed by ultra-high-performance liquid chromatography–tandem mass spectrometry methods with very low value of the lower limit of quantification (LLOQ).Results74 nurses were included, 222 urine samples and 74 self-questionnaires were collected; 1092 urine assays were performed. The percentage of nurses with internal AD contamination was 60.8% and low levels of urinary concentrations were measured. Regarding nurses with internal contamination (n = 45), 42.2% presented internal contamination by methotrexate, 37.8% by cyclophosphamide, 33.3% by ifosfamide, 17.8% by 5-fluorouracil metabolite and 6.7% by doxorubicine. Among the positive assays, 17.9% (n = 26/145) were not explained by exposure data from the self-questionnaire but this could be due to the skin contact of nurses with contaminated work surfaces.ConclusionsThis study reported high percentage of nurses with internal ADs contamination. The low LLOQ values of the used analytical methods, allowed the detection of ADs that would not have been detected with the current published methods: the percentage of contamination would have been 17.6% instead of the 60.8% reported here. Pending toxicological reference values, urine ADs concentrations should be reduced as low as reasonably achievable (ALARA principle).

Exposure assessment is a critical point for epidemiological studies on pesticide health effects. PESTEXPO study provides data on levels of exposure and their determinants in real conditions of pesticide use. We described levels of exposure in vineyards during treatment tasks (mixing, spraying and cleaning) and we analysed their determinants. Sixty-seven operators using dithiocarbamates or folpet were observed. Detailed information on the tasks (general conditions, operator, farm and equipment characteristics) were collected and dermal contamination was measured, using patches placed onto the skin on eleven body parts, and washing the hands at the end of each phase. The spraying phase represented roughly half of the contamination, whereas mixing and equipment cleaning accounted for 30% and 20% of the contamination, respectively. The main determinants of exposure were the number of phases, the characteristics of the equipment, the educational level of the operator and his status (farm -worker or -owner) and the general characteristics of the vines. Algorithms were built to estimate daily external contamination, according to these characteristics during mixing, spraying or equipment cleaning. With additional information of frequency and duration of use, they will enable to develop exposure indices usable in epidemiological studies on farmers’ health.

IntroductionAntineoplastic drugs (AD) are potentially carcinogenic and/or reprotoxic molecules. Healthcare professionals are increasingly exposed to these drugs and can be potentially contaminated by them. Internal contamination of professionals is a key concern for occupational physicians in the assessment and management of occupational risks in healthcare settings. Objectives of this study are to report AD internal contamination rate in nursing staff and to identify factors associated with internal contamination.Methods and analysisThis trial will be conducted in two French hospital centres: University Hospital of Bordeaux and IUCT-Oncopole of Toulouse. The target population is nurses practicing in one of the fifteen selected care departments where at least one of the five studied AD is handled (5-fluorouracil, cyclophosphamide, doxorubicin, ifosfamide, methotrexate). The trial will be conducted with the following steps: (1) development of analytical methods to quantify AD urine biomarkers, (2) study of the workplace and organization around AD in each care department (transport and handling, professional practices, personal and collective protection equipments available) (3) development of a self-questionnaire detailing professional activities during the day of inclusion, (4) nurses inclusion (urine samples and self-questionnaire collection), (5) urine assays, (6) data analysis.Ethics and disseminationThe study protocol has been approved by the French Advisory Committee on the Treatment of Information in Health Research (CCTIRS) and by the French Data Protection Authority (CNIL). Following the opinion of the Regional Committee for the Protection of Persons, this study is outside the scope of the provisions governing biomedical research and routine care (n°2014/87). The results will be submitted to peer-reviewed journals and reported at suitable national and international meetings.Trial registration number NCT03137641.

Objectives Physical contact with treated crops, animals or other surfaces is responsible for the transfer of pesticides to the worker’s skin in agricultural tasks and makes their cutaneous absorption possible. In the Bordeaux area (France), the PESTEXPO study described levels of pesticide exposure and identified their determinants during re-entry and harvesting in vineyards. Method Between 2002 and 2007, 46 days of work involving re-entry tasks and 48 harvesting days were observed to analyse exposures to dithiocarbamates or folpet. The potential determinants were generated from the following parameters collected on standardised forms during field observations: i)general conditions of the task, ii)operator characteristics, iii)estate characteristics, iv) task conditions and v)characteristics of the last treatment involving folpet or dithiocarbamates, including delay since treatment. Dermal contamination was assessed using patches placed on the skin and hand-washing at the end of each working phase. Results Daily median contamination was 1 967.7 μl of mixture during re-entry (90e percentile: 5 045.3 μl) and 18.7 μl during harvesting (90e percentile: 911.4 μl). Contamination level was strongly correlated to the type of task. For re-entry, the highest contaminations were observed during raising of wires and cutting of branches. During the harvest, the contamination was maximal for grape-picking. The delay since the last treatment and the rate of active ingredient per hectare played a role, together with meteorological factors, crop and farm characteristics, gloves and clothes. Conclusions Our results underline the necessity to take into account exposures during re-entry and harvest when considering pesticide exposure, both for epidemiological research and preventive action.

Purpose Bupivacaine-induced myotoxicity is associated with mitochondrial bioenergetic alterations. The impact of the duration of bupivacaine treatment on mitochondrial energy production remains undetermined. Here, we assessed, in vivo , the alteration of mitochondrial metabolism following different durations of bupivacaine exposure (40, 56, or 112 hr) that correspond to 5, 7, or 14 repeated injections of 0.25% bupivacaine, respectively. Methods Rats were divided randomly into seven different groups: one control group (no catheter); three groups with normal saline injections (1 mL·kg −1 ) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr, respectively; and three groups with 0.25% bupivacaine injections (1 mL·kg −1 ) every eight hours via a femoral nerve catheter for 40, 56, and 112 hr. Psoas and gracilis muscle samples located within the bupivacaine infusion-diffusion space were investigated. To estimate mitochondrial respiratory capacity, the protein content of the mitochondrial respiratory chain apparatus was evaluated by measuring citrate synthase activity. To measure mitochondrial respiratory function, adenosine diphosphate-stimulated oxygen consumption was measured by polarography in saponin-skinned muscle fibres using glutamate-malate or succinate as energy substrates. Results In psoas and gracilis muscles, saline solution had no effect on the two mitochondrial parameters. Bupivacaine induced a significant decrease in the citrate synthase activity in psoas (r 2  = 0.74; P  < 0.001) and gracilis muscle (r 2  = 0.52; P  < 0.001), and there was a significant decrease in the adenosine diphosphate-stimulated oxygen consumption using glutamate or succinate as substrates in both muscles ( P  < 0.001). Conclusions The severity of bupivacaine-induced myotoxicity is closely linked to the duration of bupivacaine exposure in the muscle fibres located close to the catheter tip.