[Assessment of the risk of occurrence of musculoskeletal disorders in a production unit]. / État des lieux du risque de survenue de troubles musculosquelettiques dans une unité de production.

INTRODUCTION: In 2018, according to the latest report from the French National Cancer Institute (INCa), approximately 400,000 new cases of cancer in France were identified. Fifty-four percent were represented by men and 46% by women. The number of new cases increased between 2010 and 2018 (+6,000 cases for men and 23,000 for women). Hospital pharmacies caring for cancer patients must absorb this flow without having additional human resources or without being able to increase the capacity of the chemotherapy reconstitution unit. And this always while ensuring a quality according to the legal requirements. This increase of activity and the centralization of chemotherapy preparations bring with it new problems: musculoskeletal disorders (MSDs). The objective of this work is, through the improvement of work quality, to prevent and monitor the appearance of MSDs in pharmacy technician team. METHOD: Initially, using the Nordic questionnaire, an inventory of the pain and genes felt by the staff according to location and duration was conducted with pharmacy technician team. Secondly, an assessment of the risk of occurrence of MSDs in the pharmacy technician team according to the tasks performed was carried out using the Borg CR10 scale and the Occupational Safety and Health Administration (OSHA) checklist. RESULTS/DISCUSSION: The prevalence of musculoskeletal complaints over the last twelve months and the last seven days within the sample was highest for the wrists/hands (67% and 56%) and head/neck (56% and 33%). The severity index of musculoskeletal problems at work was 50% for the elbow region and 33% for the wrist/hand region. According to the OSHA checklist, the workstations for the preparation of cytotoxics and the workstations for the preparation of analgesics intended for the intrathecal route obtained a score greater than 5, which is equivalent to a risk of occurrence of MSDs. On the positions evaluated using Borg's CR10 scale, the following body regions saw a significant increase in the strain felt after a day of production: head/neck (P-value 0.04), upper back (P-value 0.03), lower back (P-value 0.03) and legs (0.04). CONCLUSION: This work made it possible to produce a map of the body regions affected, to identify the positions at risk and to assess the level of risk. Several approaches have been defined to prevent MSDs for the pharmacy technician team. Staff training, by one of the physiotherapists, in muscle warm-ups before a production day is planned. In the continuity of this approach, an expertise by an ergonomist, which could not be carried out due to the health situation and the preventive measures would be essential in order to put in place additional preventive and curative actions.

A fully validated simple new method for environmental monitoring by surface sampling for cytotoxics.

A wipe sampling procedure followed by a simple ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneous quantification of six cytotoxic drugs: 5-fluorouracil (5FU), doxorubicin (DOXO), epirubicin (EPI), ifosfamide (IF), cyclophosphamide (CP) and gemcitabine (GEM), as surrogate markers for occupational exposure. After a solid-phase extraction of wiping filter on 10 × 10 cm surface, the separation was performed within 6.5 min, using a gradient mobile phase and the analytes were detected by mass spectrometry in the multiple reaction ion monitoring mode. The method was validated according to the recommendations of the US Food and Drug Administration. The method was linear (r2 > 0.9912) between 2.5 and 200 ng per wiping sample (25 to 2000 pg/cm2) for 5FU, doxorubicin and epirubicin and between 0.2 and 40 ng per wiping sample (2 to 400 pg/cm2) for cyclophosphamide, ifosfamide and gemcitabine. The lower limits of quantification were 2.5 ng (25 pg/ cm2) for 5FU, doxorubicin and epirubicin, and 0.2 ng (2 pg/cm2) for CP, IF and GEM. Within-day and between-day imprecisions were <14.0, 10.6, 11.1, 8.7, 11.2 and 10.9% for 5-fluorouracil, doxorubicin, epirubicin, ifosfamide cyclophosphamide and gemcitabine, respectively. The inaccuracies did not exceed 2.7, 10.9, 1.1, 4.5, 1.6 and 2.9% for the studied molecules, respectively. This new sensitive validated method for surface contamination studies of cytotoxics was successfully applied on different localizations in hospital. This approach is particularly suitable to assess occupational exposure risk to cytotoxic drugs.

[Pharmaceutical consultations in oncology: Implementation, one-year review and outlooks]. / Consultations pharmaceutiques en oncologie : mise en place, bilan à un an et perspectives.

OBJECTIVES: The oral route is becoming increasingly important in the panel of anti-cancer therapeutics, but it generates difficulties (adherence, management of adverse effects...). In order to secure medication management, the pharmaceutic team chose to set up pharmaceutical consultations. Its objectives are multiple: understanding of treatment for better adherence, pharmaceutical analysis, enhancement of the city-hospital link. This work presents the setting up of the pharmaceutical consultations and makes an assessment after one year. METHODS: The initial step was a meeting with institutional health professionals who work with patients to define the place, the objectives, and the patients targeted by the pharmaceutical consultation. The targeted patients are all patients receiving temozolomide and some patients initiating oral chemotherapy, considered at risk, on medical solicitation. Documents were created to standardize practices in the team from the collection of information and pharmaceutical analysis until the conduct of the consultation and the consultation report (integrated into the computerized patient's medical file). Activity indicators were defined and collected. RESULTS: Over one year, 65 pharmaceutical consultations were conducted, of which 23 % resulted in pharmaceutical interventions. The average duration of consultation was 34minutes. The whole team (four pharmacists and two residents) was involved in this activity. CONCLUSIONS: Pharmaceutical consultations help secure medical care of patients, providing tools, dedicated and personalized time, pharmaceutical analysis, etc. Ultimately, the goal is to accompany the patient throughout his treatment by having follow-up pharmaceutical consultations, in collaboration with community pharmacists thanks to the city-hospital link that we have established.

Stability of sufentanil and baclofen mixtures for intrathecal analgesia at different concentrations in polypropylene syringes.

BACKGROUND: Intrathecal analgesia is a method using various molecules alone or in combination. Among these, the association sufentanil/ baclofen is widely used. Instead of moving patients to the few expert centers taking charge of these specific preparations, it could be better to transport syringes to peripheral centers managing pump refilling. That is why, it is interesting to demonstrate the stability of the mixture, and so to be able to ensure the best transport conditions of syringes. METHODS: A stability indicating UPLC-DAD method was developed and validated according to the ICH guidelines. Four mixtures of sufentanil baclofen stored in 5±3°C and 25±2°C were evaluated for seven days and compared to the initial observed concentrations. RESULTS: The stability is demonstrated only for preparations stored at 5±3°C for seven days thanks to relative concentrations (95% confidence intervals of the mean of 3 samples) systematically positioned between 90% and 110%. On the other hand, after few days, degradation products of sufentanil appeared for all mixtures stored at 25°C±2°C. CONCLUSION: This study shows the stability of a weakly and a highly concentrated mixture of sufentanil and baclofen solutions in polypropylene syringes stored at 5±3°C for seven days. This result will allow the transport of the preparation under optimal conditions. Advance preparations for intrathecal pump refills could also be feasible.

Validated chromatographic method for the simultaneous determination of eight drugs (morphine, ropivacaine, bupivacaine, baclofen, clonidine, sufentanil, fentanyl and ziconotide) for intrathecal analgesia.

Intrathecal analgesia has increased over the past two decades in various indications: chronic refractory pain from cancerous or non-cancerous origins, spasticity. These different indications involve the use of different molecules alone or in combination such as morphine, ropivacaine, bupivacaine, fentanyl, sufentanil, clonidine, baclofen and ziconotide. Pump refills are prepared at the pharmacy under a laminar flow hood. An analytical control should be carried out before release of the preparation. A new method of analytical control by chromatography has been developed and validated according to the International Conference on Harmonization guideline in order to secure the production process.