Evaluation of the risk of occupational exposure to antineoplastic drugs in healthcare sector: part II - the application of the FMECA method to compare manual vs automated preparation.

Healthcare workers handling antineoplastic drugs (ADs) in preparation units run the risk of occupational exposure to contaminated surfaces and associated mutagenic, teratogenic, and oncogenic effects of those drugs. To minimise this risk, automated compounding systems, mainly robots, have been replacing manual preparation of intravenous drugs for the last 20 years now, and their number is on the rise. To evaluate contamination risk and the quality of the working environment for healthcare workers preparing ADs, we applied the Failure Mode Effects and Criticality Analysis (FMECA) method to compare the acceptable risk level (ARL), based on the risk priority number (RPN) calculated from five identified failure modes, with the measured risk level (MRL). The model has shown higher risk of exposure with powdered ADs and containers not protected by external plastic shrink film, but we found no clear difference in contamination risk between manual and automated preparation. This approach could be useful to assess and prevent the risk of occupational exposure for healthcare workers coming from residual cytotoxic contamination both for current handling procedures and the newly designed ones. At the same time, contamination monitoring data can be used to keep track of the quality of working conditions by comparing the observed risk profiles with the proposed ARL. Our study has shown that automated preparation may have an upper hand in terms of safety but still leaves room for improvement, at least in our four hospitals.

Cost and effectiveness of autologous haematopoietic stem cell transplantation and high-efficacy disease-modifying therapies in relapsing-remitting multiple sclerosis.

BACKGROUND: Autologous haematopoietic stem cell transplantation (AHSCT) is a highly effective one-off treatment for relapsing-remitting multiple sclerosis (RR-MS), potentially representing an optimal front-loading strategy for costs. OBJECTIVE: Exploring cost/effectiveness of AHSCT and high-efficacy disease-modifying treatments (HE-DMTs) in RR-MS, estimating costs at our centre in Italy, where National Health Service (NHS) provides universal health coverage. METHODS: Costs (including drugs, inpatient/outpatient management) for treatment with AHSCT and HE-DMTs were calculated as NHS expenditures over 2- and 5-year periods. Cost-effectiveness for each treatment was estimated as "cost needed to treat" (CNT), i.e. expense to prevent relapses, progression, or disease activity (NEDA) in one patient over n-years, retrieving outcomes from published studies. RESULTS: Costs of AHSCT and HE-DMTs were similar over 2 years, whereas AHSCT was cheaper than most HE-DMTs over 5 years (€46 600 vs €93 800, respectively). When estimating cost-effectiveness of treatments, over 2 years, mean CNT of HE-DMTs for NEDA was twofold that of AHSCT, whereas it was similar for relapses and disability. Differences in CNT were remarkable over 5 years, especially for NEDA, being mean CNT of HE-DMTs €382 800 vs €74 900 for AHSCT. CONCLUSIONS: AHSCT may be highly cost-effective in selected aggressive RR-MS. Besides priceless benefits for treated individuals, cost-savings generated by AHSCT may contribute to improving healthcare assistance at a population level.

Monitoring surface contamination for thirty antineoplastic drugs: a new proposal for surface exposure levels (SELs).

BACKGROUND: Chemotherapy drugs are widely used to treat cancer, but their active compounds represent a danger for workers who could be exposed to them. However, they aren't yet included in directive CE No. 1272/2008 and the European Biosafety Network has only recommended a limit value of 100 pg/cm2 for surface contamination. Thus, it is crucial to assess surface contaminations in healthcare environments. Currently, the technique of choice is surface wipe test combined with liquid chromatography tandem mass spectrometry to achieve high sensibility. MATERIAL AND METHODS: A campaign involving Careggi University Hospital (Florence, Italy) was performed from January 2020 to December 2021, collecting 1449 wipe samples between administration units, preparation unit, and personnel gloves. From the obtained data, the 90th percentile was calculated for 30 antiblastic drugs and proposed as surface exposure levels (SELs); while from data concerning personnel glove contamination, weekly contamination was estimated. RESULTS: In the 2-year period only 417 wipe samples were found positive (28.8%), the majority of which regard samples coming from administration unit bathrooms. The proposed SELs are almost all <100 pg/cm2, except for few drugs which produce higher contamination on bathroom surfaces. Also, the estimation of pharmacy personnel's glove contamination highlighted very low results (ng/week). CONCLUSIONS: Deeply established protocols and procedures for safe handling of ADs allow for obtaining excellent cleaning results and thus a safer work environment, however, the risk of cytostatic contaminations cannot be avoided in healthcare workplaces, and thus a harmonization of classification and labeling of chemotherapy drugs throughout the European Union should be done. Med Pr. 2022;73(5):383-96.

Long-term SARS-CoV-2 Asymptomatic Carriage in an Immunocompromised Host: Clinical, Immunological, and Virological Implications.

PURPOSE: SARS-CoV-2 infection in immunocompromised hosts is challenging, and prolonged viral shedding can be a common complication in these patients. We describe the clinical, immunological, and virological course of a patient with eosinophilic granulomatosis with polyangiitis, who developed the status of long-term asymptomatic SARS-CoV-2 carrier for more than 7 months. METHODS: Over the study period, the patient underwent 20 RT-PCR tests for SARS-CoV-2 detection on nasopharyngeal swabs. In addition, viral cultures and genetic investigation of SARS-CoV-2 were performed. As for immunological assessment, serological and specific T-cell testing was provided at different time points. RESULTS: Despite the patient showing a deep drug-induced B and T adaptive immunity impairment, he did not experience COVID-19 progression to severe complications, and the infection remained asymptomatic during the follow-up period, but he was not able to achieve viral clearance for more than 7 months. The infection was finally cleared by SARS-CoV-2-specific monoclonal antibody treatment, after that remdesivir and convalescent plasma failed in this scope. The genetic investigations evidenced that the infection was sustained by multiple viral subpopulations that had apparently evolved intra-host during the infection. CONCLUSION: Our case suggests that people with highly impaired B- and T-cell adaptive immunity can prevent COVID-19 progression to severe complications, but they may not be able to clear SARS-CoV-2 infection. Immunocompromised hosts with a long-term infection may play a role in the emergence of viral variants.

Implementing Early Phase Treatments for COVID-19 in Outpatient Settings: Challenges at a Tertiary Care Center in Italy and Future Outlooks.

We present a brief commentary illustrating the current COVID-19 outpatient treatment options in Italy. We also report our experience setting up a service dedicated to these patients in the wake of the rise in COVID-19 cases observed in January 2022. We also gathered data on the daily costs faced by our outpatient service, based at a tertiary care center located in Florence, Italy. We present them with some considerations on future outlooks on the use of outpatient treatment in COVID-19.

Analytical strategies for assessing occupational exposure to antineoplastic drugs in healthcare workplaces.

BACKGROUND: Cytotoxic antineoplastic drugs (ADs), widely used in treating cancer, are considered hazardous in the workplace and thus require safe handling practices. An analytical protocol for environmental and biological AD monitoring in the healthcare environment has been developed, since Europe lacks clear guidelines and regulations for cytostatic preparation and handling. MATERIAL AND METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for measuring contemporaneously 20 multi-class cytostatic compounds and urinary α-fluoro-ß-alanine, whereas platinum was detected by inductively coupled plasma mass spectrometry (ICP-MS). Sampling procedures and analytical conditions were optimized and the assays were validated. Environmental AD monitoring data, collected in 2009-2017, for a total of 3749 wipe tests and 57 720 determinations, was evaluated. RESULTS: The proportion of positive samples gradually decreased from 11.7% in 2010 to 1% in 2017, however, 2266 determinations were positive. No urine sample had detectable concentrations of any of the 4 drugs considered (0/398 samples). CONCLUSIONS: These improvements are so large that the key role played by the new, more stringent rules for preparing and administering ADs is evident. Hence, the analytical method involving multi-element determinations allows for a more thorough and complete investigation into the AD contamination of work environments. Med Pr 2018;69(6):589-604.

A retrospective observational analysis to evaluate the off-label use of bevacizumab alone or with irinotecan in recurrent glioblastoma.

BACKGROUND: Recurrent glioblastoma is nearly always fatal, with median survival rates of approximately 12-14 months. Previous phase II clinical trials showed promising results with bevacizumab, alone or in combination with irinotecan, in patients with recurrent glioblastoma. OBJECTIVE: To assess whether the survival of patients with recurrent glioblastoma receiving bevacizumab alone or with irinotecan in everyday practice is comparable to that reported in clinical trials. SETTING: This was a retrospective observational study conducted at a single hospital in Italy. METHOD: Patients with recurrent glioblastoma who had received bevacizumab alone or with irinotecan from January 2009 to September 2011 were included in our study. MAIN OUTCOME MEASURE: Progression-free survival (PFS) and overall survival (OS), and rates of PFS and OS at 6 months. RESULTS: Median PFS was 5.1 months in the bevacizumab group (n = 9) and 15.4 months in the bevacizumab + irinotecan group (n = 10), with 6-month PFS rates of 45 and 69%, respectively. Median OS was 6.8 months for bevacizumab alone and 11.1 months for bevacizumab + irinotecan, with 6-month OS rates of 100 and 90%, respectively. CONCLUSION: Although the number of patients included is not sufficient to allow a conclusive statement about the place of bevacizumab in the treatment of recurrent glioblastoma, the data appear promising, and are consistent with the results of clinical trials.