An Easily Expandable Multi-Drug LC-MS Assay for the Simultaneous Quantification of 57 Oral Antitumor Drugs in Human Plasma

Oral anticancer drugs have led to significant improvements in the treatment of multiple tumor entities. However, in patients undergoing oral antitumor therapy, plasma concentrations are highly variable, resulting in risks of reduced therapeutic effects or an increase in side effects. One important tool to reduce this variability is therapeutic drug monitoring. In this work we describe a method to simultaneously quantify the plasma concentrations of 57 oral antitumor agents. Quantification of these drugs was achieved using liquid chromatography coupled to an Orbitrap mass spectrometer. The method was fully validated according to the FDA guidelines and constitutes a simple and robust way for exposure monitoring of a wide variety of oral anticancer drugs. Applicability to clinical routine was demonstrated by the analysis of 71 plasma samples taken from 39 patients. In summary, this new multi-drug method allows simultaneous quantification of 57 oral antitumor drugs, which can be applied to exposure monitoring in clinical studies, taking into account the broad variety of oral antitumor drugs prescribed in clinical routine.

User-Centred Design of a Final Results Report for Participants in Multi-Sensor Personal Air Pollution Exposure Monitoring Campaigns

Using low-cost portable air quality (AQ) monitoring devices is a growing trend in personal exposure studies, enabling a higher spatio-temporal resolution and identifying acute exposure to high concentrations. Comprehension of the results by participants is not guaranteed in exposure studies. However, information on personal exposure is multiplex, which calls for participant involvement in information design to maximise communication output and comprehension. This study describes and proposes a model of a user-centred design (UCD) approach for preparing a final report for participants involved in a multi-sensor personal exposure monitoring study performed in seven cities within the EU Horizon 2020 ICARUS project. Using a combination of human-centred design (HCD), human–information interaction (HII) and design thinking approaches, we iteratively included participants in the framing and design of the final report. User needs were mapped using a survey (n = 82), and feedback on the draft report was obtained from a focus group (n = 5). User requirements were assessed and validated using a post-campaign survey (n = 31). The UCD research was conducted amongst participants in Ljubljana, Slovenia, and the results report was distributed among the participating cities across Europe. The feedback made it clear that the final report was well-received and helped participants better understand the influence of individual behaviours on personal exposure to air pollution.

1400. Pretomanid in the Treatment of Patients with Tuberculosis in the United States: the Bedaquiline, Pretomanid and Linezolid (BPaL) Accelerated Monitoring (BAM) Project

Background In August 2019 the U.S. FDA approved pretomanid as part of a 6-month all-oral BPaL (bedaquiline, pretomanid, and linezolid) regimen for treating pulmonary extensively drug-resistant (XDR) or treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB). In the study supporting approval, 89% of patients had a favorable outcome, and all reported ≥ 1 adverse event. We describe the reported use of BPaL in the United States. Methods Using the 2020 CDC Report of a Verified Case of Tuberculosis (RVCT) MDR TB supplemental form, TB programs and providers submitted data for patients who began taking BPaL between Aug 1, 2019 and May 1, 2020, for retrospective descriptive analysis. Results Programs and providers reported 17 TB patients aged a mean of 41 years (range 23–76) who received BPaL: 11 (65%) were male; 15 (88%) were non-U.S. born; 15 (88%) had pulmonary TB disease only; two (12%) had both pulmonary and extrapulmonary disease. Of all patients, 16 had Mycobacterium tuberculosis isolated from sputum and 7 (44%) had cavitary disease. The preliminary drug susceptibilities were 8 MDR patterns, 8 pre-XDR, and 1 unreported. Three patients received BPaL as their only treatment; six first received treatment for drug-susceptible TB, and eight received other regimens for MDR TB before BPaL. Eleven (65%) patients had ≥ 1 side effect reported during any TB treatment, including peripheral neuropathy (n=5), depression (n=4), vestibular dysfunction (n=3), and vision changes (n=3). Timing related to specific TB drug use was not reported. Sixteen (94%) patients received less than the approved initial dose of 1200 mg linezolid daily, and 15 (88%) patients underwent monitoring of linezolid exposure. All 16 patients with M. tuberculosis in initial sputa converted to negative culture results within 6 months of starting treatment. At 12 months after BPaL initiation, all patients had completed treatment, without TB recurrences or deaths reported. Conclusion In the early period after FDA approval, most U.S. patients received BPaL off-label with an initial linezolid dose lower than the approved 1200mg yet still achieved good outcomes. Most reported patients underwent some monitoring of linezolid exposure. Monitoring of BPaL use is important and should continue. Disclosures All Authors: No reported disclosures

Trends in Airborne Chrysotile Asbestos Fibre Concentrations in Asbestos Cement Manufacturing Factories in Zimbabwe from 1996 to 2016

Zimbabwe has two major factories that have been manufacturing chrysotile asbestos cement products since the 1940s. Exposure monitoring of airborne fibres has been ongoing since the early 1990s. This study examines trends in personal exposure chrysotile asbestos fibre concentrations for the period 1996–2016. Close to 3000 historical personal exposure measurements extracted from paper records in the two factories were analysed for trends in exposure. Exposure over time was characterised according to three time periods and calendar years. Mean personal exposure chrysotile asbestos fibre concentrations generally showed a downward trend over the years in both factories. Exposure data showed that over the observed period 57% and 50% of mean personal exposure chrysotile asbestos fibre concentrations in the Harare and Bulawayo factories, respectively, were above the OEL, with overexposure being exhibited before 2008. Overall, personal exposure asbestos fibre concentrations in the factories dropped from 0.15 f/mL in 1996 to 0.05–0.06 f/mL in 2016—a decrease of 60–67%. These results can be used in future epidemiological studies, and in predicting the occurrence of asbestos-related diseases in Zimbabwe.

User-Centred Design of a Final Results Report for Participants in Multi-Sensor Personal Air Pollution Exposure Monitoring Campaigns

Using low-cost portable air quality (AQ) monitoring devices is a growing trend in personal exposure studies enabling a higher spatio-temporal resolution and identifying acute exposure to high concentrations. Comprehension of results by participants is not guaranteed in exposure studies. However, information on personal exposure is multiplex, which calls for participant involvement to maximise communication output and comprehension. This study describes a user centred design (UCD) approach for preparing a final report for participants involved in a multi-sensor personal exposure monitoring study performed in seven cities within the EU Horizon 2020 ICARUS project. Using a combination of human-centred design (HCD), human-information interaction (HII) and design thinking approaches, we iteratively included participants in the framing and design of the final report. User needs were mapped using a survey (n=82), and feedback on the draft report was obtained from a focus group (n=5). User requirements were assessed and validated using a post-campaign survey (n=31). The UCD research was conducted amongst participants in Ljubljana, Slovenia and the results report was distributed among the participating cities across Europe. The feedback received made it clear that the final report was well-received and helped participants better understand the influence of individual behaviours on personal exposure to air pollution.

AN INVENTORY OF OCCUPATIONAL CANCER STUDIES AND THEIR EXPOSURE ASSESSMENT METHODS IN IRAN

Introduction: The presence of occupational carcinogens in workplaces in Iran is not well characterized, and little is known about the burden of occupational cancer in Iran and other Middle East countries. Objectives: This study aimed to provide an overview of exposure assessments used in or informative for epidemiological studies on occupational cancer in Iran. Methods: Studies estimating occupational exposures applied to or informative for occupational cancer risk up to January 2021 in Iran were identified through different databases. Results: Forty-nine publications from 2009 to 2020 were included. The exposure monitoring studies were conducted mainly in gasoline refueling stations, foundries, construction industry, and manufacturing, and some of the case-control studies also reported increased risk of cancers in relation to work in those industries. Conclusion: Occupational cancer epidemiology in Iran is at an early stage. Both epidemiological and exposure monitoring studies are generally limited in size to provide robust evidence. A coherent strategy to estimate the occupational cancer burden in Iran should start with systematic monitoring of occupational carcinogens for use in hazard control and research.