Total Value of Ownership and Overall Equipment Effectiveness analysis to evaluate the impact of automation on time and costs of therapeutic drug monitoring

Abstract Total Value of Ownership (TVO) and Overall Equipment Effectiveness (OEE) analysis are novel tools capable of monitoring and analyzing industrial processes by assessing the efficiency of the entire instrumental equipment and calculating instrument capacity utilization. Such integrated analysis, measuring quality indicators of the testing process, could also provide new perspectives and methodologies for the workflow organization of clinical laboratories. In this study, TVO and OEE were employed for the evaluation of two different configurations of a therapeutic drug monitoring sector, comparing the results obtained for immunosuppressant (ISD) and anti-epileptic drugs (AED) analysis as well as checking their quantitative performance in terms of limit of quantification, accuracy and precision. TVO analysis was performed for ISDs, including the Total Direct Labor Time, Total Cycle Time and Turnaround Time as well as cost of testing. Instruments' performance and workload were assessed using OEE indicator, studying Availability, Performance and Quality factors. Total Cycle Time for a batch was 3.55 h, decreasing of 1.5 h in the new setting where personnel are engaged for 0.98 h, 25% of total testing time. The calculated cost per sample was 6.60 euro. Availability values were significantly higher for automated sample-handling system and ISDs analysis by LC-MS. Higher Performance values were obtained for LC-MS system for AED and other TDM. Quality values were >0.94 for all instruments. TVO and OEE proved to be applicable to clinical laboratory environment, quantifying benefits and costs of newly developed semi-automated therapeutic drug monitoring sector. This novel approach based on an integrated analysis may help activity planning and quality improvement and could be used in the future for benchmarking progress as a product/process comparison tool in other laboratory fields

Linguistic profile automated characterisation in pluripotential clinical high-risk mental state (CHARMS) conditions: methodology of a multicentre observational study

Introduction: Language is usually considered the social vehicle of thought in intersubjective communications. However, the relationship between language and high- order cognition seems to evade this canonical and unidirectional description (ie, the notion of language as a simple means of thought communication). In recent years, clinical high at-risk mental state (CHARMS) criteria (evolved from the Ultra-High-Risk paradigm) and the introduction of the Clinical Staging system have been proposed to address the dynamicity of early psychopathology. At the same time, natural language processing (NLP) techniques have greatly evolved and have been successfully applied to investigate different neuropsychiatric conditions. The combination of at-risk mental state paradigm, clinical staging system and automated NLP methods, the latter applied on spoken language transcripts, could represent a useful and convenient approach to the problem of early psychopathological distress within a transdiagnostic risk paradigm. Methods and analysis: Help-seeking young people presenting psychological distress (CHARMS+/− and Clinical Stage 1a or 1b; target sample size for both groups n=90) will be assessed through several psychometric tools and multiple speech analyses during an observational period of 1-year, in the context of an Italian multicentric study. Subjects will be enrolled in different contexts: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa—IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Mental Health Department—territorial mental services (ASL 3—Genoa), Genoa, Italy; and Mental Health Department—territorial mental services (AUSL—Piacenza), Piacenza, Italy. The conversion rate to full-blown psychopathology (CS 2) will be evaluated over 2 years of clinical observation, to further confirm the predictive and discriminative value of CHARMS criteria and to verify the possibility of enriching them with several linguistic features, derived from a fine-grained automated linguistic analysis of speech. Ethics and dissemination: The methodology described in this study adheres to ethical principles as formulated in the Declaration of Helsinki and is compatible with International Conference on Harmonization (ICH)-good clinical practice. The research protocol was reviewed and approved by two different ethics committees (CER Liguria approval code: 591/2020—id.10993; Comitato Etico dell’Area Vasta Emilia Nord approval code: 2022/0071963). Participants will provide their written informed consent prior to study enrolment and parental consent will be needed in the case of participants aged less than 18 years old. Experimental results will be carefully shared through publication in peer- reviewed journals, to ensure proper data reproducibility. Trial registration number DOI:10.17605/OSF.IO/BQZTN

Deciphering Diseases and Biological Targets for Environmental Chemicals using Toxicogenomics Networks

Exposure to environmental chemicals and drugs may have a negative effect on human health. A better understanding of the molecular mechanism of such compounds is needed to determine the risk. We present a high confidence human protein-protein association network built upon the integration of chemical toxicology and systems biology. This computational systems chemical biology model reveals uncharacterized connections between compounds and diseases, thus predicting which compounds may be risk factors for human health. Additionally, the network can be used to identify unexpected potential associations between chemicals and proteins. Examples are shown for chemicals associated with breast cancer, lung cancer and necrosis, and potential protein targets for di-ethylhexyl-phthalate, 2,3,7,8-tetrachlorodibenzo-p-dioxin, pirinixic acid and permethrine. The chemical-protein associations are supported through recent published studies, which illustrate the power of our approach that integrates toxicogenomics data with other data types

Inverse association of colorectal cancer prevalence to serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in a large Appalachian population

Background Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants that affect metabolic regulation, inflammation, and other factors implicated in the development and progression of colorectal cancer (CRC). However, the link between these compounds and CRC remains unknown. In this cross-sectional study, we investigated the association of CRC diagnosis to PFOA and PFOS blood levels in a large Appalachian population. Methods Participants were 47,359 adults ≥ 21 years of age and residing in six PFOA-contaminated water districts in the mid-Ohio Valley (N = 47,151 cancer-free adults, 208 cases of primary CRC). All participants completed a comprehensive health survey between 2005 and 2006; serum levels of PFOA, PFOS, and a range of other blood markers were also measured. Medical history was assessed via self report and cancer diagnosis confirmed via chart review. Results CRC showed a strong inverse, dose–response association with PFOS serum levels (odds ratio (OR) adjusted for potential confounders = 0.2, 95% confidence interval (CI) 0.2,0.3) for highest vs. lowest quartile of PFOS, P-trend \u3c 0.00001) and a significant, but more modest inverse association with PFOA (adjusted OR = 0.6 (CI 0.4, 0.9) for highest vs. lowest quartile, P-trend = 0.001). These inverse associations were stronger in those diagnosed within the previous 6 years and resident in the same water district for a minimum of 10–15 years preceding assessment. The relationship between PFOA and CRC was also more pronounced in men and leaner adults, and showed a stronger linear trend at lower exposure levels. Conclusions In this large cross-sectional study, we found a strong, inverse association between PFOS and likelihood of CRC diagnosis and a significant, although more modest inverse association between PFOA and CRC. If confirmed in prospective investigations, these findings may aid in identifying new strategies for CRC prevention and treatment and inform future studies regarding mechanisms underlying CRC pathogenesis