Can we increase efficiency of CT lung cancer screening by combining with CVD and COPD screening? Results of an early economic evaluation

Objectives Estimating the maximum acceptable cost (MAC) per screened individual for low-dose computed tomography (LDCT) lung cancer (LC) screening, and determining the effect of additionally screening for chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD), or both on the MAC. Methods A model-based early health technology assessment (HTA) was conducted to estimate whether a new intervention could be cost-effective by calculating the MAC at a willingness-to-pay (WTP) of €20k/quality-adjusted life-year (QALY) and €80k/QALY, for a population of current and former smokers, aged 50–75 years in The Netherlands. The MAC was estimated based on incremental QALYs gained from a stage shift assuming screened individuals are detected in earlier disease stages. Data were obtained from literature and publicly available statistics and validated with experts. Results The MAC per individual for implementing LC screening at a WTP of €20k/QALY was €113. If COPD, CVD, or both were included in screening, the MAC increased to €230, €895, or €971 respectively. Scenario analyses assessed whether screening-specific disease high-risk populations would improve cost-effectiveness, showing that high-risk CVD populations were more likely to improve economic viability compared to COPD. Conclusions The economic viability of combined screening is substantially larger than for LC screening alone, primarily due to benefits from CVD screening, and is dependent on the target screening population, which is key to optimise the screening program. The total cost of breast and cervical cancer screening is lower (€420) than the MAC of Big-3, indicating that Big-3 screening may be acceptable from a health economic perspective. Key Points • Once-off combined low-dose CT screening for lung cancer, COPD, and CVD in individuals aged 50–75 years is potentially cost-effective if screening would cost less than €971 per screened individual. • Multi-disease screening requires detailed insight into the co-occurrence of these diseases to identify the optimal target screening population. • With the same target screening population and WTP, lung cancer-only screening should cost less than €113 per screened individual to be cost-effective.

Ein non-target Ansatz zur Identifizierung von Komplexbildnern in atmosphärischen Aerosolen und Regenwasser

<p>Atmosphärische Aerosolproben aus der Gas- und Flüssigphase bestehen aus zahlreichen organischen Substanzen. So beinhaltet sekundäres organisches Aerosol (SOA) bis zu 100 000 verschiedene organische Substanzen, welche durch Oxidation von biogenen und anthropogenen volatilen organischen Verbindungen (VOC) gebildet werden. Einige davon können zusammen mit Metallkationen von Eisen, Kupfer oder Mangan Komplexe in Aerosolpartikeln ausbilden. Solche Komplexe können photochemische Umwandlungsreaktionen auslösen und tragen zur verbesserten Löslichkeit von Metallionen in die atmosphärische Flüssigphase bei. Komplexbildner sind deswegen wichtige, aber nur schwer identifizierbare, organische Bestandteile von Aerosolpartikeln. In dieser Studie haben wir eine Flüssigkeitschromatographie mit hochauflösender Massenspektrometrie (LC/HR-MS) gekoppelt um ein Non-Target-Screening (NTS) durchzuführen, der den selektiven Nachweis von Komplexbildnern in Aerosolpartikelextrakten ermöglicht. Hierfür wurde ein T-Stück zwischen LC Auslass und der Ionenquelle eingebaut um eine Nachtrennsäulen-Komplexierung mit einer 155 µM FeCl<sub>3</sub> Lösung umzusetzen. Anschließend werden die erhaltenen Massenspektren auf die drei charakteristischen Eisenkomplexe [M-H+FeCl<sub>3</sub>]<sup>-</sup>, [M-2H+FeCl<sub>2</sub>]<sup>-</sup> und [M-3H+FeCl]<sup>-</sup> untersucht, dabei betragen die Massenunterschiede (∆<em>m/z</em>) zwischen dem Signal des jeweiligen Komplexbildners und des Eisenkomplexes 160,8416, 124,8648 und 89,8959. In Aerosolpartikelproben aus Deutschland und China konnten bis zu 29 verschiedene Di- und Tricarbonsäuren als Komplexbildner nachgewiesen werden, selbst bei niedrigen Extrakt Konzentrationen von nur 50 nM. Ohne Nachtrennsäulen-Komplexierung mit Eisen werden noch 13 Komplexbildner identifiziert, welche durch Hintergrund Eisenspuren aus dem Analysesystem komplexiert werden. Zumindest für die am höchsten konzentrierten Komplexbildner ist der vorgeschlagene Screening-Ansatz somit auch ohne Geräteumbau anwendbar, besonders attraktiv ist dies für den Einsatz in der Routineanalytik. Neben Carbonsäuren wurden 4-Nitrophenol und 4-Nitrocatechol als weitere Komplexbildner in Regenwasserproben entdeckt, was die Anwendbarkeit der Methode auf andere Matrices und auf eine Reihe verschiedener Komplexbildner zeigt. </p>

Target Screening of Hydroxylated and Nitrated Polycyclic Aromatic Hydrocarbons in Surface Water Using Orbitrap High–Resolution Mass Spectrometry in a Lake in Hebei, China

Polycyclic aromatic hydrocarbon (PAH) derivatives are mutagenic, carcinogenic, teratogenic and bioaccumulative pollutants. Investigations on hydroxylated PAHs (OH–PAHs) and Nitrated PAHs (NPAHs) in surface water are not enough. In this study, optimization and validation of an analytical method targeting nine kinds of OH–PAHs and one kind of nitrated PAH in environmental water samples are presented. The method was validated for linearity, limits of detection and quantification and recovery using spiked matrix. The linear range of most target compounds was 0.1–200 ng∙mL−1. However, the linear range of 1–hydroxy pyrene and 3–hydroxy benzo[a]pyrene started at 1 ng∙mL−1 and the linear range of 1–hydroxy phenanthrene and 9–hydroxy benzo[a]pyrene could not reach 200 ng∙mL−1. All the correlation coefficients (r2) were over 0.997. The instrumental limits of detection (LOD) and method detection limits (MDL) ranged from 0.01 to 0.67 ng∙mL−1 and 1.11 to 2.26 ng∙L−1, respectively. With this method, a lake in Hebei province, China, were screened. Three kinds of target compounds were detected. The average concentration was around 2.5 ng∙L−1, while the highest concentration reached 286.54 ng∙L−1.

Untargeted Analysis of Lemna minor Metabolites: Workflow and Prioritization Strategy Comparing Highly Confident Features between Different Mass Spectrometers

Metabolomics approaches provide a vast array of analytical datasets, which require a comprehensive analytical, statistical, and biochemical workflow to reveal changes in metabolic profiles. The biological interpretation of mass spectrometric metabolomics results is still obstructed by the reliable identification of the metabolites as well as annotation and/or classification. In this work, the whole Lemna minor (common duckweed) was extracted using various solvents and analyzed utilizing polarity-extended liquid chromatography (reversed-phase liquid chromatography (RPLC)-hydrophilic interaction liquid chromatography (HILIC)) connected to two time-of-flight (TOF) mass spectrometer types, individually. This study (introduces and) discusses three relevant topics for the untargeted workflow: (1) A comparison study of metabolome samples was performed with an untargeted data handling workflow in two different labs with two different mass spectrometers using the same plant material type. (2) A statistical procedure was observed prioritizing significant detected features (dependent and independent of the mass spectrometer using the predictive methodology Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA). (3) Relevant features were transferred to a prioritization tool (the FOR-IDENT platform (FI)) and were compared with the implemented compound database PLANT-IDENT (PI). This compound database is filled with relevant compounds of the Lemnaceae, Poaceae, Brassicaceae, and Nymphaceae families according to analytical criteria such as retention time (polarity and LogD (pH 7)) and accurate mass (empirical formula). Thus, an untargeted analysis was performed using the new tool as a prioritization and identification source for a hidden-target screening strategy. Consequently, forty-two compounds (amino acids, vitamins, flavonoids) could be recognized and subsequently validated in Lemna metabolic profile using reference standards. The class of flavonoids includes free aglycons and their glycosides. Further, according to our knowledge, the validated flavonoids robinetin and norwogonin were for the first time identified in the Lemna minor extracts.

Evaluation of Sample Preparation Methods for Non-Target Screening of Organic Micropollutants in Urban Waters Using High-Resolution Mass Spectrometry

Non-target screening (NTS) has gained interest in recent years for environmental monitoring purposes because it enables the analysis of a large number of pollutants without predefined lists of molecules. However, sample preparation methods are diverse, and few have been systematically compared in terms of the amount and relevance of the information obtained by subsequent NTS analysis. The goal of this work was to compare a large number of sample extraction methods for the unknown screening of urban waters. Various phases were tested for the solid-phase extraction of micropollutants from these waters. The evaluation of the different phases was assessed by statistical analysis based on the number of detected molecules, their range, and physicochemical properties (molecular weight, standard recoveries, polarity, and optical properties). Though each cartridge provided its own advantages, a multilayer cartridge combining several phases gathered more information in one single extraction by benefiting from the specificity of each one of its layers.

Suspect and non-target screening of chemicals in clothing textiles by reversed-phase liquid chromatography/hybrid quadrupole-Orbitrap mass spectrometry

The global manufacturing of clothing is usually composed of multistep processes, which include a large number of chemicals. However, there is generally no information regarding the chemical content remaining in the finished clothes. Clothes in close and prolonged skin contact may thus be a significant source of daily human exposure to hazardous compounds depending on their ability to migrate from the textiles and be absorbed by the skin. In the present study, twenty-four imported garments on the Swedish market were investigated with respect to their content of organic compounds, using a screening workflow. Reversed-phase liquid chromatography coupled to electrospray ionization/high-resolution mass spectrometry was used for both suspect and non-target screening. The most frequently detected compound was benzothiazole followed by quinoline. Nitroanilines with suspected mutagenic and possible skin sensitization properties, and quinoline, a carcinogenic compound, were among the compounds occurring at the highest concentrations. In some garments, the level of quinoline was estimated to be close to or higher than 50,000 ng/g, the limit set by the REACH regulation. Other detected compounds were acridine, benzotriazoles, benzothiazoles, phthalates, nitrophenols, and organophosphates. Several of the identified compounds have logP and molecular weight values enabling skin uptake. This pilot study indicates which chemicals and compound classes should be prioritized for future quantitative surveys and control of the chemical content in clothing as well as research on skin transfer, skin absorption, and systemic exposure. The results also show that the current control and prevention from chemicals in imported garments on the Swedish market is insufficient. Graphical abstract