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PurposeThe objective of this study was to conduct a systematic review and meta-analysis to evaluate the cancer risks among firefighters in the time course and from different geographical areas.MethodA PubMed search was performed to identify cohort studies about cancer risk and firefighting presented with standardized incidence ratios (SIRs) or standardized mortality ratios (SMRs). Using random-effect models, meta-relative risk estimates (mSIRs, mSMRs) and 95% confidence intervals (CI) were assessed. Cohort studies with employment starting before 1950 were classified as “old”, studies starting between 1950 and 1970 as “medium”, and later studies as “new”.ResultsThe general cancer risk of firefighters was similar to the general population, but mSMR decreased over time (new studies: mSMR = 0.81, 95% CI 0.70–0.92). We observed an increase of mSIR for melanoma of the skin and prostate cancer as well as a decrease of mSIR for stomach cancer with later employment onset. For those cancer sites, we did not observe a secular trend of mSMRs. Regional differences between relative cancer risks were particularly observed for bladder cancer.ConclusionsAmong other things, innovative firefighting techniques and better personal protective equipment have provided a safer and healthier working environment for firefighters over time leading to a reduction of overall cancer incidence and mortality ratios. Increased general preventive medical checkups and possible additional screenings for firefighters might have led to more findings of malignant melanoma of the skin and prostate cancer in the recent past.

The COVID-19 pandemic changed the future of work sustainably and led to a general increase in mental stress. A study conducted during the second and third pandemic wave with a retrospective survey of the first wave among 1,545 non-healthcare workers confirmed an increase in anxiety and depression symptoms and showed a correlation with the occupational SARS-CoV-2 infection risk. This online follow-up survey aims to examine changes in mental distress as the pandemic progressed in Germany and to identify factors influencing potential changes. Longitudinal data from 260 subjects were available for this analysis. Mental distress related to anxiety and depression symptoms, assessed by the Patient Health Questionnaire-4 (PHQ-4), and occupational risk factors were solicited at the end of 2022 and retrospectively at the fifth wave. Categorized PHQ-4 scores were modelled with mixed ordinal regression models and presented with odds ratios (OR) and 95% confidence intervals (95% CI). A previous diagnosis of a depressive or anxiety disorder was a strong risk factor for severe symptoms (OR 3.49, 95% CI 1.71-7.11). The impact of occupational SARS-CoV-2 infection risk on mental distress was increased, albeit failing to reach the formal level of statistical significance (high risk OR 1.83, 95% CI 0.59-5.63; probable risk OR 1.72, 95% CI 0.93-3.15). Mental distress was more pronounced in those with a previous diagnosis of anxiety and depression. Confirmed occupational risk factors were protective measures against occupational SARS-CoV-2 infection perceived as inadequate, chronic work-related stress, overcommitment, reduced interactions with fellow-workers, and work-privacy conflicts. The pandemic had a negative impact on anxiety and depression symptoms among the studied non-healthcare workers, particularly early in the pandemic, although this effect does not appear to be permanent. There are modifiable risk factors that can protect workers' mental health, including strengthening social interactions among employees and reducing work-privacy conflicts.

A comprehensive guide to statistical hypothesis testing with examples in SAS and R When analyzing datasets the following questions often arise: Is there a short hand procedure for a statistical test available in SAS or R? If so, how do I use it? If not, how do I program the test myself? This book answers these questions and provides an overview of the most common statistical test problems in a comprehensive way, making it easy to find and perform an appropriate statistical test. A general summary of statistical test theory is presented, along with a basic description for each test, including the necessary prerequisites, assumptions, the formal test problem and the test statistic. Examples in both SAS and R are provided, along with program code to perform the test, resulting output and remarks explaining the necessary program parameters. Key features: • Provides examples in both SAS and R for each test presented. • Looks at the most common statistical tests, displayed in a clear and easy to follow way. • Supported by a supplementary website http://www.d-taeger.de [http://www.d-taeger.de/] featuring example program code. Academics, practitioners and SAS and R programmers will find this book a valuable resource. Students using SAS and R will also find it an excellent choice for reference and data analysis.

Urine-based biomarkers are a rational and promising approach for the detection of bladder cancer due to the proximity of urine to the location of the tumor site and the non-invasive nature of its sampling. A well-known and highly investigated biomarker for bladder cancer is survivin. For detection of very small amounts of urinary survivin protein a highly sensitive assay was developed. The assay is based on the immuno-PCR technology, more precisely a solid-phase proximity ligation assay (spPLA). The limit of detection for the survivin spPLA was 1.45 pg/mL, resulting in an improvement of the limit of detection by a factor of approximately 23 compared to the previously in-house developed survivin ELISA. A key step in development was the initial isolation of survivin by a molecular fishing rod based on magnetic beads. Interfering matrix compounds pose a special challenge for further analytical application, but can be overcome by this isolation step. The assay is designed to work with only 500 μL of voided urine. The survivin spPLA showed a sensitivity of 30% and specificity of 89% for bladder cancer detection in this study of 110 bladder cancer cases and 133 clinical controls. Moreover, the results demonstrated again that survivin is a useful complementary marker in combination with UBC ® Rapid by increasing the overall sensitivity to 70% with a specificity of 86%. Although the performance for detection of bladder cancer was rather low, the herein developed assay might serve as a new tool for survivin biomarker research in diverse human fluids, even if the biological matrix is complex or survivin is only present in small amounts.

Background Clinical trials have shown the benefits of lung cancer screening (LCS) in certain high-risk groups using low-dose high-resolution computed tomography (LDCT). Risk groups are usually defined by age and tobacco use. Exposure to asbestos dust is an important occupational risk factor for lung cancer. Since 2014, the German Social Accident Insurance (DGUV) has introduced annual LCS for high-risk groups (EVA-LCS). In addition to occupational asbestos dust exposure, the population at risk is defined by age (≥ 55 years) and tobacco consumption (≥ 30 pack-years). The health services research project EVALUNG aims to evaluate the EVA-LCS using a combination of quantitative and qualitative methods. Methods The quantitative part will be based on a secondary data analysis of routine administrative and medical data from the EVA-LCS. The results of the individual screening rounds will be analysed in a cross-sectional design. Primary endpoints are participation patterns, the rate of findings requiring further diagnostic investigation, the detection of lung cancer including tumour stage and characteristics, and the notification and recognition of asbestos-related occupational diseases. Secondary endpoints include false-positive and false-negative findings, incidence of other cancers, and all-cause and cancer-related mortality. To avoid selection bias, a complete set of anonymised data (approximately 22,200 individuals as of 12/2021) from the EVA-LCS will be transmitted for use in EVALUNG. A sub-sample will be used to perform longitudinal analyses and explore a linkage with cancer registry data. Another component is the development and piloting of quality indicators. Qualitative interviews will be conducted to analyse the perceptions, satisfaction, and potential psychological effects of EVA-LCS participants. Interviews with participating physicians will focus on their attitudes and knowledge regarding LCS. A further aim is to develop an evidence-based decision aid. Discussion The EVALUNG concept is based on various complementary approaches, enabling a comprehensive evaluation of the EVA-LCS and the identification of optimization potentials. The quality of the data is crucial for the validity of the quantitative analyses. One way to address potential limitations is to link the data with cancer registry data. The results may contribute to the planning and development of a national LDCT lung cancer screening programme in Germany.

PurposeDue to a potential exposure to several definite or probable carcinogens, the IARC classified manufacturing of art glass, glass containers, and pressed ware as probably carcinogenic to humans in 1993 (Group 2A). Purpose of this study was to update the evidence from recently published scientific reports.MethodsWe searched for peer-reviewed articles published between 1993 and 2018 and combined result in terms of a meta-analysis. Overall, we considered twelve articles for a meta-analytic approach published after 1992.ResultsFrom a meta-analysis we derived a standardized incidence ratio (mSIR) and a standardized mortality ratio (mSMR) for lung cancer in men of 1.25 (95% CI 0.97–1.59) and 1.41 (95% CI 1.11–1.77), respectively. The estimated odds ratio (mOR) from five case–control studies was 1.25 (95% CI 0.90–1.73). Associated with an employment in glass factories, the estimated mSMR for larynx cancer was 2.38 (95% CI 1.23–4.16) based on two cohort studies; the mOR from four case–control studies was 1.35 (95% CI 0.73–2.52). Reports on elevated cancer risks at other sites were not consistent.ConclusionsOnly few studies assessed cancer risk solely in glass workers. Gained evidence from more recent reports supports the IARC rating from 1993. Our combined results add limited evidence to a moderately elevated risk for cancer of the airways.

Background Malignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin. Methods For a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performance of both markers and tested factors potentially influencing marker concentrations like age, sample storage time, and MM subtype. Results Calretinin was able to detect all major subtypes except for sarcomatoid MM. Calretinin showed a similar performance in Australian and German men. At a pre-defined specificity of 95% the sensitivity of calretinin reached 71% and that of mesothelin 69%, when excluding sarcomatoid MM. At 97% specificity, the combination with calretinin increased the sensitivity of mesothelin from 66% to 75%. Sample storage time did not influence the results. In controls the concentrations of calretinin increased 1.87-fold (95% CI 1.10–3.20) per 10 years of age and slightly more for mesothelin (2.28, 95% CI 1.30–4.00). Conclusions Calretinin could be verified as a blood-based marker for MM. The assay is robust and shows a performance that is comparable to that of mesothelin. Retrospective analyses would not be limited by storage time. The high specificity supports a combination of calretinin with other markers. Calretinin is specific for epithelioid and biphasic MM but not the rarer sarcomatoid form. Molecular markers like calretinin and mesothelin are promising tools to improve and supplement the diagnosis of MM and warrant further validation in a prospective study.

ObjectivesCalretinin and mesothelin are molecular markers for the detection of malignant mesothelioma at early stages. Our objective was the re-evaluation of factors influencing calretinin and mesothelin concentrations in plasma of cancer-free men in order to minimise false-positive tests when using commercial assays approved for clinical diagnostics.SettingThis re-evaluation used data and archived blood samples of the population-based Heinz Nixdorf Recall Study (HNRS) collected from 2011 to 2014.ParticipantsThe present analysis comprised of 569 cancer-free men at the time of blood sampling (median age 70 years) from HNRS.Primary and secondary outcomesMesothelin plasma concentration was determined using ELISA and CLEIA (chemiluminescent enzyme immunoassay). Calretinin plasma concentration was assessed using ELISA.ResultsCompared with the previous determination of concentrations, we detected less false-positive tests using the commercial assays. In this analysis, we found nine false-positive calretinin tests using the ELISA (specificity 98.4%, 95% CI 97.0% to 99.2%) and 24 false-positive mesothelin tests using both ELISA and CLEIA (specificity 95.8%, 95% CI 93.8% to 97.2%). We confirmed renal dysfunction as major predictor of elevated marker concentrations. Mesothelin was additionally affected by bronchitis. Furthermore, elevated inflammation values and hypertension only affected the mesothelin concentration determined by ELISA.ConclusionsThe newly available assays of calretinin and mesothelin approved for clinical diagnostics showed high specificities in the population-based cohort of elderly men without a malignant disease. The current evaluation provides a basis to consider influencing factors in order to further improve the diagnostic procedure.

Malignant mesothelioma (MM) is a severe disease mostly caused by asbestos exposure. Today, one of the best available biomarkers is the soluble mesothelin-related protein (SMRP), also known as mesothelin. Recent studies have shown that mesothelin levels are influenced by individual genetic variability. This study aimed to investigate the influence of three mesothelin (MSLN) gene variants (SNPs) in the 5′-untranslated promoter region (5′-UTR), MSLN rs2235503 C > A, rs3764246 A > G, rs3764247 A > C, and one (rs1057147 G > A) in the 3′-untranslated region (3′-UTR) of the MSLN gene on plasma concentrations of mesothelin in 410 asbestos-exposed males without cancer and 43 males with prediagnostic MM (i.e., with MM diagnosed later on) from the prospective MoMar study, as well as 59 males with manifest MM from Germany. The mesothelin concentration differed significantly between the different groups (p < 0.0001), but not between the prediagnostic and manifest MM groups (p = 0.502). Five to eight mutations of the four SNP variants studied were associated with increased mesothelin concentrations (p = 0.001). The highest mesothelin concentrations were observed for homozygous variants of the three promotor SNPs in the 5′-UTR (p < 0.001), and the highest odds ratio for an elevated mesothelin concentration was observed for MSLN rs2235503 C > A. The four studied SNPs had a clear influence on the mesothelin concentration in plasma. Hence, the analysis of these SNPs may help to elucidate the diagnostic background of patients displaying increased mesothelin levels and might help to reduce false-positive results when using mesothelin for MM screening in high-risk groups.