Derivation of occupational exposure limits: Differences in methods and protection levels

Frameworks for deriving occupational exposure limits (OELs) and OEL-analogue values (such as derived-no-effect levels [DNELs]) in various regulatory areas in the EU and at national level in Germany were analysed. Reasons for differences between frameworks and possible means of improving transparency and harmonisation were identified. Differences between assessment factors used for deriving exposure limits proved to be one important reason for diverging numerical values. Distributions for exposure time, interspecies and intraspecies extrapolation were combined by probabilistic methods and compared with default values of assessment factors used in the various OEL frameworks in order to investigate protection levels. In a subchronic inhalation study showing local effects in the respiratory tract, the probability that assessment factors were sufficiently high to protect 99% and 95% of the target population (workers) from adverse effects varied considerably from 9% to 71% and 17% to 87%, respectively, between the frameworks. All steps of the derivation process, including the uncertainty associated with the point of departure (POD), were further analysed with two examples of full probabilistic assessments. It is proposed that benchmark modelling should be the method of choice for deriving PODs and that all OEL frameworks should provide detailed guidance documents and clearly define their protection goals by stating the proportion of the exposed population the OEL aims to cover and the probability with which they intend to provide protection from adverse effects. Harmonisation can be achieved by agreeing on the way to perform the methodological steps for deriving OELs and on common protection goals.     

Predicting survival in anaplastic astrocytoma patients in a single-center cohort of 108 patients

Purpose

Stereotactic radiation therapy (SRT) and immune checkpoint inhibitors (ICI) may act synergistically to improve treatment outcomes but may also increase the risk of symptomatic radiation necrosis (RN). The objective of this study was to compare outcomes for patients undergoing SRT with and without concurrent ICI.

Methods and materials

Patients treated for BMs with single or multi-fraction SRT were retrospectively reviewed. Concurrent ICI with SRT (SRT-ICI) was defined as administration within 3 months of SRT. Local control (LC), radiation necrosis (RN) risk and distant brain failure (DBF) were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. Wilcoxon rank sum and Chi-square tests were used to compare covariates. Multivariate cox regression analysis (MVA) was performed.

Results

One hundred seventy-nine patients treated with SRT for 385 brain lesions were included; 36 patients with 99 lesions received SRT-ICI. Median follow up was 10.3 months (SRT alone) and 7.7 months (SRT- ICI) (p = 0.08). Lesions treated with SRT-ICI were more commonly squamous histology (17% vs 8%) melanoma (20% vs 2%) or renal cell carcinoma (8% vs 6%), (p < 0.001). Non-small cell lung cancer (NSCLC) compromised 60% of patients receiving ICI (n = 59). Lesions treated with SRT-ICI had significantly improved 1-year local control compared to SRT alone (98 and 89.5%, respectively (p = 0.0078). On subset analysis of NSCLC patients alone, ICI was also associated with improved 1 year local control (100% vs. 90.1%) (p = 0.018). On MVA, only tumor size ≤2 cm was significantly associated with LC (HR 0.38, p = 0.02), whereas the HR for concurrent ICI with SRS was 0.26 (p = 0.08). One year DBF (41% vs. 53%; p = 0.21), OS (58% vs. 56%; p = 0.79) and RN incidence (7% vs. 4%; p = 0.25) were similar for SRT alone versus SRT-ICI, for the population as a whole and those patients with NSCLC.

Conclusion

These results suggest SRT-ICI may improve local control of brain metastases and is not associated with an increased risk of symptomatic radiation necrosis in a cohort of predominantly NSCLC patients. Larger, prospective studies are necessary to validate these findings and better elucidate the impact of SRT-ICI on other disease outcomes.

     

Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL‐2 and/or BIM

Acute myeloid leukemia (AML) is a disease of the elderly population and survival remains poor after failure of hypomethylating agents (HMA). The BCL‐2 inhibitor venetoclax demonstrated activity as monotherapy and in combination with chemotherapy or HMA in AML. In this case series, patients with secondary AML (sAML) not eligible for intensive chemotherapy and refractory to HMA were treated with venetoclax within a named patient program at our tertiary cancer center in Salzburg, Austria. Between April 2017 and September 2018, seven patients with sAML received venetoclax therapy. Two out of seven patients achieved a complete remission upon venetoclax initiation with a PFS of 505 days and 352 days and another patient achieved complete peripheral blood blast clearing within nine days after start of venetoclax. Among the venetoclax responders, primary refractory disease to prior HMA therapy was documented, 2 patients harbored IDH1/IDH2 mutations and one patient had an antecedent myeloproliferative neoplasm. High BCL‐2 and/or BIM expression in myeloblasts was found in venetoclax responders and response was significantly associated with overall survival (responders: 364 days versus non‐responders: 24 days, P = 0.018). Venetoclax monotherapy is safe and is able to induce durable responses in elderly patients with secondary AML after treatment failure with HMA.     

Endocardial/epicardial versus endocardial encircling cryoablation for ventricular tachycardia: A randomized trial

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Exploring the effectiveness of a specialized therapy programme for burnout using subjective report and biomarkers of stress

The increasing prevalence of stress-related disorders such as burnout urges the need for specialized treatment approaches. Programmes combining psychotherapy and regenerative interventions emerge to be the most successful. However, evaluated therapy programmes are scarce and usually involve subjective symptom quantification without consideration of physiologic parameters. The aim of the present exploratory, single-group study was the multimodal investigation of the effectiveness of a specialized holistic therapy programme by assessing symptoms and biological markers of chronic stress. Seventy-one in-patients (39 men/32 women; age 46.8 ± 9.9 years) of a specialized burnout ward with the additional diagnosis of burnout (Z73.0) in conjunction with a main diagnosis of depressive disorder (F32 or F33) according to the International Classification of Diseases (ICD)-10 were included in the study. In addition to symptomatology, the stress-responsive biomarkers heart rate variability (HRV) and serum brain-derived neurotrophic factor (BDNF) were measured in patients at admittance to and discharge from the burnout ward applying a 6-week specialized treatment programme. At discharge, patients showed a significant reduction of symptom burden and a significant increase in serum BDNF, while HRV remained unchanged. The findings implicate that the therapy programme may have beneficial effects on symptomatology and neuroplasticity of patients with burnout. As therapy was often supplemented by psychopharmacological treatment, a relevant influence of antidepressant medication especially on BDNF has to be considered.     

Self‐rated health,symptoms and health behaviour of upper secondary vocational students by field of study

This article examines the self‐rated health, symptoms and health behaviour of upper secondary vocational students in Finland. The data consist of the responses of first‐ and second‐year vocational students (n = 34 554) to the 2013 School Health Promotion Survey. The data were analysed statistically and processed separately for girls and boys. Associations between self‐rated health, symptoms and health behaviour and fields of study were examined by cross‐tabulation. Statistical significance was measured using the chi‐squared test. Self‐rated health, symptoms and health behaviour were found to have a statistically significant association with field of study (p < 0.001). Vocational students in different fields had different experiences of health, different symptoms and different health behaviours. The results complement existing evidence about disparities in well‐being among young people in the context of education.     

Nationwide treatment patterns and survival of older patients with prostate cancer

Objectives

To examine the clinical features, applied treatments, and survival of older patients with prostate cancer compared with younger patients.