Improved prognostic stratification of patients with isocitrate dehydrogenase-mutant astrocytoma.

Prognostic factors and standards of care for astrocytoma, isocitrate dehydrogenase (IDH)-mutant, CNS WHO grade 4, remain poorly defined. Here we sought to explore disease characteristics, prognostic markers, and outcome in patients with this newly defined tumor type. We determined molecular biomarkers and assembled clinical and outcome data in patients with IDH-mutant astrocytomas confirmed by central pathology review. Patients were identified in the German Glioma Network cohort study; additional cohorts of patients with CNS WHO grade 4 tumors were identified retrospectively at two sites. In total, 258 patients with IDH-mutant astrocytomas (114 CNS WHO grade 2, 73 CNS WHO grade 3, 71 CNS WHO grade 4) were studied. The median age at diagnosis was similar for all grades. Karnofsky performance status at diagnosis inversely correlated with CNS WHO grade (p < 0.001). Despite more intensive treatment upfront with higher grade, CNS WHO grade was strongly prognostic: median overall survival was not reached for grade 2 (median follow-up 10.4 years), 8.1 years (95% CI 5.4-10.8) for grade 3, and 4.7 years (95% CI 3.4-6.0) for grade 4. Among patients with CNS WHO grade 4 astrocytoma, median overall survival was 5.5 years (95% CI 4.3-6.7) without (n = 58) versus 1.8 years (95% CI 0-4.1) with (n = 12) homozygous CDKN2A deletion. Lower levels of global DNA methylation as detected by LINE-1 methylation analysis were strongly associated with CNS WHO grade 4 (p < 0.001) and poor outcome. MGMT promoter methylation status was not prognostic for overall survival. Histomolecular stratification based on CNS WHO grade, LINE-1 methylation level, and CDKN2A status revealed four subgroups of patients with significantly different outcomes. In conclusion, CNS WHO grade, global DNA methylation status, and CDKN2A homozygous deletion are prognostic in patients with IDH-mutant astrocytoma. Combination of these parameters allows for improved prediction of outcome. These data aid in designing upcoming trials using IDH inhibitors.

Explorative analyses on spatial differences in the desire for social distance toward people with mental illness in a diverging city.

Introduction: Stigma is an individual and societal process based on attitudes and power and relates to both spatial disparities and social distinction. In this study, we examined differences in desire for social distance toward people with mental illness within a city using social and spatial information. Methods: ANOVAs and Scheffé post-hoc tests analyzed varying desires for social distance toward people with mental illness within Leipzig (East Germany). Joint Correspondence Analyses (JCA) explored correspondences between desire for social distance, socio-economic status, age, life orientation, social support, duration of living in Leipzig, and shame toward having a mental illness in five city districts of Leipzig in LIFE study participants (by Leipzig Research Center for Civilization Disease, data collected 2011-2014 and 2018-2021, n = 521). Results: Stigma varied among Leipzig's districts (F(df = 4) = 4.52, p = 0.001). JCAs showed that a higher desired social distance toward people with mental illness corresponded with spatial differences, high levels of pessimism, high shame of being mentally ill, low social support, low socio-economic status, and older age (75.74 and 81.22% explained variances). Conclusion: In terms of stigma, where people with mental illness live matters. The results identified target groups that should be addressed by appropriate intervention and prevention strategies for mental health care.

Traffic noise annoyance in the LIFE-adult study in Germany: Exposure-response relationships and a comparison to the WHO curves.

BACKGROUND: Noise annoyance is the second-highest cause of lost disability-adjusted life-years due to environmental noise in Europe. Evidence on exposure-response relationships (ERRs) for traffic noise annoyance with more accurate exposure values is still needed. OBJECTIVES: In an analysis of the population-based LIFE-Adult study in Leipzig, Germany, we aimed to investigate the effect of road, railway (train and tram), and aircraft noise on high annoyance (HA). METHODS: Traffic exposure data was taken for 2012 and data on noise annoyance was evaluated between 2018 and 2021. HA was defined according to international standardized norms. We calculated risk estimates using logistic regression, controlling for age, sex, and socioeconomic status, and compared our ERRs with those from the last WHO review on this topic. RESULTS: Aircraft noise had the highest relative risk for noise-related HA (OR = 12.7, 95% CI: 9.37-17.10 per 10 dB Lden increase). The road and railway traffic risk estimates were similar to each other (road: OR = 3.55, 95% CI: 2.78-4.54; railway: OR = 3.31, 95% CI: 2.77-3.97 per 10 dB Lden increase). Compared to the WHO curves, the proportion of highly annoyed individuals was somewhat lower for road and rail traffic noise, but higher for aircraft noise. DISCUSSION: Aircraft noise is particularly annoying. There were differences between our study's ERRs and those in the WHO review, especially for aircraft noise. These differences may be partly explained by the improved accuracy of the exposure values, as we considered secondary road networks and tram noise, and by a lack of a nighttime flight ban at the Leipzig airport. Geographical, regional and climatic variations, inconsistency in HA cut-offs, as well as temporal developments in the annoyance experience may also explain the differences. Since ERRs serve as a basis for decision making in public policies, regular updates of the curves based on new evidence is recommended.

Traffic-Related High Sleep Disturbance in the LIFE-Adult Cohort Study: A Comparison to the WHO Exposure-Response-Curves.

Sleep is negatively affected by environmental noise. In the present study, we investigated self-reported high sleep disturbances (being "highly sleep disturbed"-HSD) from road traffic (primary and secondary road networks), rail (train and tram) and air traffic noise in the LIFE-Adult cohort study in Leipzig, Germany. For this, we used exposure data from 2012 and outcome data of Wave 2 (collected during 2018-2021). HSD was determined and defined according to internationally standardized norms. The highest risk for transportation noise-related HSD was found for aircraft noise: the odds ratio (OR) was 19.66, 95% CI 11.47-33.71 per 10 dB increase in Lnight. For road and rail traffic, similar risk estimates were observed (road: OR = 2.86, 95% CI 1.92-4.28; rail: OR = 2.67, 95% CI 2.03-3.50 per 10 dB Lnight increase). Further, we compared our exposure-risk curves with the curves of the WHO environmental noise guidelines for the European region. The proportion of individuals with HSD for a given noise level was lower for rail traffic but higher for aircraft noise in the LIFE study than in the WHO curves. For road traffic, curves are not directly comparable because we also included the secondary road network. The results of our study add to the body of evidence for increased health risks by traffic noise. Moreover, the results indicate that aircraft noise is particularly harmful to health. We recommend reconsidering threshold values for nightly aircraft exposure.

Event dependent overall survival in the population-based LIFE-Adult-Study.

BACKROUND: Information about the direct comparability of big data of epidemiological cohort studies and the general population still is lacking, especially regarding all-cause mortality rates. The aim of this study was to investigate the overall survival and the influence of several diagnoses in the medical history on survival time, adjusted to common risk factors in a populations-based cohort. METHODS: From 10,000 subjects of the population-based cohort LIFE-Adult-Study (Leipzig Research Centre for Civilization Diseases), the medical history and typical risk factors such as age, smoking status and body-mass-index (BMI) were assessed. The survival status was identified from the saxonian population register. Univariate and multivariate analyses were used to determine the influence of the medical history and risk factors on overall survival. To develope an optimal model, the method by Collet [1] was used. RESULTS: The mortality rate of the participants is approximately half the mortality rate expected for the german population. The selection bias in epidemiological studies needs to be considered whenever interpreting results of epidemiological cohort studies. Nevertheless we have shown that several diagnoses proved to have a negative influence on overall survival time even in this relatively healthy cohort. This study showed the significantly increased mortality risk if the following diseases are reported in medical history of the participants in a large population-based cohort study including adults aged 18 and over: diabetes mellitus (HR 1.533, p = 0.002), hypertension (HR 1.447, p = 0.005), liver cirrhosis (HR 4.251, p < 0.001), osteoporosis (HR 2.165, p = 0.011), chronic bronchitis (HR 2.179, p < 0.001), peptic ulcer disease (HR 1.531, p = 0.024) and cancer (HR 1.797, p < 0.001). Surprisingly, asthma has the opposite effect on survival time (HR 0.574, p = 0.024), but we believe this may be due to an overrepresentation of mild to moderate asthma and its management, which includes educating patients about a healthy lifestyle. CONCLUSION: In the LIFE-Adult-Study, common risk factors and several diseases had relevant effect on overall survival. However, selection bias in epidemiological studies needs to be considered whenever interpreting results of epidemiological cohort studies. Nevertheless it was shown that the general cause-and-effect principles also apply in this relatively healthy cohort.