Before, During, and After the First Wave of COVID-19: Mortality Analyses Reveal Relevant Trends in Germany and its States until June 2020.

OBJECTIVE: Well-established mortality ratio methodology can contribute to a fuller picture of the SARS-CoV-2/COVID-19 burden of disease by revealing trends and informing mitigation strategies. This work examines respective data from Germany by way of example. METHODS: Using monthly and weekly all-cause mortality data from January 2016 to June 2020 (published by the German Federal Statistical Institute) for all ages,<65 years and≥65 years, and specified for Germany's federal states, we explored mortality as sequela of COVID-19. We analysed standardized mortality ratios (SMRs) comparing 2020 with 2016-2019 as reference years with a focus on trend detection. RESULTS: In Germany as a whole, elevated mortality in April (most pronounced for Bavaria) declined in May. The states of Hamburg and Bremen had increased SMRs in all months under study. In Mecklenburg-Western Pomerania, decreased SMRs in January turned monotonically to increased SMRs by June. Irrespective of age group, this trend was pronounced and significant. CONCLUSIONS: Increased SMRs in Hamburg and Bremen must be interpreted with caution because of potential upward distortions due to a "catchment bias". A pronounced excess mortality in April across Germany was confirmed and a hitherto undetected trend of increasing SMRs for Mecklenburg-Western Pomerania was revealed. To meet the pandemic challenge and to benefit from research based on data collected in standardized ways, national authorities should regularly conduct SMR analyses. For independent analyses, national authorities should also expedite publishing raw mortality and population data, including detailed information on age, sex, and cause of death, in the public domain.

[Epidemiological Studies on the Association between Chronic Exposure to Road Traffic Noise and Blood Pressure: A Systematic Review with Meta-Analyses]. / Epidemiologische Studien zu chronischen Straßenlärm-Expositionen und dem Blutdruck: Ein systematischer Review mit Metaanalysen.

AIM: The aim of this study was to review epidemiological studies on the association between chronic exposures to road traffic noise and prevalence of arterial hypertension as well as blood pressure by using meta-analyses. METHODS: A systematic literature search in the databases Medline® and Web of science™ as well as the database OpenGrey was conducted to identify suitable studies, namely epidemiological observational studies assessing objective exposures to road traffic noise at the subject's home place with analysis of their potential associations with arterial hypertension or blood pressure. Whenever possible, overall effects for the different relationships were estimated with meta-analyses. For statistical analyses R for windows was used. RESULTS: A total of 31 eligible studies were identified. Meta-analyses were conducted for potential association between road traffic noise and prevalence of arterial hypertension in adults and for association with systolic and diastolic blood pressure in adults and children. There was a significant (p<0.01) increase of risk for arterial hypertension in adults when exposed to chronic road traffic noise with an increment of 7% per 5 dB(A). Overall effects for systolic blood pressure were positive but weak for children as well as adults without any statistical significance. For diastolic blood pressure there appeared to be no relationship with chronic exposure to road traffic noise in either of the two groups. CONCLUSION: Considering the multiple methodological limitations of studies examined as well as the high level of heterogeneity in all random effects models, the estimated overall effects must be interpreted with caution. To examine potential associations between road traffic noise and arterial hypertension or measured blood pressure appropriately, more prospective cohort studies are necessary with precise assessments of noise exposure as well as clinical endpoints and with adjustments for relevant cofactors.

Contribution of Occupational Health to multidisciplinary team work for COVID-19 prevention and management.

INTRODUCTION: The SARS-CoV-2/Covid-19 pandemic is a challenge for public health and occupational medicine and developing prevention and protection strategies needs expertise from many disciplines. To make prevention successful, individuals have to be motivated to participate and, in turn, motivation depends on understanding how and why prevention measures are implemented. We present a structured approach (the Cycle of prevention) which involves different stakeholders and perspectives to develop, and monitor, prevention strategies in transparent and effective ways.

(Side) effects of the rule of the road and neurophysiology on traffic safety: A hypothesis.

Nowadays, the roots of left-hand traffic (LHT) and right-hand traffic (RHT) - including fighting on horse-back and whipping horses that are drawing carriages - are at an all-time low; thus, it is time to assess and appreciate the nexus of road-safety practices and human neurophysiology. We hypothesize that safety of LHT and RHT can be associated with neurophysiology. We summarize scattered empirical research into plausible links between neurophysiological aspects such as handedness, eye movement bias, and hemispheric lateralisation and how safe, in theory, LHT vs. RHT may be for whom. The scarcity and limitations of empirical data into road traffic accidents associated with LHT or RHT are surprising. Even though it was claimed that countries with LHT have lower collision rates than countries with RHT some 50 years ago, we lack informative analyses of traffic accidents in countries with either LHT or RHT which consider plausibly associated neurophysiology. Overall, we predict that LHT (with the driver sitting on the right) is safer than RHT. As 'the rule of the road' and neurophysiology may have important unrecognized "side" effects, we suggest that (and how) this rationale should be tested.

Premature Deaths, Statistical Lives, and Years of Life Lost: Identification, Quantification, and Valuation of Mortality Risks.

Mortality effects of exposure to air pollution and other environmental hazards are often described by the estimated number of "premature" or "attributable" deaths and the economic value of a reduction in exposure as the product of an estimate of "statistical lives saved" and a "value per statistical life." These terms can be misleading because the number of deaths advanced by exposure cannot be determined from mortality data alone, whether from epidemiology or randomized trials (it is not statistically identified). The fraction of deaths "attributed" to exposure is conventionally derived as the hazard fraction (R - 1)/R, where R is the relative risk of mortality between high and low exposure levels. The fraction of deaths advanced by exposure (the "etiologic" fraction) can be substantially larger or smaller: it can be as large as one and as small as 1/e (≈0.37) times the hazard fraction (if the association is causal and zero otherwise). Recent literature reveals misunderstanding about these concepts. Total life years lost in a population due to exposure can be estimated but cannot be disaggregated by age or cause of death. Economic valuation of a change in exposure-related mortality risk to a population is not affected by inability to know the fraction of deaths that are etiologic. When individuals facing larger or smaller changes in mortality risk cannot be identified, the mean change in population hazard is sufficient for valuation; otherwise, the economic value can depend on the distribution of risk reductions.

[Deaths in nine regions of Italy in February/March 2020: "Mortality Excess Loupe" for SARS-CoV-2/COVID-19-Epidemiology in Germany]. / Todesfälle in neun Regionen Italiens im Februar/März 2020: "Mortalitäts-Exzess-Lupe" für SARS-CoV-2/COVID-19-Epidemiologie in Deutschland.

Italy is particularly affected by SARS-CoV-2/COVID-19. Recently, Colombo and Impicciatore compared the deaths in 1084 selected municipalities between 21 February 2020 and 21 March 2020 with deaths in the same time period in 2015 to 2019. We extend analyses of data from the Italian National Institute of Statistics (ISTAT) and calculate SMRs for all causes of death in the nine selected regions of Italy, separately for men and women and summarized. We analyze the effect of covariables by Poisson modelling and discuss the limitations of the current elaborations. We conclude: In agreement with Colombo and Impicciatore, in the particular corona situation, this "mortality excess loupe" - assuming otherwise constant determinants of death - can be a virus-test-independent tool to determine mortality effects of SARS-CoV-2. The current "loupe" is focused on municipalities with increases of more than 20% deaths in March 2020 compared to the average deaths on the same days in 2015-2019. The time window of investigation could be opened before 21 February 2020 to detect masked increases in mortality before the first "COVID-19 death" was ascertained. The current "loupe" conveys pronounced mortality increases also in regions that were not considered to be corona hotspots. In this respect, even in the absence of representative virus test results, mortality data can be important indicators of the distribution or spread of a newly acting factor. Overall, it is advisable to carry out SMR analyses for Germany on a regular basis, differentiated by region, gender, age group and cause of death. Such analyses can contribute to the early detection and evaluation of the severity of a deadly pandemic ("burden of disease") as well as to monitoring the dynamic spread of a factor such as SARS-CoV-2. SMR analyses can also be used to assess and evaluate both desired and undesired effects of measures taken against SARS-CoV-2/COVID-19 - and possibly other epidemics or pandemics.

Hypothesis: ubiquitous circadian disruption can cause cancer.

Circadian disruption (CD) was implicated in chains of cancer causation when the International Agency for Research on Cancer classified shift-work involving circadian disruption as probably carcinogenic in 2007. In the following decade, epidemiological studies into causal concepts associated with circadian disruption were inconclusive. Unappreciated complexity with an exclusive focus on shift-work, light-at-night, sleep, and melatonin in regard to circadian disruption may be accountable. With compelling non-epidemiological evidence, we posit that ubiquitous circadian disruption causes cancer and, moreover, that this is unexplored epidemiologically. This hypothesis offers a novel explanation why numerous studies in shift-workers evince inconsistent results: If circadian disruption is a ubiquitous causal phenomenon, confining assessments to the workplace, ignoring circadian disruption at play, and potential misclassification of 'who' is 'when' and 'how much' exposed to circadian disruption may disallow detecting the existence and magnitude of cancer risks. The rationale herein provides plausible explanations for previous observations and makes falsifiable predictions.

[Why is the "Number of Premature Deaths Due to Environmental Exposures" not Appropriately Quantifiable?] / Warum ist die "Anzahl vorzeitiger Todesfälle durch Umweltexpositionen" nicht angemessen quantifizierbar?

Epidemiological studies and their applications in regulations of hazardous substances (e. g. by WHO, USA, EU) often quantify effects of environmental exposures on populations ("burden of disease") by calculating "numbers of premature deaths due to exposure". A recent example is the study by Schneider et al., commissioned by the German Federal Environmental Agency (Umweltbundesamt), into the burden of disease caused by exposures to nitrogen dioxide (NO2) in Germany. The authors assessed the proportion of premature deaths due to exposure by the "Attributable Fraction" (AF). However, true numbers of premature deaths caused by NO2 could be much higher or smaller. Indeed, Robins and Greenland showed in 1989 that the AF approach is inappropriate. Despite its far-reaching relevance for epidemiology and public health, their seminal work was not adequately taken into consideration, possibly due to its sophisticated level of mathematical argumentation. Our contribution illustrates - with simple examples - unappreciated but important pitfalls. We recommend that the concept of "number of premature deaths" be abandoned and "years of life lost due to exposure" be provided instead, calculated per capita. However, "years of life lost due to exposure" should not be stratified by age or causes of death (diseases). Furthermore, we show that "Disability Adjusted Life Years" (DALY) do not provide a meaningful measure to evaluate the effect of environmental exposures on populations.

Computing sleep deficiency.

Sleep deficiency is a major public health concern. Since epidemiological studies play an important role in public health evaluations, this theoretical paper pursues answers to the question: 'How can we compute sleep deficiency as informative measures of exposures or doses in observational research?' Starting from the social jetlag concept and based on the chronodisruption rationale, we illustrate and discuss five approaches (one established and four untested, each with unique strengths and limitations) to quantify sleep deficiency by focusing on the timing and duration of sleep. Hitherto, social jetlag and chronodisruption rationale were neither explicitly proposed nor developed as assessments of sleep deficiency but, as we suggest, could potentially be utilized to this end. This first foray into computing sleep deficiency in epidemiological studies makes clear that laboratory, field and epidemiological collaboration is pre-requisite to elucidating potential (co-)causal roles of sleep deficiency in disease endpoints.

Night shift work and breast cancer: a pooled analysis of population-based case-control studies with complete work history.

Night shift work has been suspected to increase breast cancer risk but epidemiological studies have been inconsistent due to heterogeneous assessment of exposure to night work. To overcome this limitation, we pooled data of five population-based case-control studies from Australia, Canada, France, Germany, and Spain into a single harmonized dataset using a common definition of night work including 6093 breast cancer cases and 6933 population controls. The odds ratio for breast cancer in women who ever worked at night for at least 3 h between midnight and 5 a.m. as compared to never night workers was 1.12 (95% CI 1.00-1.25). Among pre-menopausal women, this odds ratio was 1.26 [1.06-1.51], increasing to 1.36 [1.07-1.74] for night shifts ≥ 10 h, 1.80 [1.20-2.71] for work ≥ 3 nights/week, and 2.55 [1.03-6.30] for both duration of night work ≥ 10 years and exposure intensity ≥ 3 nights/week. Breast cancer risk in pre-menopausal women was higher in current or recent night workers (OR = 1.41 [1.06-1.88]) than in those who had stopped night work more than 2 years ago. Breast cancer in post-menopausal women was not associated with night work whatever the exposure metric. The increase in risk was restricted to ER+ tumors, particularly those who were both ER+ and HER2+ . These results support the hypothesis that night shift work increases the risk of breast cancer in pre-menopausal women, particularly those with high intensity and long duration of exposure. Risk difference between pre- and post-menopausal women deserves further scrutiny.

Shift work that involves circadian disruption and breast cancer: a first application of chronobiological theory and the consequent challenges.

OBJECTIVES: In 2007, the International Agency for Research on Cancer classified shift work involving circadian disruption (CD) as probably carcinogenic to humans. Circadian disruption could be conceptualised as the overlap of activity, such as work, with an individual's biological night. The latter can be approximated from a worker's chronotype (or morning/evening preference). Few previous studies have taken chronotype into account when assessing CD caused by shift work. Our objective was to test the hypothesis that women working during their biological night would be at increased risk of breast cancer. METHODS: We used data from our case-control study of breast cancer to investigate associations between shift work involving CD and breast cancer risks. Previously, we had assumed that everyone working in jobs which involved work for two or more shifts between midnight and 05:00 hours was equally exposed to CD. In the present analyses, we reclassified as unexposed those who had a late chronotype in which their preferred bedtime was 2 hours after the end of their shift. RESULTS: Only 30 of 1385 night jobs changed classification and the overall finding (OR 1.17, 95% CI 0.98 to 1.41) was not different to the original finding when chronotype was not considered. CONCLUSIONS: We found virtually no difference between our new and old classifications of exposure. However, we were not able to calculate the total number of chronodisrupted shifts over a lifetime in order to assess dose and nor were we able to determine how many women were exposed to CD when doing shifts which began before midnight. Our first practical application highlights challenges for future chronobiology-based research.

Person-directed, non-pharmacological interventions for sleepiness at work and sleep disturbances caused by shift work.

BACKGROUND: Shift work is often associated with sleepiness and sleep disorders. Person-directed, non-pharmacological interventions may positively influence the impact of shift work on sleep, thereby improving workers' well-being, safety, and health. OBJECTIVES: To assess the effects of person-directed, non-pharmacological interventions for reducing sleepiness at work and improving the length and quality of sleep between shifts for shift workers. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase, Web of Knowledge, ProQuest, PsycINFO, OpenGrey, and OSH-UPDATE from inception to August 2015. We also screened reference lists and conference proceedings and searched the World Health Organization (WHO) Trial register. We contacted experts to obtain unpublished data. SELECTION CRITERIA: Randomised controlled trials (RCTs) (including cross-over designs) that investigated the effect of any person-directed, non-pharmacological intervention on sleepiness on-shift or sleep length and sleep quality off-shift in shift workers who also work nights. DATA COLLECTION AND ANALYSIS: At least two authors screened titles and abstracts for relevant studies, extracted data, and assessed risk of bias. We contacted authors to obtain missing information. We conducted meta-analyses when pooling of studies was possible. MAIN RESULTS: We included 17 relevant trials (with 556 review-relevant participants) which we categorised into three types of interventions: (1) various exposures to bright light (n = 10); (2) various opportunities for napping (n = 4); and (3) other interventions, such as physical exercise or sleep education (n = 3). In most instances, the studies were too heterogeneous to pool. Most of the comparisons yielded low to very low quality evidence. Only one comparison provided moderate quality evidence. Overall, the included studies' results were inconclusive. We present the results regarding sleepiness below. Bright light Combining two comparable studies (with 184 participants altogether) that investigated the effect of bright light during the night on sleepiness during a shift, revealed a mean reduction 0.83 score points of sleepiness (measured via the Stanford Sleepiness Scale (SSS) (95% confidence interval (CI) -1.3 to -0.36, very low quality evidence). Another trial did not find a significant difference in overall sleepiness on another sleepiness scale (16 participants, low quality evidence).Bright light during the night plus sunglasses at dawn did not significantly influence sleepiness compared to normal light (1 study, 17 participants, assessment via reaction time, very low quality evidence).Bright light during the day shift did not significantly reduce sleepiness during the day compared to normal light (1 trial, 61 participants, subjective assessment, low quality evidence) or compared to normal light plus placebo capsule (1 trial, 12 participants, assessment via reaction time, very low quality evidence). Napping during the night shiftA meta-analysis on a single nap opportunity and the effect on the mean reaction time as a surrogate for sleepiness, resulted in a 11.87 ms reduction (95% CI 31.94 to -8.2, very low quality evidence). Two other studies also reported statistically non-significant decreases in reaction time (1 study seven participants; 1 study 49 participants, very low quality evidence).A two-nap opportunity resulted in a statistically non-significant increase of sleepiness (subjective assessment) in one study (mean difference (MD) 2.32, 95% CI -24.74 to 29.38, 1 study, 15 participants, low quality evidence). Other interventionsPhysical exercise and sleep education interventions showed promise, but sufficient data to draw conclusions are lacking. AUTHORS' CONCLUSIONS: Given the methodological diversity of the included studies, in terms of interventions, settings, and assessment tools, their limited reporting and the very low to low quality of the evidence they present, it is not possible to determine whether shift workers' sleepiness can be reduced or if their sleep length or quality can be improved with these interventions.We need better and adequately powered RCTs of the effect of bright light, and naps, either on their own or together and other non-pharmacological interventions that also consider shift workers' chronobiology on the investigated sleep parameters.