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.

COVID-19: Heterogeneous Excess Mortality and "Burden of Disease" in Germany and Italy and Their States and Regions, January-June 2020.

Total mortality and "burden of disease" in Germany and Italy and their states and regions were explored during the first COVID-19 wave by using publicly available data for 16 German states and 20 Italian regions from January 2016 to June 2020. Based on expectations from 2016 to 2019, simplified Standardized Mortality Ratios (SMRs) for deaths occurring in the first half of 2020 and the effect of changed excess mortality in terms of "burden of disease" were assessed. Moreover, whether two German states and 19 Italian cities appropriately represent the countries within the European monitoring of excess mortality for public health action (EuroMOMO) network was explored. Significantly elevated SMRs were observed (Germany: week 14-18, Italy: week 11-18) with SMR peaks in week 15 in Germany (1.15, 95%-CI: 1.09-1.21) and in week 13 in Italy (1.79, 95%-CI: 1.75-1.83). Overall, SMRs were 1.00 (95%-CI: 0.97-1.04) in Germany and 1.06 (95%-CI: 1.03-1.10) in Italy. Significant SMR heterogeneity was found within both countries. Age and sex were strong modifiers. Loss of life expectancy was 0.34 days (1.66 days in men) for Germany and 5.3 days (6.3 days in men) for Italy [with upper limits of 3 and 6 weeks among elderly populations (≥65 years) after maximum potential bias adjustments]. Restricted data used within EuroMOMO neither represents mortality in the countries as a whole nor in their states and regions adequately. Mortality analyses with high spatial and temporal resolution are needed to monitor the COVID-19 pandemic's course.

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.

COVID-19 and healthcare workers: a rapid systematic review into risks and preventive measures.

OBJECTIVE: The COVID-19 pandemic is demanding for occupational medicine and for public health. As healthcare workers (HCWs) fight impacts of SARS-CoV-2 on front lines, we must create safe work environments through comprehensive risk assessments, evaluation and effective implementation of counter-measures. We ask: 'What does current literature report on health risks at workplaces regarding COVID-19?' and 'What do current studies report on the effectiveness of enacted preventative recommendations?' METHODS: As a snapshot of early HCW research, on 26 April 2020, we conducted a rapid systematic literature search in three databases (PubMed, Web of Science and PsycInfo) for COVID-19-related health outcomes and preventive measures in healthcare-associated workplaces. RESULTS: 27 studies were identified as relevant for exploring the risk of infection, 11 studies evaluated preventive measures. The studies described that SARS-CoV-2 impacts significantly on HCW's health and well-being, not only through infections (n=6), but also from a mental health perspective (n=16). 4 studies reported indirect risks such as skin injuries, one study described headaches to result from the use of personal protective equipment. Few studies provided information on the effectiveness of prevention strategies. Overall, most studies on health risks as well as on the effectiveness of preventive measures were of a moderate-to-low quality; this was mainly due to limitations in study design, imprecise exposure and outcome assessments. CONCLUSIONS: Due to widespread exposure of HCW to SARS-CoV-2, workplaces in healthcare must be as safe as possible. Information from HCW can provide valuable insights into how infections spread, into direct and indirect health effects and into how effectively counter-measures mitigate adverse health outcomes. However, available research disallows to judge which counter-measure(s) of a current 'mix' should be prioritised for HCW. To arrive at evidence-based cost-effective prevention strategies, more well-conceived studies on the effectiveness of counter-measures are needed.

Perinatal photoperiod and childhood cancer: pooled results from 182,856 individuals in the international childhood cancer cohort consortium (I4C).

Experimental evidence suggests that perinatal light imprinting of circadian clocks and systems may affect downstream physiology and cancer risk in later life. For humans, the predominant circadian stimulus is the daily light-dark cycle. Herein, we explore associations between perinatal photoperiod characteristics (photoperiod: duration of daylight as determined by time-of-year and location) and childhood cancer risk. We use pooled data on 182,856 mothers and babies from prospective birth cohorts in six countries (Australia, Denmark, Israel, Norway, UK, USA) within the International Childhood Cancer Cohort Consortium (I4C). Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In line with predicted differential dose-responses, restricted cubic splines indicate a potential non-linear, non-monotonic relationship between perinatal mean daily photoperiod (0-24 h) and childhood cancer risk. In a restricted analysis of 154,121 individuals who experienced third trimester photoperiods exclusively within the 8-16-h range, the relative risk of developing childhood cancer decreased by 9% with every hour increase in third trimester mean daily photoperiod [HR: 0.91 (95%CIs: 0.84-0.99)]. In conclusion, in this first study of perinatal photoperiod and childhood cancer, we detected an inverse ["protective"] linear association between third trimester mean daily photoperiod and childhood cancer risk in the 8-16-h set of the total study population. Limited statistical power impeded the investigation of risks with individuals exposed to more extreme photoperiods. Future studies are needed to confirm differential photoperiod-associated risks and further investigations into the hypothesized circadian imprinting mechanism are warranted.

IARC 2019: "Night shift work" is probably carcinogenic: What about disturbed chronobiology in all walks of life?

In June of 2019, a working group convened by the International Agency for Research on Cancer [IARC] concluded that "night shift work" is probably carcinogenic to humans (a Group 2A carcinogen). This was based on sufficient evidence of cancer and strong mechanistic evidence in experimental animals and limited evidence from human epidemiological studies. The biological basis from experimental work is clear and compelling: Disturbed chronobiology such as due to alterations in the light-dark schedule which shift-workers experience is associated with carcinogenicity. But is it correct to assume in epidemiological studies that "night shift work" provides the same dose of disturbed chronobiology to all night workers and that disturbed chronobiology from activities outside of work does not count? Both chronobiological theory and supporting evidence suggest that much-needed future epidemiology should address these questions and should consider disturbed chronobiology in all walks of life.

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.

Exercise time cues (zeitgebers) for human circadian systems can foster health and improve performance: a systematic review.

BACKGROUND: Circadian system time cues (zeitgebers) acting synergistically at the right times can foster chronobiological homeostasis and ultimately health. Modern 24/7 societies are challenging chronobiological homeostasis and public health. Exercise has been discussed as a potential zeitgeber for the human circadian system. Thus, if timed correctly, exercise may help in maintenance of chronobiological homeostasis and foster public health amidst increasingly challenging 24/7 lifestyles. OBJECTIVE: To test, using a systematic review of the literature, the following hypothesis: exercise is a zeitgeber for the human circadian system. DATA SOURCES: The PubMed database was systematically searched on 19 October 2017 for relevant scientific studies and reports concerning chronobiology and exercise. Eligibility criteria were defined to include articles considering exercise as a potential zeitgeber for human circadian rhythmicity or chronobiological effects of exercise on health and/or physical performance. Cognitive effects and effects on children were excluded from the synthesis. RESULTS: Our systematic literature search and synthesis is compatible with the validity of the hypothesis. We report that potential exercise-zeitgeber properties may be used to improve health and performance. CONCLUSIONS: Informed timing of exercise, specific to the circadian rhythm phase and zeitgeber exposure of the individual, must be advocated in performance and disease contexts as an adjunct therapeutic or preventative strategy and physical enhancer.

Ford and Edison in a modern regulatory environment: the first-in-human trial of night-work and artificial light.

A thought experiment places Henry Ford and Thomas Alva Edison in a modern regulatory environment. In a utopian occupational world devoid of night-shifts or artificial light, Ford wants to experiment with "working through the night". To support Ford's project, Edison offers his patented electric lamps to "turn nights into days". An ethics committee [EC] does not approve the night-work experiment and Utopia's Food and Drug Administration [FDA] does not approve the potential medical device as safe for use by humans. According to the EC and FDA, complex effects on circadian biology and thus safety of work and light at night are not understood. The thought experiment conveys that we should pay more attention to possible risks of work and light at chronobiologically unusual times.

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.

The discovery of slowness: Time to deconstruct Gretzky's and Messi's predictive brains.

Jafari and Smith hypothesized that time during games may pass slower for the world's best football player, Lionel Messi, from Argentina. This hypothesis leads to two questions: How can we explain such temporal paradox and how could this explain his dominant performances? Remarkably, the Argentinian's case was preceded by the equally astonishing case of Wayne Gretzky: The Canadian considered ice hockey as a rather slow game and was the best player in the sport's history. Whether Messi's and Gretzky's motor neurons fire faster, (inter)act differently or whether other mechanisms are at (inter)play warrants targeted research. A further explanation for such dominance of football and ice hockey, respectively, could be that both athletes "buy time": To this end, automized motor skills may allow their predictive brains to make better use of time than other players to read the games and plan ahead. Deconstructing predictive minds of outperforming individuals like Gretzky and Messi could provide unique options to elucidate how differential time perception may make performances in athletes, and beyond, more swift and more efficient.