key: cord-0318497-n8iffrke authors: Montagnese, S.; Zarantonello, L.; Formentin, C.; Giusti, G.; Mangini, C.; Isherwood, C.; Ferrari, P.; Paoli, A.; Mapelli, D.; Rizzuto, R.; Toppo, S.; Skene, D.; Vettor, R.; Costa, R. title: Sleep and circadian indices for planning post-pandemic university timetables date: 2022-01-08 journal: nan DOI: 10.1101/2022.01.05.22268660 sha: 6129b3e011b590257d3dcd431d6c414d38a5bc49 doc_id: 318497 cord_uid: n8iffrke The aims of the present study were to obtain sleep quality and sleep timing information in a group of university students, and to evaluate the effects of a circadian hygiene education initiative. All students of the University of Padova (approximately 64,000) were contacted by e-mail (major campaigns in October 2019 and October 2020) and directed to an ad hoc website for collection of demographics and sleep quality/timing information. Participants (n=5740) received one of two sets of circadian hygiene advice ('A regular life' or 'Bright days and dark nights'). Every month, they were then asked how easy it had been to comply, and provided with the advice again. At any even month from joining, they completed the sleep quality/timing questionnaires again. Information on academic performance was obtained post hoc, together with representative samples of lecture (n=5972) and exam (n=1800) timings, plus lecture attendances (n=25,302). 52% of students had poor sleep quality and 82% showed signs of sleep deprivation. Those who joined in October 2020, after several months of lockdown and distance learning, had better sleep quality, less sleep deprivation and later sleep habits. The 'Bright days and dark nights' advice resulted in earlier get-up time/midsleep compared to the 'A regular life' advice. Significant changes in most sleep quality and sleep timing variables were observed in both advice groups over time, also in relation to pandemic-related events characterising 2020. Early-chronotype students had better academic performances compared to their later chronotype counterparts. In a multivariate model, sleep quality, chronotype and study subject were independent predictors of academic performance. Taken together, these results underlie the importance of designing circadian-friendly university timetables. Chronotype reflects an individual's natural inclination to place their activity/sleep within different intervals of the 24-hour day, and is partly genetically determined (Ashbrook et al., 2020) . Children tend towards earlier, morning chronotypes, whereas adolescents and young adults exhibit a sharp change towards eveningness (which is more pronounced/prolonged in males), but then mature adults/older individuals become progressively more morning-like (Roenneberg et al., 2004) . Latechronotype individuals are penalised by the Western "social clock" which forces them to study/work/function during the early part of the day, counter to their natural biological clock (Gentry et al., 2021) . It has been reported that early classes/early school tests in evening-type adolescents adversely affect their academic performance, especially in scientific subjects (Zerbini et al., 2017) , and that changes in school start times may help improve sleep Meltzer et al., 2021) and, possibly, also grades (Zerbini et al., 2017) . Less but similar information is available on the relationship between study timetables, sleep timing/length and academic performance in university students (Li et al., 2018 , Beşoluk et al., 2011 Smarr and Schirmer, 2018) . In addition, there are also studies on the effects of sleep deprivation on university students' athletic performance and wellbeing (Hodge et al., 2012; Bolin, 2019) . The aims of this study were to obtain comprehensive sleep quality/timing information, and to evaluate the effects of a university welfare-based circadian hygiene initiative -directed at all students -on sleep and academic performance. As the study progressed, it became apparent that novel information could also be obtained on the effects of the pandemic-related lockdown on sleepwake behaviour. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 An ad hoc full-responsive website was created for collection of the relevant information, with either an Italian or English interface to choose from. All active students at the University of Padova (approximately 64,000) were contacted by the university welfare offices on 28 October 2019 with an e-mail message including a brief description of the initiative and its aims, an invitation to participate, and a "call to action" button leading to the website (https://sleeprhythm-unipd.it/). This could only be accessed by use of the personal Shibboleth University of Padova username/password. Students who joined the initiative went on to receive reminders on the 28 th of each subsequent month to access the website again to provide additional information and receive advice. The website was always open for newcomers to join; access after each reminder was possible for 7 days. On joining for the first time, students were asked to provide information on demographics, sleepwake timing, night sleep quality and diurnal sleepiness. They then received one of two sets of circadian hygiene advice with similar, expected effects ("A regular life" or "Bright days and dark nights", Figure 1 ). Every month after joining, they were asked how easy it had been to comply with the advice and were provided with the advice again. At every even month from joining, they were asked to complete demographic, sleep-wake timing, night sleep quality and diurnal sleepiness information again. They were also asked how easy it had been to comply, and finally, they were provided with the advice again (Supplementary Table 1 ). An additional information/recruitment campaign was run on 28 October 2020 that excluded any student who had already joined. Information on the participating students' career parameters was obtained from the career office post hoc. Representative samples of the timings of electronic room bookings for lectures/exams and of recorded, anonymous lecture attendances were also obtained post hoc. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; https://doi.org/10.1101/2022.01.05.22268660 doi: medRxiv preprint 6 (very likely). The component scores are summated to provide a total score (range: 0-24); a score of ≥ 11 is considered abnormal (Johns, 1991) . The self-morningness/eveningness (Self-ME) questionnaire (Turco et al., 2015) . This is a validated, single-question assessment of chronotype through which participants qualify themselves as definitely morning, morning, evening or definitely evening types. The ultra-Short version of the Munich ChronoType Questionnaire (µMCTQ) (Ghotbi et al., 2020) . This is an adaptation of the MCTQ (Roenneberg et al., 2003) from 17 to 6 essential questions, allowing for a quick assessment of midsleep (i.e. the midpoint, expressed as clock time, between sleep onset and sleep offset), social jetlag (in this instance, the uncorrected difference between midsleep on free and work/study days) and sleep duration. Social jetlag was both treated as a continuum variable and also qualified as positive (difference between midsleep on free and work/study days > +20 min), absent (-20 min < difference < +20 min) and negative (difference < -20 min) (Korman et al., 2020) . Two alternative sets of advice (novel in their formulation but grounded in circadian practice; Abbot et al., 2015) were provided (and remained the same on every subsequent "refresh" monthly reminder) with similar, expected effects exerted via two different forms of habits' adjustment (Facer-Childs et al., 2019) . Both included elements of the recommendations routinely provided to patients with either a formal diagnosis and/or features of delayed sleep phase type (Abbot et al., 2015) , which is common in adolescents and young adults. "A regular life", encouraging participants to regularize habits in relation to sleep-wake timing, meals, and exercise ( Figure 1A ). This intervention did not include advice on light exposure, as while the idea of sleep, meals and exercise at regular times is extremely intuitive and easily interpreted, that of "light at regular times" seems less so. Therefore, when planning the intervention, we reasoned that advice on "light at regular times" would be prone to misinterpretation. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; https://doi.org/10.1101/2022.01.05.22268660 doi: medRxiv preprint "Bright days and dark nights", encouraging participants to advance their sleep-wake, meals, and exercise timing, and to maximise/minimise light exposure in the first/second part of the day, respectively ( Figure 1B ). The user-friendly, short format of the interventions was chosen to maximise the likelihood of them being read and considered by young, healthy individuals on a monthly basis, and most likely on the screen of their mobile phone. Along the same lines, we did not modulate advice in relation to photoperiod or daylight saving time (DST), deliberately opting for repeated, identical advice, which could be read, re-read (on refresh) and memorised easily, hopefully becoming part of the students' routine. This being a University-based welfare initiative all students were provided with advice, i.e. none served as "placebo". Compliance. Participants subjectively rated their compliance with each piece of advice received on a 0 (never) to 10 (all the time) visual-analogue scale. Information was obtained from the student career offices about each student's university course, course year, total number of exams passed, total number of "credits" (i.e. packages of formal lectures/practicals of variable length, depending on study subjects) and average marks (0-30, 18= pass) at fixed dates of the year, on a three-monthly interval (28 October 2019, 28 January 2020, 28 April 2020, 28 July 2020 and 28 October 2020). These data were then matched with the "join the initiative" date, and organised as baseline (T0) and subsequent time intervals. Studies were classed as health&medical (M), science&technology (S) and social&humanities (H), based on Italian Ministry of University and Research reference tables. Courses have variable duration: most have a three plus two year structure (in this instance students who went on to attend their master's were qualified as fourth or fifth year), while a minority have a four to six year duration. Based on the All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; https://doi.org/10.1101/2022.01.05.22268660 doi: medRxiv preprint information they provided and on University of Padova criteria, students were classified as on-site, commuters or off-site (i.e. non-compulsory lectures and/or registered for exams only). Significant differences in sleep-wake and other parameters were observed between students pursuing M, S and H studies, which were thought to depend, to some extent, on lectures timing/duration and/or exams timing. Thus, a sample of electronic room bookings for lectures (n=5972) was obtained post hoc on a representative week (4-10 November 2019, i.e. close to study start; lectures were arbitrarily qualified as morning/afternoon if they started prior to/later than 13:00 h, respectively) and a sample of anonymous students' recorded attendances (electronic swipe inswipe out, n=25,302; multiple swipe ins -swipe outs, n=7765) on 30 October 2020. This date was chosen because, due to novel, pandemic-related rules, all students were asked to swipe in -swipe out electronically. Finally, a sample of exam booking times was obtained, on a representative week [9-13 September 2019 (n=1800 bookings)]; again, exams were arbitrarily qualified as morning/afternoon if they started prior to/later than 13:00 h, respectively. The initiative was approved by the University of Padova (16 July 2019 board meeting). Students were asked to accept/tick a general data protection regulation (GDPR)-compliant informed consent, including the wording "data may be used anonymously, in aggregate fashion for scientific purposes". The study plan was then approved by the local ethics committee. Descriptive results are expressed as mean±SD/SE or as count/percentage. Normality was tested for by the Shapiro-Wilk's test. Differences between normally distributed variables were examined by Student's t test/one way ANOVA (post hoc: Scheffé test). Differences between non-normally distributed variables were examined by Mann-Whitney U test/Kruskal-Wallis ANOVA (post hoc: median test). Bonferroni correction for multiple comparisons was applied as appropriate. The All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; effects of the circadian hygiene initiative and academic performance over time were analysed by repeated measures ANOVA (no missing data imputation procedures applied); Female students had earlier sleep-wake timing habits, more night awakenings, worse sleep quality and more daytime sleepiness compared to male students (Table 1 ). In addition, they had earlier midsleep on both study and free days, and they more commonly classified themselves as morning chronotypes. Finally, their sleep duration was longer on free days ( October 2019 cohort. Of note, the two cohorts were comparable in age and female/male ratio, and any students who joined in between or later were excluded for purposes of this specific comparison. Questionnaire completion rates decreased over time (Supplementary Table 1 ). While several hundred students completed the questionnaires at any given T (Supplementary Table 1 ), a total of 30 completed all even study times up to T12 in the "A regular life" group, and 28 in the "Bright days and dark nights" group. The two groups were comparable for sleep quality/timing, and female/male, study subject and chronotype ratios. Significant differences between the two intervention groups were observed in get-up time and in the latency between wake-up and get-up time until T10 (earlier get-up time and shorter latency in the "Bright days and dark nights" group). Statistical significance was lost when T12, which coincided with the transition from DST to standard time (ST), was included (Figure 2A-B) . At this moment, it was the behaviour of the "A regular life" group that changed the most (Figure 2A -B), with the return to ST facilitating them more than their counterparts who had already been advised to go to bed and get up earlier. Along the same lines, a trend difference (0.05
H>S), age (positive correlation), sleep quality (positive correlation) and sex (F>M) were associated with a higher number of exams passed/credits acquired, while study subject (H>M>S), chronotype (M>E) and sleep quality (positive correlation) were associated with better marks (Supplementary Table 4 ). All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; https://doi.org/10.1101/2022.01.05.22268660 doi: medRxiv preprint Poor sleep quality was common, with over half of the students reporting abnormal, albeit mild, sleep disruption. Despite reasonable sleep duration, social jetlag -a marker of sleep deprivation during study days -was also extremely common. All such abnormalities were less pronounced in the October 2020 compared to the October 2019 cohort, suggesting that long periods of full/partial lockdown and distance learning (thus less pressure from the "social clock") made it easier for students to follow their inclination towards later sleep timing, and to sleep better. This is supported also by the large decrease in social jetlag observed in commuters between October 2019 and April 2020, and is in line with similar, albeit mostly retrospective and unpaired observations in varying populations (Korman et al., 2020; Hallman et al., 2021; Blume et al., 2020; Gao et al., 2020; Leone et al., 2020; Partinen et al., 2020; Cellini et al., 2021) and also in University students (Wright et al., 2020; Marelli et al., 2021) . Most of the above studies on the effects of COVID-19-related lockdown measures and circadian/sleep variables in students and other populations were initiated during the pandemic, asking participants to provide pandemic and pre-pandemic information (the latter by recall) at a single moment in time. This methodology can be, of course, accepted but is far from ideal, because recollection of sleep-wake information (as recollection of other subjective variables) has been associated with both recall bias (Sukul et al., 2020) and summary distortion (Montagnese et al, 2009) . By contrast, we were able to acquire repeat circadian/sleep information prior to and during the pandemic in a clean, longitudinal fashion, and with high time resolution. The "Bright days and dark nights" advice resulted in earlier get-up time/earlier midsleep and decreased latency between wake-up and get-up time, with no impact on sleep duration. These are desirable, relevant effects in young adults (Bjorvatn et al., 2009) , and were observed within the context of "a low intensity" intervention to promote healthy circadian behaviours in university students. One must remember that expectations on the real life effects of educational interventions in healthy individuals are low, as unsolicited advice is rarely complied with, there is an inherent resistance to changing habits (dietary advice is the most common reference in this respect; Kapur et All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; https://doi.org/10.1101/2022.01.05.22268660 doi: medRxiv preprint al., 2008; Martis et al., 2018) and this is even more pronounced in healthy individuals, who have limited incentive to do so. Also, while we opted for a comprehensive baseline sleep-wake assessment, the intervention was circadian in its essence, and meant to affect sleep timing rather than sleep quality variables, which is what happened. The effect on sleep timing was observed despite students reporting difficulties in complying with sleep advice, and may be due, in part, to them finding it easier to follow light environment advice. This type of light advice, in a population that makes large use of portable devices (Gringas et al., 2015) in the evening/early night hours for study and recreational purposes, may indeed be crucial, also explaining part of the differences in the effects of the "Bright days and dark nights" and the "A regular life" advice. Being a Universitybased educational initiative, the study obviously lacks a placebo arm, and some of the methodological rigour associated with pre-ordinated design. On the positive side though, the ecological nature of the presented results provides a phenomenal amount of real-life information, which may be useful to plan similar initiatives or more formal studies in future. The initial response to the initiative, as measured by standard e-mail marketing indices, compares very favourably with average responses to Italian work/education-related initiatives in which candidate participants were contacted by email [https://www.mailup.com/; unique e-mail opens: 51.6 (our initiative) vs. 10.0%; unique link clicks: 2.9 vs. 0.5%; unique link clicks per unique e-mail opens: 5.7 vs. 4.8%]. Completion of questionnaires/compliance decreased considerably over time, suggesting feasibility issues with the initiative recall/refresh frequency, which may need modulating. It should be highlighted, however, that our intervention, lasting one year and based on monthly monitoring, was much longer and included considerably more time points than the few published similar interventions (Hershen and O'Brien, 2018; Illingworth et al., 2019; van Rijn et al., 2020; Semsarian et al., 2021) . For example, Semsarian and co-authors (Semsarian et al., 2021) report 35% participation on second contact; our was similar, with 32% of students responding at T1 (Supplementary Table 1 ). In addition, lower completion rates after T0 do not necessarily imply lack of compliance with the advice received on joining the initiative. In addition, should more or less All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; 1 6 compliant students adhere to some or all the received "Bright days and dark nights" advice over long periods (for example, it is very easy to imagine them making a habit of using the night-shift function on their portable devices), its positive effects may cumulate over time. Selection bias in relation to varying compliance levels is possible but unlikely, as students who completed all procedures at all times did not have distinctive demographic/sleep features. Finally, while it is possible to hypothesise that the "Bright days and dark nights" advice provided to the small number of students with a definitely morning chronotype and/or a negative social jetlag may have been counterproductive, it should be highlighted that even definitely morning students had a social jetlag which was close to one hour, thus most likely benefitting from the suggestions received. The published, original and also review/meta-analytic literature on education (mostly sleep but also circadian) aimed at adolescents (Chung et al., 2017; Illingworth et al., 2019; van Rijn et al., 2020) or university students (Dietrich et al., 2016; Hershen and O'Brien, 2018; Semsarian et al., 2021) is not conclusive, it is based on shorter programmes, yielding generally short-lived effects. In addition, it suggests that more consistent interventions compared to ours in terms of provision of information on the science/medical evidence behind the advice delivered tend to result in increased knowledge but not necessarily in significant changes in sleep/circadian habits (Illingworth et al., 2019; van Rijn et al., 2020) . Along the same lines, and despite being very appreciative of the importance of entrainment dynamics [synchronisation between the endogenous and the solar clock (Roenneberg and Merrow, 2007) ], our intervention was aimed at reducing the time gap between the students' endogenous clock and the social one, because for the time being lesson/exam times, like most social constraints, cannot be changed in the real world. So while the advice provided might not have necessarily favoured/paralleled entrainment in natural conditions, it will have hopefully helped the students functioning in their real world, with all its imposed time constraints, including lesson/exam times and DST. The time course of sleep timing/quality between October 2019 and October 2020 suggests that the mixture of full/partial lockdown, distance learning and the transition to/from DST all had All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; https://doi.org/10.1101/2022.01.05.22268660 doi: medRxiv preprint profound and intertwining effects, with any form of relaxation of the "social clock" resulting in delayed sleep timing, longer sleep duration and better sleep quality. These changes were always more obvious in evening types. Evening types also had worse academic performance compared to their more morning counterparts, within any study subject area. This is only partially in line with previous observations in high school students, whose performance was affected by chronotype mostly for scientific subjects (Zerbini et al., 2017) . Average marks increased over time, albeit very slightly. This might be explained by the fact that there is a selection process throughout university, with specific subjects -which may be more interesting for the students -being usually concentrated towards the end of their careers. However, it should be highlighted that the Italian system does not allow for a significant amount of choice/changes of the core curriculum, and these choices are probably of limited impact over the course of a single year, which was our analysis period. Alternative possibilities include some form of progressive familiarisation with the exam system, especially for younger students, or even distance learning during 2020 affecting both students' preparation and professors' attitudes. In the current study, both sleep quality and chronotype independently predicted academic performance, together with study subject. Based on these data and the observed, institutional differences in lecture timing/duration and exams timing between study subjects, two approaches could be envisaged: i) delaying science&technology timetables by 30-60 minutes (overall study day duration would allow to accommodate this as the last swipe out for the science&technology students was between 30 and 45 minutes earlier compared to the other two study subjects; Table 3) ; ii) acquiring chronotype information from students (by the one-question Self-ME, which is fast and convenient), and taking these into account when designing timetables, with a view to limit pressure on evening chronotypes. This not only seems feasible and worth investigating but may also become necessary in the post-pandemic era, which will presumably be still characterised by the need to avoid large groups of students attending lectures at any given time. Thus should lectures/exams timetable shifts remain necessary in large universities such as ours, they should probably be better All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; 1 8 designed to maximise academic performance. Similar approaches (i.e. acquisition and use of chronotype information to design work shifts) have already proven effective in terms of sleep length in workers from major industries (Vetter et al., 2015) . In addition, the advice shown to be easier to follow (i.e. advice on meal timing and light environment from "Bright days and dark nights") could readily be provided to students when they register at the University as part of their induction package. In conclusion, this large and comprehensive set of baseline data, the response and compliance to the educational initiative, the time course of sleep timing in the year of the pandemic, and the observed differences in academic performance by chronotype all underlie the importance of designing circadian-friendly university timetables. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 Author PF is the Chief Executive Officer and owner of ReMedia Srl, which received compensation for the development of the full-responsive website. No conflict of interest to declare for any of the other authors. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; https://doi.org/10.1101 https://doi.org/10. /2022 groups. Significant differences between the two groups were observed in compliance to sleep advice (A), which was greater in the "A regular life" group (p time <0.0001, p group=0.045, p interaction n.s.). Compliance to all types of advice increased over time in both groups (p time All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; https://doi.org/10.1101/2022.01.05.22268660 doi: medRxiv preprint 1 always significant, with no further differences between groups and no interactions). Values are expressed as means ± 95% Confidence Intervals. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted January 8, 2022. ; 2 8 (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (22.2-22.6) STSQS Bed time (hh:mm µMCTQ Sleep onset study days Self-morningness/eveningness questionnaire; µMCTQ: Ultra-Short Munich ChronoType Questionnaire *** p<0.001, ** p<0.01 H vs M p<0.001, p<0.05 H vs S °°°p <0.001, °°p <0.01, °p <0.05 M vs S The authors are grateful to Gioia Grigolin, Rosa Nardelli, Valentino Callegari, and Elena Carnevali, at the University of Padova, for their invaluable help with the technical and logistic aspects of the initiative.