Sleep regularity is a stronger predictor of mortality risk than sleep duration: A prospective cohort study.

Abnormally short and long sleep are associated with premature mortality, and achieving optimal sleep duration has been the focus of sleep health guidelines. Emerging research demonstrates that sleep regularity, the day-to-day consistency of sleep-wake timing, can be a stronger predictor for some health outcomes than sleep duration. The role of sleep regularity in mortality, however, has not been investigated in a large cohort with objective data. We therefore aimed to compare how sleep regularity and duration predicted risk for all-cause and cause-specific mortality. We calculated Sleep Regularity Index (SRI) scores from > 10 million hours of accelerometer data in 60 977 UK Biobank participants (62.8 ±â€…7.8 years, 55.0% female, median[IQR] SRI: 81.0[73.8-86.3]). Mortality was reported up to 7.8 years after accelerometer recording in 1859 participants (4.84 deaths per 1000 person-years, mean (±SD) follow-up of 6.30 ±â€…0.83 years). Higher sleep regularity was associated with a 20%-48% lower risk of all-cause mortality (p < .001 to p = 0.004), a 16%-39% lower risk of cancer mortality (p < 0.001 to p = 0.017), and a 22%-57% lower risk of cardiometabolic mortality (p < 0.001 to p = 0.048), across the top four SRI quintiles compared to the least regular quintile. Results were adjusted for age, sex, ethnicity, and sociodemographic, lifestyle, and health factors. Sleep regularity was a stronger predictor of all-cause mortality than sleep duration, by comparing equivalent mortality models, and by comparing nested SRI-mortality models with and without sleep duration (p = 0.14-0.20). These findings indicate that sleep regularity is an important predictor of mortality risk and is a stronger predictor than sleep duration. Sleep regularity may be a simple, effective target for improving general health and survival.

Causal Association Between Subtypes of Excessive Daytime Sleepiness and Risk of Cardiovascular Diseases.

BACKGROUND: Excessive daytime sleepiness (EDS), experienced in 10% to 20% of the population, has been associated with cardiovascular disease and death. However, the condition is heterogeneous and is prevalent in individuals having short and long sleep duration. We sought to clarify the relationship between sleep duration subtypes of EDS with cardiovascular outcomes, accounting for these subtypes. METHODS AND RESULTS: We defined 3 sleep duration subtypes of excessive daytime sleepiness: normal (6-9 hours), short (<6 hours), and long (>9 hours), and compared these with a nonsleepy, normal-sleep-duration reference group. We analyzed their associations with incident myocardial infarction (MI) and stroke using medical records of 355 901 UK Biobank participants and performed 2-sample Mendelian randomization for each outcome. Compared with healthy sleep, long-sleep EDS was associated with an 83% increased rate of MI (hazard ratio, 1.83 [95% CI, 1.21-2.77]) during 8.2-year median follow-up, adjusting for multiple health and sociodemographic factors. Mendelian randomization analysis provided supporting evidence of a causal role for a genetic long-sleep EDS subtype in MI (inverse-variance weighted ß=1.995, P=0.001). In contrast, we did not find evidence that other subtypes of EDS were associated with incident MI or any associations with stroke (P>0.05). CONCLUSIONS: Our study suggests the previous evidence linking EDS with increased cardiovascular disease risk may be primarily driven by the effect of its long-sleep subtype on higher risk of MI. Underlying mechanisms remain to be investigated but may involve sleep irregularity and circadian disruption, suggesting a need for novel interventions in this population.

The effect of text message reminders on compliance with Twin Block appliances: A randomised controlled trial.

AIMS: The aim of this study was to evaluate whether text reminders influence patient compliance with Twin Block appliances. The null hypothesis was that there was no statistically significant differences in Twin Block compliance between those who receive text reminders and those that do not. DESIGN: Single-blind parallel randomised controlled clinical trial. SETTING: Health Service Executive (HSE) orthodontic outpatient clinic in Dublin, Ireland. PARTICIPANTS: A total of 59 patients aged 11-15 years with a 5a Index of Orthodontic Treatment Need (IOTN grade) starting treatment with Twin Block appliances. METHODS: A computer-generated unstratified allocation sequence was used to randomise the participants into the control group (CG) or the text group (TG). Both groups were asked to wear their appliances full-time. In addition to the same verbal and written instruction received by the CG, the TG received text message reminders to wear their appliances every 3 days. The primary outcome measure was wear time reported by Theramon® sensors embedded in the appliances. Data on wear time were uploaded from the Theramon® sensors onto cloud software. Participants in both groups were asked to fill out wear diaries and submit these at each visit. Treating clinicians and the primary investigator were blinded to the allocation group. Participants were followed up for 4 months. Participants were not blinded to their treatment group. RESULTS: In total, 29 participants were allocated to the CG and 30 to the TG. The data for 53 participants were analysed, 24 from the CG and 29 from the TG. The median hours/day of wear recorded using the Theramon® sensors was 13.77 (interquartile range [IQR] = 10.19) for the CG and 17.72 (IQR = 5.62) for the TG. The difference in wear time recorded was not statistically significant (P = 0.16). CONCLUSION: The study concluded that text message reminders had no statistically significant influence on patient compliance with Twin Block appliances.

Genome-wide gene by environment study of time spent in daylight and chronotype identifies emerging genetic architecture underlying light sensitivity.

STUDY OBJECTIVES: Light is the primary stimulus for synchronizing the circadian clock in humans. There are very large interindividual differences in the sensitivity of the circadian clock to light. Little is currently known about the genetic basis for these interindividual differences. METHODS: We performed a genome-wide gene-by-environment interaction study (GWIS) in 280 897 individuals from the UK Biobank cohort to identify genetic variants that moderate the effect of daytime light exposure on chronotype (individual time of day preference), acting as "light sensitivity" variants for the impact of daylight on the circadian system. RESULTS: We identified a genome-wide significant SNP mapped to the ARL14EP gene (rs3847634; p < 5 × 10-8), where additional minor alleles were found to enhance the morningness effect of daytime light exposure (ßGxE = -.03, SE = 0.005) and were associated with increased gene ARL14EP expression in brain and retinal tissues. Gene-property analysis showed light sensitivity loci were enriched for genes in the G protein-coupled glutamate receptor signaling pathway and genes expressed in Per2+ hypothalamic neurons. Linkage disequilibrium score regression identified Bonferroni significant genetic correlations of greater light sensitivity GWIS with later chronotype and shorter sleep duration. Greater light sensitivity was nominally genetically correlated with insomnia symptoms and risk for post-traumatic stress disorder (PTSD). CONCLUSIONS: This study is the first to assess light as an important exposure in the genomics of chronotype and is a critical first step in uncovering the genetic architecture of human circadian light sensitivity and its links to sleep and mental health.

Time spent in outdoor light is associated with mood, sleep, and circadian rhythm-related outcomes: A cross-sectional and longitudinal study in over 400,000 UK Biobank participants.

BACKGROUND: Light has powerful effects on mood, sleep, and the circadian system. Humans evolved in an environment with a clear distinction between day and night, but our modern environments have blurred this distinction. Negative effects of light exposure at night have been well characterized. The importance of daytime light exposure has been less well characterized. Here we examine the cross-sectional and longitudinal associations of time spent in daytime outdoor light with mood, sleep, and circadian-related outcomes. METHODS: Participants were drawn from the UK Biobank cohort, a large study of UK adults (n = 502,000; 37-73 years old; 54% women). RESULTS: UK Biobank participants reported spending a median of 2.5 daylight hours (IQR = 1.5-3.5 h) outdoors per day. Each additional hour spent outdoors during the day was associated with lower odds of lifetime major depressive disorder (95% CI OR:0.92-0.98), antidepressant usage (OR:0.92-0.98), less frequent anhedonia (OR:0.93-0.96) and low mood (OR:0.87-0.90), greater happiness (OR:1.41-1.48) and lower neuroticism (incident rate ratio, IRR:0.95-0.96), independent of demographic, lifestyle, and employment covariates. In addition, each hour of daytime light was associated with greater ease of getting up (OR:1.46-1.49), less frequent tiredness (OR:0.80-0.82), fewer insomnia symptoms (OR:0.94-0.97), and earlier chronotype (adjusted odds ratio; OR:0.75-0.77). Auto-Regressive Cross-Lagged (ARCL) models were used to examine the longitudinal association of time spent in outdoor light at baseline with later mood-, sleep- and circadian-related outcomes reported at time point 2. Overall, longitudinal associations support cross-sectional findings, though generally with smaller effect sizes. LIMITATIONS: Future studies that examine the intensity of daytime light exposure at the ocular level are needed. CONCLUSIONS: Our findings suggest that low daytime light exposure is an important environmental risk factor for mood, sleep, and circadian-related outcomes.

Predicting lapses of attention with sleep-like slow waves.

Attentional lapses occur commonly and are associated with mind wandering, where focus is turned to thoughts unrelated to ongoing tasks and environmental demands, or mind blanking, where the stream of consciousness itself comes to a halt. To understand the neural mechanisms underlying attentional lapses, we studied the behaviour, subjective experience and neural activity of healthy participants performing a task. Random interruptions prompted participants to indicate their mental states as task-focused, mind-wandering or mind-blanking. Using high-density electroencephalography, we report here that spatially and temporally localized slow waves, a pattern of neural activity characteristic of the transition toward sleep, accompany behavioural markers of lapses and preceded reports of mind wandering and mind blanking. The location of slow waves could distinguish between sluggish and impulsive behaviours, and between mind wandering and mind blanking. Our results suggest attentional lapses share a common physiological origin: the emergence of local sleep-like activity within the awake brain.

Orthodontic therapy teaching review at Trinity College Dublin.

INTRODUCTION: The aim of this teaching review was to obtain feedback from graduates of the Orthodontic Therapy course from the School of Dental Science, Trinity College Dublin, which was established in 2014. MATERIALS AND METHODS: A focus group, comprising of one to two graduates from each of the five years of the orthodontic therapy course, convened to obtain feedback. Thematic analysis was used to analyse the feedback transcribed from the focus group. RESULTS: Multiple themes emerged including enthusiasm, commitment, educational support, peer support and satisfaction. The graduates found the course challenging but very rewarding, helped by support from the university, mentors and peers. Satisfaction was very high from all participants with 100% reporting they would recommend the course. Suggestions emerged regarding the delivery of specific didactic components of the course and increased engagement with the specialist orthodontic mentors to ensure teaching is standardised for all trainees. CONCLUSION: The course is rated very highly by the graduates and completion of this training has had a positive impact on their job satisfaction. Members of the focus group provided constructive feedback on the delivery of the course, which will contribute to its refinement for future trainees.

High sensitivity and interindividual variability in the response of the human circadian system to evening light.

Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (<30 lux) environmental light-stimuli at extreme ends of the circadian system's dose-response curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30-300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose-response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18-30) were exposed to a dim control (<1 lux) and a range of experimental light levels (10-2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock's role in human health and disease.

Traits related to bipolar disorder are associated with an increased post-illumination pupil response.

Mood states in bipolar disorder appear to be closely linked to changes in sleep and circadian function. It has been suggested that hypersensitivity of the circadian system to light may be a trait vulnerability for bipolar disorder. Healthy persons with emotional-behavioural traits associated with bipolar disorder also appear to exhibit problems with circadian rhythms, which may be associated with individual differences in light sensitivity. This study investigated the melanopsin-driven post-illumination pupil response (PIPR) in relation to emotional-behavioural traits associated with bipolar disorder (measured with the General Behavior Inventory) in a non-clinical group (n = 61). An increased PIPR was associated with increased bipolar disorder-related traits. Specifically, the hypomania scale of the General Behavior Inventory was associated with an increased post-blue PIPR. Further, both the full hypomania and shortened '7 Up' scales were significantly predicted by PIPR, after age, sex and depressive traits were controlled. These findings suggest that increased sensitivity to light may be a risk factor for mood problems in the general population, and support the idea that hypersensitivity to light is a trait vulnerability for, rather than symptom of, bipolar disorder.

The pupillary light reflex distinguishes between circadian and non-circadian delayed sleep phase disorder (DSPD) phenotypes in young adults.

This study investigated the utility of the pupillary light reflex as a method of differentiating DSPD patients with delayed melatonin timing relative to desired/required sleep time (circadian type) and those with non-delayed melatonin timing (non-circadian type). All participants were young adults, with a total of 14 circadian DSPD patients (M = 28.14, SD = 5.26), 12 non-circadian DSPD patients (M = 29.42, SD = 11.51) and 51 healthy controls (M = 21.47 SD = 3.16) completing the protocol. All participants were free of central nervous system acting medications and abstained from caffeine and alcohol on the day of the assessment. Two pupillary light reflex measurements were completed by each participant, one with a 1s dim (~10 lux) light exposure, and one with a 1s bright (~1500 lux) light exposure. Circadian DSPD patients showed a significantly faster pupillary light reflex than both non-circadian DSPD patients and healthy controls. Non-circadian patients and healthy controls did not differ significantly. Receiver operating characteristic curves were generated to determine the utility of mean and maximum constriction velocity in differentiating the two DSPD phenotypes, and these demonstrated high levels of sensitivity (69.23--100%) and specificity (66.67-91.67%) at their optimal cut offs. The strongest predictor of DSPD phenotype was the mean constriction velocity to bright light (AUC = 0.87). These results support the potential for the pupillary light reflex to clinically differentiate between DSPD patients with normal vs. delayed circadian timing relative to desired bedtime, without the need for costly and time-consuming circadian assessments.

Increased vulnerability to attentional failure during acute sleep deprivation in women depends on menstrual phase.

Study Objectives: To investigate sex differences in the effect of sleep deprivation on performance, accounting for menstrual phase in women. Methods: We examined alertness data from 124 healthy women and men (40 women, 84 men; aged 18-30 years) who maintained wakefulness for at least 30 hr in a laboratory setting using a constant routine protocol. Objective alertness was assessed every 2 hr using a 10 min psychomotor vigilance task. Subjective alertness was assessed every hour via the Karolinska Sleepiness Scale. Results: Women in the follicular phase of the menstrual cycle demonstrated the poorest level of performance. This poor performance was most pronounced at times corresponding to the typical sleep episode, demonstrating a window of vulnerability at night during this menstrual phase. At 24 hr awake, over 60 per cent of their responses were lapses of >500 ms and over one-third of their responses were longer lapses of at least 3 s in duration. Women in the luteal phase, however, were relatively protected from alertness failure, performing similar or better than both follicular-phase women and men. Conclusions: These results have important implications for education and intervention programs for shift workers, specifically during times of vulnerability to attentional failure that increase risk of injury.

Increased Sensitivity of the Circadian System to Light in Early/Mid-Puberty.

CONTEXT: Late adolescence is marked by a delay in sleep timing, which is partly driven by a delay shift of the circadian timing system. This study examined whether the sensitivity of the circadian system to light-the primary entraining stimulus to the circadian system-differs between pre- to mid-pubertal and late to postpubertal adolescents. OBJECTIVE: The study was designed to determine the influence of puberty on the sensitivity of the circadian system to light in humans. METHODS: Melatonin suppression to low and moderate light levels was assessed in 38 pre- to mid-pubertal (9.1-14.7 years) and 29 late to postpubertal (11.5-15.9 years) adolescents. They received 1 hour of four light levels on consecutive nights: approximately 0.1 (near-dark baseline condition), 15, 150, and 500 lux. One group received evening light beginning at 11:00 pm (n = 39); a second group received morning light beginning at 3:00 am (n = 28). Salivary melatonin was sampled every 30 minutes. Melatonin suppression for 15, 150, and 500 lux was calculated relative to unsuppressed baseline levels in the 0.1 lux setting, within individuals. RESULTS: The pre- to mid-pubertal group showed significantly greater melatonin suppression to 15 lux (9.2 ± 20.5%), 150 lux (26.0 ± 17.7%), and 500 lux (36.9 ± 11.4%) during evening light exposure compared to the late to postpubertal group (-5.3 ± 17.7%, 12.5 ± 17.3%, and 23.9 ± 21.7%, respectively; P < .05). No significant differences were seen between developmental groups in morning melatonin suppression. CONCLUSION: These results indicate support for a greater sensitivity to evening light in early pubertal children. The increased sensitivity to light in younger adolescents suggests that exposure to evening light could be particularly disruptive to sleep regulation for this group.

The reliability of Little's Irregularity Index for the upper dental arch using three dimensional (3D) digital models.

AIM: To investigate the inter-examiner variability of contact point displacement measurements (used to calculate the overall Little's Irregularity Index (LII) score) from digital models of the maxillary arch by four independent examiners. METHODS: Maxillary orthodontic pre-treatment study models of ten patients were scanned using the Lava(tm) Chairside Oral Scanner (LCOS) and 3D digital models were created using Creo(®) computer aided design (CAD) software. Four independent examiners measured the contact point displacements of the anterior maxillary teeth using the software. Measurements were recorded randomly on three separate occasions by the examiners and the measurements (n=600) obtained were analysed using correlation analyses and analyses of variance (ANOVA). RESULTS: LII contact point displacement measurements for the maxillary arch were reproducible for inter-examiner assessment when using the digital method and were highly correlated between examiner pairs for contact point displacement measurements >2mm. The digital measurement technique showed poor correlation for smaller contact point displacement measurements (<2mm) for repeated measurements. The coefficient of variation (CoV) of the digital contact point displacement measurements highlighted 348 of the 600 measurements differed by more than 20% of the mean compared with 516 of 600 for the same measurements performed using the conventional LII measurement technique. CONCLUSIONS: Although the inter-examiner variability of LII contact point displacement measurements on the maxillary arch was reduced using the digital compared with the conventional LII measurement methodology, neither method was considered appropriate for orthodontic research purposes particularly when measuring small contact point displacements.

Can the intra-examiner variability of Little's Irregularity Index be improved using 3D digital models of study casts?

OBJECTIVES: To compare contact point displacement measurements, used to determine the Little's Irregularity Index (LII) score on study casts and digital models of study casts by an independent examiner. METHODS: The contact point displacement measurements of the six maxillary anterior labial teeth were measured on ten study casts using digital callipers and their associated digital models using Creo Parametric software on five occasions following scanning using a LAVA Chairside Oral Scanner (LCOS) three-dimensional (3D) intra oral scanner. Means, standard deviations and coefficients of variation (CoV) were determined, data analyses (Pearson's correlation coefficients (PCCs) and Intraclass correlation coefficients (ICCs)) and statistical analyses (three and two-way analyses of variance (ANOVAs) and Independent Sample Student's t-tests) were carried out (p<0.05). RESULTS: Significant positive correlations for the contact point displacement measurements were evident between all measurement time points for the study casts (r>0.978; p<0.0001 and ICC>0.910; p<0.0001) and the digital models (r>0.963; p<0.0001 and ICC>0.986; p<0.0001). The CoV results showed that the contact point displacement measurement data from the digital models was more reproducible than the study casts. Of the 50 Independent Sample Student's t-tests, 21 significant increases (p<0.042) were reported in contact point displacement measurements <2.9 mm for the digital models compared with the study casts. CONCLUSION: The use of 3D digital models can improve the reliability of LII measurements by reducing the subjectivity associated with choosing the anatomic tooth contact points and the awkwardness of measuring the contact point displacements on study casts using a cumbersome calliper technique. CLINICAL SIGNIFICANCE: Intra-examiner variability in the measurement of LII is still evident with digital models suggesting that either improved software specifically aimed at the orthodontic community be identified or a new method for measuring anterior incisor crowding be sought.