Effects of Exposure to Intermittent versus Continuous Red Light on Human Circadian Rhythms, Melatonin Suppression, and Pupillary Constriction

Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21–28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm−2 s−1), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Circadian phase shift responses to light (h ± SEM).

<p>Circadian phase shift responses are shown for 6 h of exposure to continuous red light, intermittent red light and darkness, or bright white light near the onset of melatonin secretion. By convention, negative values indicate phase delay shifts. Using a linear mixed-effects model for comparing phase resetting responses, bright white light elicited a larger response than either red light condition (<i>P</i><0.003). Phase shifts were similar in response to continuous versus intermittent red light (<i>P</i> = 0.69), and did not differ across physiologic measures (<i>P</i> = 0.35). Data were also analyzed using one-way ANOVA, whereby asterisks (*) indicate significant differences in response to bright white light versus continuous red light, and daggers (^†) indicate significant differences in response to bright white light versus intermittent red light. Phase resetting did not differ between red light conditions.</p

Protocol for assessing circadian phase shift responses and melatonin suppression.

<p>(<b>A</b>) Subjects took part in a 6-day laboratory study. Circadian rhythms were assessed using constant routine (CR) procedures before and after an experimental light exposure session. During the CR procedure, subjects were exposed to <5 lux of ambient light. During the light exposure session, subjects were exposed to 6 h of continuous red light (631 nm, 13 log photons cm⁻² s⁻¹), intermittent red light and darkness (∼1 min on, 1 min off), or bright polychromatic white light (2,500 lux; 4000K) starting 1 h before habitual bedtime. (<b>B</b>) The narrow-bandwidth red light stimulus was generated using a light-emitting diode and delivered to subjects' eyes using a modified Ganzfeld dome. The spectral emission of the LED stimulus is shown.</p

Melatonin levels and pupillary constriction during nocturnal light exposure.

<p>(<b>A</b>) Melatonin profiles are shown for participants exposed to 6 h of continuous red light (left), intermittent red light and darkness (center), or bright white light (right) near the onset of melatonin secretion. Black traces show the melatonin rhythm on the day prior to light exposure, and gray traces show melatonin on the day of the light exposure session. Melatonin concentrations during light exposure were individually adjusted using Z-score values obtained during the first constant routine procedure. Vertical dotted lines indicate the onset and offset of the light exposure session. (<b>B</b>) The area under the curve (AUC) of the melatonin profile during light exposure is shown for each subject, expressed as a percentage of his AUC measured in dim light. Values less than 100% therefore indicate light-induced melatonin suppression, whereas values that exceed 100% indicate that the AUC was higher during the light exposure session relative to the AUC measured in dim light on the previous day. The open circles show responses for subjects <i>crl30</i> and <i>irl31</i>, who exhibited substantial resetting of circadian rhythms, as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096532#pone-0096532-g003" target="_blank">Figure 3</a>. (<b>C</b>) The pupillary light reflex is shown during the first 50 min of exposure to continuous red light (left), alternating red light and darkness (center), and bright white light (right). (<b>D</b>) The median pupillary light response is shown for individual subjects during the 50-min fixed gaze period, expressed relative to the dark pupil. Horizontal dotted lines in <b>C</b> and <b>D</b> indicate pupil diameter in darkness, and data in <b>C</b> are binned at intervals of 15.625 s, corresponding to one-quarter of an intermittent lights-on pulse. In <b>A</b> and <b>C</b>, the mean ± SEM is shown. In <b>B</b> and <b>D</b>: crl, continuous red light; irl, intermittent red light; bwl, bright white light.</p

Circadian phase shift responses were similar for exposure to continuous versus intermittent red light.

<p>(<b>A</b>) Circadian responses are shown for individual subjects exposed to 6 h of continuous red light, intermittent red light and darkness, or bright white light. Circadian phase shifts are shown for melatonin (MLT), cortisol (Cort), core body temperature (CBT), forehead skin temperature (FST), and heart rate (HR). By convention, negative values show phase delay shifts. Horizontal lines show the grand mean for each light exposure condition, with the corresponding values shown at the top of the plot. (<b>B</b>) Most subjects exposed to continuous red light exhibited a small resetting response (left), but one participant showed a phase delay shift comparable in magnitude to bright white light exposure (right). (<b>C</b>) Likewise, in response to intermittent red light and darkness, circadian phase measured before and after light exposure was similar in most subjects (left); however one subject showed a large phase delay shift (right). In <b>B</b> and <b>C</b>, representative subjects are shown, with the circadian rhythm of core body temperature (CBT) shown before and after exposure to light (black and gray traces, respectively). Vertical lines show the timing of the fitted minimum for the CBT rhythm. Phase shift values are shown at the top of each plot, and the corresponding subject code is shown on the bottom right.</p

Sleep duration and growth outcomes across the first two years of life in the GUSTO study

Background and Aim: Short sleep duration is thought to be a factor contributing to increased body mass index (BMI) in both school-age children and adults. Our aim was to determine whether sleep duration associates with growth outcomes during the first two years of life.Study design: Participants included 899 children enrolled in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study. Anthropometric data (weight and body length) and parental reports of sleep duration were collected at 3, 6, 9, 12, 18, and 24 months of age. A mixed-model analysis was used to evaluate the longitudinal association of BMI and body length with sleep duration. In subgroup analyses, effects of ethnicity (Chinese, Indian, and Malay) and short sleep at three months of age (?12?h per day) were examined on subsequent growth measures.Results: In the overall cohort, sleep duration was significantly associated with body length (??=?0.028, 95% confidence interval [CI] 0.002–0.053, p?=?0.033), but not BMI, after adjustment for potential confounding factors. Only in Malay children, shorter sleep was associated with a higher BMI (??=??0.042, 95% CI ?0.071 to ?0.012, p?=?0.005) and shorter body length (??=?0.079, 95% CI 0.030–0.128, p?=?0.002). In addition, shorter sleep was associated with a higher BMI and shorter body length in children who slept ?12?h per day at three months of age.Conclusion: The association between sleep duration and growth outcomes begins in infancy. The small but significant relationship between sleep and growth anthropometric measures in early life might be amplified in later childhood.<br/