To study the incidence of sepsis and neonatal intensive care unit (NICU) costs as a function of the human milk (HM) dose received during the first 28 days post birth for very low birth weight (VLBW) ...infants.
Prospective cohort study of 175 VLBW infants. The average daily dose of HM (ADDHM) was calculated from daily nutritional data for the first 28 days post birth (ADDHM-Days 1-28). Other covariates associated with sepsis were used to create a propensity score, combining multiple risk factors into a single metric.
The mean gestational age and birth weight were 28.1 ± 2.4 weeks and 1087 ± 252 g, respectively. The mean ADDHM-Days 1-28 was 54 ± 39 ml kg(-1) day(-1) (range 0-135). Binary logistic regression analysis controlling for propensity score revealed that increasing ADDHM-Days 1-28 was associated with lower odds of sepsis (odds ratio 0.981, 95% confidence interval 0.967-0.995, P=0.008). Increasing ADDHM-Days 1-28 was associated with significantly lower NICU costs.
A dose-response relationship was demonstrated between ADDHM-Days 1-28 and a reduction in the odds of sepsis and associated NICU costs after controlling for propensity score. For every HM dose increase of 10 ml kg(-1) day(-1), the odds of sepsis decreased by 19%. NICU costs were lowest in the VLBW infants who received the highest ADDHM-Days 1-28.
Abstract
Introduction:
Racial differences exist in sleep duration and circadian timing, however it is unknown whether these differences extend to cognitive performance. The current study investigated ...the role of ancestry on sleep and performance before and after a 9h advance of the sleep/wake episode.
Methods:
Twenty African-Americans (9F; 32.1 ± 7.5yr) and 17 European-Americans (8F; 29.7 ± 5.7yr) completed the study. Participants were scheduled to four baseline days each with 8h time in bed based on their habitual sleep schedule such that sleep and circadian rhythms were aligned. The sleep-wake schedule was then advanced 9h earlier (misaligned) for three days. Total sleep time (TST) was assessed with actigraphy. The Automated Neuropsychological Assessment Metrics (ANAM) test battery was administered every 3h each day starting 2h after waking. Tests included a simple reaction time task (SRT) and Stanford sleepiness scale (SSS). Mixed model ANOVAs assessed the effects of ancestry (African-American or European-American) and condition (aligned or misaligned) on sleep and performance.
Results:
TST was reduced on misaligned days compared to baseline (F=18.67, p<0.001) and African-Americans slept less compared to European-Americans (F=8.58, p<0.01), especially on the first two misaligned days when the difference was 47 and 59 minutes respectively (F=6.67, p<0.01). Compared to baseline, misalignment increased SSS ratings (F=72.69, p<0.001), but did not affect the number of lapses (F=0.02, p=0.90) or median reaction time (RT)(F=0.02, p=0.88) on the SRT. While there was no effect of ancestry on SSS (F=0.22, p=0.64), there was a trend for lapses (F=3.55, p=0.07) and median RT (F=2.80, p=0.10) to be higher for African-Americans. On misaligned days, African-Americans performed worse than European-Americans at times corresponding to the end of baseline sleep (lapses, F=7.16, p<0.05; median RT, F=5.16, p<0.05).
Conclusion:
Racial disparities in sleep may be more prominent when the sleep episode is shifted, and there may be racial differences in the circadian regulation of performance. Results have implications for the sleep and performance of individuals undertaking shiftwork or transmeridan travel.
Support (If Any):
R01NR007677(CIE).
Introduction
The prophylactic administration of clotting factor concentrate is currently the most effective strategy for the prevention of joint bleeding. As new agents with different mechanisms of ...action and administration schedules are developed, it will be important to study them in relevant preclinical models.
Aim
The aim of this study was the standardization of a mouse haemarthrosis model in a haemophilia mouse and the development and validation of a comprehensive bleeding assessment system, the Bleeding Severity Score (BSS).
Methods and Results
Four outcome measurements were assessed, two of which, the extra‐articular bleeding score and intra‐articular bleeding score, were determined to be the most reliable and were summarized into a BSS which was validated using a mouse haemarthrosis variability model.
Conclusion
Using this model, the haemostatic effect of prospective drugs can be assessed in a clinically relevant joint bleeding model and will significantly increase the value of preclinical studies.
Disturbed sleep and on‐the‐job sleepiness are widespread problems among night shift workers. The pineal hormone melatonin may prove to be a useful treatment because it has both sleep‐promoting and ...circadian phase‐shifting effects. This study was designed to isolate melatonin’s sleep‐promoting effects, and to determine whether melatonin could improve daytime sleep and thus improve night time alertness and performance during the night shift. The study utilized a placebo‐controlled, double‐blind, cross‐over design. Subjects (n=21, mean age=27.0 ± 5.0 years) participated in two 6‐day laboratory sessions. Each session included one adaptation night, two baseline nights, two consecutive 8‐h night shifts followed by 8‐h daytime sleep episodes and one recovery night. Subjects took 1.8 mg sustained‐release melatonin 0.5 h before the two daytime sleep episodes during one session, and placebo before the daytime sleep episodes during the other session. Sleep was recorded using polysomnography. Sleepiness, performance, and mood during the night shifts were evaluated using the multiple sleep latency test (MSLT) and a computerized neurobehavioral testing battery. Melatonin prevented the decrease in sleep time during daytime sleep relative to baseline, but only on the first day of melatonin administration. Melatonin increased sleep time more in subjects who demonstrated difficulty in sleeping during the day. Melatonin had no effect on alertness on the MSLT, or performance and mood during the night shift. There were no hangover effects from melatonin administration. These findings suggest that although melatonin can help night workers obtain more sleep during the day, they are still likely to face difficulties working at night because of circadian rhythm misalignment. The possibility of tolerance to the sleep‐promoting effects of melatonin across more than 1 day needs further investigation.
Context: Both light and melatonin can be used to phase shift the human circadian clock, but the phase-advancing effect of the combination has not been extensively investigated.
Objective: The ...objective of the study was to determine whether phase advances induced by morning intermittent bright light and a gradually advancing sleep schedule could be increased with afternoon melatonin.
Participants: Healthy adults (25 males, 19 females, between the ages of 19 and 45 yr) participated in the study.
Design: There were 3 d of a gradually advancing sleep/dark period (wake time 1 h earlier each morning), bright light on awakening four 30-min bright-light pulses (∼5000 lux) alternating with 30 min room light < 60 lux and afternoon melatonin, either 0.5 or 3.0 mg melatonin timed to induce maximal phase advances, or matching placebo. The dim light melatonin onset was measured before and after the treatment to determine the phase advance.
Results: There were significantly larger phase advances with 0.5 mg (2.5 h, n = 16) and 3.0 mg melatonin (2.6 h, n = 13), compared with placebo (1.7 h, n = 15), but there was no difference between the two melatonin doses. Subjects did not experience jet lag-type symptoms during the 3-d treatment
Conclusions: Afternoon melatonin, morning intermittent bright light, and a gradually advancing sleep schedule advanced circadian rhythms almost 1 h/d and thus produced very little circadian misalignment. This treatment could be used in any situation in which people need to phase advance their circadian clock, such as before eastward jet travel or for delayed sleep phase syndrome.
The hypothesis that increased blood pressure reactivity to stress is an early risk marker of hypertension was tested in a 1994 follow-up of the 1974 to 1978 Air Traffic Controller Health Change Study ...sample.
Assessments in 1974 to 1978 included physical examinations and recordings (every 20 minutes for 5 hours) of both workload (planes within controller airspace) and blood pressure reactivity. Individual differences in reactivity were used to predict 1994 self-report of ever having been told by a physician to take antihypertensive medication, assessed in a telephone survey of 218 respondents who were normotensive or stage 1 hypertensive in 1974 to 1978.
Each SD increase in baseline systolic reactivity was associated with a 1.7 (p <.019) increase in the relative-odds of 1994 hypertension, after controlling for age, body mass index, and clinic systolic and diastolic blood pressure at clinical examination, with effects comparable for baseline normotensives and stage 1 hypertensives.
A 20-year follow-up of originally normotensive and stage I hypertensive workers suggests that increased systolic blood pressure reactivity to work stress is associated with long-term risk of hypertension.
Bright light can phase shift human circadian rhythms, and recent studies have suggested that exercise can also produce phase shifts in humans. However, few studies have examined the phase-shifting ...effects of intermittent bright light, exercise, or the combination. This simulated night work field study included eight consecutive night shifts followed by daytime sleep/dark periods (delayed 9 h from baseline). There were 33 subjects in a 2 x 2 design that compared 1) intermittent bright light (6 pulses, 40-min long each, at 5,000 lx) versus dim light and 2) intermittent exercise (6 bouts, 15-min long each, at 50-60% of maximum heart rate) versus no exercise. Bright light and exercise occurred during the first 6 h of the first three night shifts. The circadian phase marker was the demasked rectal temperature minimum. Intermittent bright-light groups had significantly larger phase delays than dim-light groups, and 94% of subjects who received bright light had phase shifts large enough for the temperature minimum to reach daytime sleep. Exercise did not affect phase shifts; neither facilitating nor inhibiting phase shifts produced by bright light.
We compared the contributions of bright light during the night shift and dark goggles during daylight for phase shifting the circadian rhythm of temperature to realign with a 12-hour shift of sleep. ...After 10 baseline days there were 8 night-work/day-sleep days. Temperature was continuously recorded from 50 subjects. There were four groups in a 2 x 2 design: light (bright, dim), goggles (yes, no). Subjects were exposed to bright light (about 5,000 lux) for 6 hours on the first 2 night shifts. Dim light was < 500 lux. Both bright light and goggles were significant factors for producing circadian rhythm phase shifts. The combination of bright light plus goggles was the most effective, whereas the combination of dim light and no goggles was the least effective. The temperature rhythm either phase advanced or phase delayed when it aligned with daytime sleep. However, when subjects did not have goggles only phase advances occurred. Goggles were necessary for producing phase delays. The most likely explanation is that daylight during the travel-home window after a night shift inhibits phase-delay shifts, and goggles can prevent this inhibition. Larger temperature-rhythm phase shifts were associated with better subjective daytime sleep, less subjective fatigue and better mood.
Various combinations of interventions were used to phase-delay circadian rhythms to correct their misalignment with night work and day sleep. Young participants (median age = 22, n= 67) participated ...in 5 consecutive simulated night shifts (2300 to 0700) and then slept at home (0830 to 1530) in darkened bedrooms. Participants wore sunglasses with normal or dark lenses (transmission 15% or 2%) when outside during the day. Participants took placebo or melatonin (1.8 mg sustained release) before daytime sleep. During the night shifts, participants were exposed to a moving (delaying) pattern of intermittent bright light (~5000 lux, 20 min on, 40 min off, 4-5 light pulses/night) or remained in dimlight (~150 lux). There were 6 intervention groups ranging fromthe least complex (normal sunglasses) to the most complex (dark sunglasses + bright light + melatonin). The dim light melatonin onset (DLMO) was assessed before and after the night shifts (baseline and final), and 7 h was added to estimate the temperature minimum (Tmin). Participants were categorized by their amount of reentrainment based on their final Tmin: not re-entrained (Tmin before the daytime dark/sleep period), partially re-entrained (Tmin during the first half of dark/sleep), or completely re-entrained (Tmin during the second half of dark/ sleep). The sample was split into earlier participants (baseline Tmin = 0700, sunlight during the commute home fell after the Tmin) and later participants (baseline Tmin > 0700). The later participants were completely re-entrained regardless of intervention group, whereas the degree of re-entrainment for the earlier participants depended on the interventions. With bright light during the night shift, almost all of the earlier participants achieved complete re-entrainment, and the phase delay shift was so large that darker sunglasses and melatonin could not increase its magnitude. With only room light during the night shift, darker sunglasses helped earlier participants phase-delay more than normal sunglasses, but melatonin did not increase the phase delay. The authors recommendthecombination of intermittent bright light during the night shift, sunglasses (as dark as possible) during the commute home, and a regular, early daytime dark/sleep period if the goal is complete circadian adaptation to night-shift work.
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