Weren't these earlier ones enough to get your doctor to set up a stroke protocol?
Oh well, incompetence reigns supreme in stroke. This repeat research is a direct result of not having a database of stroke research and protocols. Which our
fucking failures of stroke associations should have set up decades ago. You're screwed along with your children and grandchildren that have strokes.
Abstract
Background:
Stroke patients admitted for rehabilitation often lack sufficient daytime blue light exposure due to the absence of natural light stimulation and are often exposed to light at unnatural time points.
We hypothesized that artificial light imitating daylight, termed naturalistic light, would stabilize the circadian rhythm of plasma melatonin and serum cortisol levels among long-term hospitalized stroke patients.
Methods: A quasi-randomized controlled trial. Stroke patients in need of rehabilitation were randomized between May 1, 2014, and June 1, 2015 to either a rehabilitation unit equipped entirely with always on naturalistic lighting (IU), or to a rehabilitation unit with standard indoor lighting (CU). At both inclusion and discharge after a hospital stay of at least 2 weeks, plasma melatonin and serum cortisol levels were measured every 4 hours over a 24-hour period. Circadian rhythm was estimated using cosinor analysis, and variance between time-points.
Results: A total of 43 were able to participate in the blood collection. Normal diurnal rhythm of melatonin was disrupted at both inclusion and discharge. In the IU group, melatonin plasma levels were increased at discharge compared to inclusion (
2.9; IQR: −1.0 to 9.9
, p = 0.030) and rhythmicity evolved
p = 0.007). In the CU group, melatonin plasma levels were similar between discharge and inclusion and rhythmicity evolved. Overall, both patient groups showed normal cortisol diurnal rhythms at both inclusion and discharge.
Conclusions: This study is the first to demonstrate elevated melatonin plasma levels and evolved rhythmicity due to stimulation with naturalistic light.
Key words: Stroke; Rehabilitation; Circadian rhythm; Light; Melatonin; Cortisol
MANUSCRIPT
Introduction
Interventional uses of light have attracted growing
interest since the recent discovery of the blue
light absorbing Melanopsin-expressing photosensitive
ganglion cells (ipRGCs) in the retinal ganglion cell layer. Especially a subtype of ipRGCs (M1) pass the
highest amount of light stimulation through the optic nerve and retinohypothalamic
tract to the master circadian clock system in the suprachiasmatic nucleus (SCN).
Several studies indicate that sunlight is the strongest
entrainment for the circadian rhythm because of the sensitivity for
short-wavelength blue light [1].
Light
stimulation to the SCN also happens through the intergeniculate leaflet (IGL), which
appears to be an important secondary route for sunlight entrainment [2].
The SCN affects
melatonin and cortisol in a manner involving the oscillation system within the SCN
and its direct autonomic connection with peripheral tissue.
Melatonin is produced from
serotonin in the pineal gland, and its circuitous pathway is regulated by the SCN.
Light normally inhibits melatonin secretion, such that it is low during the day
and peaks late at night, and this temporal pattern is relatively unaltered by
changes in sleep habits
[3]. During hospitalization,
critically ill patients reportedly exhibit low melatonin levels and a disrupted diurnal melatonin
rhythm [4,5]. Patients with cortical stroke also show
decreased melatonin secretion [6-8] and a disturbed diurnal rhythm [9]. Although the physiological
explanation of this phenomenon is unknown. It is possible that the initial edema
and widespread cortical
lesions may affect areas projecting to the IGL, impairing light perception to
the SCN, and through that disrupting circadian rhythm regulation [6].
Another
well-known circadian-regulating hormone, cortisol, synchronizes
peripheral circadian oscillators and controls 60% of the circadian
transcriptome [10]. Cortisol
secretion is controlled by the SCN, where neuronal projections signal directly
to the paraventricular hypothalamic nucleus (PVH) and dorsomedial
hypothalamus (DMH). Cortisol levels normally
rise around midnight, peak in the early morning, and decrease again around 9
a.m. Cortisol is reportedly elevated in response to external stimulus, such as hospital admission and
surgery [11,12]. However, it seems likely that
cortisol is more stable than melatonin in critically ill patients exposed to
diurnal disruption [13].
Hospitalization and circadian rhythm
disruption reportedly have negative consequences [14]. Patients admitted for post-stroke rehabilitation
carry a high risk of circadian disruption due to the duration of
hospitalization and immobilization. This combination deprives patients of
natural light from the sun, subjects them to many hours of artificial light
from the evening and nighttime indoor hospital lighting.
LED (light-emitting diode) technologies
support the development of artificial light with specific wavelengths. Together
with computerized technology, this enables the production of lamps that can imitate
the natural sunlight spectrum and rhythm—termed naturalistic light, circadian
light, or dynamic lighting. Melatonin levels are influenced by light
interventions [15], and several studies show that
short-wave light is an isolated melatonin manipulator [16-19]. Previously tested light
interventions have not detectably altered melatonin levels in patients in
real-hospital settings [20,21]. However, no studies have
investigated the influence of naturalistic light on melatonin
levels and its diurnal rhythm.
In the present study, we aimed to
determine whether naturalistic light could stabilize the circadian rhythm of
melatonin and cortisol, and increase the expected low plasma melatonin levels
in stroke patients admitted for rehabilitation.
Materials and Methods
Study design and
Participants
This study was performed
in the Stroke Rehabilitation Unit, Department of Neurology, Rigshospitalet,
Copenhagen. The methods have been previously described in detail [14]. Briefly, the study included stroke patients
who required over 2 weeks of in-hospital rehabilitation during the
period from May 1st of 2014 to June 1st of 2015. Patients
were excluded if they were unable to give consent due to their awareness
status, severe aphasia, or less than 2 weeks of
hospitalization in the rehabilitation unit. We conducted a parallel randomized
controlled trial with two arms: an intervention group admitted to a rehabilitation
unit equipped with naturalistic light (IU), and a control
group admitted to a rehabilitation unit with standard indoor lighting (CU). No
safety precautions were necessary regarding assessments and interventions. The
study was approved by the Danish scientific ethics committee (H-4-2013-114) and
the Danish Data Protection Agency (2007-58-0015), and is registered at ClinicalTrials.gov (Identifier: NCT02186392).
Randomization
Randomization was
performed by non-blinded stroke nurses (quasi-randomization) at the acute stroke
unit (with normal standard light conditions). The nurses were not involved in
the study and were simply following normal procedure regarding the relocation
of patients to the two rehabilitation units.
Naturalistic light
intervention
In all areas of the
intervention rehabilitation unit, a 24-hour naturalistic lighting
scheme was implemented using multi-colored LED-based luminaires (lamps) managed
by a centralized lighting controller according to the lighting scheme (Chromaviso,
Denmark). The lighting was dim in the morning (from 7 am), increased
to reach maximum illuminance around betweennoon and 3 pm with
strong inclusion of the blue light spectrum, and then dimmed again throughout
the evening with diminishment of the blue light spectrum, ensuring no IpRGC stimulation
during nighttime. The luminaires were located in the ceiling and at
the wall behind the beds, and theThis
naturalistic lighting scheme ran constantly throughout the inclusion period.
Due to the complexity and the need for
comprehensive technical description of the light, the light intervention ispresented in details in
the method description paper [14]where
the irradiance profiles can be found in figure 3a and 3b. The technical light
description is produced in accordance with CIE TN 003 following
the principles of Lucas et al. [22].Normal
ceiling luminaries
were installed in the CU.
They had new fluorescent tubes installed prior to the
inclusion in order to uniform the
light in all areas of the CU. The
technical light description regard the
irradiance profiles for the IU can
be found in figure 3a and for CU in 3b in
West et al.[14]
Measurements
All
acute stroke patients underwent standard initial examinations. Additionally,
the Morningness-Eveningness Questionnaire (MEQ) was
performed at both inclusion and discharge to determine the distribution of circadian
classes. Daily life in the patient ward was best suited to morning types, such
that evening-type circadian class could potentially interfere with outcome for these
patients. The MEQ is validated for determining individual circadian rhythm [23], and divides patients into five
types: Definitely
Evening Type, Moderately Evening Type, Neither Type, Moderately
Morning Type, and Definitely Morning Type. The highest scores indicate the morning
type.
Blood samples
Blood
samples were collected at both inclusion and discharge
(hospital treatment complete/done) for
measurement of
melatonin and cortisol levels at 4-hour intervals, seven
times over a 24-hour period: 08 a.m., noon, 04 p.m., 08 p.m., midnight, 04 a.m.,
and again at 08 a.m. To prevent external factors other than light from influencing
plasma melatonin and serum cortisol levels, the participants were asked to avoid
parameters which could influence the blood levels [14]
(Table S1). Travel to different time
zones and regular night work within the last 14 days were registered. The
instructions were given both verbally and in writing. To avoid circadian stimulation, blood
collection was performed in dim lighting from an old
incandescent bulb, which has very low emission of the blue light spectrum. During
collection, the lamp was pointed towards the arm, away from the patient.
Blood samples were centrifuged
directly after collection, and plasma and serum were separated. Samples were immediately
stored at −50°C, and within 30 hours were stored at −80°C until further
analysis.
Biochemical analysis
Plasma melatonin concentrations were analyzed by
use of a Melatonin Direct Radioimmunoassay (LDN Labor Diagnostika Nord GmbH and
Co. Nordhorn) according to the kit instructions. The limit of detection was 2,3
pg/mL,the measuring range was
2.3 - 1000 pg/mL and the analytical between-run coefficient of variations were
19,6% at 24 pg/mL and 14% at 70 pg/mL.
Serum cortisol concentrations were determined on a
Cobas e 411 analyzed (Roche Diagnostics, Basel, Switzerland) by an
electro-chemiluminescence immunoassay.The
limit of detection was 0.5 nmol/L, the measuring range was 2 - 17500 nmol/L and
the analytical between-run coefficient of variation was 3% at 330 nmol/L.
MRI radiological classification
MRI
sequences were performed, and brain lesions were classified
according to volume
and anatomic localization by a neuro-radiologist. The infarction volume
(in cm3) was calculated by measuring the infarction size in the coronal,
transversal, and sagittal planes. All scans were performed using a 1.5
Tesla MR scanner (Siemens, General Electrics), and included the following
sequences: a sagittal T2-weighted turbo spin echo sequence (FSE), an axial T2-weighted
FSE, an axial fluid attenuation inversion recovery (FLAIR) sequence, an axial 3
scan trace diffusion-weighted imaging sequence, a sagittal 3D T1WI sequence,
and an axial susceptibility-weighted imaging sequence.
Outcomes
This study was part of a
larger investigation of the effects of light on human rehabilitation
patients health as measured by psychological parameters,
biochemical parameters, fatigue, and sleep. As this subject is a relatively new
scientific field, the study was considered an exploratory investigational
study. We chose five primary endpoints, including melatonin and cortisol levels
and rhythmicity in the present study.
Statistical analysis
All analyses
were performed using SAS (SAS Inst.
Inc., Cary, NC USA, 9.4). A p value of <0.05 was considered
significant. Between-group differences regarding basic demographic parameters
were calculated using the t-test for
continuous variables, and chi-square-test for categorical
variables. Normally distributed
continuous variables were expressed as mean ± standard
deviation (SD). The melatonin plasma levels and cortisol serum levels were not
normally distributed; therefore, these data were expressed as median and
interquartile range (IQR).
Data were logarithmically transformed prior to mixed
model analysis, and were subsequently transformed back to empirical fractiles to achieve parametric distribution,
which were then converted to percentage variance ((x−1) * 100). The deviation of calculated cosinor rhythmicity was expressed as
standard error (SE). Cosinor rhythmicity
was analyzed assuming a 24-hour time-period [24]. The data were fitted to a combined
cosine and sine function: y = M + k1COS(2pt/24) + k2SIN(2pt/24). The
24-hour rhythms of each group were further characterized by the following rhythm
parameters: mesor (rhythm-adjusted average about which oscillation occurs),
amplitude (difference between the highest and lowest values of the fitted
cosinor curve), and times of peak and nadir [24,25]. Data analyses were performed using the
GPLOT procedure in SAS. Mixed model analysis was performed in SAS to describe
the variance
between time-points of the diurnal rhythm of melatonin and cortisol at
inclusion and discharge in each unit.
Infarction size was correlated to
melatonin and cortisol mean values using regression analysis. Infarction
location was included as a confounding element by analysis of covariance. The Wilcoxon
signed-rank test was used to describe within-group changes from inclusion to
discharge. The mMelatonin
mean plasma values were calculated from all time-points together (24 h). Due to
the preserved diurnal rhythm, cortisol mean serum values were further divided
into day (high-secretion phase; 24–12 h) and night (low-secretion phase; 12–24 h)
values. Melatonin plasma levels did not show a diurnal rhythm in either unit;
thus, the division of mean melatonin values into further stages was not
relevant.
Results
Among 256 screened patients who required in-hospital neurorehabilitation, 90 met our
inclusion criteria, of whom 73 avoided meeting exclusion criteria, death, and
severe illness until discharge. Of these 73 included patients, 30 dropped out
before discharge, while the remaining 43 patients completed the study (Figure
1). The main reasons for missed
blood collection were the patient’s discomfort with the procedure, and technical
complications with the first 9 included patients. Patients were also excluded from blood collection due
to fragile veins and low hemoglobin concentration. Melatonin data from one patient were excluded due to prescribed
melatonin treatment. Cortisol data were excluded due to very high cortisol
values resulting from respiratory distress in one patient who unexpectedly died
a few hours after the last blood sampling. NIHSS (Included N=43; 5.0 (±4.2);
excluded N=30; 7.8 (±6.4): p=0.04) and Barthel (Included N=43; 56.9 (±30.0);
excluded N=30; 39.1 (±31.2): p=0.02) scores were calculated in the group of excluded patients and indicated
significant worse disability scores compared to the included participants (table
S2).
[Figure 1]
A total of 33 patients were willing
and able to sufficiently answer the MEQ. The two groups did not significantly differ
in circadian class distribution (chi-square test) (Table 1). Table 1 presents the
demographic data. The two groups were well matched, except regarding the number
of smokers (IU 13, CU 16, p = 0.02). Pre-analytical
variability was estimated to be equal among the patients based on the
information collected before blood sampling, and was therefore not included as
a confounding or interaction element.
[Table 1]
Circadian rhythm of melatonin and cortisol
At both
inclusion and discharge, both patient groups lacked a normal diurnal rhythm of plasma
melatonin. Melatonin plasma levels did not follow a cosinor rhythmicity in either
group, at either time-point (Table 2). Regarding the variance between time-points,
the CU group appeared to have an abnormal but diurnal melatonin rhythmicity at
inclusion (Table 3). However, this rhythmicity was absent at discharge which is
also illustrated by Figure 2,b. In the IU group at inclusion, melatonin plasma levels
only significantly differed between 08 p.m. and at discharge, melatonin levels
significantly differed between each time-point (Table S3), with elevated levels
from 08 a.m. to noon and from 08 p.m. to midnight illustrated by Figure 2,a. In
the IU group, we detected significant changes over time between inclusion and
discharge. Such differences were not evident in the CU group (Table 3).
A significant cortisol cosinor rhythm
(p < 0.0001) was detected in both patient
groups at both inclusion and discharge (Table 2, Figure 2,
ca,
db).
The CU group showed a significant amp/peak difference in cortisol values between
inclusion and discharge (p = 0.005)
which illustrate the decrease in cortisol levels between inclusion and discharge
(Figure 2,d). Cosinor
analysis and the calculated variance between time-points revealed that both
groups showed a significant cortisol rhythm at both inclusion and discharge but
that the diurnal rhythm also changes in the variance of the rhythmic pattern
between inclusion and discharge at both unit (Table 3, Table S4), which 3,b also illustrate.
The curves in Figure 3,b illustrate that the largest discrepancy between
groups was during the first part of the day, when the CU group showed decreasing
levels and the IU group showed stable levels.
[Table 2]
[Table 3]
[Figure 2]
[Figure 3]
Mean levels of plasma melatonin and serum
cortisol
Table 4
summarizes the differences in melatonin and cortisol levels between inclusion
and discharge for all patients.
[Table 4]
Melatonin plasma
values significantly increased from inclusion to discharge in the IU group (n = 23; median diff, 2.9; IQR: −1.0 to 9.9; p = 0.030), but not in the CU group (n = 19; median diff, −1.5; IQR: −7.0 to 6.3; p = 0.418) (Table
4). Figure 3,a shows the melatonin delta-curve,
illustrating the melatonin level changes between inclusion and discharge in the
IU and not in the CU groups, and supporting a 24-hour increase.
The mean day cortisol serum levels
significantly decreased from inclusion to discharge in the CU group (n = 20; median diff, −59.6; IQR: −129.4 to 13.2; p = 0.003),
but did not significantly change in the IU group (n = 22; median diff, 5.6;
IQR: −68.7 to 59.7; p = 0.945). During the
admission time-period, cortisol night values increased in the IU group, and
decreased in the CU group which is illustrated by Figure 3,b. However, these
changes were not statistical significant (Table 4).
Analysis of covariance was performed
to investigate cortical, striatocapsular, and large infarcts as confounding
factors for the influence on melatonin and cortisol levels. Cortisol and
melatonin levels were not significantly associated with these infarction types.
Regression analysis revealed that lesion size was also not significantly correlated
with melatonin (n = 27; Estimate, −0.03;
95% CI: −1.4, 0.09; p = 0.62) or
cortisol values (n = 26; Estimate, 0.027;
95% CI: −0.34, 0.88; p = 0.38) (Estimate
= diff. lesion size mm3). Regression analysis also showed that
length of hospitalization was not significantly correlated with melatonin or
cortisol levels.
Discussion
This
study is the first to investigate the Our
present results show for the first time that exposureeffect
of
a to a naturalistic light environment exposure
on melatonin and cortisol levels in stroke patients
during at least 2 weeks of hospitalization. can
stimulate rhythmicity and
increase melatonin plasma levels in
stroke patients.
At the time of inclusion in our
study, the stroke patients in both groups exhibited an eradicated normal diurnal
pattern of melatonin, with the lack of a normal peak. At discharge, the IU group
exhibited significantly increased plasma melatonin levels and a present but
abnormal diurnal rhythmicity. Conversely, the CU group exhibited significant but
abnormal diurnal rhythmicity at inclusion, which was absent at discharge. The
absent peak levels and disrupted diurnal rhythm of melatonin in our cohort is
in line with the impaired melatonin secretion and disturbed rhythmicity commonly
reported after stroke.
Since melatonin is synthetized from
serotonin, it is reasonable to believe that melatonin production could be
affected by the known reduction/disturbances of serotonin synthesis after stroke
[26,27]. This could explain the absence of a melatonin
secretion peak in our study. Furthermore, it has been suggested that widespread
cortical lesions could affect areas projecting to the intergeniculate leaflet
(IGL), potentially impairing light perception to the SCN and the pineal gland,
and disrupting circadian rhythm regulation and melatonin secretion [6]. However, we did not find that
melatonin and cortisol values were significantly correlated with lesion size, or
with cortical and striatum infarcts. Notably, not all patients underwent MRI
scanning; thus, the correlation was only calculated in a subgroup of patients,
potentially influencing the results.
Blue light exposure during the day reportedly
increases nightly melatonin secretion [28,29] and prevents the melatonin
suppression caused by light exposure at night [30]. This may explain the high melatonin
secretion in the IU group compared to the CU group. The increased melatonin levels
in the IU group appeared to persist over the 24-hour measurement period (Figure
3,a) despite the high exposure to the blue light spectrum at the start of the
day. Although the physiological explanation is not immediately evident, it may
be related to the disturbed diurnal rhythm. The CU group had reduced exposure
to blue light during the daytime, which could make the melatonin suppression more
sensitive to light [31] and inhibit melatonin secretion [32]. This might result in the CU group
having lower melatonin levels than the IU group during the daytime, as well as at
nighttime since the CU group was frequently exposed to blue light-emitting ward
lights in their rooms at night. Beta-blockers have been shown to reduce the
production of melatonin[33]. Beta-blockers are widely used in
stroke prevention and therefore in our patient cohort. However, the
distribution of beta-blockers between the two units was unequal, as there was a
greater prescription at the IU (Inclusion: IU; N=12, CU; N=6. Discharge: IU; N=18,
CU; N=8). This unequal distribution may have hypothetically decreased the melatonin
production at the IU compared with the CU.
Compared to melatonin, less is
understood about cortisol’s response to light. We found no change in cortisol
levels in the IU group, but significantly reduced cortisol levels in the CU
group. The higher cortisol levels in the IU group compared to the CU group may
be correlated with positive health effects, such as improved cognition, mood, and
well-being [18]. However, these correlations could
also be related to the light-enhanced cortical activity [34].
Unlike the melatonin rhythm, the
human cortisol rhythm does not seem to be associated with day and night.
However, cortisol secretion is dependent on the phase of light, particularly
transition periods from dark to light and, to a lesser extent, from light to
dark. The IU and CU groups showed the greatest difference in cortisol serum
levels during the first part of the day period (Table 4 and Figure 3,b). This
corresponds well with previous findings that cortisol levels increase in response
to the change from dim light to bright light exposure in the morning, but not
in the afternoon or night [18,35,36]. However, it would also be expected
that bright light would not affect cortisol levels during the afternoon or
nighttime, since cortisol production is usually low at those times.
Our results showed a discrepancy
between the circadian rhythms of melatonin and cortisol. While the normal 24-h rhythm
of melatonin secretion was eradicated, the normal 24-h rhythm of cortisol was
preserved. This preserved cortisol rhythmicity is not evident for a normal preserved
SCN function. Even in the absence of a functional SCN pacemaker, the adrenal
gland and its own clock system can still be light-entrained by gating the
sensitivity of the adrenal to ACTH via modulation of circadian corticosterone
rhythms [37]. Although stroke hypothetically leads
to IGL destruction, cortisol may be less sensitive to reduced IGL function and
impaired serotonin levels than melatonin, due to its different approaches to
light and its secondary circadian control. It remains uncertain whether this persists
throughout a patient’s hospitalization. It is possible that the preserved 24-h
cortisol rhythm resulted from a combination of the HPA axis and the autonomic
nervous system, and their activation and inhibition from the SCN.
Limitations and strengths
Patients
were randomly allocated following the normal procedure for an equal
distribution of patients to the two rehabilitations units (quasi-randomization). The
conditions in the two rehabilitation units were equal with regards to size,
form, and staff professions. The impact of daylight on the facade of the two
units was not completely identical, since the angle of sun exposure differed
between the two wings during all four seasons. However,
measurement of the incoming sunlight revealed no significant differences
between the two units [14], assuming
that levels above 200 lux were required to stimulate the circadian center [38]. As illustrated in West et al.[14] (figure 4a and 4b), there was no appreciable
difference between units in daylight exposure
at the window side bed across the year other than the use of curtains in the
IU. Figure 4a illustrate that there
was a difference in daylight exposure between IU and CU
at the bed nearest to the door, but all illuminance levels fall below the
required level of 200 lux D55 equivalent light to generate a diurnal stimulation
of the circadian center [38].Thus, we do not view
this difference as clinically important. Furthermore, it does not favor the IU.
The intervention unit had
blackout curtains that went up at 08 a.m. and down at 08 p.m. during all four
seasons. Furthermore, the naturalistic light had much higher
lux levels than the incoming natural sunlight, eliminating the influences of
natural light in the IU and of differing light exposure between beds.
Therefore, variations
in light exposure between bed positions (two beds: window side and
away-from-window side) were only relevant in the CU. It was
estimated that the lux values
lightsignificantly differed between beds during 40% of the meteorological time, over
a five-hour period, during the peak summer season, and this difference
disappeared outside the summer period. During the study period, information was
collected on all bed positions, and all patients were placed near the window at
the end of their stay due to the natural rotation in the units. Overall, we
found no differences in bed positions between patients; thus, bed positions
were excluded from the calculations.Artificial
light sources at the control unitwerenormal
indoor ceiling luminaries and a
bedside lamp. The use of these light sources could not be
measured due to the random use seen in a normal ward and >because
of the absent in manipulation of
the light sources due to the control setup.
The technical light description
regarding the ceiling light at the
control unit is described in the method description
paper
[14].
Blood testing could only be
performed for 43 participants. The two units significantly differed with
regards to smoking (p = 0.02), which we considered to be a random
finding. NIHSS and Barthel scores significantly differed between the included and
excluded participants, which was expected since the most severely impaired
patients had the most difficulties participating in blood collection. At the start of the study period, saliva
collection was tested as a method; however, our the stroke
patients showed a lack of saliva production, making this method unusable. Due to the RCT study design, all participants were equally disturbed during blood
collection, for example, by waking for evening sampling.
Strengths of this study include the
power of having two comparable units, and the ability to include data for all four
seasons, since sunlight exposure in Denmark significantly changes throughout
the year. This study was performed in a real-hospital setting; therefore, the
results reflect the real-life situation in a rehabilitation hospital ward. However,
this study was part of an exploratory investigational study in a relatively new
scientific area. Thus, more specific studies are needed to further address the
effects of naturalistic light on the levels and rhythmicity of melatonin and
cortisol.
Conclusions
The present
results indicate a physiologically influence of
naturalistic light on melatonin<
and cortisol levels in
patients hospitalized more than 2 weeks<
reflect the impact of
naturalistic light in a real-world clinical setting. There exists
a need for clinical trials in circadian rhythm
research with
real patients in a real-world clinical
setting
the field of circadian rhythm research,
and our study addresses that need. These
findingsdemonstrates a
rationale for further investigations on
demonstrate that it is
possible to increase plasma melatonin levels and to alter the circadian rhythm by
using naturalistic light in a real-hospital setting. Further trials are needed
to investigate the
exact implications of the observed circadian rhythm alterations, and to examine
the long-term effects of the circadian light intervention.
Acknowledgments
We are deeply grateful to
the stroke patients for their participation in this study. We thank service
manager Svend Morten Christiansson and architect Maj Lis Brunsgård Seligmann from
the Service Center, Rigshospitalet Glostrup, for their interest in naturalistic
light, and for making it possible to install naturalistic lighting throughout an
entire hospital ward. We thank the company ChromaViso
especially Masterin
optical engineeringTorben SkovHansenfor always being available for
technical questions and assistance regarding the light set-up
and
light description. We thank Nina Vindegaard Grønberg, MD, who was
a great help in collecting data during periods of high work pressure. Finally,
we are grateful to the health staff of the entire stroke department,
Rigshospitalet Glostrup, for their engagement and professionalism as they
provided support and logistical assistance during the project period. The last
gratitude goes to The Market Development Foundation Denmark for financing the
project.
Competing interest
The authors have declared that no competing interest
exists.
Sahil Bajaj
John R. Vanuk
Ryan Smith
Natalie S. Dailey
William D. S. Killgore