Annals of Medicine

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/iann20

BLUES - stabilizing mood and sleep with blue

blocking eyewear in bipolar disorder – a
randomized controlled trial study protocol

Helle Østergaard Madsen, Ida Hageman, Klaus Martiny, Maria Faurholt-

Jepsen, Miriam Kolko, Tone E. G. Henriksen & Lars Vedel Kessing

To cite this article: Helle Østergaard Madsen, Ida Hageman, Klaus Martiny, Maria Faurholt-
Jepsen, Miriam Kolko, Tone E. G. Henriksen & Lars Vedel Kessing (2023) BLUES - stabilizing
mood and sleep with blue blocking eyewear in bipolar disorder – a randomized controlled trial
study protocol, Annals of Medicine, 55:2, 2292250, DOI: 10.1080/07853890.2023.2292250

To link to this article: https://doi.org/10.1080/07853890.2023.2292250

© 2023 The Author(s). Published by Informa

UK Limited, trading as Taylor & Francis
Group

Published online: 18 Dec 2023.

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Annals of Medicine
2023, VOL. 55, NO. 2, 2292250
https://doi.org/10.1080/07853890.2023.2292250

Method

BLUES - stabilizing mood and sleep with blue blocking eyewear in bipolar
disorder – a randomized controlled trial study protocol
Helle Østergaard Madsena , Ida Hagemanb , Klaus Martinya,c , Maria Faurholt-Jepsena,c ,
Miriam Kolkoe,f , Tone E. G. Henriksend and Lars Vedel Kessinga,c
a
Copenhagen Affective Disorder Research Centre (CADIC), Mental Health Centre Copenhagen, Copenhagen, Denmark; bMental Health
Services, Capital Region of Denmark, Copenhagen, Denmark; cDepartment of Clinical Medicine, Faculty of Health and Medical Sciences,
University of Copenhagen, Copenhagen, Denmark; dDepartment of Research and Innovation, Division of Mental Health Care, Valen
Hospital, Fonna Health Authority, Kvinnherad, Norway; eDepartment of Ophthalmology, Rigshospitalet, Glostrup, Denmark; fDepartment
of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark

ABSTRACT ARTICLE HISTORY

Introduction: Chronotherapeutic interventions for bipolar depression and mania are promising Received 10 September
interventions associated with rapid response and benign side effect profiles. Filtering of biologically 2023
active short wavelength (blue) light by orange tinted eyewear has been shown to induce Revised 24 November
antimanic and sleep promoting effects in inpatient mania. We here describe a study protocol 2023
Accepted 26 November
assessing acute and long-term stabilizing effects of blue blocking (BB) glasses in outpatient 2023
treatment of bipolar disorder.
Patients and Methods: A total of 150 outpatients with bipolar disorder and current symptoms KEYWORDS
of (hypo)-mania will be randomized 1:1 to wear glasses with either high (99%) (intervention Bipolar disorder; mania;
group) or low (15%) (control group) filtration of short wavelength light (<500 nm). Following a chronotherapeutics; dark
baseline assessment including ratings of manic and depressive symptoms, sleep questionnaires, therapy; blue blocking;
BB-glasses; maintenance;
pupillometric evaluation and 48-h actigraphy, participants will wear the glasses from 6 PM to 8 RCT
AM for 7 consecutive days. The primary outcome is the between group difference in change in
Young Mania Rating Scale scores after 7 days of intervention (day 9). Following the initial treatment
period, the long-term stabilizing effects on mood and sleep will be explored in a 3-month
treatment paradigm, where the period of BB treatment is tailored to the current symptomatology
using a 14-h antimanic schedule during (hypo-) manic episodes (BB glasses or dark bedroom
from 6 PM to 8 AM) and a 2-h maintenance schedule (BB glasses on two hours prior to bedtime/
dark bedroom) during euthymic and depressive states.
The assessments will be repeated at follow-up visits after 1 and 3 months. Throughout the
3-month study period, participants will perform continuous daily self-monitoring of mood,
sleep and activity in a smartphone-based app. Secondary outcomes include between-group
differences in actigraphic sleep parameters on day 9 and in day-to-day instability in mood,
sleep and activity, general functioning and objective sleep markers (actigraphy) at weeks 5
and 15.
Trial registration: The trial will be registered at www.clinicaltrials.gov prior to initiation and has
not yet received a trial reference.
Administrative information: The current paper is based on protocol version 1.0_31.07.23. Trial sponsor: Lars
Vedel Kessing.

Introduction maintenance therapy aimed to minimize residual

Bipolar disorder (BD) is a severe mental disorder that
affects 1-2% of the population. The core BD symptom-
atology is week or month-long depressive and (hypo)
manic episodes separated by periods of euthymia. The
treatment of BD consists of acute interventions to
treat affective episodes as well as continuous
symptoms and prevent new episodes. Evidence sug-
gests that inter-episode residual symptoms, such as
sleep problems, cognitive deficits and mood instability
adversely affect patient wellbeing, prognosis and func-
tioning [1–4]. Thus, day-to-day mood variation is asso-
ciated with increased stress, reduced functioning and
quality of life, as well as risk of relapse and

CONTACT Helle Østergaard Madsen helle.oestergaard.madsen@regionh.dk Copenhagen Affective Disorder Research Centre (CADIC), Mental Health
Centre Copenhagen, Copenhagen, Denmark.
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which
permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been
published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
2 H. Ø. MADSEN ET AL.
hospitalization [2,4,5]. Poor inter-episode sleep is asso-
ciated with lower functioning and quality of life [3].
Moreover, sleep disturbance has been found to nega-
tively influence pharmacological treatment response in
BD patients [6].
Pharmacological mood stabilizers are associated
with side effects that can add to the risk of discontin-
uation and relapse during long-term maintenance
treatment, hence the need for new treatments [7,8]. A
task force under the International Society for Bipolar
Disorder (ISBD) has recently reviewed the current chro-
notherapeutic modalities that may be additions or
alternatives to the current treatment of BD [9].
Preliminary evidence suggests that addition of light
and dark therapies to standard interventions for
depression and mania may be associated with rapid
symptom control during acute episodes, and both
interventions display benign side effect profiles [9].
However, stronger evidence for efficacy during acute
mania is needed, and specifically, there is a scarcity of
evidence for maintenance or prophylactic potential of
chronotherapeutic approaches in BD.
Dark therapy (DT) for mania involves patients being
exposed to darkness for up to 14 h a day. An anti-
manic effect of DT was reported in two case reports
in the late 1990s [10,11]. The intervention was further
explored in a controlled trial by Barbini et al. in 2005,
in which 16 inpatients with mania were exposed to
DT for 3 days in addition to antimanic treatment as
usual (TAU) [12]. The 3-day addition of DT was associ-
ated with improved sleep and reductions in manic
symptoms, and patients were discharged earlier than
control patients receiving TAU only. However, the
treatment was poorly tolerated by patients and was
associated with practical disadvantages such as
maintaining a dark patient room, keeping the patient
in the room, the social isolation that followed, etc.
A more tolerable version of DT has been devel-
oped using orange-tinted eyewear to eliminate only
the daylight signaling portion of light; the shorter
wavelengths (<530 nm), that is blue/green, blue and
violet light [13,14]. In an inpatient RCT, 32 patients
with mania were randomized to glasses with either
blue-blocking (BB) or clear (placebo) lenses [15]. The
use of BB glasses from 6 PM to 8 AM led to a signif-
icant reduction in manic symptoms after 3 days, and
the effect increased further throughout the 7-day
trial (Cohen’s d 1.86). Participants in the BB group
obtained higher sleep efficiency, reduced activity
levels, and received less sedative and psychotropic
medication during the study period [15,16]. In the
first outpatient RCT evaluating the effects of BB
treatment on BD-related insomnia in 43 patients, BB
treatment was associated with a small advance in
chronotype, but not with improved sleep qual-
ity [17].
The neurobiological target for BB treatment is a
specialized retinal ganglion cell (RGC) strain in the
inner retina, the intrinsically photosensitive RGCs
(ipRGCs) [18]. The ipRGCs are highly sensitive to short
wavelength light (440-470 nm) and extend direct pro-
jections to the amygdala and central nuclei in the
hypothalamus with regulatory influence on circadian
rhythm and sleep, as well as mood-regulatory projec-
tions to the lateral habenula [18–20]. Via polysynaptic
pathways, the ipRGCs connect with the monoaminer-
gic nuclei of the brainstem. Diffuse blue light stimulus
has been shown to activate these nuclei within sec-
onds and subsequently activate the general cortex
within 20 min [21]. A role of the ipRGCs in both acute
light responses and more longerterm circadian adapta-
tion to changes in the light-dark cycle has been con-
firmed in clinical and rodent studies [19,22–27]. These
effects are partly obtained by direct stimulation of
mood regulatory nuclei and indirectly through regula-
tion of circadian rhythm, sleep and melatonin release
[19]. A few recent observational studies suggest that
affective disorders are associated with slight aberran-
cies of the ipRGC system [28–32]. A growing number
of experimental studies also support a super-sensitivity
to the phase-shifting effects of light as a possible trait
in bipolar disorder [33]. In sum, there is converging
evidence from multiple research disciplines supporting
the potential for chronotherapeutic interventions in
BD, and a disproportionate lack of well-powered stud-
ies on clinical effectiveness. With this study protocol,
we aim to fill a knowledge gap on the acute antimanic
effects of BB treatment in an outpatient setting and to
explore potential longer-term stabilizing effects on
mood and sleep, as proposed by the ISBD chronother-
apeutic task force [9]. We hypothesize that 7 days treat-
ment with TAU + BB glasses will lead to significant
reductions in manic symptoms compared to TAU + low
filtration glasses. Secondarily, we hypothesize that the
continued use of BB glasses for 3 months will be asso-
ciated with stabilization of mood, sleep and activity.
Patients and methods
Setting
The study will be performed at the Copenhagen
Affective Disorder Research Center (CADIC), Denmark.
Patients with BD who are treated at specialized BD
outpatient clinics within the Mental Health Center
Copenhagen will be included in a 2-arm randomized

single-blinded trial of BB or low filtration glasses as
an additive to outpatient BD TAU. Inclusion is sched-
uled to take place from February 2024 to
February 2026.
Participants
Outpatients with an existing diagnosis of BD will be
eligible for inclusion when demonstrating manic symp-
toms corresponding to a Young Mania Rating Scale
(YMRS) score > 13 and meeting ICD-10 criteria for a
hypomanic or manic episode (F31.0, F31.1). Further
inclusion criteria will be age between 18 and 60 years
and fluency in Danish. Exclusion criteria include unwill-
ingness or inability to adhere to the protocol including
the electronic self-monitoring system, severe eye disor-
der or eye trauma, use of beta blockers (suppresses
melatonin release), sleep apnea, restless legs syn-
drome, REM sleep disorder, narcolepsy, substance
abuse, prior/current use of BB glasses, current/planned
pregnancy, night shift work and suicidality (Hamilton
Depression Rating Scale, HDRS item 3 > 2).
Eligible participants will be identified by the clinical
staff at the outpatient clinics. Participants will be
referred to the investigator who will provide written
and verbal information about the study, assess eligibil-
ity and collect consent.
Interventions
Following inclusion to the study, participants will be
randomized 1:1 to wearing glasses with either
orange-tinted lenses that block nearly 100% of short
wavelength light < 500 nm (BB) (intervention group) or
clear lenses that block approximately 15% of short
wavelength light (low filtration (LF) (control group).
Participants will be instructed to wear the glasses from
6 PM to 8 AM for 7 consecutive days, including any
waking periods during the night. The glasses are
removed during sleep. Participants will be encouraged
to maintain a dark bedroom and/or use a sleep mask.
Adherence to the use of the glasses will be docu-
mented every morning along with the use of
medication.
After the initial 7-day intervention, participants will
continue to wear the allocated eyewear for a 3-month
maintenance period, where the timing of the use of
glasses can be changed according to the current
symptomatology. When patients are in depressive,
euthymic, or mixed state, the glasses are worn daily
for 2 h before planned bedtime, continuing with real
darkness in the bedroom. The dosage can be increased
Annals of Medicine 3
to the 14-h antimanic period (from 6 PM to 8 AM) if
the participant experiences symptoms of hypomania/
mania (YMRS >13). Participants will be instructed to
contact the study coordinator if they experience
emerging symptoms of mania. Moreover, participants
will perform continuous daily self-
monitoring of mood, sleep and activity in a smartphone-
based app as part of TAU [1]. Self-monitoring will also
include daily registration of the timing of the use of
the glasses in the app. All data will be available to the
investigator, who will trace emerging hypomanic/
manic episodes and contact the participant to advice
a dose increase.
During the study, participants will receive TAU in
the outpatient clinics, including mood stabilizers, psy-
choeducation and supportive interventions [34].
Outcomes and assessments
At the baseline assessment, the investigator will con-
firm the diagnosis of BD according to ICD-10 criteria
by interview based on the Schedules for Clinical
Assessment in Neuropsychiatry (SCAN) [35], evaluate
comorbidities, and collect routine socio-demographic
data (age, sex, marital/cohabitation status, employ-
ment status) as well as a psychiatric and somatic
history.
The assessment battery consists of validated instru-
ments to evaluate current manic (YMRS) [36] and
depressive (HDRS-17) [37] symptoms, general function-
ing (Functional assessment short test (FAST)) [38], sub-
jective sleep quality (Pittsburgh Sleep Quality Index
(PSQI)) and chronotype (Morningness-Eveningness-
Questionnaire (MEQ)). For objective measures of sleep
and activity, an actigraphic baseline assessment will be
performed for 48 h prior to the intervention, through-
out the initial 7-day intervention and repeated after 5
and 15 weeks (48 h). Subjective evaluations of mood,
sleep and activity will be performed daily throughout
the study using the Monsenso App [1]. A screening for
side effects will be performed at baseline and at 9 days,
5 weeks and 15 weeks.
In case participants report increased suicidality (HDRS
item 3 > 2) at any of the follow-up assessments, the inter-
vention will be discontinued for that participant. Data up
to the discontinuation will be included in the analysis.
For an overview of the timing and frequency of
outcome assessments, see Figure 1.
The primary outcome of the trial is the difference in
change in YMRS score between the intervention group
and the control group on day 9. The assessments will
be conducted by a trained and blinded investigator
4 H. Ø. MADSEN ET AL.
Figure 1. Outcome assessment.
who participates in regular joint YMRS rating sessions
with clinicians and researchers at the Copenhagen
Affective Disorder Clinic, Denmark.
Secondary outcomes include between-group differ-
ences in objective sleep markers (actigraphy) on day 9
as well as between-group differences in self-reported
day-to-day instability in mood, sleep and activity, gen-
eral functioning (FAST) and objective sleep markers
(actigraphy) at weeks 5 and 15.
Tertiary outcomes include between-group differ-
ences in self-reported diurnal rhythm (MEQ) and sleep
quality (PSQI) at week 15, as well as medicine use and
the number and duration of affective episodes and
admissions during the study period.
Assessments
Electronic smartphone-based self-monitoring – the
Monsenso App
Participants will perform day-to-day self-monitoring with
the Monsenso App [1], which is a smartphone-based
self-monitoring system that is an integral part of the
treatment at the involved outpatient clinics. The Monsenso
system includes a web-based interphase that can be
accessed by the clinical staff/research team. Participants
impute daily data on mood, sleep, activity, medication
use, etc. The app has a reminder function that can remind
participants to complete the data. Participants impute the
timing and length of their sleep and rate their mood and
activity level on a 9-point scale (−3 to + 3) where scores
from −0.5 to 0.5 reflect normal variations, scores of + 1, +
2 or + 3 correspond to mild, moderate and severe
increases, and scores of −1, −2 or −3 correspond to mild,
moderate and severe decreases. Based on these ratings,
an instability score (IS) can be estimated by applying the
root mean square successive difference (rMSSD) method
to daily ratings of mood and activity [5].
Actigraphy
An actigraph is a wrist-worn combined accelerometer
and light sensor that continuously records movement
and ambient light intensity. Previous research has
shown that wrist-worn actigraphy is well-tolerated and
feasible in manic episodes [15,39]. Activity data can be

visualized in a so-called actigram, showing a 24-h time
interval on the X-axis and sequential days on the Y-axis.
Motion activity registers as a signal: high signal activity
corresponds to wakefulness, while absence of signal
activity corresponds to sleep. Actigraphy is a validated
method of objectively measuring standard sleep param-
eters such as total sleep time, nightly awakenings and
napping (sleep fragmentation), timing of sleep, as well
as activity parameters such as intra- and inter-daily vari-
ability and average daily and nightly activity counts.
Pupillometry
Chromatic pupillometry is a swift and non-invasive
method for recording and quantifying the responsivity of
the ipRGC-system to blue light stimulation. A blue light
stimulus delivered to the eye elicits a specific extended
pupillary constriction that persists beyond the termination
of the light stimulus, a response called the post-illumination
pupillary response (PIPR). With pupillometry, a monochro-
matic blue light stimulus is presented to the eye, and the
consequent pupillary dynamics are traced with a continu-
ous recording by infrared camera. A measure of PIPR is
given as 1 – (pupil diameter after termination of the stim-
ulus relative to the pupil diameter at baseline).
Sample size calculation
Due to the scarcity of studies evaluating BB treatment
in BD, a strict sample size calculation is difficult to
conduct. From the inpatient RCT on mania [15], an
effect size of 1.86 is reported. In an outpatient setting
with milder symptomatology and potentially more
wavering compliance, we expect to see smaller effects.
With a power of 0.80 at an alpha level of 0.05, a sam-
ple of 116 will allow us to detect a minimal detectable
difference on the YMRS of 4 with an expected standard
deviation of 7. Extending the sample to 150 participants
will allow for a 30% dropout. For long-term effects of BB
treatment, this sample size will allow us to detect a
between-group treatment effect in instability scores for
mood and activity of 0.35 with a standard deviation of 0.7.
The BD outpatient clinics treat approximately 300
patients per year, 40% of whom are expected to develop
a (hypo)manic episode each year, why it seems plausible
to include 150 patients over a 2-year study period.
Randomization and blinding
Patients will be randomized on a 1:1 basis with stratifica-
tion according to sex and outpatient clinic. Before ran-
domization, participant sex and the given outpatient clinic
will be registered to determine the appropriate
Annals of Medicine 5
intervention for the included participant. Study identifica-
tion numbers will be provided consecutively within each
stratum. To avoid unblinding of the investigator, the
glasses will be kept in solid, non-transparent cases and
handed to the participant in the case, which will not be
opened until the participant has left the clinic. The ran-
domization list will be kept in a locked filing cabinet for
which the outcome assessor will have no access. The allo-
cation sequence is generated by the "sealed envelope"
tool [https://www.sealedenvelope.com/simple-randomiser/
v1/lists] and the randomization is done in the Research
Electronic Data Capture (REDCap) database.
Assessors will be blinded to the treatment assign-
ment and the blinding will be maintained throughout
the study period and data analysis process. At the begin-
ning of each assessment, participants will be instructed
not to describe or discuss the color of the lenses with
the assessor. In the event that the principal investigator
is unblinded, the assessments will be performed by
another member of the research team. Because the two
types of glasses are of different colors (clear and orange),
we cannot obtain full blinding of the participants.
Participants will be informed that we are studying
the effect of two different types of light filters without
further details, so they will not know for sure, which
condition is experimental vs. control. Participants will
be discouraged from actively seeking information
about sleep glasses during the study. We will assess
the integrity of the blinding by asking participants if
they believe they received the glasses with high or
low filtration lenses at the end of the study.
Data collection, management and analysis
At the eligibility assessment, personal information will
be obtained by interview and through access to the
electronic patient chart for details. Written informed
consent forms will be signed upon inclusion and then
kept in a locked filing cabinet. Personal information will
be collected. A password-protected list will match par-
ticipant ID numbers with personal information, and this
list will be stored apart from pseudo-anonymized data.
After 10 years, the list will be deleted and consent
forms will be maculated, after which all data are fully
anonymized. Pseudo-anonymized data will be entered
directly into the Research Electronic Data Capture
(REDCap) database. The REDCap data system fulfills
data management requirements of the Danish law and
the General Data Protection Regulation. Named authors
will have access to the final dataset. Questionnaires
will be sent electronically from REDCap to patients to
enable direct replies into the database.
6 H. Ø. MADSEN ET AL.
REDCap has a logging module which enables tracking
of the entered data. The trial sponsor will perform bian-
nual checks for missing or inconsistent data and for devi-
ations from the protocol regarding the timing of follow-up
visits. According to Danish law, there is no requirement
for an external data monitoring committee when con-
ducting clinical trials with medical equipment with exist-
ing CE (Conformité Européenne) certification as type I
medical equipment. No interim analyses are planned.
We will model between-group differences in primary,
secondary and tertiary outcomes in linear mixed model
analyses using group-by-time interactions and a ran-
dom intercept for the participant. We will perform sen-
sitivity analyses to assess the effect of clinical or
socio-demographic variables that were not balanced at
randomization. The main outcome will be analyzed
according to the intention to treat principle. Missing
data will be handled as missing-at-random. The analyses
will be performed in the statistical software package R.
Ethics and dissemination
Informed consent will be obtained from all participants
prior to inclusion. The study will be approved by the
Research Ethics Committee under the Danish National
Center for Ethics. Data will be handled according to the
General Data Protection Regulation and the study will
be registered in the central registry for research in the
Capital Region of Denmark (Privacy). In accordance
with the recommendations of the International
Committee of Medical Journal Editors, the proposed
trial will be registered in www.clinicaltrials.gov before
initiation. There is great international interest in new
treatment paradigms in BD and the results will be pub-
lished in international peer-reviewed journals and pre-
sented at national and international conferences. The
research team works closely with the outpatient clinics
and the clinical academic group developing BD treat-
ment in the Capital Region of Denmark, and knowl-
edge dissemination is therefore immediate in this area.
In previous studies, the use of BB glasses has only been
associated with minor side effects such as headaches or
pain from insufficient fitting of the frames. Thus, we do not
expect the treatment to pose a risk to participants.
Discussion
The cornerstone of BD- treatment remains pharmaco-
logical treatment with mood stabilizers that effec-
tively treat manic and depressive episodes and
prevent relapse. Unfortunately, the medication can be
associated with side effects and discontinuation in
the long-term regime that is often required [7].
Although the current evidence base is limited,
BB-therapy may constitute an effective treatment
addition [17,15,16].
The ISBD chronotherapeutic task force has made spe-
cific suggestions on methods to expand the evidence
base for the chronotherapies [9,40]. The presented study
seeks to address some of these suggestions to obtain a
strong design. The strengths of the study include a ran-
domized, blinded design, a relevant sample size and the
inclusion of both objective and subjective circadian out-
comes such as rest-activity and sleep-wake cycle assess-
ment in addition to mood assessment. Moreover, the
study is the first to assess the effects of extended DT
beyond the acute phase of mania/hypomania. The
3-month follow up period is however not sufficient to
directly address potential benefits regarding long-term
stabilization and prevention of relapse. Moreover, our
design includes patients with a rather mild symptom load
and the results may not be fully generalizable to the full
range of patients with BD. There are also inherent limita-
tions to a design involving a placebo intervention that
cannot be fully blinded. We do not expect this to be a
significant issue as the use of sleep glasses or blue block-
ers has not received great attention in Denmark. We are
mindful of the risk of dropout from the low filtration
group if participants become aware that they are receiv-
ing a placebo or low efficacy treatment. However, we do
not expect this to affect our primary acute outcome mea-
sured after the initial 9 days.
With this study, we aim to add to the evidence base
for a potential antimanic treatment with minimal side
effects and rapid response. Moreover, through explora-
tions of several secondary circadian outcomes, we aspire
to add to the growing knowledge base on the effects of
light interventions and the role of circadian regularity in
affective disorders [41].
Authors contributions
HM, KM, IH, TEGH, MFJ, MK, LVK has contributed to the study
concept and design. HM has drafted the protocol and the first
version of the current manuscript. All authors provided critical
revision of the protocol and manuscript for important intellec-
tual content. All authors read and approved the final manuscript.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
The project has received financial support from the Capital
Region of Denmark and the Jascha Foundation. Eye wear is

donated by Melamedic. The funding agencies or company
have had no role in the conception or the planning of the
study nor will they have any authority in the analysis, inter-
pretation, or dissemination of activities.
ORCID
Helle Østergaard Madsen http://orcid.org/0000-0003-2000-8264
Ida Hageman http://orcid.org/0000-0002-4175-0946
Klaus Martiny http://orcid.org/0000-0002-7317-5958
Maria Faurholt-Jepsen http://orcid.org/0000-0002-0462-6444
Miriam Kolko http://orcid.org/0000-0001-8697-0734
Tone E. G. Henriksen http://orcid.org/0000-0002-5343-342X
Lars Vedel Kessing http://orcid.org/0000-0001-9377-9436
Data availability statement
After publication of the results, anonymized data can be
made accessible on request.
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