R E S E A R C H A R T I C L E Open Access
Effectiveness of medication in cluster
, Andreas Khouri
, Tina Katharina Amann
, Charly Gaul
, Peter Kropp
, Yannic Siebenhaar
Background: The aim of this work is to analyze the reports on cluster headache attacks collected online in the
citizen science project CLUE with respect to the effectiveness of drugs taken during the attacks. The collection of
data within the framework of citizen science projects opens up the possibility of investigating the effectiveness of
acute medication on the basis of a large number of individual attacks instead of a simple survey of patients.
Methods: Data from 8369 cluster headache attacks, containing information about acute medication taken and the
assessment of its effect, were collected from 133 participants using an online platform and a smartphone app. Chi-
square tests were used to investigate whether the effect of the three recommended acute drugs differs when
distinguishing between participants with chronic or episodic cluster headache. Furthermore, it was investigated
whether there are differences between smokers and non-smokers in the assessment of the effect of the acute
Results: Our participants rated the effectiveness of sumatriptan 6 mg s.c. as significantly better than oxygen and
zolmitriptan nasal spray. Oxygen is considered to be significantly better in episodic versus chronic cluster headache,
and sumatriptan is considered to be significantly better in chronic versus episodic cluster headache. Smokers rate
the effect of oxygen as significantly better than non-smokers.
Conclusions: Despite some methodological limitations, web-based data collection is able to support findings from
clinical trials in a real world setting about effectiveness of acute cluster headache treatment in several situations.
Keywords: Cluster headache, Acute medication, Effectiveness, Citizen science
Patients suffering from cluster headaches experience the
most intense pain of all primary headache disorders [1,2].
Some randomized clinical trials investigated the effect-
iveness of different acute treatments. The effect of suma-
triptan 6 mg s.c , .zolmitriptan 5 mg nasal spray 
and the inhalation of pure oxygen  was demonstrated.
Further studies also distinguished between chronic
and episodic cluster headache [6–8] and investigated
whether there are differences between smokers and non-
smokers . This is of interest because there are signifi-
cantly more smokers than nonsmokers among cluster
headache patients than in the general population .
The purpose of this work is the analysis of cluster head-
ache attack reports collected online in the citizen science
project CLUE (https://cluster.kopfschmerz-radar.de/)with
respect to the effect of drugs taken during the attacks. The
CLUE project targeted cluster headache patients in
German-speaking countries (Germany, Switzerland,
Austria). No restriction on the age of the participants was
given. The acquisition of participants was mainly done by
communications of the cluster headache self-help groups
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* Correspondence: firstname.lastname@example.org
Institute of Information Systems, University of Applied Sciences Hof, Hof,
Full list of author information is available at the end of the article
Drescher et al. BMC Neurology (2021) 21:174
to their members. The cluster headache self-help groups
are organized in the Bundesverband der
Clusterkopfschmerz-Selbsthilfe-Gruppen (CSG) e.V.
(https://www.clusterkopf.de). This umbrella organization
informed its members about the project.
This approach offers the possibility to verify those
findings and their clinical impact in a real-world setting
based on patients’daily observations.
The collection of medical data via the web offers the
possibility to collect a larger amount of data for a longer
period of time in a larger region compared to other
studies. However, we are aware of the shortcomings of
this approach and will discuss these in detail.
The CLUE project
The CLUE project has been collecting data regarding
cluster headache attacks using a web app as well as a
smartphone app since March 2018. For data analysis, all
data are anonymized. Participants can register in the
project at any time and then start reporting their cluster
headache. During the registration process, participants
are informed about privacy issues. With their registra-
tion, they give their consent to participate.
The study was approved by the Ethics Committee of
the Medical Faculty of the University of Rostock (refer-
ence number A 2017–0091).
The purpose of the prospective study was to examine
the effect of drugs taken during cluster headache attacks.
The aim was to investigate whether there are differences
in drug effectiveness between participants with chronic
and episodic cluster headache. Furthermore, differences
in effectiveness between smokers and non-smokers were
to be investigated.
Between March 21, 2018 and June 25, 2020, 315
German-speaking participants mainly from Austria,
Germany and Switzerland registered in the project and
reported their attacks. The reported attacks had to have
occurred within the specified time period, they could be
reported subsequently by July 5, 2020 at the latest. The
diagnosis of cluster headache was performed using a
headache questionnaire, which covers the diagnostic cri-
teria of the International Headache Society (Inter-
national Classification of Headache Disorders, ICHD-3
(beta version), 2). Participants with neither episodic nor
chronic cluster headache were excluded. 282 participants
remained in the sample. Table 1shows the frequency
with which the required symptoms were reported by
these 282 participants.
In addition, the Fagerström test was used to determine
the nicotine dependence of smokers [11,12]. We deter-
mined the length of the participation period in the pro-
ject as the difference between the dates of the first and
the last attack reported by the participant plus one. We
included participants in the study if they participated for
at least 10 days and reported at least 6 cluster headache
attacks. In addition, participants who reported more
than 25% of their attacks lasting longer than 180 min or
equal 0 min were excluded.
For the analysis of the effectiveness of the drugs, a pa-
tient was only considered if he or she reported at least
three attacks with the drug under consideration.
To compare the effectiveness of individual drugs, only
attacks in which only one or two drugs were taken were
considered. It was also requested that the dose taken
should not be zero.
During the registration process, baseline characteristics
were obtained including gender, year of birth, place of
residence, occupational group (working (full-time, part-
time), not working (pupil or student, retired, un-
employed)) as well as shift work information (shift work:
yes or no).
To record the individual cluster headache attacks, the
participants entered information about the onset and
end of the attack, the medication used and its dosage.
The medication selection included sumatriptan, zolmi-
triptan, oxygen, lidocaine, ergotamine tartrate and
‘other’. The effectiveness of the drugs was recorded in
three steps (yes, little, no). Other data, such as food and
beverages consumed, which were not relevant for the
present evaluation, were recorded for each attack.
For the analysis, individual profile data were linked to
the data of each attack.
As mentioned above we use a web app and a smart-
phone app to record the attacks. The overall system is
described in . The recording mask is presented in
the supplementary material to this publication. To assess
Table 1 Symptoms according the ICHD-3 (beta) definition and
Symptom Frequency (N= 282)
conjunctival injection and/or lacrimation 254 (90%)
nasal congestion and/or rhinorrhoea 267 (95%)
eyelid oedema 124 (44%)
forehead and facial sweating 139 (49%)
forehead and facial flushing 68 (24%)
sensation of fullness in the ear 124 (44%)
miosis and/or ptosis 186 (66%)
Drescher et al. BMC Neurology (2021) 21:174 Page 2 of 8
the intensity of pain we use a numerical pain scale,
which is described in .
The data were analyzed using the R language and the R-
studio environment .
Chi-square tests were used to compare the distribution
of the participants in the different groups like gender,
cluster headache type (chronic, episodic) and the smok-
ing and non-smoking groups.
Welch’s t-test was used to compare the age distribu-
tions of the several groups.
Chi-square tests were used to compare the effective-
ness of drugs in different groups. The groups could rep-
resent different drugs (e.g. sumatriptan, oxygen),
different cluster headaches (chronic, episodic) or the
smoking and non-smoking groups. The effectiveness of
the drugs was divided into two classes (“yes”and “little/
no”) in accordance with . The duration of participa-
tion and the number of reported attacks varied greatly
among the participants. To ensure that individual partic-
ipants with a large number of reported attacks did not
dominate any result, the density distribution for each pa-
tient was included in the calculation of the Chi-square.
The different number of attacks was then taken into ac-
count when calculating the statistical error of the
The final data set consisted of 13,649 cluster headache
attacks of 139 participants who fulfilled the requirement
of having reported at least 6 attacks within at least 10
days of participation. Of these, 133 participants (100
males; 33 females; ratio 3.0:1) also provided information
about acute medication for 8369 attacks. This informa-
tion included the drug taken, the dose and an assess-
ment of its effectiveness.
Table 2summarizes the characteristics of the
Table 3divides the participants into smokers and non-
smokers and into episodic and chronic cluster headache
sufferers. The results of the statistical tests in the right-
hand column show the balance of the groups in terms of
gender distribution, age and cluster headache type.
In 6726 of the 8369 attacks, the intake of only one
drug was reported. The distribution of medication in
these cases is shown in Fig. 1. In addition, the figure
provides information on the number of participants
reporting for each medication. Since each participant
could report attacks with different medications, the sum
of participants in Fig. 1is greater than the total number
of participants indicated above.
Due to the low case numbers, only the three most
common medications, oxygen, sumatriptan 6 mg s.c. and
zolmitriptan 5 mg nasal spray, were considered for the
investigation of drug effectiveness. Although reporting
oxygen flow was not mandatory, most participants
(95.6%) reported plausible values between 4 and 20 l/
min. The median was 13 l/min, the mode 15 l/min.
First, the effectiveness of all three drugs under consid-
eration was examined and compared with each other.
Figure 2shows the three drugs with their effectiveness
in the three gradations “yes”,“little”and “no”. As men-
tioned above, the effectiveness classes “little”and “no”
were merged into one class for the investigation of the
Comparing in pairs the assessment of the partici-
pants using sumatriptan or zolmitriptan or oxygen,
their assessment of the effectiveness of the respective
drug gives the following picture: The effect of suma-
triptan 6 mg s.c. is estimated to be significantly better
than that of oxygen, (p< 0.001, OR = 2.8), that of zol-
mitriptan 5 mg nasal spray not better than that of
oxygen (p= 0.49) and the effect of sumatriptan 6 mg
s.c. as significantly better than that of zolmitriptan 5
mg nasal spray (p< 0.001, OR = 3.2).
A comparison of the effect of the drugs by cluster
headache type showed that oxygen is estimated to be
significantly more effective for the treatment of episodic
than of chronic cluster headache (p< 0.001, OR = 2.0).
Sumatriptan 6 mg s.c. is estimated to be significantly
more effective for the treatment of chronic than of epi-
sodic cluster headache (p= 0.03, OR = 2.2). For zolmi-
triptan 5 mg nasal spray (p= 0.39) there is no difference
in the estimation of the effect between chronic and epi-
sodic cluster headache.
Figure 3shows the effectiveness of the drugs consid-
ered with the difference in headache type in chronic and
episodic cluster headache.
Table 2 Patients’characteristics
Male 100 (75%)
Female 33 (25%)
Mean ± SD 42.3 ± 10.4
Type of CH
Episodic 98 (74%)
Chronic 35 (26%)
Smoker 78 (59%)
Non-Smoker 55 (41%)
CH Cluster headache
Except for age
Drescher et al. BMC Neurology (2021) 21:174 Page 3 of 8
The Fagerström test was used to investigate the nico-
tine dependence of our participants. The mean Fager-
ström score in our sample of smokers is 3.9. Twenty-
seven of the smokers smoke more than 20 cigarettes per
day and are therefore considered heavy smokers. This
corresponds to a proportion of 35%.
Comparing the drug effects between the smoking and
non-smoking groups, the following picture emerged:
Oxygen helps smokers significantly better than non-
smokers (p= 0.001, OR = 1.7). Non-smokers rate the ef-
fect of triptans slightly better than smokers, although the
differences are not or just as significant (sumatriptan 6
mg s.c.: p= 0.10, OR = 2.0; zolmitriptan 5 mg nasal spray:
p= 0.05, OR = 1.8). Figure 4shows the corresponding
Finally, we investigated whether the estimation of the
drug effect improves when two of the drugs under con-
sideration were taken. Twenty-five participants used
both oxygen and sumatriptan 6 mg s.c. in 366 attacks, 18
participants took both oxygen and zolmitriptan 5 mg
nasal spray in 331 attacks.
It was ascertained that the use of sumatriptan 6 mg s.c.
in combination with oxygen does not improve the effect-
iveness (p= 0.43). The effectiveness of taking oxygen and
zolmitriptan 5 mg nasal spray together is considered to
be worse than taking only oxygen (p= 0.02, OR = 1.8) or
Table 3 Division of participants into smokers and non-smokers and into episodic and chronic cluster headaches
Frequency 78 (59%) 55 (41%) Statistic
Gender (male / female) 61 (78%) / 17 (22%) 39 (71%) / 16 (29%) χ
Age [y], mean ± SD 41.3 ± 10.2 43.7 ± 10.8 p= 0.20
CH –Type (episodic / chronic) 57 (73%) / 21 (27%) 41 (75%) / 14 (25%) χ
Frequency 98 (74%) 35 (26%) Statistic
Gender (male / female) 74 (76%) / 24 (24%) 26 (74%) / 9 (26%) χ
Age [y], mean ± SD 41.7 ± 10.8 43.7 ± 9.5 p= 0.31
Except for age
Fig. 1 Distribution of the medications for attacks with only one medication reported
Drescher et al. BMC Neurology (2021) 21:174 Page 4 of 8
only zolmitriptan (p= 0.08, OR = 1.6). Figure 5shows
the corresponding distributions.
We analyzed 13,649 cluster headache attacks from
139 patients collected in the citizen science project
Diagnosis of cluster headache was based on ICHD-3
beta criteria (ICHD-3 beta, 2013). Compared to the
more recent ICHD-3 (2018), the ICHD-3 beta in-
cludes “sensation of fullness in the ear”which was
reported by 44% of the patients. The focus was on
Fig. 2 Effectiveness of the three medications under investigation
Fig. 3 Effectiveness of the three medications under investigation by cluster headache type
Drescher et al. BMC Neurology (2021) 21:174 Page 5 of 8
investigating the effectiveness of acute medication,
with particular emphasis on distinguishing between
the smoking and non-smoking groups and gender.
Furthermore, the investigations differentiated be-
tween participants with episodic and chronic cluster
headache. Since there were also three options for
specifying medical effectiveness, we had to decide
whether we wanted to combine “yes/little”or “little/
no”to calculate an OR. In accordance with study
, we decided to combine “little/no”as well.
The most commonly used drugs for the acute treatment
of cluster attacks used were oxygen, sumatriptan 6 mg s.c.
Fig. 4 Effectiveness of the three medications under investigation by smoker and non-smoker
Fig. 5 Effectiveness of combinations of the three medications under investigation
Drescher et al. BMC Neurology (2021) 21:174 Page 6 of 8
and zolmitriptan 5 mg nasal spray. Comparing these three
in terms of effectiveness, it was found that sumatriptan 6
mg s.c. was reported as being significantly more effective
than zolmitriptan 5 mg nasal spray and oxygen. The com-
parison of the latter two did not show any significant dif-
ference. These results are consistent with [3–5].
Differentiating the cluster headache types chronic and
episodic in terms of the effect of the drugs, oxygen is
significantly more effective in episodic than in chronic
cluster headache. In the case of triptans, no difference
can be observed in these two groups. These results con-
firm the study by Pearson et al. (2019) , but contra-
dict two other studies. One study examined 124 patients
(73% episodic and 27% chronic) and tested the effective-
ness of oral zolmitriptan compared to placebos for both
groups. Although they found a positive effect for epi-
sodic cluster headache, they noticed no effect in patients
suffering from chronic cluster headache . Another
study found that subcutaneous sumatriptan was less ef-
fective for chronic cluster headaches than for episodic
cluster headache .
Another result is the differentiation of drug effective-
ness between the smoking and non-smoking groups.
Here oxygen causes significantly better effects in
smokers than in non-smokers. This is in accordance
with , where differences between the effectiveness of
sumatriptan and oxygen were studied. No significant dif-
ferences in the effectiveness were revealed. However,
when men and smokers were analyzed it was observed
that their response to oxygen was significantly stronger.
An explanation might be the higher mean hemoglobin
concentration in smokers compared to non-smokers
which increases the oxygen delivery . No such differ-
ence is found for triptans.
Our participants have a fairly high average Fagerström
score of 3.9, and the proportion of heavy smokers is also
high at 35%. Fagerström and Furberg calculated an aver-
age Fagerström score for smokers in Germany of 2.8
, and in a study by Lampert et al. the proportion of
heavy smokers in Germany was reported to be 28% .
However, triggered by the non-smoking campaigns of
recent years, the proportion of heavy smokers and thus
also the average Fagerström score in Germany may have
increased in recent years.
Another interesting result is the investigation of the
combined intake of a triptan and oxygen. For both trip-
tans, the effect of the triptan is not improved if oxygen
is additionally applied.
However, we cannot say whether the drugs were taken
together or whether some time elapsed between taking
the first and second drug. In addition, we also do not
know which of the two was used first.
A strength of the study is the data collection in a real
world setting by apps, so the data and the conclusions
are based on a large number of attacks of every partici-
pant, which is superior to obtaining data by a question-
naire. Also these data address real life while a
questionnaire is based on perceptions which can be
shifted retrospectively. On the other hand, participants
could join or leave the study at any time. Even though a
minimum participation period of 10 days was required,
it cannot be guaranteed that participants actually re-
ported all their attacks during this period. Selective
reporting by the participants could also not be ruled out.
Furthermore, the diagnosis of cluster headache has not
been confirmed by a physician. However, the question-
naire is based on the ICHD-3 (beta version) criteria and
oxygen, nasal and subcutaneous triptans require pre-
scription by a physician which indirectly confirms the
diagnostic accuracy of our questionnaire.
Of course, the results on the effectiveness of acute
treatments are not absolute, because the participants are
taking the drugs they know will help them. We have no
information about what acute treatments a participant
had tried before and may have found less helpful. We
also do not have information about when during an at-
tack the medication was taken and how quickly it
Furthermore, we have no information on prophylactic
therapies. Therefore, our study cannot provide any infor-
mation about their influence on the drug effectiveness.
Overall, it can be said that the collection of study data
within the framework of a citizen science project like
CLUE can be an interesting addition to other clinical stud-
ies. This type of data collection allows nationwide data
collection over a longer period of time with a large num-
ber of patients. Of course, in view of the weaknesses de-
scribed above, the results obtained can only be interpreted
with the necessary caution and should always be verified.
ICHD: International Classification of Headache Disorders; IHS: International
Headache Society; SD: Standard deviation; CLUE: Project ‘Clusterkopfschmerz
erforschen”, funded by the German Federal Ministry of Education and
The online version contains supplementary material available at https://doi.
Additional file 1. Supplementary Material: Online questionnaire to
record the attacks.
The Institute of Information Systems (iisys) is supported by the Foundation of
Upper Franconia and by the State of Bavaria.
Drescher et al. BMC Neurology (2021) 21:174 Page 7 of 8
JD made significant contributions to the conception and realization of the
data collection, accompanied the data analysis and contributed to the
writing of the manuscript. Together with TA, AK developed the statistical
method for analyzing the data. Both carried out large parts of the data
analysis. CG contributed significantly to the medical conception of the data
collection. CG and PK interpreted the medical results of the study and made
significant contributions to the writing of the manuscript. YS helped develop
the method for statistical analysis of the data. JS accompanied the entire
research process and contributed significantly to the writing of the
manuscript. All authors read and approved the final manuscript.
This work was supported by the German Federal Ministry of Education and
Research (BMBF –Project 01BF1701). Open Access funding enabled and
organized by Projekt DEAL.
Availability of data and materials
The datasets used and/or analyzed during the current study are available
from the corresponding author on reasonable request.
Ethics approval and consent to participate
The study was approved by the Ethics Committee of the Medical Faculty of
the University of Rostock (reference number A 2017–0091). We confirm that
all methods were performed in accordance with the relevant guidelines and
When collecting the data, neither the name and address nor the exact date
of birth is recorded. Furthermore, we encourage the participants to use a
neutral email address which does not disclose their names. Since the data
was collected largely anonymously, there were no further conditions
imposed by the ethics committee.
During the registration process, participants are informed about privacy
issues. A data protection declaration complies with the requirements of the
German data protection and data security laws.
With their registration, they give their consent to participate. We thus
received the informed consent of all participants in the study.
As described in , no data analysis starts directly from the migraine attack
database. Instead, all necessary attack data are extracted from the database
while skipping the link to the email address. This ensures that researchers
analyzing the data cannot reproduce the connection between the attack
data and the participants having reported the attacks.
Consent for publication
Dr. Gaul has received honoraria for consulting and lectures within the past 3
years from Allergan Pharma, Lilly Germany, Novartis Pharma, Hormosan
Pharma, Grünenthal, Sanofi-Aventis and TEVA. He does not hold any stocks
of pharmaceutical companies. All other authors declare that there is no con-
flict of interest.
Institute of Information Systems, University of Applied Sciences Hof, Hof,
Institute of Medical Psychology and Medical Sociology, University
of Rostock, Rostock, Germany.
Migraine and Headache Clinic Königstein,
Received: 26 November 2020 Accepted: 12 April 2021
1. Gooriah R, Buture A, Ahmed F. Evidence-based treatments for cluster
headache. Ther Clin Risk Manag. 2015;11:1687–96. https://doi.org/10.2147/
2. Headache Classification Committee of the International Headache Society
(IHS). The international classification of headache disorders, 3rd edition
(beta version). Cephalalgia. 2013;33(9):629–808. https://doi.org/10.1177/
3. The Sumatriptan Cluster Headache Study Group. Treatment of acute cluster
headache with sumatriptan. N Engl J Med. 1991;325(5):322–6. https://doi.
4. Cittadini E, May A, Straube A, Evers S, Bussone G, Goadsby PJ. Effectiveness
of intranasal zolmitriptan in acute cluster headache: a randomized, placebo-
controlled, double-blind crossover study. Arch Neurol. 2006;63(11):1537–42.
5. Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster
headache: a randomized trial. JAMA. 2009;302(22):2451–7. https://doi.org/1
6. Bahra A, Gawel MJ, Hardebo JE, Millson D, Breen SA, Goadsby PJ. Oral
zolmitriptan is effective in the acute treatment of cluster headache.
Neurology. May 2000;54(9):1832–9. https://doi.org/10.1212/WNL.54.9.1832.
7. Gobel H, Lindner V, Heinze A, Ribbat M, Deuschl G. Acute therapy for cluster
headache with sumatriptan: findings of a one-year-long-term study.
Neurology. 1998;51(3):908–11. https://doi.org/10.1212/WNL.51.3.908.
8. Millson DS. How effective are triptans in the treatment of episodic and
chronic cluster headache. Ital J Neurol Sci. 1999;20(2 Suppl):S69–71. https://
9. Schindler EAD, Wright DA, Weil MJ, Gottschalk CH, Pittman BP, Sico JJ.
Survey analysis of the use, effectiveness, and patient-reported tolerability of
inhaled oxygen compared with injectable sumatriptan for the acute
treatment of cluster headache. Headache. 2018;58(10):1568–78. https://doi.
10. Schürks M, Kurth T, de Jesus J, et al. Cluster headache: clinical presentation,
lifestyle features, and medical treatment. Headache. 2006;46(8):1246–54.
11. Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO. The fagerstrom test
for nicotine dependence: a revision of the fagerstrom tolerance
questionnaire. Br J Addict. 1991;86(9):1119–27. https://doi.org/10.1111/j.13
12. Pomerleau CS, Majchrezak MI, Pomerleau OF. Nicotine dependence and the
Fagerstrom tolerance questionnaire: a brief review. J Subst Abus. 1989;1(4):
13. Wogenstein F, Gaul C, Kropp P, Scheidt J, Siebenhaar Y, Drescher J. Design
and implementation of a platform for the citizen science project migraine
radar. IT. 2018;60(1):11–9.
14. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual
Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain),
McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire
(SFMPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale
(SF-36 BPS) and Measure of Intermittent and Constant Osteoarthritis Pain
(ICOAP). Arthritis Care Res. 2011;63(S11):240–52.
15. R Core Team. R: a language and environment for statistical computing.
Vienna: R Foundation for Statistical Computing; 2017. https://www.R-project.
16. Pearson SM, Burish MJ, Shapiro RE, Yan Y, Schor LI. Effectiveness of oxygen
and other acute treatments for cluster headache: results from the cluster
headache questionnaire, an international survey. Headache. 2019;59(2):235–
17. Fagerström K, Furberg H. A comparison of the fagerström test for nicotine
dependence and smoking prevalence across countries. Addiction. 2008;
18. Lampert T, von der Lippe E, Müters S. Verbreitung des Rauchens in der
Erwachsenenbevölkerung in Deutschland: Ergebnisse der Studie zur
Gesundheit Erwachsener in Deutschland (DEGS1) [Prevalence of smoking in
the adult population of Germany: results of the German Health Interview
and Examination Survey for Adults (DEGS1)]. Bundesgesundheitsblatt
Gesundheitsforschung Gesundheitsschutz. 2013;56(5-6):802–8. German.
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Drescher et al. BMC Neurology (2021) 21:174 Page 8 of 8
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