The Effect of Osteopathic Treatment on Nocturia

Abstract

A pilot study on manual Osteophatic treatment of Nocturia.

Full text

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THE INTERNATIONAL
ACADEMY OF OSTEOPATHY
“The Effect of Osteopathic Treatment on Nocturia”
Author: Janne Egede Høyrup. Osteopathy student - 5
th
year
Promotor: Marie-Anne Tenbült. D.O.-MRO, BSc
Statistician: Nina Breinegaard, PhD
Scientific article to obtain the title of Osteopath – DO
Academic year: 2015

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Acknowledgement
The study presented was carried out under the supervision of Marie-Anne Tenbült,
D.O. Osteopath, teacher at the IAO. Thank you for your always fast replies and constructive
feedback during the entire process.
The statistical analyses were kindly carried out by statistician Nina Breinegaard, PhD. Thank
you, Nina.
I would like to thank my private and professional network for helping me with the collection of
participants. I would also like to thank all of the participants in the study for their participation
and cooperation.
I am particularly grateful to Lotte Brath, D.O. Osteopath, for her inspiration, encouragement
and valuable talks over the years. Without her I would never have taken on this path.
And lastly, I would like to thank my family: My father, Jens Hoyrup, Dr. phil. (history and
philosophy of science) for moral support and valuable talks about the nature of science, and
my son for his patience and his loving presence.

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Abstract
Title:
“The Effect of Osteopathic Treatment on Nocturia”.
Introduction
Nocturia is a condition in which the individual has to wake up at night to urinate. It disturbs the
nightly sleep, night after night, year after year. Nocturia is a very common condition, which is
generally overlooked and mostly not treated, as it is considered to be “an inconvenience that
comes with age”. But lack of sleep implies a severe risk to physical health, mental health and
general well being. It is therefore of immense importance to find safe and effective ways of
treating nocturia.
Methodology
The study was a pilot study, one-group, pretest-posttest involving 15 persons of mixed sex,
aged between 25 and 55 years. Average age 46 years. The pre- and post-tests included two
identical two-week questionnaires, filled in daily by the patients, listing the number of their
nightly voids, etc. The intervention was two osteopathic “black box treatments”.
Results
Following treatment, there was a significant decrease in the mean total number of times the
patients woke up to void compared to before treatment. On average, the patients woke up to
void 5.2 times less during a two-week period, with a 95% confidence interval ranging from 2.3
to 8.1 times (p-value=0.002). This corresponds to a 32% reduction. After excluding
measurements from nights with prior alcohol intake, the reduction was 40%. (p-value < 0.001).
Conclusion
The short-term effect of the treatment was significant, and the adverse events were minor. The
safety and the cost-efficiency was high. Due to the positive result, it is reasonable to assume

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that the osteopathic treatment had a positive effect on the nightly sleep, with subsequent
benefits to health. To truly evaluate this, it is advised to electronically monitor sleep, which
was not done in this pilot study due to practical limitations.
Keywords:
Osteopathy; osteopathic treatment; alternative treatment; safe treatment; nocturia; nykturi;
nightly urination, mechano-transduction; arterial rule; urinary bladder; bladder; lower urinary
tract symptoms; LUTS; sleep deprivation; fragmented sleep; circadian rhythm; ADH;
antidiuretic hormone; vasopressin; desmopressin.

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Introduction
Background
Nocturia is the complaint that the individual has to wake at night one or more times to void
(meaning to urinate) (Kerrebroeck et al 2002; Sundhed.dk 2012). Nocturia is a very common
condition in both sexes (Bosch, Weiss 2010, Redeker 2012) that has been highly overlooked
(Marinkovic et al 2004), and often is not treated, as it is widely considered to be an
unavoidable annoyance which comes with age.
Nocturia is a chronic condition. The prevalence increases with age (Kim et al 2011; Tikkinen
et al 2009), but also younger individuals may suffer from nocturia (Bosch, Weiss 2010).
Recently, the severity of the problem is gradually getting more attention. Aarhus University,
Denmark, now has a research team investigating the severity and effects of nocturia
(Politiken.dk 2015).
As nocturia disrupts the nightly sleep, it is a risk for physical health, mental health and general
well-being (Foster 2013; Marinkovic 2004; NIH 2012; Kim et al 2011). It is, therefore, of great
importance to find safe and effective ways of treating nocturia.
Aetiology
The aetiology of nocturia is multifactorial. Simplified, it can be divided into four categories:
1. Nocturnal or general polyuria caused by various factors, e.g., kidney-function and the
hormonal system.
2. Reduced bladder capacity caused, e.g., by lack of elasticity in the urinary bladder
tissue and surroundings, by trophic changes, by scar tissue and adhesions or by
neurological imbalances.
3. Obstruction of the urinary bladder outflow preventing full voiding, e.g., caused by
prostatic hyperplasia or bladder neck stenosis.
4. Disturbances in the nervous system, either local, segmental or central.

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According to a review (Goessaert et al 2014), “reduced bladder capacity and nocturnal polyuria
are the main underlying lower urinary tract-related conditions”. The review concludes that
“treatment is often inadequate and a more individualized approach seems to be necessary”. An
Australian study (Klingler et al 2009) evaluated the principal causes of nocturia to be:
• 17% global polyuria.
• 33% nocturnal polyuria (NP).
• 16,2 reduced functional capacity <250 ml.
• 21.2% had mixed forms of NP and reduced bladder capacity.
• 12.6% suffered from other causes.
The definition of “normal bladder capacity” varies, but it is usually set between 400-600 ml.
(WebMD 2014) or 400-500 ml., women more, if trained (Sircar 2011). Thus, 250 ml. is a far
less than the normal capacity, meaning that if the limit was set to <400 ml, the percentage of
nocturia caused by reduced functional capacity would have shown to been higher.
The importance of sleep
According to circadian neuroscientist Dr. Russell Foster (Foster 2013), the following are
reasons to take sleep seriously:
• Sleep increases: concentration, attention, decision-making abilities, creativity, social
skills and health (including mental health).
• Sleep decreases: mood changes, stress, anger, impulsive behaviour and the tendency to
drink and take drugs.
He mentions various serious risk factors connected to sleep deprivation and disruption:
• Micro sleep while driving ! accidents.
• Poor judgement ! major catastrophes.
• Significantly higher risk of diabetes and obesity.
• Stress, cardiovascular diseases and decreased immunity.
• Mental illness, e.g., paranoia, bipolar disorder.

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• Physical illness, e.g., cancer.
Nocturia has been linked to various risk factors e.g.,:
• Risk of falling (Vaughan 2010).
• Higher death rate among elderly men (Lightner 2012).
• Increased risk of coronary heart disease and death (Lightner 2012).
• Anxiety in Parkinson’s patients (Rana et al 2015).
The link is unconfirmed, but the sleep disruption is highly suspected.
Treatments
The most commonly used drug, Desmopressin, is a synthetic analogue of antidiuretic hormone
(ADH/vasopressin) (FDA 2013), which “appears to offer a modest benefit for the treatment of
nocturia in generally healthy adults, with adequate safety” (Ebell, Radke, Gardner 2014). It
seems, however, to be rarely used, compared to how many people suffer from nocturia. The
adverse events are (Pro.medicin.dk 2014):
• Very common side effect (>10%): Headaches.
• Common side effects are (1-10%): Fatigue, nausea, vomiting, dry mouth, abdominal
pain, diarrhoea, constipation, oedema, hypertension, hyponatremia, dizziness, bladder
and urinary tract symptoms.
When treating with Desmopressin, it is advised that “all patients should be monitored for the
development of hyponatremia” (Ebell, Radke, Gardner 2014). Common symptoms of
hyponatremia are: confusion, convulsions/seizures, fatigue, headache, irritability, loss of
appetite, nausea, restlessness, vomiting and muscle spasm, cramps or weakness. “When the
amount of sodium in fluids outside cells drops, water moves into the cells to balance the levels.
This causes the cells to swell with too much water. Brain cells are especially sensitive to
swelling, and this causes many of the symptoms of hyponatremia” (Dugdale et al 2013).
Hyponatremia can lead to seizures, brain swelling, and death (FDA 2013).

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In cases where the nocturia originates from benign prostatic hyperplasia (BPH), other
treatments are available, e.g., surgery (Andrés et al 2015; Tietze et al 2015) and various drugs
(Araki, Kaplan 2013; Gorgel et al 2013; Yokoyama, Kumon 2004).
Bladderneck stenosis can be treated by surgery, and lack of detrusor-sphincter coordination by
biofeedback (Palmer 2010; Zu et al 2010).
A study done using Chinese acupuncture showed beneficial effects from 10 treatments of 20
minutes each (Cevik, Işeri 2013).
No earlier studies of osteopathic treatment of nocturia were found.
Null Hypothesis
H0: The osteopathic treatment will not provide any decrease in the mean number of times of
nightly bladder voiding, when comparing a two-week period prior to and post treatment.
Hypothesis
The aim of the study was to decrease nocturia, with classical osteopathic treatment based on
the findings of an osteopathic examination, with a main focus on improving the function and
elastic properties of the urinary bladder and surrounding and connected tissues, by treating
these three parameters.
1. Mobility in the lumbo-pelvic area.
a. Generally: to optimize the vascularisation, as more mobility increases
vascularisation.
b. Locally: to influence the tissues on a cellular level via mechano-transduction
(Jahed et al 2014), and by breaking fibrous adhesions and scar tissues.

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2. Vascularisation of the lesser pelvis, especially the urinary bladder, ureter and
surrounding tissues, in order to optimize the vitality and health of the cells in these
tissues.
3. Balancing of the autonomic nerve innervation of the kidneys, the ureters, the urinary
bladder, the sphincter muscles and the arteries in those regions.
General osteopathic philosophy especially the three principles mentioned below, is the
foundation of the study:
1. The arterial rule (Lewis 2012a+b ; Peeters 2014; Still 2007)
2. Structure and function are interrelated (Lewis 2012b+c; Peeters 2014)
3. The body possesses self-healing properties (autocorrection) (Levis 2012a; Peeters
2014)
A. T. Still ones said: “not two cases were the same so nothing should be done by formula” He
taught his students to study anatomy and to think (Lewis 2012b). To honour basic osteopathic
philosophy in general, a “black box” treatment was chosen. The trial, therefore, tests the
efficiency of osteopathic treatment and approach as a whole, as opposed to singular techniques.
The hypothesis of the study is, hence, that this treatment works.
Physiology, anatomy and anatomical topography must be used in practice.
Following are some examples of the physiology and anatomical relationships one should have
in mind when treating nocturia:
“The sensation of bladder distension arises from the stretch receptors found in the walls of the
bladder. The sensation of imminent voiding associated with maximal bladder filling originates
in the periurethral striated muscles” (Sircar 2011). Thus, the muscle wall tension in the bladder
itself and pulls from the ureter onto the Trigonum (periurethral striated muscles) of the bladder
wall are influencing the signal of “urge to urinate”. Tonus must be normalized.

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Vascularisation in the region is important to restore and maintain healthy tissue.
Vasoconstriction of the arterial wall is induced by the sympathetic nervous system (Schueke,
Schulte, Schuemacher 2011a). Hypertension in the arterial wall decreases the blood supply.
Arterial tonus must be normalized.
The thorax, diaphragm and abdominal muscles play a role in keeping the pelvic area
vascularised (drained) on the venous and lymphatic side. The diaphragm is the second most
important pump for lymphatic and venous circulation and engine of the visceral mobility
(Barrix 2011). The suction effect of the pressure differences between the thorax and abdomen
counteracts vascular congestion of the lesser pelvis. Especially in males, disrupted venous
return is crucial, as a congested prostate disrupts the bladder outflow. Both portal and caval
venous return must be optimized.
The plexus hypogastricus superior and inferior run between the sacrum and the rectum
(Schueke, Schulte, Schuemacher 2011b), and also the plexus sacralis exits here. Therefore,
faecal-congestion and posterior adhesions must be treated. Generally, adhesions in the lesser
pelvis should be treated, especially in women, due to effects from caesarean section,
hysterectomy, infections, endometrioses, fibromas, cysts, etc.
Methodology
Study design
The study was a pilot study, one-group, pretest-posttest, involving 15 persons of mixed sex.
There was no control group, and it was non-blinded. A two-week questionnaire, filled in daily
by the patients themselves, was used to record the number of times each patient woke up at
night to void and their liquid intake (including alcohol) one hour before bedtime etc.
The same two-week questionnaire (Appendix-1) was filled in by the patients three times: once
before the treatment, once immediately after the second and last treatment, and a third time
eight weeks after last treatment. The third and last questionnaire is, as predicted, not taken into
account in this article, due to time limitations.

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Procedure of intervention and measurements
The intervention was a “black box treatment”. The same therapist treated all patients. Each
patient received two classic osteopathic treatments, based on the individual findings, combined
with a fixed treatment scheme (Appendix-2). There were 4 to14 days between the treatments.
The first consultation duration was 75 minutes, the second 45 minutes. At the first
consultation, approximately 30 minutes were spent on anamnesis and examination. No internal
techniques were used.
All patients were clearly instructed not to instigate any changes in their daily routines
regarding sports/exercises, bedtime, diet, or of what and how much they drank before bedtime
(Appendix-3).
The following outcome measurements were recorded for each patient before and after the
treatment:
1. Total number of times the patient woke up to urinate during the two-week period.
2. Total number of times the patient woke up to urinate during nights with no prior
alcohol intake during the two-week period.
Since the number of nights with alcohol intake was not the same for all individuals and
before/after treatment for the same individual, the mean was calculated for nights with no
alcohol intake, and this mean was multiplied by 14 to get a standardized measure of the total
number in a two-week period that was comparable across individuals.
A paired t-test was used to compare measurements before and after treatment. The significance
level was set to 5%.
Subjects

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Subjects were found through the author’s network. 25 patients showed interest in the trial.
Seven were not willing to fill out the required questionnaires. One subject was excluded due to
enlarged prostate, and one due to pregnancy. This left 15 subjects. 15 completed the trial.
Baseline characteristics of the included patients:
Total
15 patients
Male
6
Female
9
Age (years)
27 to 54
Age (years) in Average
46
Duration of Nocturia (years)
1.5 to 10
Inclusion criteria
The inclusion criteria were:
• Men and women suffering from nocturia, but otherwise healthy.
• No requirements on frequency.
• Aged between 25 and 55 years.
Exclusion criteria
Excluded from the study were those with:
1. Heart, liver, kidney and lung diseases.
2. Chronic leg swelling and/or known high blood pressure (BP). Slightly high or well-
medicated BP was accepted.
3. Diabetes.
4. Other sleep disorders.
5. Hormonal diseases.
6. Depression at present time.
7. Diagnosed enlarged Prostate.
8. Pregnancy.

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9. Severe scarring after, for example, hysterectomy or caesarean section, after patient’s
own definition. Ordinary scars were accepted.
10. Women with known severe ptosis of the uterus. Slight ptosis was accepted.
11. Osteoporosis.
Medications were evaluated to establish whether the medicine could interfere with the trial.
Safety
All patients had their blood pressure measured, and all patients were examined by classical
osteopathic methods. All relevant safety tests were performed.
Ethics
Internal techniques (rectal or vaginal) would most likely improve the result, but in order to
keep the study completely non-invasive, internal techniques were excluded.
All patients gave their informed written consent to participate in the study, to undergo the
treatment and to let the collected data be published. All patients’ identity is anonymised.
All patients signed an agreement beforehand that the information they would give in the health
questionnaires prior to participation, and in the two-weeks questionnaires before and after
treatment, would be truthful (Appendix-4).
Research
The research for this study is based on database research, particularly PubMed, BMJ, NIH
(U.S. National Institute of Health), FDA (U.S. Food and drug administration), IAO
(International Academt of Osteopathy) Library and other professionally relevant journals. E-
books and syllabi from the IAO and various books from Thieme publishing were the source of
anatomy and physiology, visceral manipulation and osteopathic techniques.
Results

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Following treatment, there was a significant decrease in the number of times the patients woke
up to urinate compared to before treatment (p-value=0.002). On average, the patients woke up
5.2 times less during a two-week period, with a 95% confidence interval ranging from 2.3 to
8.1 times. This corresponds to a 32% reduction (95% CI = 13% to 51%).
After excluding measurements from nights with prior alcohol intake, the difference between
before and after treatment was even more significant (p-value < 0.001), and the mean decrease
was 6.2 times during a two-week period, with a 95% confidence interval ranging from 3.4 to
8.9 times. This is a reduction of 40% (95% CI = 24% to 57%).
Outcome
Mean
before
Mean
After
Difference
(95 % CI)
%Reduction
(95% CI)
No. of times
15.6
10.4
5.2 (2.3-8.1)
32% (13%-51%)
No. of times
(no alcohol)
15.6
9.4
6.2 (3.4-8.9)
40% (24%-57%)
Table 1: The number of times the patients woke up to urinate during a 2-week period, before
and after treatment, (including all nights and including only nights with no prior alcohol
intake). Mean of the 15 patients before and after, mean difference, and percentage reduction
after treatment.!
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Figure 1: Plot of the number of times each patient woke up to urinate during a 2-week period
before and after treatment including all nights (left panel) and including only nights with no
prior alcohol intake (right panel). Each line represents a patient.
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Adverse events
There were two reports of adverse events.

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• One female with a uterine fibroma of 7 cm. reported difficulties holding the urine,
when running after the treatment. This lasted for one day only after the first treatment.
• One male with “general congestion” and very severe trophic changes in the membrana
obturatoria bilaterally, reported sharp pain in the groin area for one night only after the
first treatment.
No other adverse events were reported.
Discussion
This study was done as a pilot study, to evaluate the effect of the treatment, the method and the
entire approach. Two treatments were chosen in order to prove an effect, but more treatment is
advised in order to obtain even better results.
Interpretation of the results
It cannot be rejected that the results of this study were significant. Whether the effect is purely
placebo, purely physiological, a combination or something different cannot be decided, due to
the lack of a control group. The number of subjects was small, therefore, there is a risk that the
group does not represent the general population.
It is reasonable to suspect that the decreased urge to urinate at night has a positive effect on
nightly sleep, and therefore, on overall health, but this cannot be concluded.
Osteopathic treatment vs. hormonal medication
The aim of ADH-mimicking medication is to decrease the production of urine (FDA 2013). It
does not aim to improve the function and elastic properties of the urinary bladder and
surrounding tissues, as part of the osteopathic treatment does. Thus, hormonal medication and
osteopathic treatments can be complementary treatments.
Nocturia is a complex matter. In order to choose the right treatment for each patient, it would
be useful to screen each individual both osteopathically and classically prior to treatment, to
establish the underlying causes of the condition (see aetiology).

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The most relevant, non-invasive and safest treatment method should be used. Only where
satisfying results are not obtained, should other treatments be considered.
Procedure; choice of study design and method
It was decided not to use a control group, as the patient group was so small. Dividing the group
into two would simply eliminate statistical significance.
To test placebo effects, double blinding is commonly used, but with this kind of treatment, the
therapist will always know whether patients are given the real treatment or not. Therefore, it
can at most be blinded on the patients’ side. An alternative design would be to let the patients
choose the treatment they prefer, e.g., medication, physical therapy or osteopathic treatment.
The placebo would then be close to even for the various groups, as patients could choose the
treatment in which they believe.
Black box -a dilemma
The principle that every scientific study should be replicable, conflicts with the nature of
osteopathic treatment and manual medicine in general, as two therapists will never perform a
treatment the same way, even if following a fixed treatment scheme. Different patients will
also have different causes for the same symptoms (Lewis 2012b). Treating with a number of
exclusively predetermined techniques would not test the osteopathic treatment and approach.
Measurements
Prior to deciding the method of measurement,! sponsoring for electronic monitoring was
applied for, but not obtained. Due to practical and financial limitations, questionnaires were
chosen as the method of measurement. Questionnaires for a two-week period before and after
treatment were used to measure the effect.
It was noted down how many times the patients woke up to urinate, not the exact times and
duration of the sleep. The questionnaires had at least four disadvantages:

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1. The coherent sleep gained did not show in the statistics. Some patients reported that
after treatment, they could sleep undisturbed for six to seven hours, as opposed to only
four hours before the treatments. But the statistics were still the same: They woke up
one time per night.
2. The evaluation period was too short. Holidays and parties with alcohol intake affected
the statistics, especially during the second and third piriod. Therefore, additional
statistics were extracted solely on days with no alcohol intake during the last hour
before bedtime.
3. Possibility for bias. To present a true picture, the patients had to remember how many
times they woke up at night, and note it correctly in the morning.
4. The patients do as they please. Patients were strictly instructed not to make any notes
at night, but several did so. Cognitive action and turning on the lights at night may
affect the level of arousal, and thereby disturb the production of ADH, resulting in a
higher urine production, which counteracts the aim of the study. All patients received
written guidance (Appendix-3) on how the questionnaire should be completed.
Nevertheless, half did not read it, and one person even made her own handwritten
scheme, missing “a few” important points. 1/3 failed to write notes in the first
questionnaire about sensation of general fitness. It was originally planned to extract
statistics on this, but with 1/3 of the numbers missing in the first questionnaires, the
information was useless.
Conclusion
The null hypothesis H0 of no treatment effect was rejected and the treatment was found to
have a significant positive effect on nocturia. Whether the effect is purely placebo, purely
physiological, a combination or something different cannot be concluded. It also cannot be
determined whether or not another therapist would obtain similar results.
The short-term effect was significant, and the adverse events were minor. The safety and the
cost-efficiency was high.

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However, the number of subjects was small; therefore there is a risk that the group did not
represent the general population.
The author has analysed possible reasons for the lesser effect in some patients. An obvious
component shared by the patients who did not respond very well is an ineffective breathing
pattern. These patients’ “breathing waves” were not palpable above the pubic symphysis, as it
was in the rest of the group. It is the author’s impression that breathing and the function of the
diaphragm play an important role, and thus need to be treated.
Recommendations for later studies:
A minimum of three to four treatments is recommended, possibly more, dependent on
individual severity, cause, and combination of causes.
It is advised to avoid the two-week questionnaires used in this trial due to the reasons
described in the discussion. Questionnaires should only serve for additional notes about liquid
intake and changes in routines, and they should by filled in exclusively during daytime. As an
alternative to the questionnaires, electronic monitoring of sleep is recommended. This gives
greater accuracy and lesser risk of disturbing the patient’s sleep. Validated devices can be
purchased at Maribo Medico, Denmark.
References
A-B-C-D-E-F
Andrés et al 2015
http://www.ncbi.nlm.nih.gov/pubmed/25745792 (accessed 15.3.2015).
Title: “Laser transurethral resection of the prostate: Safety study of a novel system of
photoselective vaporization with high power diode laser in prostates larger than 80mL”.
Araki, Yokoyama, Kumon 2004
http://www.ncbi.nlm.nih.gov/pubmed/15157011 (accessed 15.3.2015).

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Title: “Effectiveness of a nonsteroidal anti-inflammatory drug for nocturia on patients with
benign prostatic hyperplasia: a prospective non-randomized study of loxoprofen sodium 60 mg
once daily before sleeping”.
Barrrix 2011
Syllabus of the Diaphragm. Version 2011 page 18.
• “The diaphragm is the second most important pump for lymphatic and venous
circulation”.
• “The diaphragm is the “engine” of visceral mobility”.
Bosch, Weiss 2010.
http://www.ncbi.nlm.nih.gov/pubmed/20620395 (accessed 12.3.2015).
Title: “The prevalence and causes of Nocturia”.
• “Nocturia is common across populations. It is most prevalent in older people but it
also affects a significant proportion of younger individuals”.
• “In practice up to 1 in 5 or 6 younger people consistently wake to void at least twice
each night. In some studies younger women appeared more likely to be affected than
men. Up to 60% of older people void 2 or more times nightly”.
• “Since the condition is highly multifactorial, frequency-volume charts are invaluable
tools for the diagnosis of underlying factors and for treatment selection”.
Cevik, Işeri 2013
http://www.ncbi.nlm.nih.gov/pubmed/24494323 (accessed 15.3.2015).
Title: “Treatment of nocturia symptoms with acupuncture”.
Dugdale et al, NIH 2013
http://www.nlm.nih.gov/medlineplus/ency/article/000394.htm (accessed 17.3.2015).

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Title: “Hyponatremia”.
• “Sodium is found mostly in the body fluids outside the cells. It is very important for
maintaining blood pressure. Sodium is also needed for nerves, muscles, and other
body tissues to work properly”.
• “When the amount of sodium in fluids outside cells drops, water moves into the cells to
balance the levels. This causes the cells to swell with too much water. Brain cells are
especially sensitive to swelling, and this causes many of the symptoms of
hyponatremia”.
• “Common symptoms: confusion, convulsions, fatigue, headache, irritability, loss of
appetite, muscle spasms or cramps, muscle weakness, nausea, restlessness, vomiting”.
Ebell, Radke, Gardner 2014
http://www.ncbi.nlm.nih.gov/pubmed/24704009 (accessed 16.3.2015).
Title: “A systematic review of the efficacy and safety of desmopressin for nocturia in adults”.
• “Desmopressin appears to offer a modest benefit for treating nocturia in generally”
healthy adults with adequate safety”.
• “All patients should be monitored for hyponatremia”.
FDA 2013 (U.S. Food and drug administration)
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProvid
ers/ucm125561.htm (accessed 21.3.2015).
Title: “Information for Healthcare Professionals: Desmopressin Acetate (marketed as DDAVP
Nasal Spray, DDAVP Rhinal Tube, DDAVP, DDVP, Minirin, and Stimate Nasal Spray)”.
• “Certain patients taking desmopressin are at risk for developing severe hyponatremia
that can result in seizures and death”.
• “All desmopressin formulations should be used cautiously in patients at risk for water
intoxication with hyponatremia”.

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• “Desmopressin is a synthetic analogue of vasopressin, an antidiuretic hormone that
prevents excessive water loss in the urine. Desmopressin in combination with
excessive fluid consumption can result in hyponatremia, an imbalance between
intracellular and extracellular sodium. This imbalance can lead to seizures, brain
swelling, and death”.
Foster 2013
http://www.ted.com/talks/russell_foster_why_do_we_sleep# (accessed 17.3.2015).
Title of the TED-talk: “Why do we sleep”.
• Sleep deprivation causes (11.05-14.05); Craving for stimulances (coffee, alcohol,
sugar, nicotin and drugs); Poor memory; Increased impulsiveness; Microsleep (10:20)
(31% of drivers sleep during driving at least ones in their life); Overall poor
judgement
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fatal accidents (10.58); Obesity (12.20), Sustained stress (12.56)
(leading to decreased immunity; Lack of memory ; Diabetes 2, High blood pressure
and subsequently cardio-vascular disease etc.)
• 5 hours sleep or less pr. night
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Increased risk of Obesity by 50% (12.25)
• Mental illness and sleep disruption (17.15)
• Schizophrenia – altered sleep patterns (17:57)
• Mental illness and sleep are physically linked within the brain (18.31).
• Sleep disruption precedes certain types of mental illness, ex. bipolar disorder (19:15)
• Stabilizing sleep reduces level of paranoia (19.38)
• List of reasons to take sleep serious (20.35-21.10)
o Good sleep increases: Concentration; Attention; Decision making; Creativity;
Social skills and Health.
o Good sleep decreases: Mood changes; Stress; Levels of anger; Impulsivity and
Tendency to drink and take drugs.
• Jim Butcher quote: “sleep is god, go worship” (21:31)

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G-H-I-J-K-L
Gorgel et al 2013
http://www.ncbi.nlm.nih.gov/pubmed/24267123 (accessed 15.3.2015).
Title: “The effect of combined therapy with tamsulosin hydrochloride and meloxicam in
patients with benign prostatic hyperplasia symptoms and impact on nocturia and sleep quality”.
Goessaert et al 2014
http://www.ncbi.nlm.nih.gov/pubmed/25379877 (accessed 17.3.2015).
Title: “Nocturnal enuresis and nocturia, differences and similarities - lessons to learn?”.
• “Reduced bladder capacity and nocturnal polyuria are the main underlying lower
urinary tract-related conditions. There is a link with sleep disorders, although it is not
clear whether this is a cause or consequence. Physical and mental health are
comprised in both conditions, however, in different ways”.!
• “In nocturia, cardiovascular disease and fall injuries are important comorbidities,
mainly affecting the older nocturia population”.!
• “For both conditions, treatment is often inadequate and a more individualized
approach seems to be necessary”.!
Jahed et al 2014
http://www.ncbi.nlm.nih.gov/pubmed/24725427 (accessed 20.4.2014).
Title: “Mechanotransduction pathways linking the extracellular matrix to the nucleus”.
• “Cells contain several mechanosensing components that transduce mechanical signals
into biochemical cascades”.
Kaplan 2013
http://www.ncbi.nlm.nih.gov/pubmed/24120798 (accessed 15.3.2015).

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24!
Title: “Re: Non-steroidal anti-inflammatory drugs for lower urinary tract symptoms in benign
prostatic hyperplasia: systematic review and meta-analysis of randomized controlled trials”.
Kerrebroeck et al 2002.
http://www.ncbi.nlm.nih.gov/pubmed/12445092 (accesed13.03.2015).
Title: “The standardization of terminology in Nocturia: report from the standardization
subcommittee of the International Continence Society”. The pdf-file can be downloaded here:!
www.ics.org/Publications/ICI_3/v2.pdf/abram.pdf (accessed 15.3.2015).
• “Nocturia is the complaint that the individual has to wake at night one or more times
to void”.
Kim et al 2011
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138848/ (accessed 14.3.2015).
Title: “Impact of Nocturia on Health-Related Quality of Life and Medical Outcomes Study
Sleep Score in Men”.
Klingler et al 2009
http://www.ncbi.nlm.nih.gov/pubmed/19229953 (accessed 17.3.2015).!
Title: “Nocturia: an Austrian study on the multifactorial etiology of this symptom”.!
• “Nocturia had a high impact on bothersome score, strong associations with poor
health and other LUTS”.!
Lewis 2012
Title of book: “A.T. Still, From the dry bone to the living man”.
a. Chapter 11 “Miracles are still performed”, pp 129-130 (and many other sites in book).

!
25!
o “He (author: A. T. Still) replied: “ The same law of nature which has been
obstructed, permitting those growth to form, when re-established will absorb
them””.
b. Chapter 10 “Lightening bone setter” pp116-118.
o “From the flux and pneumonia cases Still learned that just as different
infectious diseases show characteristic signs and symptoms they also show
characteristic patterns of muscle contraction and joint irradiation related to
the “spinal centres” connected neurologically to the site of infection. He
reasoned that joint restriction and muscle tension initiated “a stoppage of
fluids in the body””. “He also learned that pneumonia (and all other
infectious diseases) could have predisposing or exiting causes”.
c. Chapter 13 “FIND IT, FIX IT AND LEAVE IT. Pp 166 (and many other sites in the
book).
o “not two cases were the same so nothing should be done by formula”.
Lightner 2012
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508707/ (accessed 15.4.2014).
Title:!”Nocturia is associated with an increased risk of coronary heart disease and death”.
M-N-O-P-Q-R
Marinkovic 2004
http://www.bmj.com/content/328/7447/1063 (accessed 18.4.2014).
• “Nocturia, or frequent urination at night time, is a common but poorly reported and
largely misunderstood urological disorder in adults. Although many people awaken
during the night to urinate, the condition has received little attention in the medical
literature, and definitions vary widely”.

!
26!
• “Doctors tend to overlook nocturia as a possible source of medical problems
associated with the resultant loss of sleep, and patients tend not to report the condition
to their doctors until it becomes unbearable or their quality of life during daytime
hours is severely compromised”.
• “Nocturia has a role in numerous aspects of people's health and wellbeing,
contributing to fatigue, memory deficits, depression, increased risk of heart disease,
gastrointestinal disorders, and, at times, traumatic injury through falls”.
• “Adequate, restful sleep is important to everyone, regardless of age. Our entire way of
life, our health, happiness, and ability to function at home and at work suffer from
inadequate rest”.
• “Evidently nocturia is more complex and important a condition than recognised so
far. Identifying nocturia, determining its causes, and treating it effectively are keys to
improving patients' quality of life”.
NIH 2012
http://www.nhlbi.nih.gov/health/health-topics/topics/sdd/why (accessed 15.3.2015).
Title: “Why Is Sleep Important?”.
Palmer 2010
http://www.ncbi.nlm.nih.gov/pubmed/20425100 (accessed 3.4.2015).
Title of article: “Biofeedback in the management of urinary continence in children”.
• “Biofeedback has been shown to be very effective in children to correct incontinence
secondary to dysfunctional voiding, as well as in treating giggle incontinence and to
help resolve vesicoureteral reflux”.
Peeters 2014
E-book titled “Integration”. Chapter 6, pp 356-357.

!
27!
• “1. Structure and function”. Page 356.
• “2. The body as a unit”. Page 356.
• “3. The arterial rule”. Page 356.
• “4. Autocorrection”. Page 357.“If the osteopath is occupied with removing or
reducing the mechanical, neurological, vascular and metabolic stress factors, the
body’s capacity to heal will improve”.
• 5. “Desease and health”. Page 357. “While the classical medical disciplines strive to
treat and cure the disease”, “the osteopath will aim to positively influence the health”.
Politiken.dk 2015
http://politiken.dk/forbrugogliv/sundhedogmotion/ECE2563036/forskere-skal-undersoege-
hvor-farligt-nattetisseri-er/ (accessed 27.2.2015).
Title translated into English: “Researchers will examine how dangerous nocturia is. A common
sleep problem with serious consequences must now be mapped”.
• "Nocturia is a serious problem. It is not just a stupid, small cosmetic thing. It destroys
night's sleep, and it has important implications for people. It can be felt throughout the
body", said Jens Peter Norgaard. “He is the daily research director of Urology at
Ferring Pharmaceuticals in Copenhagen, and now an adjunct professor at the
Department of Clinical Medicine at Aarhus University, where they are now starting to
research the phenomenon”.
Pro.medicin.dk 2014
http://pro.medicin.dk/Medicin/Praeparater/4788 (accessed 15.3.2015).
Rana et al 2015
http://www.ncbi.nlm.nih.gov/pubmed/25668297 (accessed 21.3.2015).
Title: “Association between nocturia and anxiety in Parkinson's disease”.

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28!
• “Results: The study found a significant association between anxiety and nocturia
primarily driven by all PD (=Parkinson Desease) patients (P
<
0.0001), with greater
significance found for the male patients (P
<
0.0001) than female patients (P
=
0.021)”.
Redeker 2012
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3389347/ (accessed 15.3.2015).
Title: “Nocturia, Sleep and Daytime Function in Stable Heart Failure”.
• “Nocturia is common, severe, and closely associated with decrements in sleep and
functional performance and increases in fatigue and sleepiness in patients with stable
HF” (HF= Heart Failure).
• “Although it is often presumed that nocturia leads to disturbed sleep, it is also
plausible that awakening results in the perception of the need to void. Awakenings may
result from a host of environmental, social, psychological, and health-related reasons,
including sleep disordered breathing (SDB), that are closely associated with poor
sleep architecture and decrements in sleep continuity. Resulting decreases in slow
wave sleep may lead to decreased secretion of renin and aldosterone, and decreased
REM sleep may lead to increased urine flow and decreased osmolality. These factors
may lead to nocturia”.
S-T-U-V-W-X-Y-Z
Schueke, Schulte, Schuemacher 2011
Title of book: “Atlas of anatomy. Head and Neuroanatomy”.
a. Chapter: Neuroanatomy 21.5 D. page 325: “Sympathetic effect on arteries”
Title of book: “Atlas of anatomy. Neck and internal organs”.
b. Chapter: Abdomen and pelvis 10.13 page 175 and 14.2 pp 308+309. See pictures.

!
29!
Sircar 2011
Title of the book: “Fundamentals of the medical physiology”. Chaptor 65, pp. 406-409.
• “Urinary bladder. General model: Elasticity. The bladder is a structure whose elastic
properties make it possible to store large volumes of urine with only a small tension in
its walls”. Page 406.
• The sensation of the bladder distension arises from the stretch receptors found in the
walls of the bladder. The sensation of imminent voiding associated with maximal
bladder filling originates in the periurethral striated muscle. These sensations ascend
in the dorsal columns of the spinal chord to reach the pontine and suprapontine
micturition centers”. Page 407.
• “The bladder capacity is the bladder volume at which voiding is irresistible. It is
normally 400-500 mL. It is higher in woman who have trained themselves to retain
large volumes of urine”. Page. 409.
• “Normally, the bladder pressure remains almost constant during filling up to the point
of voiding. Page 409.
• “The desire to void occurs when the bladder feels full”. Page 409.
Sundhed.dk 2012
https://www.sundhed.dk/sundhedsfaglig/laegehaandbogen/nyrer-og-urinveje/symptomer-og-
tegn/nykturi/ (accessed 13.03.2015). The Danish doctors handbook, online version in Danish.
Still 2007
Title of book: “Autobiography of Andrew T. Still”, Version 1, second edition. Pp 106-108.
Tietze et al 2015
http://www.ncbi.nlm.nih.gov/pubmed/25765088 (accessed 15.3.2015).

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30!
Title: “Laser Therapy for Bladder Outlet Obstruction: A Prospective Analysis of All Patients
Receiving Treatment with the GreenLight XPS 180-Watt Laser System after Introduction at a
Single Center”.
Tikkinen et al 2009
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714949/ (accessed 15.4.2014).
Title: “A Systematic Evaluation of Factors Associated With Nocturia—The Population-based
FINNO Study”.
Vaughan et al 2010
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222329/ (accessed 15.4.2014).
• “Nocturia is independently associated with incident falls in older, community-
dwelling men and women without a recent history of falling”.
WebMD 2014
http://www.webmd.com/urinary-incontinence-oab/picture-of-the-bladder. (accessed 5.4.2015).
• “The normal capacity of the bladder is 400 to 600 mL”.
Zu et al 2010
http://www.ncbi.nlm.nih.gov/pubmed/20369699 (accessed 3.4.2015).
Title of article: “Chronic prostatitis with non-neurogenic detrusor sphincter dyssynergia:
diagnosis and treatment”.
• “Pelvic floor biofeedback has satisfactory short-term effects in the treatment of these
patients” (Chronic prostatitis patients with LUTS and NNDSD).
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