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The Contribution of Acupuncture
and Moxibustion to Healthcare,
an Evidence-based Approach
Ineke van den Berg-de Lange
ISBN:
Printed by media te Schiedam
Cover design by Anouk en Ineke van den Berg
Layout by Ton Everaers
© 2010 C. van den Berg - de Lange
All rights reserved. No part of this thesis may be reproduced or transmitted in any form or by any
means, electronic or mechanical, including photocopying, recording, or any information storage
and retrieval system, without prior written permission from the copyright owner.
针灸与艾灼对于保健的贡献：一个以实证为基础的方法
De bijdrage van acupunctuur en moxa-therapie
aan de gezondheidszorg, een op bewijsmateriaal
gebaseerde benadering
Proefschrift
ter verkrijging van de graad van doctor aan de
Erasmus Universiteit Rotterdam
op gezag van de rector magnificus
Prof.dr. H.G. Schmidt
en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op
donderdag 9 december 2010 om 15.30 uur
door
Geboren te Enschede
Prof.dr. M.G.M. Hunink
Prof.dr. J. W. Roos – Hesselink
Prof.dr. B. W. Koes
Prof.dr. M. J. Verhoef
Dr. J. J. Duvekot
Chapter 1 Prologue and General Introduction
Chapter 2 Health-related quality of life in patients with
musculoskeletal complaints in a general
acupuncture practice: an observational study.
I. van den Berg, L. Tan, H. van Brero, K.T. Tan,
A.C.J.W. Janssens, M.G. M. Hunink.
Acupuncture in Medicine 2010;28:130-135
Chapter 3 Anti-inflammatory actions of acupuncture, a
review of the literature.
F.J. Zijlstra, I. van den Berg-de Lange,
F.J.P.M. Huygen, J. Klein,
Mediators of Inflammation, 2003, 12(2): p. 59-6
Chapter 4 Complex regional pain syndrome type 1 may
be associated with menstrual cycle disorders: a
case-control study.
I. van den Berg, Y.S. Liem, F. Wesseldijk,
F.J. Zijlstra, M.G.M. Hunink.
Complementary Therapies in Medicine,
2009;17:262-8
Chapter 5 Natural History of Breech Presentation:
Prognostic Value of Ultrasound in the
Generation R study.
I. van den Berg, L R Arends, E A P Steegers,
V.W.V. Jaddoe, M.G.M.Hunink, J J Duvekot.
Submitted for publication
Chapter 6 -Effectiveness of acupuncture-type
interventions versus expectative policy to
resolve breech presentation: a meta analysis.
Van den Berg I, Bosch J.L, Jacobs B, Bouman I,
Duvekot J.J, Hunink M.G.M.
Complementary Therapies in Medicine, 2008
Apr;16(2):92-100.
-Correction of nonvertex presentation with
moxibustion
Ineke van den Berg, Lidia R. Arends,
Johannes J. Duvekot.
Letter to the editor: American Journal of
Obstetrics and Gynecology 2010 203:2
Chapter 7 Cost-effectiveness of Breech Version by
Acumoxa for women with a breech foetus at 33
weeks gestation: a modelling approach.
I. van den Berg, G.C. Kaandorp, J.L. Bosch,
J.J. Duvekot, L.R. Arends, M.G.M. Hunink,
Complementary Therapies in Medicine, 2010
Apr;18(2):67-77.
Chapter 8 Summary, General discussion, and Epilogue
Chapter 9 Nederlandstalige samenvatting
Chapter 10 Appendices
-Glossary
-Abstracts of Chinese concepts in TCM
Chapter 11 Contributing authors
List of publications and presentations
PhD portfolio
Dankwoord
About the author
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Chapter 1
10
Chapter 1
11
Complex pain problems, prevention of injuries and recurrent complaints, as
well as complementary care related to pregnancies, take an important place
in the daily practice of physical therapy. More than 32 years ago, when I was
searching for more treatment modalities in my practice as a physiotherapist,
I came into contact with classic acupuncture through an acupressure trai-
ning program: ‘Shiatsu according to Tokujiro Namikoshi’ and learned that
this form of preventive healthcare already has been in existence for more
than 3,000 years. Inspired, I studied acupuncture for six years, according
to traditional Chinese medicine and Chinese herbal medicine, while con-
tinuing to practice as a physiotherapist. After an extra traineeship in China
I was awarded my ‘Bachelor’s Degree in Acupuncture and Chinese Herbal
Medicine’.
Since 1988, I have increasingly applied the knowledge and skills I obtained
in the area of acupuncture and Chinese herbal medicine in my own practice
and in the process, it became clear to me that it yielded very good results
in many of my patients. Patients deserve the best of both worlds when it
comes to their health. Ideally healthcare blends the best of both worlds by
offering patients healthcare options from the perspective of both Western
and complementary medicine. During the acupuncture treatment sessions,
but also during my standard consultations with general practitioners, I spoke
with many of them (the patient, her companion, and her GP) about inte-
gration of traditional Chinese medicine in Western healthcare. From these
discussions it became clear that there is a significant amount of distrust re-
garding the application of acupuncture and moxibustion or, for that matter,
complementary medicine in general. This distrust may be largely ascribed,
I believe, to the ‘unknown, unloved’ phenomenon. The lack of (Dutch)
evidence-based studies about the efficacy of the use of acupuncture is likely
to be a major contributing factor.
In view of my positive experiences and the good results reported by the
patients themselves, I felt more and more driven to reduce this distrust.
After much deliberation, I did so in two ways: first, by performing studies
in an academic setting that would enable the translation of evidence-based
research into evidence-based practice, and secondly, by establishing a
scientifically recognizable and thus more reliable position for complemen-
tary medicine. The question I asked myself was, “Would it be possible in the
Netherlands to conduct and report scientifically sound studies in the area of
complementary medicine?”
The answer came from the field of epidemiology. Knowledge in this area
is indispensable in order to address questions related to traditional medi-
cine in a sound manner. The field of epidemiology is concerned with the
frequency with which diseases occur and the (causative) factors that might
be implicated. This discipline sees the human being as one whole orga-
nism, rather than the sum of many separate organs, and disease as a multi-
factorial complex process. Furthermore, methodology is the very essence
of this type of research. Central in clinical epidemiology is quantification
of the effects of diagnostic tests and of treatment as well as establishing an
individual’s risk for the occurrence of disease or its progression. Note that
epidemiologists do not devise new diagnostic tools or treatment methods,
but rather quantify the benefit of using them. This is of interest not only to
the physicians and therapists, who develop or apply treatments, but also to
policymakers - and of course the patient.
The importance of synergy between modern medicine and complementary
health care and the clinical value of blending these disciplines appeals greatly
to me. I aim to identify the strengths and limitations of acupuncture and
moxibustion, as described in Traditional Chinese Medicine, and evaluate
how these therapies can be implemented in modern medicine, taking the
perspective of patients, physicians, complementary therapists, health insu-
rers, and healthcare policymakers.
12
Chapter 1
13
Although recent international publications have featured articles describing
the effectiveness of Traditional Chinese Medicine (TCM), little has been
published about the implementation of TCM in today’s healthcare in the
Netherlands. In this thesis, we tried to bridge this gap and interpret how
TCM, and specifically acupuncture and moxibustion, can demonstrate its
value in today’s medicine as it is practiced in a Western country. To ac-
complish this aim we used a range of epidemiologic techniques leading to
evidence-based results.
In this introduction we will first describe acupuncture and moxibustion and
review fundamental research of the working mechanisms.
Acupuncture is one of the components of TCM. It can be described as the
ancient practice of piercing specific points of the body with fine needles
that are applied to relieve pain, to induce surgical anesthesia, and to serve
therapeutic purposes 1 (Figure 1).The use of acupuncture is based on more
than 3000 years of experience and study. Indeed, the oldest surviving book
about acupuncture, the Hungdi Neiging Suwen, was published in 200 BC. It
systematically describes a wealth of detail in patient care and cure2.
Moxibustion involves burning the herb Mugwort (Artemisia Vulgaris) either
directly on the skin or indirectly over acupuncture points, which decreases
inflammation by increasing white blood cell count in the area (Figure 2).
The acupuncturist selects certain acupuncture points, modalities and Chi-
nese herbs, depending on which TCM-syndrome type presents itself. For
instance, if the TCM diagnosis is Cold dominate Bi syndrome, like in rheu-
matoid arthritis, moxibustion is the preferred choice.
Acupuncture, (针砭: zhēnbiān), or acupuncture together with moxibus-
tion (针灸 zhēnjiǔ:)5 is not, nor has it ever been, a complete singular and
independent system of medicine. In addition to acupuncture, the whole
spectrum of TCM embraces many other forms of healing, such as Chi-
nese herbal medicine, moxibustion, exercise, diet, and massage. Although
banned by law in China at the beginning of the 20th century, TCM con-
tinued to be practiced as folk medicine until Mao Tse-tung (毛澤東) rein-
tegrated TCM into China’s health care. President Nixon’s visit to China in
1972 encouraged the Western interest in acupuncture, which in turn led
to a significant growth in the study and practice of evidence-based acu-
1a. Needles used in ancient acupuncture
1b. Huang Ti, the Yellow Emperor. According to Chinese legend he is the third of the first
emperors in Chinese history. The beginning of Huang-ti's reign, traditionally given as 2697 BC
(when Huang-ti was 7 years old), is usually taken as the beginning of Chinese history.
1c. Huangdi Neijing (黃帝內經), also known as ‘The Inner Canon of Huangdi or Yellow
Emperor's Inner Canon’, is an ancient Chinese medical text that has been treated as the
fundamental doctrinal source for Chinese medicine for more than two millennia and until today.
2a Common Wormwood. (Artemisia
vulgaris LINN.)
2b Moxa rolls as used in general
acupuncture practice
2 c Subject: Moxa burning of foot. Artist:
Kunisada Utagawa (1786-1864 )
Moxibustion
14
Chapter 1
15
puncture. Several reports have indicated the effectiveness of acupuncture
when used to treat many conditions that often do not respond to con-
ventional treatment – such as chronic neck and lower back pain, knee and
hip osteoarthritis, epicondylitis lateralis, and fibromyalgia 6-18. Furthermore,
acupuncture treatment has also produced positive results for the relief of
morning sickness in early pregnancy 19, breech presentation 20, menopausal
problems 21, and headaches 22 . Moxibustion has been shown to be effective
for the treatment of rheumatoid arthritis 23, pain suppression 24, and for the
correction of breech presentation 20. Thus, it appears that it would be in-
correct to label TCM as “alternative” in the sense of alchemy and (modern)
witchcraft. Given its history and scope, it is far less “alternative” than the art
of medicine that is considered conventional in the West.
Even without the help of modern scientific equipment, ancient Chinese
scholars discovered - through observation - many now-familiar aspects of
biomedical science, such as the various effects of emotional stress on the
immune system. Traditional acupuncturists are no less schooled than Wes-
tern clinicians in their understanding of how the body functions, although
to this day they use terminology that reflects Chinese medicine’s cultural
and historic origins. In modern China, allopathic medicine and TCM are
used side-by-side and TCM is now taught at Chinese universities. In addi-
tion, its results are reproducible under experimental conditions. As part of
their medical school training, Chinese physicians must learn both medical
systems, TCM and Western medicine. Today, TCM is practiced throughout
China in allopathic hospitals, in traditional hospitals and in conjunction with
allopathic medicine. Subsequently, hybrids of both forms of medicine have
been developed.
Acupuncture is not only used by the Chinese. The Egyptians described
their medical treatments in the Papyrus Ebers, 1550 BC, and referred to
vessels that could correspond to the 12 main and a few minor meridians
of acupuncture. Principles of acupuncture are also applied by the Inuit who
live in our globe’s northern regions, the Bantu of South Africa, Arabs, and
by a cannibalistic tribe in Brazil 25 . Broadening the scope of acupuncture
outside China, Ben Kavoussi argues that Chinese natural philosophy and
medicine have significant cognitive and epistemic similarities with certain
esoteric health beliefs of pre-Christian Europe 26. Following this line of argu-
ment, the non-decorative tattoos of the Stone Age mummies testify to the
awareness of body locations suited to treat pain. These are now considered
as acupuncture points, and it would seem therefore that a form of pain
treatment, similar to TCM, was being practiced 5200 years ago in Central
Europe 27.
Five fundamental principles form the primary concepts of TCM; these are
listed in the text box below.
In accordance with these five fundamental principles, TCM endorses the
principle of salutogenesis as the working mechanism of acupuncture. This is
explained as follows. The human body is continually undergoing a process
of injury, reaction and recovery. The healthy body is capable of responding
to harmful influences with a curing process through which a new stabi-
lity is achieved and the damage is repaired. This is called the self-healing
mechanism, or: salutogenesis (salus= health; genesis= origin). Maintaining
balance in building up and breaking down the body’s organism is vital for
all life forms.
Common ‘damaging stimuli’ (= injuries) and subsequent recoveries are part
of our life-system, and necessary for our physical development, the health
of our immune system and human growth. This is important, too, for our
course in life and our personal, emotional development and growth. Thus,
TCM sees the human body as a system of dynamic interactions, rather than
NATURAL LAWS GOVERN THE UNIVERSE.
Humans are part of the universe and therefore exist according to and subject to those laws.
THE NATURAL ORDER OF THE UNIVERSE IS HARMONIOUS AND ORGANIZED.
A life lived according to these laws will be harmonious.
THE UNIVERSE IS DYNAMIC; CHANGE IS A CONSTANT.
Lack of change is contrary to the universe and therefore causes illness.
ALL LIFE IS INTERCONNECTED
Onset of disease is described as an imbalance in homeostasis, reflected in changes in mulple
pathways that are interconnected and interdependent
HUMANS ARE A PART OF THE UNIVERSE, AND INTIMATELY CONNECTED TO THE ENVIRONMENT AND
THUS THE UNIVERSE.
Health is affected by the environment.
16
Chapter 1
17
an ensemble of anatomical units. Healthcare is then to be seen as a science
of systems engineering, and therein differs from Western modern medicine.
Modern medicine, notably in Cartesian thinking, stresses the accuracy and
details of unit structures and unit functions within the human body1.
Chinese is a pictographic language. Chinese words are pictures, rather
than sequences of letters. Similarly, Chinese thinking tends towards holistic
processing of information and emphasizes the big picture over details 29.
Therefore, the Chinese discuss many issues simultaneously in an apparently
haphazard order. In other words: “Nothing is settled until everything is”.
This holistic thinking contrasts with the Westerner’s linear approach. For
those rooted in the Western paradigm it is difficult, if not impossible, to
understand the Eastern paradigm and vice versa – without causing tension
between Western and Eastern scientific thinking.
To explain acupuncture, the TCM-teachers use metaphors, for instance the
metaphor of the body as a landscape with a network of channels, rivers
and waterways: the 14 (12+2) main meridians (with their 361 acupunc-
ture points) are the channels. In the body, then, vital energy (Qi) circulates
through a complex network of meridians just beneath the skin, but also
within blood vessels. Each meridian corresponds to an organ or organ sys-
tem 30-31.
Although acupuncture is a long-established system of healthcare, and is re-
lied upon by millions of people in China and elsewhere in Asia, it is still rela-
tively unexplored in the West. However, in spite of the dominant position
of modern regulated Western medical practice throughout the world, the
relationship between acupuncture and Western medicine is evolving. In-
creased use of complementary therapies is being reported in many areas of
health care, particularly in those specialties in which conventional medicine
can offer no complete cures.
1 Descartes compared the human body to a machine, a healthy man to a well made clock: “All
science is certain, evident knowledge. We reject all knowledge which is merely probable and
judge that only those things should be believed which are perfectly known and about which
there can be no doubts”, and “I do not recognize any difference between the machines made
by craftsmen and various bodies that nature alone composes.” [28].
Acupuncture is characterized by its primary aim of restoring and promoting
health, whereas in Western medicine the primary aim is eliminating disease.
Although these aims can be reconciled, in practice the differences in attitude
toward illness and healthcare are striking. For example, in ancient China,
patients used to pay their TCM doctor as long as they remained healthy,
seeing that only then they could earn the money to pay their doctor. In
modern medicine, however, the doctor is paid for providing a cure in case
of illness.
The diagnostic methods for the TCM acupuncturist are: questioning, in-
spection and palpitation, percussion, listening and smelling. The objectives
of the TCM practitioner are to understand both the essence of the patient
and the nature of the disease. Only after reaching these understandings will
the acupuncturist decide which points to treat, similarly to a GP making a
choice among medical treatments.
There are several types of acupuncture treatment. The traditional form
uses a combination of classical points, some of which may be farther down
from or opposite to the affected area. The Chinese character for acupunc-
ture point also means “hole” 32, reflecting the idea that at such a point the
needle can get entrance to deeper tissue layers. Another form of treatment
involves the application of small and superficial needles encircling the symp-
tomatic area (locus dolendi therapy, or: dry needling therapy) 33. Inserting
needles in points selected per treatment session from an array of classical
points makes the treatment personalized and patient tailored.
Sometimes acupuncture points can be identified by anatomical markings
such as eyebrows, hairlines or skin creases. Also, the distance between
points is not measured by a standard method because body sizes differ.
Instead, distances are measured by a metric called the “body inch”, which
equals the distance between the distal joint (the knuckle nearest to the
fingernail) and the middle joint of the middle finger of the patient. Apart
from the described points, needles can be placed anywhere in areas of local
tenderness (Chinese term; “ah-shi” point), penetrating from a fraction of a
centimeter to several centimeters, depending on the thickness of the flesh
and muscle at a given location.
For a glossary of English and Chinese acupuncture terms used in this
thesis, see Appendix 1. For some background reading on medical acu-
puncture, see Appendix 2
18
Chapter 1
19
The needles are extremely
fine, so the insertion is al-
most painless. Modern acu-
puncture needles are made
out of stainless steel and
come in various lengths and
gauges of width (figure 3).
These needles are dispos-
able and used only once.
Sensations such as tingling,
heaviness, soreness, and
pressure may or should
occur (“Qi”,34). Sensations
may also occur around the
acupuncture point, along
the meridian of which the
point is part of, and even in areas far from the point of insertion. Simulta-
neously, the acupuncturist feels a ‘tug’ on the needle, described in ancient
Chinese text books as “like fish biting on a fishing line” 35. Langevin intro-
duced the term “needle grasp” for this phenomenon 36. Using the needle
actions, movements, or warmth treatments on these points (moxibustion),
the acupuncturist invites the patient to trigger the self-healing mechanism
and to de-block or move the stagnation in life-energy, and thus restore the
equilibrium between physical, emotional and spiritual aspects. Depending
on the message the acupuncturist wants to transmit, the needle may be left
untouched or manipulated manually, electrically or with moxibustion during
the treatment session. Following acupuncture treatment, one normally feels
immediately animated, or relaxed. However, some patients may only expe-
rience the sense of regeneration a few days later, or sometimes not at all.
Since each patient is unique, the duration and frequency of each treatment
will vary. A session may last from 45 minutes to more than an hour 37. Ge-
neraly, after six to twelve sessions, or fewer in acute situations, there will
be a response to the treatment: recovery of the main complaint or a more
generalized sense of improvement, such as more restful sleep, less painful
menstruation, or a better circulation.
Many factors may influence the outcome. Animal research has shown that
the placebo effect or suggestibility is not the determining factor. Modern
technology has made it possible to use electrical stimulation or laser with-
out acupuncture needle stimulation 38.
Evidence-based medicine aims to apply the best-available evidence together
with the physician’s expertise and patient’s values to optimize decision mak-
ing 39-40. It seeks to assess the quality of evidence of the risks and benefits
of treatments 41-42. While some find traces of the origin of evidence-based
medicine in ancient Greece, others trace its roots to TCM 43 (2).
The main questions when researching medical treatments are:
1. How does it work? (Basic science)
2. Can it been applied to humans? (Translational research)
3. Does it work under strictly-controlled conditions? (Efficacy studies)
4. How effective is it in actual practice? (Effectiveness research)
5. Is it efficient to use? (Cost-effectiveness and cost-efficiency research)
Providing an evidence-base for acupuncture means that we must connect
the results of acupuncture treatment from bench (1) to bedside (2) and
transform it to practice (3), the community (4), and ultimately, society (5).
Only then can prior (dis-)belief lead to posterior belief and acceptance of
its benefit (Bayesian thinking). All these steps are necessary to meet the
biomedical ethics principle that ‘the authorized healing should be based
on an improvement that is more than what happens in the placebo arm
of a randomized controlled trial’. It is known that acupuncture outcomes
are individualized and diverse. Therefore it is important to develop re-
search methods that are consistent with the aims and philosophical basis of
acupuncture, but also comply with the evidence-based medicine principles
within the biomedical tradition44.
Not researched in this thesis, however, is the understanding of the placebo
effect in TCM. Much has been written about verum (real) acupuncture, pla-
cebo (minimal or sham) acupuncture and the not yet understood placebo
mechanisms 45-51. TCM trials and Cochrane reviews often conclude that the
value of verum acupuncture is unclear, and sometimes not different from
2 Taoism is the most influential root of Oriental Medicine. The Taoists main focus was on the
observable and natural laws of the universe and the implications for human beings’ relationship
to the universe. 2500 years (5000BC - 500BC) of observational studies form the background
and philosophy of TCM.
Acupuncture needles
20
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21
placebo acupuncture 52. However, please note that half of the FDA trials on
medical therapies do not show superiority to placebo medication. Turner et
al. showed that over 30% of RCT’s studying the efficacy of antidepressants
are unpublished53. Of those published, 94% demonstrate benefit whereas
of all FDA trials, only 51% show positive findings.
Modern acupuncture research, spanning some 50 years, has focused on
finding physiological evidence for the effect of acupuncture in five distinct
and different fields 54:
- the endogenous opioid system;
- anti-inflammatory actions;
- neuro-imaging;
- connective tissue;
- electrical properties.
Endogenous opioid systemstudies, mostly done in animal studies during
the period 1970-1980, focused on acupuncture analgesia. Pioneers were
Bruce Pomeranz and Ji- Sheng Han. Most of these studies used electro acu-
puncture and measured behavioral pain thresholds. They listed the path-
ways of the drug antagonist, the immunoassays and the histology, and laid
the foundation for basic science studies of acupuncture.
More than 17 converging lines of evidence emerge from the published
studies. The following are the main conclusions:
a) Many different opiate antagonists block acupuncture analgesia. Low
frequency electro acupuncture seems to be associated with reduced
presence of nerve growth factor (NGF) and brain-derived neurotrophic
factor in the hippocampus and NGF in the striatum in mice, and there-
fore induces modifications in brain neurotrophins 55. Adenosine levels
in tissue near the needle insertion points were 24 times greater af-
ter treatment, and mice with normal adenosine function experienced
a two-thirds drop in paw pain. In contrast, mice that were genetically
engineered to have no adenosine function gained no benefit from the
treatment.
b) Rats deficient in endorphins show poor acupuncture analgesia;
c) Endorphin levels rise in blood and cerebrospinal fluid during acupunc-
ture analgesia;
d) Acupuncture analgesia is enhanced by protecting endorphins from en-
zyme degradation;
e) Acupuncture analgesia is transmitted to a second animal by cerebrospi-
nal fluid transfer and this effect is blocked by naloxone;
f) mRNA for proenkephalin rises in the brain and pituitary with acupunc-
ture analgesia;
g) Levels of c-fos gene protein are elevated in endorphin-related areas of
the brain during acupuncture analgesia.
There are a few caveats of the endogenous opioid studies. First, you need
quite a strong stimulus to reach the effect: using electro acupuncture 1-6
V, 0.2-3 mAmps, for 10-30 minutes; or using manual acupuncture with 0.3
mm needles (as opposed to the usual 0.16-0.2 mm needles). Also, the ef-
fects are short-lived and last at most a few days. Finally, the results are not
always specific to acupuncture points or meridians. More information can
be found on http://www.acupunctureresearch.org.
Anti-inflammatory actions of acupuncture are mediatedvia the reflexive
central inhibition of the innate immune system. Both laboratory and clinical
evidence point to the existence of a negative feedback loop between the
autonomic nervous system and the innate immunity. There is also experi-
mental evidence that the electrical stimulation of the vagus nerve inhibits
macrophage activation as well as the production of TNF, IL-1beta, IL-6,
IL-18, and other proinflammatory cytokines. The use of acupuncture as an
adjunct therapy to conventional medical treatment for a number of chronic
inflammatory and autoimmune diseases seems plausible and should be vali-
dated by confirming its cholinergicity 3, 23, 56-57.
Neuroimaging research is the latest area of acupuncture research, logically
following the endogenous opioid area. Neuroimaging studies have mostly
focused on the noninvasive functional magnetic resonance imaging (fMRI)
technique, some on PET, or MEG/EEG. Converging evidence from fMRI
studies has demonstrated that acupuncture stimulation can modulate neural
activities in a wide cortico-subcortical network, particularly the limbic sys-
tem, the brainstem, and the cerebellum.
22
Chapter 1
23
Hui and colleagues published a very interesting finding: acupuncture was
associated with a decrease in the fMRI-BOLD signals, whereas these sig-
nals increased when subjects received a sharp pain stimulus. The authors
interpret this finding as a pain-reducing effect of acupuncture through de-
activation of a limbic-paralimbic- neocortical network as well as activation
of somatosensory brain regions 58. The amygdala, located in the medial
temporal lobe as part of the limbic system, plays a dominant role in the af-
fective encoding 59. Acupuncture-related modulation of activity in the amyg-
dala may contribute to stress reduction 60. The results of different studies
strongly suggest that acupuncture may mobilize these intrinsically organized
dynamic functional systems to mediate its diverse effects 61-63.
There are caveats: most of the stimuli used in de fMRI studies relied on the
‘de-Qi’ sensation and / or electro acupuncture, and studies were predominantly
conducted with healthy individuals 64. Nevertheless, chronic pain and other pain
conditions are now being studied with the use of fMRI as well. Furthermore, it
is unclear how long effects may last; and effects may overlap with a placebo ef-
fect 65. However, Kong and colleagues showed that (placebo) acupuncture and
analgesia may be configured through multiple brain pathways and mechanisms,
although verum acupuncture produced greater fMRI signal decrease in pain-
related brain regions during the application of calibrated heat pain stimuli 48, 66.
The interaction between expectancy and acupuncture analgesia is under
investigation. Positive expectations will amplify acupuncture analgesia, doc-
umented by sensory ratings and fMRI. In subjects with a high expectancy
of relief, the clinical ratings of pain relief were similar for placebo acupunc-
ture and verum acupuncture, although fMRI changes were greater in verum
acupuncture. Placebo expectancy can be considered to induce a top-down
effect, modulating the pain in the brain. Acupuncture, however, can be
considered to induce a bottom-up effect, based on Tjen and Longhurst’s
finding that long-term EA-related inhibition of sympathoexcitatory cardio-
vascular responses induced opioids and GABA in the rostral ventrolateral
medulla, but not nociceptin 48, 67. Napadow and colleagues showed an ef-
fect of acupuncture on the cortical plasticity of the brain in patients with the
carpal tunnel syndrome, suggesting that chronic pain patients respond to
acupuncture differently than healthy controls, through a coordinated limbic
network including the hypothalamus and amygdala 68.
Connective tissue studies have been largely pioneered by Helene Langevin.
The research areas are the anatomical, mechanical, and biochemical effects
of needling and facial stretch on loose subcutaneous connective tissue and
the extracellular matrix 36. Extracellular matrix cells cause re-growth and
healing of tissue. In human fetuses, for example, the extracellular matrix
works with stem cells to grow and re-grow all parts of the human body,
and fetuses can re-grow anything that gets damaged in the womb. It was
long believed that the matrix stops functioning after full development, but
its function as a device for tissue regeneration in humans in terms of injury
repair and tissue engineering is being further researched (repair or replace-
ment of portions of or whole tissues, i.e., bone, cartilage, blood vessels,
bladder, skin etc.).
Several authors have suggested that acupuncture meridians may corres-
pond with connective tissue 69-70. Langevin and colleagues used ultrasound
imaging and gross anatomical sections to locate the meridians in the hu-
man arm, and then by palpation of the ‘holes’ identified the acupuncture
points on these meridians. According to Langevin, acupuncture meridians
are often located in-between muscles, coinciding with the points where
two connective tissue planes come together. Her previous research has
shown that more pullout force is required to remove the needle from these
points. More than 80% of acupuncture points were found to be located on
connective tissue planes, three of the six meridians were on fascial planes
between muscles, and two of the meridians were located on intramuscular
fascial planes 71.
Histological studies showed the working of the “needle grasp” in connec-
tive tissue 36, 72. Inserting the acupuncture needle causes water movements
in the extracellular matrix. The tension of the connective tissue decreases
after stretching of the extracellular matrix. This phenomenon demonstrates
that needle manipulation in acupuncture treatment activates (bidirection-
ally) the connective tissue. Furthermore, tissue stretch is believed to medi-
ate inflammation 50.
There are some caveats regarding connective tissue studies as well: Both
the physiologic and clinical significance are as yet unclear; most studies were
performed in healthy subjects or animal models; the duration of the effect
is unknown and the distance of the effect is unclear. These basic science
studies are nevertheless promising.
24
Chapter 1
25
Electrical properties were reviewed by Andrew Ahn and colleagues 73. The
underlying hypothesis is that the acupuncture points are located where
the skin resistance is low, and this low resistance may follow the meridian
routes. Becker provided electrical conductivity maps of the skin at specific
acupuncture points 74. Studies about acupuncture points were poor in qual-
ity and yielded discrepant results, with insufficient evidence to draw conclu-
sions. There is some evidence for a large spatial variability in skin resistance
and the existence of low resistance points with a diameter of 1-4 mm. The
question is if those low resistance points are actual acupuncture points?
Studies about the meridians were generally higher in quality. Seven of the
nine studies showed positive associations between acupuncture meridians
and lower electrical impedance and higher capacitance, but the evidence
from these studies is unfortunately insufficient to draw conclusions. Besides,
most studies concerned healthy subjects, in whom the resistance of the
meridians most likely was not a reflection of a imbalance in health. Interest-
ingly, Ahn and colleagues obtained positive results of electrodermal stimu-
lation of specified acupuncture points (Jing points) in subjects with chronic
pelvic pain 75, although a preferential flow of charge along the meridian was
reported. Further research and confirmation is needed.
The caveats of electrical properties studies are many: there are multiple
confounders to the electrical measurements, the studies done so far are of
poor quality, the physiological and clinical significance is unclear, and so is
the duration of the effect of the treatment.
All-in-all, the peer-reviewed literature on the physiological effects of acu-
puncture shows multiple findings pointing towards a real and multi-dimen-
sional effect, suggesting that scientific claims made by acupuncturists are valid.
Evidence-based medicine practitioners prefer blinded randomized con-
trolled trials (RCTs) whenever possible. RCTs are high on the hierarchy of
evidence, and only a meta-analysis of several well-designed RCTs is con-
sidered reliable evidence in modern Western medicine. Blinding of patients
and researchers is advocated when designing RCTs, although not always
possible. For example, it is practically impossible to blind a patient to the
fact whether or not they have undergone coronary artery bypass surgery,
and similar problems exist in TCM-research.
A control treatment in acupuncture research must be credible, regardless of
whether the needling (placebo or verum) is performed by a single therapist
or by several therapists. The fact that there has been no proven placebo
for acupuncture has been a problem and has often confounded research
findings. Apart from that, to successfully use blinding in acupuncture efficacy
studies using the placebo needle (using minimal acupuncture or the non-
penetrating needle 76) (Figure 4), it is recommended that a strictly standard-
ized needling pro-
cedure is used to
minimize differences
between therapists
77. Furthermore, in
some (Eastern) cul-
tures it will be hard
to find people who
are not familiar with
acupuncture and
with the needling
sensation who could
participate naïvely
in controlled acu-
puncture studies.
Inevitably, as in all
controlled studies,
wishful thinking may
influence the results.
A solution could be
to conduct unblinded
pragmatic studies 78,
which are easier to
interpret and reflect
treatment effects in a study population similar to real world practice, that is,
patients are cognizant of the treatment received. Pragmatic studies demon-
strate effectiveness in practice and include placebo effects. This is no differ-
ent than what happens in studies evaluating surgery.
The Streitberger needle 76
The Streitberger (placebo) needle
1 Needle handle 2 Needle 3 Blunt tip of placebo needle
4 Plastic ring 5 Plastic cover 6 Skin 7 Dermis
8 Muscle 9 Sharp tip acupunctureneedle
26
Chapter 1
27
Translational research is a way of thinking about and conducting scientific
research to make the results applicable to the population under study. In
medicine this implies translating findings from basic research quickly and
efficiently into medical practice and, thus, into meaningful health outcomes
– physical, mental, or societal outcomes. It seeks to move “from bench
to bedside” (Table 1). An important element of quality healthcare, and es-
pecially in complementary healthcare, is that it be patient-centered with
a focus on the patient, including his or her preferences, values, and be-
liefs. Therefore additional types of patient-centered measures were devel-
oped, including patient satisfaction, decision regret, patient preference, and
health-related quality of life 44, 79-80. Typically, translational research involves
moving the findings made at the laboratory bench through the process of
animal studies, animal testing and small-scale human trials in order to de-
termine whether the new treatment deserves testing on a wider scale.
Interestingly, translational research in acupuncture is initiated the other way
around: from bedside to bench.
The diversity of TCM, with a proliferation of styles and schools of practice
81, is problematic for researchers schooled in the Western tradition. Never-
theless, comparing known standard treatment effects and costs with those
of acupuncture treatments may help researchers demonstrate evidence of
comparative effectiveness and cost-efficiency. There is a pitfall, however, in
that assessing the clinical effect of acupuncture in state-of-the-art placebo-
controlled randomized clinical trials is based on the assumption that distinct
well-defined reproducible parts of acupuncture treatment exist, whereas in
reality acupuncture consists of a multi-dimensional treatment with several
interacting components 82 . This difficulty can be circumvented by utilizing
pragmatic study designs 10, 83-84 to assess the whole treatment-system rather
than evaluating the individual parts separately(3). Although pragmatic stud-
ies give no answers about contextual factors inherent to the placebo ef-
fect 85, they may be helpful to demonstrate comparative effectiveness and
cost efficiency. According to internationally accepted thresholds for cost-
effectiveness, acupuncture was found to be a cost-effective treatment strat-
egy in patients with e.g. chronic neck pain 8 6, low back pain 9, 87-88, oste-
oartitis 89-90, headache 91, allergic rhinitis 92, dysmenorrhea 93, and breech
presentation 94.
Researchers summarized all acupuncture case reports published between
1966 and 1993, and found 395 instances of complications 9 5. Many were
minor, such as bruising or fainting, but 216 were serious, including several
cases of pneumothorax and injury to the spinal cord. Only one death due to
acupuncture was reported, caused by a needle penetrating the pericardium.
Others reported the development of a Pott’s puffy tumor after acupuncture
3 In traditional acupuncture, the treatment effects are based on both specific and non-specific
effects of treatment. Needling, moxibustion and cupping produce specific treatment effects
whereas practitioner’s enthusiasm and the process of making a diagnosis produce non-specific
effects.
Providing evidence-base for acupuncture.
Providing an evidence-base for acupuncture means we must connect the results of acupuncture
treatment from bench (1) to bedside (2) and transform it to practice (3) and the community (4).
Area
Basic Science
>fundamen-
tal research
Medical diagnosis
and biomedical
perceptions >clini-
cal research
Improve peo-
ple’s health
Patient centered
outcomes
Safety
Preventive
medicine
Economic
evaluation
Studies
Animal studies
Efficacy studies:
(Randomized)
Clinical trials
Efficacy studies: (Ran-
domized) Clinical trials
Effectiveness
research:
Pragmatic
trials
Cost effective-
ness studies
Cost-con-
sequence
studies***
Result in
Practitioners inter-
pretation of change,
and practitioners
perspective
Individualized
outcome tools,
Questionnaires like
SPOT-ACM* [44]
or ChQoL**[80]
Check list
Guidelines
Implementation
in health care
and public health
* A set of patient-centered outcome tools for acupuncture and Chinese medicine: MYMOP,
MCQ, W-BQ12, PEI, SF-6D, optional combined with a problem-specific questionnaire [44]
** Chinese Quality of Life instrument: three domains with four or five facets. Physical Form
domain (complexion, sleep, stamina, appetite and digestion, climate adjustment); Spirit domain
( consciousness, thinking, spirit of eye, verbal expression); and Emotional domain (joy, anger,
depressed mood, fear, worry)[80]
*** In cost-consequence studies, all the costs and outcomes are measured and presented out in
a table, which may allow for a wider variety of outcomes and be more useful for decision-makers
[79].
28
Chapter 1
29
therapy 96. In a large cohort, only 1 significant complication (pneumothorax)
out of 7831 acupuncture treatment sessions was reported, representing
0.01% of patients 97. White 98 reviewed significant adverse events associa-
ted with acupuncture in order to provide evidence on which to base efforts
to improve the safety of acupuncture practice. He concluded that according
to the evidence from 12 prospective studies which surveyed more than a
million treatments, the risk of a serious adverse event with acupuncture is
estimated to be 0.05 per 10,000 treatments, and 0.55 per 10,000 individu-
al patients. This risk may be considered extremely low, below that of many
common Western medical treatments. A meta-analysis of acupuncture for
low back pain concluded that the range of adverse events reported is wide
and that some events, specifically trauma and some episodes of infection,
are likely to be avoidable 8.
Commenting on the relative safety of acupuncture compared with modern
Western treatments, the NIH consensus panel stated that “The incidence
of adverse effects (of acupuncture) is substantially lower than that of many
drugs or other accepted medical procedures used for the same condition.
For example, musculoskeletal conditions, such as fibromyalgia, myofascial
pain, and tennis elbow are conditions for which acupuncture may be benefi-
cial, are often treated with, among other things, anti-inflammatory medica-
tions (aspirin, ibuprofen, etc.) or with steroid injections. The latter modern
medical interventions have a known potential for deleterious side effects
but are still widely used and are considered acceptable treatments.” 99
The mission of this thesis is to research and disseminate scientific inquiry
into the traditional Chinese medicine system, which includes acupuncture
and moxibustion. We hope that the reader will come to understand that
TCM approaches can be evaluated by evidence-based methods of clinical
research. With quantitative and qualitative research addressing clinical ef-
ficacy, cost-effectiveness and efficiency, physiological mechanisms, patterns
of use and theoretical foundations, we tried to bridge the gap between
Eastern and Western medical science and demonstrate the added value of
acupuncture and moxibustion blended into today’s medicine in a Western
country.
The thesis consists of three parts. Part one, the general approach, intro-
duces the use of acupuncture in a general practice. The observational study
(chapter 2) presents the health-related quality of life in patients with mus-
culoskeletal complaints in a general acupuncture practice. Musculoskeletal
complaints are associated with a large medical and societal burden. Although
acupuncture is a frequently used therapy for musculoskeletal complaints,
little is known about the effect on health-related quality of life (HRQoL).
The aim of this pragmatic study was to gain insight into whether the HRQoL
of patients undergoing routine acupuncture treatment for musculoskeletal
complaints differs with that in a Dutch population sample; and to investigate
changes in HRQoL during the course of acupuncture treatment.
In the second part we discuss also using TCM in the diagnosing of pa-
tients with complex regional pain syndrome type 1 (CRPS1). CRPS1 can
develop after severe trauma or surgery in the limbs. The estimated over-
all incidence rate of CRPS was 26.2 per 100,000 person years (95% CI:
23.0-29.7) 100, and seventy-five percent of CRPS1 patients are female. The
etiology of CRPS1 remains unclear, and there is no consensus on optimal
ma nagement. Pain is the most common symptom in this disease, and other
symptoms include allodynia, abnormal skin color and temperature change,
hyperalgesia edema, abnormal sudomotor activety, tremor dystonia and
trophic / motor disturbances 101. One year after the initiating trauma, 22%
of all patients report the combination of symptoms related to CRPS1, with
substantial interference in daily life activities.
Chapter 3 gives a review of the literature about a number of inflammatory
diseases, including CRPS1, in which acupuncture treatment was initiated as
a complementary therapy or replacement for conventional pharmacologi-
cal intervention. In addition, the anti-inflammatory action of acupuncture,
mediated by neural immune reflexes, i.e. the cholinergic anti-inflammatory
pathway of the central nervous system, is hypothesized.
The pilot study in chapter 4 reports a different TCM-approach to diagnose
the patient with CRPS1, by questioning the menstrual cycle conform TCM,
which might eventually lead to a new treatment approach: “diagnosis is not
the end, but the beginning of practice” (citation, Martin H. Fischer).
The topic of the third part of the thesis is breech presentation. In breech
presentation the baby enters the birth canal with the buttocks or feet first
30
Chapter 1
31
as opposed to the normal head first presentation. This malposition of the
fetus is noteworthy after 30 weeks of conception. No subjective symptoms
are found in most cases, and it is only discovered by prenatal examination.
We describe, in chapter 5, the development and tracking of nonvertex po-
sition (mainly breech position) throughout pregnancy and the prognostic
value of ultrasound in predicting nonvertex presentation at delivery in the
Generation R study. We aimed to get better information about the natural
history of the position of the fetus that leads to breech at delivery. In addi-
tion, we performed a systematic review and meta-analysis of the existing
literature about (randomized) controlled trials on the acupuncture-type in-
terventions on Zhiyin (BL 67) to elicit a version of a fetus in breech position
in chapter 6, including a letter about the same topic.
In chapter 7 we report the results the modeling approach of a decision
analysis and cost analysis of breech version by acumoxa offered to women
with a breech fetus at 33 weeks of gestation. In this modeling approach,
with sensitivity analysis we also considered the selective use of a) Moxa, b)
the manipulation using external cephalic version, and c) home-births. As
a result of the first two methods we found a greater opportunity for pa-
tients to consider home-births. Using the data of the pooled result of RCTs,
Cochrane Database Systematic Review and data from the Dutch Perinatal
Database, we found acumoxa effective and less costly than standard care in
the Netherlands. With regard to this treatment it is interesting to note that
it is the partner of the pregnant woman who provides the specific treatment
to her: always on the same described acupoint, using the same tempera-
ture of the moxa. However, unlike the acupuncturist, the partner does not
use the standard intake protocol of the non-specific treatment effects as
practitioners’ enthusiasm and the time consuming process of making a TCM
diagnose.
Finally, in chapter 8, the main findings are summarized and discussed.
Appendices have been added to help the reader gain a better understan-
ding of the abbreviations, statistical and Chineseacupuncture terms used
in this thesis (Appendix 1). Further nonprofessional background reading on
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78. Wettig D. Potential unblinding of ART study. Acupunct Med. Mar 2006;24(1):38;
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80. Leung K, Liu F, Zhao L. Development and validation of the Chinese quality of life
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82. Paterson C, Dieppe P. Characteristic and incidental (placebo) effects in complex
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83. Vickers AJ, Rees RW, Zollman CE, et al. Acupuncture for chronic headache in primary
care: large, pragmatic, randomised trial. BMJ. Mar 27 2004;328(7442):744.
84. van den Berg I, Tan L, van Brero H, Tan KT, Janssens AC, Hunink MG. Health-related
quality of life in patients with musculoskeletal complaints in a general acupuncture
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types of healthcare. In: MacPherson H, Hammerschlag R, Lewith G, Schnyer R, eds.
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86. Willich SN, Reinhold T, Selim D, Jena S, Brinkhaus B, Witt CM. Cost-effectiveness
of acupuncture treatment in patients with chronic neck pain. Pain. Nov 2006;125(1-
2):107-113.
87. Witt CM, Jena S, Selim D, et al. Pragmatic randomized trial evaluating the clinical and
economic effectiveness of acupuncture for chronic low back pain. Am J Epidemiol. Sep
1 2006;164(5):487-496.
88. Cummings M. Modellvorhaben Akupunktur - a summary of the ART, ARC and GERAC
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effectiveness of acupuncture treatment in patients with osteoarthritis pain. Eur J Health
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treatment in patients with headache. Cephalalgia. Apr 2008;28(4):334-345.
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in women and men with allergic rhinitis: a randomized controlled study in usual care.
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93. Witt CM, Reinhold T, Brinkhaus B, Roll S, Jena S, Willich SN. Acupuncture in patients
with dysmenorrhea: a randomized study on clinical effectiveness and cost-effectiveness
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94. van den Berg I, Kaandorp GC, Bosch JL, Duvekot JJ, Arends LR, Hunink MG. Cost-
effectiveness of breech version by acupuncture-type interventions on BL 67, including
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96. Wu CT, Huang JL, Hsia SH, Lee HY, Lin JJ. Pott’s puffy tumor after acupuncture therapy.
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Chapter 2
Ineke van den Berg
Loek Tan
1 H van Brero
K Tinka Tan
A Cecile J W Janssens
1 M G Myriam Hunink
Acupuncture in Medicine 2010;28:130-135
40
Chapter 2
41
Musculoskeletal complaints are associated with a large
medical and societal burden. Although acupuncture is a frequently used
therapy for musculoskeletal complaints, little is known about the effect on
health-related quality of life (HRQoL).
The aim of this study was to (i) compare the HRQoL of pa-
tients undergoing routine acupuncture treatment for musculoskeletal com-
plaints with a Dutch population sample; (ii) investigate changes in HRQoL
during the course of acupuncture treatment.
An observational study of 26 patients between 18 and 65 years
of age in a single acupuncture practice was performed. HRQoL was mea-
sured on eight functional domains using a RAND-36 health survey at base-
line and after six and 12 treatment sessions. Baseline RAND-36 scores
were compared to data from a Dutch population sample (n=1063) using
t test, and longitudinal data were analysed using repeated measurement
analyses.
At baseline, patients had significantly lower RAND-36 scores
compared to the Dutch population sample for three domains: role-physical
limitations (51.9 vs 79.4; p<0.001), bodily pain (49.3 vs 79.5; p<0.001)
and social functioning (75.5 vs 86.9; p=0.005). During the course of treat-
ment, RAND-36 scores increased significantly for five domains: physical
functioning (79.3 vs 97.4; p<0.001), role-physical functioning (51.4 vs
94.1; p<0.001), bodily pain (47.3 vs 95.7, p<0.001), social functioning
(74.5 vs 92.0, p<0.001) and vitality (69.1 vs 85.7; p<0.001).
The observed improvements in HRQoL suggest a subjective,
clinically relevant, benefit of routine acupuncture therapy in treating muscu-
loskeletal complaints.
In Western countries, musculoskeletal complaints are an important cause of
disability, morbidity1,absence from work2 and increased healthcare costs3,4.
In a large population-based study in The Netherlands, 75% reported ha-
ving had musculoskeletal complaints during the past year and 44% repor-
ted chronic musculoskeletal pain1. About half of these people contacted a
health professional for their symptoms, which indicates a large demand on
healthcare services.
Although the number of patients using acupuncture in Western countries
is growing5- 7, and musculoskeletal complaints are common in acupuncture
practice8, little is known about the outcome of acupuncture in a general
acupuncture practice in treating musculoskeletal complaints and preventing
its consequences. Several randomised controlled trials (RCTs) have demon-
strated evidence for the reasonable efficacy of acupuncture in pain-relief and
disease-specific outcomes for a variety of musculoskeletal conditions such as
chronic lower back pain, chronic neck pain, knee and hip osteoarthritis9 -13.
RCTs generally only collect limited data, but for clinical relevance it is also
important to know whether patients’ lives improve.
Two German observational studies have demonstrated subjective benefi-
cial effects of routine acupuncture practice for osteoarthritic pain and rou-
tine acupuncture practice by showing clinically relevant improvements in
health-related quality of life (HRQoL) over time, that is, in general, patients
are very satisfied, not only with the treatment, but also with the effects of
the treatment8,14. These studies, however, offer limited information on the
additional benefit of acupuncture for musculoskeletal complaints in other
countries, because in Germany, a non-conventional therapy such as acu-
puncture is reimbursed by statutory sickness funds15.
The purpose of this study was to investigate in an observational study the
effect of acupuncture on HRQoL in treating musculoskeletal complaints.
We compared HRQoL profiles of patients seeking acupuncture treatment
for musculoskeletal symptoms with HRQoL profiles of a Dutch population
sample before and after treatment, and investigated changes in HRQoL
during the course of acupuncture treatment. We expected a lower HRQoL
prior to the treatment compared to the general population and an effect of
acupuncture on HRQoL, but we had no prior hypotheses about the mag-
nitudes of the effects.
42
Chapter 2
43
This observational study was performed in the Northwestern region of The
Netherlands, between September 2002 and September 2003. Patients in
this study visited the routine acupuncture clinic (http://www.acupunctuur-
vanbrero.nl/) on their own initiative. All consecutive patients (age 18- 65
years), who had musculoskeletal complaints eligible for acupuncture treat-
ment, had no previous experience of acupuncture and gave written in-
formed consent, were included. Excluded were pregnant or breastfeeding
women, patients suffering from a terminal disease, patients receiving any
other form of treatment for their complaints besides self-medication and
patients participating in another clinical study. Patients were diagnosed and
treated by the licensed acupuncturist (HvB) according to a Dutch social
insurance classification system16 which is based on the 10th edition of the
International statistical classification of diseases and related health problems
(ICD-10) from the World Health Organization17. Data were collected ac-
cording to guidelines for registration of personal data.
Data from a community survey were used to compare the health status of
the study-population. The controls (1063 persons, age range 18- 89) were
randomly selected from the population register of a comparable area as the
treated group and were participants of this population-based Dutch RAND-
36 validation study18.
A licensed acupuncturist, with over 30 years of working experience, per-
formed all acupuncture treatments. All participants were treated according
to the principles of traditional Chinese medicine (TCM), meaning that the
treatment frequencies as well as the number of needles and the used acu-
puncture points were determined individually for each patient and were
adjusted to the patients’ TCM profile during the course of therapy. On
ave rage, eight needles were used with a range of two to 12 needles per
session. The treatment end point was 12 individualised sessions.
HRQoL was measured using a validated Dutch language version of the
RAND-36-item health survey 1.0 (RAND-36) which was adapted from the
standardised short form (SF)-36 health survey18,19. Physical and mental health
summery scores were derived from the eight RAND-36 scales: physical func-
tioning, role functioning limitations due to poor physical health, bodily pain,
general health, vitality, social functioning, role functioning limitations due to
mental and poor emotional health. The SF-36 is designed for use in popu-
lations, not for drawing conclusions about HRQoL status at the individual
level, as MYMOP and NHQ are20,21. HRQoL was measured before the start
of the first acupuncture treatment (baseline measurement) and immediately
after six and 12 treatment sessions. Additionally, patients were asked for the
duration of their symptoms on the basis of which they were categorised into
either acute (symptoms present <3 months) or chronic (symptoms present
>3 months) patients. The Medical Ethics Committee Erasmus MC gave a
declaration of no objection for publication (MEC-2009-422).
Scores for each scale of the RAND-36 were computed from the raw data
according to the Dutch language version RAND-36 guidelines18. For each
scale, responses to the corresponding survey-items were summed and
converted to a 0- 100 scale, in which 100 indicates the best possible func-
tioning. Differences in age and sex distribution between the study sample
and the general population sample were tested using t test and χ² test.
Mean baseline RAND-36 scores were compared with the Dutch popula-
tion, and compared between patients with acute and chronic symptoms
using t tests18. To evaluate the clinical relevance of the mean RAND-36
changes, differences of >5 points were considered as clinically relevant17.
To assess the course of HRQoL over time, the longitudinal data were ana-
lysed using a mixed model analysis for repeated measurements22. With this
procedure, the contribution of the within-subject variation was taken into
account and participants with incomplete follow-up data were included in
the analysis. We examined the overall course over time for each scale by
comparing estimated means using a mixed model analysis with the number
of treatment sessions (0, 6 and 12), age and sex as covariates. The estima-
ted means at treatment 12 were compared to the Dutch population sample
and tested using t tests18.
44
Chapter 2
45
We also explored differences in HRQoL between acute and chronic patients
at baseline by comparing the mean RAND-36 baseline scores using t tests.
We additionally performed an exploratory analysis of differences in HRQoL
changes over time between chronic and acute patients by adding duration
of symptoms and the interaction effect of duration of symptoms treatment
in the repeated measurements analysis. Bonferroni correction was used to
adjust for testing all eight scales of the RAND-36, resulting in the use of a
significance level of p<0.006 (0.05/8) for all tests we performed23,24. t Tests
and χ² tests were performed using SPSS V.11 and longitudinal analyses were
performed using the SAS Proc Mixed procedure in SAS V.9.13.
In total, 26 patients who met the inclusion criteria agreed to participate in
the study. All completed the first and second assessments and 23 patients
(88.5%) completed the third assessment. No adverse events were report-
ed. Seventeen patients (65%) received treatment for chronic symptoms
and nine (35%) for acute symptoms. Table 1 shows that 58% of participants
were women, and mean age of 42.6 years (range 22 62), which was not sig-
nificantly different from the Dutch population sample (65% women, mean
age 44.1 years, range 18 89). The mean treatment period was 6.9 weeks
between baseline and the sixth treatment session and 8.4 weeks between
the sixth and the 12th treatment session (table 1). Treatment consisted of
12 sessions with an average duration of 30 min, administered over an ave-
rage period of 14 weeks.
At baseline, the total study sample had significantly lower scores on the RAND-
36 scales role-physical functioning (51.9 vs 79.4; p<0.001), bodily pain (49.3
vs 79.5; p<0.001) and social functioning (75.5 vs 86.9; p=0.005) compared
to the Dutch population sample (figure 1 and table 2). No significant diffe-
rences between both populations were found for the other RAND-36 scales.
Five out of eight RAND-36 scales showed significantly higher scores after
treatment compared to baseline (table 2) physical functioning, role-physical
functioning, bodily pain, social functioning and vitality. The mean RAND-
36 scores after treatment were higher than the Dutch population sample
scores for all eight RAND-36 scales (figure 2). The difference was statistical-
ly significant for the physical functioning (p<0.001), bodily pain (p<0.001),
general health (p<0.001) and mental health scores (p=0.001)
Baseline RAND-36 scores for acute patients were 15 points lower for bodi-
ly pain on role-physical functioning scores compared to chronic patients,
but differences between acute and chronic patients were only statistically
significant for the differences in bodily pain scores (p<0.05). The improve-
ment in the five out of eight RAND-36 scales reported in table 2 was ob-
served in both acute and chronic patients.
We compared HRQoL of patients undergoing routine acupuncture treat-
ment for musculoskeletal complaints to the normal population and de-
scribed the perceived changes in physical and mental health during the
course of acupuncture treatment. Patients with musculoskeletal complaints
had lower RAND-36 scores on role-physical functioning, bodily pain and
social-functioning at baseline, significantly improved HRQoL during treat-
ment on five out of eight scales and had higher RAND-36 scores at follow-
up on all scales compared to controls.
Before discussing our results, two important methodological issues need
to be addressed. First of all, it is important to keep in mind that the design
of this study does not permit any causal inferences concerning the effect of
acupuncture itself, since no control group of patients was evaluated longitu-
dinally to assess the impact of possible placebo effects, as patients went to
the acupuncture clinic on their own initiative, likely with a prior open view
regarding the effectiveness of acupuncture.
Second, the small number of patients provided us with insufficient statistical
power to incorporate possible confounding factors in our model or compare
the age and sex distribution between groups in more detail. Also, we had
limited statistical power for the exploratory analyses of differences between
46
Chapter 2
47
acute and chronic patients and for other clinically interesting comparisons.
While the statistical power increased by using the repeated measurement
procedure with three measurements per patient, still the possibilities for
subgroup analyses were limited.
Our study demonstrated that the HRQoL of patients seeking acupuncture
treatment for musculoskeletal symptoms differed significantly from the nor-
mal population. At baseline, HRQoL of both acute and chronic patients was
lower on the RAND-36 role-physical functioning, bodily pain and social
functioning scales compared to the Dutch population sample. The diffe-
rence was most prominent for the physical health dimensions (role-physical
Sex (% women) 58 78 47 65
Age (mean, SD) 43 (10.6) 44 (10.3) 42 (11) 44
Diagnosis (n)
Aspecific lower back pain
Ischialgia
Epicondylitis lateralis
Osteoarthritis
Neck pain
(3)
(2)
(2)
(1)
(1)
Aspecific lower back pain
Ischialgia
Epicondylitis lateralis
Osteoarthritis
Neck pain
RSI
Pain in upper extremity
Chronic headache
Other musculoskeletal complaints
(2)
(1)
(2)
(1)
(3)
(3)
(2)
(2)
(1)
Duration treatment period
Treatment 0-6
Treatment 6-12
7 weeks
8 weeks
Mean
7 weeks
9 weeks
Mean
7 weeks
8 weeks
Characteristics of the study population
0
100
Physical
functioning
Role-physical
functioning
Bodily
pain
General
health
Vitality
Social
functioning
Mental
health
Role-emotional
functioning
Total study
sample
Dutch population
sample
Health-related quality of life scores of the total study sample and the Dutch population
sample. Depicted values are mean scores of R AND-36 scales at baseline. The centre of the
graph represents the lowest score possible for each scale. At a significance level of p<0.006 (p
value adjusted using Bonferroni correction), significant differences between the total study sample
and the Dutch population sample were found for RAND-36 role-physical functioning (p<0.001),
bodily pain (p<0.001) and social functioning (p<0.001) scales.
48
Chapter 2
49
functioning and bodily pain). These findings are similar to results from a pre-
vious study in patients suffering from musculoskeletal pain who did not visit
an acupuncturist for their symptoms25, suggesting that patients who seek
acupuncture treatment are not a subgroup with particular HRQoL profiles,
neither physically nor mentally.
The longitudinal findings of this study showed that the HRQoL of patients
seeking routine acupuncture improved significantly during the course of
treatment. This improvement in physical and mental health during the
course of acupuncture treatment concerned the dimensions physical func-
tioning, role-physical functioning, bodily pain, social functioning and vita-
lity. The observed improvements were most pronounced in the course
of the first six treatments for both acute and chronic patients. Although it
is unusual that both acute and chronic patients require the same number
of treatments, the researcher chose this fixed number in both groups for
statistical reasons to deal with the small number of patients in the treatment
group. For all RAND-36 scales, the observed improvement was larger than
the five points considered clinically relevant17.
The most distinct improvements were observed with regard to the scales
role-physical functioning, bodily pain and social functioning, indicating that
the largest improvements were symptom-related. Importantly, for these
RAND-36 scales--in which a lower score compared to the Dutch popula-
tion sample was found at baseline-- the scores after treatment were higher
than the scores of the Dutch population sample. In the Dutch population
sample the age was older and therefore might reduce their HRQoL scores.
However, given that the mean age is the same and that the very old are only
a small part of the total sample, we think it is unlikely that the differences are
only explained by an effect of age. Considering the normal baseline results
compared to the population sample, the observed improvements with re-
gard to the RAND-36 scale physical functioning was significantly higher than
the mean score of the Dutch population sample. It should be noted that
the better health on all scales compared to the general population may be
due to response shift, which is defined as an adaptation to changing health,
Physical health
Physical functioning
Role-physical functioning
Bodily pain
General health
Mental health
Vitality
Social functioning
Mental health
Role-emotional functioning
79 (2.3)
51 (6.8)
47 (4.3)
83 (3.7)
69 (4.9)
75 (4.9)
84 (2.9)
96 (4.2)
93 (1.5)
81. (5.6)
84. (2.9)
85. (4.0)
81 (3.9)
91 (4.3)
87 (3.2)
97 (4.3)
97 (0.9)
94 (5.3)
96 (1.7)
86 (3.5)
86 (4.3)
92 (4.6)
89 (3.7)
95. (4.9)
Health-related quality of life in a general acupuncture practice at baseline and after 6 and
12 treatments
Values are mean RAND-36 scores, as estimated by SAS Proc Mixed analyses, with standard
errors.
Health-related quality of life scores of the Dutch population sample and the total study sample
at the end of treatment. Depicted values are mean scores of RAND-36 scales at the end of the
treatment period. The centre of the graph represents the lowest score possible for each scale.
At a significance level of p<0.006 (p value adjusted using Bonferroni correction), significant
differences between the total study sample and the Dutch population sample were found for
RAND-36 scales physical functioning (p<0.001), bodily pain (p<0.001) general health (p<0.001)
and mental health (p=0.001).
50
Chapter 2
51
a beneficial mental process that can help in adapting to a new situation26.
Response shift is more likely to occur when the disease experience is new,
intense or pervasive27. Two-thirds of our population had long lasting mus-
culoskeletal complaints, who may no longer expect improvement of their
symptoms. All the patients were treated by the same acupuncturist what
might affect the generalisability of our findings.
The understanding of the holistic model of acupuncture treatment embed-
ded in Chinese medicine is limited by a lack of inquiry into the dynamics of
the process where “the whole is greater than the sum of the parts”28 -31. Pa-
terson and Britten32 found that treatment effects were perceived as changes
in symptoms, changes in energy and changes in personal and social identity.
After treatment, the study population had a significantly higher score on the
RAND-36 scales for general health and mental health as compared to the
general population. The longitudinal results of this study suggests that pa-
tients experience acupuncture as relevant for their recuperation, also sup-
ported by the fact that the majority of the study population completed the
full course of 12 treatment sessions, even though acupuncture is often only
partially reimbursed after prescription and often leads to private expenses.
Our findings support the view that acupuncture therapy has beneficial ef-
fects in patients with musculoskeletal complaints. This is in concordance
with the findings of two previously mentioned observational studies that
reported beneficial effects of acupuncture on HRQoL8,14 and with a variety
of RCTs on the efficacy of acupuncture in treating musculoskeletal com-
plaints9,10,12,13,33,34. In order to obtain a more accurate and robust evidence
for the role of acupuncture in daily practice with regard to musculoskeletal
complaints and its consequences, more extensive randomised controlled
research is needed. For instance, we suggest conducting a large controlled
study on the usefulness of acupuncture across multiple acupuncture prac-
tices and for specific musculoskeletal complaints. Also, the characteristics
of patients that seek acupuncture treatment for musculoskeletal complaints
need to be addressed in detail. Furthermore, it seems necessary to as-
sess whether the apparent benefit patients obtain from acupuncture treat-
ment also translates to less disability, morbidity and absence from work and
healthcare expenses in the long term.
In conclusion, this study demonstrated that patients who sought acupunc-
ture treatment for musculoskeletal complaints in an out-patient acupuncture
clinic showed a lower HRQoL at baseline, mainly with respect to physical
domains. During the course of acupuncture treatments, patients experi-
enced significant, clinically relevant improvement in HRQoL. Therefore,
acupuncture should be considered as treatment option for patients with
musculoskeletal complaints in general practice.
The authors thank the Dutch Association for Acupuncture (NVA), which, in
part, supported this study with an unrestricted grant.
Funding Dutch Association for Acupuncture (NVA), van Persijnstraat 17 te
Amersfoort, Postbus 2198, 3800 CD Amersfoort; nva@acupunctuur.nl,
http://www.acupunctuur.nl.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Medical
Ethics Committee Erasmus MC who gave a declaration of no objection for
publication (MEC2009-422).
Provenance and peer review Not commissioned; externally peer reviewed.
• Standard assessments of quality of life include eight dimensions
• Twenty six patients with musculoskeletal disorders showed signifi-
cant deficits in three dimensions
• Five dimensions showed improvement after a course of acupunc-
ture
52
Chapter 2
53
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Implications of findings from studies of response shift. Health Qual Life Outcomes
2004;2:14.
27. Sprangers MA, Moinpour CM, Moynihan TJ, et al. Assessing meaningful change in quality
of life over time: a users’ guide for clinicians. Mayo Clin Proc 2002;77:561 71.
28. Cassidy CM. Chinese medicine users in the United States. Part II: preferred aspects of
care. J Altern Complement Med 1998;4:189 202.
29. Gould A, MacPherson H. Patient perspectives on outcomes after treatment with
acupuncture. J Altern Complement Med 2001;7:261 8.
30. Paterson C, Britten N. Acupuncture for people with chronic illness: combining qualitative
and quantitative outcome assessment. J Altern Complement Med 2003;9:671 81.
31. Alraek T, Baerheim A. `An empty and happy feeling in the bladder.’: health changes
experienced by women after acupuncture for recurrent cystitis. Complement Ther Med
2001;9:219 23.
32. Paterson C, Britten N. Acupuncture as a complex intervention: a holistic model. J Altern
Complement Med 2004;10:791 801.
33. Witt CM, Jena S, Brinkhaus B, et al. Acupuncture for patients with chronic neck pain.
Pain 2006;125:98 106.
34. Ratcliffe J, Thomas KJ, MacPherson H, et al. A randomised controlled trial of acupuncture
care for persistent low back pain: cost effectiveness analysis. BMJ 2006;333:626.
Chapter 3
Freek J. Zijlstra
Ineke van den Berg
Frank J.P.M. Huygen
Jan Klein
Mediators of Inflammation, 2003, 12(2): p. 59-6
56
Chapter 3
57
Acupuncture has a beneficial effect when treating many diseases and pain-
ful conditions, and therefore is thought to be useful as a complementary
therapy or to replace generally accepted pharmacological intervention. The
attributive effect of acupuncture has been investigated in inflammatory di-
seases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid
arthritis, epicondylitis, complex regional pain syndrome type 1 and vascu-
litis.
Large randomised trials demonstrating the immediate and sustained effect
of acupuncture are missing. Mechanisms underlying the ascribed immuno-
suppressive actions of acupuncture are reviewed in this communication.
The acupuncture-controlled release of neuropeptides from nerve endings
and subsequent vasodilative and anti-inflammatory effects through calcito-
nine gene-related peptide is hypothesised. The complex interactions with
substance P, the analgesic contribution of ß-endorphin and the balance be-
tween cell-specific pro-inflammatory and anti-inflammatory cytokines tu-
mour necrosis factor-α and interleukin10 are discussed.
In China, acupuncture has been used in the treatment of several diseases
for at least 5200 years. In Europe and the USA, this integral part of tra-
ditional Chinese medicine has become a visible component of the health
delivery system and has steadily claimed its usefulness in complementary
medicine. Although sometimes without a clear objective beneficial effect,
an increasing number of patients, especially those suffering from chronic
diseases, are seeking acupuncture treatment and pursue (lay claims to) ad-
ditional healthcare. Consequently, this increases costs, even though it does
not always provide a clear objective beneficial effect1.
The widespread application of acupuncture includes the treatment of in-
fections, inflammatory diseases like rheumatoid arthritis, autonomic dys-
function, neurological diseases like migraine, pain, cardiovascular diseases,
pulmonary diseases like asthma, drug abuse, psychological disorders and
many other illnesses2. Based on the effects seen in this variety of diseases,
acupuncture could be divided into two main subjects: acupuncture analgesia
and curative acupuncture. In general, analgesia is obtained by short-term
acupuncture, whereas curative acupuncture requires long-term acupunc-
ture treatment procedures.
Traditional Chinese acupuncture is characterised by a holistic approach to
the management of the disease. The skill of the acupuncturist lies in the abil-
ity to work not only with a clear-cut diagnosis, but also takes into account
the complex pattern of disease-related factors. The exact pattern and de-
gree of disharmony is unique for each individual. Therefore, the practitioner
of traditional acupuncture will approach each patient with a perso nalised
treatment plan. This plan focuses on improving the overall well-being of the
patient, rather than the isolated treatment of specific symptoms or disease.
The basic health concept in traditional Chinese medicine consists of the
body’s vital energy (Qi), circulating unidirectionally through a complex net-
work of channels (meridians) just beneath the skin, but also moving within
blood vessels. It permeates organs and tissues, and is behind all physiologi-
cal processes. Health is the harmonious, uninterrupted flow of Qi, and dis-
ease ensues when there is disruption of Qi flow. Factors that can affect Qi
flow include emotional states such as anxiety, stress, anger, fear or grief,
poor nutrition, weather conditions, hereditary factors, infections and trau-
ma. By inserting needles, the acupuncturist tries to recover the equilibrium
58
Chapter 3
59
(the equal and dynamic opposite qualities of Yin and Yang) between physi-
cal, emotional and spiritual aspects of the individual, and to improve e nergy
flow and energy quality. Additional activation can be obtained through ma-
nipulation of the needle or electro-stimulation at different frequencies. The
most common manifestations of Yin and Yang in diseases are excess and
deficiency states. Health is defined as the balance of Yin and Yang3. Im-
provement of local blood circulation, distribution and bloodletting could
be the main aspects of which acupuncture-derived effects in inflammatory
diseases could be attributed4. In the case of inflammation, differential ef-
fects of acupuncture on acute and chronic stages of the disease could be
considered, more or less expressed by clinical symptoms like burning pain,
redness, swelling, changing temperature and loss of function.
Beyond these manifestations, inflammatory mediators could represent sub-
sequential mechanisms that are involved, but could also represent disease
activity. For example, in inflammatory bowel disease, the blood flow is in-
creased and vascular resistance diminished5, whereas the release of differ-
ent inflammatory mediators is time and region dependent and could be
influenced by external factors6–8.
In acupuncture, the insertion of a needle induces marked changes close
to the needle in all the different tissues that are penetrated. These pe-
ripheral events might improve tissue function through vasodilatation in the
skin due to axon reflexes, which cause an immediate flare reaction9. This
vasodilative effect could be caused by the release of calcitonin gene-elated
peptide (CGRP) upon stimulation of Aδ or C fibres10,11. The local release
of β-endorphin could be responsible for the short-term analgesic effect,
whereas the neuropeptide-induced release of anti-inflammatory cytokines
could be derived from lymphocytes and secondary activating cells, such as
macrophages. In the periphery, the real level of CGRP is of crucial impor-
tance. Usually CGRP has been shown to be pro-inflammatory, but in low
doses it has a potent anti-inflammatory action12. In this respect the release
of another neuropeptide, substance P, is not likely to attribute to this phe-
nomenon13, but could regulate CGRP release from nerve endings14. In the
present review, a hypothesis is presented concerning the anti-inflammatory
action of needle acupuncture through a dose’-related and time-related re-
lease of CGRP and a hypothesised preferential shift to the subsequent for-
mation of anti-inflammatory cytokines.
In the following, a number of inflammatory diseases will be reviewed in
which acupuncture treatment was initiated as a complementary therapy
or replacement for conventional pharmacological intervention. Then, the
role of mediators of inflammation in acupuncture will be discussed and a
proposed mechanism of action to use acupuncture will be hypothesised.
Numerous uncontrolled trials as well as a limited number of controlled tri-
als have been published with contradictory and conflicting results after the
shortterm or long-term use of acupuncture in the treatment of asthma. In
most studies, a relatively small number of patients were included, whereas
methodological procedures were incompletely described. Various outcome
parameters such as lung function, quality-of-life questionnaires and reduc-
tion of medication were used to reflect improvement of the disease.
The use of acupuncture to suppress the daily intake of orally given cor-
ticosteroids and inhaled β2-adrenergic agonists was investigated15. In an
open trial, patients with bronchial asthma were treated by acupuncture.
This resulted in a good therapeutic effect (96% effective rate). Patients ini-
tially were treated in 15 consecutive sessions and received 10 follow-up
treatments to consolidate the curative effect as marked by a decrease of
corticosteroid intake and diminished use of aerosols. The investigator con-
cluded that at least 30 sessions in 3 months should be offered to initiate this
effect, followed by 10 more sessions per year to prevent a relapse. The
extensive treatment with acupuncture could explain the lack of effect seen
in other studies.
In a double-blind cross-over study, the effect of 2 weeks of acupuncture
treatment on patients with stable asthma was investigated16 . Although a
significant improvement of the quality of life and a reduction of the usage
of inhaled β2-adrenergic agonists was observed, the respiratory function
was not affected. This is in contrast with another placebocontrolled study
in which patients with moderate persistent asthma, who were only treated
with inhaled β2-adrenergic agonists, received a treatment with acupunc-
ture four times17. This relatively short course of treatment did not affect
daily intake of inhaled β2-adrenergic agonists. No changes in lung functions,
bronchial hyper-reactivity or symptom scores were observed.
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Chapter 3
61
In a randomised, controlled study, both the additive effect of acupuncture
to conventional therapy and the immune-modulating effects on patients
with allergic asthma was monitored18. All patients were treated 12 times
for 30 min over a period of 4 weeks. Subjective parameters like the pa-
tients’ general wellbeing, and more objective parameters like biochemi-
cal measurements in blood, were determined before and after completion
of the acupuncture treatment. General well-being significantly improved
in the acupuncture group (79%) in comparison with the control group
(47%). Furthermore, lymphocyte proliferation and CD3+ and CD4+ cells
increased, whereas the number of eosinophils significantly decreased in the
acupuncture group.
Single application of laser acupuncture performed in a double-blind, place-
bo-controlled, crossover study to investigate the protective effect on cold
dry air hyperventilation-induced bronchoconstriction revealed no significant
protection in paediatric and adolescent patients19. Forced expiratory vol-
ume and the expiratory flow were unaffected by single laser acupuncture.
In 1991, Kleijnen et al. published a systematic review of 13 controlled clinical
trials pertaining to the use of acupuncture in the treatment of asthma during
the period 1963 -198920. Only three studies of acceptable quality resulted
in favourable effects. Recently, other systemic reviews and meta-analyses of
all randomised clinical trials in the published literature comparing acupunc-
ture at real and placebo points in asthmatic patients were performed. The
period 1970 - 2000 was evaluated by Martin et al21. Peak expiratory flow
rate, forced expiratory volume and forced vital capacity were collected as
objective outcome parameters. In this analysis, no significant overall effect
of acupuncture to reduce asthma could be confirmed. After induction of
broncho-constriction, however, a significant effect was observed. The au-
thors concluded that this meta-analysis was limited due to shortcomings of
the individual trials and a not clearly described use of placebo acupuncture.
Others who reviewed the efficacy of acupuncture in asthma concluded that
up to now evidence is lacking, also due to inadequately performed inves-
tigations22,23. In conclusion, mainly based on clinical outcome parameters,
there is presently not enough evidence to make specific recommendations
about the value of acupuncture in the treatment of asthma (Table 1).
Treatment by acupuncture is frequent among adults with asthma and rhi-
nosinusitis, and therefore should be taken into account by health-care
providers1,24. In acute sinusitis, acupuncture resulted in an improvement
in children with chronic and recurring frontal sinusitis25. In the treatment
of seasonal allergic rhinitis, acupuncture has been proven to be effective.
In a small single-blind crossover study, acupuncture (three times a week
during a 4-week period) improved subjective symptom scores, although a
reduction in medication was not observed26 . In allergen-provoked rhinitis
acupuncture, acupuncture therapy was not effective when regarding the
objective criteria, although again symptoms scores as registered in the di-
ary of complaints revealed a reduction27. Desensitisation of allergic rhinitis
using acupuncture endermic points of the head with the extract of positive
allergens proved to be effective in an open study including 102 cases. Af-
ter a follow-up of 2 years, a significant population (72%) showed a cura-
tive effect, mainly reflected by a reduced diameter of redness and reduced
swelling of the skin28 . In an open study, the positive effect of acupuncture
on atrophic rhinitis was demonstrated. The improvement was documented
by functional changes of the nasal mucosa (mucociliary transport, secreted
volume and surface temperature)29.
The use of alternative medicine in bowel diseases was already investigated
almost two decades ago. Significantly more patients with irritable bowel
syndrome (11%) appeared to consult practitioners of alternative medicine
than patients with Crohn’s disease (4%)30. Nowadays, traditional and com-
Asthma +/- 15-20
Rhinitis + 25-29
Ulcerative Colitis + 32-34
Rheumatoid Arthritis +/- 35-39
Epicondylitis + 41-46
Complex Regional Pain Syndrome + 49-52
(+) significant effect or (+/-) no clear disease related effect
Summarised effects of acupuncture in inflammatory diseases
62
Chapter 3
63
plementary therapies such as acupuncture are more frequently combined
in the treatment, relief and control of Crohn’s disease31. Until now, only
li mited data is available for the complementary use of acupuncture in ulcer-
ative colitis with or without moxibustion32–34. These data, however, indicate
that acupuncture could attribute to recovery in patients with active inflam-
matory bowel disease.
In another autoimmune disease, rheumatoid arthritis, which sometimes also
results in the development of Crohn’s disease, successful treatment with
acupuncture35 and moxibustion has been reported36,37. Although the results
clearly showed a beneficial effect in the reduction of symptomatic pain,
the small sample size is a matter of concern. In other placebo-controlled
cross-over studies, in a large number of patients with rheumatoid arthritis,
acupuncture could not attribute to any improvement in general health, pain
request or the examination of the number of swollen joints, nor to a di-
minished analgesic intake38,39. Until now, the usefulness of acupuncture as a
complementary and alternative medical therapy in rheumatoid arthritis still
has to be demonstrated in large randomised trials40.
The clinical efficacy of acupuncture was also investigated in chronic lateral
epicondylitis of the elbow (tennis elbow). The immediate analgesic effect of
a single acupuncture stimulation in a placebo-controlled single-blind trial has
been reported41. In a comparative study, both classical and superficial need-
le insertion was studied in a short-term treatment schedule stimulating five
selected acupuncture points during 10 treatments in 3 weeks42. Classical
acupuncture was only superior to superficial needle insertion after all treat-
ments were applied, but not at 3-month and 1-year follow-ups. Laser treat-
ment applied to the same acupuncture points, however, did not improve
subjective and objective outcome parameters significantly in comparison
with a placebo43 . Psychosomatic factors could attribute significantly in the
positive short-term effects of pain reduction44. As seen in the improvement
of outcome parameters including pain scores, function, disability, strength
and quality of life, short-term effects are promising45 but acupuncture failed
to stabilise the disease and did not contribute to further recovery46.
Recently, we confirmed that complex regional pain syndrome type 1
(CRPS1), formerly indicated as posttraumatic sympathetic dystrophy or
Sudeck’s atrophy, developed in one or more extremities, and should also
be considered as the result of an inflammatory reaction after neurogenic
stimulation47,48. Two case reports49,50 and two randomised trials predomi-
nantly focused on pain reduction51,52 have published improvements after
long-term acupuncture treatment. Other symptoms of inflammatory re-
actions including swelling, mobility, temperature and redness were also
observed. In comparison with placebo-treated patients, no significant im-
provement of these parameters could be proven.
Inflammation of the vascular system could attribute to some of the afore-
described inflammatory diseases. The promotion of blood circulation by
acupuncture could positively affect the enrolment of the whole cascade of
inflammatory mediators that are undoubtedly involved in the subsequent
processes during chronic inflammation53,54. In the context of migraine, neu-
rogenic inflammation could also play an important role55. Elevated plasma
levels of CGRP during headache suggest that this initial inflammatory media-
tor is involved. In general, acupuncture has additional value in the treatment
of primary headaches.56,57.
Neuropeptides Substance P
Neurokinin A
Neuropeptide Y
Vaso-active Intestinal Peptide
Bradykinin
Calcitonine Gene Related Peptide
β-Endorphin
Cytokines IL-1β, IL-2, IL-4, IL-6, IL-10
IFN-γ, TNF-α
Other vaso-active substances Nitric oxide
Eicosanoids
Serotonin
Inflammatory mediators reported in acupuncture
64
Chapter 3
65
In general, inflammation is associated with increasing temperature, oede-
ma, redness, pain and loss of function. Furthermore, the direct and indirect
effects of individual neuropeptides, cytokines and vasoactive mediators47
could be considered to play an intermediate role during and after acupunc-
ture has been assessed. Assuming local blood flow is indeed stimulated by
acupuncture58,59, the neurogenic formation of vasoactive mediators could
regulate blood flow and blood distribution to affected organs and tissue af-
ter inflammation has been initiated. Acupuncture activates the defence sys-
tems. It influences specific and non-specific cellular influx, activation of cell
proliferation and regulation of subsequently involved cells that will result in
a complex mechanism of transport, further breakdown and clearance of all
bioactive mediators60 (Table 2).
Calcitonine gene-related peptide is a potent vasodilator10 that has been
shown to have a physiological and pathological role in neurogenic inflamma-
tion, migraine, thermal injury, circulatory shock, pregnancy and menopause,
hypertension and heart failure, and has been proven to be cardioprotec-
tive61. Both substance P and CGRP have important roles in oedema forma-
tion and inflammation, and when transported centrally these neuropetides
can cause excitation62.
In patients with CRPS1, blood samples did not show an elevation of sub-
stance P and neurokinin A, whereas neuropeptide Y, CGRP, bradykinin and
vasoactive intestinal peptide (VIP) were increased four-fold63. Intraneural
substance P contributes to the severity of inflammation64. After intra-arte-
rial infusion in the human forearm, substance P provoked vasodilatation,
flushing and plasma extravasation65. In musculocutaneous flaps in the rat,
increased blood flow affected by acupuncture was comparable with the
effects observed after injection of substance P and CGRP59. In rats, acu-
puncture induced the release of substance P from peripheral terminals of
primary sensory neurons66. After repeated electro-acupuncture, significant-
ly higher concentrations of substance P and other neuropeptides such as
neurokinin A and neuropeptide Y were found in the rat brain67. The acute
release of neuropeptides can be mimicked and easily provoked after ap-
plication of capsaicin, the bioactive substance of red pepper. Acupuncture
could diminish capsaicin-induced oedema in the rat paw, indicating a promi-
nent role for substance P and other neuropeptides68. In dogs, the concen-
trations of substance P were determined in the skin, muscle and subcutis
of acupoints and control points, showing an increased release of substance
P after acupuncture69. On the other hand, an observation in rabbit tooth
pulp showed that, after an initial substance P release had already been
evoked, electroacupuncture suppressed this release70. In humans, during
labour, the content of substance P in serum declined after acupuncture
had been applied71, but increased in patients suffering from fibromyalgia72.
In both observations the analgesic effect of acupuncture was significant. In
samples taken from the saliva of healthy subjects, the release of substance P
was hardly affected after acupuncture, although neuropeptide Y and CGRP
were markedly increased73.
Needling of acupuncture points could result in activation of afferent fibres
of peripheral nerves, which induces the release of endogenous opiate pep-
tides from nerve cells. Beta-endorphins are believed to play an important
intermediate role in the regulation of the analgesic effects obtained through
acupuncture74,75. Beta-endorphin concentrations in spinal fluid and plasma
of horses, however, were not elevated after acupuncture76. Although pre-
natal acupuncture treatment in women significantly reduced the duration
of labour, serum levels of β-endorphin were not influenced77. In another
study, however 90 patients suffering from various painful disorders were
subjected to acupuncture. Plasma bendorphin levels were increased consid-
erably increase, resulting in an elevated immunologic response78 reflected
by lymphocyte markers CD3, CD4 and CD8. In curative (long-term) acu-
puncture, interactions between b-endorphins and cytokines could there-
fore result in an increased formation of anti-inflammatory cytokines79 such
as interleukin (IL)-10 and/or a diminished production of pro-inflammatory
cytokines, possibly being the most prominent mechanism of action underly-
ing the attributive effect of acupuncture in chronic inflammatory diseases.
Very recently, the existence of regulatory IL-10-dependent T-cell popula-
tions was documented in allergic diseases80.
Recently, the effect of acupuncture on regulation of cytokine production in
asthma has been published8 1. Clinical signs of asthma improved markedly.
In peripheral blood of asthmatic patients, the mean IL2 and IL-6 plasma lev-
els were decreased, whereas interferon (IFN)-γ, IL-4 and tumour necrosis
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Chapter 3
67
factor (TNF)-α were increased. After acupuncture IFN-γ, IL2, IL-4 and IL-6
were elevated and TNF-α was reduced. In allergic rhinitis, plasma concen-
trations of IL-2, IL-6 and IL-10 were determined before and after acupunc-
ture in comparison with healthy controls82. In all allergic rhinitis patients, IL-
10 levels were increased prior to real acupuncture, placebo acupuncture or
non-treatment. In the acupuncture group IL-10 was reduced, whereas IL-2
was hardly affected and IL-6 remained unchanged after therapy. In rheuma-
toid arthritis, IL-2 levels were lower than in the healthy controls36,37. After
acupuncture, this reduced IL-2 production was elevated. In a rat model for
ulcerative colitis,83 acupuncture and moxibustion inhibited the expression of
pro-inflammatory cytokines IL-1β and IL-6.
In conclusion, the (im)balance between T helper 1 cell-derived and T hel-
per 2 cell-derived pro-inflammatory and anti-inflammatory cytokines was
reset by acupuncture.
As some observations highlight the stimulating effects of acupuncture to
muscle afferents and blood flow through autonomic reflexes, the attribu-
tive effect of nitric oxide (NO) through local release and/or induction after
electrostimulation should also be considered84. Significant and persistent
increases in the arteriolar diameter were observed after electroacupunc-
ture. This effect was abolished in the presence of nitro-L-arginine methyl
ester (L-NAME), indirectly indicating that NO plays a key role in the primary
mechanisms that are involved in microcirculation. From rat studies, it has
been shown that NO levels were increased in rat striatum after cerebral
artery occlusion, ischaemia and reperfusion. Electroacupuncture antago-
nised the ischaemia-elicited release of NO85. The anticonvulsant effect of
electroacupuncture might be related to the decrease of the nitric oxide syn-
thases neuronal nitric oxide synthase and inducible nitric oxide synthase86.
From these preliminary results it is not clear whether central effects evoked
by electro-acupuncture are more pronounced than those observed in the
circulatory system, especially when inflammation occurs and the endothe-
lial-derived nitric oxide synthase produces sustained amounts of NO87.
Furthermore, a disturbed microcirculation through shunting of arterioles is
also evoked by serotonin, another reasonable explanation why acupuncture
could be (only) effective for the short-term treatment of migraine.
Controlled studies Non-treated controls
Placebo needled acupuncture
Placebo (non) invasive acupuncture
Laser
Superficial (‘minimal’)
‘Wrong’ acupoints
Penetrating/invasive acupuncture
Disease-related acupuncture
Individualised acupuncture
Style Chinese traditional acupuncture
Japanese superficial acupuncture
Western-oriented acupuncture
Treatment schedule Single treatment
Frequency
Repeated treatments short term
Repeated treatments long term
Follow-up treatment
Needle Point selection per session
Number of acupoints used
Number of needles inserted
Depth of insertion, needle type
Duration of needling
Stimulation Manual
Electrical
Blinding Patient
Acupuncturist
Physiotherapist
Assessor
Statistician
Co-interventions Moxibustion
Herbs
Physical therapy
Pharmaceutical intervention
Variables in acupuncture
68
Chapter 3
69
In general, acupuncture trials include a limited number of patients. These trials
are heterogeneous regarding patients, interventions and outcome measures
and (therefore) present contradictory results. Most obvious is the need for
well-designed and larger clinical trials88. Research in the area of complemen-
tary medicine such as acupuncture should be performed and evaluated at the
same high-quality standards as research in the use of conventional therapies.
In some studies, acupuncture points that were used in the placebo groups
could be effective according to traditional Chinese medicine. Therefore, with
regard to the standardised choice of acupuncture points in the set-up of re-
peatedly applied acupuncture in placebo acupuncture controlled clinical trials,
the main problem to be solved is to determine the originally individualised
treatment strategy that includes this approach.
A matter of debate is the set-up of randomised trials comparing placebo, pla-
cebo or non-treatment. A placebo needle has been designed, with which it
could be possible to stimulate an acupuncture procedure without penetrating
the skin89. In this set-up, placebo-treated patients experienced less ‘de-Qi’ pain
sensation, also expressed by a diminished visual analogue scale pain. Another
acceptable approach could be the inclusion of placebo laser acupuncture90, but
it is preferred that placebo acupuncture is used, when not actively involved
meridians are needled or superficial pricking is applied. Based on functional
magnetic resonance imaging of the whole brain, it has however been dem-
onstrated that superficial pricking revealed more signal intensity than minimal
applied acupuncture91. From a pharmacotherapeutical point of view (kinetics,
dynamics and dose finding), it is difficult to make comparisons between diffe-
rent acupuncture techniques that are used in not well-described studies. First,
from traditional Chinese medicine, acupuncture should be considered and
applied as an individually based therapy. Many factors and variables will influ-
ence the outcome of the therapy, such as: which of the acupoints and how
many acupoints are chosen per treatment session? what is the reproducibility
of the matrix of chosen acupoints? what is the type, depth, direction and ma-
nipulation of the inserted needle? what is the needle retention time and the
length of the session? what is the frequency and total number of treatments?
what is the follow-up? and what are the maintenance treatments?92 (Table
3) Furthermore, for Western
scien tists, the main part of the
literature describing Chinese
and Japanese trials performed
on acupuncture is only avail-
able as translated abstracts.
Not only is there a marked
difference between Chinese
and Japanese acupuncture, but
Western educated and qualified
acupuncturists apply acupunc-
ture differently in comparison
with ancient acupuncturists.
In some studies performed in
Western countries, Chinese
guest scientists collaborated in these studies, and they were the ones who
performed the acupuncture treatments during their stay. As a consequence,
some specific methodological information is missing, which makes it virtually
impossible to continue or repeat treatment schedules for specific purposes
(Fig. 1). Recently, standards for reporting the outcome of controlled acu-
puncture trials have been published93–96. Because the intensity and frequency
of acupuncture as a complementary therapy will be individually chosen, one
should also consider the subtype of the disease. In asthma, for instance, some
aspects such as allergic, acute, chronic, exercise or cold-induced asthma
should be considered, which will certainly affect the outcome of the acu-
puncture therapy. In most studies, subjective parameters (e.g. visual analogue
scale pain, life questionnaires) are used. In open and single-blinded trials,
the results clearly depend on the sample size and the number of repeated
measurements. Objective parameters (e.g. forced expiratory volume in one
second (FEV1), oedema or secreted volume and surface temperature) better
reflect the attributive effect of acupuncture in the recovery from inflamma-
tory diseases, but do not distinguish between primary and secondary events.
Therefore, documented research on underlying mechanisms indicating the
specific release or inhibitory action on the formation of inflammatory media-
tors such as substance P, CGRP, β-endorphin and cytokines would undoubt-
edly indicate whether acupuncture is advisable as a complementary therapy
and confirm preliminary results.
A number of studies describing the
application of acupuncture in inflammatory disease
have been published. Conclusions are difficult to be
made, due to different acupuncture techniques used
and insufficiently described methodology. (Drawing
by Theodoor van Baars.)
70
Chapter 3
71
The underlying mechanism of acupuncture could be that, after antidromic
stimulation of the nociceptor, CGRP, substance P and β-endorphin are all re-
leased. Initially, substance P will activate mast cells and in a later phase also
macrophages to secrete inflammatory mediators. As a consequence, the mast
cell will not only secrete serotonin and histamine, but also cytokines such as
TNF-α. In turn, TNF-α could prime sensory nerve endings97. The activation of
mast cells and mast cell-mediated inflammation is regulated by NO98. Macro-
phages will produce a number of cytokines and eicosanoids. In the blood
vessel, CGRP will directly or indirectly affect vasodilation and extravasation via
the stimulation of NO99,100. VIP and bradykinin. Delayed dilatation to brady-
kinin is cyclooxygenase-2 dependent101, whereas prostaglandin E2 potentiates
bradykinin and induces pain. Substance P regulates the vasodilator activity of
CGRP through the action of proteases from mast cells14. In calcitonin/alpha
calcitonin gene-related peptide knockout mice, nociceptive hypersensibility
was reduced102. Furthermore, it has been shown that both CGRP and VIP
counteract nicotine-induced sweating103. The suppressing or potentiating ef-
fects of substance P and CGRP on metacholine-mediated cholinergic sweating,
however, were dose dependent104,105. The ability of sweating to regulate skin
temperature is well known and is more pronounced in men than in women.
In women with chronic pelvic pain, intravenous infusion with CGRP resulted
in a significant increase of skin temperature and complaints in comparison with
healthy volunteers, whereas VIP did not provoke pain nor affect tempera-
ture106, suggesting the existence of a neurovascular disorder. There has been
some evidence that hot flashes observed in menopausal women are due to
up-regulation of CGRP receptors following ovarian hormone deficiency107. In
ovari-ectomised rats, the greatest vasodilation and skin temperature increase
was observed after CGRP, with less effect of VIP and the smallest effect seen
after substance P108. In men who showed hot flashes after castration due to
prostate carcinoma, plasma CGRP levels were elevated109. These results sug-
gest that the vasodilative and skin temperature increasing effect of CGRP could
be due to a diminished amount of (female) sex steroids. This could explain the
higher incidence of migraine in woman110 and menstrual-related migraine55,111,
and the prevalence of some diseases in women, such as CRPS147,48 and carpal
tunnel syndrome112. In addition, studies on gender differences in pressure pain
threshold in healthy humans showed a significant decrease in females in com-
parison with males113.
In general, the acute, short-term and long-term effects of acupuncture are
comparable with actions observed by the use of capsaicin. Capsaicin is the
bioactive component of chili pepper. Application of capsaicin to the skin114-
116 or mucous membranes117 initially results in irritation and hyperaesthesia.
This momentary effect is attributed to the release of substance P from pe-
ripheral sensory C fibres. Repeated application of capsaicin would result
in a depleted secretion of substance P from neurons. During inflammation
these effects are more pronounced118. It is conceivable that the simultane-
ous release of CGRP will follow the same cascade of secretion. The antino-
ciceptive effects of a capsaicin analogue, civamide, when given orally to rats,
have been described119. Besides the receptor related effects of this vanilloid
receptor agonist and neuronal calcium channel blocker, proposed actions
Schematic overview of proposed interplay between nerve cells and inflammatory cells,
and site of action of acupuncture and capsaicin or antagonists: role of neuropeptides, cytokines,
nitric oxide and eicosanoids. NOS, Nitric oxide synthase; SP, substance P; Th, T helper.
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73
could also include inhibition of the neuronal release of CGRP and substance
P120. That could explain the acute120 and prophylactic properties121 of this
substance in the treatment of cluster headaches. In concordance with these
findings, therapeutic (needle) acupuncture induces peripheral events that
might improve tissue function and induce local pain relief, based on mecha-
nisms that include axon reflexes, release of neuropepties such as CGRP,
anti-inflammatory actions of neuropeptides like substance P, and local re-
lease of β-endorphin. Furthermore, sympathetic inhibition could occur and
levels of stress hormones and sex steroids could be reduced. Intense and
frequently applied acupuncture gives rise to more pain, which could be due
to high amounts of secreted CGRP (comparable with initial effects of capsa-
icin) when the inflammatory effect is predominant. Pain relief sometimes is
observed after some days of treatment, possibly due to the delayed release
of β-endorphins and the accumulated dose needed to be effective2 through
IL-10 formation79,122-124. IL-10 formation is limited, as has been shown in
IL-10-dependent T-cell populations80.
As already stated in the Introduction, high levels of CGRP have been shown
to be pro-inflammatory but, on the contrary, CGRP in low concentrations
exerts potent anti-inflammatory actions12. The main attributive effect of sub-
stance P could be the feedback regulation of CGRP release from nerve end-
ings13,14. The effects of neuropeptides may vary from one organ or tissue to
another. The presence and timedependent contribution of mast cells, ma-
crophages and other inflammatory cells to produce mediators that activate
or counteract the inflammatory process may be of crucial importance125
(Fig. 2). Therefore, a well-performed and frequently applied ‘low-dose’
treatment of acupuncture could provoke a sustained release of CGRP with
anti-inflammatory activity, without stimulation of pro-inflammatory cells.
That could be the explanation why acupuncture only seems to be beneficial
in the treatment of some inflammatory conditions.
A number of observations on the anti-inflammatory actions of acupunc-
ture have been published, representing open studies and randomised tri-
als. Both short-term and long-term treatment schedules were performed,
with varying number of acupuncture points, acupuncture frequency and
additional application of electro-stimulation. The value of complementary
acupuncture in the treatment of inflammatory diseases is still questioned.
In asthma, the highest effective rate observed was obtained after a high
number of frequently applied acupuncture sessions were performed, then
reduced, and then performed at least 10 times per year to prevent relapse15.
In rhinitis, results that were mainly obtained from open trials suggest a com-
plementary effect of acupuncture after allergen provocation. In inflamma-
tory bowel disease and rheumatoid arthritis, the usefulness of acupuncture
still has to be demonstrated in large randomised trials. In epicondylitis and
CRPS1, the attributive immunosuppressive effect of acupuncture has not
yet been properly investigated, although a reduction of pain has been ob-
served. From preliminary results it is conceivable to hypothesise that CGRP
has a prominent role in the acupuncture-affected regulation of acute, sub-
acute and chronic inflammation, regarding the vasodilative properties of this
neuropeptide. Substance P should be considered to counteract the release
of CGRP from nerve endings, whereas the balance of the mast cell derived
pro-inflammatory TNF-α and the T-cell derived anti-inflammatory IL-10
could contribute to the development of the chronic stage of the inflam-
mation. In this respect, acupuncture as a maintenance treatment could be
beneficial to reduce inflammation. Evidence from large randomised trials,
including follow-up measurements of mediators of inflammation, both at
the site of inflammation and in the periphery, should be obtained to prove
the immunologic effects of acupuncture.
The authors thank Ivan L. Bonta (Emeritus professor of Pharmacology, Eras-
mus MC Rotterdam, The Netherlands) for reviewing the paper.
74
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Chapter 4
Ineke van den Berg
Ylian S. Liem
Feikje Wesseldijk
Freek J. Zijlstra
M.G. Myriam Hunink
Complementary Therapies in Medicine, 2009;17:262-8
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Complex regional pain syndrome type 1 (CRPS1) can de-
velop after severe trauma or surgery in the limbs, and presents with chro-
nic, changes in temperature, edema and dysfunction. Seventy-five percent
of CRPS1 patients are female. While neurological and inflammatory com-
ponents have been proposed, the etiology remains unclear. No consensus
on optimal management of CRPS1 exists.
In traditional Chinese medicine, menstrual disorders are related to the state
of women’s constitution and therefore identify their pain patterns. A clas-
sification by constitution might improve the pain management in CRPS1 pa-
tients. It is unknown whether associations exist between menstrual-cycle-
conditions and CRPS1.
To investigate whether a specified menstrual condition is associated
with the risk of developing CRPS1.
A population-based case-control study of CRPS1 was conduc-
ted among Dutch women aged 18-82; i.e. 34 women with CRPS1 and
147 controls. A standard questionnaire consisting of 59 menstrual-cycle-
symptom-based questions was administered. From this questionnaire, 15
CRPS1-related questions (DRQ 15) were analyzed. We used multivariate
logistic regression to obtain odds ratios and 95% confidence intervals (CI)
for specified menstrual disorders adjusting for age, oral contraceptives, hys-
terectomy and age at menarche ≤ 12 and ≥ 17 years.
On the basis of the DRQ 15, women with CRPS1 were 5.3
(95%CI 2.1, 12.9) times more likely to have menstrual disorders than com-
parable controls.
Our results suggest that selected menstrual conditions are
associated with the risk of developing CRPS1.
Complex regional pain syndrome type 1 (CRPS1, also known as reflex sym-
pathetic dystrophy, Sudeck’s dystrophy or posttraumatic dystrophy) is an
extremely painful disorder of the soft tissues, which develops as a dispro-
portionate consequence of traumas and is most common in the limbs1-3. It
is marked by various autonomic and vasomotor disturbances such as diffuse
pain, spreading edema, changes in temperature disturbances and impaired
active range of motion4-7. CRPS1 is diagnosed by the Bruehl criteria (Table
1) after exclusion of other reasons for the pain or dysfunction8. Established
by consensus between clinicians and basic scientists, these criteria are prac-
tice-based rather than mechanism-based, which might be a reason for pos-
sible late recognition and treatment of CRPS1.
The number of persons suffering from chronic CPRS1 in the Netherlands
is estimated at 20,000; and effective treatment is not available9. Various
theories concerning the patho-physiological mechanism of CRPS1 have
been proposed. A change in sympathetic activity10, inactivity11, neurogenic
inflammation12 and an inflammatory response13 have all been suggested as
possible originate mechanisms for CRPS1. Worldwide there seems to be
a gender disposition to the effect that 75% of patients are women, with a
median age of onset of 46 years. Menstrual cycle-related problems in the
year before CRPS1 developed are described14. An association between the
development of CRPS1 and cumulative endogenous estrogen exposure is
not found15.
Nevertheless, as early as 1966, Von Zedlitz described the positive effects
of sex hormones in the treatment of CRPS116,17. In contrast to Von Zedlitz,
Janson et al. described that postmenopausal women (age > 50) who re-
ceived hormone replacement therapy reported more muscular pain than
those without this therapy18,19. Furthermore, changes in estrogen are cor-
related with a variety of effects in the central nervous system (CNS), such
as changes in pain transmission, headache, dizziness, nausea, temperature
regulation, and mood. The fluctuating estrogen levels during ovarian cycles
and over the lifespan therefore cause predictable changes in serotonin sys-
tems in women20,21.
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87
To our knowledge, no study has been conducted on a possible associa-
tion between CRPS1 and specified menstrual disorders. We assumed there
might be such an association from the point of view of traditional Chinese
medicine (TCM) in which menstrual disorders can identify pain patterns.
TCM takes a holistic approach to the management of chronic disease in re-
lation to the patient’s underlying condition and vital body energy (Chi)22,23.
Thus, the chronic complaints in CRPS1 may be linked to characteristics of
other organ systems as predictors of clinical success; pattern recognition on
the basis of diagnosis and therapy. This implies a shift of focus away from the
disease process in a particular organ to the process in the whole organism
or ‘system’.
We report a pilot study aimed at investigating whether women’s risk of
developing CRPS1, as assessed by a specified TCM condition as proxy, is
predicted through a validated TCM-questionnaire of the menstrual cycle
and therefore is associated with described anomalies of the menstrual cycle
in pre-menopausal women. If so, this questionnaire might provide an ad-
ditional tool for the early diagnosis of CRPS1.
In this population-based case-control study we included 34 women with
CRPS1 (mean age 48.8, range 19-68) and 147 women without CRPS1
(mean age 44.5, range 18-82). The women in the case group had been
referred to the pain clinic of Erasmus MC, the Erasmus University Medi-
cal Center, Rotterdam, the Netherlands after initial diagnosis by their GP.
The diagnosis was confirmed by an anesthesiologist specialized in chronic
pain management, who applied the Bruehl criteria (Table 1)1. These pa-
tients participated in several studies performed between 2001 and 2004
either to investigate the pathophysiology of CRPS1 or the effects of specific
treatments for it12,24. Exclusion criteria were a major trauma or systemic
disease and CRPS1 type 2 with causal nerve lesion. The control group was
a convenience sample of women traveling on the same day on the Rot-
terdam subway, and who agreed to be interviewed when passing the gate
of the subway station nearest to Erasmus MC. They had been matched for
the age distribution expected for women
with CRPS1. In addition they had been
matched for the past or present use of oral
contraceptives, for the following reason.
CRPS1 typically develops after minor trau-
mas such as bone fracture and sprains3.
Oral contraceptive users appear to reach
the menopause with a bone density 2-3%
higher than that of non-users, and would
therefore seem to be at lower risk25,26.
This study is part of a larger study about
the effects of acupuncture on pain and skin
temperature in patients with CRPS1. The
Erasmus MC medical ethical review board
approved the study, and all patients signed
a written informed consent form.
The questionnaire was a forward/back-
ward translation into the Dutch language
of the German version of the TCM Ques-
tionnaire. It contained 59 items concer-
ning six aspects of the menstrual cycle in a
woman’s fertile age27 . The six aspects de-
scribed (1) the menstrual cycle (8 symp-
tom questions (sq), (2) pre-menstrual syn-
drome (9 sq), (3) amount of blood loss (13
sq), (4) menstrual pain (9 sq), (5) color of
the lips of the mouth (6 sq), and (6) o ther
complaints (14 sq). Other complaints
were questions about headache, flush-
es, palpitations, perspiration, cold hand
and feet, urinating problems, loneliness,
and hyperventilation. Eighteen additional
questions addressed profession, general
medical history, specific medical history of
which is disproportion-
ate to any inciting event
of other reasons
for pain or dysfunction
Patient reports presence of at least
one in each category
Doctor reports at least one
of two or more categories
4 Categories
Vasomotor:Temperature asymmetry and / or skin colour asymmetry
Sensory: Hyperalgesia or allodinia
Sudomotor / oedema: Oedema and / or sweating changes and / or sweating asymmetry
Motor / trophic: Impairment of motor function, including weakness, tremor, and dystonia. Atrophy of the
hair, nails, and other soft tissues. Alterations in hair growth. Loss of joint mobility and range of motion.
Criteria of Bruehl: Diagnostic criteria for Complex Regional Pain Syndrome type 1
88
Chapter 4
89
CRPS1, oral contraceptive use, age at menarche, age at menopause, and
hysterectomy.
IB and FJPMH administered the questionnaire about the menstrual cycle. The
women in the case group received the questionnaire from the doctor and
completed it at home, after their visit to the hospital. In an accompanying let-
ter, the women were asked to recall their menstrual cycle before the use of
oral contraceptives or before hysterectomy or other interventions, and before
the last years of menopause. It is well known that bleeding pattern changes
considerably over the last years before menopause. Controls completed the
questionnaire on the spot.
On the basis of the literature, we assumed that the pattern most related to
CRPS1 would be painful obstructive syndrome (POS)23,28-30. In POS, only
particular menstrual cycle related symptoms are to be taken into account.
Prior to the analysis, a set of fifteen questions related to the POS syndrome
(therefore CRPS1 related) was selected from the full questionnaire (Table
2). Symptoms addressed in the questionnaire were noted as present or
absent.
The data were analyzed using SPSS 11.0 for Windows, SPSS Inc., Chicago,
IL. Demographic characteristics of patients and controls were compared
using the Mann-Whitney U test for age and the Chi-square test for oral
contraceptive use.
We tested the hypothesis that women in the case group would have more
symptoms than the control group. To dichotomize the measure of expo-
sure, a cut-off point was determined from the distributions of numbers of
positive answers of patients and controls in a histogram (Fig. 1). Because
the distributions partly overlapped, the cut-off point was determined as the
intersection of the distributions. After viewing the data, we defined a POS
related menstrual syndrome if more than six questions of the set were an-
swered positively. Mean number of positively scored menstrual symptoms
was calculated for both groups.
Proportions of women with the menstrual syndrome were compared using
odds ratios (ORs) and confidence intervals (CIs) as measures of association.
PMS:
Are you tense, emotional or depressed before your menstruation?
12 (37.5)
37 (8.2)
0.156
Menstrual Cycle:
Do your menstrual periods always start later (1-7 days) than the expected 28 days?
Do you have an extra craving for sweet food?
3 (9.4)
9 (28.1)
6 (2.0)
42 (6.1)
0.214
0.959
Menstrual Pain:
Do you have strong stinging pain during your menstruation?
11 (31.4)
34 (7.5)
0.099
Amount of blood loss:
Other menstrual complaints:
Do you suffer from insomnia during the menstruation?
7 (21.9)
18 (4.8)
0.112
Other complaints:
Do you feel lonely?
Do you suffer from heart palpitations?
4(13)
9 (28.1)
19 (2.7)
28 (6.1)
0.997
0.179
Set 15 selected menstrual cycle symptoms questions, related to POS syndrome, and therefore CRPS1 related.
90
Chapter 4
91
Chi-square tests were
performed to assess the
relationship between
the presence of the
menstrual syndrome
and the factors age ≤
50, hysterectomy, oral
contraceptives and age
at menarche ≤ 12, and
≥ 17 years.
In multivariate logistic
regression analyses, the
relation between the
presence of the men-
strual syndrome (as de-
pendent variable) and
the presence of CRPS1
(as independent vari-
able) was adjusted for age, age at menarche (≤ 12 and ≥ 17 years), cur-
rent or past oral contraceptive use, and a history of hysterectomy. A p-value
(two sided) ≤ 0.05 was considered to be statistically significant. Subgroup
analyses were performed for the factors age ≤ 50 and age > 50, due to the
age reference range expected for women with CRPS19.
We constructed a ROC curve
with the number of positive
answers as test variable and
the Bruehl criteria as refer-
ence standard (Table 1). Sen-
sitivity and specificity of the
selected set of questions were
calculated for scores higher
than the cut-off value of six
positive answers. Subsequent-
ly we calculated the area un-
der the curve to compare the
discriminative ability of the set
of questions with the refer-
ence standard.
The case group and the control group did not significantly differ with regard
to age (p = 0.17) and oral contraceptive use (p = 0.86).
The mean number of positively scored menstrual symptoms in the patient
group was significantly higher than that in the control group: 6.4 (se 0.56)
versus 3.6 (se 0.24) (p < 0.001) (Fig. 1). Eighteen of the 34 women in the
patient group (53%) gave more than six positive answers; versus 22 of the
147 in the control group (15%). The odds ratio of having more than six
positively scored menstrual symptoms for patients compared to controls
was 6.4 (95%CI 2.2-14.4, p < 0.001). The univariate analyses revealed no
significant relationship between the presence of the POS syndrome (more
than six positive answers) and the factors: age ≤ 50 years, hysterectomy,
use of oral contraceptives, and age at menarche ≤ 12 and ≥ 17 years. Mul-
tivariate logistic regression analysis revealed no significant effects for current
Number of positive answers in the DRQ 15
12
11
10
9
8
7
6
5
4
3
2
1
0
%
30
20
10
0
controls
patients
Histogram of the total number of positive answers
(in percentage) for the set of 15 symptoms.
Factors associated with diagnosis of confirmed CRPS1 among questioned patients and
controls.
ROC Curve
1 - Sp ecifi city
1.00.75.50.250.00
Sensitivity
1.00
.75
.50
.25
0.00
ROC curve for the set of 15 questions
related to CRPS1, resulting in an area under the
curve of 0.77. With a fixed cut-off value (>6 positive
answers), the sensitivity is 64% and the specificity is
85%.
>6 positive answers 18/34
(53%)
22/147
(15%)
6.4
(2.2—14.4) < 0.001
Multivariate regression: age, age at menarche
(≤12 and ≥17 years) current or past oral con-
traceptive use, and a history of hysterectomy
5.2
(2.1—12.9) <0.001
Multivariate regression:
20 patients with age ≥50 years
15.5
(4.4, 53.9) < 0.001
Multivariate regression:
14 patients with age ≤50 years
2.6
(0.8, 8.8) 0.06
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Chapter 4
93
age, age at menarche (≤ 12 and ≥ 17 years), current or past oral contra-
ceptive use, or a history of hysterectomy. Adjusted for these covariates the
OR was 5.2 (95%CI: 2.1-12.9, p < 0.001).
Additional multivariate analysis with current age as an interaction term de-
monstrated that age was a significant effect modifier (p = 0.02).
Analyses in the two subgroups according to age showed that the odds ratio
was 15.5 (95%CI: 4.4, 53.9, p < 0.001) in the group of patients (n = 20)
aged ≥ 50 years. The odds ratio for patients under the age of 50 years
(n = 14) was 2.6 (95%CI: 0.8, 8.8, p = 0.06) (Table 3).
The ROC curve depicted in Fig. 2 shows an area under the curve of 0.77
in the selected set of questions, with a sensitivity of 64% and a specificity of
85% for the cut-off value of six positive answers.
This pilot study is the first population-based case-control study in which
the development of CRPS1 was associated with anomalies of the men-
strual cycle in pre-menopausal women. We investigated whether the
risk of developing CRPS1 is associated with 15 POS representing dis-
orders of the menstrual cycle (DRQ 15). Overall, compared to con-
trols, women with CRPS1 were found to be significantly more likely to
confirm more than six symptoms even after adjustment for age, age at
menarche (≤ 12, and ≥ 17), oral contraceptives use and hysterectomy,
with an adjusted odds ratio of 5.2. In addition, the ROC curves suggest that
the DRQ 15 has a good discriminative power in women with CRPS1 and
can be used as additional tool for the early diagnosis and additional TCM
treatment of CRPS1. Subgroup analyses showed that the association be-
tween CRPS1 and the menstrual syndrome was stronger for women over
50 years of age.
Our findings suggest a close relationship between CRPS1 and mood, physi-
cal and behavioral symptoms, of the sort described by Freeman and Bruehl
as well as in Chinese medical textbooks31-33. Actual association between
psychological and behavioral factors and CRPS1 remain controversial be-
cause the lack of methodological high-quality studies. In the literature, the
majority of studies showed no relation, although some studies have ob-
served psychological factors as anxiety, depression, somatisation and hypo-
chondria in the maintenance of CRPS134.
Disproportionate pain, related to menstruation has also been described in
patients with mood and anxiety disorders, and women with fibromyalgia
(FM)35-37. FM and CRPS1 show similarities in age distribution, male-female
ratio, pain characteristics and sensory signs and symptoms. In CRPS1, mo-
tor, autonomic and trophic changes are part of the criteria (Table 1), but
only occasionally reported in FM38.
In the present study, 15% of women in the control group were classified as
having menstrual disorders. Likewise, in a case control study by Freeman et
al. 15% of controls had a highly positive score in the daily symptom report
questionnaire on premenstrual symptoms31.
The difference in prevalence of chronic widespread pain between men and
women cannot be explained by sex hormones alone21,35,39. For example,
studies in rodents have shown differences in pain modulation systems of
males and females40.
The Chinese medicine theory might provide another explanation for the
adult female disposition in CRPS1. The penetrating vessel (Chong Mai), to-
gether with the directing vessel (Ren Mai) regulates the uterus and menstru-
ation. The penetrating vessel controls all the blood connecting channels,
and clarifies the connection between disharmony of blood in the uterus
and the development of muscular pains. It also demystify why women are
more prone to external invasions during menstruation: depletion blood in
the penetrating vessel induces a vacuity of the blood connecting channels
and therefore the space between the skin and muscles (Cou Li) becomes
empty and assessable for invasion by external pathogenic factors caused by
traumas41. Perhaps women who are familiar with excessive bleeding du-
ring their period, also experience more bleeding at injuries. When, e.g.
the fractured limb is fixed in plaster, their ongoing bleeding causes internal
pressure and maybe damage the soft tissues. Further examination of this
theory is needed.
Several limitations of the study, which may have caused bias, need to be
mentioned. First, the case-control design did not show the incidence of
CRPS1 to be estimated on the basis of our data. For the same reason, the
OR may have been overestimated. Although the groups were comparable
with respect to age and oral contraceptive use (Table 2), we adjusted for
age, oral contraceptives, hysterectomy, and age at menarche. It may well
94
Chapter 4
95
be that the effect observed was caused by other, unmeasured, differences
between both groups. Third, the questionnaire used in this study has not
yet been validated by Western criteria27. However, well trained traditional
Chinese medicine practitioners use this questionnaire worldwide to identify
the pattern of disharmony that prevails in patients with a particular pain
condition42.
In order to keep information bias to a minimum, participants completed the
whole questionnaire with the 59 symptoms rather than only the selected 15
disease-related symptom questions (DRQ15). In addition, because participants
were not aware of the study hypothesis, recall of exposure was probably not
affected. In this pilot study we used a convenience sample for the controls, for
several reasons. First, we wanted to find out if the menstrual cycle question-
naire, which may likely arouse shame, was a questionnaire that was fair and
well to answer. Second, could we recruit volunteers of the target age for this
survey? Further, it might be considered unwise to commit to an expensive full-
fledged study if a postulated relationship is not first observed in a convenience
sample. Nevertheless, the convenience sample data could weaken the results
of our study.
Finally, not all women still had a menstrual cycle, or regulated their cycle was
through the use of oral contraceptives. Our results may then have been influ-
enced by recall bias.
The results of the subgroup analyses show a stronger association between
CRPS1 and the menstrual syndrome for of the over-50s. This result seems
counterintuitive, since we would have expected older, post-menopausal
women not to remember their menstrual cycle pattern as well as younger
women did. We therefore expected to find a weaker association in the older
age group. Chinese medicine theory might provide an explanation. The mean
age of onset of CRPS1 in women is 46 years19. At that time of their life, wo men
are in their peri-menopausal period and have lost the positive healing effect
of new blood production and powerful blood circulation related to menstrua-
tion. This, in combination with the natural energy-loss during lifetime, makes
them more vulnerable to the development of CRPS1. However, regardless of
the difference in OR between the older and younger women, the ORs were
clinically relevant in both, although in the younger age group not statistically
significant, possibly due to the low sample size of this group. Studies with
larger samples are needed to confirm our findings for the different age groups.
The finding of a clear association between more than six positive answers in
the DRQ15 and the development of CRPS1 should be interpreted cautiously,
as the sample size was limited and therefore the CIs wide. Likewise, issues
of replication and replicability deserve attention in further prospective studies
considering CRPS1 and additional menstrual variables.
For many years, attempts have been made to merge the Western and Chi-
nese systems of medicine. However, for the merging process to have any
clinical relevance, comparisons must be based on diagnostic and/or thera-
peutic similarities rather than on semantics. If practitioners proceed care-
fully, the two systems can enrich each other22. The diagnosis of CRPS1,
which is still practice-based, could be further differentiated by using TCM
diagnostic methods.
In conclusion, in this pilot study we successfully demonstrated that defined
menstrual disorders are associated with the development of CRPS1. The
results of our study suggest a menstrual-cycle-related imbalance in the con-
stitution of women with CRPS1, notably those aged over 50. This may also
explain the predisposition of menopausal women to CRPS1.
A validation study of the usefulness of the DRQ 15 is an essential next step.
Selected menstrual disorders should be considered, and a menstrual cycle
history should be included in the evaluation of chronic CRPS1 patients. The
traditional Chinese medicine questionnaire used in this study could contrib-
ute to the early recognition and diagnosis of female CRPS1 patients.
We thank Ko Hagoort for editorial critique, and Frank J.P.M. Huygen, MD,
PhD for including patients in the Erasmus MC Pain Treatment Centre.
96
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Chapter 5
Ineke van den Berg
Lidia R. Arends
Eric A. P. Steegers
Vincent W.V. Jaddoe
M.G. Myriam Hunink
Johannes J. Duvekot
Submitted for publication
102
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To describe the natural history of singleton breech presenta-
tion in a cohort study and determine the value of ultrasound in predicting
nonvertex delivery. Ultimately this could help define the optimal time win-
dow during which effective preventive version strategies can be performed
to avoid nonvertex presentation at birth.
The study was embedded in the Generation R Study, a prospec-
tive cohort study from early fetal life onward, of 7135 singleton pregnancies.
Ultrasound at approximately 20 and 30 weeks of gestation was performed
to establish the fetal position. Odds ratios and sensitivity and specificity of
ultrasound in predicting nonvertex presentation at delivery were calculated.
Of 7135 pregnancies, 3315 (46.5%) were in a nonvertex position
at 20 weeks decreasing to 1259 (17.6%) at 30 weeks and 307 (4.3%) at
delivery. Fetal position at 20 weeks was not predictive of nonvertex pre-
sentation at birth (OR 1.1, 95% CI 0.89 to 1.41, p = 0.33). Ultrasound-
confirmed nonvertex position around 30 weeks was highly predictive of
nonvertex presentation at delivery (OR 28.45, 95% CI 20.96 to 38.62,
p<0.0001; sensitivity and specificity 83.0% and 85.3%), especially in nul-
liparous women (OR 53.97, 95% CI 36.1-80.8, p<0.0001) and preterm
deliveries (OR 47.89, 95% CI 18.28 - 125.49, p<0.0001).
Fetal ultrasound findings at 30 weeks were highly predictive,
ultrasound at 20 weeks showed no value in predicting nonvertex presenta-
tion at delivery.
The presence of an ultrasound -confirmed breech position around 30 weeks
could be used as an indication to monitor the fetal position and consider
the use of version strategies, which can be performed safely and effectively.
Keywords nonvertex, breech, fetal presentation, ultrasound, prediction,
sensitivity and specificity
Little is known about the natural behaviour of the fetus in utero, espe-
cially regarding the preferred fetal position. There are three main presenta-
tions of the fetus: cephalic (or vertex), nonvertex transverse and nonvertex
breech. In pregnancies at term a nonvertex position is seen in about 3-4%
of singleton fetuses, with a constant incidence over time 1-4.
After it was demonstrated that planned cesarean section lowered neonatal
mortality and morbidity compared with planned vaginal delivery for the
term fetus in breech position 5, cesarean section became more common
practice for term breech delivery in many countries 6. However, cesarean
section is not without direct maternal risks 7-8. Additionally, in subsequent
pregnancies, there is an increased risk of adverse events like scar dehis-
cence or uterine rupture and abnormal placentation 9-14.
Ultrasound examination during pregnancy is a useful diagnostic tool to iden-
tify fetal and placental anomalies, to follow fetal growth and to determine
fetal and placental position and is considered safe in pregnancy 15. Ultra-
sound is usually performed at different stages of gestation and provides
different levels of detail at different stages. The fetal position is routinely
determined from the first trimester onwards. An impressive cohort study,
with inclusion data between 1987-1991, examined the natural history of
fetal position throughout pregnancy using ultrasound and reported that a
nonvertex fetus at 35 weeks had a 45% chance of spontaneous version by
the time of delivery1.
During the course of pregnancy, the fetus turns more and more into vertex
position. Prior to 32 weeks of gestation, spontaneous version of the fetus
to vertex position occurs more frequently than after 32 weeks 4, 16-17. Many
possible physiologic mechanisms may lead to (persistent) breech position.
At present, several interventions are in use to promote version of the fetus
into nonvertex position in order to prevent nonvertex presentation at deliv-
ery. The major evidence-based approaches to correct nonvertex presenta-
tion before delivery are breech version acumoxa (BVA) performed between
33 and 36 weeks 12 and external cephalic version performed between 36
and 40 weeks of gestation 18. Better understanding of the natural pathway of
fetal position could give insight into the optimal timing of these interventions
in case of nonvertex position.
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Chapter 5
105
study were recruited from these 8,880 individuals (Figure 1). The inclusion
criterion was a viable singleton pregnancy at enrolment. Exclusion criteria
were the following: major fetal anomalies, gestational age > 25 weeks at
enrolment, missing data of the 20 and /or 30 weeks ultrasound, and missing
data of fetal presentation at delivery. If more than two ultrasound examina-
tions were performed we used findings from those carried out at the initially
scheduled visits of 20 and 30 weeks of gestation.
Ultrasound examinations of the fetal position were performed using an Alo-
ka® model SSD-1700 (Tokyo, Japan) or the ATL-Philips® Model HDI 5000
(Seattle, WA, USA).
n=8880
Consented to prenatal phase
Viable pregnancy at enrolment
n = 8652
Normal pregnancies
with singleton live birth
n= 228 Excluded
93 Multiple pregnancies
41 Major fetal anomalies
68 Miscarriage or perinatal death
26 Medical termination of pregnancy
n = 1517 Excluded
339 Late enrolment, gestational age > 25 weeks
1178 Missing data of 20 and /or 30 weeks ultrasound and
presentation at delivery
n = 7135
Pregnancies for analysis of natural history of singleton breech fetuses
Flow chart of inclusion of participants in the substudy of the Generation R longitudinal
cohort .
We hypothesized that an additional ultrasound around 30 weeks gestational
age predicts the probability of nonvertex presentation at delivery. This of-
fers the opportunity to monitor the fetal position and guide the use of spe-
cific prenatal care that may correct nonvertex position, provided these can
be performed safely and effectively.
The aim of our study was to describe the natural history of nonvertex pre-
sentation in a large cohort study and to determine the value of ultrasound
performed at 20 and 30 weeks of gestation in predicting nonvertex delivery.
The present study was embedded in the Generation R Study, a population-
based prospective cohort study from fetal life until young adulthood in a
multi-ethnic urban population in Rotterdam, the Netherlands. The cohort
comprises 9778 mothers and their children born between April 2002 and
January 2006 19-20.The study was approved by the Medical Ethics Com-
mittee of Erasmus University MC, Rotterdam. Written informed consent
was obtained from all participants. Data on fetal ultrasound studies were
collected prospectively. Gestational age was established based on the first
ultrasound. Pregnant women were subsequently examined twice during
pregnancy, in mid (18-24 weeks) and late (> 25 weeks) (mean 30 weeks,
range 25 – 32 weeks) gestation. The individual time schemes depended on
the specific gestational age at enrollment as described previously 21. Eighty-
eight per cent of ultrasound examinations were performed in a research
setting at a regional health facility in Rotterdam; 12% in one of five hospitals
in the vicinity under guidance of Generation R staff.
Although ECV was not protocolized in our cohort, subgroup analyses were
performed to evaluate the number of women with a fetus at 36 weeks
gestation followed in the Erasmus MC to whom the ECV was offered and
performed, including the treatment effect.
Of the 9,778 mothers participating in the Generation R Study, 91%
(n=8,880) were enrolled during pregnancy 15. Participants in the present
106
Chapter 5
107
Of the 7135 singleton pregnancies studied, 307 (4.3%) had a nonvertex pre-
sentation at delivery: 297 breech (4.2%) and 10 transverse (0.1%). Figure 2
shows the natural history in detail of the fetal presentation during pregnancy,
i.e. position at 20 weeks, 30 weeks and the presentation at delivery overall.
Of the 7135 pregnancies, 3315 (46.5%) were in a nonvertex position at 20
weeks decreasing to 1259 (17.6%) at 30 weeks and 307 (4.3%) at delivery.
The ultrasound examination of the fetal position was part of a more com-
prehensive exam in which fetal abnormalities were determined. In the
Netherlands, in low risk pregnancies, only one ultrasound is offered around
20 weeks of gestation. All sonographers were experienced and underwent
additional training according to the guidelines from the Fetal Medicine Foun-
dation to achieve optimal reproducibility 15, 20.
The presentation at birth was documented by the midwife or gynecolo-
gist who attended the delivery. For all participants it was known whether
the pregnancy resulted in live birth, miscarriage, stillbirth, neonatal death
or elective termination. Fetal position at delivery was known for 99.8% of
these pregnancies. Breech and transverse presentation were combined as
nonvertex presentation, since usually delivery will be performed by cesar-
ean section 22. In this study, deliveries were defined as preterm if they took
place after the 30 weeks ultrasound and before 37 weeks of gestation.
The primary endpoint was nonvertex presentation at delivery. In predicting
breech and transverse presentation at delivery the ultrasound findings at 20
weeks and 30 weeks were considered.
For type of presentation, we calculated odds ratios (ORs), and 95% con-
fidence intervals (CIs), as well as p values. Statistical significance was set at
a level of α = 0.05. To determine the clinical performance of both ultra-
sounds, we used five statistical assessments: pretest probability, sensitivity,
specificity, positive predictive value, and negative predictive value. Sensitiv-
ity was defined as the fraction of nonvertex presentations at delivery that
was predicted correctly by the ultrasound examination, whereas specificity
was defined as the fraction of cephalic presentations at delivery that was
predicted correctly. Positive predictive value was defined as the probability
of a non-vertex presentation at delivery conditional on a non-vertex posi-
tion on ultrasound. Negative predictive value was defined as the probability
of a vertex presentation at delivery conditional on a vertex position on ul-
trasound. Subgroup analysis was performed for nulliparous versus multipa-
rous pregnancies, and for preterm versus term deliverStatistical analysis was
performed with SPSS version 17 for Windows (SPSS Inc, Chicago, IL, USA).
OR
(95% CI)
Test probability
(%)
Sensitivity
(%)
Specificity
(%)
PPV
(%)
NPV
(%)
20 weeks of
gestation
1.12
(0.89-1.40)
2.1 49 54 5 96
-Nullipara
(n = 4015)
1.40
(1.07 -1.84)
52 57 5 96
-Multipara
(n = 3072)
0.73
(0.47 - 1.13)
42 50 4 95
30 weeks of
gestation
28.45
(20.96 - 38.62)
4.3 83 85 20 99
-Nullipara^
(n=4015)
53.9
(36.07-80.76)
87 89 27 99
-Multipara^
(n= 3072)
10.93
(6.70-17.82)
72 81 15 99
-Term delivery
≥36 weeks
(n= 6982)
27.80
(20.10-38.45)
83 85 19 99
-Preterm deliv-
ery <36 weeks
(n=153)
60.00
(15.42-233.47)
84 90 60 98
Performance values of ultrasound in predicting nonvertex position at delivery based on
nonvertex presentation at 20 or 30 weeks of gestation (n= 7135)
OR: Odds Ratio
CI: Confidence interval
Test probability : the proportion of patients with the target disorder, out of all the patients with
the symptoms(s), both those with and without the disorder: P(D+) = D+ / (D+ + D-) where
D+ indicates the number of patients with target disorder, D- indicates the number of patients
without target disorder, and P(D+) is the probability of the target disorder.
PPV: Positive Predictive Value.
NPV: Negative Predictive Value.
108
Chapter 5
109
Table 1 shows the ultrasound performance measures of all women at 20
weeks and at 30 weeks of gestation in order to predict nonvertex pre-
sentation at birth. In the same table, the results of subgroup analyses are
presented performed on the ultrasound performance measures at 20 and
30 weeks of gestation overall and in the subgroups of nulliparae and mul-
tiparae. Parity was known in 7087 (99.3%) of pregnancies. Of all cephalic
presentations at delivery (n=6828), 5824 (85.3%) already had a cephalic
position at 30 weeks of gestation (Table 2). Of all nonvertex presentations
at delivery (n=307), 255 (83.1%) already had a nonvertex position at 30
weeks of gestation (Table 2).
There were differences between nulliparous (n=4015) and multiparous
pregnancies (n=3072): 4.8% (n= 195) of the nulliparae vs. 2.0% (n=
60) of the multiparae had a nonvertex presentation both at 30 weeks of
gestation and at delivery, whereas 0.7% (n= 29) vs. 0.8%. (n=23) had a
cephalic presentation at 30 weeks of gestation and delivered in nonvertex
presentation. Of the nulliparae, 10.5% (n=420) had a nonvertex position
at 30 weeks of gestation versus 18.8% (n=576) of the multiparae, and had
turned to cephalic presentation before delivery.
The natural history in detail of the fetal presentation during pregnancy,
i.e. position at 20 weeks, 30 weeks and the presentation at delivery overall.
Presentation
Fetus
20
US
30
US Birth
All (100%)
n =7135
Nulliparae
n= 4015*
Multiparae
n=3072*
Term delivery n=6982 (97.9%)
>= 36 weeks
Preterm delivery n=153 (2.1%)
< 36 weeks
N N N 128 (1.8%) 101 (2.5%) 27 (0.9%) 117 (1.7%) 11 (7.2%)
C N N 127 (1.8%) 94 (2.3%) 33 (1.1%) 120 (1.7%) 7 (4.2%)
N C N 23 (0.3%) 15 (0.4%) 8 (0.3%) 23 (0.3%) 0 (0%)
C C N 29 (0.4%) 14 (0.3%) 15 (0.5%) 26 (0.4%) 3 (2.0%)
N N C 530 (7.4%) 211 (5.3%) 316 (10.3%) 526 (7.5%) 4 (2.6%)
C N C 474 (6.6%) 209 (5.2%) 260 (8.5%) 466 (6.7%) 8 (5.2%)
N C C 2634 (36.9%) 1432 (35.7%) 1179 (38.4%) 2578 (36.9%) 56 (36.6%)
C C C 3190 (44.7%) 1939 (48.3%) 1234 (40.2%) 3126 (44.8%) 64 (41.8%)
Total % 100% 100% 100% 100% 100%
Combinations of presentation during the natural pathway of the singleton pregnancies.
*48 missings (0.7%) in parity
US = ultrasound
US 20= US around 20 weeks gestation
US 30= US around 30 weeks gestation
C=Cephalic presentation
N= Nonvertex, thus breech and transverse presentation
110
Chapter 5
111
Of all included pregnancies (n=7135), 6982 (97.9%) delivered at term and
153 (2.1%) at < 36 weeks of gestation. Table 1 also shows the ultrasound
performance measures at 30 weeks of gestation for nonvertex presentation
at delivery subdivided for preterm and term delivery, with the highest odds
ratio for preterm delivery. (OR 60.00, 95%CI 15.42-233.47).
Using the ultrasound performance measures at 20 weeks of gestation com-
pared with the ultrasound performance measures at 30 weeks of gestation,
the percentage of missed nonvertex presentations (proportion false nega-
tives, 1-sensitivity) was 51% versus 17% with a corresponding probability
of a nonvertex presentation at delivery following a negative ultrasound of
4% versus 1%. The post-positive-test probability of nonvertex at delivery
is 5% versus 20%. The p-values of all ultrasound performance measures at
30 weeks of gestation were highly significant, i.e. smaller than 0.0001 for all
calculated odd ratios (Table 1), whereas the p-values of the measures at 20
weeks were not significant.
Subgroup analysis showed that, of the 1259 nonvertex fetuses at 30 weeks,
256 were observed in the Erasmus University Medical Center. Only 16 of
these women were offered an ECV at 36 weeks of gestation, and one re-
sulted in cephalic presentation at term.
In contrast with figure 2, figure 3a, b, c and table 2 presents individualized
details on the various combinations of position during pregnancy, i.e. posi-
tion at 20 weeks, 30 weeks and the presentation at delivery. During preg-
nancy, the fetal position of 3318 (46.5%) fetuses did not change, whereas
128 (1.8%) already had a nonvertex presentation at 20 and 30 weeks of
gestation. The latter number is 41.7% of all neonates born in nonvertex
presentation. However, of all nonvertex positioned fetuses at 20 weeks
(n=3315) only 3.9% was nonvertex at birth.
This study evaluated the fetal position determined by ultrasound through-
out pregnancy and the prevalence and the course of the nonvertex position
in the Generation R study. We found that determination of the fetal position
by ultrasound at 20 weeks of gestation does not predict fetal presentation at
delivery. However, the examination at 30 weeks of gestation has substan-
Individualized details
on the various
combinations of position
during pregnancy, i.e.
position at 20 weeks,
30 weeks and the
presentation at delivery.
a) all study participants.
b) nullipareous women.
c) multipareous women.
A
B
C
112
Chapter 5
113
tial ability to predict nonvertex presentation at delivery, and may have an
impact on prenatal decision making. We found clear statistically significant
differences between nulliparae and multiparae with regard to the individual
presentations during pregnancy.
Since a nonvertex position on the 30 weeks ultrasound is highly predictive
of fetal presentation at delivery, it appears valuable as the initiating mo-
ment for interventions that elicit version of the nonvertex fetus and prevent
nonvertex presentation at delivery, notably moxibustion, external cephalic
version (ECV), hypnosis, or other complementary and additive therapies 23.
The most frequent physiological fetal movement during pregnancy is from
nonvertex into vertex presentation 24. Few studies have been performed
to evaluate the value of ultrasound performed during pregnancy to predict
nonvertex presentation at delivery 1, and most studies were retrospective,
and /or dated 25-26 or assessed after 28th 27 or 31st week of gestation 28. It is
suggested that spontaneous version is completed by the 37th week of preg-
nancy: no further spontaneous movement is likely to occur after this time
because of the size of the fetus in relation to the size of the uterus 25, 29-30.
Others are of the opinion that spontaneous version of a nonvertex position
at 35 weeks of gestation is still likely 1.
One of the areas of research in the Generation R study is designed to iden-
tify early developmental problems in the child. Although the prevalence of
nonvertex at delivery is low, pregnancies involving nonvertex presentations
and nonvertex deliveries have a higher incidence of complications than
pregnancies with vertex presentations 6, 31. Some intrinsic factors that may
be responsible for nonvertex presentation at delivery, such as placental,
uterine or fetal anomalies 32, can be identified with the additional ultrasound
at 30 weeks 1, 15. Decision criteria for implementing an extra ultrasound
as a screening test for every pregnant woman at 30 weeks gestation, per-
formed by experienced sonographers, should include test accuracy, cost of
screening, and the prevalence and natural history of the disease. Test accu-
racy (sensitivity, negative predictive value, specificity, and positive predictive
value) was demonstrated by our findings (Table 1 and 2).
Reducing nonvertex presentation in the population leads to fewer cesar-
ean sections and fewer complications in both the mother and the new-
born. Previously we modeled costs and benefits of moxibustion treatment
in women with ultrasound-confirmed nonvertex presentation. It appeared
that if 16% or more women offered Moxa complied, it was more effective
and less costly than expectant management of the nonvertex presentation
33. Additionally, both the American College of Obstetricians and Gynecolo-
gists (ACOG) and the British Royal College of Obstetricians and Gynecolo-
gists (RCOG) recommend that all women with an expected uncomplicated
nonvertex pregnancy at term should be offered ECV 34-35. This procedure is
successful in 50 to 60% of cases and is usually performed by a gynecologist
as of 36 weeks gestation 36-37. On the other hand, ECV may have serious
complications, such as perinatal death and need for emergency cesarean
delivery. 30, 38-40. Also, a spontaneous reversion rate of 3% has been re-
ported. In addition, ECVs generate costs. Not all women will accept ECV
treatment: reported rates of maternal refusal of ECV range from 18 to 76%
41. Conversely, proportions of women potentially suitable for ECV who
were not offered treatment range from 4 to 33%. 42-43. Interestingly, during
the study period, ECV was not routinely in use in the Netherlands. Unfor-
tunately, data on ECV were not uniformly recorded in this study and there-
fore, possible undertaken ECV’s were not known for the whole population.
Our subgroup analysis showed that during the study period, ECV was not
offered as widely as advised and not really successful in a university teaching
hospital. Therefore, we concluded that in our cohort ECV was only rarely
offered and infrequently successful. Inclusion of the ECVs, however, might
well have given greater weight to the argument made.
We have shown the highly predictive value of ultrasound findings at 30
weeks of gestation for predicting the presentation at delivery. Further in-
vestigation into the risk factors and potential mechanisms of nonvertex pre-
sentation is indicated. We recommend close monitoring of women with
known or suspected risk factors for a persistent nonvertex presentation.
Moreover, investigators should explore the possibilities of external cephalic
version and acupuncture-type interventions in order to avoid a nonvertex
presentation at term 33.
Early recognition of atypical presentation could lead to a new strategy for
preventive measures in mothers at high risk for nonvertex delivery, and
possible extra care and follow up of the fetus. Especially in developing coun-
tries, where the number of children per mother is high and the public
health system is more precarious, these relatively inexpensive and safe in-
terventions could support maternal and child care.
Further research should focus on preventive strategies for known predic-
tors for nonvertex presentation at delivery, so as to ensure a good start of
114
Chapter 5
115
the newborn’s life and good health for the mother. In this way, fetal and
maternal morbidity and mortality could be reduced.
In the Generation R study, the 20 weeks fetal ultrasound findings showed
no predictive value for nonvertex presentation at delivery. The ultrasound
at 30 weeks of gestation, however, was highly predictive of nonvertex pre-
sentation at delivery. The presence of an ultrasound-confirmed breech po-
sition of the fetus around 30 weeks of gestation could be used as an indica-
tion to monitor the fetal position and consider the use of version strategies
provided these can be performed safely and effectively. Further research is
needed to evaluate the effectiveness of these additional preventive thera-
pies.
The authors thank Ko Hagoort and members of the ART group for their
helpful comments on the text.
The Generation R Study is conducted by the Erasmus Medical Center in
close collaboration with the School of Law and Faculty of Social Sciences
of the Erasmus University Rotterdam, the Municipal Health Service Rot-
terdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam
and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR),
Rotterdam. We gratefully acknowledge the contribution of general practi-
tioners, hospitals, midwives and pharmacies in Rotterdam. The first phase
of the Generation R Study is made possible by financial support from the
Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam
and the Netherlands Organization for Health Research and Development
(ZonMw). Vincent Jaddoe, received an additional grant from the Nether-
lands Organization for Health Research and Development (ZonMw, Grant
No. 2100.0074).
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38. Grootscholten K, Kok M, Oei SG, Mol BW, van der Post JA. External cephalic version-
related risks: a meta-analysis. Obstet Gynecol. Nov 2008;112(5):1143-1151.
39. Collins S, Ellaway P, Harrington D, Pandit M, Impey LW. The complications of external
cephalic version: results from 805 consecutive attempts. Bjog. May 2007;114(5):636-
638.
40. Hutton EK, Hofmeyr GJ. External cephalic version for breech presentation before term.
Cochrane Database Syst Rev. 2006(1):CD000084.
41. Rijnders M, Offerhaus P, van Dommelen P, Wiegers T, Buitendijk S. Prevalence, outcome,
and women’s experiences of external cephalic version in a low-risk population. Birth
(Berkeley, Calif. Jun 2010;37(2):124-133.
42. Raynes-Greenow CH, Roberts CL, Barratt A, Brodrick B, Peat B. Pregnant women’s
preferences and knowledge of term breech management, in an Australian setting.
Midwifery. Jun 2004;20(2):181-187.
43. Yogev Y, Horowitz E, Ben-Haroush A, Chen R, Kaplan B. Changing attitudes toward
mode of delivery and external cephalic version in breech presentations. Int J Gynaecol
Obstet 2002;79:221-224
Chapter 6
Ineke van den Berg
Johanna L. Bosch
Ben Jacobs
Irene Bouman
Johannes J. Duvekot
M.G. Myriam Hunink
Complementary Therapies in Medicine, 2008 Apr;16(2):92-100.
120
Chapter 6
121
A systematic review of studies assessing the effectiveness of
acupuncture-type interventions (moxibustion, acupuncture, or electro-
acupuncture) on acupuncture point BL 67 to correct breech presentation
compared to expectant management, based on controlled trials.
Articles published from 1980 to May 2007 in databases
of Medline, EMBASE, the Cochrane Central Register of Controlled Trials,
AMED, NCCAM, Midirs and reference lists.
Studies included were original articles; randomised
controlled trials (RCT) or controlled cohort studies; acupuncture-type in-
tervention on BL 67 compared with expectant management; ultrasound
confirmed breech presentation and position of the fetus after treatment
confirmed with ultrasound, position at delivery, and/or the proportion of
caesarean sections reported.
Three reviewers independently extracted data. Dis-
agreements were resolved by consensus.
Of 65 retrieved citations, six RCT’s and three cohort
studies fulfilled the inclusion criteria. Data were pooled using random-ef-
fects models. In the RCT’s the pooled proportion of breech presentations
was 34% (95% CI: 20-49%) following treatment versus 66% (95% CI:
55-77%) in the control group (OR 0.25 95% CI: 0.11-0.58). The pooled
proportion in the cohort studies was 15% (95% CI: 1-28%) versus 36%
(95% CI: 14-58%), (OR 0.29, 95% CI: 0.19-0.43). Including all studies the
pooled proportion was 28% (95% CI: 16-40%) versus 56% (95% CI: 43-
70%) (OR 0.27, 95% CI: 0.15-0.46).
Our results suggest that acupuncture-type interventions on
BL 67 are effective in correcting breech presentation compared to expec-
tant management. Some studies were of inferior quality to others and fur-
ther RCT’s of improved quality are necessary to adequately answer the
research question.
In pregnancies at term, 3-4% of singleton fetuses present by the breech1,2.
Since the results of the Term Breech Trial in 2000 demonstrated a reduction
in infant mortality and morbidity with planned caesarean sections compared
with planned vaginal delivery in fetuses in breech presentation, caesarean
sections have become common practice in many Western Countries for
term breech deliveries3-9. An increase in caesarean sections for breech po-
sition, however, has distinct disadvantages including an increased risk of
maternal urinary tract infection, haemorrhage, wound infection, and scar
dehiscence or uterine rupture during subsequent labour and higher costs10.
Another, non-invasive, method to correct breech presentation comes from
traditional Chinese medicine (TCM), which involves the activation of acu-
puncture-point Zhiyin, Bladder 67 (BL 67)11-13; BL 67 is located beside the
outer proximal corner of the toenail of the fifth toe (Fig. 1). In 1984, a con-
trolled cohort trial of the Cooperative Research Group in China, reported
that the proportion of cephalic presentations following treatment was 81%
in the intervention group (n = 241) versus 49% in the control group (n
= 264)14. Since this Chinese study, various studies have been performed,
u sing acupuncturepoint-moxibustion, acupuncture, or electro-acupuncture,
to correct breech presentation. In correcting breech position, acupuncture
on point BL 67 is sometimes used in conjunction with heat through moxi-
bustion, or electric stimulation15-17.
Moxibustion is the burning of a roll of specially prepared herbs containing
Artemisia vulgaris or other Artemisia species (‘mugwort’; the Japanese name
for it is moxa) to stimulate acupuncture points without needling18,19. The
temperature intensity of the moxibustion is just below the individual toler-
ability threshold, causing hyperaemia from local vasodilatation.
The purpose of this study was to perform a systematic review of reported
studies to evaluate the effectiveness of acupuncture-type interventions on
BL 67 (moxibustion, acupuncture, and electro-acupuncture) compared to
expectant management to correct breech presentation.
122
Chapter 6
123
A literature search was performed in Medline (Pub Med), EMBASE, Cochrane
Central Register of Controlled trials, AMED (Allied and Complementary Me-
dicine), NCCAM (The National Centre for Complementary and Alternative
Medicine), and Midirs (Midwifery Information Service)20. The reference lists of
the literature found were searched for more articles. We contacted the origi-
nal authors for further information if necessary. Key words for the search were
“moxibustion AND breech”, “acupuncture AND breech”, “pregnancy AND
moxibustion”. Articles were not masked for language, author or journal.21-23
A study was included if the following criteria were met: (a) it was an original
article; (b) published from 1980 to May 2007; (c) presenting results of an
RCT or a cohort study including a control group; (d) of a traditional Chinese
medicine acupuncture-type intervention of acupuncture point BL 67 in which
(e) breech presentation was confirmed with ultrasound and (f) the authors
reported one of the following outcome measures: position of the fetus after
treatment confirmed with ultrasound, position of the baby at delivery, and/
or number (and percentage) of caesarean sections. A study was excluded if
sample size was not reported.
Three authors (IvdB, BJ, and IB) independently selected and reviewed the
articles and evaluated all reports for inclusion and exclusion criteria. Next,
the same reviewers independently extracted the data concerning study de-
sign, patient characteristics, intervention, and outcomes. Disagreements
were resolved by consensus.
The primary outcome of our analysis was the proportion of breech pre-
sentations following the period of the acupuncture-type intervention. In
addition, we assessed and explored each relevant methodological aspect
individually.24 We also analysed possible treatment side effects.
To detect the presence of publication bias, we constructed a funnel plot in
which we plotted the sample size of the study population as a function of
the natural logarithm of the odds of a fetus in breech presentation25.
The results within the intervention group and the expectant management
group were tested for heterogeneity using the χ²-test (p = 0.05) and the
Higgins I2 test26. Randomeffects models take into account the variation with-
in a study, but also variation between the various studies. Using random-
effects models, we pooled the proportion breech presentations following
the treatment-period of the intervention groups and of the expectant ma-
nagement groups27.
Furthermore, we calculated the pooled OR with the 95% CI of breech pre-
sentations following the period of treatment of the intervention groups and
of the expectant management groups28. The data of the RCT’s and the ob-
servational cohorts with a control group were pooled separately and jointly.
All analyses were performed in SAS (Proc Mixed for Windows 8.2 1999-
2001, SAS Institute Inc., Cary, NC, USA) and Excel (Microsoft Windows
Excel 2000 professional, Microsoft Corporation, Phoenix USA), using the
formulas described by Laird and Mosteller27.
Moxibustion of ZhiYin, Bladder 67.
124
Chapter 6
125
Our search identified 65 studies, of which we excluded 15 on the basis of
the abstract and 43 studies on the basis of the full text (Fig. 2). In total seven
articles met the inclusion criteria and were included in our study (Table 1).
Six RCT’s were described in five articles15,17,29-31, that is, one paper repor ted
on two RCT’s17. In two articles the results of three cohort stu dies with con-
trol groups were described16,32, that is, one article reported on two patient
cohorts16. The research findings from studies reported in the same source,
applied the treatments in different randomly selected group of subjects and
therefore we believe the independent assumption is reasonable16,17.
To detect publication
bias, we constructed
funnel plots (Fig. 3).
The data points for
the included studies
are symmetrically dis-
tributed in an inverted
funnel shape suggest-
ing the absence of
publication bias.
The characteristics of
the included studies
are shown in Table 1 a
and b. Six of the nine
studies used moxibus-
tion,15-17,29,30,32 among which one study performed combined moxibustion
with needling15. One study used acupuncture31, and two studies electro-
acupuncture stimulation of BL 6716,17. RCT’s were computer randomised
and written informed consent was obtained in all studies. In one study the
evaluator was blinded to the participant’s group allocation29.
5 Articles
including 6 RCT’s
2 Articles including
3 cohorts with controls
Overall analysis using 9 trials from 7 studies
Excluded on titles and abstracts
15 Study lectures
7 Articles TCM intervention BL 67
Excluded 43 articles
2 Subject not Bl 67
4 Other disorder
9 Working Moxa / acupuncture
6 Study Design: Review
4 Study Design: Case Report
5 Other control group
3 Breech presentation not confirmed US
3 Comments on Article
6 Other reason (available from author)
1 Overlapping patient population
50 Full-text Articles
obtained
65 Total of citations retrieved
51 Identified by Library search
14 Identified in Reference Lists
Flowchart of the reviewed literature. From the initial search, a total of 65 abstracts
were retrieved.
Funnelplot
0
50
100
150
200
250
300
350
400
450
-4 -3 -2 -1 0 1
LN Odds Ratio
Sample size
Cohort
RCT
Funnel plot. The funnel plot shows the number
of patients included in the study versus the natural logarithm
of the odds ratio of breech presentation after treatment.
The data points are symmetrically distributed in an inverted
funnel shape indicating that the presence of publication bias is
unlikely.
Flowchart of the reviewed literature. From the initial search, a total of 65 abstracts were
retrieved. Of these 65 abstracts, 15 were study lectures12,13,34,46 —57 . Of the remaining 50
abstracts, the full papers were retrieved and evaluated for the additional selection criteria. The
following articles were excluded: in two studies the intervention was not performed on BL
6758,59; in four studies no acupuncture-type intervention was used for other disorders60— 63; nine
articles were about the mechanism of Moxa18,19,33,36,64 —68; six articles were reviews43,69—73; four
articles were case reports51,74—76; two articles were cohort studies with controls retrospectively
assessed from the Chinese literature77,78; three articles had no comparable control group.79—81
In three studies the breech presentation was not confirmed with US.11,14,82 Three were opinion
papers83 —85 and six articles were excluded
for other reasons.7,13,86— 89 Two articles reported on overlapping patient populations of which we
included only the most recent study32,38.
126
Chapter 6
127
Demographics of the studies included in the analysis
RCT
Cardini, F64 2005 Italy Caucasian 65 31 58 31 14+? ‡
Neri, I. 12 2004 Italy Caucasian 112 30.1 (3.6) 114 31.7 (14.7) 8+6
Habek, D. 66 2003 Croatia Caucasian 34 22 (3.1) 33 23 (1.3) n/r
Cardini, F.65 1998 China Chinese 130 25.2 130 25.5 9+0
Li, Qinghua 14 1996 China Chinese 32 22-36 31 22-36 n/r
Li, Qinghua14 1996 China Chinese 48 22-36 31 22-36 n/r
Total 421 397
Cohort with control group
Kanakura, Y.13 2001 Japan Japanese 133 28.4 224 n/r n/r
Kanakura, Y. 13 2001 Japan Japanese 191 n/r 217 n/r n/r
Cardini, F. 63 1993 Italy Chinese 23 20-37 18 22-31 n/r
Total 347 459
Overall 768 856
Study,
First author
Mean Gestational age
at inclusion (weeks) Intervention Group Treatment time per point
(min)
Treatment frequency
(per day)
Treatment period
(weeks) Controls
RCT
Cardini F.64 33 Moxa 15 1 1-2 EM
Neri, I.12 33.7 a Acupuncture +Moxa 10 2c 1-2 EM
Habek, D.66 34 Acupuncture 30 1 1-3 EM
Cardini, F.65 33 Moxa 15 1-2 1-2 EM
Li, Qinghua 14 28* Moxa 20 n/r 1-6 c EM
Li, Qinghua 14 28* Electro-acupuncture 30 n/r 1-6 c EM
Cohort with control group
Kanakura, Y.13 28 * Moxa d 5 1 until correction EM
Kanakura, Y.13 28 * Electro-acupuncture 5 n/r n/r EM
Cardini, F.63 33 Moxa 15 1 5-40 days EM Æ
TCM-type interventions on BL 67
‡ 22 % of Italian participants temporarily or definitively interrupted the treatment because of uncomfortableness due to Moxa
n/r not reported
EP Expectant Policy
n/r Not reported
a SD 0.7
* Minimal gestational age
b Per week
c Sessions
d BL 67 used in combination with 5 other acupuncture points
Æ Retrospective controls
128
Chapter 6
129
Heterogeneity was found between all the studies (χ² = 9.3 (p-value =
0.001); the estimated natural logarithm of the odds ration (ln OR) and the
approximate 95% confidence intervals (CI) varied between the nine studies
(Fig. 4). The Higgins I2 value (=96.2%) is close to 100% implies that there
is high heterogeneity across the studies. Therefore, we use a random-ef-
fects approach to take into account this variability26. The random-effects
model was used to pool the outcomes27.
No significant harmful ef-
fects of moxibustion on
women or their infants
were reported during or
immediately after per-
forming the treatment;
that is, no signs of fetal
distress, preterm uterine
contractions or maternal
cardiovascular changes oc-
curred33. In the two RCT’s
of Cardini, however,
cases of preterm prema-
ture rupture of the mem-
brane (PPROM) were re-
ported in the intervention
groups29,30. In the Italian
study, two cases of pre-
term deliveries were de-
scribed, one certain, due
to PPROM, one suspect-
ed which occurred at 34
weeks of gestation, and no
PPROM was recorded in
the control group29. After
delivery of the described
cases by caesarean section, there were no consequences for the neonates
described. In the Chinese study, no adverse events occurred during treat-
ment. Preterm rupture of the membrane (PROM) occurred in three cases
at 37 weeks gestation, which was at least 2 weeks after completion of treat-
ment30.
In some studies withdrawal from the study was reported29,30,34. The main
reported reasons were the aggravation of respiratory symptoms and un-
comfortableness on exposure to the moxa smoke. Other reasons were
uterine contractility, mild hypertension, and reluctance to comply29,30,34.
Eight of the nine studies demonstrated that treatment on BL 67 was effec-
tive in correcting breech presentation whereas in one study poor compli-
ance of the clients led to interruption of the study and no effect could be
demonstrated29 (Table 2). In the pooled RCT’s, 421 women were included
in the intervention group and 397 women in the expectant management
(control) group (Table 2). The pooled RCT’s demonstrated a significant
effect of the intervention: the proportion of breech presentations in the
intervention group was 34% versus 66% in the control group (OR 0.25,
95% CI: 0.11-0.58) (Table 2, Fig. 4).
In the pooled controlled cohort series, the proportion of breech presen-
tations in the intervention group was 15% (n = 347) versus 36% in the
control group (n = 459) (OR 0.29, 95% CI: 0.19-0.43) (Table 2, Fig. 4).
Combining all studies, the proportion of breech presentations in the inter-
vention group was 28% (n = 768) versus 56% in the control group (n =
856) (OR 0.27, 95% CI: 0.15-0.46) (Table 2, Fig. 4).
In this systematic review, we found a beneficial effect of acupuncture-type
interventions stimulating BL 67 to induce a version to cephalic presenta-
tion compared to expectant management. Whereas the effect was more
pronounced absolutely in the RCT’s, the effect was more pronounced in a
relative sense in the cohort studies. In the cohort series, the percentage of
breech presentations was halved with intervention, but this was not statisti-
cally significant, which may have been due to the limited sample size. The
pooled result of the RCT’s and that of all studies combined demonstrated a
Odds ratio’s (log scale) and 95% confidence
intervals of breech presentations. Odds ratio’s (log scale)
and 95% confidence intervals of breech presentations
following the period of treatment of the intervention
groups and of the expectative policy groups for
acupuncture-type intervention for individual studies and
the pooled results. N = total of subjects. The plot shows
substantial heterogeneity in the estimated effects among
the studies.
130
Chapter 6
131
clinically and statistically significant reduction in breech presentations.
As a rule, cohort series generally demonstrate a larger effect than RCT’s
and are more likely to reach statistical significance. In contrast, we found
that the pooled RCT’s demonstrated a larger absolute effect than the co-
hort studies and the effect was significant in the pooled RCT’s whereas
in the pooled cohort studies it was not. A possible explanation for these
findings is that the gestational age at the time of inclusion in two cohort
studies was lower than in the RCT’s16. Prior to 32 weeks gestational age,
spontaneous version occurs more often than after 32 weeks (11.5% versus
6.3% to a nadir of 1.7% after 40 weeks)1,13,32. This will have an effect in
both the intervention group and the expectant management group resulting
in lower proportions of breech presentation and a smaller absolute effect of
the intervention in the cohort studies compared to the RCT’s. It has been
suggested that also patient age and condition, female babies, fetal motor
activity and room temperature during treatment could play a role in the ef-
fectiveness of acupuncture-type interventions on correcting breech presen-
tations14,35. Overall there are few well designed studies exploring the role of
these covariates in relation to different treatment designs. The decision was
made not to conduct a meta-analysis including these covariates due to the
significant differences in the intervention type. Further studies are necessary
to establish the related results.
The mechanism of stimulation of BL 67 has, in part, been scientifically in-
vestigated. One study of the morphological basis and relationship between
BL 67 and the viscera showed that seven segments (L2-S1) of the uterus
and the sensory innervation of BL 67 overlap36. Other authors suggested
that the stimulation of BL 67 increases cortico-adrenal secretion, placental
estrogens, and changes in prostaglandin levels, leading to raised basal tone of
the uterus and enhanced movement of the fetus, thus making version more
likely11,16,33,37-40. The explanation that version of the fetus would be purely
based on a reflex action of moxibustion mediated by a dermatome must be
rejected, because stimulation of BL 67 performed in cases of intrauterine
fetal death failed to produce version38. According to the acupuncture point
of view, one of the functions of BL 67 is to stimulate the activity of the fetus,
which may be an important mechanism to induce spontaneous version. Fur-
thermore, it seems likely that the technique may be more successful in com-
plete breech presentation than in frank or footling breech presentation29,41.
In this systematic review data from nine studies were extracted, reviewed,
Cardini, F.64 65 43 66.2 58 37 63.8 1.09
Neri, I. 12 112 52 46.4 114 71 62.3 0.52
Habek, D. 66 34 8 23.6 33 18 54.6 0.26
Cardini, F. 65 130 32 24.4 130 68 52.3 0.29
Li, Qinghua 14 32 8 25.0 31 26 83.9 0.06
Li, Qinghua 14 48 9 18.7 31 26 83.9 0.04
0.25
(0.11, 0.58)
Kanakura, Y. 13 133 10 7.5 224 59 26.3 0.23
Kanakura, Y. 13 191 21 10.5 217 57 26.1 0.33
Cardini, F. 63 23 7 30.4 18 11 61.1 0.28
0.29
(0.19, 0.43)
0.27
(0.15, 0.46)
Outcomes of the individual studies and pooled outcomes
132
Chapter 6
133
compared, and pooled odds ratios were reported. Many systematic re-
views only consider randomised controlled trials (RCT’s), which are gene-
rally considered the state-of-the-art study design for evaluation of interven-
tions. Linde, however, suggested that non-randomised studies might also
be useful in a systematic review to get a more comprehensive overview of
current practice and to inform future research42. Therefore, in our litera-
ture search, we also considered non-randomised studies.
A limitation of our systematic review, as with other reviews, was that the
possibility of publication bias cannot be ruled out, even though our funnel
plot did not demonstrated the presence of publication bias. We searched
different sources to identify all RCT’s and cohort studies with controls of
TCM interventions on BL 67 for correction of breech presentation, but
were not able to retrieve any unpublished studies. Although the use of acu-
puncture is widespread in China and Russia, our literature search retrieved
only four eligible trials from China and none from Russia. Databases only
partially cover literature from these countries and it is possible that uniden-
tified eligible trials from these countries exist.
Another limitation of our study was that the sample sizes of RCTs included
were relatively small and details of the study design and certain outcomes
were sometimes not reported. For example, in three RCT’s, the caesarean
section rate was described15,30,31. Some consider caesarean section as an
important outcome of the treatment effect. However it should be noted
that the number of caesarean sections performed is not only determined by
the effect of treatment but also by other factors such as many other medical
indications as well as the women’s own preferences. In the included studies
elective caesarean deliveries for breech presentations were not studied.
Furthermore, among the included studies, a variety of acupuncture-type
interventions (moxibustion, moxibustion combined with acupuncture, acu-
puncture alone, and electro-acupuncture) and protocols were used. Al-
though of the included studies the most commonly used method was moxi-
bustion, with a protocol of once a day for 15-20 min for as long as 1-2
weeks. The effect of these different interventions is unknown and beyond
the scope of the current review. A Cochrane review on this topic, however,
also concluded that there was no consensus in the literature with respect
to the best regimen43.
In contrast to our study, the Cochrane review focused on the treatment of
Bl 67 with acumoxa only and concluded that moxibustion may help to cor-
rect breech presentation but that the number of studies was too small to
demonstrate effectiveness with statistical significance.
Other limitations of our study are the poorly defined and reported charac-
teristics of the women and fetuses, and outcomes of treatment in the origi-
nal studies after treatment and at term and restricted our ability to adjust for
differences in case mix and outcome measures (Table 1).
With the available data it was impossible to find a significant relation be-
tween acupuncture-type interventions of BL 67 and preterm birth due to
PPROM. To assess the frequency of the possible relation, further studies
are required.
Nevertheless, not only the method of stimulation and different protocols,
but also ethnic, cultural and educational differences could account for the
different results reported in the different studies.
Another limitation is that we could not adjust for parity because parity was
often not reported, two studies were performed with only primigravid
women29,30. Among the included studies that considered parity, only one
study demonstrated a significant difference between primi- and multipa-
rae15. The success rate of version to cephalic presentation may be related
to the fact that the uterus of a multipara already reached the maximum
length and so there is more room for version of the fetus. From the 37th
week, spontaneously movement into cephalic presentation is not longer
likely to occur, in either primiparae or multiparae44. In one study, parity
was even found to be the only significant factor in predicting the success of
external cephalic version45.
Finally, the primary outcome measures of interest in RCTs that evaluate acu-
puncture-type interventions for correction of breech presentation would
have been fetal presentation at the time of delivery, preferably adjusted for
covariates. Secondary outcome measures of interest would be mode of
delivery and neonatal outcome, including safety, morbidity and mortality.
Relevant covariates would be parity, type of breech presentation, active-
fetal-movements, location of the placenta, the amount of amniotic fluid,
educational level, culturally defined expectations of therapy, previous cae-
sarean sections, reason for performing previous caesarean section, and the
women’s viewpoint with respect to vaginal versus caesarean delivery.
134
Chapter 6
135
In addition, the ideal study design may be placebocontrolled RCT, but due
to the relative contraindication to the use of moxibustion during pregnancy
in other locations than BL 67 it is not feasible to use a placebo moxa treat-
ment. Besides that, a placebo intervention would quickly be identifiable as
placebo by the patient and her partner through the informed consent pro-
cedure and through information about moxibustion on the Internet.
Based on the results of our study, the effect of using acupuncture-type
interventions on BL 67 to correct breech presentation seems promising.
Our results, however, are influenced by the variety of the included stud-
ies. Therefore, before making this adjuvant treatment to standard Western
healthcare, we recommend to conduct a largescale RCT in which moxibus-
tion is compared to expectant management. We recommend moxibustion,
as this method is inexpensive, readily available, safe, client-friendly, and can
be performed at home by the partner of the pregnant woman. In addition,
more characteristics of the participants, such as parity, fetal position, both
after treatment and at time of delivery, maternal and fetal complications, in-
formation of external cephalic version and its outcome, and the number of
caesarean sections with the reasons for performing them, should be moni-
tored. Also, womens preferences, the acceptance of the smell and warmth
of the moxibustion treatment, quality of life of the women, and healthcare
and non-healthcare costs should be assessed.
Our systematic review of the current literature shows a beneficial effect
of using acupuncture-type interventions on BL 67 to induce correction of
a breech presentation compared to expectant management. Our results,
however, are influenced by the existing differences in design of the current
studies and further RCT’s of improved quality are necessary to adequately
answer this question.
We have no conflict of interest to declare. All authors and researchers in-
volved state to be independent from the funding organisation (NVA). The
authors’ work was independent of the funding organisation. The funding
organisation had no involvement in the study design, data collection and
analysis, writing of the manuscript, or in the decision to submit this article
for publication.
Authorship contribution: The authors assure that all authors included in this
paper fulfil the criteria of authorship and that there is no one else who fulfils
the criteria but who has not been included as an author. Guarantor: The
corresponding author, Ineke van den Berg, states to accept full responsibi-
lity for the work and conduct of the study, to have had full access to the data
and to have controlled the decision to publish.
The authors thank members of the ART group for their assistance in the
data analyses and their helpful comments on the text. We also thank the
Dutch Association for Acupuncture (N.V.A.) who, in part, supported this
study.
136
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With great interest we read the article by Vas et al.1 This systematic review
and meta-analysis exhaustively discusses 7 studies comparing moxibustion
and other methods for correction of nonvertex presentation. The major
conclusion is that with regard to the correction of nonvertex presentation,
there is a beneficial effect of moxibustion applied at the acupuncture point
BL 67.
However, this study has some limitations. The studies included in the re-
view use a variety of control groups. The treatment in some of the control
groups is only observational, so women in these groups get no treatment
at all,2-4 while women in other control groups get interventions such as
postural inducement of version5-7 and acupuncture on BL 67.8 Besides, the
treatment groups in the studies included in the review also use a variety of
treatments. Some of the treatment groups only get moxibustion,2,4,7,8 while
other treatment groups get acupuncture3 or knee-to-chest posture next to
moxibustion.5,6
It would have been more justified if the 2 studies with observational control
groups vs moxibustion alone in the treatment groups were separated from
the other studies. From these other studies, it would be justified to separate
the studies in which moxibustion plus knee-to-chest posture is compared
to only knee-to-chest posture. In this way, the results of the moxibustion
treatment would have been more interpretable for clinical use.
In March 2008, we published a systematic review of studies assessing the
effectiveness of acupuncture-type interventions (moxibustion, acupuncture,
or electro-acupuncture) on acupuncture point BL 67 to correct breech pre-
sentation compared to expectant management, based on controlled trials.9
Several of the 9 studies reviewed overlap with those reviewed by Vas et al.1
Unfortunately, Vas et al1 were obviously unable to make a comparison with
our review. By design we included only studies that used a control group
without any intervention. We concluded that the current literature shows a
beneficial effect of using acupuncture-type interventions on BL 67, including
moxibustion, to induce correction of a breech presentation compared to
expectant management.
Ineke van den Berg, MSc Departments of Epidemiology and Radiology Eras-
mus University Medical Center PO Box 2040 3000 CA Rotterdam, The
Netherlands ineke.vandenberg@erasmusmc.nl
Lidia R. Arends, PhD Department of Biostatistcs Erasmus University Medi-
cal Center Rotterdam, The Netherlands
Johannes J. Duvekot, MD, PhD
Department of Obstetrics and Gynecology Erasmus Medical Center
Academic Hospital Rotterdam
Rotterdam, The Netherlands
1. Vas J, Aranda JM, Nishishinya B, et al. Correction of nonvertex presentation with
moxibustion: a systematic review and metaanalysis. Am J Obstet Gynecol 2009;201:241-
59.
2. Cardini F, Weixin H. Moxibustion for correction of breech presentation: a randomized
controlled trial. JAMA 1998;280:1580-4.
3. Neri I, Airola G, Contu G, Allais G, Facchinetti F, Benedetto C. Acupuncture plus
moxibustion to resolve breech presentation: a randomized controlled study. J Matern
Fetal Neonatal Med 2004;15:247-52. 4.
4. Cardini F, Lombardo P, Regalia AL, et al. A randomised controlled trial of moxibustion
for breech presentation. BJOG 2005;112:743-7.
5. Lin YP, Zhang DQ, Hao YQ, Duan XW. Combination of moxibustion at point Zhiyin and
knee-chest position for correction of breech presentation in 63 cases. Zhongguo Zhen
Jiu 2002;22:811-2.
6. Yang FQ. The comparison of knee chest position coordinated with moxibustion on
Zhiyin with knee chest position alone for correcting breech presentation. Sichuan
Zhong Yi 2006;24:106-7.
7. Chen ?. Moxibustion on zhiyin acupoint for treatment of 80 cases with fetal malposition.
Shaanxi Zhong Yi 2007;28:334-5.
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145
8. Neri I, De Pace V, Venturini P, Facchinetti F. Effects of three different stimulations
(acupuncture, moxibustion, acupuncture plus moxibustion) of BL.67 acupoint at small
toe on fetal behaviour of breech presentation. American Journal of Chinese Medicine
2007;35:27-33. 9. van den Berg I, Bosch JL, Jacobs B, Bouman I, Duvekot JJ, Hunink
MG. Effectiveness of acupuncture-type interventions versus expectant management to
correct breech presentation: a systematic review. Complement Ther Med 2008;16:92-
100.
Chapter 7
Ineke van den Berg
Guido C. Kaandorp
Johanna L. Bosch
Johannes J. Duvekot
Lidia R. Arends
M.G. Myriam Hunink
Complementary Therapies in Medicine, 2010 Apr;18(2):67-77.
148
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149
To assess, using a modelling approach, the effectiveness and
costs of breech version with acupuncture-type interventions on BL67 (BVA-
T), including moxibustion, compared to expectant management for women
with a foetal breech presentation at 33 weeks gestation.
A decision tree was developed to predict the number of caesarean
sections prevented by BVA-T compared to expectant management to rectify
breech presentation. The model accounted for external cephalic versions
(ECV), treatment compliance, and costs for 10,000 simulated breech pre-
sentations at 33 weeks gestational age. Event rates were taken from Dutch
population data and the international literature, and the relative effective-
ness of BVAT was based on a specific meta-analysis. Sensitivity analyses
were conducted to evaluate the robustness of the results.
We calculated percentages of breech pre-
sentations at term, caesarean sections, and costs from the third-party payer
perspective. Odds ratios (OR) and cost differences of BVA-T versus expec-
tant management were calculated. (Probabilistic) sensitivity analysis and ex-
pected value of perfect information analysis were performed.
The simulated outcomes demonstrated 32% breech presenta-
tions after BVA-T versus 53% with expectant management (OR 0.61, 95%
CI 0.43, 0.83). The percentage caesarean section was 37% after BVA-T
versus 50% with expectant management (OR 0.73, 95% CI 0.59, 0.88).
The mean cost-savings per woman was € 451 (95% CI € 109, € 775; p =
0.005) using Moxibustion. Sensitivity analysis showed that if 16% or more
of women offered moxibustion complied, it was more effective and less
costly than expectant management. To prevent one caesarean section, 7
women had to use BVA-T. The expected value of perfect information from
further research was € 0.32 per woman.
The results suggest that offering BVA-T to women with a breech
foetus at 33 weeks gestation reduces the number of breech presentations at
term, thus reducing the number of caesarean sections, and is cost-effective
compared to expectant management, including external cephalic version.
In pregnancies at term, about 3-5% of singleton foetuses present in breech
position1. Caesarean section has become common practice for term breech
deliveries in many Western countries2-6, but is not without disadvantages.
Apart from the 1.29 relative risk (95% CI 1.03-1.61) of immediate severe
maternal morbidity2,7, there is the risk of adverse effects on subsequent preg-
nancies4,8-11. Potential complications include deep-vein thrombosis, pulmonary
thrombo-embolism, need for transfusion, puerperal infection, postpartum
hemorrhage, neonatal respiratory distress, maternal urinary tract infection,
wound infection, and scar dehiscence or uterine rupture during subsequent
labor. Moreover, a higher number of caesarean sections could entail higher
societal costs. Therefore, viewed from various perspectives, it would seem
important to find ways to correct breech presentation before delivery.
One option is a procedure called external cephalic version (ECV), re-
commended by the American College of Obstetricians and Gynaecologists
(ACOG) and the British Royal College of Obstetricians and Gynaecologists
(RCOG)12,13. This procedure is successful in 50 to 60% of cases and is usu-
ally performed by a gynaecologist starting at 36 weeks gestation14,15. On
the other hand, serious complications, such as perinatal death, need for
emergency caesarean deliveries and a spontaneous reversion rate of 3%
have been reported15-19. In addition, ECVs generate costs.
Another, non-invasive, method to correct breech presentation comes from
traditional Chinese medicine. Named Breech Version Acumoxa, the moxi-
bustion of acupuncturepoint Zhiyin, Bladder 67 (BL67, located beside the
outer proximal corner of the toenail of the fifth toe), was first reported
in 1980 as a safe and non-invasive way to correct breech presentation20.
Since this Chinese study, various controlled studies in other countries have
evaluated the merits of breech version by acupuncture-type interventions
on BL 67 (BVA-T) including acupuncture-point-moxibustion, acupuncture,
or electro-acupuncture21-26. Moxibustion is the burning of a roll of herbs
(Artemisia Vulgaris = Moxa) to stimulate acupuncture points without needle
insertion. The sticks are readily available, safe and user-friendly and can be
applied by anyone following skilled instruction27-29.
A systematic review and meta-analysis of studies reporting the results of
randomized controlled trials (RCTs) on acupuncture-type interventions on
BL 67 versus expectant management showed that the pooled proportion of
150
Chapter 7
151
breech presentations was 34% (95% CI: 20-49%) in the treatment group
versus 66% (95% CI: 55-77%) in the control group30. In this meta-analysis,
three of the six studies used moxibustion, the other three used acupunc-
ture, electro-acupuncture, and a mixture of moxibustion and acupuncture
on BL 67.
In general, there is growing willingness of hospital departments and pa-
tients to adopt complementary care, provided it is safe31-33. More specifi-
cally in obstetrics, health-care providers are recognizing the favourable eco-
nomic impact of low-cost, complementary therapies34. However, to decide
whether BVA-T should be offered alongside the standard care of expectant
management to correct breech presentation policymakers need more de-
tailed information.
Our aim was to generate information by a decision-analytic approach about
the projected effectiveness and costs of BVA-T compared with expected
management including associated procedures such as external cephalic ver-
sion, in order to reverse breech presentation after the 33rd-week gestation
and reduce the number of caesarean sections at term.
A decision tree was constructed to assess the effectiveness and costs of two
strategies – “BVA-T” and “expectant management” (EM) - to facilitate spon-
taneous cephalic version of a foetus in breech position at 33 weeks gesta-
tion35,36 (Fig. 1). Box 1 explains the terminology related to decision models
in general. Outcome measures for effectiveness were percentage of breech
presentations at term/delivery and percentage of caesarean sections. Costs
were defined as third-party payer costs.
The model started at 33 weeks gestation and followed the time path until
1 week after delivery. At the starting point, breech presentation had been
confirmed with ultrasonograph (US). In both strategies, a second US was
performed at 36 weeks gestation. The model took into account events such
as refusing BVA-T, lack of compliance to BVA-T, and spontaneous version.
Both strategies included the option to have an ECV performed by a gynae-
cologist from 36 weeks gestation. Furthermore, in both strategies all births
took place in hospital, assisted by a midwife or gynaecologist depending on
the mother’s and foetus’s health status. BVAT implied two instructional vis-
its to an acupuncturist at 33 and 34 weeks gestation, with daily treatments
performed at home, applied by the partner, during the intervening week.
EM implied that the midwife would be in a "wait and see mode" until 36
weeks gestation. The model was consistent with the recommendation of
the Dutch obstetric organization that healthy pregnant women are cared
Decision tree for the decision of whether to add BVA-T to rectify breech presentation
in generally healthy 33 weeks pregnant women with a breech baby. This decision model was
also developed to predict the number of caesarean sections prevented by comparing BVA-T with
expectant management (EM) to rectify breech presentation, including treatment compliance, and
costs and associated event as external cephalic version (ECV). Shown is the generic framework
of the model. The square node at the far left symbolizes the choice between BVA-T and EM.
The tree is fully displayed only for the EM arm, but the BVA-T arm has the same detail. Generally
healthy 33 weeks pregnant women with a breech baby cycle through the tree and are at risk for
breech presentation at term and the risk of caesarean section at delivery. The square indicates the
choice between BVA-T and EM, circles represent potential chance consequences, and triangles
signify six different outcomes. The decision tree included five clones, after which it followed the
branch indicated with C1 till C5. The numbers between brackets indicate the variables with their
probabilities (Table 1).
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Chapter 7
153
for by well-trained midwives whereas women with maternal and/or foetal
complications are referred to a gynaecologist. Breech presentation at 36
weeks gestation is a reason for referral, in which case responsibility of care
shifts to the gynaecologist. The decision model was constructed in TreeAge
Pro 2006 (release 1.2, TreeAge Software, Inc. Williamstown, USA).
Box 2 explains the terminology related to effectiveness. Table 1 lists the
mean probabilities, 95% confidence intervals, and distributions of the vari-
(1) Acceptance Moxa Cardini F., et al. 0.84 (0.77,0.89) Beta(123, 24)
(2) Stay breech between week 33-36 SC van den Berg I., et al.* 0.66 (0.54,0.77) Beta(45.38, 23.48)
(3) Stay breech between week 33-36 Moxa van den Berg I., et al. *0.34 (0.21,0.5) Beta(13.73, 26.22)
(4) Stay breech between week 36-+ SC Hofmeyr G.J., et al. Θ0.80 (0.74,0.85) Beta(175, 44)
(5) RR stay breech between week 36-+ Moxa Hofmeyr G.J., et al. † 0.38 (0.18,0.8) Log-Normal(-1.31, 0.83)
(6) Spontaneous breech at term Janssen P.A., et al. ‡0.01 (0.00,0.02) Beta(7, 855)
(7) Vaginal breech delivery Rietberg C.C.Th., et al. ‡0.20 (0.19,0.21) Beta(2835, 11423)
(8) Cephalic delivery by midwife (hospital) Janssen P.A., et al. 0.57 (0.54,0.59) Beta(743, 571)
(9) Emergency cephalic caesarean by midwife (hospital) Janssen P.A., et al. 0.18 (0.15,0.21) Beta(135, 608)
(10) Emergency cephalic caesarean by gynecologist Janssen P.A., et al. 0.12 (0.09,0.15) Beta(68, 503)
(11) Emergency cephalic caesarean by midwife (home) Janssen P.A., et al. 0.06 (0.05,0.08) Beta(55, 807)
(12) Maternal factors and the probability of a planned home birth Anthony S., et al. §1/3 home births
Overview of all variables included in the model with their references.
The numbers before the variables correspond with the numbers after the chance nodes in Figure 1.
* Pooled result of RCT’s
Θ Cochrane Database Systematic Review
§ Only used in sensitivity analysis for homebirth in the Netherlands
‡ Confirmed by data from the Dutch Perinatal Database
is a mathematical approach to making decisions
based on weighing risks and benefits in an explicit quantitative manner.
are visual representations of decision analytical models
which depict all possible choices or strategies (at the ,
depicted with a square), the consequences of these choices (at
, depicted with circles), and the outcomes of these consequences
(at the , depicted with triangles or rectangles).
is an assessment of both the costs and ef-
fectiveness associated with different management strategies for a health-
care problem.
is the viewpoint taken in performing the analysis which can
be the patient, the physician, the department, the hospital, the third-
party payer, the health-care system, or society.
are the input parameters in the model that together deter-
mine the optimal decision, e.g. effectiveness of treatment, costs of treat-
ment.
Explanation of terminology related to decision models in general
154
Chapter 7
155
ables entered into the model. The data were retrieved from a PubMed
literature search restricted to English-language reports, and confirmed by
data from the Dutch Perinatal Database and from expert opinions. The
probabilities of included events and interventions were based on clinical
practice in maternal and neonatal maternity care in the Netherlands4,37-43.
The probability that a woman would accept BVA-T and the probability of
persistent breech presentation between weeks 33 and 36 following BVA-T
or EM (Table 1) were retrieved from a systematic review and meta-analy-
sis30.
Box 3 explains the terminology related to costs. Table 2 shows details of the
cost items. Costs were assessed according to Dutch guidelines and from a
third-party payer perspective. All costs related to the diagnosis and treat-
ments of breech presentation were included44-46. In addition, both strategies
included the costs of prenatal and postnatal care for 8 days after delivery,
care provided by midwives and auxiliary maternity care.
Direct costs were assessed for BVA-T, ECV, caesarean section, breech vagi-
nal birth, cephalic vaginal birth (gynaecologist) and cephalic vaginal birth
(midwife).
In-hospital costs were retrieved from Diagnosis-Treatment-Combinations
(DTCs) and from the financial department of the Bronovo Hospital in the
Hague, which is a regional hospital, the type of institution where babies
in the Netherlands are usually delivered. DTCs come with fixed prices
for treatment of patients with specific diagnoses and cover the complete
process from the first specialist consultation to the final outpatient visit47.
The DTCs applicable here do not differentiate between the different types
of caesarean sections, but rather give weighted averages. Out-of-hospital
costs were retrieved from the Dutch Association of Acupuncture (NVA),
the Royal Dutch Organization of Midwives (KNOV), and “Maatzorg Preg-
nancy and Baby Care’’ - an organization specialized in postnatal care at
home. Indirect costs and costs of subsequent pregnancies were not taken
into account. Costs are reported in 2006 Euros.
is the expected benefit of a treatment.
The is a measure of association of exposure and out-
come (event) and equals the odds of risk in the exposed group divided by
the odds of risk in the control group. The OR equals the cross product in
a 2x2 table of exposure vs outcome. In the context of treatment the OR
is a measure of the effectiveness of the treatment and equals the odds
of the risk of the outcome in the treated group divided by the odds of
the risk of the outcome in the control group. An OR<1 indicates an ef-
fective treatment, OR=1 an ineffective treatment, and OR>1 a harmful
treatment.
The is a measure of association of exposure
and outcome (event) and equals the risk in the exposed group minus the
risk in the control group. In the context of treatment the RD is a measure
of the effectiveness of the treatment and equals the risk of the outcome
in the treated group minus the risk of the outcome in the control group.
A RD<0 indicates an effective treatment, RD=0 an ineffective treat-
ment, and RD>0 a harmful treatment.
The is the number of patients
that need to be treated to avoid one event in a defined time period and is
the inverse of the absolute risk reduction. In formula form: NNT = - 1/R
Explanation of terminology related to effectiveness
costs are costs associated with medical
procedures, hospital admissions, outpatient visits, medication, therapeu-
tic interventions, patient care, and overhead.
are costs for the building and administration.
are future costs and costs induced by
the chosen strategy.
Explanation of terminology related to costs
156
Chapter 7
157
Box 4 explains the terminology related to decision models in general. Two
main analyses were performed, namely without (0%) and with (100%) im-
plementation of ECV. We calculated proportions of breech presentations at
term and caesarean sections, and third-party payer costs for each strategy.
€
Interventions Moxa Office visit acupuncturist, Moxa sticks and echo by midwife NVA, KNOV,
NatuurApotheek®
158.50
ECV Admission, honorarium gynecologist DTC 885.45
Prenatal Gynecologist DTC 518.26
Midwife KNOV 343.00
Delivery Caesarean section Hospital, salaries gynecologist, pediatrician and an-
esthesiologist, admission and overhead costs,
incl. stay mother and child in hospital *
DTC + overhead
regional hospital
5,075.67
Assisted breech vaginal birth Hospital, salaries gynecologist, pediatrician and anes-
thesiologist, admission, nurse and overhead costs
DTC + overhead
regional hospital
1,916.49
Assisted cephalic vaginal
birth (gynecologist)
Hospital, salaries gynecologist and anesthesiolo-
gist, admission, nurse and overhead costs
DTC + overhead
regional hospital
1,827.93
Assisted cephalic vagi-
nal birth (midwife)
hospital, salaries midwife, admis-
sion, nurse and overhead costs
DTC 721.50
Postnatal Caesarean Midwife/gynecologist, maternity nursing (to add with *) DTC/ KNOV,
www.progeria.nl
637.20
Vaginal birth Midwife, maternity nursing (8 days at home) KNOV, www.
progeria.nl
1,564.70
The included costs per procedure in the decision tree.
A is a strategy that is less expensive and more
effective than the alternative strategy and is thus superior to the alter-
native. If dominance exists, the cost-effectiveness ratio is meaningless.
The is the incremental
cost divided by the gain in effectiveness compared to the next best
strategy and should be calculated in the setting of non-dominance to
determine whether more money is justified by the gain in effect.
is a ‘’what-if’’ analysis. By varying the value of
variables in the decision model we can explore the effect on the out-
come and evaluate whether alternative assumptions would change the
decision.
In all variable values are mod-
elled with distributions instead of deterministic values. Variable values
are picked at random from the distributions for each variable and the
outcomes are calculated. This is repeated multiple (e.g. 10,000) times
which yields distributions of the outcomes and from which we can de-
termine the probability that one strategy is preferred over another.
determines the potential benefit
of further research.
is the ex-
pected incremental benefit of the optimal strategy based on accurate
estimates of all the variables should these become available through
further research compared to the benefit of the optimal strategy based
on current information.
Explanation of terminology related to analyzing decision models
158
Chapter 7
159
Next, we calculated the odds ratios (OR) of BVAT versus EM for the pro-
portion of breech presentation and caesarean sections and we calculated
the difference in third-party payer costs between the strategies.
We took the inverse of the absolute risk difference (RD) to calculate the
number of women - needed-to-treat with BVA-T to prevent one caesarean
section.
Our initial analyses were based on 100% hospital births, which were as-
sisted by a gynaecologist or midwife. Cultural differences in birth settings,
however, do exist. For example, in the Netherlands, many home-births
take place and midwives provide basic care to pregnant women and serve
as an arbitrator for the admission of more complex pregnancies to gynaeco-
logists48. To specifically
evaluate the effect of
these cultural differ-
ences, we performed
sensitivity analyses in
which we extended
our original decision
tree and added the
proportions of home-
births (i.e., 33.3%)
versus hospital-births
(66.7%) (Fig. 2).
In our initial analyses,
breech presentation
at 33 weeks gestation
was always confirmed
by US. In practice, however, this is not always done. In additional sensitivity
analyses, therefore, we adopted a 20 to 100% range of confirmed breech
presentations rather than 100%. In addition, the acceptance rate of BVA-T
was varied from 0 to 100% to demonstrate the impact on total costs.
All probabilities were modelled with beta or lognormal distributions (Table
1). Probabilistic sensitivity analysis, using 10,000 second-order Monte Car-
lo simulations, was performed and provided the 95% confidence intervals
around the estimates. In addition, this analysis provided the probability that
EM rather than BVA-T would be the optimal strategy.
Value of information analysis was performed to determine the potential
benefit of further research. We calculated the expected value of perfect
information (EVPI), which is the expected incremental benefit of the optimal
strategy based on exact accurate estimates of all the variables compared to
the benefit of the optimal strategy based on current information. Since ob-
taining exact accurate estimates of parameter values is impossible (it needs
a study with an infinite sample size evaluating all parameters), EVPI is the
upper limit of the expected benefit of further research49-51.
Table 3 shows the main simulated outcomes of the initial analyses. Without
the option of ECV at 36 weeks gestation, the proportion of breech presen-
tation at term after BVA-T was 32%; that after EM 53%. The corresponding
figures for the analysis in which ECV was performed were 12% and 19%.
Without the option of ECV, the proportion of caesarean sections after BVA-
T was 37%; that after EM 50%. The corresponding figures for the analysis
in which ECV was performed were 23% and 28%, respectively. To prevent
one caesarean section, seven women with a foetus in breech presentation
at 33 weeks gestation would need to be treated with BVA-T.
Substantial differences in costs were observed between vaginal births and
caesarean births.
In both analyses, the mean direct costs for BVA-T were somewhat lower
than those for EM. The difference mainly resulted from the lower propor-
tion of caesarean births associated with the BVA-T-strategy.
Extension of the decision tree in which home-births
were included. The numbers between brackets indicate the
probabilities corresponding with Table 1.
160
Chapter 7
161
Sensitivity analyses were performed to evaluate the effect of the probability
of a planned home birth and by varying the input parameters over the ac-
ceptance rate of BVA-T. Sensitivity analyses, in which 33.3% of all hospital
births were altered to home-births and care given by the midwife, demon-
strated similar percentages of breech presentations compared to the main
analyses and a decrease in the percentages of caesarean sections and a
decrease in total costs (both with and without ECV). The percentage caesa-
rean section was 35% after BVA-T versus 49% after EM without the option
Analysis- No ECV performed Mean (%) OR (95% CI) Probability SC
preferred
Number to treat
to prevent one
Caesarean
Moxa 36.6 0.73 (0.59, 0.88) 0.0008 7.3
Standard Care 50.3
Analysis- ECV performed
Moxa 23.1 0.83 (0.67, 0.98) 0.001 21.0
Standard Care 27.8
Simulated outcomes (mean of 10,000 subjects) of BVA-T and expectant management
strategies for women at 33 weeks gestation with a foetus in breech presentation.
Analysis- No ECV performed Mean (€) Cost Difference
(95% CI)
Probability SC
preferred
Moxa 4595 451 (109,775) 0.0052
Standard Care 5046
Analysis- ECV performed
Moxa 4523 404 (72,864) 0.0073
Standard Care 4927
Analysis- No ECV performed Mean (%) OR (95% CI) Probability SC preferred
Moxa 32.0 0.61 (0.43, 0.83) 0.0008
Standard Care 52.9
Analysis- ECV performed
Moxa 11.6 0.62 (0.45, 0.84) 0.001
Standard Care 18.8
4400
4500
4600
4700
4800
4900
5000
5100
5200
5300
0% 20% 40% 60% 80% 100%
Perce ntage w ome n w ho a ccept Moxa
Expected Costs
Expectant
Management
Moxa if 100% breech
presentation US
confimed
Moxa if 50% breech
presentation US
confimed
Moxa if 20% breech
presentation US
confimed
Two-way sensitivity analysis in which the percentage of women who accept
BVA-T and the percentage of breech presentations that were confirmed by ultrasound (US)
were varied. The different discontinuous lines show the impact of these variables on the total
costs of BVA-T. There is no influence of change in these variables on the total costs of expectant
management. (a) Shows the strategies without ECV. The intersections of BVA-T with expectant
management are at 16.0, 21.4 and 37.7%. (b) The strategies with ECV. The intersections of
BVA-T with expectant management are at 17.6, 23.6 and 41.5%.
Moxa = Breech version by Acumoxa
SC = Standard Care
ECV = External Cephalic Version
CS = Caesarean Section
162
Chapter 7
163
of ECV (OR 0.71, 95% CI 0.56, 0.88); whereas this was 20% versus 25%
respectively, if ECV was performed (OR 0.80, 95% CI, 0.64, 0.97).
The mean direct costs were € 4369 after BVA-T versus € 4890 after EM
without ECV (cost difference € 520; 95% CI, € 135, € 883); whereas this
was € 4230 versus € 4658, if ECV was performed (cost difference € 428,
95% CI € 79, € 941).
The results of sensitivity analyses performed on the percentage US-con-
firmed breech presentations at 33 weeks and the acceptance rate of BVA-
T on the expected total costs are demonstrated in Fig. 3a and b, for the
strategies without and with ECV respectively. If 100% of breech presenta-
tions are US-confirmed and the BVA-T compliance rate is 16.0% or more
without ECV, or 17.6% or more with ECV, BVA-T was less costly than EM. If
20% of breech presentations are USconfirmed, the BVA-T strategy was less
costly compared with EM at a BVA-T compliance rate of 37.7% and 41.5%
for the strategy without and with ECV, respectively.
In all scenarios and for all outcomes the probability that EM was preferred
(i.e. the probability that BVA-T would not be favourable compared to EM)
was less than 1% (Table 3). Assuming BVA-T was implemented instead of
EM, the EVPI without and with ECV was € 0.32 and € 0.37 per woman,
respectively.
This modelling exercise aimed at evaluating the effectiveness and costs of
BVA-T compared with EM for women with a foetus in breech position at 33
weeks gestation. Our analyses are consistent with a significant decrease in
breech presentation after treatment with BVA-T, both with and without the
option of ECV, when compared with EM. Consequently, BVA-T is associated
with significantly fewer caesarean sections and therefore notably decreases
the third-party payer costs. Although additional costs were attributed to
BVA-T, its effectiveness corresponded with lower total costs. The results
were robust in sensitivity analyses in which we varied the percentage of
breech presentations confirmed by US and the BVA-T compliance rate, and
considered the Dutch situation in which 33% of births take place at home.
In the Netherlands, midwifery-led care is only permitted when the foetus
is in cephalic presentation. Our analysis showed that with BVA-T, without
ECV, there is a 21% decrease in foetuses in breech presentation at term.
These mothers with foetuses in cephalic presentation at 36-week gesta-
tion stay with or may return to midwifery-led care. Some authors showed
that midwifery-led care does not lead to higher maternal or neonatal risk
associated with planned home birth52,53. In addition, the value of informa-
tion analysis showed that, compared to implementing BVA-T based on the
currently available evidence, perfect information on the probabilities in the
model obtained from further effectiveness and cost research would result in
a minimal gain in expected benefit. We showed in our model with 10,000
second-order Monte Carlo simulations, that if BVA-T was implemented in-
stead of EM, with the currently available evidence, the low EVPI makes
further research of the cost effect of implementing BVA-T unnecessary.
Nevertheless, we do recommend performing a well-designed RCT in a
Western setting, with special attention to the safety of the Moxa technique,
in line with an ongoing study in Spain54. To our knowledge, no other study
has evaluated both the effectiveness and costs of BVA-T compared with EM.
The results of this study, however, could guide informed decision making on
the implementation of BVA-T for women with a diagnosed foetus in breech
presentation after 33 weeks of gestation.
Some limitations of our study and the intervention itself should be men-
tioned. For one, the effectiveness data in the model had been retrieved
from a meta-analysis of six RCTs in which we demonstrated positive effects
of acupuncturetype interventions on BL 67, where moxibustion was used
in four of the six RCT’s30. Since heterogeneity was found between these
studies, the random-effects model of DerSimonian and Laird55 was used to
pool the outcomes, thereby allowing heterogeneity in the true treatment
effects. The random-effects model takes into account the variability across
the studies and results in wider confidence intervals than does the fixed-
effects model, which ignores the between-study heterogeneity. Part of the
heterogeneity might perhaps be explained by specific study characteristics
such as patients’ mean age or ethnicity. In a meta-regression the study char-
acteristics are put as covariates in a regression analysis with the estimated
treatment effect of the study as dependent variable. Ideally, these covariates
164
Chapter 7
165
should be specified in advance to reduce the risk of post hoc conclusions
prompted by inspecting the available data56.
Especially when the number of studies is small, any covariate of which the
value differs between the studies will be significantly related to the hetero-
geneity among the studies, and hence is a potential explanation of it. It is
clear, however, that most of such `explanations’ will be entirely spurious57.
In this regard, Lee concluded that none of the results of our meta-analysis
of the six RCTs, according to ethnicity or the type of intervention, avoided
heterogeneity58. However, as pointed out above, almost every study char-
acteristic would be related to the heterogeneity between the studies and
could therefore easily be based on spurious relationships. Also because
the covariates proposed by Lee were not specified in advance, we think
his conclusion should be interpreted with caution. However, we agree
with Lee58 that it would be interesting to explore the heterogeneity across
studies as soon as a sufficient number of studies is available for a meta-
regression. Furthermore, Vas et al. published a systematic review, which
included Chinese studies59. In their analyses they evaluated in the pooled
result two different treatments in the control group: expectant manage-
ment and knee-to-chest-posture versus the combined effects of moxibus-
tion with or without another technique. These results should be viewed
with caution, and therefore, in this modelling exercise, we still stand for the
use of the parameter-distribution of van den Berg et al, where the controls
were treated with expectant management.
A second limitation of our analysis is that the follow up period was limited
to 8 days postpartum and our study focused on the direct results of BVA-
T on delivery mode. Therefore, indirect costs as well as effects and costs
of subsequent pregnancies were not taken into account. Their inclusion,
however, might well have given greater weight to the argument made60-63.
Third, costs of BVA-T may have been overestimated in our analysis, as these
costs included two visits to a licensed acupuncturist and two confirmative
US examinations. Costs could be reduced through the use of low-cost "self-
explanatory home Moxa kits" which can be ordered through the Internet.
However, as breech position may be associated with congenital malforma-
tions, placenta praevia, and malformations of the uterus, we recommend
that pregnant women undergo an US before she and her foetus are ex-
posed to Moxa64,65.
Finally, the working mechanism of moxibustion is not completely known.
A systematic Cochrane review concludes that there is no consensus in the
literature with respect to the best regimen27 suggesting that the working
mechanism remains unknown. The effect of moxibustion on version might
be due to the odour, the temperature, or even the specific acupuncture
location28,66-69. From the acupunctural point of view, BL 67 stimulates the
activity of the foetus, which may be an important mechanism to induce
spontaneous version. Moreover, it seems likely that the technique may be
more successful in complete breech presentations than in frank or footling
breech15,21,70 suggesting that the foetus itself plays a role in inducing version.
Further research on the specific working mechanism and side-effects of
Moxa is therefore needed.
Thought provoking is the possible beneficial effect of BVA-T in low-income
countries and in rural areas far removed from medical centres. Women
in these settings are less likely to undergo ECV or a caesarean section for
breech presentation. The non-invasive and non-pharmaceutical BVA-T
could therefore reduce infant and maternal morbidity, mortality, and medi-
cal costs in countries where poverty is an obstacle to obtaining medical
care75.
The results of this decision analysis suggested that for the rectification of
a foetus in breech presentation in women at 33 weeks gestation, BVA-T
reduced the number of breech presentations at term, the number of cae-
sarean sections, and was less costly when compared to expectant manage-
ment, including ECV.
No competing financial interests exist. This work was partly supported by
the Dutch Association for Acupuncture (N.V.A.). All authors and research-
ers involved state to be independent from the funding organization (NVA).
166
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167
The authors’ work was independent of the funding organization. The fund-
ing organization had no involvement in the study design, data collection and
analysis, writing of the manuscript, or in the decision to submit this article
for publication.
The authors thank Leslee Deacon, Ko Hagoort and members of the ART
group for their helpful comments on the text, and thank the Dutch Associa-
tion for Acupuncture (N.V.A.) which for financial support.
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Chapter 8
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Chapter 8 Summary
175
To provide more evidence-based results of traditional Chinese Medicine
(TCM) applied to Western medicine, we studied TCM in integrated health-
care. The studies in this thesis represent a range of scientific approaches
to elucidate possible beneficial effects of acupuncture and moxibustion, as
rooted in traditional Chinese medicine. Three fields of TCM were studied
in different epidemiological ways.
First, Health related quality of life (HRQoL) was studied in a general prac-
tice for acupuncture. Although the number of patients using acupuncture in
Western countries is growing, particularly among women, and musculosk-
eletal complaints are common in acupuncture practice, little is known about
the quality of life of these patients. In the first part of this thesis, we studied
the quality of life in a cohort of patients seeking treatment for musculoske-
letal complaints at a general practice for acupuncture.
Second, we investigated a chronic, complex, painful and inflammatory di-
sease, Complex regional pain syndrome (CRPS1). The chronicity of this di-
sease combined with its complexity suggests that a holistic and personalized
approach could be beneficial. More and more patients with CRPS, who do
not respond well to any experimental pharmaceutical treatment regimen,
turn to complementary methods that may relieve the pain, activate the
diminished nutritive blood flow and help them to overcome movement
anxiety and disuse or even emotional amputation of the affected limb.
Third, we considered breech presentation, for which an acupuncture-like
treatment can be performed without needles and using a single prescribed
point. Interestingly, the treatment can be provided by the woman’s partner,
so that no therapeutic relationship with the TCM practitioner is needed.
In breech presentation the baby enters the birth canal with the buttocks
or feet first as opposed to the normal head-first position. In many coun-
tries, caesarean section is the most common way to deliver a breech baby
but, like any major surgery, caesarean section involves risks for mother and
child, and for subsequent pregnancies.
To start with, presents an observational study on the effect of acu-
puncture on health-related quality of life in patients with musculoskeletal com-
plaints. Quality of life was reported by the patients themselves in a validated
questionnaire. For the group as a whole quality of life clearly improved over the
course of treatment. Pre-treatment values on three domains – notably reflecting
symptomatology – were lower than values for the Dutch population, but the
post-treatment scores on these domains were even higher than the popula-
tion values. The observed improvements suggest a subjective, clinically relevant,
benefit of acupuncture therapy in treating musculoskeletal complaints.
, is a review of the literature on the attributive effect of acu-
puncture in inflammatory diseases. At the time of the study, 2003, a number
of observations on the anti-inflammatory actions of acupuncture had been
published, representing open studies and randomized trials. In asthma, acu-
puncture was most effective after an initial quick succession of treatments.
In rhinitis, results that were mainly obtained from open trials suggest a com-
plementary effect of acupuncture after allergen provocation. In inflamma-
tory bowel disease and rheumatoid arthritis, the usefulness of acupuncture
still had to be demonstrated in large randomized trials. In epicondylitis and
complex regional pain syndrome type 1 (CRPS1), the immunosuppressive
effect of acupuncture had not yet been properly investigated, and was only
described in the classical Chinese textbooks. In these conditions, however,
acupuncture had resulted in pain relief. As a possible mechanism underlying
the observed effect we proposed that acupuncture releases the vasodilator
neuropeptide CGRP from nerve endings. In this respect, acupuncture as a
maintenance treatment could be beneficial to reduce inflammation.
presents a case-control study investigating whether a spe-
cified menstrual condition described in TCM as related to CRPS1, could
be associated with the risk of developing CRPS1. Women suffering from
CRPS1 and a random selection of other women completed in this pilot
study a questionnaire on menstrual cycle symptoms. Statistical analysis of
the answers revealed that the women with CRSP1 were over five times
more likely to have had specified menstrual disorders than the controls.
The results suggest that specific menstrual disorders are associated with the
development of CRPS1. The TCM questionnaire used in this study could
contribute to the early recognition and diagnosis of female CRPS1 patients.
The third part, chapters 5, 6, and 7, is about nonvertex presentation during
pregnancy and birth and additional therapies offered by a TCM practitioner
during pregnancy to induce ‘spontanious’ version of the nonvertex fetus.
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Chapter 8 Summary
177
In we described the natural history of singleton breech pre-
sentation in a large cohort study and determined the prognostic value of
ultrasound performed at 20 and 30 weeks of gestation in predicting non-
vertex delivery. Ultrasound-confirmed nonvertex position around 30 weeks
of gestation was highly predictive of nonvertex presentation at delivery,
especially in nulliparous women and preterm deliveries. Ultimately, the
presence of an ultrasound-confirmed breech position of the fetus around 30
weeks of gestation could be used as an indication to closely follow the fetal
position and consider the use of version strategies, provided these can be
performed safely and effectively, to avoid nonvertex presentation at birth.
is a systematic review including a meta-analysis of the litera-
ture. We sought to shed light on the question whether moxibustion, acu-
puncture, or electro-acupuncture stimulating a specific point on the small
toe could correct breech presentation of the fetus with a sustained effect
until delivery. On the basis of pooled results from six randomized controlled
trials and three cohort studies we conclude that these acupuncture-type
interventions resulted in more corrected breech presentations than wait-
and-see management and a reduced number of caesarian sections. The
results held for the subset of randomized controlled trials as well as for all
studies combined. In a ‘letter to the editor’ we pointed out some diffe-
rences in our study with a comparable review from another group (Ad-
dendum chapter 6).
Finally, in we evaluated the cost-effectiveness of breech ver-
sion by the above-mentioned acupuncture-type intervention for pregnant
women with a breech fetus at 33 weeks of gestation. We did so by applying
a modeling approach that compared this strategy with standard care in the
Netherlands, with or without an external cephalic version at 36 weeks of
gestation. At 36 weeks of gestation, when the fetus is still in nonvertex posi-
tion, external cephalic version is offered. Since one third of women in the
Netherlands prefer a planned home birth, we performed sensitivity analy-
ses to account for the consequences of a fetal breech presentation during
planned home births. Outcome measurements were the delivery mode
and the costs. Indeed, the modeling approach showed that acupuncture-
type interventions are both less costly and more effective than expectant
management with or without external cephalic version.
In this thesis, we focused mainly on when, why and how to implement
Traditional Chinese Medicine (TCM) into a healthcare concept in the Ne-
therlands. We tried to demonstrate the value of Traditional Chinese Medi-
cine in an epidemiological way, with evidence-based results as acceptable
‘stepping stones’, acquired communication tools to bridge TCM and tradi-
tional western medicine.
Indeed, it was possible to conduct and report scientifically sound studies
in the area of complementary medicine in the Netherlands. It appeared
that many Dutch citizens have already found their way to the general acu-
puncture clinic for treatment of their musculoskeletal problems, and have
learned that acupuncture improves their health-related quality of life.
The diseases researched in this thesis, CRPS 1 and breech presentation,
are mostly women’s health problems. As demonstrated by the results, our
main conclusion is that in these areas acupuncture, when added to standard
care, is more effective and, as shown in breech version acumoxa, less costly
than standard care alone. These encouraging outcomes still stand when ef-
fectiveness- and cost arguments play a role at the social level.
Although evidence-based medicine is becoming the “gold standard” for
clinical practice, it carries limitations. As a major limitation, evidence-based
medicine applies to larger populations, with the risk of losing sight of the
individual patient. As Tonelli has said: “The knowledge gained from clinical
research does not directly answer the primary clinical question of what is
best for the patient at hand” and he suggests that evidence-based medicine
“should not discount the value of clinical experience” 1. However, the aim
of medical decision-making is to perform a complete formal assessment of
every aspect that is relevant to the decision. Clinicians should be proactive
in decision making, and consider the problem from multiple perspectives.
This includes taking patients’ preferences and rare events into conside-
ration, modeling the decision problem, and explicitly integrating risks, be-
nefits, costs and values. This all will help both patients and doctors cope
with uncertainty and fear. Milt Weinstein, an expert in the area of medical
decision making, once said “The decision will be made, if not actively then
by default” 2.
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Chapter 8 Summary
179
One other obstacle to overcome before applying an additional ‘new’ thera-
py, and one of the stepping stones to cross over should be the credo “First
do no harm” (Hippocrates oath).
The reviews and results of the study about the prognostic value of ultra-
sound on the natural pathway of the presentation of the fetus are of im-
portance to both the clinician and the TCM practitioner. Having knowledge
of this basic information is imperative before one can decide on the best
possible therapy for each individual patient.
There is no doubt that acupuncture research is beginning to be taken seri-
ous. Peer reviewed literature shows the strength and limitations of Tradi-
tional described Chinese Medicine in many clinical and epidemiological dis-
ciplines. In the Netherlands, the academic infrastructure into TCM research
is fragile, but developing. However, this thesis is only the first stepping stone
of the Dutch crossover between TCM and conventional western medicine,
although the main conclusion of this thesis may seem clear and unambi-
guous.
Yet, there are different ways of looking at TCM. Therefore, in this final
chapter, we will present the perspectives of, respectively, the patient and
her family, the general practitioner, the TCM practitioner, the health insur-
ers, and the policymakers and health economics researchers.
After presenting these five different perspectives, we will elucidate how
science could provide deeper understanding of the possibilities of acupunc-
ture in complementary healthcare and, in additionally, the role of science in
the world of complementary medicine practitioners.
The results that will most likely catch the eye of the patient and her family
include characteristics attributable to their health perspective compared to
that of the Dutch population. When confronted with a (chronic) disease,
people may go in search for other ways to manage their main complaint:
pain. Patients may have found information about acupuncture practices via
all kinds of new and old media, or have been told about acupuncture by
others. However, although more and more patients in western countries
turn to acupuncture, 3-5 and musculoskeletal complaints are common in
acupuncture practice 6, 7, little is known about the outcome of using acu-
puncture treatments.
In the Netherlands, acupuncture treatments can be entered into without a
referral from the GP. In the study presented in this thesis (chapter 2), most
patients found their way to the TCM practitioner themselves, and com-
pleted the acupuncture treatment, even if they had to (partly) pay them-
selves. Licensed professional acupuncturists in the Netherlands stand for
accurate information about acupuncture. Therefore the (naïve(1) study) pa-
tients were informed about the likely benefits and risks of acupuncture, and
the acupuncturist obtained an informed consent before commencing with
the treatments.
Interestingly, at the beginning of the treatments the quality-of-life scores of
the naïve study patients were significantly lower compared to the Dutch
population sample pertaining to the three physical domains: role-physical
limitations, bodily pain and social functioning, in contrast to mental health
summary scores. During the course of treatment, the scores increased sig-
nificantly for five domains: physical functioning, role-physical functioning,
bodily pain, social functioning and vitality. Notable improvements in the last
two qualities were observed by the patients’ relatives, who then were or
may in the future be more inclined to turn to an acupuncturist as well when
developing musculoskeletal complaints themselves.
The occurrence of CRPS1 after trauma or surgery is still not completely
understood. The continuing pain, abnormal limb temperature, edema and
dysfunction have great impact on the patients’ daily functioning and quality
of life. De Mos and colleagues 8 provided an overview of the current under-
standings on the pathogenic mechanisms that underlie CRPS1. Western di-
agnostics often involve a spate of laboratory tests and measurements, which
might be a reason for possible late recognition and treatment of CRPS1.
Chinese diagnostic methods stress the practitioners’ perceptions, judg-
ment, intuition and experience. The TCM practitioner takes stock of what
she sees, hears, smells and feels. She will also lend a willing ear to the
patient’s feelings and (other) complaints, and enquire about daily activities.
The patient and the TCM practitioner work together to define the patient’s
present condition and to find reasons for any aberrations. Just as in any cell
of the body the DNA is stored as a template of the entire organism, Chi-
nese philosophy states that any part of the body (pulse, tongue, ear, men-
1 naïve means no previous experience of acupuncture treatments
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Chapter 8 Summary
181
strual cycle) reflects information about the whole. This diagnostic thinking is
reflected and researched in chapter 4.
In my clinical work, I inform the women with CRPS1 about the TCM diag-
nosis, and discuss the possible cause of their disease. Often they recognize
the pattern of imbalance and accept this as a reliable explanation for the
delayed recovery of the trauma that somehow initiated CRPS1. They are
then more motivated to work on improvement using exercise and diet.
Also in the area of preventive medicine, patients find or are offered TCM
treatments. In the Netherlands, when a breech diagnosis is made, there
is a more than 80% chance of a cesarean section 9. The pregnant woman
or both parents may take the view that it would be preferable to avoid this
major surgery and start searching for more information. Currently there are
more than 26,000 websites pointing them to potential operation-sparing
Moxa-treatment by the acupuncturist! In the decision analysis (chapter 7),
we demonstrated that in the total sample, where breech presentation is
confirmed by ultrasound at 33 weeks, only seven women would need to
be treated with breech version by acupuncture-type interventions on BL 67
to avoid a cesarean section.
After the intake consultation with the acupuncturist, the parents may want
to discuss with their GP issues arising from this private consultation and
ask him/her to arrange the referral. Patients appreciate reliable information
from their GPs and specialists on TCM as well 10, and almost 75% of the
Dutch population feels the need to consult the GP about complementary
medicine 11. Two thirds of the Dutch population wants their GP to be in fa-
vor of the treatment and 98% would like to see their GP keeping pace with
the treatment results 12. However, it is the patient’s obligation to explore
the new perspectives and suggestions offered by their doctor.
The populations studied in this thesis can be found in the waiting rooms
of a GP or a pain-specialist (musculoskeletal problems and CRPS1) or a
GP, midwife or gynecologist (breech presentation). Traditionally, the clini-
cian used to be the sole decision maker in healthcare, but nowadays, two-
way communication is the basis of good healthcare. A GP or midwife will
support the parents in co ming to terms with the new situation and share
with them how others have managed in similar circumstances. The GP or
midwife cannot be expected to have all the answers, but they will help to
find them. Overall, GPs are of the opinion that it is their task to provide
their patients with (evidence-based) information about (additive) comple-
mentary and alternative medicine (CAM) treatment possibilities; 75% think
they must be knowledgeable about the most applied CAM treatments and
that their patients should communicate with them about CAM 13.
The majority of the GPs have focused on studying conventional western
medicine. Therefore the notion that a pinprick - often in a part of the body
far removed from the affected area - can cure an illness, is alien to them.
Even when told by patients about their recovery after acupuncture, GPs
will find this hard to believe without evidence-based and published results.
Some doctors or patients may even wonder how one can practice such a
form of medicine.
However, just as a doctor will prescribe paracetamol because she knows
its effect on the patient’s body, an acupuncturist will needle a certain point
because of the known consistent reactions of the diseased human body.
And yet both, the doctor and the acupuncturist, may have only a limited
understanding of the pathway of the bodily effects of their respective treat-
ments. Nevertheless, our observational study on the effect of acupuncture
on health-related quality of life in patients with musculoskeletal complaints
lends itself to giving the GP an insight in TCM in a general acupuncture
practice.
The second part of the thesis deals with making diagnoses. To make a cor-
rect diagnosis, a GP has to explore all the possible reasons for the symp-
toms, which may take some time. GPs may fail to clearly diagnose CRPS1,
even after specialist tests and advice. The pathophysiology of CRPS1 is
poorly understood. Worldwide there seems to be a gender disposition to-
ward CRPS1: 75% of patients are women, with a median age of 46 years.
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Chapter 8 Summary
183
Menstrual cycle-related problems in the year before CRPS1 developed have
been described, but an association between the development of CRPS1
and cumulative endogenous estrogen exposure has not been found 8.
In chapter 4, we investigated whether the risk of developing CRPS1 is associ-
ated with the TCM painful obstructive syndrome (POS). In TCM, menstrual
disorders are related to the state of women’s constitution and therefore men-
strual disorders identify their pain patterns. We selected, translated and admin-
istered a special questionnaire on disorders of the menstrual cycle to find an
additional way to diagnose CRPS1. The results suggest that selected menstrual
conditions are associated with the risk of developing CRPS1. Based on this
knowledge the GP may be recommended to include a menstrual cycle history
in the evaluation of her female chronic CRPS1 patients. While the TCM ques-
tionnaire about menstrual symptoms and signs could contribute to the early
recognition and diagnosis of complex pain problems in women, the derived
questionnaire related to POS could help diagnose CRPS1.
The third part of this thesis concerns breech presentation. The results
(chapters 5 and 6) could help both the GP and midwife to make an in-
formed decision on the implementation of Moxa for women with a diag-
nosed fetus in breech presentation after 33 weeks of gestation. Watson and
colleagues, showing that the accuracy of assessment of breech presentation
depends on the individual obstetric care provider, reported that 57.1% of
the breech presentations were identified correctly14.
When breech presentation is confirmed by ultrasound at 30 weeks and
when no (relative) contra-indications for acupuncture-type interventions
are present, Moxa treatment can be started at 33 weeks gestational age.
The period in-between seems the right time window for the GP, gynecolo-
gist and midwife to discuss the mother’s and her fetus’s condition and the
possibility of TCM treatment with the TCM practitioner. In clinical decision
making, patients and doctors assumingly speak the same language, but their
focus will differ. The GP and midwife have to weigh the health state of both
the mother and her fetus, as well as psychosocial issues. It is the GP’s res-
ponsibility to interpret the patient’s progress and to guide her and / or her
partner in collaboration with the TCM practitioner. She should be aware of
current trends in CAM, including possible interactions with other medica-
tion 15.
There are no legal restrictions to practice TCM in the Netherlands. “Full
service” Chinese medical practitioners can provide Chinese herbal therapy,
Chinese (eastern) nutritional counseling and Asian body work, in addition
to acupuncture. Licensed acupuncturists are differently trained than medical
acupuncturists in providing acupuncture services. A western medical diag-
nosis can only be made by a medical doctor. Even training among licensed
acupuncturists can vary widely. Some graduate programs include training
in all aspects of Chinese Medicine, including Chinese herbal therapy, food
therapy and body work.
The TCM approach is interesting in that it offers simultaneous therapies
for the treatment of pain and many other concurrent somatic (e.g. edema)
and psychological disturbances (e.g. insomnia). The acupuncturist’s most
important skill is to know which acupuncture point is used to pierce the
skin in relation to which disease. With her knowledge, the acupuncturist
can differentiate and personalize what in western medicine is collectively
described under one name. Compare the many words in the Inuit language
describing the great varieties of snow.
However, one of the pitfalls that the TCM practitioner has to guard against
is a tendency to act as a GP. As seen in chapter 2, the typical out-patient is
not referred by the GP and the main complaint is physical dysfunction. In
the consultation process of attentive listening to and observing the patient,
and helping them with the lifting and untangling of the habitual and stagna-
ting flow of Qi – or tangled ideas – the TCM practitioner should be aware
of ‘red flags’ in the patient’s medical history, similar to recognizing ‘red flags’
in physiotherapy. Any ‘red flags’ should alert to possible boundaries of the
treatment, upon which the GP must be consulted. TCM indeed has always
been concerned with guaranteeing safety for the patient. However, a good
contact with the GP and other caregivers is in the interest of all concerned;
therefore the patient should always be asked to consent to providing their
GP with details of the consultation. Of course it is the patient’s right to re-
fuse such consent.
A special area for TCM is maternity care and obstetrics. Some general con-
ditions that in modern medicine are treated with drugs that may harm the
unborn baby had better be treated by acupuncture in order to avoid the risk
of harmful side-effects. Acupuncture has shown effective in treating certain
184
Chapter 8 Summary
185
problems that may occur during pregnancy 16, such as extreme morning
sickness17 18 19 , malposition of the fetus 20, or depression during pregnancy21 .
Traditionally, specific treatments are also given to the mother during the
pregnancy to aid the fetus’s development.
Although the practice as described in chapters 5 and 6 is familiar to every
acupuncturist, some issues need to be addressed. When a woman with a
fetus in breech presentation comes to the clinic, her overall state of health
is also taken into account in the personalized needle prescription. Extra
needles may be added to Bl 67 to cover additional problems of mother and
child. However, even then, in all cases intervention is kept to a minimum.
Additionally, any personal preferences should be taken into account and
the practitioner would do well to mention the smell and warmth involved
in the moxibustion treatment. Continuing education in obstetrics should be
recommended for TCM practitioners working in obstetrics.
The most important goal of a health insurance company is to offer a wide
variety of programs and services that can help improve health and well-
being of their clients while saving and planning for future costs. One way to
do so is to add complementary medicine therapies to the personal indem-
nity insurance. The most researched therapy is acupuncture. Being safe and
cheap in itself, it can even prevent interventions such as cesarean sections,
and thus also save money, as described in chapter 7.
Furthermore, apart from its given equal or more positive results, acupunc-
ture treatment usually spans a longer period – and may therefore contri-
bute to ’natural’ recovery as a result of the body’s self-healing capacity. If
this should happen, the more expensive (diagnostic) interventions may be
superfluous. However, this positive aspect would be more convincing if
the health insurers can be encouraged to take more initiatives to conduct
related research.
Evidence-based medicine aims to address the persistent problem of clini-
cal practice variation with the help of various tools. The mixed record of
evidence-based medicine are rooted in the traditional perspective of the
clinician as sole decision maker 22 . Multifaceted implementation strategies
that take the collaborative nature of medical work into consideration pro mise
more effective changes in clinical practice, as evidenced by the popularity of
complementary and alternative medical therapies. The main issue of the cur-
rent credentialing debate is the question: “Who resolves which providers and
therapies will be accepted as safe, effective, appropriate, and reimbursable?”
Please note, right now, this debate is especially vital in the patient associations,
who urge the health insurance companies to initiate more research.
In the Netherlands, personal indemnity insurance for practitioners covers
acupuncture. That is, under the pressure of several powerful patient as-
sociations, the health insurance companies in the Netherlands have been
found willing to (partly) reimburse acupuncture treatment, as it is shown
to be a relative safe intervention 23, 24. Most insurance companies refund
acupuncture (not herbs) costs up to a set maximum if the practitioner is a
member of one of the three professional organizations. (NVA, NAAV and
NVTC, see appendix 1: glossary)
In the Netherlands there is no governmental involvement whatsoever
in courses for acupuncture. In the USA, Canada, France and Germany,
however, state legislatures and professional medical organizations have
deve loped mechanisms to license physicians and other conventional non-
physician providers of CAM 25.
Healthcare policy makers, researchers, and providers continually receive
large amounts of information from patient organizations, TCM practitioners
and doctors. They still wonder, however, whether this information actually
provides the right answers about the different effect outcomes of TCM.
People who resort to acupuncture and Chinese medicine for long-term
health problems have been found to experience a range of different effects
and results 26. A precondition for studying the effectiveness of TCM is to
develop outcome measures that include as many of these diverse effects
as possible. Similar problems face researchers investigating other types of
complementary therapies and the even more complex interventions of in-
tegrative care. Verhoef and colleagues have developed outcome measures
for integrative care 27 and suggested that a combination of objective mea-
sures, self-report questionnaires and qualitative methods is required 28.
186
Chapter 8 Summary
187
Pragmatic studies like HRQoL and cost-effectiveness studies are important
to show patients’ willingness and compliance to accept and undergo the
TCM therapy. Alas, such studies are rare. In western countries, musculoske-
letal complaints are an important cause of disability, morbidity 29, absence
from work 30 and increased healthcare costs 31, 32. In a large population-
based study in the Netherlands, 75% reported having had musculoskeletal
complaints during the past year, and 44% reported chronic musculoskeletal
pain33. About half of those contacted a health professional for their symp-
toms, thus drawing considerably on healthcare services. Denying the real
practice, this study did not take into account those who turned to CAM
practitioners such as acupuncturists.
It is clear that the health economics researcher needs the systematic review
to efficiently integrate existing information and provide data for rational
decision making. Systematic reviews notice whether scientific findings are
consistent and can be generalized across populations, settings, and treat-
ment variations, or whether findings vary significantly by particular subsets.
Indeed, our meta-analyses in particular can increase power and precision
of estimates of breech-version-acupuncture-type-treatment (BVA-T) and
breech presentation at delivery, while limiting possible bias.
The results described in chapters 5 should also help policy makers to make
informed decisions regarding the implementation of an additional ultra-
sound study in pregnant women at 33 weeks. Informed birthing decisions
cannot be made without information on success rates of all strategies, and
any necessary tradeoffs between the two 34, 35. We showed that implemen-
tation of Moxa for women with a diagnosed fetus in breech presentation
after 33 weeks of gestation could contribute to a lower number of breech
newborns. Additionally, even when the effectiveness of the TCM treatment
equals standard care, the health (economics) researcher should pay more
attention to the benefits of TCM treatment: avoiding the risks of medical
drugs, the relatively small side-effects and the relative cost-effectiveness of
the TCM treatment compared to standard treatment 23.
In chapter 7 we performed a value of information analysis (VOI). This analy-
sis was introduced to estimate the expected benefit of a further study. Thus,
VOI analysis evaluates uncertainty resulting in a formal comparison of the
expected benefit and the cost of a proposed study. Interestingly, in using
this justified method to study a 3,000 year old intervention as moxibustion,
which likely will still work 3,000 years from now, we met a difficulty to apply
within the formula. In the formula, the years that the intervention is possibly
working in this area is in the divider! Consequently, additional information
about new studies about moxibustion seems to be always low.
Furthermore, the VOI showed that if one assumes that breech version
acumoxa treatment was implemented in the care for women with a fetus
in breech at 33 weeks of gestation (instead of waiting and observing), the
expected value of perfect information, (the result of a real RCT as now
modeled), without and with external cephalic version, was only € 0.32 and
€ 0.37 per woman.
All in all, there is a role for the health economics researcher in the field
of additional research. New pragmatic studies of the currently-used TCM
therapies, as well as better understanding of behavioral traits of chronic
(pain) patients in their search for relief, care and support may bring to light
the limited ability to adequately control the use of TCM. On the other
hand, policymakers now advocate the implementation of evidence based
techniques in healthcare.
The following questions still need to be answered:
• Do the Dutch embrace complementary healthcare? If so, what are the
consequences? Are there any dangers? Or does it contribute to good
health in our society?
• What roles do the complementary medicine practitioners in the Nether-
lands envisage? What do they find important? Where are their loyalties?
Are there any data on these aspects?
• What already moves millions of people in the western world to use
Chinese medicine as a cure for bodily complaints? Why is it that this cu-
rative system, including acupuncture, moxibustion, qi gong and herbal
medicine, fits so well in the modern wellbeing and health concept?
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Chapter 8 Summary
189
Hopefully this thesis invites the reader towards a collaborative understan-
ding that will allow TCM to be applied to modern diseases and to be evalu-
ated by evidence-based methods of clinical research. As Ted Kaptchuk said:
“Acupuncturists require flexibility, the ability to treat the whole person and
the recognition of the legitimacy of Chinese diagnostic categories for selec-
ting treatment. Western researchers generally require reproducibility, stan-
dardization, and blind assessment. While each side makes some compro-
mises, the authenticity of both sides remains undiminished. A new synthesis
is created and one can even speak of a new era of responsible and honest
relationship between Chinese medicine and biomedicine.” 36
We have seen that the Netherlands healthcare system gives room to com-
plementary healthcare. Notably, many chronically ill already seek comple-
mentary treatment; a number of health insurers indeed (partly) covers such
treatment through a supplementary health insurance plan. The world of
medical science tends to frown upon this practice of complementary treat-
ment, and it has still not decided whether it is dealing with quackery or reli-
able treatment methods. Here, the task of science is to scrupulously study
aspects of complementary healthcare and to publish the results.
I contend, however, that the current research focuses almost exclusively
on the strictly orthodox variants of complementary healthcare, for example
by emphasizing a practitioner’s unidirectional approach and by discoura ging
clients’ access to Western modern medical care. There is no doubt that
society should fight - and already is fighting - such practices .
But does this focus give a true picture of, for example, the role of acu-
puncture in complementary healthcare and the world of complementary
medicine practitioners? As a TCM practitioner and an acupuncturist myself,
I believe that there is still not enough room allocated in the big house of
medical healthcare to the different types of complementary care.
Secondly, it strikes me that the concept of ‘complementary healthcare as
part of the general healthcare’ is often associated with national healthcare
problems such as quackery, doctors’ delay and patients’ delay. We should
not forget that it is not the common acupuncturist or other complementary
healthcare practitioner but rather the opportunistic ‘quack’ who perpetrates
the (negative) stereotype of complementary care in the public mind. This
stereotype is repeatedly reinforced, especially when evidence of the lack of
proper care is found when a ‘quack’ counsels terminally ill patients without
consulting their doctors, and stories abound in the popular media. Then, I
fear, complementary care is often wrongly associated, consciously or un-
consciously, with quackery and even criminal practices, while a general lack
of understanding and isolation of the individual patient looms in the back-
ground. As a result, applying integrative medicine as part of western mod-
ern care for the modern well-informed patient may come under scrutiny
as well.
Finally, I suggest that scientific knowledge and modern evidence-based in-
sights about complementary care are disregarded in general, or at least are
rarely brought up, which I find deeply regrettable. Since science aims to be
objective and truth-seeking, science can be the bridge to put the debate in
order. This holds true at least for the Western world, with its long-standing
tradition of adequate evidence-based research into the effectiveness and
safety of complementary care, and its professed willingness to seriously
consider implementation of complementary care.
Complementary care and complementary medicine practitioners are by no
means new phenomena. Science has a great opportunity and a clear task to
shape the social debate and include these phenomena into a more balanced
practice of Western medicine. To this end, science should strive to bring
into the limelight the whole range of views and insights encountered in the
world of complementary medicine practitioners.
Currently, however, it appears that science is not actively engaged in fur-
thering this task. A good example is the lukewarm reception of the work of
top researchers such as McPherson, Langevin, Pomeranz, Paterson, Hui,
Kong and Ahn 37-40. Based on years of modern evidence-based research by
these world-renowned experts in the field of acupuncture, their studies are
true eye-openers to the many opportunities for using acupuncture and the
great variety of uses available.
190
Chapter 8 Summary
191
Especially when there is evidence suggesting that acupuncture is as effec-
tive as other active therapies, the use of acupuncture should be consid-
ered more closely, and acupuncture should receive more credit than it
does presently46. In spite of thorough reviews and discussions in the peer
reviewed journals, including JAMA 41, Lancet 42, BMJ 43, 44 and Pain 45, West-
ern healthcare has rather neglected the experts’ findings, which is one of
the reasons why these conclusions have hardly reached the politicians and
other policy-makers. The world of science has the opportunity to play an
unbiased role in the study and dissemination of information about the use
of acupuncture and moxibustion; the aim of evidence-based research is the
eventual implementation of studied interventions such as acupuncture. Un-
fortunately, right now it appears that universities may not to see their par-
ticipation in the social debate as a major responsibility. However, I strongly
contend that scientists do have a social task here in view of the very objec-
tivity that characterizes their work.
There is no doubt that TCM research is beginning to be taken seriously. The
literature shows work in many clinical and epidemiological disciplines. In
the Netherlands, the academic infrastructure of TCM research is fragile, but
developing. Indeed, this thesis gives positive observations confirming that
implementation of complementary healthcare and complementary medi-
cine practices are justified in modern Western medicine.
Additionally, the areas of acupuncture I researched showed a reliable health
science, with additive qualities for (chronically) ill people and for preventive
care in obstetrics. Secondly, we showed that the holistic point of view, used
in the specific acupuncture consultation about the menstrual cycle may be
the key to acupuncture’s therapeutic success in pain relief. Nevertheless,
safety issues need to be addressed. Therefore, in this thesis we plea for an
additional ultrasound study in pregnant women at 30 weeks, not only for
its prognostic value, but also to build in a tool to select only women with a
low risk pregnancy for additionally offered CAM therapies.
Patient safety is the responsibility of the therapist practicing TCM or the
TCM doctor, which means a membership of a professional organization.
This guarantees the professional conduct of their members and adopts rules
of ethics, privacy and patient information, including complaints and disciplin-
ary proceedings. In addition, members are obliged to follow annual training.
The high standards of hygiene, sterility and safety during the treatment are
set by the professional organization.
Acupuncture research brings many professionally working acupuncturists
into direct contact with traditionally trained academic colleagues from a
variety of different backgrounds. I trust this will lead to more recognition,
collaboration and intervision of each other’s capacities. Science should em-
brace the fact that it is empowered to raise its voice in the social debate on
the complementary-care-searching practices of the mature, modern and
assertive patient.
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Chapter 9
198
Chapter 9 Samenvatting
199
Dit proefschrift richt zich op de toepassing van de traditionele Chinese ge-
neeskunde binnen de westerse geneeskunde. Om meer evidence-based
resultaten van de traditionele Chinese geneeskunde (TCG) te kunnen
toepassen in de westerse geneeskunde, bestudeerden we de TCG geïn-
tegreerd in de gezondheidszorg. De studies in dit proefschrift vertegen-
woordigen een scala van wetenschappelijke benaderingen van mogelijke
positieve effecten van acupunctuur en Moxa therapie, zoals deze verankerd
zijn in de traditionele Chinese geneeskunde
De aanpak was gericht op onderzoek naar de volgende drie medische aan-
dachtsgebieden door middel van verschillende epidemiologische metho-
den, namelijk:
1. Onderzoek naar de gezondheidsgerelateerde kwaliteit van leven van
patiënten in een algemene praktijk voor acupunctuur.
2. Onderzoek naar Traditionele Chinese geneeswijzen bij chronische in-
flammatoire aandoeningen, waaronder het complex regionaal pijnsyn-
droom (CRPS1)
3. Onderzoek naar de effectiviteit en de kosten van een TCG behandeling
om “spontane draaiing” van stuitligging gedurende de zwangerschap te
bewerkstelligen.
Ad 1. Onderzoek naar de gezondheidsgerelateerde kwaliteit van
leven van patiënten in een algemene praktijk voor acupunctuur
Als eerste hebben we, in een pilotstudy, de gezondheidsgerelateerde kwa-
liteit van leven (HRQoL) bij patiënten in een particuliere praktijk voor acu-
punctuur bestudeerd. Steeds meer mensen in westerse landen nemen hun
toevlucht tot acupunctuur. Op eigen initiatief melden patiënten met rug-,
spier- en gewrichtspijnen ( de zogenoemde musculo-skeletale aandoenin-
gen) zich. Er is echter maar weinig bekend over het verschil in HRQoL
tussen deze groep patiënten in vergelijking met de HQRoL van de Neder-
landse populatie. Bovendien is er weinig bekend over de HRQoL van die
patiënt voor en na de acupunctuurbehandeling.
Hoofdstuk 2 beschrijft daarom een observatiestudie naar het effect van acu-
punctuur op de gezondheidsgerelateerde kwaliteit van leven bij patiënten met
musculo-skeletale aandoeningen. De 26 patiënten, die nooit eerder behandeld
zijn met acupunctuur, vulden voor en na de behandeling een gevalideerde vra-
genlijst in (RAND-36). De RAND-36 is een door de patiënt zelf in te vullen
vragenlijst naar algemene gezondheid, zowel psychisch als lichamelijk, verdeeld
in 8 domeinen. Door het invullen van deze vragenlijst kan worden gemeten in
hoeverre het functioneren in welk domein wordt gehinderd. De algemene con-
clusie luidt dat voor de groep als geheel de kwaliteit van leven duidelijk verbe-
terd was in de loop van de behandeling. Voorafgaand aan de behandeling waren
de waarden op drie domeinen - in het bijzonder die domeinen die gerelateerd
waren aan lichamelijke klachten - lager dan de waarden voor de Nederlandse
bevolking. Na de acupunctuurbehandeling waren de scores op deze domeinen
zelfs hoger. De na de acupunctuurbehandeling waargenomen verbeteringen
suggereren een subjectief, klinisch relevante verbetering in de HRQoL, bij de
behandeling van klachten aan het bewegingsapparaat.
Ad 2 Onderzoek naar Traditionele Chinese geneeswijzen bij
chronische inflammatoire aandoeningen, waaronder het complex
regionaal pijnsyndroom (CRPS1)
In het eerste deel, hoofdstuk 3, wordt een overzicht van de wetenschappelijke
literatuur over het toegeschreven effect van acupunctuur bij ontstekingsziekten
beschreven. Op het moment van de studie, (2003), waren een aantal obser-
vaties over de ontstekingsremmende werking van acupunctuur gepubliceerd
in de vorm van open en gerandomiseerde trials. Hieruit kunnen de volgende
conclusies worden getrokken. Bij astma bleek acupunctuur het meest effec-
tief als de acupunctuurbehandelingen snel toegepast werden en elkaar snel
opvolgden. Bij rhinitis suggereren de uitkomsten, die hoofdzakelijk verkregen
waren uit open trials, een gunstig effect van acupunctuur na blootstelling aan
allergenen. Bij inflammatoire darmziekten en reumatoïde artritis moet het nut
van acupunctuur nog blijken uit grote gerandomiseerde trials. Het immuno-
suppressieve effect van acupunctuur, zoals beschreven in de klassieke Chinese
leerboeken, was voor epicondylitis en complex regionaal pijnsyndroom type
1 (CRPS1) nog niet goed onderzocht. Niettemin resulteerde acupunctuur bij
deze aandoeningen wel in meetbare pijnverlichting.
Als een mogelijk mechanisme dat ten grondslag zou kunnen liggen aan het
waargenomen effect voeren wij aan dat het vaatverwijdende neuropeptide
CGRP vrijkomt onder invloed van de acupunctuurbehandeling. Wat dit betreft
zou acupunctuur als onderhoudsbehandeling een gunstige invloed kunnen
hebben op het verminderen van de ontsteking en daarmee de pijn.
Het tweede gedeelte, hoofdstuk 4, betreft het Complex Regionaal Pijnsyn-
droom (CRPS1): een chronische aandoening die gepaard gaat met veel pijn,
200
Chapter 9 Samenvatting
201
zwellingen en temperatuurverschillen in armen of benen. Andere sympto-
men die kunnen optreden zijn bewegingsbeperkingen, een verandering in
het zweetpatroon, verkramping van handen en voeten (dystonie) en veran-
deringen in huid, haargroei en nagelgroei. CRPS1 stond voorheen overigens
bekend onder de naam posttraumatische dystrofie (PD), Südeckse dystrofie
of sympathische reflexdystrofie. Het is niet bekend waarom sommige men-
sen onder bepaalde omstandigheden CRPS-1 ontwikkelen als complicatie
van een breuk of kneuzing en andere mensen onder dezelfde omstandig-
heden deze invaliderende complicatie juist niet ontwikkelen. Vroege her-
kenning van CRPS1 is echter belangrijk, omdat men in dat geval snel met
de behandeling te beginnen. Hierdoor kan mogelijk worden voorkomen
dat het ziektebeeld ernstiger wordt. De diagnose CRPS-1 wordt overwe-
gend gesteld op grond van de klachten en het lichamelijk onderzoek. Er
zijn momenteel geen laboratoriumtesten voorhanden om de diagnose te
bevestigen. Wel is bekend dat rond 75% van de CRPS1 patiënten vrouw is.
In dit hoofdstuk wordt een patiënt-controle onderzoek gepresenteerd
waarin is onderzocht of een vooraf omschreven menstruatieverstoring -
zoals beschreven in de TCG - kon worden geassocieerd met het risico op
het ontwikkelen van CRPS1. De pilot-studie beschrijft een groep van 34
vrouwen die lijden aan CRPS1, en gediagnosticeerd door een anesthesist,
en een controle groep van groep van 147 willekeurig geselecteerde andere
vrouwen die niet aan CRPS1 lijden. Beide groepen vulden een vragenlijst
in over 59 mogelijke symptomen bij een menstruatiecyclus. Uit de statisti-
sche analyse van de antwoorden hierop bleek dat de vrouwen met CRSP1
5,2 keer vaker de specifiek beschreven menstruatiestoornis hadden dan de
vrouwen uit de controlegroep. De resultaten tonen aan dat de in de TCG
beschreven, aan CRPS gerelateerde menstruatieverstoring is geassocieerd
met de ontwikkeling van CRPS1 ooit. Toepassing van de uitkomsten van
deze vragenlijst, zoals die gebruikt wordt in de anamnese in de TCG prak-
tijk, zou kunnen bijdragen aan het tijdig herkennen en diagnosticeren van
vrouwelijke CRPS1 patiënten.
Ad 3. Onderzoek naar de effectiviteit en de kosten van een TCG
behandeling om “spontane draaiing” van stuitligging gedurende de
zwangerschap te bewerkstelligen
In het derde deel, de hoofdstukken 5, 6, en 7, worden de nonvertex pre-
sentatie (stuit- en dwars-ligging) tijdens de zwangerschap en geboorte en
de effectieve, aanvullende en complementaire therapieën vanuit de TCG
beschreven. Door deze TCG behandeling is het mogelijk gebleken om op
deze manier iets eerder tijdens de zwangerschap de ‘spontane’ versie van
de nonvertex foetus te initiëren, en wel voorafgaand aan periode waar de
uitwendige versie (ECV)uitgevoerd wordt (Figuur 1). Daarmee kan de ECV
in een aantal gevallen uiteindelijk worden voorkomen. Tijdens de zwanger-
schap kan de foetus met het achterwerk of stuit naar beneden liggen. Deze
ligging is niet optimaal voor het baren. Keert de foetus zich niet tijdens de
zwangerschap, dan is in 80% van de zwangerschappen van een eenling uit-
eindelijk een keizersnee nodig. Aan die ingreep zijn naast de gezondheidsri-
sico’s voor moeder en kind, ook hoge kosten verbonden. Bovendien heeft
deze operatie een nadelige invloed op verloop en gezondheidszorg bij de
volgende zwangerschappen.
In hoofdstuk 5 hebben we het natuurlijke verloop van eenlingzwanger-
schappen met stuitligging beschreven in een groot cohort-onderzoek: Ge-
neration R. We hebben gekeken naar het percentage stuitliggingen bij de
bevalling. Daarnaast onderzochten we de voorspellende waarde van echo-
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Chapter 9 Samenvatting
203
grafie bij 20 en 30 weken in de zwangerschap op de ligging bij de geboorte.
Gebleken is dat stuitligging, bevestigd door echografie rond 30 weken in de
zwangerschap, een hoge voorspellende waarde heeft voor de ligging tijdens
de geboorte. Dit speelt vooral bij een eerste zwangerschap of een vroeg-
geboorte. Een stuitligging rond week 30 is een indicatie om de moeder en
de positie van haar foetus goed te volgen. Daarnaast kunnen dan ook aan-
vullende en bewezen effectieve behandelingen worden overwogen om de
stuitligging te keren (Figuur 1). Hierbij geldt wel het voorbehoud dat deze
behandelingen ook veilig kunnen worden uitgevoerd.
In de Chinese en westerse wetenschappelijke literatuur worden vele on-
derzoeken beschreven met TCG gerelateerde behandelmethoden om de
foetus in stuitligging gedurende de zwangerschap te keren. De belangwek-
kendste TCG behandeling is de Moxa therapie. Moxa therapie behande-
ling (moxeren) maakt geen gebruik van naalden, maar van een brandende
Moxa-staaf. Dit is een rol aangestoken bijvoetskruid (Artemisia Vulgaris), die
ongeveer een duimbreedte boven een acupunctuurpunt wordt gehouden.
De toegediende warmte is de prikkeling van het acupunctuurpunt. De be-
handeling spitst zich toe op één enkel aangewezen acupunctuurpunt aan de
buitenzijde van de kleine teen (ZhiYin, BL 67). Het interessante van deze
behandeling is dat ze, na een introductie en instructie van de acupunc-
turiste, aan de partner van de zwangere vrouw kan worden geleerd. De
partner kan vervolgens, in de aansluitende 14 dagen, de moxa-therapie zelf
thuis geven. Dit zonder verdere tussenkomst van een beoefenaar van de
traditionele Chinese geneeskunst.
Hoofdstuk 6 is een systematische review met een meta-analyse van de we-
tenschappelijke literatuur van de TCG-gerelateerde behandeltechnieken
van acupunctuurpunt ‘Blaas 67’. De vraag die beantwoord moest worden
was of moxibustion, acupunctuur, of electro-acupunctuur waarbij een be-
paald punt op de kleine teen wordt gestimuleerd, kan leiden tot kering van
de stuitligging en behoud van de nieuwe positie tot de geboorte. Op basis
van de gezamenlijke resultaten van zes gerandomiseerde, gecontroleerde
trials en drie cohort-studies concluderen we dat deze acupunctuurtoepas-
singen leiden tot meer hoofdliggingen dan bij een afwachtende houding.
De bijlage bij dit hoofdstuk is een ‘letter to the editor’ waarin we hebben
gewezen op enkele verschillen in onze resultaten ten opzichte van een
vergelijkbare review van een andere onderzoeksgroep.
Ten slotte wordt in hoofdstuk 7 de kosteneffectiviteit behandeld van de
kering van stuitligging bij 33 weken in de zwangerschap met behulp van
bovengenoemde acupunctuur-toepassingen. Met behulp van een simula-
tiemodel is deze behandelingsmethode vergeleken met de gebruikelijke
standaardzorg in Nederland (dus met of zonder uitwendige kering bij 36
weken). In het model wordt de uitwendige kering voorgesteld in de situ-
atie dat er nog steeds sprake is van stuitligging bij 36 weken. Aangezien een
derde van de zwangere vrouwen in Nederland de voorkeur geeft aan een
geplande bevalling thuis, hebben we sensitiviteitsanalyses toegepast waarin
rekening werd gehouden met de gevolgen van stuitligging bij geplande be-
vallingen thuis. Er waren twee invalshoeken belicht: de wijze van bevallen
en de kosten. Uit de berekeningen bleek dat de acupunctuur-toepassingen
(i.c. de moxa-therapie) minder kostbaar zijn en effectiever, dan een afwach-
tende houding met of zonder uitwendige kering rond 36 weken zwanger-
schapsduur.
Hopelijk nodigt dit proefschrift de lezer uit om aan de hand van diverse
evidence-based conclusies tot inzicht te komen dat de TCG toegepast zou
kunnen worden bij ziekten van deze tijd. Daarbij is, voor de validering van
de TCG-behandelingen klinisch onderzoek noodzakelijk.
We hebben gezien dat het Nederlandse zorgstelsel ruimte voor aanvullen-
de gezondheidszorg geeft. Opvallend is dat chronisch zieken zelf al op zoek
gaan naar een aanvullende behandeling met acupunctuur. Een aantal zorg-
verzekeraars dekt inderdaad (gedeeltelijk) een dergelijke behandeling door
middel van een aanvullende ziektekostenverzekering. De wereld van de
medische wetenschap heeft de neiging de wenkbrauwen te fronsen bij deze
praktijk van de complementaire behandeling met acupunctuur en moxa-
therapie. De volgende vraag dringt zich op: ‘gaat het hier om kwakzalverij
of om een betrouwbare behandelmethode?’ Het is de taak van de weten-
schap om in het debat over de complementaire zorg nauwgezet aspecten
van de complementaire zorg te bestuderen en de resultaten te publiceren.
Naar mijn mening richt momenteel het huidige onderzoek naar complemen-
taire geneeswijzen zich vrijwel uitsluitend op de strikt orthodoxe varianten
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Chapter 9 Samenvatting
205
van complementaire gezondheidszorg. Er is geen twijfel dat de maatschap-
pij zou moeten vechten - en nu ook al doet – tegen dergelijke praktijken.
Maar geeft deze focus een getrouw beeld van wat bijvoorbeeld de rol van
acupunctuur in de gezondheidszorg is? Als (complementair) zorgverlener
denk ik dat het huis van de gezondheidszorg vele kamers kent. De comple-
mentaire zorg is een van die kleine kamers in dat huis. Maar dat blijft in het
huidige onderzoek nog sterk onderbelicht.
Het valt me op dat het begrip ‘complementaire gezondheidszorg’ als on-
derdeel van de ‘algemene gezondheidszorg’ vaak wordt geassocieerd met
een te late diagnosestelling en het daardoor mogelijk te laat adequaat be-
handelen van patiënten. Maar de doorsnee complementaire zorgverlener
die hier leeft en werkt, is toch niet bepalend voor dat beeld. Integendeel,
die associatie is er eerder een waarbij het bewijs van het gebrek aan in-
tegratie van complementaire zorgverleners gevonden wordt in crimineel
gedrag van een ‘kwakzalver met tunnelvisie’.
Ten slotte valt mij op dat de wetenschappelijke kennis en moderne evidence-
based inzichten over complementaire zorg en de complementaire zorgver-
lenerwereld opvallend weinig aan bod komen in de meningsvorming van re-
guliere artsen en zorgverleners, politici en gezondheidseconomen, of althans
zelden worden aangevoerd. Dat vind ik betreurenswaardig.
Met haar belofte van objectiviteit en waarheidsvinding mag de wetenschap in
staat worden geacht om orde te brengen in dit debat. Omdat de wetenschap
streeft naar objectieve resultaten en zoekt naar de waarheid, zou de weten-
schap juist in staat moeten zijn om deze orde te brengen. Dit geldt in ieder
geval voor de westerse wereld. Deze heeft immers een lange traditie van vol-
doende evidence-based onderzoek naar de effectiviteit en veiligheid van zorg,
en is bereid om serieus de uitvoering van aanvullende zorg te overwegen.
Op dit moment blijkt echter dat de wetenschap zich toch niet voldoende actief
bezighoudt met deze taak. Een goed voorbeeld is de lauwe ontvangst van het
werk van toponderzoekers en wereldberoemde experts op het gebied van
acupunctuur, zoals McPherson, Langevin, Pomeranz, Paterson, Hui, Kong en
Ahn. Gebaseerd op jaren van evidence-based onderzoek zijn de resultaten
van hun studies echte eye-openers om inzicht te verwerven over de wer-
kingsmechanismen van de acupunctuur en mogelijkheden voor het gebruik
van acupunctuur en moxa therapie. Zij concluderen een grote verscheiden-
heid van beschikbare toepassingen.
Dit alles overziend ben ik van mening dat wanneer uit kwalitatief goed epi-
demiologisch onderzoek blijkt dat acupunctuur even effectief en veilig is als
andere werkzame therapieën, de implementatie van acupunctuur binnen
de gezondheidszorg moet worden bevorderd. Acupunctuur zou meer kre-
diet moeten krijgen dan momenteel het geval is. Ondanks publicaties in de
peer reviewed tijdschriften, met inbegrip van de hoogwaardige tijdschriften als
JAMA, Lancet, BMJ, en Pain, hebben de deskundigen deze bevindingen in de
westerse gezondheidszorg nogal verwaarloosd. Dat zou een reden kunnen
zijn waarom deze conclusies de politici en andere beleidsmakers nauwelijks
hebben bereikt. Het doel van evidence-based onderzoek zou - naar mijn me-
ning - moeten zijn dat bij positieve onderzoeksresultaten ook daadwerkelijk
nagegaan wordt of de onderzochte interventies (als de acupunctuur en moxa-
therapie) kunnen worden geïmplementeerd in de gezondheidszorg.
Gelukkig wordt onderzoek naar acupunctuur en moxa-therapie tegenwoordig
steeds meer serieus genomen. De literatuur toont dit in vele klinische en epi-
demiologische disciplines aan. In Nederland is onderzoek naar de werkzaam-
heid van traditionele Chinese geneeswijzen in ontwikkeling. Met dit proef-
schrift, als eerste stap(steen), tonen we de meerwaarde van de onderzochte
acupunctuur en moxa therapie aan op de verschillende gebieden van de ge-
zondheidszorg. Het onderzoek naar de werking en effectiviteit van de TCG
brengt vele professioneel werkende acupuncturisten in direct contact met de
regulier geschoolde artsen met diverse specialismen. Ik vertrouw erop dat dit
zal leiden tot meer erkenning, samenwerking en intervisie van elkaars capaci-
teiten.
De wetenschap heeft hier een opdracht en zou zich mede ten doel moeten
stellen al die verschillende opvattingen over en inzichten in de (complemen-
taire) zorgverlenerwereld - na onderzoek - over het voetlicht te brengen.
Hierdoor wordt het maatschappelijk debat evenwichtiger.
Uit het onderzoek is gebleken dat acupunctuur en moxa-therapie aanvul-
lende waarde hebben voor (chronisch) zieken en voor de preventieve zorg
in de verloskunde. Daarnaast hebben we laten zien dat duiding van de men-
struele cyclus, zoals die wordt gebruikt in de specifieke TCG-anamnese, de
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Chapter 9 Samenvatting
207
sleutel zou kunnen zijn tot meer begrip in complex regionaal pijnsyndroom
bij vrouwen.
Veiligheid is misschien wel het belangrijkste onderwerp in de gezondheids-
zorg. In dit proefschrift houden we een pleidooi voor een extra echo on-
derzoek bij zwangere vrouwen rond 30 weken zwangerschapsduur. Dit is
in de eerste plaats vanwege de veiligheid van moeder en kind. In de tweede
plaats heeft de echo rond de 30e week zwangerschap een sterk voorspel-
lende waarde op de ligging van de foetus (stuit-, dwars- of hoofdligging)
tijdens de bevalling. Daardoor is deze echo ook een objectief handvat om
deze vrouwen bewezen effectieve (complementaire) therapieën aan te
kunnen bieden en beter te begeleiden rond hun bevalling.
Veiligheid voor de patiënt is de verantwoordelijkheid van de praktiserend
TCG therapeut of TCG-arts. Daar horen verplichtingen bij, zoals het lid zijn
van een professionele organisatie. Deze staat dan garant voor de kwaliteit
van de beroepsuitoefening door de leden en hanteert gedragsregels en
regels betreffende ethiek, privacy en informatieverstrekking aan de patiënt,
inclusief klacht- en tuchtrechtspraak. Daarnaast zijn de leden verplicht om
jaarlijkse nascholingsdagen te volgen. De door de beroepsvereniging ge-
stelde hoge eisen op het gebied van hygiëne, steriliteit en veiligheid tijdens
de behandeling zijn vanzelfsprekend.
Het belang van deelname aan het maatschappelijk debat wordt niet altijd
gezien als de ‘core business’ van de wetenschappers. Maar dat de weten-
schappelijke kennis onvoldoende tot de politiek en de media doordringt,
lijkt mij niet alleen een zaak van politici en journalisten, maar ook één die de
wetenschap zich moet aantrekken. Wetenschappers hebben hier dan ook
een maatschappelijke taak.
Chapter 10
- Glossary
- Abstracts of Chinese concepts in
Traditional Chinese Medicine
210
Chapter 10 Appendix
211
Acupuncture In Standard Chinese, acupuncture is called 针砭 (zhēnbiān).
The related word 针灸 (zhēnjiǔ) refers to acupuncture together
with moxibustion [1].
AA Acupuncture analgesia
Body-Inch system Acupuncture points can be identified by anatomical markings
such as eyebrows, hairlines or skin creases. The distance be-
tween points is not measured by a standard method because
everyone’s body is a different size. Instead, distances are mea-
sured by a metric called the “body inch,” which equals the dis-
tance between the distal joint (the knuckle nearest the fingernail)
and the middle joint of the middle finger. In Chinese: “cun” or
“t-sun.”
CAM Complementary and Alternative Medicine
CSF Cerebrospinal fluid, Liquor cerebrospinalis, continuously pro-
duced and absorbed, is a clear bodily fluid that occupies the
subarachnoid space and the ventricular system within the brain
and around the surface of the brain and spinal cord
DAOM Doctorate program for TCM in the United States
De-Qi “De-Qi” is the term used for the sensation felt when an acu-
puncturist reaches the level of “Qi” in the patient’s body, and is
the communication between patient and acupunctu rist. De-Qi
may feel like distention or an electrical impulse, sometimes ra-
diating, in the area of the acupoint used. Once de-Qi has been
reached, the acupuncturist will leave the needle in place and
the sensation will fade [2]. De-Qi is not a necessary or integral
aspect of acupuncture techniques.
EA Electro acupuncture
EBM Evidence-based medicine
Extracellular matrix The extracellular matrix serves two main purposes. First, it pre-
vents the immune system from triggering from the injury and
responding with inflammation and scar tissue. Next, it facilitates
the surrounding cells to repair the tissue instead of forming scar
tissue.
FDA trials Food and Drug Administration (FDA). Agency of the U.S. federal
government authorized by Congress to inspect, test, approve,
and set safety standards for foods and food additives, drugs,
chemicals, cosmetics, and household and medical devices.
(http://www.britannica.com/EBchecked/topic/1498744/clinical-
trial/292858/Clinical-trials-design)
GP General Practitioner
IM Integrative medicine.
LRP Low resistance points
MDD Medical Devices Directive, covers the regulatory requirements
of the European Union for Medical Devices. Active implant-
able devices (e.g. pacemakers, implantable infusion pump) are
covered by a separate directive, the Active Implantable Medical
Devices Directive.
Moxibustion Moxibustion works with acupuncture and the other modalities
of TCM to restore balance and health to the body. Moxibus-
tion and acupuncture are often of equal importance in treating
many conditions, particularly in the most traditional practices.
Moxibustion is the use of the herb mugwort (artemisia vul-
garis), moxa in Chinese, to apply heat directly or indirectly
to the body in order to warm body regions and acupunc-
ture points, stimulate circulation, encourage a smooth flow
of blood and qi, and protect against cold and dampness.
Moxibustion is particularly effective in the treatment of chronic
problems, “deficient conditions” (weakness), and in the treat-
ment of the elderly.
mRNA Is the template for protein synthesis; the form of RNA that car-
ries information from DNA in the nucleus to the ribosome sites
of protein synthesis in the cell
NAAV Nederlandse Artsen Acupunctuur Vereniging; www.naav.nl.
Negative pre-
dictive value
The proportion of patients with negative test results who are
correctly identified as not having the target disorder [3].
212
Chapter 10 Appendix
213
NVA Nederlandse Vereniging voor Acupunctuur, www.acupunctuur.nl.
The NVA accredits six schools. Some of these schools accept
students without any medical background. However, to join
the NVA they must have been trained as a medic or paramedic
training of four years or equivalent. The NVA accredits four
courses for Chinese herbal medicine. The NVA is the only pro-
fessional organization with an accreditation process, a curricu-
lum and set standards.
NVTC Nederlandse vereniging voor Traditionele Chinese Geneeskunde;
www.zhong.nl. Requires training in TCM similar to the NVA
but used to require a less in-depth medical training than that
required for paramedics. For that reason some insurance com-
panies do not reimburse their members
Odds Ratio (OR) The odds ratio is a way of comparing whether the probability
of a certain event is the same for two groups. An odds ratio
of 1 implies that the event is equally likely in both groups. An
odds ratio greater than one implies that the event is more likely
in the first group. An odds ratio less than one implies that the
event is less likely in the first group. http://www.cmh.edu/stats/
definitions/or.htm
Placebo An inert, or dummy, drug. Placebos are sometimes prescribed
for maladies with no known scientific treatment or in cases in
which an ailment has not yet been diagnosed. They are also
used in tests involving responses to new drugs. In a blind test
the patient does not know whether he or she is given the real
drug or a placebo. In a double blind test neither the patient nor
the physician knows.
Positive predic-
tive value
The proportion of patients with positive test results who are
correctly diagnosed as having the target disorder.[3]
Pre-test probability The probability of the target disorder before a diagnostic test
result is known.
, where n(D+) indicates the
number of patients with the target disorder, n(D-) indicates the
number of patients without the target disorder, and p(D+) is the
probability of the target disorder.
Qi Central to Taoist world view and practice is the concept of qi .
Qi is life-force: that which animates the forms of the world. It
is the vibratory nature of phenomena -- the flow and tremoring
that is happening continuously at molecular, atomic and sub-
atomic levels.
In China, the understanding of qi is inherent in the language. For
instance: the literal translation of the Chinese character meaning
“health” is “original qi.” The literal translation of the character for
“vitality” is “high quality qi.” The literal translation of the charac-
ter meaning “friendly” is “peaceful qi.”
Qi Gong A method of breathing and movement to improve the body
energy and prevention of disease.
RCT Randomized Controlled Trial
Sensitivity The fraction of people with the disease that the test correctly
identifies as positive.
Sham, minimal or
placebo acupuncture
Acupuncture needles are inserted randomly and less deeply
around the painful area while avoiding the meridians.
Specificity The fraction of people without the disease that the test correctly
identifies as negative.
Tai Chi A slow movement exercise to strengthen the body and maintain
good bodily functions.
TCM Traditional Chinese Medicine
Translational
research:
Translational research, with its focus on removing barriers to
multi-disciplinary collaboration, has the potential to drive the
advancement of applied science. An attempt to bridge these
barriers has been undertaken particularly in the medical domain
where the term translational medical science has been applied
to a research approach that seeks to move “from bench to bed-
side”.
Verum acupuncture In verum acupuncture, needles are inserted up to 1-1/2 inches
(4 cm) deep at “meridians” and other prescribed locations until
the patient is said to experience a numbing sensation, called
'De-Qi'.
WHO World Health Organization
214
Chapter 10 Appendix
215
Yin / Yang The traditional works “Treatise on Febrile Diseases” and “The
Yellow Emperor’s Classic” consider yang as positive and yin as
negative. Yang people react to disease in an aggressive, active,
progressive, and warm way. For example, if a yang person has
a cold, his pulse speeds up, temperature rises, face reddens,
throat becomes sore, body pain intensifies, and thirst occurs.
Contrarily, yin people react to disease in a negative, passive,
cool way. If a yin person - the very old and very young in par-
ticular - contracts an acute upper respiratory infection, he or she
loses energy and develops a yellowish complexion and a slow,
weak pulse; usually there is no fever or coughing. Although
they seem healthy, yin people are resistant to cure and require
extensive therapy. A Chinese doctor prescribes tonics for yin
problems and sweating agents or antipyretics for yang problems.
According to Chinese thinking, an entity called Qi is
in existence in the greater world (universe) and in
the lesser world (human being) (1). Like the ancient
Greek concept “pneuma”, qi is a sustaining life force
that neither can be seen nor measured. Qi, blood
and body fluids are fundamental substances in the
human body to sustain normal vital activities as well
as carrying out the physiological functions of the or-
gans, tissues and meridians. Generally speaking the word Qi relates to both
substance and function. The Chinese distinguish between the inner and the
outer Qi. The inner Qi is the life energy in a living body. The outer Qi re-
lates to the weather and the air. The inner Qi has three main functions: the
Ying Qi is to nourish the body, the Wei Qi is to protect the body, and the Qi
is to move around and to put energy in action wherever it is needed. The
inner Qi derives its energy from food, water and air. The inner and outer
Qi can communicate through one’s respiratory system, which is vital for life.
The relation between Qi and health is discussed extensively in the canonical
textbook Huang Ti Nei Ching ( Inner Classic of the Yellow Emperor) (2):
‘Health is the harmonious, uninterrupted flow of Qi, made possibly by the
perfect balance between Yin and Yang. Disease will ensue when the Qi not
flows’. Transmission of this energy from side to side, top to bottom and
from the inside to the outside of the body – and thus reaching balance – is
of great importance for a person’s health.
In acupuncture, needling at specific points modifies the underlying Qi, af-
fecting inner organs, pain perception, and inflammatory processes. When
the Qi is stimulated or tempered, sensations such as tingling, heaviness,
soreness, and pressure may or should occur (“de-Qi”, (3)).
Each meridian corresponds to an organ or organ system (4, 5).
The ultimate goal of the TCM practitioner is to restore and maintain a bal-
anced state of Qi in the individual.
Factors that can affect Qi flow include personal emotional states such as
anxiety, stress, anger, fear or grief, or physical conditions such as poor nu-
216
Chapter 10 Appendix
217
trition, weather conditions, hereditary factors, infection and trauma. Also
failure to develop emotionally in the various stages of life can be seen as
stagnation, to be restored by acupuncture or other TCM-treatments.
The aspects of life that are touched by acupuncture include complex func-
tions common to all levels of evolution, including microcirculation and im-
mune function, etc. Acupuncture can also restore dysfunctions such as sleep
disturbances and menstrual cycle problems, which sometimes may occur
even quite some time after the actual initiating trauma or disease Figure 1).
Many modalities of acupuncture make use of various forms of physical stim-
ulations (pressure, heat, sound, electricity and (laser) light) to achieve that
the body can interact with these field energies effectively and at advantage.
The field concept is equivalent to the Qi concept (1). In Western science,
only physicists and mathematicians have a real feel about these ‘nothings’
and ‘non-sense’ (invisible and untouchable). Worldwide a variety of ap-
proaches to acupuncture therapy have been developed. But this variety
does not suggest that one is better than the others. Evidence based results
should help stimulate both the dialogue and research amongst practitioners
and Western doctors.
The Chinese expressed the Qi concept using their doctrine of Yin and Yang,
in which everything is an amalgam of two opposites. Yin is associated with
physical substance, water, blood, the dark side of the hill or the female
principle. Yang is associated with activity, fire, Qi, the sunny side of a hill or
the male principle. They complement one another and may explain rela-
tionships between dynamic interactions in the human body. Therefore, the
guiding rule to cure disease is to regulate or harmonize the Yin and Yang in
the body so as to restore balance again.
The Yin-Yang balance was considered to be constantly dynamic and fluctua-
ting, striving to ‘a perfect and dynamic balance’. If one was out of balance,
in an energetic sense, the treatment principle would be to re-establish that
balance. The Yin-Yang balance is inherently built into our bodies, such as
acid- vs. base (pH in body fluid), sympathetic vs parasympathetic, or adre-
nergic vs. cholinergic. Western medicine has yet to appreciate this principle
of treating the human body as a system. In Western medicine, system biol-
ogy, researched and described by Jan van der Greef, departs from this point
of view (6).
The proper quality, distribution and flow of Qi is of extreme importance in health.
218
Chapter 10 Appendix
219
Yin /Yang is the Dao of Heaven/Earth
The common thread in the 10,000 Beings
The father and mother of change and
transformation
The root and beginning of life and death...
To cure illness one must search the root
Along with the notion of Qi, TCM recognizes a subtle energy system by
which Qi is circulating through the body in a network of chanels or 'meri-
dians' (Figure 3)
The Ching-Luo (the meridians) have the following functions:
• To guide the flow of blood and Qi (life en-
ergy)
• To harmonize Yin and Yang
• To animate the muscle and bone
• To ease the joints
They serve as the energy transmission channels
running between the internal organs and be-
tween the interior and exterior of the body. This
communication function can bring the message
of illness to the surface, and thus facilitates ma-
king a diagnosis and treating the disease through
actions on the surface. The meridians apparently
have many features quite similar or parallel to
the sympathetic and para sympathetic nerves.
Modern symbol of Yin and Yang, the concept of oppossing unities.
Yin and Yang are neither materials nor energy. TCM is an area where the Yin-Yang theory is used
to understand complicated health relationships in the body.
The Wu-Hsing Dynamic Model first appeared in the Su Ching (about 1000
B.C.). Hsing in Chinese means motion, action and interaction, and Wu
means five. It is therefore also (wrongly) referred to as five-element system
(water, fire, wood, metal and earth). It is a dynamic model applied to the
organic system of humans that establishes their mutual relationships in a
systemic way. Confucius’ writings about morality (1000 BC) served as a
foundation for Chinese education, and this model. He derived five cardinal
relationships: between ruler and ruled, between husband and wife, par-
ents and children, older and younger brothers and fiend and friend. The
rigorous adherence of those relationships yielded harmony and balance. In
medicine, this model can provide useful guidance through the five cardinal
relationships, both in diagnosis and in therapy.
Many ‘laws’ and treatment principles such as Yin-Yang laws and the Wu-
Hsing Dynamic Model are not philosophical concepts but rather scientific
deductions from long observations of system operations, and described in
scientific studies (Figure 4).
According to Taoist cosmology, Yin-Qi and Yang-Qi – the primordial feminine and masculine
energies – produce what are known as the “Five Elements.” These, in turn, give birth to the “ten-
thousand things,” i.e. all of manifest existence. The Five Elements are Wood, Fire, Earth, Metal
and Water. (http://www.tuina.com.au/5-elements.html)
Five elements
220
Chapter 10 Appendix
221
1. Maciocia, G., The Foundations of Chinese Medicine. 1989: Churchill Livingstone.
68,69, 127-140, 160-195.
2. Alev Wilk, I., The Necessity Of Qi Sensation (De Qi). Medical Acupuncture, 2001.
13(1).
3. Altman, D.G. and J.M. Bland, Diagnostic tests 2: Predictive values. BMJ, 1994.
309(6947): p. 102.
1. Wei LY. Theoretical Foundation of Chinese Medicine: A Modern Interpretation Recent
advances in acupuncture research. New York: Institute for advanced Research in Asian
Science and Medicine, Inc. ; 1979. p. 49-89.
2. Hungdi Neiging Suwen. 2nd ed. Baltimore: Williams and Wilkins; 200 BC.
3. Alev Wilk I. The Necessity Of Qi Sensation (De Qi). Medical Acupuncture 2001;13(1).
4. Kaptchuk TJ. Acupuncture: theory, efficacy, and practice. Ann Intern Med 2002 Mar
5;136(5):374-83.
5. Kaptchuk TJ. Chinese Medicine, The Web that has no Weaver. Great Britain: Rider;
1983.
6. van der Greef J, Martin S, Juhasz P, Adourian A, Plasterer T, Verheij ER, et al. The
Art and Practice of Systems Biology in Medicine: Mapping Patterns of Relationships. J
Proteome Res 2007 March 21, 2007;6(4):1540-59.
Chapter 11
224
Chapter 11 Contributing authors
225
Department of Biostatistics, Erasmus MC, University Medical
Center Rotterdam, Rotterdam, The Netherlands,
And:
Institute of Psychology, Erasmus University
Rotterdam, Rotterdam the Netherlands
Department of Epidemiology and Radiology, Erasmus
University Medical Center Rotterdam, The Netherlands
The Rotterdam Institution for Training Midwives,
Rotterdam, The Netherlands
Clinic for Acupuncture and Physical Therapy, Zandvoort, The Netherlands
Department of Obstetrics and Gynecology, Division of
Obstetrics and Prenatal Medicine, Erasmus MC, Erasmus
University Medical Center, Rotterdam, the Netherlands
Program for Assesment of Radiological Technology
Department of Epidemiology, and Radiology, Erasmus University
Medical Center Rotterdam, Rotterdam, The Netherlands
And:
Department of Health Policy and Management,
Harvard, School of Public Health, Boston, USA
Department of Anesthesiology, Erasmus Medical
Centre, Rotterdam, The Netherlands
The Rotterdam Institution for Training Midwives,
Rotterdam, The Netherlands
The Generation R Study Group, Erasmus University Medical
Center, Sophia Children’s Hospital Rotterdam, the Netherlands
And:
Department of Epidemiology, Erasmus University Medical
Center Rotterdam, Rotterdam, The Netherlands
Department of Epidemiology, Erasmus University Medical
Center Rotterdam, Rotterdam, The Netherlands
Department of Epidemiology and Biostatistics, Erasmus University
Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Anesthesiology, Erasmus Medical Centre
Rotterdam, Rotterdam, The Netherlands
Department of Epidemiology, Erasmus University Medical
Center Rotterdam, Rotterdam, The Netherlands
Department of Obstetrics and Gynecology, Division of
Obstetrics and Prenatal Medicine, Erasmus MC, Erasmus
University Medical Center, Rotterdam, the Netherlands
And:
The Generation R Study Group, Erasmus University Medical
Center, Sophia Children’s Hospital, Rotterdam, the Netherlands
Unipolis, Amsterdam, The Netherlands
226
Chapter 11 Contributing authors
227
Department of Epidemiology,
Erasmus University Medical, Center Rotterdam,
Rotterdam, The Netherlands
Department of Anesthesiology, Erasmus Medical
Centre, Rotterdam, The Netherlands
Department of Anesthesiology, Erasmus Medical
Centre, Rotterdam, The Netherlands
228
Chapter 11 List of publications
229
- Health-related quality of life in patients with musculoskeletal complaints in a
general acupuncture practice: an observational study.
I. van den Berg , L. Tan, H. van Brero, K.T. Tan, A. C. J.W. Janssens, M.G.
M. Hunink.
Acupuncture in Medicine 2010;28:130-135
- Correction of nonvertex presentation with moxibustion.
I.van den Berg, L. R. Arends, J. J. Duvekot. Letter to the editor:
American Journal of Obstetrics and Gynecology 2010 203:2
- Cost-effectiveness of Breech Version by Acumoxa for women with a breech
foetus at 33 weeks gestation: a modelling approach.
I. van den Berg, G. C. Kaandorp, J. L. Bosch, J. J. Duvekot, L. R. Arends,
M.G. M. Hunink.
Complement Ther Med. 2010 Apr;18(2):67-77. Epub 2010 Feb 7.
- Complex regional pain syndrome type 1 may be associated with menstrual
cycle disorders: a case-control study.
I. van den Berg, Y.S. Liem, F. Wesseldijk, F.J. Zijlstra, M.G.M. Hunink.
Complement Ther Med 2009;17:262-8.
- Effectiveness of acupuncture-type interventions versus expectative policy to
resolve breech presentation: a meta analysis.
Van den Berg I, Bosch J.L, Jacobs B, Bouman I, Duvekot J.J, Hunink MGM.
Complement Ther Med. 2008 Apr;16(2):92-100.
- Anti-inflammatory actions of acupuncture, a review of the literature.
Zijlstra, F.J., van den Berg-de Lange, I., Huygen, F.J., Klein, J.,
Mediators Inflamm, 2003.12(2): p. 59-69
Abstracts presented at the following national and international
conferences:
- Abstract and poster: Effect of acupuncture on pain and inflammation in
patients with Complex Regional Pain Syndrome type 1. A small ran-
domized controlled trial. I. van de Berg, F. J. Zijlstra, F. Huygen, M.
G.M. Hunink, ICCMR 2010, 5th International Congress on Comple-
mentary Medicine Research, Tromsø, Norway.
- Abstract and poster presentation: Effect of acupuncture on pain and in-
flammation in patients with Complex Regional Pain Syndrome type 1.
A small randomized controlled trial. I. van den Berg, F.J. Zijlstra, F.
Huygen, M.G.M. Hunink. Society for Acupuncture Research 2010 In-
ternational Conference Translational Research in Acupuncture: Bridg-
ing Science, Practice & Community. March 19-21, 2010 - Chapel Hill,
North Carolina, USA.
- Abstract and poster presentation: Health-related quality of life in patients
with musculoskeletal complaints in a general acupuncture practice: an
observational study. Poster presentation. I. van den Berg, L. Tan, H. van
Brero, K.T. Tan, A. C. J.W. Janssens, M.G. M. Hunink. Poster presenta-
tion, 2nd European Conference for Integrative Medicine, Berlin - No-
vember 20 - 21, 2009
- Abstract and poster presentation: Cost-effectiveness of Breech Version
by Acumoxa for women with a breech foetus at 33 weeks gestation: a
modelling approach. I. van den Berg , G. C. Kaandorp, J. L. Bosch, J. J.
Duvekot, L. R. Arends, M.G. M. Hunink Poster presentation 2nd Euro-
pean Conference for Integrative Medicine, Berlin - November 20 - 21,
2009
- Abstract and poster presentation: I. van den Berg, G. Kaandorp, J.L.
Bosch, W. Hop, J.J. Duvekot, M.G.M. Hunink. Fewer Caesarean sec-
tions with the aid of Breech-version Acumoxa: Decision analysis of ef-
fectiveness and cost. Annual Conference of the society for Acupuncture
Research 10 Years post-NIH Consensus Conference, Baltimore, USA
2008
230
Chapter 11 List of publications
231
- Abstract and oral presentation: van den Berg - de Lange I, Wesseldijk
F, Zijlstra F.J, Menstrual Cycle Disorders: Indication of Predisposition
in Development of Complex Regional Pain Syndrome1?, 14 th Annual
Symposium on Complementary Health Care, London, UK, 2007, FACT
- Abstract and oral presentation: I. van den Berg, G. Kaandorp, J.L. Bosch,
W. Hop, J.J. Duvekot, M.G.M. Hunink. The effectiveness and cost-ef-
fectiveness of Breech Version Acumoxa compared to standard care to
correct breech presentation, 13 th Annual Symposium on Complemen-
tary Health Care, Exeter, UK, 2006, FACT
- Abstract and oral presentation: I. van den Berg, B.Jacobs, I. Bouman,
J.L. Bosch, M.G.M. Hunink, Effectiveness of acupuncture-type interven-
tions to resolve breech presentation compared to expectative policy,
a meta-analysis, 12 th Annual Symposium on Complementary Health
Care, Exeter, UK, 2005, FACT
- Abstract and oral presentation: van den Berg–de Lange I, Wesseldijk F,
Niehof S, Huygen FJPM, Zijlstra FJ Registration of effects after acupunc-
ture in complex regional pain syndrome by computer-assisted video
thermography. 10 th Annual Symposium on Complementary Health
Care, London, UK, 2003, FACT
- 7t h World congress of Chinese Medicine 2010, 1-2 October 2010, The
Hague, The Netherlands
- International Acupuncture Congress,19./20. September 2009, Olten,
Switzerland. Presentation of the Dutch translation of the booklet: Natural
pain relief techniques for childbirth using acupressure; promoting a natu-
ral labour and partner involvement. COPYRIGHT Debra Betts 2003 ©.
ISBN 0-473-04467-6
- ETCMA SYMPOSIUM March2009: Research: What, How and for
Whom? Zurich, Switzerland, 2009
- NAAV, December 8, 2007, Bunnik, The Netherlands
- Acupuncture and Science. Jubilee congress 30 years NVA, March 14,
2007, Ermelo, The Netherlands
- Chronic CRPS and acupuncture: a new approach. Symposium Integra-
tion of Eastern & Western Medicine, 2006, Amsterdam, The Nether-
lands
- Effectiveness of acupuncture-type interventions to resolve breech pre-
sentation compared to expectative policy, a meta-analysis, Symposium
Integration of Eastern & Western Medicine, 2006, Amsterdam, The
Netherlands
232
Chapter 11 PhD Portfolio
233
Name PhD student: Clasina (Ineke) van den Berg – de Lange
Erasmus MC Department: Radiology and Epidemiology
Research School: Netherlands Institute for Health
Sciences (NIHES)
PhD period: 2004-2010
Promotor: Prof. dr. M.G.M. Hunink
Co-promotor: Dr. J.J. Duvekot
General academic skills
- Introduction to Medical Writing, NIHES, Rotterdam, 2003
- Introduction to Statistical Software, NIHES, Rotterdam, 2004
Research skills
MSc in Clinical Epidemiology, NIHES, Rotterdam, 2002-2004 (total study
workload of approximately 120 ECTS): various courses in research meth-
odology, including: Principles of Research in Medicine and Epidemiology,
Study Design, Clinical Decision Analysis, Advanced Medical Decision Analy-
sis, Introduction to Data-analysis, Regression Analysis, Topics in Evidence-
based Medicine, Meta-analysis, Advanced Course on Diagnostic Research.
Postdoctoral training, since 2000
In-depth courses
TCM: Practical Shāng Hán Lùn Diploma Course, 2010
Course mindfulness, 2010
Course Scientific English (4 ECT)
Traineeship transposition Therapy mrs. Shinka, Macedonia, 2003
Traineeship in International Trainingscentre of Dongzhimen Hospital, Bei-
jing, China, 2001
Nei Jia Stems & Branches Course, The Anglo Dutch institute for oriental
medicine, Overveen, the Netherlands. 2000
Psychopunctuur Basic Emotional Structuring Test (BEST) Dr. Med. H.
Calehr. 1995-2001
Academic and professional activities
2003-present Member of weekly ART (Assessment of Radiological
Technologies) meeting
National and international conferences Attended
- London. Integrated Care and the management of Chronic illness: the
Patient’s agenda for healthy living, 2009.
- the Kennispoort verloskunde conferentie2008, 2009
- Annual Meeting of The Dutch Association for Acupuncture (Utrecht,
Netherlands) in 2004, 2005, 2006, 2007, 2008, and 2009
- Congres Supplement Plus, 2009
Travel grants
- The Dutch Association for Acupuncture (N.V.A.)
Teaching activities since 2000
2009-2010 Developed the Minor: Inleiding Evidence based Integratieve
Geneeskunde
2009-2010 Teaching 4th year medical students during their VO4, Eras-
mus MC,
2005-2007 Visiting teacher Rijksuniversiteit Groningen (RUG), Compli-
mentary Medicine, Groningen, the Netherlands
2005-2007 Teacher Acupuncture and Chinese Herbal Medicine (The
Anglo Dutch institute for oriental medicine,Supervisor re-
search projects, Overveen, the Netherlands
1986-2005 Teacher, professional training Meer Bewegen voor Ou deren,
Sportraad Zuid-Holland, ‘s Gravenhage, the Netherlands
Supervising research projects of BSc and MSc students
2010 Christel Romeijn , Genesis Kozdras, and Wierin Binda
Medical Sciences: Elective course 3rd year, Department of Obste-
trics & Gynaecology
Title: ‘Factors associated with non-vertex position of the singeleton
fetus at term’
234
Chapter 11 PhD Portfolio
235
2009 Marielle Kornet, and Marieke de Kruijf, The Rotterdam Institution
for Training Midwives, Rotterdam, The Netherlands.
Title: “Is het verminderen van een zwangerschapsdepressie met
behulp van acupunctuur mogelijk, om het maternale sterftecijfer
te verlagen”
2009 Joyce Vaandrager, and Jantine Buxbaum, The Rotterdam Institution
for Training Midwives, Rotterdam, The Netherlands
Title: NIET-medicamenteuze aanpak pijnbehandeling tijdens de
baring bij laagrisico zwangeren: evidence based practice in NL
2008 Loek Tan, Master of Science Degree (Medical Sciences), Erasmus
University Rotterdam, the Netherlands
Title: Health-related quality of life in patients with musculoskele-
tal complaints in a general acupuncture practice: an observational
study.
2006 Josine Simons, Academy for Physiotherapy “Thim van der Laan”
Nieuwegein, The Netherlands.
Title: Developmental Coordination Disorder - Mijn kind is ‘onhan-
dig’. Een multidisciplinaire aanpak bij kinderen met DCD.
2005 Ben Jacobs, and Irene Bouman, The Rotterdam Institution for
Training Midwives, Rotterdam, The Netherlands.
Title: Systematic review of the use of moxibustion for correction of
breech presentation
2004 Marijke Moes, and Barbara van Gelderen, Hogeschool Rotterdam
department Physiotherapy, Rotterdam, The Netherlands.
Title: The Possible Relation between Menstrual Disorders and Pre-
disposition to CRPS1
236
Chapter 11 Dankwoord
237
‘Als je ergens weinig van weet is er maar één manier: in die wereld stappen’
Het tot stand komen van een proefschrift gaat niet vanzelf. Een proefschrift
is een leesbare getuige van het groeiproces dat je als wetenschappelijk on-
derzoeker doormaakt. Er zijn ongelofelijk veel mensen die mij de afgelopen
jaren hierbij enorm hebben geholpen. Bij dezen dank ik iedereen hartelijk
die aan dit proefschrift heeft meegewerkt. Een aantal mensen bedank ik
graag in het bijzonder.
Prof. dr. Myriam Hunink, dank voor je moed, de vrijheid, maar ook voor het
vertrouwen en je inzet voor mijn opleiding tot wetenschapper in dit inter-
disciplinaire onderzoeksveld. Je scherpe blik, je volledige toewijding aan
de wetenschap, je ‘search for excellence’ en je pragmatisme hebben me
enorm geïnspireerd. Bij jou, als voorzitter van de ART-groep, vond ik mijn
eerste serieuze baan in de wereld van de wetenschap. Daarbij bracht je mij
ook in contact met de wereld van de statistiek. Binnen de epidemiologie en
na het halen van de door jou aanbevolen Master in de epidemiologie heb je
mij gemotiveerd om aan mijn ‘Doctors-roman’ te gaan werken. Het belang
van een goede onderzoeksopzet, het belang van publiceren en presenteren
in het Engels waren daarbij de belangrijkste lessen. Samen hebben we vele
verhaallijnen besproken, en samen zijn we blij verrast door dit proefschrift.
Dr. Hans Duvekot, een betere co-promotor had ik me niet kunnen wensen.
Je open geest en je humor, maar ook je steun die ik nodig had om zaken die
in de verschillende projecten stug liepen te verwerken, zorgden voor een
veilige plek waar we - ook - heel veel om en met elkaar hebben gelachen.
Het bijwonen van een keizersnee, een bevalling van een tweeling, maar
ook je zorg voor je patiënten, waren toefjes op de taart. Ik heb mateloze
bewondering voor je vermogen om zelfs in de zo verdrietige periode rond
en na het overlijden van je vrouw bereikbaar en open te zijn. Aan vier
stukken in dit proefschrift hebben we samengewerkt. Ik hoop dat we in de
toekomst nog mooie studies samen tot stand mogen brengen.
Prof. dr. Eric Steegers, ik voel me zeker thuis op de afdeling Verloskunde:
overleg, ook over nieuwe onderzoeksopzetten, is altijd mogelijk bij jou.
Daarnaast kreeg ik op jouw afdeling de ruimte om te overleggen met de
verloskundigen en de gynaecologen. Jullie duidelijke betrokkenheid bij je
patiënten en de zorg voor hen stelde mij gerust en heb ik als imponerend
ervaren. Ook wil ik jou en dr. Vincent Jaddoe bedanken voor het begeleiden
en mogelijk maken van de samenwerking tussen de afdelingen Epidemiolo-
gie, Gynaecologie en Generation R. Ook Claudia Kruithof was behulpzaam
met het speuren in de data van deze studie, dank daarvoor.
‘Als je wilt dat je droom uitkomt, moet je stoppen met dromen’
(Josephine Baker)
Mijn aanwezigheid op de Erasmus Universiteit begon echter al eerder: op
de afdeling van het Pijnbehandelcentrum van het Erasmus Medisch Cen-
trum. Dankzij de uitnodiging van dr. Freek Zijlstra mocht ik als begeleider
van een controlegroep deelnemen aan een studie van patiënten met CRPS
type 1. Freek, zonder jou had ik hier nooit gestaan, mijn dank is groot. Met
alle ‘ups en downs’ bleef je ook tijdens de lastige jaren bereikbaar voor me,
zonder, maar gelukkig ook samen met je meelevende vrouw Nel. Altijd
opgenomen en welkom voel ik me bij jullie! Van jou, Freek, heb ik geleerd
goed voorbereid naar congressen te gaan en daar ook optimaal te genieten
en te presteren. Dat is werkelijk een nieuwe hobby van me geworden.
Prof.dr. Jan Klein, beste Jan, je moed om de studie met een omstreden
behandeling als acupunctuur toe te staan op je afdeling, en mij ook in de
afgelopen jaren positief te blijven steunen, is opvallend en echt bijzonder!
Samen met de hulp van prof. dr. Frank Huijgen, dr. Sjoerd Niehof en Freek
Zijlstra, maar ook met de hulp van de studenten Marijke Moes, Barbara van
Gelder en dr. Feikje Wesseldijk is veel onderzoek verricht waaruit ook publi-
caties zijn voortgekomen. Het was een ongelofelijk interessante tijd. Juist
door de verschillende inzichten en opleidingen van een ieder heb ik veel
mogen leren, mijn dank daarvoor. Daarnaast bedank ik de patiënten die in
dit proefschrift beschreven zijn voor hun deelname aan de onderzoeken.
‘Zelfs een mars van duizend mijl begint met de eerste stap.’
(Lao Tse)
Inmiddels werkzaam bij Myriam, kwam de NIHES, de opleiding tot klinisch
epidemioloog. Een periode van nieuwe inzichten, veel studeren en al mijn
vragen mogen stellen. Daar ontmoette ik Sandra Spronk, wat een plezier
en een goede vriendschap hebben we samen nu al weer jaren. Straks wer-
238
Chapter 11 Dankwoord
239
ken we ook samen als post doc bij de ART-groep, waarin onder anderen
alle promovendi van Myriam zich bevinden. Jouw gedegenheid, focus en
doorzettingsvermogen zijn een voorbeeld, maar gelukkig lachen we ook
graag bij onze eerste kop thee van de donderdag! En natuurlijk Ylian Liem,
mijn kamer-mate: zonder jouw inzet en warme vertrouwen was ik nooit
een ‘statistiek-wonder’ geworden. Jij deelde als een van de eersten mijn
enthousiasme voor de diagnostische TCM-tools voor de CRPS-studie en
zeker ook door jouw hulp is het een vernieuwend artikel geworden. Ylian,
je woont nu wel in Denemarken, maar geweldig bedankt voor alle bijzon-
dere momenten en steun. Natuurlijk ook het plezier op de ART- kamer met
Guido Kaandorp en Majanka Heijenbrock, het op de voor jou zo kenmer-
kende manier de zaken fijntjes duidelijk maken, waren bijzonder voor me.
Rody Ouwendijk, het was een eer om jouw paranimf te mogen zijn.
Lid zijn van de ART-groep betekent: steeds wisselende collega’s met ver-
schillende invalshoeken, opleidingen, interesses en ideeën, die ondanks die
wisselingen toch ook als een soort aangetrouwde familie voelt. Soms taart
van Koekela, soms een party, zelfs een trouwerij in Roemenië! Wat een
thuis voelen is dat, naast veel discussie en hard werken in die roerige tijden!
Hug en hulde voor Nathalie, Raluca, Bart, Tessa, Farzin, Bob, Shuman, Bas,
Edwin, Tim, Karin, Joke, Jolande, Ilse, Loek, Jan- Jaap, Rachel en Taye. Dank
voor jullie hulp met het Engels en ja, ook met de computer!, de inspiratie,
de humor en de koffierondjes.
Cecile Janssens, dank voor alle begeleiding, het medeauteur zijn en je ge-
zellige aanwezigheid op de kamer. Je bent zo’n positieve en fijne collega
voor me geweest. Hoeveel werk er zich op je bureau had opgestapeld, je
maakte tijd voor een praatje, zocht een voorbeeld of we luisterden lekker
naar muziek op You Tube. Bedankt voor al je raad en positieve input.
Een bijzonder contact door de jaren heen is ook prof. dr. Hans Büller. Hans,
door jouw steun, bekendheid met acupunctuur en nieuwsgierigheid, maar
ook door je duidelijkheid over de mogelijkheden en onmogelijkheden bin-
nen het Erasmus Universitair Medisch Centrum heb jij, als voorzitter van
de Raad van Bestuur, mij een kader gegeven om te groeien en ook om mij
binnen de faculteit thuis te voelen. Dank voor het vertrouwen!
Ben Jacobs en Irene Bouman, Joyce Vaandrager en Jantine Buxbaum, Marieke
de Kruijf en Marielle Kornet, studenten van de opleiding tot verloskundige,
dank voor het verzamelen en bestuderen van de literatuur, wij gaan vast het
laatste stukje nog opschrijven.
De promotiecommissie
Mijn dank gaat uit naar de leden van de promotiecommissie: prof. dr. Huib
Pols, prof. dr. Frank Huygen, dr. Saskia Gischler, dr. Niek Exalto en dr. René
Severijnen, en in het bijzonder naar de leden van de leescommissie: prof.
dr. Jolien Roos-Hesselink, prof. dr. Bart Koes en prof. dr. Marja Verhoef. Marja,
jou dank ik in het bijzonder, jouw presentatie in Exeter, Engeland over de
plaats die Complementaire Geneeskunde (CAM) in het medisch curriculum
kan innemen, was mijn kennismaking met de integratie van CAM, inclusief
de patiëntenzorg, in het onderwijs aan de studenten geneeskunde. Zo is
het allemaal voor mij op zijn plaats gevallen! Fijn dat je voor de promotie uit
Canada wilt overkomen.
Inspiration
Many people have contributed to this dissertation. Inspiration for the topic
‘Moxibustion and Breech presentation’ and the need of additional publi-
cations came from Dr. Cardini and Debra Betts. Thanks for your inspiring
support during our contact moments, we will meet again and combine our
skills and know-how in a dynamic team….
Hans van Brero, Tinka Tan en inspireerden me met hun data voor de
HRQoL-studie. Dank voor het vele werk gedaan voor deze studie.
Sponsoren
Harm Elsinga en Albert de Vos van de Nederlandse Vereniging voor acupunc-
tuur, vaak hebben jullie een goed woordje voor me gedaan. Ik bedank jullie
graag voor financiële sponsoring van congresbezoeken, stukjes onderzoek
en drukkosten van posters, etcetera. Charles Wauters en Nicole Hermans
van de ‘Natuurapotheek’, dank voor jullie meeleven en klankborden door
de jaren heen, met als klap op de vuurpijl sponsoring van de receptie, en
natuurlijk Willem en Conny van Meer, van drukkerij ’Balmedia’. Door jullie
hulp en inzet is het werkelijk een herkenbaar proefschrift geworden: zacht
aanvoelend, om de softe sector invoelbaar te maken. Een harde kaft om
zo de harde waarden van evidence-based medicine te vertegenwoordigen,
240
Chapter 11 Dankwoord
241
gebonden als in opgenomen in de gezondheidszorg en zichtbaar veel zorg
en aandacht voor de lay-out van het proefschrift:
非常感谢！(Fēicháng gǎnxiè!, enorm bedankt!)
‘Oh help…’
Die Biostatistiek: Lidia Arends, al ben je niet altijd eenvoudig te pakken te
krijgen, op het ‘moment suprême’ en voor de statistische problemen wist ik
je altijd te vinden, zelfs een keer op zondag. En zo ben je op vier artikelen
medeauteur. Wim Hop, wij komen elkaar vaak tegen bij de koffiemachine en
dan ben je altijd bereid en bereikbaar voor advies. Ik geniet van jullie ‘zake-
lijke’ en warme vriendschap en wetenschappelijke interesse in de resultaten
van de acupunctuur en BL 67- studies. Dank ook voor jullie kritische blik bij
het tot stand komen van de beschrijving van de gebruikte statistiek bij mijn
artikelen.
Mijn dagelijkse en altijd aanwezige dank gaat ook uit naar de mensen ont-
breken op de artikelen, maar van wie ik weet dat zonder hun hulp er
helemaal geen artikelen of posters gepubliceerd waren! Dan doel ik met
name op Nano Suwarno, de helpdesk medewerker, voor de computeron-
dersteuning, voor mij als zij-instromer onmisbaar. Nano, je lacht me al die
jaren toe en maar zelden uit! En Ton Everaers dan, de graficus die alle pos-
ters en de lay-out van dit proefschrift voor zijn rekening nam. De dames
van het secretariaat: Hetty Gerritse die mijn pdf-jes weer terugbracht naar
Word-bestanden en de drukproef mee-corrigeerde en Marion Boltjes die
de agenda’s, faxen en kleurenprints regelde en die beiden altijd weer een
opbeurend praatje hadden als er alweer een afwijzing na het submitten
binnenkwam. Erica Kroos, samen hebben wij het promotietraject adminis-
tratief doorgeworsteld: Erica, dank voor je voelsprieten en warme zorg
wanneer ik met lastige zaken worstelde, zakelijk of privé. Louis Volkers, ook
zo bijzonder: je bent de bibliothecaris die mij hielp met zoeken naar litera-
tuur, impact factors van mogelijke tijdschriften om in te publiceren en met
een glimlach de EndNote files iedere keer weer zó wilde aanpassen dat de
referenties klopten. Zelfs Ton Molendijk van het bureau van de Pedel heeft
me geholpen om een mooie plek en tijdstip te vinden voor de verdediging.
Dank - dank - dank daarvoor...
In een wat dipperige periode - hoort erbij, maar toch - brak een belangrijk
en positief moment aan toen ik halverwege mijn schrijfperikelen via de cur-
sus ‘Medical Writing’ in contact kwam met David Alexander en Ko Hagoort.
Jullie hebben mijn ‘te creatief’ schrijven, mijn schrijfangst en tobben met
het medisch Engels verandert in leesbare stukken. Ko, vooral door jouw
luisterend oor en schriftelijke ondersteuning is het proefschrift juist een
leesbare verwoording geworden van mijn gedachtegoed, bevindingen en
ervaringen. Ik hoop dat wij nog jaren mogen samenwerken bij het publice-
ren en leesbaar maken van komend nieuw onderzoek.
‘Een week heeft zeven dagen, dat zou iets langer mogen zijn’
Na alle collega’s op de universiteit bedank ik ook mijn fijne collega’s Liesbeth
Wagter, Hanneke Noort en Remko en Esther Lieshout. Liesbeth, jij bleef ge-
interesseerd luisteren naar de frustraties die het doen van wetenschappelijk
onderzoek soms bij mij opriepen. Gelukkig vonden we elkaar in het samen
werken in Praktijk Rodenrijs en het genieten van de bereikte resultaten.
Dank voor je opvang als ik weer in het buitenland was. Hanneke, dank voor
je hulp bij het vertalen van de patiëntenfolder en je bemoedigende prikkels
en wandelingen samen. Remko, ik mis je enorm in de praktijk, maar fijn dat
het zo goed gaat in je eigen praktijk in Leusden. Esther, dank voor je steun
en positieve mailtjes, en het vertrouwen van jullie om peetouder van Tho-
mas te mogen zijn. Daar komt gelukkig nu meer tijd voor.
Ook de begripvolle patiënten van Praktijk Rodenrijs die mij mijn afwezigheid
gunden en de daarbij horende onrust accepteerden, bedank ik.
Last but not least: het thuisfront. Familie, vriendinnen en vrienden, leden van
het koor en de Tai Chi groep, dank voor jullie altijd warme belangstelling,
die, zeker tijdens de laatste loodjes, een echte oppepper was. And special:
Marcelien, met zes kinderen om ons heen hadden we al diepe gesprekken,
goede samenwerking en schaterlachen, en ja, nu nog steeds: THANX.
Mijn tweelingzus, Louise, wat fijn dat er congressen in Amerika zijn! Dank
voor je support met het corrigeren van de tekst. Geweldig dat je er bij kunt
zijn…
Roos en Anouk, ik ben blij dat jullie, als dochters en ook als paranimfen, bij
deze belangrijke gebeurtenis in mijn leven betrokken zijn. Roos, al zit je in
242
Chapter 11 Dankwoord
243
het hoge Noorden, juist de laatste jaren houd je me via de telefoon in de
gaten, dat waardeer ik zeer. Wouter en Anouk, bedankt voor het mogen
brainstormen over mijn argumentatie. Deze werd hierdoor scherper. Wou-
ter, wat bijzonder dat je zo dicht bij zit en me in stressmomenten tijdens de
laatste fase van het proefschrift er ook voor me was. Anouk, jaren geleden
begon je hulp al en had vele aspecten. Het begon met het geven van bij-
lessen statistiek, je gaf een doorslaggevende ‘second opinion’ bij de laatste
data-analyses, en als klap op de vuurpijl, is jouw prachtige foto de voorkant
van dit proefschrift. Maar ook het samen skypen, soms tot diep in de nacht,
wat knapte ik daar van op! Als je al zo balancerend met mij kan omgaan,
word je vast een uitstekende psycholoog en puzzelaar!
Mijn broer Kees en zijn vrouw Irene, mijn schoonfamilie en in het bijzonder
mijn ouders dank ik voor hun steun in de afgelopen jaren. Papa en Mama,
jullie blijvende interesse, vele koppen thee en soms champagne, maar ook
jullie voorbeeld van enthousiasme voor het leven motiveerden en steunden
mij tijdens het tot stand komen van dit proefschrift. Heel bijzonder om het
samen te gaan beleven.
Het meest bijzonder voor mij blijf jij, Jelle. Bijna eertig jaar samen delen we
in innige erbondenheid, ertrouwen en oorthuizen. Door alle drukke
bezigheden heen als stel en als gezin, afgewisseld met veel banen, hobby’s
en interesses, bleef je mij motiveren, kookte je voor me en liet me ‘s nachts
doorwerken. Het boekje is er, het lege-nest-syndroom geheeld, het is een
mooi pad geweest. We hebben dit toch maar weer mooi samen geklaard.
Kom maar op met die nieuwe reis, met als motto:
‘Follow your passions, but do not put all your eggs in one basket!’
244
Chapter 11 About the author
245
Ineke van den Berg-de Lange was born on May 5th, 1955 in Enschede, the
Netherlands. She graduated from the Haags Montessori Lyceum, HBS-b in
The Hague, in 1973. That same year she started her study physical therapy
at the SUPA in Utrecht. In 1978 she graduated and started to work as a
physical therapist in Capelle aan den IJssel, and moved to Berkel en Roden-
rijs in 1978. In 1983 she founded ‘Rodenrijs‘, her own private clinic for
physical therapy and Complementary Medicine.
Alongside to the physical therapy Van den Berg practices as an acupunctu-
rist, shiatsu therapist and herbalist for more than 30 years, with a special
interest in obstetrical problems and complex pain disorders as CRPS type
1. In 2002, next to her work in her own clinic, she started as researcher
at the Erasmus Medical Center, joining the Pain Treatment Center, under
supervision of Prof. Dr. Jan Klein and Prof. Dr. Frank Huygen. In 2003 she
entered as researcher at the department of Epidemiology and Radiology of
the Erasmus University MC, Rotterdam, supervised by Prof. Dr. Myriam
Hunink which research resulted in this dissertation. Van den Berg obtained
a Master’s Degree in Clinical Epidemiology at the Netherlands Institute
for Health Sciences (NIHES) in Rotterdam in 2004. Part of the research
presented in this dissertation was performed under supervision of Dr. J.J.
Duvekot at the department of Obstetrics and Gynecology.
Ineke van den Berg is married to Jelle van den Berg and they have two
daughters, Roos and Anouk, and a son, Wouter.
