<b>Bijsluiter</b>. De hyperlink naar het originele document werkt niet meer. Daarom laat Woogle de tekst zien die in dat document stond. Deze tekst kan vreemde foutieve woorden of zinnen bevatten en de opmaak kan verdwenen of veranderd zijn. Dit komt door het zwartlakken van vertrouwelijke informatie of doordat de tekst niet digitaal beschikbaar was en dus ingescand en vervolgens via OCR weer ingelezen is. Voor het originele document, neem contact op met de Woo-contactpersoon van het bestuursorgaan.<br><br>====================================================================== Pagina 1 ======================================================================

<pre>TABLE   OF CONTENTS
Table of contents                                          1
FOREWORD                                                   1
1     Introduction                                         3
      1.1    Cover term                                    3
      1.2    The effect of context in psychotherapy        4
      1.3    The effect of context in healthcare           5
      1.4    Purpose                                       6
      1.5    Questions                                     7
2     Method                                               9
3     Summary and points for consideration                11
      3.1    Context factors and explanations             11
      3.1.1 Context factors                               11
      3.1.2 Explanations                                  12
      3.2    Points for consideration                     13
      3.2.1 Methodology                                   13
      3.2.2 Outcome measures                              13
      3.2.3 Specific disorders                            14
      3.2.4 Ethical aspects                               14
4     Results                                             17
      4.1    Patient-related factors                      17
      4.1.1 Worry and anxiety                             17
      4.1.2 Confidence and hope                           18
      4.1.3 Expectations, suggestion and motivation       20
      4.1.4 Self efficacy and control                     22
      4.1.5 Catastrophising and pessimism                 23
      4.1.6 Attributions                                  24
      4.2    Physician-related factors                    25
      4.2.1 Expectations                                  25
      4.2.2 Status                                        26
      4.3    Factors in the physician-patient interaction 27
      4.3.1 Social relationship                           27
      4.3.2 Verbal activity                               28
      4.3.3 Topic of discussion                           29
      4.3.4 Emotional disclosure                          31
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<pre>       4.4   Affective communication                              33
       4.4.1 Social conversation, humour                          33
       4.4.2 Empathy , emotional support                          33
       4.4.3 Patient-centredness                                  35
       4.5   Instrumental communication                           37
       4.5.1 Providing information                                37
       4.5.2 Needs of the patient                                 39
       4.5.3 Influencing cognitions                               41
5      Summary of underlying mechanisms                           45
       5.1   Stress reduction                                     45
       5.2   Classical conditioning, the learning effect          46
       5.3   Expectancy, expectations                             47
       5.4   Psychoneuroimmunology                                48
       5.5   Conclusion                                           49
Notes                                                             51
Literature                                                        55
Appendix A Invitational Conference on Research into the Effect of
             Context in Healthcare                                71
Appendix B Consulted experts                                      75
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<pre></pre>

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<pre>The Effect of Context in Healthcare - A Programming Study
by Dulmen, A.M., Bensing, J.M.
NIVEL (Netherlands Institute for Research into Healthcare)
PO Box 1568, 3500 BN Utrecht
The Hague, March 2001
ISBN: 9014655-5
This programming study has been commissioned by the Advisory Council on
Health Research (RGO) as part of the project on Context Effects that is taking
shape within the Consultative Committee of Sector Councils for Research and
Development (COS) in collaboration with the Advisory Council for Research on
Nature and Environment (RMNO). The study was made possible by a financial
contribution from the COS Coordination Fund.
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<pre>FOREWORD
Therapeutic measures carried out in the healthcare field owe their efficacy to a
varying (but generally speaking substantial) extent to what are commonly known
as general therapeutic factors, placebo factors or non-specific factors. These are
factors that cannot be attributed to the mechanisms of action of specific
preparations or procedures, but refer instead to the context in which the treatment
takes place, and especially the physician-patient relationship. This is why we also
sometimes speak of context factors.
The best evidence of the existence of context factors can be found in the history
of healthcare. Until the early part of the last century, numerous preparations were
being given or procedures applied which we now know cannot possibly have any
effect, but which nevertheless did sometimes work. It is worth noting that
placebo or context factors need not necessarily be inert substances. Context
factors can also have added therapeutic value in relation to "specific" medicines
or other specific therapeutic procedures.
In scientific research into the efficacy of specific treatments, placebo or context
factors are often regarded simply as an annoyance. If, however, they are viewed
from the perspective of medical treatment as a whole, it is extremely important
that we try to unravel precisely which mechanisms (to be described in
psychological and/or physiological terms) play a role. This field of research is full
of pitfalls. That is why the Advisory Council on Health Research has asked
NIVEL to conduct what is termed a “programming study”, i.e. to take stock of
what is known about context factors with a view to laying down guidelines for
possibly meaningful scientific research. The study was financed from the
coordination fund of the Consultative Committee of Sector Councils for
Research and Development (COS).
The results of this programming study are now available. The RGO is delighted
that NIVEL, in the person of Dr A.M. van Dulmen, has discharged its task in an
exemplary fashion. On 26 September 2000 an “invitational conference” was
devoted to this report, with a view to making recommendations for further
scientific research on this basis. For a brief summary see Appendix A.
                                                                            1
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<pre>2</pre>

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<pre>1          INTRODUCTION
Healthcare in the 20th century is characterised, inter alia, by rapid developments
in the therapeutic field. Despite the growth in therapeutic possibilities, there does
not, in general, appear to be a one-to-one relationship between a medical
intervention and its therapeutic effects. This is because, in addition to specific
effects of physical or pharmacological interventions and the natural course of
complaints and diseases, all kinds of non-specific therapeutic effects also occur
within the healing process (Turner et al., 1994; Kleijnen et al., 1994). These effects
appear to be responsible for a considerable proportion of the therapeutic effects
(White, 1988) and therefore make a positive contribution to the practice of
healthcare. Thus it is not only the nature of a medical treatment but also the
manner and the setting in which that treatment takes place that impact on the
health of the patient concerned. There is unfortunately still a great deal of
uncertainty over the mechanisms involved, and the therapeutic value and
curative effect of the physician-patient relationship is, in general, underestimated
(Sullivan, 1993; van der Geest, 1995; Roberts, 1995). In the interests of the
quality of healthcare, however, it is important that we gain a clearer
understanding of this issue. Knowledge of this kind can assist us in adjusting
treatment programs, in making an adequate assessment of the effects of a given
therapeutic agent and also in utilising these factors to their best advantage. This
view has already been endorsed in a 1993 advisory report from the Health
Council of the Netherlands (p. 208).
1.1        COVER     TERM
This report sets out to clarify the nature of the phenomenon and possible
research opportunities. It provides an overview of scientific research recently
conducted in this field. The first thing we must do is to define our terms: exactly
what phenomenon is it that we are trying to get to the bottom of? In considering
placebo or non-specific effects, we often think of the effect that is imparted by the
ritual of administering a pill. The fact that even patients who know that they are
being given a placebo can nevertheless respond positively shows, however, that
there are, in addition to that ritual, a range of other factors relating to the patient,
the physician and the physician-patient relationship (Park & Covi, 1965;
Bergmann et al., 1994). A single factor - such as, for example, the patient's
expectations or the status of the physician - is a world within itself. The relative
contribution made by each of these factors is unknown. In reality, what we are
dealing with is a cover term embracing different elements which point in the
                                                                               3
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<pre>same direction, but which refer to different phenomena and processes and are
explained by different theories (Bensing, 2000).
We often speak in this context of non-specific effects or placebo effects. However,
it has been pointed out from various quarters that terms such as placebo and non-
specific effects have certain shortcomings. Among these is the widespread
connotation of the term placebo as being an inactive agent, since this implies that
the active mechanism of a verum (i.e. the specific effects) is known. Moreover,
a distinction between the terms non-specific and specific effects is ambiguous,
since this erroneously creates the impression that the activity of a verum would
not be distorted by non-specific effects (Roberts et al., 1993).
In randomised controlled trials (RCTs), attempts have been made to study the
specific effects separately from the natural course and the non-specific effects.
However, because non-specific effects also interact with specific factors, the
magnitude of the effect of a specific preparation is also ultimately dependent on
the influence of non-specific factors (Lindahl & Lindwall, 1982). It is therefore
also important to investigate what these non-specific factors are and the extent
to which they interact with the specific factors (Kleijnen et al., 1994). The efficacy
of any medical intervention is therefore dependent on the circumstances or rather
the interpersonal context in which a medical contact takes place. Consequently,
instead of referring to non-specific factors in this report we shall, as far as
possible, speak of “the effect of context in healthcare” 1 . It is a curiously paradoxical
that the more we know about the active components of placebo factors, the more
specifically we are able to cite these. The value of the cover term is thereby
reduced.
“The Effect of Context in Healthcare” has much in common with a topic that is
considered relevant by the Advisory Council for Research on Nature and
Environment (RMNO) - namely, "the context effects of the environment". Hence
the RMNO is also supporting this study. Following on from this project, the
RMNO is planning to conduct a study into the interaction between non-specific
environmental factors (nature and the environment) and the perception of
sickness and health. The results of the present study may offer some leads in this
respect.
1.2        THE   EFFECT OF CONTEXT IN PSYCHOTHERAPY
The mechanisms at work in psychotherapy have long been the subject of
speculation. The effect of psychotherapy is said to be no more than that of a
        4
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<pre>placebo treatment, in which the acts of arousing positive expectations, showing
interest and recognising an individual as being in need of help are important
factors (Prioleau et al., 1983; van Dijck, 1986; Shapiro & Shapiro, 1997). A
comparable effect is to be found in hypnotherapy, which is said to function
primarily as a method of generating positive expectations (van Dyck &
Hoogduin, 1990). Although context effects in psychotherapy lie outside the remit
of this report, they may well serve as a guideline for research into the effect of
context in healthcare, since there is considerable overlap between the two
phenomena. In short, this means that in both psychotherapeutic and medical
practice, patients present with symptoms in the expectation that the care provider
has a solution to the problem. The position of dependency in which patients find
themselves tends to mean that that they are receptive to suggestion, support and
attention from the provider. These aspects are significant irrespective of the
nature of the psychological or medical intervention.
1.3         THE    EFFECT OF CONTEXT IN HEALTHCARE
As with context effects in psychotherapy, the effect of context in healthcare has
a bearing on a broad range of factors within medical practice (i.e. factors
pertaining to the patient, the physician and the physician-patient relationship)
which are not consciously directed at the nature of the symptoms, the complaints
or the disorder in question. There is, as it were, a continuum of complaint-
influencing factors which run the gamut of intentionality, ranging from actions
that are less intentional (e.g. patient expectations or the physician's white coat)
to those that are more intentional (e.g. showing interest, patient-centredness or
influencing behaviour). The nature of a treatment that has been labelled as
effective - that is to say a treatment whose therapeutic component is theoretically
underpinned (Grünbaum, 1986) - does not, therefore, fall into this category,
whereas the context within which the treatment is administered does. In the case of
disorders for which no effective medical treatment exists (e.g. chronic benign
pain (CBP), chronic fatigue syndrome (CFS) or irritable bowel syndrome (IBS)),
the fact of actually deciding against therapeutic intervention can be interpreted as
being a recognised therapeutic. The nature of a disorder can therefore play a role
in the effect of context in healthcare. It is, incidentally, also possible for a certain
therapeutic procedure to be effective in relation to a particular disorder or patient
due to its specific components, whereas in a different disorder or patient, the
same procedure is effective primarily as a result of the positive expectations that
the procedure arouses. There will, moreover, also be disorders (a fracture, for
example) in which context effects play a negligible role. In most cases, neither the
physician nor the patient is aware of the context effects.
                                                                                5
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<pre>The complex character of this phenomenon is highlighted in a passage from a
recent interdisciplinary exploration of the placebo effect (Harrington (Ed.), 1997):
        "...Placebo effects are influenced by patient-healer interpersonal
        relationships and are increased in pleasant, non-threatening,
        efficient clinical settings with doctors who are perceived by patients
        as warm, likeable, and interested in them. A positive placebo effect
        occurs more frequently in patients with manifest or free-floating
        anxiety and with expectation of improvement by patients, doctors,
        and staff. Expectation of improvement, however, may be indepen-
        dent or overlap with factors such as optimism, enthusiasm, hope,
        faith, belief, motivation, and conditioning. (Shapiro & Shapiro, p.
        30)..."
The influence of context in healthcare is not only manifested in the unconscious
positive health effects that may result from a visit to a physician. A medical
consultation can also have a less beneficial effect on the patient. The reason for
the existence of this so-called “nocebo” effect can be found, inter alia, in the
phenomenon of reactive or “white-coat” hypertension, which refers to patients
whose blood pressure is higher in a physician's consulting room than it is at
home.
1.4         PURPOSE
The health effects (both positive and negative) of patient-related and physician-
related factors and those of the interaction between physician and patient are
central to this study. The question is, precisely which factors pertaining to the
patient (such as expectations or confidence), the physician (expectations, status)
and the physician-patient interaction (instrumental and affective communication)
contribute to the efficacy of a medical intervention and how do they do so. We
shall be disregarding factors associated with the pharmacokinetics of (placebo)
medication, the therapeutic effect of the ritual (impressive instruments, the costs
of an intervention) or with the psychophysiological effects of perceptible
characteristics of medication (de Craen et al., 1996). Due to the complexity of this
phenomenon, factors which presuppose a broader context - such as the influence
of the media on the perception of symptoms and the presentation of complaints -
will also be disregarded. Nor will this study set out to prove the existence of the
placebo effect. The fact that a placebo effect exists is frequently well known, but
precisely why and how it functions is usually more complicated (Roberts, 1995).
        6
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<pre>As far as possible, the therapeutic effect of context will be viewed in the light of
measurable physiological, immunological or psychological changes in the patient.
Since it is not clear in advance whether context variables have a specific or
general effect on health and moreover since specific physiological parameters are
only available for a few disorders (e.g. hypertension, diabetes), both specific
physiological (blood pressure or blood glucose) and generic (general state of
health, functional status) outcome measures are relevant (Kaplan et al., 1989).
Whilst a great deal of research has already been conducted in the above areas
individually, the significance of the frequently inter-related findings in relation
to medical practice is generally left undiscussed. In this study we shall be bringing
together those investigations that are of relevance to medical practice. Having
discussed the literature, we shall provide a summary of possible explanations.
This should ultimately result in answers to the question that concerns the RGO,
namely whether it is necessary to investigate the effect of context in healthcare
and if so, what precisely needs to be investigated and how.
1.5        QUESTIONS
This study is therefore aimed at answering the following questions:
1. What is the relationship2 between physiological, immunological or
psychological outcome measures (blood glucose, blood pressure, immunological
parameters, cortisol, general state of health, anxiety) and context factors
pertaining to the patient (e.g. expectations, confidence, anxiety), the physician
(e.g. expectations, status) and the physician-patient interaction (e.g. the showing
of interest, patient-centredness)?
2. What explanations can be given for the phenomena that are identified (e.g.
anxiety reduction, stress reduction, the satisfaction of expectations (expectancy),
the learning effect (classical conditioning), (psychoneuro)immunology (T cells
and natural killer (NK) cells)?
3. How feasible is it to investigate the effect of context in healthcare?
4. If question 3 can be answered in the affirmative, what questions does the
research need focus on?
                                                                             7
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<pre>2           METHOD
The questions have been answered by reviewing the literature. Owing to the
extent of the material, this did not prove to be an exhaustive review, since the
diversity of investigations made even a quantitative meta-analysis impossible.
What we have done is to extract from various disciplines those studies that
promised to be of relevance to the effect of context in healthcare. On the basis
of existing knowledge and additional conversations with experts (see Appendix
B), we have endeavoured to produce as complete a picture as possible. In those
areas where empirical studies were either unavailable or insufficient, opinion-
based articles have been consulted.
We began by conducting a literature search in Medline with which we selected
controlled experimental and field studies, reviews and opinion-based articles
published between 1990 and 1998 (inclusion criteria). Reviews based on
comparative research were used to gain an understanding of the state of affairs
within a specific field of research. Letters, editorials and historical articles were
disregarded.
Finally, the abstracts were evaluated by two researchers. The following search
terms3 were used:
placebo effect: 431 hits, 60 of which satisfied the inclusion criteria.
White coat: 90 hits, of which 34 satisfied the inclusion criteria.
Nocebo: produced 14 hits.
In order to answer questions 1 and 2, the following combinations of search terms
were also used:
Expectancy*/expectation*/motivation and stress/anxiety: 205 hits, 13 selected.
Expectancy*/expectation*/motivation and outcome measures: 1970 hits, 55 selected.
Physician-patient relationship and stress/anxiety: 126 hits, 15 selected.
Physician-patient relationship and outcome measures: 509 hits, 24 selected.
Stress/anxiety and outcome measures: 2686 hits, 142 selected.
Sometimes the same publications were identified via different search terms.
Reference lists in the selected publications were screened for potentially relevant
cross-references, with articles published before 1990 also being considered at this
stage.
                                                                              9
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<pre>3            SUMMARY          AND POINTS FOR CONSIDERATION
In view of the extent of the discussion in the literature, it was considered useful
first of all to provide a summary of the most significant outcomes and points for
consideration. In this chapter we shall therefore begin by systematically reporting
the results of the research. A justification of these results can be found in the next
chapter. This chapter then goes on to present points for consideration that are
relevant to research into the effect of context in healthcare.
3.1          CONTEXT      FACTORS AND EXPLANATIONS
3.1.1        CONTEXT FACTORS
This study of the literature has identified a number of factors pertaining to the
patient, the physician and the physician-patient interaction which to a greater or
lesser extent contribute to the efficacy of a medical intervention. These factors
are, of course, also interrelated and to some extent overlap. In the interests of
clarity and convenience of comparison, however, they will in this chapter be
considered separately. The following are the factors that have come to the fore:
1.    Factors pertaining to the patient
a.    The need to be regarded as likeable and to fulfil the expectations of the
      physician.
b. The degree of concern and anxiety prior to the consultation.
c. Confidence in the physician and the treatment.
d. .Experiences (positive and negative) of previous treatments; in
      other words, the treatment history.
e. The presence of expectations (positive and negative), fed by these
       previous experiences or by information from the world around.
f. The degree of self-efficacy; that is to say, the belief that symptoms
      can be influenced by one's own actions.
g. The degree of perceived control over the situation.
h. The presence of catastrophising cognitions and pessimism.
i. The attribution of complaints to internal or external circumstances.
2.      Factors pertaining to the physician
a.      The expectations (positive or negative) of the physician and his priorities
        with regard to patient or treatment, which are sometimes unconsciously
        conveyed to the patient.
b.      The (perceived) status of the physician.
                                                                             11
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<pre>3.     Factors pertaining to the physician-patient interaction
a.     The motor activity that is inherent in the verbal expression of the reason
       for the patient's visit.
b.     The emotional charge of the conversation between physician and patient.
c.     The giving of (verbal and non-verbal) attention and support to the patient.
d.     The extent to which a physician gives a patient the space to advance his
       own ideas, explanations and emotions in addition to the complaints that
       he has been experiencing.
e.     The extent to which a physician pays attention to how the patient
       perceives the complaints.
f.     Offering an explanation for the symptoms that are presented with
       reference to a specific diagnosis and related information.
g.     Supplying a solution to the complaints in the form of treatment or advice.
h.     Recognising and influencing (persistent) misconceptions about complaints,
       disorders and therapeutic management by the physician.
i.     The need to satisfy (or not to satisfy) the expectations of the other party.
A number of these factors - such as confidence and positive expectations, the
experience of being in control of the situation, the expression of emotions and
receiving attention and support - have a positive effect on health. Other factors -
such as anxiety, helplessness and negative experiences and expectations - have
an unfavourable effect.
3.1.2      EXPLANATIONS
Several explanations have been advanced for the effect of context factors (see
Chapter 5). For three of these explanations, empirical evidence has frequently
been adduced, namely explanations based on the conditioning theory,
explanations from the field of psychoneuroimmunology and explanations that
have emerged from the study of psychotherapy. Classical-conditioning theory
offers an explanation for both the positive and the negative context effects. This
is because many of the "neutral" factors pertaining to a medical setting - e.g. the
physician, the hospital, the physical examination, an injection or the form and
colour of drugs - can evoke an association with the effects and experiences of
previous treatments. Psychoneuroimmunology shows that all manner of
functional connections exist between psychological, neurological and
immunological processes, via which these areas "communicate" with each other.
Psychoneuroimmunological research not only points to the link between context
effects and the response of the immune system, but also to the link between
context effects and the resurgence of certain specific disorders, such as Epstein-
Barr virus, the common cold and AIDS. Finally, psychotherapy research
       12
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<pre>underlines the non-specific contribution that is made by an empathic approach
on the part of the physician and by encouraging patients to talk about their
concerns, preoccupations and anxieties.
3.2         POINTS    FOR CONSIDERATION
3.2.1       METHODOLOGY
A research program on the Effect of Context in Healthcare will provide a
stepping stone for research which may shed light on one or more facets of this
issue. Based on the research that has been included in this programming study,
one can draw the following conclusions, which are, at the same time, points for
consideration in the context of future research.
- Most of the research has been performed in relatively small groups.
- Blood pressure or pain are the most widely used objectively measurable
    outcomes; however, their relationship to a patient's state of health is not
    always clear.
- Usually there are no follow-up measurements, which play an important role
    in measuring effects on the general state of health.
- Expectations of the patient prior to a visit to the physician are only sporadically
    explored.
- Expectations of care providers are not generally measured.
- As far as conditioning effects are concerned, it is necessary to take an
    individual's treatment history into consideration.
- The role of self-efficacy and helplessness continues to be underestimated in
    connection with research into the impact of stress on health.
- In general, little consideration is given in research to the cognitions of patients
    and physicians.
- There is often no control group to monitor the spontaneous recovery from
    complaints and for the regression towards the mean4 .
- Research with patients is lagging behind research with trial subjects. It is only
    patients, however, who experience both the stress and the support of a
    discussion with a care provider. Research into context effects in a laboratory
    setting therefore has little relevance.
- It is important to take into account the intermediate role of mood and of the
    patient's personal characteristics. Negative (nocebo) context effects are examined
    far less often than positive (placebo) effects.
3.2.2       OUTCOME MEASURES
Research into the effect of context in healthcare has hitherto focused on a small
number of outcome measures, most notably anxiety and blood pressure. As far
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<pre>as the improvement of objectively measurable health is concerned, physiological
outcome measures would appear to be suitable. In addition, subjective (i.e.
patient-reported) measures of health (quality of life, compliance, anxiety) are
important because the healthcare seeking behaviour and the role of patient are
determined more by health as experienced by the patient than by objectively
measurable health. If, for example, research is aimed at changing patients'
healthcare seeking behaviour, subjective outcome measures would appear to take
priority.
3.2.3       SPECIFIC DISORDERS
Context factors play a role in a range of disorders, including unexplained somatic
complaints such as chronic (benign) or acute pain, hypertension, IBS and chronic
fatigue. Context factors also appear to play an important role of chronic, more
or less irreversible disorders, such as asthma, diabetes, gastric ulcers, rheumatism
and cancer. In all of these disorders it is known that emotional arousal and stress
can aggravate the complaints. After all, each disease has its repercussions both
on the body and on the mind. Thus every experience that an individual has
undergone will impact on his state of health (Jamison, 1996). This explains why
the mere fact of talking with a physician about what a patient is feeling and
experiencing (emotional disclosure) can have a positive effect on the perception
of the disorder. It therefore makes little sense to confine research into context
effects to a particular patient group. It is quite possible that for specific disease
categories one particular approach will be more successful than another: for
example, research among hospitalised medical patients suggests that patients with
gastro-intestinal disorders chiefly express psychological problems at an emotional
and cognitive level, whereas patients with cancer tend to display vegetative/
somatic symptoms (vonAmmon Cavanaugh & Wettstein, 1989). For these
different patient groups, an approach that is aimed at changing cognitions might
not be expected to be as successful. Research should therefore preferably be
directed at homogeneous groups of patients.
3.2.4       ETHICAL ASPECTS
One of the factors upon which research into the effect of context in healthcare
might possibly be focused is research into (response) expectations and other
associated cognitions and emotions on the part of the patient. One important
source of expectations lies in the present requirement of informed consent, which
means that a patient has to be informed about a proposed therapeutic
intervention. Informed consent can be interpreted in two ways. On the one hand,
it relates to the Medical Treatment Agreements Act (WGBO), which came into
force in 1995. The quality of the contact between physician and patient plays a
        14
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<pre>central role in this Act. Besides stipulating that a patient has the right to inspect
his dossier, the WGBO also obliges a physician to give the patient complete and
explicit information about the treatment, including expected side effects and
possible alternatives. This obligation is based on the fact that only a well-
informed patient can give the legally required consent (informed consent) to
medical treatment.
Another form of informed consent relates to the fact that patients must be
informed about participation in medical research. The Medical Research
Involving Human Subjects Act (WMO) came into force recently. Under this Act,
patients must be informed about the research in writing and they must then also
give their written consent to participate in the research.
For many of the studies that are proposed here - for example, research into the
influence of previous (therapeutic) experiences on health effects - the informed-
consent requirement will not present any problems. This is because there is no
question of withholding information or an appropriate treatment from someone,
but rather of investigating the effects of the patient's subjective experiences being
taken into account (or else not being taken into account). In the case of
intervention research, the informed-consent requirement could well pose
problems. There is, at present, no solution to this problem.
A further problem is the fact that it is difficult to conduct "blind" research into the
efficacy of medical interventions other than by prescribing medication. After all,
the care provider does not know what procedures he is carrying out. The same
problem is encountered in connection with the study of effects in the field of
psychiatry (Andrews, 1999). One solution to this problem might be to always
have the effects of an intervention measured by an independent reviewer under
"blind" conditions.
                                                                             15
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<pre>16</pre>

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<pre>4          RESULTS
This chapter is directed at the first of the questions posed in this programming
study regarding the relationship between physiological, immunological or
psychological outcome measures, on the one hand, and factors pertaining to the
patient, the physician and the physician-patient interaction, on the other. The
results of the identified studies have been grouped according to independent
variables and presented in the form of tables.
4.1        PATIENT-RELATED          FACTORS
4.1.1      WORRY AND ANXIETY
Regardless of the nature of a medical intervention, it is likely that any form of
care will result in a reduction of worry (van de Kar et al., 1992a). As a result, the
immune response is boosted and physiological changes take place, which in turn
help to alleviate the complaints. It is also possible that the uncertainty
surrounding a visit to a physician may itself provoke anxiety, which can have an
unfavourable effect on the physical complaints. Studies by Gaskin et al. (1992),
Fowlie et al. (1992), Wiebe et al. (1994), van Dulmen et al. (1995) and Rietveld
and Prins (1998) demonstrate the existence of a positive relationship between the
degree of anxiety and the experiencing of pain and other physical complaints,
including asthmatic and diabetic complaints (Table 4.1.1). It appears that anxiety
can lead to a reduction in the activity of NK cells (Fredrikson et al., 1993). There
appears to be a correlation between anxiety and the amount of information that
a patient is given (Street, 1991): too little information is not good, but neither is
too much. The stream of information that is received from the physician can also
provoke anxiety (Hadjistavropoulos et al., 1998). Viewed from a physiological
and psychological perspective, there is considerable overlap between anxiety and
pain (Gross & Collins, 1981). This makes it likely that interventions aimed at
reducing anxiety also impact on pain complaints and that the effect of a medical
intervention will be reduced if no explicit consideration is given to a patient's
worries or anxiety. The only way to reduce anxiety and thus physical complaints
would be to offer a solution in the form of medical treatment. It is worth noting
that patients' anxiety can also cause them to downplay the seriousness of their
complaints when talking to the physician.
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<pre>Table 4.1.1 Worry and anxiety in the patient
 Authors        Subjects    Design          Context  Outcome         Results
                                            variable measure
 Gaskin et al., 60 pain     correlational   anxiety  pain            more anxiety,
 1992           patients                             complaints      more pain
 Fowlie et al., 43 IBS      prospective,    anxiety  abdominal       more anxiety,
 1992           patients    follow-up                complaints      more
                                                                     complaints
 Wiebe et al.,  35 diabetes prospective,    anxiety  diabetic        more anxiety,
 1994           patients    correlational            complaints      more
                                                                     complaints
 van Dulmen 110 IBS         prospective     anxiety  abdominal       more anxiety,
 et al., 1996a  patients    follow-up                complaints      more
                                                                     abdominal
                                                                     complaints
 Rietveld &     40 asthma   pre-/post-test, anxiety  asthmatic       more anxiety,
 Prins, 1998    patients    randomised               complaints      more
                            groups                                   complaints
 Fredrikson et 27 cancer    pre-/post-test, anxiety  NK-cell         more anxiety,
 al., 1993      patients    control group            activity,       lower
                                                     number of       resistance
                                                     monocytes
                                                     and T cells
 Street, 1991   41 GP       observational   anxiety  medical         more anxiety,
                patients    study                    information     more info.
4.1.2        CONFIDENCE AND HOPE
According to Oh (1991), the factors generated by an empathic physician such as
confidence and hope, form the essence of the context effects. Hope and
confidence play a role via the expectations on which they are based. Someone
can have confidence in the physician, in his diagnosis, in the treatment or in
healthcare in general. All sorts of factors can increase confidence, such the
provision of a prognosis, affective contact (Morales, 1994), the reputation of the
physician and even the way he dresses (McKinstry & Wang, 1991).
In general, the confidence that a person has in his physician is associated with an
improvement in the state of health that is reported by the patient (Safran et al.,
1998) (Table 4.1.2). Confidence in a positive outcome in response to stressful
situations appears to be associated with improvement in immune function
          18
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<pre>Table 4.1.2 Confidence on the part of the patient
 Authors        Subjects      Design       Context       Outcome      Results
                                           variable      measure
 Safran et al., 6024 GP       cross-       confidence    general      more
 1998           patients      sectional                  states of    confidence,
                                                         health       better health
 Segerstrom     50 healthy    prospective  confidence    immune       confidence
 et al., 1998   patients      cohort                     function     promotes
                                                                      immune
                                                                      function
 Anderson &     106 NIDDM pre-/post-       confidence    need for     confidence
 Dedrick,       patients      test                       monitoring   reduces need
 1990
(Segerstrom et al., 1998). T cells and NK cells, both of which are important in the
battle against infectious diseases and cancer, appear to increase in numbers as a
result. In a clinical setting, this could mean that whenever a physician arouses
positive expectations in a patient, beneficial health effects may also ensue. Both
effective reassurance and clear information from the physician can contribute to
such expectations (see section 4.3).
Confidence can have negative as well as positive effects, since it can discourage
patients from themselves playing an active role. This phenomenon was
confirmed in a study by Anderson & Dedrick (1990). In general, the degree of
confidence which a patient has in the physician thus gives rise to positive effects.
The physician can reinforce this confidence.
It is worth noting that a physician can also reinforce confidence mistakenly. A
recent ethnographic study of explanations for misplaced optimism in lung cancer
patients receiving palliative treatment reveals what a major impact the way in
which physicians impart information can have on patient confidence (The, 1999).
The fact that physicians and patients have conflicting points of view and different
frames of reference (the physician is concentrating primarily on the effect of the
treatment, the patient on getting better) means that information is wrongly
interpreted and the patient derives optimism from the physician's words.
Disappointing outcomes (relapses) in the course of the disease process come as
an even harder blow for these optimistic patients. It also appears that patients
frequently do not want to hear the hard truth.
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<pre>4.1.3      EXPECTATIONS, SUGGESTION AND MOTIVATION
The confidence that a person has in a treatment is closely tied in with his
expectations. It is therefore also questionable whether confidence can be
investigated in isolation from expectations. Patients' expectations with regard to
the nature and the effect of care in general, or of medical intervention in
particular, have an important bearing on the effect of a treatment. These
expectations can be both positive and negative. As a result, contact with a
physician can either have a favourable or an unfavourable effect on health
complaints. In general, patients have high expectations of the effect of an invasive
therapeutic intervention such as a hysterectomy (Marchant-Haycox et al., 1998).
Studies by Luparello et al. (1970), Goodenough et al. (1997) and Pohl et al. (1997)
demonstrate that if patients are expecting effects, then they will sometimes also
experience them (self-fulfilling prophecy) (Table 4.1.3). Isenberg et al. (1992)
reach the same conclusion on the basis of their literature search in relation to
asthmatic patients. Moreover, Jensen & Karoly (1991) have shown that trial
subjects who are more motivated to respond experience a greater effect from a
placebo pill. Studies by Voudoris et al. (1989, 1990) show how important it is,
when prescribing a therapeutic drug, to take into account a patient's conditioning
history prior to that treatment. A new treatment may be less effective in someone
with bad experiences as a result of the conditioned response to context factors
that hinder the action of the characteristic component (interaction effect). In
order to enhance therapeutic effects, a physician should take note of the
experiences of a patient with previous disorders and treatments. In this
connection, Bügel and van Everdingen (1998) state the need to know a patient's
treatment history. A physician will usually enquire about objective experiences
of diseases and treatments when taking a patient's history. However, the patient's
experiences of diseases and treatments - such as successful therapies, but also
diagnoses that are either too late or are missed - do not, as a rule, come up for
discussion. It is precisely these experiences which - whether directly or indirectly,
via their influence on expectations and anxiety (based on the principal of
conditioning) - are contributory factors in determining the success of a medical
intervention. Expectations can also have a negative impact on health, in which
case one would speak of a nocebo effect. If, for example, a patient's blood
pressure has been extremely high during a previous visit to the physician, then
that patient will anticipate this happening again on a subsequent occasion, which
will result in increased sympathetic activity and thus higher blood pressure
(Janssen & Thien, 1995). Negative expectations can also be generated from what
an individual experiences in his immediate environment, what he is told by the
media or, in general, as a result of incorrect information (Vermeire, 1995; Hahn,
       20
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<pre>Table 4.1.3 Expectations on the part of the patient
Authors        Subjects    Design        Context variable Outcome      Results
                                                           measure
Luparello et   20 asthma pre-/post- expectation and        effects of  expectation and
al., 1970      patients    test, double suggestion with    medication suggestion
                           blind         regard to                     determine
                                         medication                    effects
Goodenoug 117              pre-/post- expectation          effects of  ointment with
h et al., 1997 children    test, control regarding         ointment    suggestion
                           group         analgesic                     works better
                                         placebo                       than without
                                         ointment
Pohl et al.,   40          2x2           expectation       perceived   expectation
1997           patients    balanced      regarding         symptoms    influence
                           placebo       hypoglycaemic                 perception of
                                         symptoms                      symptoms
Jensen &       86          RCT, pre-     motivation and    analgesic   stronger
Karoly,        healthy     /post-test    expectation       effect of   motivation,
1991           patients                  regarding         placebo     greater effect
                                         placebo
Voudoris et    20          RCT, pre-     expectation       analgesic   placebo
al., 1989      healthy     /post-test    regarding effect effect       response can
               patients                  of analgesic                  be conditioned
Voudoris et    40          RCT, 2x2      expectations      analgesic   conditioning
al., 1990      healthy     factorial     regarding         effect      more effective
               patients                  analgesic                     than
                                         placebo                       expectation
Jewett et al., 18 allergic post-test,    expectation       allergic    reaction
1990           patients    control       regarding         reaction to dictated by
                           group         allergic reaction active or   expectations,
                                                           placebo     rather than the
                                                           injection   type of injection
Kvale et al.,  31 cancer pre-/post-      expectation of    nausea and only symptoms
1991           patients    test          symptoms          vomiting    if they are
                                                                       expected
Bovbjerg et    20 cancer pre-/post-      expectation of    immune      previous
al., 1990      patients    test          symptoms          function    expectations,
                                                           and nausea adverse effects
Kincheloe et 77 dental     pre-/post- suggestion and       pain from   the more pain is
al., 1991      patients    test, control expectation re- injection     expected, the
                           group         garding placebo               greater the pain
                                         ointment
                                                                               21
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<pre>1997; Spiegel, 1997). Such effects may well be described as nocebo effects.
Provision of good information is thus, in itself, important to an individual's state
of health, since patients will otherwise become caught up in negative
expectations.
Studies by Bovbjerg et al. (1990), Jewett et al. (1990) and Kvale et al. (1991)
demonstrate that the expectation which a patient already has prior to a visit to a
physician is more determinative for the outcome of the contact than the
expectation that is aroused by suggestion from the care provider. For the
purposes of research into context effects, it would thus appear that it is always
important to take into account the expectations that patients have in advance of
a medical intervention, either as a result of previous experiences (treatment
history) or information from a third party.
4.1.4      SELF EFFICACY AND CONTROL
The perception of symptoms appears to a significant degree to be determined by
the extent to which an individual believes he can exert a positive influence over
his complaints. It is precisely these so-called self-efficacy expectations that appear
to have a positive effect on the perception of complaints, since they influence
both a person's emotions and behaviour (Kores et al., 1990). For the patient this
means that he not only desires information relating to the explanation of
complaints, but also information about the possibilities of adopting effective
behaviour in coping with complaints.
Self-efficacy is the extent to which an individual has the feeling of being able to
exercise control over a situation. Situations which patients perceive to be
uncontrollable have adverse effects on health in terms of blood pressure, cortisol
levels (Wittersheim et al., 1985, Nyström et al., 1998, Peters et al., 1998), immune
response (Peters et al., 1999) and quality of life (Cunningham et al., 1991) (Table
4.1.4). In general, it is possible that situations in which someone feels himself to
be in a dependent position (as, for example, during a visit to the physician) may
have adverse effects. Results of a study by Lynch et al. (1992) also suggest the
importance of taking heed of an individual's personality structure and individual
cognitions (e.g. the extent to which an individual considers himself to be in
control of his situation). A possible explanation for the mediating effect of con-
trol emerges from research by Matthews et al. (1980). They investigated how
much attention trial subjects paid to predictable and unpredictable events.
Unpredictable events appeared to receive greater attention than predictable ones
and (as a consequence) resulted in the reporting of more aversive physiological
reactions. A feeling of control therefore appears to be important for patients. This
        22
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<pre>Table 4.1.4 Self-efficacy and control
 Authors        Subjects    Design        Context       Outcome      Results
                                          variable      measure
 Wittersheim    20 patients randomised, coping          cortisol     coping
 et al., 1985               control       strategies                 strategies are
                            group                                    associated with
                                                                     cortisol
 Peters et al., 24 patients 2x2 factorial degree of     blood        less control,
 1998                                     control       pressure and higher BP and
                                                        cortisol     cortisol
 Peters et al., 82 patients 2x2 factorial degree of     immune       effort
 1999                                     control and   response     stimulates,
                                          effort when   and NK-cell uncontrol-
                                          confronted    activity     lability reduces
                                          with stress                response
 Cunningham 273 cancer pre-/post-         self-efficacy quality of   more self
 et al., 1991   patients    test,                       life         efficacy, higher
                            correlational                            quality
justifies the pursuit of “shared decision-making”, whereby a patient maps out a
treatment program in conjunction with the physician, instead of simply receiving
instructions without discussion.
4.1.5        CATASTROPHISING AND PESSIMISM
Besides favourable cognitions, including self-efficacy and other positive
expectations, a patient may also be weighed down with dysfunctional cognitions
such as catastrophising thoughts, which can cause and perpetuate physical
complaints. Catastrophising cognitions appear to fluctuate much more over time
than the above-mentioned self-efficacy cognitions and also to be more susceptible
to environmental influences (van Dulmen et al., 1997) (Table 4.1.5). Studies by
Affleck et al. (1987), Sorbi and Tellegen (1988), Strauman et al. (1993), Antoni et
al. (1994), van Dulmen et al. (1996a) and Robinson-Whelen et al. (1997),
involving a variety of physical complaints and disorders (migraine, rheumatism,
CFS, IBS), demonstrate that pessimistic thoughts and feelings of helplessness can
have an adverse impact on physical complaints, general state of health, immune
function and medicine consumption. This suggests that any attempt by a
physician to give a more positive turn to a patient's feelings and beliefs can have
the effect of alleviating physical complaints (see section 4.5.3).
                                                                             23
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<pre>Table 4.1.5 Catastrophising and pessimism
 Authors      Subjects    Design        Context        Outcome       Results
                                        variable       measure
 Sorbi &      29          correlational catastro-      migraine      more cata-
 Tellegen,    migraine                  phising        attacks       strophising
 1988         patients                  cognitions                   cognitions, more
                                                                     attacks
 Affleck et   92          cross-        expressions    functional    more
 al., 1987    rheumatic   sectional,    of             problems      expressions,
              patients    correlational helplessness                 greater problems
 Antoni et    65 patients cross-        negative       subj.         more negative,
 al., 1994    with CFS    sectional,    beliefs about  severity of   severe
                          correlational complaints     disorder      complaints
 van          105 IBS     prospective, catastro-       medical       more cata-
 Dulmen et    patients    follow-up     phising        consump-      strophising,
 al., 1997                              cognitions     tion and      higher
                                                       severe        consumption
                                                       abdominal     and more
                                                       complaints    complaints
 Robinson-    50 healthy prospective, pessimistic      general state more
 Whelen et    patients    cohort        outlook on     of health     pessimistic,
 al., 1997                              life                         poorer health
 Strauman et 38 patients pre-/post-     negative self- immune        negative self-
 al., 1993                test, control image          function      image, poorer
                          group                                      immune
                                                                     function
4.1.6       ATTRIBUTIONS
Attributions are the causes to which an individual attributes events, such as
diseases and accidents. They may refer to unchangeable external circumstances,
e.g. the consequences of a chemical disaster, or they may be more internally
oriented, as when someone knows that his health behaviour leaves something to
be desired. The persistent attribution of somatic complaints to physical causes
appears to perpetuate those complaints (van Dulmen et al., 1995, Vercoulen et al.,
1996) (Table 4.1.6). Aside from the fact that the nature of the attributions
determines what steps a person will take to influence his situation (Robbins &
Kirmayer, 1991), causal attributions also appear to be capable of exerting direct
influence over the immune system (Segerstrom et al., 1996).
         24
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<pre>Table 4.1.6 Attributions
  Authors        Subjects   Design        Context      Outcome      Results
                                          variable     measure
  vanDulmen      120 IBS    prospective   somatic      medical      attributions
  et al., 1995   patients   follow-up     attributions con-         have negative
                                                       sumption,    effect
                                                       course of
                                                       complaint
  Vercoulen      246 CFS    prospective   somatic      fatigue      attributions
  et al., 1996   patients   follow-up     attributions complaints   have negative
                                                                    effect
  Segerstrom     86 HIV-    correlational internal     decrease in  attributions
  et al., 1996   positive                 attributions T helper     accelerate
                 patients                              cells        decrease
This suggests that a physician enquiring about the factors to which a patient
attributes his complaints or disorder as well as any consequent influence of these,
can help to strengthen the body's natural resistance or elicit an improvement in
the complaints experienced.
4.2          PHYSICIAN-RELATED          FACTORS
It is likely that factors such as the expectations that a physician has of a given
intervention and his confidence in his own actions may impact on the efficacy of
an intervention via the patient. However, research into factors pertaining to the
physician appears to be scarce.
4.2.1        EXPECTATIONS
Physicians can exert influence over the effect of a given treatment by the way in
which they introduce that treatment to a patient. For example, a study into the
influence of a physician's expectations on the reduction of pain in 46 chronic-pain
patients indicates that the more physicians expect a patient's pain to be relieved,
the more this pain does, in fact, diminish (Galer et al., 1997). According to the
researchers, these results suggest that physicians in a subtle way transmit their
expectations to the patients. Wirth (1995) has even demonstrated that the
expectations of the physician are more determinative for health effects in the
patient than the expectations of the patient himself. This probably arises from the
patient's need to be liked and to satisfy the expectations of the physician. We
know of no study that has investigated whether patients report greater
                                                                            25
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<pre>improvement in their complaints when both physician and patient have the same
expectations of the intervention.
4.2.2      STATUS
Besides a care provider's expectations, that person's status will also contribute to
the effects of a medical treatment. The higher social status of the care provider
appears to play an especially important role within alternative medicine.
Research into the influence of social status has up until now principally been
directed at blood pressure. Blood pressure measured by nurses appears, in
general, to be lower than that measured by physicians (Moutsos et al., 1967;
Mancia et al., 1987; Veerman & van Montfrans, 1993). Long et al. (1982) have
also investigated the influence which the status of the care provider has on blood
pressure. Using a group of 40 trial subjects, they looked into the way in which
blood pressure responded to the presence of a person in a white coat who was
introduced as a physician and the same person in casual clothing who was
introduced by his first name. All trial subjects were found to have higher blood
pressure during the discussion with the person with the white coat than during
the same conversation with the person in casual clothing. This finding could
provide an explanation for the “white coat” phenomenon (i.e. the fact that blood
pressure or blood glucose is higher when measured by a physician than when the
measurement is carried out at home by the patient himself). It is possible that the
difference in the responsibility of the care provider plays a role here. High blood
pressure has greater implications in the presence of a physician than in the
presence of a nurse (The, 1999). However, Lynch et al. (1980) showed that even
in the presence of a clinical trial manager who has the same status as the trial
subject, the blood pressure shows a greater increase than in the absence of that
trial manager (see also sections 4.3.1 and 4.3.2). An explanation for this is
provided by Cacioppo et al. (1990), who demonstrated in 27 trial subjects that the
mere idea that one is being observed can elicit subtle physiological reactions in
the form of a decrease in skin resistance.
It is worth noting that the literature also reports white-coat effects with regard to
blood glucose measurements, although these have been far less widely
investigated. According to Bodansky (1993), this is usually a case of
measurements performed at home (which, unlike automatic 24-hour blood
pressure measurements, are reported by the patients themselves) being portrayed
in an excessively positive light. However, Campbell et al. (1991; 1992) have
shown that manipulation of measurements is uncommon and furthermore that
it is not a question of measurements being incorrectly performed. The
phenomenon may possibly be linked to the fact that stress can also bring about
       26
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<pre>a rise in blood glucose values. However, this was ruled out by Campbell et al.
(1992), who, based on the levels of cortisol in the blood of diabetes patients,
made a reasonable case for there not being any difference between the levels of
stress experienced in hospital and at home. Further research is therefore still
needed into whether reactive hyperglycaemia does, in fact, exist and what factors
it is influenced by.
4.3         FACTORS     IN THE PHYSICIAN-PATIENT INTERACTION
The literature containing research into the psychophysiological effects of the
physician-patient interaction is structured according to the continuum mentioned
in the Introduction, which ranges from physician actions with a low level of
intentionality (verbal activity, topic of discussion) to those with a high level of
intentionality (patient-centredness, influencing of cognitions). At the bottom of
the continuum are factors that are inextricably connected with medical contact,
such as the existence of a social relationship, verbal activity and the topic of
discussion. In addition, a consultation may be characterised to a greater or lesser
extent by the contribution that is made by the patient and the space allowed for
this by the physician. Thus the content of the conversation is further determined
by the points that are raised by the patient, meaning that that the role of the
physician within the continuum increases accordingly.
4.3.1       SOCIAL RELATIONSHIP
The contact between physician and patient can be viewed as a special form of
social relationship in which a variety of aspects such as dependency, interest
shown in a patient, empathy, differences in status, control and exchange of
information all have a role to play. Social support has an important function in
any social relationship. This is all the more applicable in the case of physician-
patient interaction, since the degree of social support is related to the course of
diseases and disorders (Cohen, 1988).
From this point of view, it is therefore also reasonable to assume that forms of
interaction that exist between a physician and a patient can have varying degrees
of "healthiness". Research into the effect of social support on health and sickness
has up until now principally been directed at cardiovascular activation. From this
it appears that the degree of social support has a favourable effect on the blood
pressure and other cardiovascular parameters (Kamarck et al., 1998).
                                                                          27
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<pre>4.3.2       VERBAL ACTIVITY
Apart from the content of the discussion between physician and patient, evidence
has been found that talking in itself provokes cardiovascular reactions (Lynch et
al., 1980; Silverberg & Rosenfeld, 1980; Liehr, 1992; Stein & Boutcher, 1993; le
Pailleur & Landais, 1994; le Pailleur et al., 1996) (Table 4.3.2).
Table 4.3.2 Verbal activity
 Authors        Subjects     Design       Context     Outcome    Results
                                          variable    measure
 Silverberg & 24             pre-/post-   talking     blood      talking increases
 Rosenfield,    hypertension test                     pressure   blood pressure
 1980           patients
 Liehr, 1992    109 healthy  pre-/post-   talking vs  blood      talking increases
                patients     test         listening   pressure   blood pressure
                             crossover                           more than listening
 Stein &        34 patients  pre-/post-   talking/    blood      talking increases
 Boutcher,                   test         not         pressure,  blood pressure
 1993                                     talking     pulse
 le Pailleur & 35            prospective  talking     blood      talking increases
 Landais,       hypertension                          pressure   blood pressure
 1994           patients
 le Pailleur et 42           pre-/post-   talking     blood      blood pressure
 al., 1996      hypertension test                     pressure   during talking
                patients     crossover                           higher than during
                                                                 silences
 le Pailleur et 50           pre-/post-   talking     blood      no blood-pressure
 al.,1998       hypertension test                     pressure   increase during
                patients     crossover                           silences
These findings suggest that the verbal activity of talking is, in itself, a sufficient
explanation of the white-coat phenomenon. It appears that the higher the resting
value of the blood pressure, the greater the rise in blood pressure, so that the
increase in blood pressure in hypertensive individuals when they are talking is
greater than that in normotensive individuals (Lynch et al., 1981). The extent of
the reaction is comparable with that of a regular exercise stress test (Thomas et
         28
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<pre>al., 1992), does not change as a result of the use of antihypertensives (Lynch et al.,
1982a; Dimsdale et al., 1992) and occurs both in an experimental and a medical
setting (Lynch et al., 1982b). It would appear that in hypertensive individuals, the
normal response of an increase in blood pressure in reaction to everyday
situations (such as communication) is exaggerated.
There is evidence that people with cardiovascular disorders such as essential
hypertension do, indeed, experience problems with interpersonal communication
(Weiner, 1979). Perhaps they experience talking as a stressor per se, or else the
findings are linked to the fact that the majority of consultations take place
between a man and a woman (Millar & Accioly, 1996). It is also possible that the
uncontrollability that is experienced may bring about an increase in blood
pressure as a result of the dependent position in which a patient finds himself
during a visit to the physician (Peters et al., 1998).
It should be noted that Malinow et al. (1986) have shown that the blood pressure
of deaf people also rises while signing. The rise in blood pressure is therefore not
simply connected with the motor activity of talking, but also with the stressful
communicative procedure itself. In general however, studies of the reactions to
psychological stressors of people with white-coat hypertension do not produce
corresponding conclusions. According to some authors, there is no connection
(Siegel et al., 1990), while others maintain that such a connection does exist
(McGrady & Higgins, 1990; Lantelme et al., 1997).
It has meanwhile become customary in medical practice to remeasure blood
pressure after a rest period. A period of four minutes was recently recommended
in this context (Bakx et al., 1999). Research confirms that blood pressure does, in
point of fact, fall during repeated measurements, perhaps as a result of adaptation
to the procedure (Antivalle et al., 1990: Mancia et al., 1991; le Pailleur et al.,
1998). Apart from the influence of a medical intervention, variation in blood
pressure does, therefore, appear to be inherently associated with visits to a
physician.
4.3.3       TOPIC OF DISCUSSION
According to Malinow et al. (1986) and Linden (1987), the motor activity
involved in talking is not the only factor that is responsible for the increase in the
blood pressure. (Table 4.3.3). The content of the words that are spoken
(emotional versus neutral) appears to have an even greater effect on the blood
pressure, in view of the positive relationship that has been identified between the
level of the blood pressure and discussion of stressful events (le Pailleur et al.,
1996; Liehr et al.,1997; Fontana & McLaughlin,1998). This does not appear to be
                                                                            29
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<pre>explained by the fact that hypertensives, compared with normotensive
individuals, are more prone to psychosocial dysfunction (Fark, 1993).
Table 4.3.3 Topic of discussion
 Authors        Subjects     Design       Context      Outcome      Results
                                          variable     measure
 Linden,        31 patients  pre-/post-   emotional    blood        increase in
 1987                        test, cross- vs neutral   pressure     blood pressure
                             over         discussion                in emotional
                                                                    discussion
 le Pailleur et 42           pre-/post-   stressful vs physical     increase in
 al., 1996      hypertension test, cross- neutral      complaints   blood pressure
                             over         discussion                when discussing
                                                                    stressful events
 Liehr et al.,  60 patients  pre-/post-   emotional    blood        bigger increase
 1997                        test         vs neutral   pressure     during
                                          discussion                emotional
                                                                    discussion
 Fontana &      33 patients  correla-     perception blood          stress increases
 McLaughlin                  tional       of stress    pressure     blood pressure
 , 1998
 Eisenberg et 13             prospective relaxation    blood        relaxation
 al., 1991      hypertension cohort pilot              pressure,    reduces anxiety
                             study                     anxiety,     and complaints
                                                       physical
                                                       complaints
An alternative explanation for the rise in blood pressure in reaction to a visit to
a physician is offered by Nyklícek et al. (1998). Based on an extensive search of
the literature, they concluded that hypertensive individuals, due to their defensive
coping style, view stressful situations in a less negative light than normotensive
individuals, but that they respond with an increase in blood pressure due to
conditioning. The assessment of the situation, and possibly also other cognitions,
would appear to play an as yet unexplained mediating role here. There is, in fact,
evidence to suggest that an anxious and defensive personality structure (King et
al., 1990) and likewise strong avoidance behaviour (Kohlmann et al., 1996) are
         30
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<pre>related to the level of the blood pressure. Nevertheless, relaxation does not
appear to automatically lead to a marked reduction in the blood pressure
(Eisenberg et al., 1991).
Both the presence and the status of a physician, and the verbal activity and the
content of the conversation would thus appear to have a bearing on physio-
logical parameters.
4.3.4      EMOTIONAL DISCLOSURE
As was demonstrated in the previous section, unfavourable changes in blood
pressure may be perceived during the airing of emotions. This says nothing,
however, about the long-term effects of this phenomenon on health. The
stimulation of verbal disclosure of emotional experiences is widely used in
psychotherapy. In this section we shall look at what effects disclosure can have
within medical practice.
In view of the association between talking about stressful events and increases in
blood pressure, it is likely that talking with a physician about symptoms and their
perception will also impact on a person's state of health. It is, after all, a known
fact that the suppression of thoughts, feelings and behaviour demands physio-
logical effort. In the short term, that suppression can result in an increase in
autonomous activity, and in time it can even come to act as a cumulative
stressor, thus increasing the risk of physical complaints (Pennebaker & Susman,
1988). It is possible that the free expression of emotions may have non-specific
positive effects, since it gives a person the feeling that he is being looked after.
Research shows that the verbalisation of stressful experiences does, indeed, lead
to a rise in the blood pressure, but in the long term - probably as a result of
increased insight and cognitive changes - results in a better state of health in the
form of better immune function, less anxiety and lower HbA1c and blood
pressure (Orth et al., 1987; Pennebaker & Susman, 1988; Kaplan et al., 1989;
Pennebaker, 1989; Esterling et al., 1990, 1994) (Table 4.3.4).
It appears from studies in rheumatic patients that both everyday vicissitudes,
such as a quarrel or a car accident (Thomason et al., 1992), and traumatic
experiences, such as a decision or someone's death (Rimon & Laakso, 1985;
Zautra et al., 1989), are related to an objectively measurable resurgence of the
complaints. Talking about the emotions that have been experienced possibly has
important health promoting effects for these particular patients. This was, in fact,
confirmed by Kelley et al. (1997).
                                                                            31
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<pre>Table 4.3.4 Emotional disclosure on the part of the patient
  Authors     Subjects       Design    Context      Outcome         Results
                                       variable     measure
  Orth et     170            correla-  extent of    blood pressure  more
  al., 1987   hypertension   tional    disclosure                   disclosure,
              patients                                              lower blood
                                                                    pressure
  Kaplan et   45 gastric-    RATS      verbalisa-   general health, verbalisation of
  al., 1989   ulcer, 105               tion of      blood pressure, emotions
              hypertension,            emotions     blood glucose,  benefits
              59 diabetes,                          symptoms of     outcome
              43 breast-                            chemotherapy    measures
              cancer
              patients
  Kelley et   72             RCT,      emotional    pain, function  emotional
  al., 1997   rheumatoid     follow-   disclosure   & condition of  disclosure
              arthritis      up                     joints          improves
              patients                                              function upon
                                                                    follow-up
  Esterling   80 patients    pre-/     emotional    immune          the more
  et al.,                    post-     disclosure   function with   emotions are
  1990                       test                   regard to       verbalised, the
                                                    Epstein-Barr    better the im-
                                                    virus           mune function
  Esterling   57 Epstein-    RCT       talking vs   self-esteem     talking has
  et al.,     Barr virus-              writing      adaptive        more beneficial
  1994        positive                 about        coping          effects than
              patients                 stress                       writing
These studies show that it is important in research to give consideration to a
follow-up and to the intermediating role of mood. Furthermore, they suggest that
the verbalisation of emotional experiences can, in itself, have positive effects on
health. It is therefore possible that talking about the perception of a disorder
plays a major role in the therapeutic effects achieved in somatic healthcare. More
effects on health can possibly be achieved if a care provider also assists a patient
in changing his perception of the events (Murray et al., 1989). The health effects
          32
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<pre>arising from the airing of emotional stress could be directly related to the positive
correlation that exists between psychological stress and somatic symptoms
(Simon et al., 1996).
The implications of these findings for practitioners are revealed in a study by
Bensing et al. (1995), which showed that, in general, the more eye contact a GP
made with the patient, the more the patient would talk about psychosocial
problems. It is possible that, as a result of this increase in emotional disclosure by
the patient, non-verbal behaviour may also elicit physiological reactions. After
all, cognitive changes, such as a re-evaluation of a particular event, are set in
motion as a result of emotional expression and these can ultimately lead to
adaptive behaviour. This hypothesis has, to our knowledge, not yet been tested
out in practice.
4.4         AFFECTIVE        COMMUNICATION
A patient does not tell his personal story just like that. To do so he needs to feel
that he is in a trusted environment and be encouraged to do so (Suchman et al.,
1997). A good physician-patient relationship is essential in this respect. Such a
relationship can be promoted by first putting a patient at his ease. One of the
ways of doing this is by making conversation or by making a little joke.
4.4.1       SOCIAL CONVERSATION, HUMOUR
There is evidence to suggest that social conversation contributes to patient
satisfaction. It appears to give patients the feeling that they represent more than
just their illness (Hall et al., 1998). This greater satisfaction promotes compliance
and thus, indirectly, patient health. The extent to which social conversation in
itself also has a direct bearing on someone's state of health has not been
investigated. Research has, however, been conducted into the effect of humour.
From this it appears that humour has a buffering effect on stress (Yovetich et al.,
1990; Gaberson, 1991; Abel, 1998) (Table 4.4.1). This relaxing effect can be
expected to contribute to the patient's well-being.
4.4.2       EMPATHY , EMOTIONAL SUPPORT
A further important prerequisite when trying to induce a patient to talk is by
offering emotional support. Cohen and Wills (1985) showed that the perception
of support can protect an individual against the pathological influence of stressful
events. Simply the knowledge that there is a physician with whom one can
discuss one's problems can therefore have a beneficial effect. This is because the
presence of someone who has the intention of providing help appears to bring
                                                                             33
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<pre>Table 4.4.1 Social conversation, humour
 Authors      Subjects Physicians       Context      Outcome       Results
                                        variable     measure
 Yovetich     53        pre-/post-test, humour       anxiety       humour reduces
 et al., 1990 patients  control group                              anxiety
 Abel, 1998 131         cross-          humour       tension       humour reduces
              patients  sectional,                                 tension
                        correlational
 Gaberson, 15 surg.     post-test       humour vs pre-operative    humour lowers
 1991         patients                  music        anxiety       anxiety
about a reduction in anxiety and depression (Foa et al., 1991). It can be assumed,
however, that long-term improvement in a patient's state of health demands more
than simply "being there" for him. It appears that an empathic interaction, -in the
form of reassuring words or affective contact, can lead to a reduction in anxiety,
pain and blood pressure (La Monica et al., 1987; Weiss, 1990; Hwang et al., 1998)
(Table 4.4.2). It would thus appear to be worthwhile not only from an ethical
viewpoint but also in the interests of health promotion for a physician to ensure
Table 4.4.2 Empathy and emotional support from the physician
  Authors      Subjects   Design        Context          Outcome   Results
                                        variable         measure
  la Monica    656        pre-/post-    empathic         anxiety   less patient
  et al.,      cancer     test control  discussion                 anxiety with
  1987         patients   group                                    empathic nursing
                                                                   care
  Hwang et     60         pre-/post-    reassuring       pain and  reassuring words
  al., 1998    heart-     test control  words from the anxiety     reduce pain and
               surg.      group         physician vs               anxiety
               patients                 rest
  Weiss,       59 heart   within subj.  physical         anxiety   physical contact
  1990         patients   counter-      contact vs       and blood better for anxiety
                          balanced      verbal           pressure  and blood
                                        reassurance                pressure
          34
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<pre>that a patient feels at his ease during the consultation, which may possibly be
acutely stress-inducing. Psychosocial attention, empathy and support appear not
only to assist in creating and maintaining an optimal physician-patient
relationship, but also to have health-promoting effects.
4.4.3      PATIENT-CENTREDNESS
An effective approach to adopt in medical practice is patient-centred
interviewing. We speak of patient-centredness when a physician actively
stimulates input from the patient himself by paying explicit attention to the
perception of his complaints (in other words, the patient-related factors such as
anxiety, expectations and causes that are attributed to the complaints, as
discussed in Chapter 4.1) (Weston et al., 1989). Certainly when patients are
confronted with a disorder with an uncertain course, the outcome of which is to
a great extent determined by the behaviour of the patients themselves (e.g.
hypertension, diabetes or coronary heart disease), it is extremely important to
explore and discuss the views and motivation of the patient, especially since
physicians and patients frequently differ in the value that they attach to
personally relevant information (Chaitchik et al., 1992). Furthermore, the
patient's views can assist the physician in making a diagnosis (Peppiatt, 1992).
Research shows that the extent of a physician's patient-centredness contributes
to the improvement of somatic complaints in patients with headaches,
rheumatism, gastric ulcer, diabetes and breast cancer (Greenfield et al., 1985; the
Headache Study, 1986; Kaplan et al., 1989; Henbest & Stewart, 1990; Rost et al.,
1991; Henbest & Fehrsen, 1992; Lorig et al., 1993; Bertakis et al., 1998) (Table
4.4.3).
If, as was suggested earlier, hypertensive individuals do, in fact, experience
problems with interpersonal communication (Lynch et al., 1981), paying attention
to the significance of certain stressful events in their lives may contribute to the
efficacy of the treatment. A study by Lynch et al. (1982a) shows, in fact, that
blood pressure can be brought under control within fewer than ten therapy
sessions by confronting patients with the link between an increase in blood
pressure and talking about certain subjects, such as the stress that is caused by
anxiety about the high blood pressure, and by these links subsequently being
analysed and discussed in conjunction with breathing and relaxation exercises.
In addition to stimulation of input from the patient, attention paid by the
physician to the patient's individual perceptions, expectations and needs is also
important owing to the fact that a physician can only effectively reassure a patient
if he knows what is preoccupying him. In their study involving 120 patients with
functional abdominal complaints, Van Dulmen et al. (1996a) have shown that the
                                                                          35
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<pre>Table 4.4.3 Patient-centredness on the part of the physician
 Authors       Subjects   Design        Context       Outcome      Results
                                        variable      measure
 The           265        prospective "space" for     pain          more "space", less
 Headache      headache   cohort        pat. input    complaints    pain
 study, 1986   patients
 Henbest &     73 GP      prospective patient-        complaints, patient-
 Stewart,      patients   follow-up     centredness   anxiety       centredness has
 1990                                                               beneficial effect
 Henbest &     74 GP      prospective patient-        complaints, patient-
 Fehrsen,      patients   follow-up     centredness   anxiety       centredness has
 1992                                                               beneficial effect
 Greenfield    45 gastric RCT           information- functional    active informa-
 et al., 1985  ulcer                    seeking       state of      tion-seeking
               patients                               health        improves health
 Rost et al.,  61         RCT           patient       blood         beneficial effects
 1991          diabetes                 activation    glucose,      of patient-centred
               patients                 program       physical      activation
                                                      function
 Lorig et al., 224        pre-/post-    patient-      pain and      better outcomes
 1993          arthritis  test, 4-year  centred       medicine
               patients   follow-up     information   consump-
                                                      tion
 Bertakis et   509        RCT           psychosocial gen. state of attention to
 al., 1998     patients                 attention     health        emotions
                                                                    promotes health
more able internists are to correctly assess the significance of patients' complaints,
the less frequently patients need to consult the physician again after contact has
ended. A primary requirement is that physicians must give patients the "space"
to recount what it is concerning them. Recent research shows that physicians
actually do this in only 28% of cases (possibly due to lack of time). It is worth
noting that when physicians do allow their patients to say what is on their minds,
the consultation in question appears only to last an average of six seconds longer
(Marvel et al., 1999).
          36
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<pre>4.5         INSTRUMENTAL        COMMUNICATION
4.5.1       PROVIDING INFORMATION
The verbal information which a physician gives a patient will influence the
patient's expectations and thus the way he perceives his symptoms. It is even
plausible that the mere fact of naming the symptoms or making a medical
diagnosis has a therapeutic effect, since it gives a meaning to the complaints and
can provide a feeling of reassurance (Brody & Waters, 1980). Furthermore, the
formulation of a diagnosis results in the mobilisation of support and also activates
possible means of controlling the complaints. This does preassume, however, that
the diagnosis fits in with the patient's frame of reference (Bügel & van
Everdingen, 1998). The provision of information by recording a consultation on
cassette, for example, can also create a feeling of control (even if the patient never
actually refers to that information), meaning that patients have a better idea of
what to expect (Ong et al., 1995). The mere fact that many patients do actually
listen to the recording confirms that a need for information is being satisfied
(Johnson & Adelstein, 1991; Deutsch, 1992).
For the patient, the need for information is, in general, an important reason for
consulting a physician (van Kar et al., 1992b). The fulfilment of this need will
therefore also, in itself, have beneficial effects. Good information also has a
bearing on how quickly a patient recovers after an operation (Cupples, 1991).
Giving patients a recording of a discussion with the physician helps them to
retain information and also helps to reduce the number of visits to the GP, but
does not lead to a reduction in anxiety (Cupples, 1991; Hogbin et al., 1992;
Rylance, 1992; McHugh et al., 1995). The stress that is associated with a visit to
a physician can even lead to patients having difficulty remembering information
(Newcomer et al., 1999) and thus failing to follow a physician's advice properly.
Too much cortisol can damage (Bremner, 1999) the hippocampus, an
intermediate stage in the long-term storage of declarative knowledge, or else
temporarily block it off (Newcomer et al., 1999), with the result that either no
information at all is stored, or else only fragmented information. The manner in
which information is provided appears to be crucial. In particular, honest, open
and personally-tailored communication puts patients at their ease (Sardell &
Trierweiler, 1993). A good discussion technique can have positive effects. This
is underlined by the research by Hwang et al. (1998) that was referred to earlier
(section 4.4.2). Patients of physicians trained in imparting information displayed
a greater reduction in anxiety than patients of physicians who had received no
such training (Rutter et al., 1996). Furthermore, complaints appear in general to
show greater improvement when physician and patient identify the same
complaints as posing a problem (Starfield et al., 1981).
                                                                             37
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<pre>Table 4.5.1 Information-giving by the physician
Authors     Subjects    Design        Context       Outcome      Results
                                      variable      measure
Cupples, 40 CABG        randomised pre-operative anxiety and information
1991        patients    post-test     information   speed of     enhances outcome
                                                    recovery
Hogbin      67 breast   randomised consultation     level of     better informed as
et al.,     cancer      pre-/post-    with          patient      a result of cassette,
1992        patients    test          physician on  information not less anxious
                                      cassette      and anxiety
McHugh 117 cancer       prospective   information   retention of repetition of info.
et al.,     patients    RCT,                        information promotes retention,
1995                    follow-up                   and anxiety not reassurance
Rylance, 286            post-test     consultation  retention of taping consultation
1992        patients in               on cassette   information helps
            paediatric
            sector
Rutter et   36 cancer   pre-/post-    information   anxiety,     more info.
al., 1996   patients    test, control               depression, promotes control,
                        group                       feeling of   reduces anxiety
                                                    control      and depression
Starfield   135         correla-      agreement     problems     greater improve-
et al.,     patients in tional        between       presented    ment if physician
1981        internal or               physician and              and patients
            paediatric                patients                   identify same
            medicine                                             problems
Sox et al., 176         RCT           with/without  reduction    after diagnostic
1981        patients                  diagnostic    in pain,     examination,
            with non-                 examination   anxiety      patients have less
            specific                                             pain, equally
            chest pain                                           anxious
Glasunov 95 hyper-      prospective   with/without  blood        periodic
et al.,     tensives    cohort        physical      pressure,    examination
1973                                  examination   cholesterol, reduces outcome
                                                    glucose
        38
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<pre>It is worth noting that not being able to find a physical explanation also gives
meaning to the complaints. Studies by Sox et al. (1981) and Glasunov et al. (1973)
show how this process is influenced by the information that emerges from the
physical and diagnostic examination. Further examination results in less pain
complaints and lower blood pressure.
Information given by the physician therefore has an influence on patient health.
4.5.2      NEEDS OF THE PATIENT
The same information will not elicit the same effect in every patient simply
because patients have different starting situations and not all physicians impart
information in the same way. The extent of the information provided by
physicians depends in part on the need for information and the concerns of the
patient in question (Street, 1991). Research by Miller and Mangan (1983) shows
that it is worthwhile in this connection to divide patients into two categories:
patients who want as much information as possible about what is wrong with
them (“monitors”) and patients who want to know as little as possible (“blunters”)
(Table 4.5.2). If the volume of information does not conform to one of these two
coping styles, there appear to be adverse psychophysiological consequences.
Personally tailored information can only be given by adopting a patient-centred
approach (see section 4.4.3), whereby the physician is mindful of the patient's
individual needs. Depending on a person's level of education and coping style,
there are patients who find it sufficient to receive information and others who
want to be actively involved in the choice of a particular treatment (Margalith &
Shapiro, 1997). Thus "monitors" appear to have a greater need for diagnostic tests
and information, but at the same time want to play a less active role in their care
(Miller et al., 1988). It should be noted that one coping style is not, by definition,
any more effective than the other. In fact, this appears to be dependent on the
controllability of the disorder, the nature of the outcome measures (proximal or
distal) and the stage which the disease has reached (Kiyak et al., 1988).
Patients can themselves exercise control over the nature and amount of
information they receive through their individual communication style. This
appears to have beneficial effects on health, e.g. via a reduction in HbA1
(Greenfield et al., 1988). However, information alone will not be sufficient to
produce beneficial physiological effects. For example, a meta-analysis of inter-
ventions in diabetes patients reveals that information alone does not result in
better metabolic control. A more individual approach, including attention to
psychosocial factors, appears to be much more fruitful in this respect (Padgett et
al., 1988). Moreover, the content of the information can have an adverse impact
                                                                            39
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<pre>Table 4.5.2 Patient needs
 Authors      Subjects       Design        Context       Outcome        Results
                                           variable      measure
 Miller &     40             randomised, information     psycho-        a better
 Mangan,      gynaecologica pre-/post-test matched to    physiological match results
 1983         l patients                   needs         arousal and    in less
                                                         anxiety        arousal and
                                                                        anxiety
 Greenfield 73 diabetes      RCT           patient-      HbA1           advance info
 et al., 1988 patients                     centred                      improves
                                           advance                      HbA1
                                           information
 Orth et al., 170            correlational info. from    blood          discl. and
 1987         hypertensives                physician,    pressure       info. reduce
                                           disclosure by                blood
                                           patients                     pressure
 Amigo et     60             pre-/post-    negative,     blood          blood
 al., 1993    hypertensives, test, control posisitve or  pressure       pressure
              60 normo-      group         neutral                      fluctuates
              tensives                     suggestion                   according to
                                                                        nature of
                                                                        suggestion
 Larsson et   53 cancer      dyadic,       care          anxiety        better match,
 al., 1998    patients       correlational matched to                   less anxiety
                                           patients'
                                           needs
on health, e.g. by increasing the blood pressure (Orth et al., 1987; Amigo et al.,
1993).
 It will not always be easy for care providers to correctly assess the emotional and
cognitive needs of their patients. Care providers often take a different view of a
patient's complaints than the patient himself (Martin et al., 1991; Larsson et al.,
1998).
The extent to which a physician takes a patient's needs into account plays a role
in the effects which the information given by the physician elicits.
          40
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<pre>4.5.3      INFLUENCING COGNITIONS
Information given by a physician must be cognitively and emotionally processed
by the patient. This processing has an influence on the physiological activity and
on the immune system (Brosschot et al., 1991; Lutgendorf et al., 1994).
Conversely, cognitions can play a role in perpetuating physical complaints.
Negative cognitions (catastrophising, see section 4.1.5) and somatic attributions
(see section 4.1.6) appear to be capable of increasing the intensity of pain (Shutty
et al., 1990; Summers et al., 1991; Turk & Rudy, 1992; van Dulmen et al., 1997)
and perpetuating symptoms of chronic fatigue (Vercoulen et al., 1996) (Table
4.5.3). Changing such cognitions will therefore impact positively on physical
complaints (Payne & Blanchard, 1995; van Dulmen et al., 1996b) and even on
more serious disorders such as AIDS and cancer (Kiecolt-Glaser & Glaser, 1992).
According to Murray (1989), emotional expression alone, is, in point of fact,
insufficient to influence unfavourable cognitions. Active intervention on the part
of the care provider is needed if disclosure is to have a long-term effect. For
example, the provision of clear information and advice to hypertensive patients
appears to be capable of reducing misconceptions about a disorder, resulting in
better control over blood pressure (Inui et al., 1976).
Both controlled (Bradley et al., 1987; Devine & Spanos, 1990, inter alia) and
uncontrolled studies (Williams et al., 1993; van Dulmen et al., 1996a, inter alia)
have been carried out into the effects of interventions aimed at modifying
cognitions and emotions in the treatment of physical complaints in medical
practice. A meta-analysis of 51 studies into the effect of cognitive coping
strategies on the reporting of acute pain demonstrates the value of these strategies
in relation to positive expectations (Fernandez & Turk, 1989). This was
confirmed by Devine and Spanos (1990). A study by Bradley et al. (1987) shows
that alongside conventional drug treatment, simple cognitive behaviour-therapy
strategies - for example encouraging patients to perform relaxation exercises
combined with the restructuring of dysfunctional views - can provide long-term
relief of headache complaints. Studies by Wells et al. (1986) and Vasterling et al.
(1993) produce similar results. Advice from the physician, such as "Take it easy"
and "Find something to take your mind off it" may possibly have the same effect.
O'Leary et al. (1988) demonstrate the beneficial effects of cognitive behaviour
therapy in which patients receive various cognitive and behavioural tips on
coping effectively with a disorder5.
Successful cognitive interventions have a number of components in common,
namely explaining to the patient the connection between the meaning and the
perception of his complaints, encouraging physical and psychological relaxation
and identifying negative ideas and replacing them with patient-specific positive
ideas.
                                                                           41
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<pre>Table 4.5.3 Influencing of cognitions by the physician
Authors       Subjects     Physi-       Context        Outcome          Results
                           cians        variable       measure
Payne &       34 IBS       RCT,         identifying    physical         intervention has
Blanchard,    patients     follow-up &                 complaints and positive effects
1995                                    modifying      anxiety
                                        cognitions
van           110 IBS      prospec-     paying         abdominal-       positive relation-
Dulmen et     patients     tive         attention to   pain symptoms ship between
al., 1997                  follow-up somatic                            reduction in
                                        attributions                    attributions and
                                                                        complaints
Inui et al.,  102          pre-/post- discussing       knowledge,       lower blood
1976          hyper-       test,        (or not        compliance       pressure after
              tensive      control      discussing)    and              discussing patients'
              patients     group        cogn. and      blood pressure cognition
                                        attitudes
Wells et al., 24           RCT, pre- changing          anxiety, pain    less anxiety and
1986          surgical     /post-test   cogn.                           pain
              patients
Bradley et    53 rheum. RCT             discussing     pain, anxiety    etter outcomes
al., 1987     arthritis                 cognitions     and function     after discussing
              patients                                                  cognitions
Devine &      96           pre-/post- cognitive        pain sensations cogn. coping
Spanos,       patients     test,        intervention in laboratory      mechanism more
1990                       control      and positive                    effective than pos.
                           group        expectations                    expectations
Williams et 212            pre-/post- cognitive        pain intensity,  positive effects of
al., 1993     patients     test, 6-     skills,        qual. of life,   cognitive
              with chro- month          relaxation     physical         behaviour therapy
              nic pain     follow-up                   function
Vasterling    60 cancer 3x2             cognitive      nausea and       cogn. distraction
et al., 1993  patients     factorial    distraction    blood pressure reduces complaints
O'Leary et    30           RCT          information pain,               less pain, better
al., 1988     patients                  and            functional state joints, immune
              with                      cognitive      of health,       function
         42
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<pre>It is this sort of "non-specific" approach that one usually already finds to a greater
or lesser extent in medical practice. After a visit to the doctor, patients frequently
modify their ideas about the cause of their complaints and often already feel less
concerned once they have heard that they have not contracted a life-threatening
disease (van Dulmen et al., 1995). This reassurance can manifest itself in a
reduction both in physical complaints and in the accompanying intake of
medication (visits to the doctor and use of medication).
Every patient wrestles with thoughts and emotions that are connected to his
specific situation at a given moment. By getting these out into the open and
explicitly placing them on the agenda - for example, by discussing their validity -
one can effectively reassure the patient (van Dulmen et al., 1997). It is therefore
important that a physician should form a good picture of what it is that is
preoccupying the patient. The fact that physician and patient are in agreement
about the reason why the patient is feeling unwell plays an important role in the
improvement of complaints (Bügel & van Everdingen, 1998).
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<pre>44</pre>

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<pre>5           SUMMARY          OF UNDERLYING MECHANISMS
The second of the questions underlying this study relates to explanations for the
effect of context in healthcare. Many explanations have been given for the effect
of context in healthcare. For example, health effects that occur as a result of a
hospital visit in the absence of any specific therapeutic measures may possibly be
explained on the basis of theories involving the relationship between the soma
and the psyche, such as psychophysiological and psychoneuroimmunological
explanations. Furthermore, classical conditioning theory may explain how
apparently neutral factors can assume importance.
In this chapter we shall discuss the most important explanations. Global
mechanisms such as anxiety reduction or the release of endogenous opiates have
an impact on the entire body. Other mechanisms such as conditioning or the
effects of expectations, on the other hand, relate only to specific parts of the
body. Research by Montgomery and Kirsch (1996) is inconsistent with the
existence of global mechanisms. Anxiety reduction could just as easily be an
aspect as a cause of context effects (Wall, 1993).
5.1         STRESS REDUCTION
Stress plays an important role in the development and course of disorders and
in connection with therapeutic effects (Maes et al., 1987). Because secretion of
cortisol rises in situations of increased stress, the hormone cortisol is considered
to be the indicator of stress (Francis, 1979). Research into this physiological
measure of stress was for a long time hampered by the need to identify the
cortisol concentrations in the blood, and blood-tests are, in themselves, already
a stress-increasing, unnatural situation, the effect of which may possibly interact
with the effect of a particular intervention. This situation has improved now that
research has shown that cortisol can also be reliably measured in saliva (Vining
et al., 1983; Burke et al., 1985; Tarui et al., 1987). As a result, fresh light has been
shed on the individual variability in reactions to psychological stress.
Research conducted in 24 female trial subjects by Bohnen et al. (1991)
demonstrates that the increase in cortisol in response to a psychological stressor
in which trial subjects were confronted with an uncontrollable situation is
dependent upon an individual's cognitive coping style. Cognitive re-evaluation
and the ability to put the situation into perspective appear to lead to a less
marked cortisol response. It is worth noting that the relationship between chronic
stress and cortisol does not appear to be so clear-cut as that between acute stress
and cortisol. Chronic stress does not result in either an increase or a decrease in
cortisol production. If account is taken of the extent to which an individual is able
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<pre>to control the chronic stressor in question, then the relationship becomes clearer
(Vingerhoets & Assies, 1991). Furthermore, as far as immunological parameters
are concerned, it appears that the more chronic stress a person experiences in his
daily life, the greater is his immunological response to acute stressors in terms of
reduced NK cells and lymphocytes (Brosschot et al., 1994). Cortisol therefore also
has an influence on the immune system (Nomoto et al., 1994).
An important problem in research with physiological parameters as a measure
of stress is the apparent lack of any conclusive relationship between these
objectively measurable outcomes and the subjectively experienced outcomes.
Thus a person may feel more relaxed in response to a particular intervention and
yet still have a higher cortisol level (Manyande et al., 1992) and the relationship
between stress and physiological measures of stress also appears to be related to
an individual's inclination to report physical symptoms (Vingerhoets et al., 1996).
Even though physiological measures of stress are therefore not ideal at an
individual diagnostic level, related research in groups of patients would appear to
be worthwhile, since these individual variations will then be averaged out.
5.2         CLASSICAL       CONDITIONING, THE LEARNING EFFECT
According to the theory of conditioning, context effects are conditioned respon-
ses to stimuli which are present in the therapeutic (or experimental) setting. -
Neutral, unconditioned stimuli that occur concurrently with the treatment, such
as a physician, a physical examination, a hospital, an injection or a tablet, are
associated with a reduction in negative symptoms and are thus positively condi-
tioned as far as recovery and anxiety reduction are concerned. As a result of that
association, improvement can already begin to occur in response to neutral
stimuli in the absence of an active intervention. This argument is supported, inter
alia, by research indicating that the effects of placebo medication are more
marked if, during a previous phase, an active substance has been taken (Suchman
& Ader, 1992). Similarly, experience of ineffective treatments will be contributory
to a negative response to follow-up treatments. Voudouris et al. (1985) were the
first to conduct research into the conditioning effect in human beings. They
investigated what analgesic effect an inert ointment had on the experience of
pain impulses among 32 healthy trial subjects. In half of the trial subjects, the
pain impulses were experimentally increased following administration of the
ointment, while in the other half they were reduced. Individual pain thresholds
were established in advance for all trial subjects and they were "taught" that the
ointment had an effect by varying the intensity of pain after administering the
ointment (whereas the trial subjects were led to believe that the stimulation
        46
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<pre>remained the same). The results confirm that the reaction to the ointment can be
conditioned both in a negative and positive direction. In their follow-up studies,
Voudouris et al. (1989, 1990) show that the expectations of patients alone are
insufficient to explain this conditioning effect. Öhman and Soares (1998) have
also recently demonstrated that expectations are not related to the conditioned
response. These studies suggest that in order to determine the effect of a
treatment, it is important to examine how previous treatments have been
experienced by the patient concerned. The previously cited studies by Bovbjerg
et al. (1990) and Kvale et al. (1991) also demonstrate that the association of certain
stimuli (hospital, smell and taste of chemotherapy) with aversive effects (nausea
and anxiety) can trigger effects of this type. Moreover, comparable research in
27 cancer patients (Fredrikson et al., 1993) suggests that the reduced resistance
that is associated with a high level of anxiety in these patients can result in the
occurrence of a conditioned decline in the natural defence mechanism (see
section 5.4). Blood glucose concentrations also appear to be conditionable (Fehm-
Wolfsdorf et al., 1993; Stockhorst et al., 1999).
Conditioning effects thus appear to play an important role in context effects.
Physicians can enhance these effects by the way in which they approach their
patients. Although classical conditioning provides a good explanation for the
context effects, it cannot be the only explanation, since extinction would have to
occur after repeated association. In the case of expectations, however, no
extinction takes place (Kirsch, 1997). One reason for this could be that the result,
i.e. symptom reduction, is an extremely strong reinforcer: once a response
expectation has proved to be correct, it will confirm itself even without any
renewed reinforcement by an unconditioned stimulus. It therefore seems likely
that the expectations that are formed by conditioning which patients have from
their care have an important role to play in explaining context effects.
5.3         EXPECTANCY,        EXPECTATIONS
Response expectations are not only developed through conditioning, but can also
be triggered by the information that a person receives. As a result of
conditioning, a person may well expect that one particular event will follow
another, but this remains dependent on the information that the conditioned
stimulus gives about the unconditioned stimulus. Various aspects within the
physician-patient contact, such as the physician-patient relationship, confidence,
reduction in anxiety, etc, help to boost those expectations. Ultimately it is the
response expectations that are determinative for the effect of a therapeutic
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<pre>measure, not the strength of the association that underlies those expectations or
the way in which those expectations have been formed (Kirsch, 1997).
Several hypotheses have been formulated to explain the connection between
expectations and a (positive or negative) therapeutic effect. Thus the expectation
that a treatment will be effective will reduce anxiety and hence symptoms, the
patient develops a more positive attitude, and as a result regards symptoms as
being more controllable, or starts to be less avoidant of certain activities. The
question as to which of these mechanisms are effective cannot be answered on
the basis of the empirical studies that were discussed earlier.
5.4        PSYCHONEUROIMMUNOLOGY
Psychoneuroimmunology aims to study the reciprocal relationship between the
central nervous system and the immune system. Susceptibility (incidence,
duration and severity) to various disorders, such as influenza, colds, TB, allergies
and autoimmune disorders appears to be related to psychological factors such as
emotional stress (Glaser et al., 1992; Glaser et al., 1999). There is evidence to
suggest that during periods of extreme (chronic) stress the immune system is
weakened through a decline in multiplication and activity of antibodies (white
blood cells such as lymphocytes and NK cells), which are needed in order to
combat exogenous micro-organisms (antigens such as bacteria, parasites and
viruses). Thus diseases (infectious diseases, HIV and cancer) are afforded greater
opportunities (Martin, 1987; Kiecolt-Glaser & Glaser, 1995; Cohen & Herbert,
1996). Acute, short-term stress actually appears to activate the immune system,
probably as a result of an acute arousal response (Naliboff et al., 1991; Gerritsen
et al., 1996). Furthermore, a decrease in antibodies appears to take place
principally where an individual thinks he has no control over his situation and
loses the capacity to successfully avoid stressors (Pettingdale et al., 1981;
Brosschot et al., 1991, 1998). Certain hormones such as ACTH, insulin, en-
dorphin, adrenaline and cortisol, the release of which is influenced by stress,
appear to interact with the immune system. The discovery of the same peptide
receptors in the brain and other organs also demonstrates that there is a direct
connection between the mind and the body. The complexity of psychoneu-
roimmunology is also evident from the findings that immune responses can be
conditioned (Bovbjerg et al., 1990; Buske-Kirschbaum et al., 1992; Ader & Cohen,
1993).
The relationship between stress and immunological reactions is mediated by
cognitions. This was demonstrated in a study by Wiedenfeld et al. (1990) in 20
phobic patients whose immune response, measured by the number of
lymphocytes and T cells, increases as they experience greater self-efficacy, or in
        48
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<pre>other words, the more convinced they are of their own ability to control the
phobic stressor. Comparable outcomes emerge from a study by Wallbott and
Scherer (1991) in 60 trial subjects, which demonstrates that physiological
reactions to mental stressors are dependent on how an individual copes with the
stressor. In a study of 62 HIV-infected men, Goodkin et al. (1992) also found a
positive relationship between the number of NK cells and an active coping style,
with positive reinterpretation, acceptance and active seeking of help being key
factors. This ties in with the outcomes of research by Manuck et al. (1991) in 25
trial subjects, which reveals that the influence of psychological stress on the
immune system is related to an individual's cardiovascular reactions to stress. The
immune system of people who were more inclined to respond to stress with an
increase in blood pressure and pulse proved to be more susceptible to a decline
in defence mechanisms than that of individuals who lack such a rapid response.
It is possible that coping styles such as avoidance and resistance also play a role
here. It is worth noting that immunological effects of stress appear to be most
clearly reflected in changes in the number of NK cells (Brosschot et al., 1992).
As far as the clinical implications of such experimentally proven immunological
changes are concerned, it would appear to be important to measure not only the
patient's immunological parameters, but also the presence of cognitive coping
styles and the degree of cardiovascular reactivity.
5.5        CONCLUSION
It is not possible to offer a single explanation for the effect of context in
healthcare. Countless interactions are taking place inside the body between the
different systems that are responsible for hormonal, immunological and
cardiovascular responses (Sgoutas-Emch et al., 1994; Benschop et al., 1998). It
would appear important to have an understanding of an individual's conditioning
history as far as a particular treatment is concerned, since the effect of a given
treatment and the immune response are both dependent on the stimuli to which
a body has been exposed hitherto. In general, cognitions of physicians and
patients alike appear to play a major role in the interpretation of physiological
processes and of the effects of therapeutic measures.
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<pre>50</pre>

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<pre>NOTES
1  Because the terms "placebo" and "placebo effect" are still widely used, it
   is possible that they will also appear in this report. Where the term placebo
   effect is used, it refers to the positive or healing effect of the entire context
   within which a physician-patient contact takes place; nocebo refers to the
   negative effect of this context.
2  The mediating role of such factors as stress, anxiety and coping strategies
   will only be considered indirectly in this study.
3  Where no hits were found for a search term in a title, the abstract was
   screened for the indexed term.
4  "Regression towards the mean" in this case means that patients are
   inclined to consult a physician when their complaints are most severe and
   will also diminish without intervention.
5  The impression may exist that the influencing of cognitions by a physician
   is actually tantamout to pracising cognitive therapy. This might result in
   questions being raised as to the extent to which one can still speak of
   context effects in this connection. Treatment is termed cognitive therapy
   if this is all it comprises. If, however, physician-patient contact also
   includes discussion and the influencing of cognitions and emotions, then
   it is not interpreted in this way.
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<pre>Sector Councils (Sectorraden) are independent bodies comprising representatives
of the research community, the general public, trade and industry, and
government (as an advisory member). Sector Councils are, first and foremost,
engaged in identifying developments within society and, on this basis, any gaps
in knowledge that might have implications for publicly financed research. In
addition, Sector Councils are also geared towards analysing trends in science and
technology and their implications for society as a whole.
Under the Sector Councils Framework Act on Research and Development, a
system of Sector Councils operates in the following areas: healthcare, nature and
the environment, spatial planning, the agronomic sector and development
cooperation.
Being an umbrella organisation, the Consultative Committee of Sector Councils
for Research and Development (COS) provides a platform for consultation on
issues of collective interest and the organisation of projects and conferences on
such topics as the formulation of questions and the development of
methodologies. The COS also looks after the interests of the sector councils on
the basis of common standpoints. Under the Framework Act, bodies that are not
actually sector councils but operate in a similar fashion may be advisory
members of the COS - e.g. the Study Centre for Technology Trends (STT).
The COS has at its disposal a budget fixed by the Ministry of Education, Culture
and Science (OC&W) for the funding of programming studies (the coordination
fund).
       52
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<pre>NIVEL (National Institute for Research into Healthcare) is an independent
national research institute that conducts research within the healthcare field. The
aim of this study is to acquire and disseminate knowledge and an understanding
of the structure and functioning of healthcare and social services, also in relation
to other sectors of society. In this respect, NIVEL is aimed both at care users and
care providers as well as national policy-making organs. Scientific quality is
guaranteed by external certification (ISO standard 9001), and by the fact that the
research is performed at two graduate schools accredited by KNAW (the Royal
Netherlands Academy of Arts and Sciences) - CaRe and Psychology & Health.
                                                                          53
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<pre>54</pre>

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<pre>APPENDIX            A:     INVITATIONAL CONFERENCE ON
RESEARCH          INTO THE EFFECT OF CONTEXT IN HEALTH
CARE
As a result of the programming study entitled "The Effect of Context in Health
Care"
the Advisory Council on Health Research (RGO) organised a conference aimed
at establishing whether it is possible to carry out research into context factors,
and if so, how this might be accomplished. Held in Utrecht on 26th September
2000, the conference was divided into the following three parts: discussion of the
report and of the methodological and psychoimmunological problems associated
with research into context factors; scientific papers concerning the opportunities
for research; and a general discussion.
Following an introductory address by the Chairman of the RGO, Professor
H.G.M. Rooijmans, Dr A.M. van Dulmen of the Netherlands Institute for
Research into Health Care (NIVEL) presented the report and provided some
explanatory comments about the questions underlying the research and the
findings. The literature study provides an overview of context factors, for which
three explanatory mechanisms are cited: stress reduction, classical conditioning
and psychoneuroimmunological mechanisms.
Dr. A.J.M. de Craen (Clinical Epidemiology, LUMC1) looked at the
methodological problems surrounding research into context factors. There is a
publication bias because virtually only positive findings appear in the literature.
To prevent any distortion in the research results, investigators generally adopt
randomisation and blinding techniques. This widely used methodology is
inadequate in the case of research into context effects, while the alternatives
(Zelen design and pre-randomisation) are not acceptable. De Craen views the
provision of informed consent prior to randomisation as one possibility. The
patient then needs to be informed of the fact that it is important, for study
purposes, that he is not aware of the exact questions which the investigators are
seeking to answer. He also needs to be made aware of the fact that the study has
the approval of the Medical Ethics Committee. In the past, a proposal for such
1
  University of Leiden Medical Centre
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<pre>a study design was approved by the former Central Committee on Medical
Research Ethics (KEMO, which is now known as the CCMO2).
Professor C.J. Heijnen (Wilhelmina Children's Hospital, Utrecht) gave a paper
on psychoneuroimmunological aspects of context effects. A great deal of research
has been conducted into acute effects of context on various neuroimmunological
parameters (as is evident from the literature study), but very little work has been
done on the influence which context has upon the clinical course of the disease
in question. Animal-based experimental research into the influence of chronic
stress indicates that there is a relationship between individual coping strategy and
the possibility of certain disorders being induced. Context factors may possibly
lead to changes in the balance of the immune system (Th1 versus Th2 cells)
which influence the clinical course.
Three speakers then outlined their visions of the possibilities for research into
context factors.
Professor R. van Dyck (Department of Psychiatry, VUMC3 ) proposed, as a first
step, that a systematic review should be conducted among patients (and possibly
also, at a later stage, among care providers) with a view to gauging the effect of
each individual factor. Research into the role of patient preference is one
example. In the case of anxiety disorders, the non-preferred treatment appears
to be just as effective as the preferred approach. Van Dyck expected that a
number of the factors mentioned in the study actually have a negligible effect.
Only the most influential factors should be considered for further investigation.
Furthermore, he found that "bedside manner" deserves to receive more attention.
Finally, cognitive behavioural therapy is, to some extent, composed of non-
specific factors. Research should enable this technique to be applied more
efficiently.
Professor F.J.H. Tilders (Department of Pharmacology, VUMC) emphasised the
intended goal of the research: the importance for science and health care. The
goal must be clear in order to determine the research strategy. Tilders focusses
on two areas: research into the efficacy of drugs and research into context effects
in health care. Drug trials are usually expressly designed to eliminate the impact
2
  Central Committee on Medical Research Involving Human Subjects
3
  Free University (of Amsterdam) Medical Centre
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<pre>of context factors as far as possible. We might ask ourselves, however, whether
the effect of context and the specific effects of a given substance are not additive,
and whether we should not actually be striving for precisely that additive effect.
As far as health care is concerned, there is sufficient evidence to suggest that
context factors do play a role. In order to identify those factors, one might
investigate whether there are relevant differences between the treatment
outcomes that are achieved by different physicians. If this is the case, then
adoption of an open search strategy in exploring the background to that variation
might enable us to identify the crucial factors.
Professor C. van Weel (Department of Family, Social and Nursing-Home
Medicine, KUN4) approached the subject from the perspective of the general
practitioner, asking what "context" a GP has to deal with. He looked at the need
for research into context effects and made it clear that a research program would
have to be based on medical practice. One possibility would be to study the
discrepancy between "efficacy" and "effectiveness". Van Weel cited the following
four research priorities as far as family medicine is concerned: context effects and
the effectiveness of deciding against treatment (whether this be desired or
required); empowering strategies for the treatment of patients with chronic
complaints (requests for a changeover from a casuistic to a systematic approach);
critical assessment of context effects in connection with marginally effective
interventions; and the relationship between context and the desired results of the
treatment in question.
The discussion focussed on the question of whether research into context effects
is worthwhile and if so, what avenues need to be pursued.
The conclusion that was reached in the debate about the first question was a
cautious "yes". Research was considered to be possible with regard to
hypertension, diabetes mellitus, asthma, anxiety and depression. Research was
also regarded as being both feasible and relevant in connection with syndromes
of as yet unknown pathogenesis (e.g. whiplash, chronic fatigue syndrome,
irritable bowel syndrome). Sick leave and quality of life are outcome measures
that might possibly be employed.
Van Dyck wondered whether it might be possible to miss out the observational
phase of the research. The potential factors have, after all, already been
4
        Catholic University of Nijmegen
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<pre>identified. He emphasised once again the need to look for the most influential
factors (i.e. factors whose effect exceeds the natural variation in clinical course).
These factors alone should be subjected to mechanistic research.
Rooijmans foresaw problems as far as the manipulation of context factors is
concerned. How do you isolate a single factor from the other factors, and how do
you tell the patient what you are going to do?
The discussion was then directed at the influence of attributions (whereby a
patient ascribes a symptom or complaint to a specific cause). Cancer patients
were cited as an example of a patient group with a strong tendency towards
attributions. The conclusion was reached that it is possible to carry out research
into attributions in the case of both chronic and acute conditions. Attributions
have implications for the patient himself and can be modified. It emerged that
there may possibly be differences between GPs (who ask about attributions
almost as a matter of course) and specialists (who are possibly less inclined to ask
such questions), and that the very manner in which questions about attributions
are asked is a topic suitable for research.
A number of comments were made as a result of this discussion. First of all, when
considering the doctor-patient relationship it is important not to lose sight of the
influence of context factors in a broader context. Consideration must be given to
the patient's social environment and what impact this has. Furthermore, the term
"manipulation" has negative connotations. The terms that are to be used need to
be carefully chosen and explained. Finally, when designing the research it is
necessary to take cultural differences into account (consideration of ethnic
minority groups).
Professor J.M. Bensing (NIVEL) and Professor H.G.M. Rooijmans rounded off
the conference by concluding that there are sufficient grounds for continuing
along the path that has already been embarked upon and for seeking
opportunities to flesh out the research that is being conducted in this area.
Note added in proof: The fact that there is interest in this subject at international
level as well as in the Netherlands is evident from the conference entitled "The
Science of the Placebo: Toward an Interdisciplinary Research Agenda", which
was held at the National Institutes of Health in Bethesda, USA, from 19-21
November 2000.
       74
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<pre>APPENDIX B CONSULTED                    EXPERTS
As part of this study, contact has been established with various experts who in
their work have had some form of involvement with placebo or context effects.
Their ideas and views have been incorporated in this report.
-  Dr AJM de Craen,
   Clinical Epidemiology, Leiden.
   Placebos and placebo effects in clinical trials
-  Professor R van Dyck,
   Valerius Clinic, Amsterdam.
   Placebo and suggestion in psychotherapy and hypnotherapy
-  Professor L van Doornen,
   Healthcare Psychology, Utrecht.
   Psychophysiology, stress and health
-  Professor J Kleijnen,
   NHS Centre for Reviews and Dissemination, York.
   Field of research: Context effects in physician-patient contacts
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