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Familia
l amyloid polyneuropathy: elaboration of a
therapeutic patient education programme, EdAmyl
Journal:
Amyloid
Manuscript ID:
DAMY-2014-0036.R1
Manuscript Type:
Original Article
Date Submitted by the Author:
20-May-2014
Complete List of Authors:
Theaudin, Marie; CHU Bicêtre, Neurology
Cauquil, Cecile; APHP/CHU Bicêtre, Neurology
Antonini, teresa; APHP?\/Paul Brousse, CHB
algalarrondo, vincent; APHP/Beclere, cardiology
Labeyrie, Celine; APHP/CHU Bicêtre, Neurology
Aycaguer, sophie; Edusante,
Clement, Mireille; Association Française contre l’Amylose,
Kubezyk, Marie; APHP/CHU Bicêtre, Neurology
Nonnez, Geraldine; APHP/CHU Bicêtre, Neurology
Morier, Agnes; APHP/CHU Bicêtre, Neurology
Bourges, Catherine; APHP/CHU Bicêtre, Neurology
Darras, Amandine; APHP/CHU Bicêtre, Neurology
Mouzat, Laurence; APHP/CHU Bicêtre, Neurology
ADAMS, David; APHP/CHU Bicêtre, Neurology
Keywords:
ATTR amyloidosis, transthyretin, therapeutic patient education, needs
assessment, pedagogy
URL: http://mc.manuscriptcentral.com/damy
Amyloid
For Peer Review Only
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Familial amyloid polyneuropathy: elaboration of a therapeutic patient education
programme, EdAmyl
Marie Théaudin
1,2,3
, Cécile Cauquil
1,2
, Teresa Antonini
1,4
, Vincent Algalarrondo
1,5,6
, Céline
Labeyrie
1,2,6
, Sophie Aycaguer
7
, Mireille Clément
8
, Marie Kubezyk
1,2
, Géraldine Nonnez
1,2
,
Agnès Morier
1,2
, Catherine Bourges
1,2
, Amandine Darras
1,2
, Laurence Mouzat
1,2
, and David
Adams
1,2,3,6
.
1. French Reference Centre for Familial Amyloid Polyneuropathy, NNerf, Assistance
Publique Hôpitaux de Paris (APHP), HUPS, France
2. Hôpital Bicêtre, APHP, Neurology Department, Le Kremlin Bicêtre 94275 Cedex France
3. INSERM UMR788, Université Paris Sud, France
4. Hôpital Paul Brousse, Centre Hépato-Biliaire, APHP, Villejuif 94800, France
5. Hôpital Antoine Béclère, Cardiology department, APHP, Clamart 92149, France
6. Université Paris Sud, France
7. EDU-santé, 92170 Vanves Cedex, France
8. Association Française contre l’Amylose, BP 200000, 13706 Aix en Provence Cedex 3,
France
Corresponding author:
Dr Marie Théaudin, French Reference Centre for Familial Amyloid Polyneuropathy, NNerF,
Neurology Department, APHP, Hôpital Bicêtre,
78 rue du Général Leclerc,
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94275 Le Kremlin-Bicêtre, France
Telephone number: 0033 1 45213159
Fax number: 0033 1 45213149
e-mail: marie.theaudin@bct.aphp.fr
Running head: therapeutic patient education in FAP
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Abstract
Background: Transthyretin-related (ATTR) amyloidosis is an autosomal dominant disease
affecting the peripheral and autonomic nervous system, heart, eyes and kidneys. It is the most
disabling hereditary polyneuropathy in adults. The French National Reference centre for this
disease was accredited in 2005 with 10 lines of action. One of them is to inform and educate
patients about their disease to improve their care and reduce morbidities. We thus decided to
elaborate a therapeutic patient education programme, starting with patients’ needs assessment.
Methods: A qualitative research study was conducted with one-to-one semi-structured interviews
of selected individuals. Recorded interviews were analysed to identify the skills that patients
need to acquire. A therapeutic patient education programme was elaborated on the basis of these
findings. Results: 7 patients, 1 asymptomatic carrier and 2 healthy spouses were interviewed.
Analysis of the interviews showed that interviewees had a good knowledge of the disease and its
symptoms but they had difficulties explaining the disease mechanism and did not have an
adequate knowledge of the available treatment options, although they knew that liver transplant
might halt progression of the disease. ATTR amyloidosis appeared to have a major negative
impact on the patient’s physical and mental well-being. Patients feared loss of autonomy and
having to require assistance from their relatives and spouses. All interviewees were keen to
participate in a therapeutic patient education programme. Based on this needs assessment, we
identified seven skills that patients need to acquire and several pedagogical goals to be achieved
during the education programme. An interdisciplinary team then elaborated a complete
therapeutic patient education programme. Conclusion: elaboration of a therapeutic patient
education programme for ATTR amyloidosis is required to obtain useful information from the
patients themselves, and their relatives, concerning their perception of their disease. This needs’
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assessment constituted the basis for designing the first therapeutic patient education programme,
to our knowledge, for ATTR amyloidosis. After translation, this programme could be applied in
other EU countries and worldwide for this rare disease.
Keywords: familial amyloid polyneuropathy, ATTR amyloidosis, transthyretin, therapeutic
patient education, needs assessment, pedagogy, qualitative research.
Abbreviations: ATTR, transthyretin-related amyloidosis; NNerF, French National Reference
Centre for Familial Amyloid Polyneuropathy; SiRNA, Small interfering RNA; TPE, therapeutic
patient education; TTR, transthyretin.
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Introduction
Transthyretin-related amyloidosis (ATTR) is a rare disease with autosomal transmission, usually
due to a point mutation of the TTR gene [1]. It is a systemic disease, predominantly affecting the
peripheral and autonomic nervous system, but also the heart, kidneys and eyes. It is a
progressive, irreversible, disabling disease, leading to cumulative disabilities. It is also life-
threatening, as patients may die from cachexia, severe infection or cardiovascular events with a
mean survival of 7 to 12 years [2,3]. Management must be based on a multidisciplinary approach
including liver transplantation as reference therapy, pacemaker placement in 45% of patients to
treat or prevent heart conduction disorders [4] and symptomatic treatment of peripheral and
autonomic neuropathy as well as treatment of organs severely affected by amyloidosis (heart,
eyes, kidneys).
Major progress has been recently achieved in the therapeutic management of ATTR amyloidosis
with new medicines that can slow down or halt progression of amyloidogenesis [5]. Tafamidis, a
TTR stabilizer, was the first drug to be approved in Europe for stage 1 (walking unaided) ATTR
amyloidosis to slow progression of the disease. A phase 3 clinical trial with Diflunisal [6],
another TTR stabilizer, versus placebo for 2 years, showed that Diflunisal reduced the rate of
progression of neurological impairment and preserved quality of life. TTR gene silencing is a
new strategy to inhibit production of both mutant and non-mutant TTR, with either SiRNA [7] or
antisense oligonucleotides [8], for which two phase 3 clinical trials are ongoing.
ATTR amyloidosis is a worldwide disease with three main endemic areas: Portugal [9], Japan
[10
]
and Sweden [11]. Overall prevalence of ATTR amyloidosis in Japan is estimated to be 0.87-
1.1 per 10
6
inhabitants, but is as high as 11-15.5 per 10
6
inhabitants in Nagano prefecture [10].
The crude prevalence is 9.03 x 10
-6
(one in every 1,108 inhabitants) in the Povoa or Vila do
Conde districts of Northern Portugal [9] and 10.4 x 10
-6
in Skelleftea in Sweden [11]. There is a
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predominance of early-onset ATTR amyloidosis in Portugal and Japan (87% of patients develop
symptoms before the age of 40 years) and late-onset phenotypes in Sweden, France [12] and
USA (87% of patients develop symptoms after the age of 40 years).
In 2004, the French Health Authority decided to improve the care of patients with rare diseases
by creating national reference centres for rare diseases (first French national plan for rare
diseases 2005-2008) [13]. The French National Reference Centre for ATTR amyloidosis
(NNerF) is one of the 131 accredited reference centres. NNerF is a collaborative centre,
comprising the Bicêtre hospital Neurology department, the Béclère Hospital Cardiology
department and the Paul Brousse Hospital Hepatobiliary Centre. A French ATTR amyloidosis
network (Cornamyl) was also created to standardize clinical practice for this disease in France.
One of the 10 lines of action of these reference centres is to inform and educate patients about
their disease. According to the World Health Organization, therapeutic patient education (TPE)
is defined as “helping patients acquire or maintain the competencies they need to manage as well
as possible their lives with a chronic disease. It is an integral and continuing part of patient care.
It comprises organized activities, including psychosocial support, designed to make patients
aware of and informed about their disease and about health care, hospital organization and
procedures, and behaviour related to health and disease, so that they (and their families)
understand their disease and their treatment, collaborate with each other and take responsibility
for their own care as a means of maintaining or improving their quality of life” [14]. TPE has
been shown to improve the patient’s outcome and quality of life in many chronic diseases,
including diabetes, asthma, multiple sclerosis, and stroke [15-20]. However, TPE programmes
have been developed for very few rare diseases [21], especially in the context of either fatal
inherited diseases or peripheral neuropathy other than diabetic neuropathy [22,23]. We therefore
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decided to elaborate a therapeutic education programme for our French ATTR amyloidosis
patients. In this specific setting, the first step consisted of patients’ needs assessment before
designing a TPE programme. After describing this needs assessment, which identified the skills
needed to be acquired by the patients, we will briefly describe the design of our TPE programme.
Methods
Patients’ needs assessment
We conducted a qualitative study using one-to-one semi-structured interviews. Potential
individuals to be interviewed were identified by their attending neurologist (DA, MT, CC). The
number of individuals to be interviewed was determined according to the empirical saturation
criterion: inclusion of new individuals is stopped when analysis of the interviews fails to provide
any new information relevant to the objective of the study. The results obtained can then be
generalized to the overall population to which the group belongs. [24, 25]
The interviewer (SA) was experienced in qualitative research, was unknown to the interviewees
and was not an ATTR amyloidosis patient caregiver. We tried to recruit a representative sample
of the ATTR amyloidosis population, with patients presenting various stages of the disease, as
well as asymptomatic carriers and patient relatives. Interviews were recorded and then
transcribed. Interviewees were also asked to fill in a questionnaire concerning their expectations
in relation to a TPE programme.
Pedagogical goals and patients’ skills
Based on the results of the needs assessment, an interdisciplinary team, including reference
centre caregivers (neurologists, cardiologist, hepatologist, nurse, occupational therapist,
physiotherapist, social worker and psychologist) and a patients’ association representative (MC),
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determined the pedagogical goals of the patient education programme and the main skills that
patients need to acquire. One of the neurologists (MT) was responsible for coordinating
elaboration of the TPE programme.
TPE programme planning and creation of educational tools
Future educators, essentially ATTR amyloidosis caregivers cited above, as well as the patients’
association representative (MC), designed the programme and created targeted educational tools.
Results
Patients’ educational needs assessment
Empirical saturation was reached on interview of the tenth individual and no more new
individuals were interviewed beyond this point. A total of seven ATTR amyloidosis patients
(four Val30Met, 2 Ser77Tyr and one Tyr116Ser), one asymptomatic Val30Met carrier, and two
healthy (non-carrier of any ATTR mutation) spouses were interviewed. The interviewees’
demographic and clinical characteristics of ATTR amyloidosis patients and TTR mutation carrier
are summarized in Table 1.
Knowledge of the disease and its mechanism, beliefs.
Analysis of the interviews showed that interviewees had a fairly good knowledge of the
symptoms of the disease, either their own symptoms or those symptoms generally observed in
ATTR amyloidosis, although they were unable to list all of these symptoms. However, they were
confused about the cause of those symptoms: were they related to the disease or to the treatment?
Most interviewees believed that ATTR amyloidosis can affect all organs. They were unable to
clearly explain the mechanism of the disease and were unable to distinguish between TTR,
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amyloidosis or amyloid deposits. They knew that ATTR amyloidosis is a hereditary disease, but
often proposed another explanation for the disease in their case (“is it due to Chernobyl?”
“Maybe it is due to discontinuation of my hormone replacement therapy”). Interviewees reported
that several different TTR mutations were responsible, but did not know which mutation they (or
their spouse) harboured. Patients and TTR mutation carrier were usually able to easily inform
their family about their disease and its genetic transmission, but they did not understand the
value of early genetic screening. They were aware of the severe and even fatal natural history of
the disease. Interviewees considered that no treatment (i.e. medications) was available for ATTR
amyloidosis (“none of the 29 pills that my husband takes each day is designed to treat his
amyloidosis”), although six out of seven patients had undergone liver transplantation. Liver
transplantation was not considered to be a therapy; interviewees did not know whether it halted
progression of the disease or whether it just slowed the course. ATTR amyloidosis and liver
transplantation were considered to constitute a double “punishment” and tafamidis appeared to
be a source of great hope for ATTR amyloidosis patients. Patients were fairly satisfied with their
symptomatic medications, except for diarrhoea, which was a major source of disability.
Knowledge about their healthcare
Despite the considerable number of physicians, nurses and paramedics involved in their follow-
up, patients were clearly aware of the respective role of each healthcare professional and the
importance of their follow-up (“One physician for amyloidosis, one for liver transplant, another
for gastrointestinal symptoms, a cardiologist for amyloid-related heart problems.”)
They usually presented good adherence with their medications, although they did not always
comply with the dosing schedule.
Impact of the disease on physical and mental well-being
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Interviewees described ATTR amyloidosis as constituting a serious aggression (“It attacks the
motor nerves and muscles disappear”; “It attacks all of the body”) and this was all the more
stressful when there was a family history of ATTR amyloidosis. They considered this inheritance
to be “bad luck” and a curse.
Patients reported concerns in relation to their married life, as the spouse often becomes a
caregiver. Their sex life was also severely altered by the disease. Fatigue and sometimes
depression interfered with their family life and they often reported a limited social life. Young
patients often required sick leave from work, sometimes permanent, which accentuated their
social isolation.
Most patients had a poor self-image, especially because of their severe weight loss, surgical scars
and bowel and bladder dysfunctions (“You would be shocked if you saw me without clothes… I
am horrible… I think I will soon remove all the mirrors from my house”)
Due to the inevitable progression of disability, patients often require assistance from their
relatives and, even in the early stages of the disease, this constituted a significant concern for
most patients. However, relatives and friends were very supportive and most patients still made
plans for the future.
Analysis of questionnaires
Six of the seven patients and the mutation carrier said they would be keen to attend a TPE
programme on their disease.
The top nine items on which they would like to be educated, in decreasing order, were: 1.
Symptoms of the disease; 2. Liver transplant; 3. Cardiac involvement and role of a pacemaker; 4.
How to apply for social welfare; 5. Treatment of the disease other than liver transplant,
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mechanisms of action; 6. Management in the case of ongoing difficulties with medications; 7.
Post-liver transplant follow-up; 8. Cardiac follow-up; 9. Symptomatic medications for pain and
gastrointestinal symptoms.
Interviewees expressed a preference for both individual and group educational sessions, lasting
at least 90 minutes and up to half a day, for about 6 months, if possible on weekdays and not in
hospital. They would like TPE to be also accessible to family members.
Pedagogical goals and patients’ skills
Following evaluation of the patients’ needs, we identified the skills that patients need to acquire
and the pedagogical goals of our TPE programme, which are summarized in Table 2.
Targeted educational tools
The national ATTR amyloidosis reference centre educational team has created a number of
pedagogical tools to be used during educational sessions (Figure 1). A patient booklet has also
been created, to be used as a personal teaching aid.
‘Edamyl’ programme design (Figure 2)
Individual sessions
Two individual TPE sessions are planned: the first session is an educational diagnosis
assessment, performed by a nurse trained in TPE, in order to establish a relationship of
confidence between the patient and the educator. Barriers to learning and the patient’s prior
knowledge and cultural and health beliefs are identified. This initial assessment is also designed
to determine the patient’s perception of the disease experience, the patient’s knowledge of the
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disease and the most pressing concerns, to obtain information about the current disease status,
current self-care practices and to identify the patient’s expectations of the TPE programme. This
first session defines the patient’s specific pedagogical goals and objectives throughout the
discussion. The educator also presents the proposed personalized TPE programme to the patient.
The second individual session is held at the end of the programme to evaluate the skills acquired
with respect to the initially identified therapeutic education goals. Patients are also asked to
evaluate the TPE programme.
Group sessions
Seven group sessions are planned. All patients attend the first two sessions concerning the
mechanisms of the disease and its treatment (Skills 1 and 2 in Table 2). Then, according to the
individual pedagogical goals identified at the educational diagnosis assessment, each patient
attends another one to five group sessions (corresponding to Skills 3 to 7 in Table 2).
Two trained TPE educators are in charge of each group session, which may include up to 8
patients and their relatives. Groups are composed of patients at different stages of the disease,
with or without liver transplant and including asymptomatic TTR gene mutation carriers, and are
designed to be as interactive as possible.
Discussion
To our knowledge, this is the first study to describe elaboration of a TPE programme for ATTR
amyloidosis patients. TPE has been previously demonstrated to improve quality of life [16] and
usually the outcome of educated patients in many chronic diseases.
The patients’ needs assessment in this life-threatening disease showed that ATTR amyloidosis is
perceived as a severe physical and psychological aggression. It has a major impact on well-being
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and the patient’s self-image. Most diseases for which TPE programmes have been developed
[15-20] do not have such a major psychological impact on the patient. Our proposed TPE
programme differs from many other educational programmes due to the coping skills required by
the very severe course of the disease. It was therefore decided to devote considerable time to
psychological and well-being issues.
Recent publications have emphasised the value of patients’ needs assessment before elaborating
therapeutic patient education programmes [25-27], as this is the best way to develop a TPE
programme adapted to the patients’ specific needs, rather than to the caregivers’ perception of
their patients’ needs. We used semi-structured one-to-one interviews to assess the patients’
needs. This method provided more information than a questionnaire, but only a limited number
of individuals could be interviewed. Although these interviews were proposed to individuals at
different stages of the disease and presenting various demographic characteristics and although
this qualitative methodology has been previously demonstrated to provide fairly representative
results of a larger population [24, 25], the present study group may not be fully representative of
the whole ATTR amyloidosis population. However, one of these patients (MC) is a
representative of a patients’ association and actively participated in elaboration of the
programme content and educational tools, in order to design a programme corresponding as
closely as possible to patients’ needs and expectations. When this needs assessment was
performed, tafamidis was in the process to being approved in France and only a small number of
patients, who met criteria for the French temporary utilisation authorization, were treated. That is
the reason why we interviewed more transplanted patients than tafamidis-treated. We
acknowledge that questions raised by patients having a liver transplant can be different from
those on tafamidis. However, most of late-onset French patients on tafamidis still have to
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consider liver transplant [28] or in the near future, other anti-amyloid therapies [29], in case of
tafamidis failure. We will very likely have to repeat a needs assessment within 2 or 3 years to
assess new ATTR amyloidosis patients’ needs in regards to those new medications and their
impact on patients’ perception of their disease. In the meantime, patients attending TPE sessions
will be asked to evaluate these sessions and make suggestions to improve them, in order to take
into account the expectations of a larger number of patients.
Very few educational programmes have been described in the literature and most publications do
not describe the skills selected and the design of the educational programme [16]. We decided to
describe our TPE programme and inform healthcare providers managing ATTR amyloidosis
patients about the results of our patients’ needs assessment, as we are convinced that it is
essential to take the patients’ beliefs and real life experience into account in order to provide
optimal healthcare, and TPE.
As ATTR amyloidosis is a very rare disease in France, our national Cornamyl network will be
used to provide TPE sessions in 10 other satellite regional expert centres, so that patients living a
long way from Paris can also attend educational sessions, regardless of their degree of disability.
We also plan to translate our programme (including the educational tools) into other languages
so that it can be used in other European Union countries and worldwide.
Conclusions
Needs assessment of patients with ATTR amyloidosis showed that they perceive their disease as
a major psychological and physical aggression. On the basis of this assessment, an
interdisciplinary team, including caregivers and a representative of a patients’ association,
elaborated the first TPE programme for this disease, which we have called Edamyl. This TPE
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programme was approved by the French Haute Autorité de Santé in June 2013, which will allow
us to start educational sessions at the beginning of 2014. This programme will be evaluated at
one year, both in terms of improvement of patient outcome and quality of the education provided
(as assessed by patients and educators).
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Acknowledgements
The authors would like to thank Drs Djamila Boumedien and Yves Magar from Edusanté (Paris,
Ile de France, France) for their support in elaborating the educational programme.
Declaration of interest
MT has received speaker honoraria and funding for travel from Pfizer. DA has received speaker
honoraria and funding for travel from Pfizer and serves on a scientific advisory board for ISIS
and Alnylam. CC, TA, VA, CL, SA, MC, AM, CB, GN, MK, AD, LM have no competing
interests to declare.
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Assessment of patient needs to design a patient education program in systemic lupus
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Table 1. Demographic and clinical characteristics of the focus group interviewed for the needs
assessment
ATTR amyloidosis patients and asymptomatic carrier (n=8)
TTR gene mutation
Val30Met
Ser77Tyr
Tyr116Ser
5 (including 1 asymptomatic carrier)
2
1
Mean age (range) 50 years (39-68)
Gender 3 M, 5 F
Familial status Married: 4
Single : 1
Widowed : 1
Divorced : 2
With children at home: 3
Working status Active : 3
Retired: 3
Long-term medical leave : 2
Member of patients’ association 3
Internet access 7
Liver transplanted 6
On tafamidis 1
Spouses (n=2)
Age, Gender 54 and 60, 1 M and 1 F
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Table 2. The skills and main pedagogical goals patients are expected to acquire when attending
the TPE programme.
Skills Pedagogical goals
1. Knowing my disease in order to ensure
appropriate follow-up
Enumerate manifestations suggestive of the
disease
Distinguish the various manifestations
Correlate manifestations to the organ involved
Identify potentially dangerous manifestations
Explain how regular follow-up is planned
Explain the mechanism of inheritance
Explain the relationship between the gene
mutation and clinical manifestations
Understand the treatment options based on the
mechanisms of the disease
2. Understanding the role of medications Enumerate the names of all of my current
medications
Classify my medications according to their
specific role
Identify the measures to be taken if I forget to
take a pill or in case of vomiting.
3. Integrating rehabilitation as an active part of
therapy
Identify the manifestations that could be
improved or prevented with rehabilitation
Identify which rehabilitation actions can be
performed to relieve certain manifestations
4. Living with a liver transplant
Express my feelings in regards to liver
transplantation
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Verbalize my expectations about liver
transplantation
Describe the process leading to liver
transplantation
Organize my life while waiting for
transplantation
Describe the medical follow-up after liver
transplantation
Enumerate alarming symptoms that must be
reported to the liver transplant centre
Coping with difficult situations that can occur
after liver transplantation
5. Managing my self-reliance despite my disability Identify the technical aids available to maintain
my indoor and outdoor autonomy
6. Preserving my social and work life Find solutions for difficulties of everyday life (in
my family, with my friends, at work…)
Identify available resources (social worker,
occupational therapy…)
Develop support strategies
7. Coping with anxiety-generating situations Express myself about psychological difficulties
Use my own resources to cope with a suffering-
generating situation
Elaborate care strategies
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FIGURE LEGENDS
Figure 1: Examples of educational tools developed for this programme. A: “Follow-up by the
neurologist”, drawings showing (left to right and up to down): nerve conduction study, tools used
for sensory and motor examinations, weight surveillance, skin biopsy, blood pressure testing. B:
photos showing how patients can perform hand self-massage. C. Multiple examples of teaching
tools including a pearl necklace that represents the transthyretin protein, symptom cards,
magnetic cartoons with human beings to be used to make a family tree, photolanguage cards and
situation cards. D: caregivers involved in patient follow-up (physicians, occupational therapist,
psychologist, social worker, etc.)
Figure 2: Design of the EdAmyl therapeutic patient education programme. Professionals
involved in the follow-up.
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Examples of educational tools developed for this programme. A: “Follow-up by the neurologist”, drawings
showing (left to right and up to down): nerve conduction study, tools used for sensory and motor
examinations, weight surveillance, skin biopsy, blood pressure testing. B: photos showing how patients can
perform hand self-massage. C. Multiple examples of teaching tools including a pearl necklace that
represents the transthyretin protein, symptom cards, magnetic cartoons with human beings to be used to
make a family tree, photolanguage cards and situation cards. D: caregivers involved in patient follow-up
(physicians, occupational therapist, psychologist, social worker, etc.)
204x145mm (150 x 150 DPI)
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Design of the EdAmyl therapeutic patient education programme. Professionals involved in the follow-up.
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