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Abstract

Background: Transthyretin-related amyloidosis (ATTR) 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 (TPE) programme, starting with patients' needs assessment.
For Peer Review Only
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
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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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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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... While burden of care has been extensively explored in mental and neurological diseases [10,11], few studies have specifically investigated the practical and psychosocial difficulties experienced by patients with ATTRv and their families. Available data reveal that patients with this disease have difficulties in marital relationships and social life and fear of losing their functional autonomy and becoming dependent on family for help [12][13][14]. Worsening symptoms and disease-related disability often led to inability to work, and they contributed to feelings of frustration and sadness [14]. ...
... Some studies have small sample sizes and were conducted using a qualitative design [14,20,21], a methodology which is difficult to apply in routine clinical settings. Furthermore, only a few studies have examined the burden of care both from the patient's and the relative's perspective [12,18,20], and none has specifically examined the impact of professional or social support on the patient's or relative's burden. The lack of representative data on the burden in ATTRv makes it more difficult to develop ad hoc supportive interventions for patients and their families. ...
... Sixty percent of patients and key relatives stated they cried or felt depressed in the past 2 months. These findings are in line with those reported by Lopes et al. [16] about the prevalence of psychiatric problems in ATTRv patients and by Theaudin et al. [12] on marital difficulties and depression in this disease. Feelings of sadness may lead to depression and other minor psychiatric disorders [18]. ...
Article
Full-text available
Background Hereditary transthyretin amyloidosis (hATTR), alias ATTR variant (ATTRv) is a severe and disabling disease causing sensory and motor neuropathy, autonomic dysfunction, and cardiomyopathy. The progressive decline of patient’s functional autonomy negatively affects the patient’s quality of life and requires increasing involvement of relatives in the patient’s daily life. Family caregiving may become particularly demanding when the patient is no longer able to move independently. This study is focused on the psychosocial aspects of ATTRv from the patient and relative perspectives. In particular, it explored: the practical and psychological burdens experienced by symptomatic patients with ATTRv and their key relatives and the professional and social network support they may rely on; whether burden varied in relation to patients’ and relatives’ socio-demographic variables, patients’ clinical variables, and perceived professional and social network support; and, any difference in burden and support between patients and their matched relatives. Methods The study was carried out on symptomatic patients included in the ATTRv Italian national registry and living with at least one adult relative not suffering from severe illness and being free from ATTRv symptoms. Patients and relatives’ assessments were performed using validated self-reported tools. Results Overall, 141 patients and 69 relatives were evaluated. Constraints of leisure activities, feelings of loss and worries for the future were the consequences of ATTRv most frequently reported by patients and relatives. Both in patients and their relatives, the burden increased with the duration of symptoms and the level of help in daily activities needed by the patient. In the 69 matched patient-relative pairs, the practical burden was significantly higher among the patients than among their relatives, while the psychological burden was similar in the two groups. Moreover, compared to their relatives, patients with ATTRv reported higher levels of professional and social network support. Conclusions These results show that ATTRv is a disease affecting quality of life of both patients and their families. Supporting interventions should be guaranteed to patients, to facilitate their adaptation to the disease, and to their families, to cope as best as possible with the difficulties that this pathology may involve.
... For patients with diagnoses of ATTRv with PN, early disease-modifying therapy may be beneficial [73,74] and underscores the need for diagnosis as soon as possible. Genetic counseling is recommended for family members of patients, and therapeutic patient education is recommended for siblings and children [75,76]. ...
Article
Full-text available
Amyloid transthyretin (ATTR) amyloidosis with polyneuropathy (PN) is a progressive, debilitating, systemic disease wherein transthyretin protein misfolds to form amyloid, which is deposited in the endoneurium. ATTR amyloidosis with PN is the most serious hereditary polyneuropathy of adult onset. It arises from a hereditary mutation in the TTR gene and may involve the heart as well as other organs. It is critical to identify and diagnose the disease earlier because treatments are available to help slow the progression of neuropathy. Early diagnosis is complicated, however, because presentation may vary and family history is not always known. Symptoms may be mistakenly attributed to other diseases such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), idiopathic axonal polyneuropathy, lumbar spinal stenosis, and, more rarely, diabetic neuropathy and AL amyloidosis. In endemic countries (e.g., Portugal, Japan, Sweden, Brazil), ATTR amyloidosis with PN should be suspected in any patient who has length-dependent small-fiber PN with autonomic dysfunction and a family history of ATTR amyloidosis, unexplained weight loss, heart rhythm disorders, vitreous opacities, or renal abnormalities. In nonendemic countries, the disease may present as idiopathic rapidly progressive sensory motor axonal neuropathy or atypical CIDP with any of the above symptoms or with bilateral carpal tunnel syndrome, gait disorders, or cardiac hypertrophy. Diagnosis should include DNA testing, biopsy, and amyloid typing. Patients should be followed up every 6–12 months, depending on the severity of the disease and response to therapy. This review outlines detailed recommendations to improve the diagnosis of ATTR amyloidosis with PN.
... Care should include symptomatic therapy, anti-amyloid therapy to prevent further production of amyloid deposits and treatment of cardiac, renal and ocular involvement 144,145 , including the possibility of heart 146 asymptomatic carriers is necessary to detect early signs of ATTRv amyloidosis, confirm the diagnosis and initiate anti-amyloid therapy 148 . Therapeutic education for patients is also important 149 . Genetic counselling of patients and relatives is also highly recommended 143 (box 1). ...
Article
Hereditary amyloidogenic transthyretin (ATTRv) amyloidosis with polyneuropathy (also known as familial amyloid polyneuropathy) is a condition with adult onset caused by mutation of transthyretin (TTR) and characterized by extracellular deposition of amyloid and destruction of the somatic and autonomic PNS, leading to loss of autonomy and death. This disease represents a model of the scientific and medical progress of the past 30 years. ATTRv amyloidosis is a worldwide disease with broad genetic and phenotypic heterogeneity that presents a diagnostic challenge for neurologists. The pathophysiology of the neuropathy is increasingly understood and includes instability and proteolysis of mutant TTR leading to deposition of amyloid with variable lengths of fibrils, microangiopathy and involvement of Schwann cells. Wild-type TTR is amyloidogenic in older individuals. The main symptoms are neuropathic, but the disease is systemic; neurologists should be aware of cardiac, eye and kidney involvement that justify a multidisciplinary approach to management. Infiltrative cardiomyopathy is usually latent but present in half of patients. Disease-modifying therapeutics that have been developed include liver transplantation and TTR stabilizers, both of which can slow progression of the disease and increase survival in the early stages. Most recently, gene-silencing drugs have been used to control disease in the more advanced stages and produce some degree of improvement.
Article
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L’oxaliplatine (OXA) est un anticancéreux couramment employé en oncologie, son efficacité étant reconnue en première ligne dans le traitement de nombreux cancers. Cependant, son utilisation est limitée par l’apparition de neuropathies impactant la qualité de vie du patient. Pour identifier et étudier des marqueurs cliniques, plasmatiques et électrochimiques de neuropathie chronique induite par l’oxaliplatine (NPIO), deux études pilotes (LIPIDOXA et CANALOXA) ont été réalisées. Les patients de l’étude LIPIDOXA ont été inclus avant traitement par OXA et ont été évalués avant traitement, tout au long du traitement et six mois après l’arrêt. Entre mai 2014 et juin 2016, 35 patients ont été inclus. L’apparition d’une hypoesthésie thermique a été mise en évidence six mois après arrêt de l’OXA, révélateur d’un processus neurotoxique qui se poursuit même après l’arrêt du traitement. L’étude des marqueurs plasmatiques a révélé, en fin de traitement, une augmentation de la production de prostaglandines E2, un niveau moins élevé de stress oxydant chez les patients souffrant d’une neuropathie de grade 2 ainsi qu’une diminution de la concentration des triglycérides polyinsaturés associée à une tendance à l’augmentation des acides gras libres polyinsaturés. Les patients de l’étude CANALOXA, tous neuropathiques, ont été inclus en cours de traitement par OXA et évalués une seule fois. Entre avril 2016 et mars 2017, 36 patients ont été inclus. Les valeurs des conductances électrochimiques de la peau (ESC) étaient pathologiques pour un tiers des patients. Les valeurs d’ESC étaient bien corrélées avec le score de douleur neuropathique.Ces marqueurs sont cependant peu spécifiques et semblent d’apparition tardive. Aussi, ils sont difficilement utilisables en pratique clinique pour un éventuel suivi de la tolérance neurologique au traitement. Au-delà de l’apport clinique et thérapeutique modéré, ce travail renforce la compréhension de la physiopathologie de la NPIO dans le domaine de la neuropathie à petites fibres, les processus inflammatoires associés et la perturbation du métabolisme lipidique chez le patient traité par oxaliplatine.La complémentarité et les similarités de ces travaux rappellent que la prise en charge du patient doit être globale et conjuguer des éléments variés au sein desquels le patient doit rester au cœur de la gestion de la NPIO. Ce projet de recherche s’inscrit dans une dynamique d’amélioration continue et les résultats des études pilotes constituent une base pour approfondir les travaux.
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Amyloid neuropathies of acquired or genetic origin are disabling and life-threatening, until recently there were few treatment options available. Poor prognosis is related to progressive neuropathy and associated, although often underdiagnosed, cardiac involvement in specific transthyretin (TTR) gene mutations. Recent progress has modified prognosis and management of amyloid neuropathies. In TTR-familial amyloidosis with polyneuropathy, major changes have occurred over the last 30 years: better knowledge concerning genetics, phenotypes and epidemiology, and the advent of possible treatments. Liver transplantation, first performed in 1990, stopped disease progression, thus doubling survival in early onset V30M patients. More recently tetramer stabilizers (Tafamidis and Diflunisal) showed a significant reduction of progression of neuropathic scores; Tafamidis is now recommended in Stage I patients. Two multicentric clinical trials are now ongoing to evaluate TTR gene silencing by antisense Oligonucleotides (ASO) or siRNA. In the near future we should have new therapeutical options for patients with amyloid neuropathy.
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Objectives Focus on the different therapeutic patient education (TPE) programs for stroke survivors found in the literature. Verify their content and efficacy. Method A literature review was conducted by searching for entries from 1966 to 2011 in the Medline and Cochrane Library databases. The references for the accepted articles were taken into consideration and the articles corresponding to the criteria inclusion but not present within the initial search were selected. The keywords used were “self care”, “self management”, “patient education” and “stroke”. Given the multiplicity of symptoms that may be addressed in TPE programs, and following expert advice, the symptoms were grouped after expanding the bibliographic search using the following, additional keywords: “dysphagia”; “swallowing disorder”; “urinary incontinence”; “caregiver”; “fall prevention”; “falling”; “injury”; “shoulder pain”; “physical activity”; “exercise”; “aphasia” and “cognitive impairment”. Results We found 30 article abstracts. In the end, we only accepted seven articles on general TPE programs that were well structured and detailed enough. The TPE programs found in the literature were often of questionable methodological quality. The multiplicity of symptoms led to very general TPE programs that covered all possible stroke after-effects. The purpose of these programs was to reduce stress and anxiety, to improve quality of life and to alleviate psychosocial after-effects. A change in caregiver and patient behavior was observed at times. We expanded the bibliographic search to include scientific arguments that could help implement TPE programs for more specific targets. Conclusion TPE programs for stroke survivors could be improved by standardizing and assessing programs that focus on a specific problem caused by the various possible after-effects of strokes. In order to promote education for stroke survivors, specific training for health care professionals and appropriate funding are necessary.
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Ichthyoses are a heterogeneous group of rare genodermatoses. Patients and their families face difficulties related to daily care and management that may be aggravated by social isolation.Objectives To evaluate the impact of therapeutic educational programs in improving the knowledge of ichthyosis patients, and their relatives, about their disease.Patients and methods: We organized a two sessions-program of "know-how" dedicated to the overall management of ichthyoses. These sessions were conducted based on a tool specifically designed for the study, which addressed our various areas of expertise through a collective game. The participants (patients and their parents and siblings) were divided into groups, and the questions were tailored according to the participants' age. The program was conceived as a knowledge reinforcement program that took place during a weekend of education and rest, organized away from healthcare structures. Our aim was to facilitate the program in a neutral place to encourage respite care and to ensure the availability of a multidisciplinary healthcare team. After the reinforcement session, children aged from 6 to 12 years and their families acquired the targeted know-how and social skills. Benefits of TPE in the management of ichthyoses are the following: (1) the trust between patients their families and the caregivers was strengthened; (2) the context of the program encouraged self-expression, answered questions and provided mutual aid; and (3) the more self-sufficient families could better manage emergencies.
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The aim of this study was to assess the effect of Tafamidis, which slows the progression of early stages of Met30 transthyretin (TTR) familial amyloidosis polyneuropathy (FAP) in more advanced cases. The study was a prospective, non-randomized controlled trial carried out at the French national reference centre for FAP with follow-up at 1 year. Thirty-seven consecutive Met30-TTR-FAP patients were enrolled between December 2009 and July 2011, with NIS-LL (Neuropathy Impairment Score-lower limbs) > 10 and Karnofsky score > 60. Their mean (SD) age was 56.4 (19) years. Seventy-seven per cent of patients had a walking disability. Seven patients (19%) were withdrawn for adverse effects. The primary study outcome measurements, planned before data collection began, were NIS-LL and NIS-UL (upper limbs) scores and disability scores. Of the 37 patients entered into the study, 29 were evaluated at 6 months and 13 at 12 months. During the first 6 months of treatment, the mean progression of NIS-LL score was 4.8 and was similar to that during the period before treatment. Among the 45% of patients without NIS-LL progression, the NIS-UL score worsened in 55%. During the first year, 55% deteriorated with respect to disability and 38% with respect to NIS only; only two patients (7%) remained stable. Four (out of 20; 20%) patients who were previously stage 1 reached stage 2 (walking with aid) after this period. Two out of nine patients who were initially normotensive developed orthostatic hypotension. There were a total of 19 adverse events, including four febrile urinary tract infections and three severe diarrhoeas, with faecal incontinence in two. In most patients with advanced Met30 TTR-FAP, Tafamidis is not able to stop disease progression, in respect of both NIS-LL and disability. Other anti-amyloid medicines should be assessed in this context.
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Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and the heart. A therapeutic approach mediated by RNA interference (RNAi) could reduce the production of transthyretin. We identified a potent antitransthyretin small interfering RNA, which was encapsulated in two distinct first- and second-generation formulations of lipid nanoparticles, generating ALN-TTR01 and ALN-TTR02, respectively. Each formulation was studied in a single-dose, placebo-controlled phase 1 trial to assess safety and effect on transthyretin levels. We first evaluated ALN-TTR01 (at doses of 0.01 to 1.0 mg per kilogram of body weight) in 32 patients with transthyretin amyloidosis and then evaluated ALN-TTR02 (at doses of 0.01 to 0.5 mg per kilogram) in 17 healthy volunteers. Rapid, dose-dependent, and durable lowering of transthyretin levels was observed in the two trials. At a dose of 1.0 mg per kilogram, ALN-TTR01 suppressed transthyretin, with a mean reduction at day 7 of 38%, as compared with placebo (P=0.01); levels of mutant and nonmutant forms of transthyretin were lowered to a similar extent. For ALN-TTR02, the mean reductions in transthyretin levels at doses of 0.15 to 0.3 mg per kilogram ranged from 82.3 to 86.8%, with reductions of 56.6 to 67.1% at 28 days (P<0.001 for all comparisons). These reductions were shown to be RNAi-mediated. Mild-to-moderate infusion-related reactions occurred in 20.8% and 7.7% of participants receiving ALN-TTR01 and ALN-TTR02, respectively. ALN-TTR01 and ALN-TTR02 suppressed the production of both mutant and nonmutant forms of transthyretin, establishing proof of concept for RNAi therapy targeting messenger RNA transcribed from a disease-causing gene. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov numbers, NCT01148953 and NCT01559077.).
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Background Systemic Lupus Erythematosus is a chronic autoimmune disease. To prevent short-term and long-term burden of the disease, health education is an essential complement to drug therapy. Objectives The aim of this study was to collect information to design a patient education program (PEP) for patients with systemic lupus erythematosus (SLE), based as much as possible on their expectations. Methods Three different approaches were used for consulting patients: 1. A questionnaire on their expectations in terms of a PEP was sent to the members of SLE associations and offered to patients at the French reference center for SLE. 2. A focus group was conducted and 3. After the teaching sessions, satisfaction questionnaires were also evaluated. Results The patients who answered the expectations questionnaire (n=422, women/men sex ratio = 12.6) showed interest in the PEP in great numbers (70.4%). Their expectations were broad, and covered the topics of pregnancy (90% of the women under age 40), the evolution of the disease (80.8%), the respective roles of the different treatments (70.4%) and also the management of everyday symptoms: fatigue and pain (66.4%). The focus group (8 people) highlighted the need for improving how the diagnosis of the disease was delivered, and also revealed the loneliness and the guilt experienced by some patients toward their relatives. Satisfaction questionnaires confirmed these expectations for the PEP, and even extended them to new topics: the mechanism behind SLE, travel and leisure, and possible accommodations in the workplace. Conclusions the direct consultation of patients with SLE targeted by a PEP program specific to systemic lupus allowed us to confirm and adapt the topics and the content of a program designed by medical staff. Disclosure of Interest None Declared
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Given its practicality, the internet is a primary resource for patients afflicted with diseases like peripheral neuropathy. Therefore, it is important that the readily available online resources on peripheral neuropathy are tailored to the general public, particularly concerning readability. Patient education resources were downloaded from the US National Library of Medicine, Mayo Clinic, National Institute of Neurological Disorders and Stroke, Neuropathy.org, GBS/CIDP Foundation International, Hereditary Neuropathy Foundation, Charcot-Marie-Tooth Association, Foundation for Peripheral Neuropathy, and Neuropathy Action Foundation websites. All patient education material related to peripheral neuropathy was evaluated for its level of readability using the Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level. The FRE scores averaged 43.4 with only the US National Library of Medicine scoring above 60 (76.5). The Flesch-Kincaid Grade Level scores averaged 11.0. All scores were above a seventh-grade level except the US National Library of Medicine, which had a score of a fifth-grade reading level. Most Americans may not fully benefit from patient education resources concerning peripheral neuropathy education on many of the websites. Only the US National Library of Medicine, which is written at a fifth-grade level, is likely to benefit the average American.
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Familial amyloidotic polyneuropathy (FAP) in Swedish patients is associated with the same transthyretin mutation (TTRMet30) as in Portuguese, Japanese, Brazilian and Majorcan patients. Yet, the age of onset of FAP is much later in Sweden than in other populations. We have studied 239 cases of FAP from northern Sweden, their geographical distribution, differences in age of onset, and estimated prevalence and incidence rates. Cases and families concentrate mainly in two areas, around the towns of Skellefteå and Piteå. Mean age of onset was found to be later in the Piteå (58.8 +/- 10.8) than in the Skellefteå area (54.4 +/- 13.5). Unusually high figures were found for prevalence rates (91 x 10(-5) and 104 x 10(-5), respectively) in 1985. Mean yearly incidences were 3.1 x 10(-5) and 4.4 x 10(-5), respectively, over the period 1985-1989.