“JOURNAL“
KEPERAWATAN KELUARGA
“ Nurse
led, home based self help treatment for patients in primary care with chronic
fatigue syndrome: randomised controlled trial”
Disusun Oleh :
Nama : Siti wahyuni
NIM : (04.09.2302)
Kelas : C/KP/VII
PROGRAM STUDI ILMU KEPERAWATAN
SEKOLAH TINGGI ILMU KESEHATAN SURYA GLOBAL
YOGYAKARTA
2012
“ Nurse led, home based self help treatment for
patients in primary care with chronic fatigue syndrome: randomised controlled
trial”
BMJ 2010;
340 doi:(Published
23 April 2010)
- Alison J Wearden, reader in psychology1,
- Christopher Dowrick, professor of primary medical care2,
- Carolyn Chew-Graham, professor of primary care3,
- Richard P Bentall, professor of clinical psychology4,
- Richard K Morriss, professor of psychiatry and community mental health5,
- Sarah Peters, senior lecturer in psychology1,
- Lisa Riste, FINE trial manager1,
- Gerry Richardson, senior research fellow in health economics67,
- Karina Lovell, professor of mental health8,
- Graham Dunn, professor of biomedical statistics3
- on behalf of the Fatigue Intervention by Nurses Evaluation (FINE) trial writing group and the FINE trial group
Author Affiliations
- Correspondence to: A J Wearden alison.wearden@manchester.ac.uk
- Accepted 8 February 2010
Abstract
Objective To evaluate
the effectiveness of home delivered pragmatic rehabilitation—a programme of
gradually increasing activity designed collaboratively by the patient and the
therapist—and supportive listening—an approach based on non-directive
counselling—for patients in primary care with chronic fatigue syndrome/myalgic
encephalomyelitis or encephalitis (CFS/ME).
Design Single
blind, randomised, controlled trial.
Setting 186 general
practices across the north west of England between February 2005 and May 2007.
Participants 296
patients aged 18 or over with CFS/ME (median illness duration seven years)
diagnosed using the Oxford criteria.
Interventions
Participants were randomly allocated to pragmatic rehabilitation, supportive
listening, or general practitioner treatment as usual. Both therapies were
delivered at home in 10 sessions over 18 weeks by one of three adult specialty
general nurses who had received four months’ training, including supervised
practice, in each of the interventions. GP treatment as usual was unconstrained
except that patients were not to be referred for systematic psychological
therapies during the treatment period.
Main outcome measures The primary
clinical outcomes were fatigue and physical functioning at the end of treatment
(20 weeks) and 70 weeks from recruitment compared with GP treatment as usual.
Lower fatigue scores and higher physical functioning scores denote better
outcomes.
Results A total of
257 (87%) of the 296 patients who entered the trial were assessed at 70 weeks,
the primary outcome point. Analysis was on an intention to treat basis, with
robust treatment effects estimated after adjustment for missing data using
probability weights. Immediately after treatment (at 20 weeks), patients
allocated to pragmatic rehabilitation (n=95) had significantly improved fatigue
(effect estimate -1.18, 95% confidence interval -2.18 to -0.18; P=0.021) but
not physical functioning (-0.18, 95% CI -5.88 to +5.52; P=0.950) compared with
patients allocated to treatment as usual (n=100). At one year after finishing
treatment (70 weeks), there were no statistically significant differences in
fatigue or physical functioning between patients allocated to pragmatic
rehabilitation and those on treatment as usual (-1.00, 95% CI -2.10 to +0.11;
P=0.076 and +2.57, 95% CI 3.90 to +9.03; P=0.435). At 20 weeks, patients
allocated to supportive listening (n=101) had poorer physical functioning than
those allocated to treatment as usual (-7.54, 95% CI -12.76 to -2.33; P=0.005)
and no difference in fatigue. At 70 weeks, patients allocated to supportive
listening did not differ significantly from those allocated to treatment as
usual on either primary outcome.
Conclusions For
patients with CFS/ME in primary care, pragmatic rehabilitation delivered by
trained nurse therapists improves fatigue in the short term compared with
unconstrained GP treatment as usual, but the effect is small and not
statistically significant at one year follow-up. Supportive listening delivered
by trained nurse therapists is not an effective treatment for CFS/ME.
Trial registration International
Standard Randomised Controlled Trial Number IRCTN74156610.
Introduction
Patients
with chronic fatigue syndrome, also known as myalgic encephalomyelitis or
myalgic encephalitis, have a a principal symptom of fatigue that lasts at least
six months and is of sufficient severity to substantially impair functioning.1 Diagnosis is by history and exclusion of medical and
psychiatric reasons for the fatigue.2 Chronic
fatigue syndrome/myalgic encephalomyelitis or encephalitis (CFS/ME) causes
substantial disability3 and has
important consequences for healthcare use and expenditure.4 5 In the United Kingdom, the population prevalence of
CFS/ME has been estimated at 0.2-0.4%.6
Many
patients with CFS/ME do not access treatment, either because there are no
services in their area or because they are unable to attend services.6 The recent National Institute for Health and Clinical
Excellence (NICE) guidelines on CFS/ME7 state that
the condition should be managed in primary care, but current evidence about
treatment effectiveness comes from trials in secondary care. Patients with
CFS/ME in primary care differ from those seen in hospital settings.8 Treatments for CFS/ME that are effective in secondary
care may be less effective in primary care, so pragmatic trials of treatments
for patients in primary care are needed.9
A systematic
review of controlled trials of treatments for CFS/ME, including behavioural,
pharmacological, and complementary approaches, concluded that there is evidence
that cognitive behavioural therapy and graded exercise therapy are effective.10 An updated Cochrane review of cognitive behavioural
therapy for adults with CFS/ME concluded that this approach is effective at
reducing fatigue as assessed at the end of the treatment period.11 A Cochrane review of graded exercise therapy
concluded that some patients benefit from exercise, but that this approach is
not always acceptable to patients.12 Cognitive
behavioural therapy and graded exercise therapy are recommended in the NICE
guidelines, but both treatments need to be delivered by specialist therapists.7
In 2001, we
reported a new educational self help treatment for CFS/ME called pragmatic
rehabilitation. This treatment had proved successful in a hospital based trial,
with 57% of patients who received pragmatic rehabilitation recovering after 12
months compared with 6% of patients in a waiting list control group.13 Pragmatic rehabilitation has elements in common with
cognitive behavioural therapy and graded exercise therapy, but does not require
delivery by cognitive behavioural therapists or physiotherapists. Whereas
cognitive behavioural therapy usually starts with an individualised formulation
of the patient’s problem(s), pragmatic rehabilitation starts with the more
didactic presentation of an explanatory model of CFS/ME, which provides the
rationale for a graded increase in activity. The pragmatic rehabilitation activity
programme is devised collaboratively with the patient rather than prescribed on
the basis of exercise testing, as in graded exercise therapy.
We aimed to
determine whether pragmatic rehabilitation delivered in primary care by general
nurses who had received training in the technique would be an effective therapy
compared with treatment as usual by the general practitioner (GP). We added a
third arm to our trial, supportive listening, to control for supportive
therapist contact time and to allow a comparison with a therapy that is widely
available in primary care.14 A previous
primary care study showed that counselling was as effective as cognitive
behavioural therapy for a broader group of patients with chronic fatigue,15 although counselling based therapies have not
previously been trialled for CFS/ME.
Methods
The trial
was overseen by independent data monitoring and trial steering committees. We
previously published the protocol for our trial,16 and report
the methods and findings in accordance with the CONSORT guidelines for
non-pharmacological trials.17
Participants
Patients
aged 18 or over who fulfilled the Oxford criteria for CFS/ME,1 scored 70% or less on the SF-36 physical functioning
scale,18 and scored
four or more on the Chalder et al fatigue scale19 were
recruited from 186 general practices across the north west of England between
February 2005 and May 2007. The Oxford criteria1 require
that patients have a principal complaint of fatigue unexplained by other
medical and psychiatric conditions. The fatigue must be of definite onset,
affect both physical and mental functioning, and have been present for more
than 50% of the time over the past six months.
Patients were excluded if they
fulfilled diagnostic criteria for antisocial, borderline, or paranoid
personality disorders,20 had active
suicidal ideation, were unable to read or write English, were currently
undertaking systematic psychological therapies for CFS/ME, or had received
pragmatic rehabilitation in the past year.
GPs referred in accordance with a
brief diagnostic protocol and checklist, which included a list of exclusionary
tests.2
Procedure
Referred
patients were sent trial information in the post, which included brief details
of all three treatment arms, and were telephoned one week later to ascertain
whether they agreed to take part in the trial. Where patients declined to participate,
the reasons for refusal were recorded. After providing informed consent,
patients were assessed at home and their eligibility determined by a research
assistant. Eligibility was confirmed via consultation with clinically qualified
members of the team if there were any queries about inclusion or exclusion
criteria. Details of eligible patients were provided by telephone to an
independent randomisation service within two working days.
Individual
patients were randomly allocated to one of the three treatment arms using
computer generated randomised permuted blocks (with randomly varying block
sizes of 9, 12, 15, and 18), after stratification on the basis of whether the
patient was non-ambulatory (used a mobility aid on most days) and whether the
patient fulfilled London ME criteria.21 The London
ME criteria were developed in conjunction with members of patient support
groups. We stratified participants according to these criteria to enable us to
address the possibility that people fulfilling London ME criteria are different
from the rest of the sample. Where applicable, patients were assigned to
therapists in a simple random fashion. The random allocation was emailed to the
trial manager, who assigned each patient a unique study number and notified the
designated nurse therapist if the patient had been allocated to a therapy arm.
Treatments
The
pragmatic rehabilitation and supportive listening treatments consisted of 10
sessions over an 18 week period. Each programme comprised a 90 minute home
visit on week 1; one hour home visits on weeks 2, 4, 10, and 19; and 30 minute
telephone calls on weeks 3, 6, 8, 12, and 15. We delivered the treatment in
patients’ homes to enable inclusion of more severely affected patients who
might not otherwise access treatment and to assist with recruitment and
retention. Both face to face and telephone therapy sessions were taped.
Patients in the pragmatic rehabilitation and supportive listening arms were
free to consult their GP during the course of treatment. The treatments are
described in our protocol16 and in
table 1⇓.
View this table:
Table 1
Description and summary of
treatments
Training and
supervision of therapists
Therapy was
delivered by three registered, adult specialty, general nurses who had worked
in primary care but had no previous experience of CFS/ME. All three nurses
delivered both pragmatic rehabilitation and supportive listening. Four months
of training in each intervention was provided over a six month period (box),
with a period of two months when both interventions were taught and practised
in parallel (with four volunteer patients per therapy). Training for pragmatic
rehabilitation was provided by members of the trial team (members of the trial
team (RPB, RKM, SP, AJW, CD, and CCG) and Pauline Powell, a member of the
Fatigue Intervention by Nurses Evaluation (FINE) trial group), and training for
supportive listening was provided by experienced counsellors (Diana Jerman,
counselling trainer, and David Quarmby, counselling supervisor, both members of
the FINE trial group).
Outline of
training sessions provided to FINE nurse therapists
Introduction
(2 hour sessions)
·
Induction.
·
Understanding CFS/ME, reading lists.
·
How to read research papers.
·
Randomised controlled trials,
ethical issues, informed consent.
·
The structure of the FINE trial
Pragmatic
rehabilitation training (half day sessions, delivered approximately weekly)
·
Overview of therapy and outcomes.
The pragmatic rehabilitation model and the importance of providing rationales.
·
Deconditioning: the physiology.
·
Deconditioning: the rationale for
treatment, designing an activity programme, and goal setting.
·
Sleep, cortisol, circadian rhythms:
the physiology.
·
Sleep, cortisol, circadian rhythms:
the rationale for treatment, regularising sleep patterns, and goal setting.
·
Anxiety: the physiology.
·
Anxiety: the rationale for
treatment, learning to relax, and goal setting
·
Shadowing group delivery of
pragmatic rehabilitation in a hospital over eight weeks
·
The structure of treatment—how to
use the visits and phone calls. Delivering the rationale. Agenda setting.
·
Overcoming impediments to change.
·
Using techniques from motivational
interviewing.
·
Psychosocial issues—helping people
to look to the future, termination of therapy.
·
Summary, overview and getting ready
to start working with practice patients. Supervision contracts.
·
Rehabilitation issues (back to
work).
·
Practice patients started. Pragmatic
rehabilitation supervision sessions (group and individual) started
·
Relapse prevention
·
Follow up 1—Learning from practice.
·
Follow up 2—Learning from practice.
Supportive
listening training (half day sessions, delivered approximately weekly)
·
Introduction to supportive
listening, diary keeping, confidentiality, codes of conduct, and use of
supervision.
·
Background to person centred listening,
core conditions, and listening skills. What counselling is not.
·
Qualities of the listener. Beginning
therapy, engagement, and the patient’s frame of reference. Stages of the
listening relationship.
·
Helping the patient to tell a story.
Attending and listening, body language, and non-verbal messages. Reflecting
back.
·
Open questions and role plays.
·
Films/discussion. Skills exercises
(for example, using silence). Barriers to listening. Directed reading
·
Group discussion of learning and
insights. Challenge and specificity. Skills practice.
·
Practice patients started.
Supportive listening supervision sessions started.
·
Creating an emotional and physical
environment conducive to the helping relationship.
·
Telephone counselling skills.
·
Telephone counselling skills—review
and practice.
·
Review of progress, identification
of further training needs.
·
Group work. Taking action. Endings.
·
Endings. Listening skills practice.
·
Follow up 1—Reviewing practice.
Boundaries.
·
Follow up 2—Reviewing practice.
Transference issues.
·
Training sessions used a mixture of
presentations by the trainers, discussion, group activities, role play, videos,
and review of case material. Reading lists were given. Homework was set in some
sessions and reviewed at the next session.
·
Abbreviations: CFS/ME, chronic
fatigue syndrome/myalgic encephalomyelitis or encephalitis; FINE, Fatigue
Intervention by Nurses Evaluation.
Fortnightly
group and individual supervision was provided while the therapists were
treating patients. Supervision for pragmatic rehabilitation was provided in
group meetings held approximately fortnightly by RKM, a psychiatrist with
extensive experience of treating CFS/ME, and supplemented by occasional
individual supervision sessions by RPB, a clinical psychologist, experienced
cognitive behavioural therapist, and one of the people who designed the
original intervention in secondary care. Supervision for supportive listening
was provided in meetings held approximately fortnightly individually by DQ and
supplemented by occasional group supervision meetings (DQ and DJ, both
qualified and experienced counsellors).
Assessment
of treatment fidelity and quality
Treatment
fidelity and quality were assessed during discussion of individual cases and,
in the case of pragmatic rehabilitation, with frequent reference to the
pragmatic rehabilitation manual. Additionally, 85 tapes of face to face therapy
sessions from 21 patients (11 receiving pragmatic rehabilitation and 10 on
supportive listening) were selected at random from early and late stages of the
trial. Sessions were rated for fidelity and quality by five raters, all of whom
were blind to treatment allocation. Four of the five raters were independent of
the trial. Raters were given a brief, point by point description of each
treatment and asked to use this information to determine which treatment had
been delivered. They were then asked to judge the extent to which the essential
components of the treatments had been delivered by using a set of criteria
predetermined by the trial team. Finally, raters were asked to make a judgment
on the quality of delivery of the components.
Assessments
and outcomes
Patients
were assessed at entry to the trial (week 0), after treatment (week 20), and
one year after finishing treatment (70 weeks from recruitment). Assessments
were performed by trained researchers blind to treatment allocation; any
unblindings were recorded. The assessors were trained by an academic
psychiatrist (RKM) who has many years’ experience of using the screening
interview. Training included the use of videos and practice rating sessions.
Further training was provided midway through the trial to ensure continued
competence.
Baseline
assessment included a psychiatric screening interview to screen for personality
disorders and to determine anxiety and depression diagnoses (but not other
psychiatric diagnoses),22 and
recording of medical comorbidities. Participants’ postcodes were used to obtain
a measure of the relative social environment in which they lived (Townsend
deprivation index scores).23
Primary
clinical outcomes were percentage scores on the SF-36 physical functioning
scale,18 where
higher scores indicate better outcomes, and on the 11 item Chalder et al
fatigue scale,19 where lower
scores indicate better outcomes. Each item on the fatigue scale was scored
dichotomously on a four point scale (0, 0, 1, or 1); total scores of four or
more on the fatigue scale designate clinically significant levels of fatigue.
Secondary
outcomes were anxiety and depression, as measured by the anxiety and depression
subscales of the hospital anxiety and depression scales (HADS; lower scores
indicate better outcomes),24 and level
of sleep problems, as measured by scores on the four item Jenkins et al sleep
scale (lower scores indicate better outcomes).25 Our
assessment also included a full economic evaluation of the relative cost
effectiveness of pragmatic rehabilitation and supportive listening when
compared with treatment as usual, the results of which will be reported
separately.
Statistical
analysis
We aimed to
recruit 360 patients, a figure based on an estimated 20 percentage point difference
in improvement rate between the pragmatic rehabilitation and the GP treatment
as usual arms (50% improvement versus 30% improvement). A sample of this size
would give 80% power with a two sided significance level of P=0.05 and allow
for loss to follow-up of 23%. In accordance with our protocol, “improvement”
was defined as scoring less than four on the fatigue scale or improving by 50%
or more or scoring 75% or more on the SF-36 physical functioning scale.16 We revised our recruitment target to 288 in September
2006 when it became clear that our loss to follow-up was less than anticipated
(13% at 70 weeks).
Data were
analysed in accordance with our analysis plan16 and the
CONSORT guidelines,17 with
between group comparisons analysed on an intention to treat basis. Analysis of
covariance was used to allow for stratification by ambulatory status and London
ME criteria. The baseline value of the relevant outcome measure was entered as
a covariate. Firstly, a global test of equality of the three groups was
undertaken for each outcome measure in a complete case analysis. If the groups
differed, pragmatic rehabilitation was compared with supportive listening.
Secondly, if pragmatic rehabilitation and supportive listening were equivalent,
both approaches were compared with GP treatment as usual. If pragmatic
rehabilitation and supportive listening differed, they were compared
individually with GP treatment as usual.
The final
analyses involved generating both robust standard errors and corresponding
confidence intervals for the treatment effect estimates, together with
weighting adjustments to allow for missing outcomes.26 27 Potential biases in treatment effect estimates
arising from missing outcome data were investigated using inverse probability
weighting.26 27 This assumes that the mechanism for missing data is
ignorable—that is, data are missing at random.28 Standard
errors and 95% confidence intervals for parameters were calculated using robust
(sandwich) estimators, allowing for the effects of the inverse probability
weights and possible skewness (lack of normality) of the outcome data.
All formal analyses were carried out
using Stata version 9.
Results
Participants
A total of
449 patients were referred to the trial by their GPs; 78 (17%) declined to be
assessed, 15 (3%) were erroneous referrals, and 18 (4%) were ineligible for
assessment. Thus 338 patients underwent baseline assessment, after which 42
(12.4%) were excluded, leaving 296 patients to be randomised. Participant flow
through the trial, including allocation to therapists, is shown in figure 1⇓.
View larger version:
Fig 1 CONSORT
diagram showing patient flow through the trial. *One patient randomised to
pragmatic rehabilitation was treated by a therapist other than the one to whom
she was randomised. †One patient originally randomised to supportive listening
was treated with pragmatic rehabilitation, and by a different therapist from
the one originally randomised, because another person living at the same
address was receiving pragmatic rehabilitation in the trial. ‡One patient
randomised to supportive listening was admitted to the trial with an SF-36
score of 75% and completed the trial. §One patient randomised to supportive
listening subsequently received a diagnosis of multiple sclerosis and withdrew
from treatment. CFS/ME, chronic fatigue syndrome/myalgic encephalomyelitis or
encephalitis
Three
quarters (230/296 (78%)) of our sample were female. The mean age was 44.6 years
(SD 11.4). The median illness duration was 7 years (range 0.5-51.7 years,
interquartile range 3.2-12.3). Thirty three patients (11%) were non-ambulatory,
and 92 (31%) fulfilled London ME criteria. Townsend deprivation scores ranged
from -7 to 13. Eighty eight (29.7%) patients had any anxiety and/or any
depression diagnosis. Seventy four patients (25%) had one self reported medical
comorbidity that did not explain their fatigue, and 108 patients (36.5%) had
two or more comorbidities. The top three categories of medical comorbidity were
musculoskeletal disorders (63/296 (21.3%)), gastrointestinal problems including
irritable bowel syndrome (45/296 (5.2%)), and cardiovascular diseases such as
hypercholesterolaemia (41/296 (13.9%)).
Descriptive
statistics for patients allocated to each treatment arm can be seen in table 2⇓. In
accordance with our analysis plan, we did not evaluate differences in
demographic variables between the three treatment groups.
View this table:
Table 2
Demographic and baseline
characteristics of participants
Treatment
delivered
The mean
number of sessions delivered was 9.63 (SD 0.88) for patients who completed
pragmatic rehabilitation treatment and 9.5 (0.83) for those receiving
supportive listening. According to patient reports, patients allocated to
general practice treatment as usual had a median of three (range 0-16)
consultations with their GPs during the 18 week treatment period, compared with
two (0-14) for the pragmatic rehabilitation group and three (0-23) in the
supportive listening group. The median number of visits to practice nurses were
0 (range 0-22) for patients allocated to GP treatment as usual, 0 (0-4) for
those receiving pragmatic rehabilitation, and 0 (0-5) for those on supportive
listening.
From patient
reports at baseline, 264 (89%) of the 296 patients reported having received
medication in the past six months. A total of 160 patients (54%) had been
prescribed antidepressants; 49 of whom were receiving GP treatment as usual
(49% of the GP treatment as usual group), 51 of whom were receiving pragmatic
rehabilitation (54% of that group), and 60 of whom were on supportive listening
(59% of that group). Seventy nine (27%) patients had been prescribed
analgesics; 27 of whom were undergoing GP treatment as usual (27% of the GP
treatment as usual group), 30 who were receiving pragmatic rehabilitation (32%
of that group), and 22 who were receiving supportive listening (22% of that
group).29
Treatment
fidelity
We achieved
high treatment fidelity—that is, nearly all sessions were congruent with the
predefined structure and content of each therapy. Blind raters correctly
identified 42 (100%) of the 42 pragmatic rehabilitation sessions and 40 (93%)
of the 43 supportive listening sessions. Sessions were rated for quality on a 7
point scale from 1 (unacceptable) to 7 (excellent). The mean ratings were 5.24
for pragmatic rehabilitation (SD 0.93) and 4.4 for supportive listening (0.98).
There were no significant between therapist differences on quality ratings for
either therapy.
Preliminary
analysis to deal with missing data
Preliminary
analysis indicated that the main predictor of failure to provide follow-up data
was whether the participant withdrew from treatment (not applicable to GP
treatment as usual). Inverse probability weights to adjust for these missing
data were, therefore, calculated separately for participants who completed
therapy and those who withdrew from treatment in both the pragmatic
rehabilitation and supportive listening arms. A single weight was calculated
for the GP treatment as usual arm. The adjustment weights are simply the
reciprocal of the proportion of relevant participants who provided an observed
outcome.
Outcomes
Descriptive
statistics for the outcome measures at baseline, 20 weeks, and 70 weeks are
shown in table 3⇓. Our pre-designated primary outcome
point was 70 weeks, which we chose because we wanted to assess the long-term
effectiveness of pragmatic rehabilitation.16
View this table:
Table 3
Mean (SD) scores at baseline, 20 weeks, and 70 weeks
on the Chalder et al fatigue scale, the SF-36 physical functioning scale, the
Jenkins et al sleep scale, and the hospital anxiety and depression scales
(HADS)
In the initial unweighted (complete
case) analysis at 20 weeks, global tests of equality and contrasts showed
between group differences in fatigue (F2268=4.49; P=0.012), physical
functioning (F2267=5.36; P=0.005), depression (F2268=5.03;
P=0.007), and sleep (F2266=5.99; P=0.003). In all of these cases,
patients allocated to pragmatic rehabilitation did significantly better than
those receiving supportive listening (fig 2⇓).
View larger version:
Fig 2 Mean scores
on the Chalder et al fatigue scale, SF-36 physical functioning scale, Jenkins
et al sleep scale, and the hospital anxiety and depression scales (HADS)
depression subscale at baseline (week 0), after treatment (week 20), and at one
year follow-up (week 70) for patients allocated to the three treatment arms.
*Significant difference between PR and GPTAU; †significant difference between
SL and GPTAU, P<0.05 for both. GPTAU, general practitioner treatment as
usual; PR, pragmatic rehabilitation; SL, supportive listening
The final 20
week analyses involved both robust standard errors and corresponding confidence
intervals, together with weighting adjustments to allow for missing outcomes.
Compared with patients allocated to GP treatment as usual, patients allocated
to pragmatic rehabilitation had significantly improved fatigue (treatment
effect estimate -1.18, 95% CI -2.18 to -0.18; P=0.021), depression (-1.18,
-2.16 to -0.20; P=0.018), and sleep (-1.54, -2.96 to -0.11; P=0.035) at 20
weeks. Patients who received supportive listening had significantly worse
physical functioning at 20 weeks than patients who had treatment as usual
(-7.54, -12.76 to -2.33; P=0.005); supportive listening had little effect on
fatigue, anxiety, depression, or sleep. Estimated differences between the
outcomes of pragmatic rehabilitation and GP treatment as usual, and between
those of supportive listening and GP treatment as usual, are shown in table 4⇓.
View this table:
Table 4
Robust treatment effect estimates
(compared with general practitioner treatment as usual) at 20 weeks and 70
weeks on the Chalder et al fatigue scale, the SF-36 physical functioning scale,
the Jenkins et al sleep scale, and the hospital anxiety and depression scales
(HADS)
A total of 257 (87%) of the 296
patients who entered the trial were assessed at 70 weeks. In the initial
unweighted (complete case) analysis at 70 weeks, global tests and contrasts
showed a between group difference in physical functioning only (F2,249=3.37;
P=0.036). In the final weighted analysis at 70 weeks, patients allocated to
pragmatic rehabilitation did not differ significantly in physical functioning
from those allocated to GP treatment as usual (effect +2.57, 95% CI -3.90 to
+9.03; P=0.435; table 4). The treatment difference in terms of fatigue was no
longer statistically significant at 70 weeks (-1.00, -2.10 to +0.11; P=0.076),
although much of the improvement in the pragmatic rehabilitation group seen at
20 weeks appeared to be maintained. Supportive listening did not differ
significantly from GP treatment as usual on any of the outcomes at 70 weeks.
At 70 weeks, 11 patients allocated
to pragmatic rehabilitation (14%) and six patients (7%) allocated to GP
treatment as usual were no longer classified as cases of fatigue (that is,
scored less than 4 on the fatigue scale). A total of 17 patients allocated to
pragmatic rehabilitation (21%) were classified as having improved on the
physical functioning scale (that is, had scores of >70%, or had improved by
50% from baseline),16 compared
with 10 patients (12%) allocated to GP treatment as usual.
Safety of
treatment
One patient
developed a herpes simplex infection during the treatment. During the follow-up
period, one patient attempted suicide, one developed a bleeding peptic ulcer,
and one had a recurrence of cancer. Our independent data monitoring committee
was informed of all these events and considered them unrelated to the trial
treatments.
Discussion
We report on
the largest primary care treatment trial for CFS/ME to date, which has a broad
and inclusive sample of patients with a range of levels of disability. Our
study shows that, when compared with treatment as usual, pragmatic
rehabilitation has a statistically significant but clinically modest beneficial
effect on fatigue at the end of treatment (20 weeks), which is mostly
maintained but no longer statistically significant at one year after finishing
treatment (70 weeks). Pragmatic rehabilitation did not significantly improve
our other primary outcome, physical functioning, at either 20 weeks or 70
weeks. Improvements in sleep at 20 weeks were considerably smaller and no
longer statistically significant at 70 weeks, and improvements in depression at
20 weeks were no longer observed at 70 weeks. Pragmatic rehabilitation did not
have an effect on anxiety.
When
compared with GP treatment as usual at 20 weeks, supportive listening had no
significant effect on fatigue, anxiety, depression, or sleep. Supportive listening
did have a significant effect on physical functioning, however, with patients
allocated to supportive listening having worse scores. At 70 weeks, supportive
listening did not differ from GP treatment as usual on any of the outcomes.
Pragmatic
rehabilitation
Our first
conclusion is that pragmatic rehabilitation improved fatigue, sleep, and
depression while treatment was ongoing, but that the effects were no longer
statistically significant at follow-up. Pragmatic rehabilitation was less
effective in our trial than in a previous secondary care trial,13 and the proportions of patients who had recovered in
terms of fatigue and physical functioning scores at 70 weeks were smaller. We
suggest five possible reasons why pragmatic rehabilitation was not as effective
in our trial as in the earlier secondary care trial.
Firstly, the
characteristics of the patients in the two trials differ. Our patients were on
average eight years older than those in the earlier trial. The mean illness
duration in our trial (84 months) was almost three years longer than that in
the earlier trial (52 months), and some patients in our study had very long
illness durations. The mean baseline physical functioning scores among our
patients (~30%) were similar to those reported in the previous trial (~16 on a
10-30 scale). We succeeded in our aim of including more severely affected
patients, however, meaning that our sample was heterogeneous with regard to
disease severity and contained patients from across the spectrum of severity.
For example, 11% of patients in our trial were non-ambulatory and would have
been excluded from a secondary care trial.
Secondly,
ours was a pragmatic trial, and we were broad and inclusive in the application
of our trial inclusion criteria. For example, we did not require that patients
had received previous treatment for depression or sleep problems in order to
enter our trial, unlike in a previous study.30 We included
complex cases with medical or psychiatric comorbidities (which we report), as
long as these disorders did not explain the fatigue. Ten participants in the
trial, including four allocated to the pragmatic rehabilitation arm, had
received pragmatic rehabilitation more than one year before entering our trial
but still had CFS/ME, so may have been particularly difficult to treat.
Although our profile of scores on the hospital anxiety and depression scales is
similar to that in another UK primary care sample,31 illness
duration was longer in our study and we included a substantial number of
patients with medical comorbidities, which may have complicated treatment. The
latter are rarely reported in clinical trials, making a comparison of samples
difficult. Future studies or analyses may examine the impact of comorbidites,
level of disability, and chronicity on patient response to pragmatic
rehabilitation treatment.
Thirdly, in
the secondary care trial of pragmatic rehabilitation,13 the therapy
was delivered by an experienced counsellor who had developed the pragmatic
rehabilitation treatment. In our trial, pragmatic rehabilitation was delivered
by three general nurses who had no previous experience of either counselling or
delivering structured therapies. The nurses received four months of training so
had learned the therapy rather than developed it. Although our therapy quality
ratings showed our therapists to be competent, they were not as experienced at
delivering the therapy as was the practitioner in the previous trial.
Additionally, the nurses were treating a heterogeneous sample and had to deal
with a wide range of patient functioning. The evidence as to whether
inexperienced therapists can successfully treat CFS/ME is limited: a recent
benchmarking study suggests they can,32 but that
treatment effects are generally larger with more experienced therapists. It is
possible that the more complex and difficult cases of CFS/ME can only be
treated successfully by experienced therapists.
Fourthly,
although delivering the treatment in patients’ homes enabled us to reach more
patients than if the therapy had been delivered in a healthcare setting, this
approach may be non-optimal. Our nurse therapists encountered various social
barriers to treatment in patients’ homes, such as family and financial
problems, and lack of privacy. It is possible that patients with social
problems are screened out in secondary care studies, or that social problems
are dealt with before referrals are made or patients are accepted for
treatment. It is also possible that delivering treatment in patients’ homes
subtly changes the relationship between patients and therapists so that
patients are less likely to adhere to the pragmatic rehabilitation programme
when at home than when in a hospital setting.
Finally, our
treatment period may have been too short for patients with long illness
durations, and treatment effects may have been enhanced had we been able to
provide post-treatment booster sessions. We chose the duration of treatment on
pragmatic grounds, taking into account the feasibility of reproducing the
treatment programme in primary care services.
One reason for conducting our trial
was to see whether registered adult specialty general nurses could be trained
to deliver pragmatic rehabilitation. Our findings suggest that they could, but
that despite an intensive four month training period and ongoing supervision,
pragmatic rehabilitation treatment was not as effective as when delivered by a
highly experienced therapist in secondary care. Furthermore, our therapists had
a high frequency of supervision which might not be reproducible in non-trial
contexts, and would be difficult to commission.
Supportive
listening
The finding
that supportive listening is not an effective treatment for CFS/ME in primary
care is important, because treatments similar to supportive listening are
commonly available in primary care and patients for whom no other treatment is
available might be referred to them. Contrary to our expectations, supportive
listening did not improve any of our outcomes, including anxiety and
depression.
Ridsdale et
al showed that counselling was as effective as cognitive behavioural therapy
for chronic fatigue in primary care.15 Only a
quarter of the patients in Ridsdale and colleagues’ study had CFS/ME, however,
and the duration of fatigue was shorter than in our study (median illness
duration 38 months compared with 84 months in our trial). Furthermore, the
trial did not have a treatment as usual control group and the counselling
treatment may not have been as non-directive as ours.
One
interpretation of our findings is that for patients with CFS/ME of long duration
or for patients with a severe presentation, supportive listening may actually
distract patients from efforts at rehabilitation by providing a forum to
consider a range of issues of importance to the patient rather than focusing on
rehabilitation. This may also be one explanation why support groups, even if
valued by patients, are not associated with improvements in fatigue or physical
functioning.33
Strengths
and limitations
In addition to
being a large, inclusive, pragmatic, primary care trial, our study had other
strengths. We trained general nurses to deliver the therapy, thus increasing
the generalisability of our findings. Using all three nurse therapists to
deliver both treatments allowed us to determine the effectiveness of the
therapies rather than the therapists, and the random allocation of patients to
therapists will enable us to examine therapist effects in a future analysis.
Our nurse therapists achieved high treatment fidelity and the delivery of the
two treatments was of comparable quality. We had low dropout rates, and high
rates of follow-up. The interpretation of our findings is aided by the
inclusion of both a comparison arm (supportive listening) and a treatment as
usual control arm.
For all
these reasons, it is likely that our trial gives an accurate indication of the
effectiveness of nurse delivered pragmatic rehabilitation and supportive
listening for CFS/ME in primary care. The difference between the findings of
this trial and those of our previous trial in secondary care13 provides evidence that treatment approaches shown to
be effective in randomised controlled trials in hospital based outpatient clinics
may be less effective for patients in the community with longer durations of
illness.9
Conclusions
and further research
Pragmatic
rehabilitation delivered at home by trained general nurses over a period of 18
weeks improved fatigue, sleep, and depression among patients with CFS/ME, but
these effects were not maintained in the long term once treatment was
completed. Supportive listening delivered by trained general nurses was not an
effective treatment for CFS/ME in primary care. More studies are needed to
determine the optimal conditions under which pragmatic rehabilitation can be
delivered to patients in the community with CFS/ME and whether the limited
benefits seen in this trial can be sustained.
What is
already known on this topic
·
Chronic fatigue syndrome/myalgic
encephalomyelitis or encephalitis (CFS/ME) is a disabling condition with a poor
prognosis unless treated
·
There is limited evidence as to
whether CFS/ME can be managed in primary care
·
A programme of graded return to
activity based on a physiological dysregulation model of CFS/ME, called
pragmatic rehabilitation, was successful at treating fatigue when delivered in
secondary care
What this
study adds
·
An 18 week pragmatic rehabilitation
programme delivered at home by trained general nurses produced small
improvements in fatigue, sleep, and depression, but not physical functioning,
in patients with CFS/ME
·
These effects were not maintained in
the long term once treatment was completed
·
A supportive listening comparison
treatment, also delivered by trained general nurses, was not effective for
CFS/ME in primary care
·
Our study demonstrates the
importance of setting in the delivery of complex interventions, and the
necessity for replication of research
Notes
Cite this as: BMJ
2010;340:c1777
Footnotes
·
We thank all the patients who took
part in the study. We are also grateful for the assistance of the Liverpool
Primary Care Trust, the Mersey Primary Care R&D Consortium, and the staff of
the186 general practices who referred patients to our study.
·
Contributors: All authors
participated in the overall design of the study, were involved in the ongoing
management of the trial, contributed to the interpretation of the data, and
contributed to several drafts of this report. In addition, AJW, the principal
investigator, conceived the study, prepared the protocol, contributed to
training of therapists and supervision of researchers, had overall
responsibility for the day to day running of the study, interpreted the data,
and took the lead on writing the report. AJW also acts as the guarantor for the
study. CD and CCG participated in the training of therapists and the
recruitment of general practices into the study, and advised on medical exclusions
from the trial. RPB and RKM participated in the training and supervision of
therapists. RKM also trained the researchers in psychiatric interviewing and
advised on psychiatric exclusions from the trial. SP participated in training
of therapists and recruitment of patients to the trial. LR was the trial
manager, and participated in recruitment and training of research staff. LR was
also responsible for staff management and overall coordination of the study. GR
was the trial health economist and advised on trial assessments. KL advised on
recruitment of patients to the trial and participated in the design and
implementation of the therapy rating exercise. GD was the trial statistician,
and advised on randomisation and all statistical aspects of the trial, developed
the analysis plan, and performed the statistical analysis. All authors had full
access to all study data.
·
Funding: The UK Medical Research
Council (G200212) and the UK Department of Health funded the trial. The study
was sponsored by the University of Manchester. The sponsor and the funder of
the study had no role in the study design, data collection and analysis,
interpretation or reporting of this work, or the decision to submit the work
for publication. All authors are independent of the funding source.
·
Competing interests: All authors
have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available
on request from the corresponding author) and declare: (1) No financial support
for the submitted work from anyone other than their employer; (2) No financial
relationships with commercial entities that might have an interest in the
submitted work; (3) No spouses, partners, or children with relationships with
commercial entities that might have an interest in the submitted work; (4) No
non-financial interests that may be relevant to the submitted work.
·
Ethical approval: Ethical approval
for this trial was granted by the Eastern Multicentre Research Ethics
Committee, reference 03/5/62.
·
Data sharing: We will be happy to
make our dataset available to researchers, once we have finished reporting our
findings. Please contact the corresponding author.
·
The Fatigue Intervention by Nurses
Evaluation (FINE) trial writing group consists of Alison Wearden, Richard
Bentall, Carolyn Chew-Graham, Christopher Dowrick, Graham Dunn, Karina Lovell,
Richard Morriss, Sarah Peters, Gerry Richardson, and Lisa Riste.
·
The FINE trial group consisted of
Colette Bennett, Richard Bentall, Laura Booth, Joanna Brocki, Greg Cahill, Anna
Chapman, Carolyn Chew-Graham, Susan Connell, Christopher Dowrick, Graham Dunn,
Deborah Fleetwood, Laura Ibbotson, Diana Jerman, Karina Lovell, Jane Mann,
Richard Morriss, Sarah Peters, Pauline Powell, David Quarmby, Gerry Richardson,
Lisa Riste, Alison Wearden, and Jennifer Williams.
This is an
open-access article distributed under the terms of the Creative Commons
Attribution Non-commercial License, which permits use, distribution, and
reproduction in any medium, provided the original work is properly cited, the
use is non commercial and is otherwise in compliance with the license. See: .
References
- Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, et al. A report—chronic fatigue syndrome: guidelines for research. J R Soc Med1991;84:118-21.
- Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A, et al. The chronic fatigue syndrome—a comprehensive approach to its definition and study. Ann Intern Med1994;121:953-9.
- Komaroff AL, Fagioli LR, Doolittle TH, Gandek B, Gleit MA, Guerriero RT, et al. Health status in patients with chronic fatigue syndrome and in general population and disease comparison groups. Am J Med1996;101:281-90.
- Bombardier CH, Buchwald D. Chronic fatigue, chronic fatigue syndrome, and fibromyalgia—disability and health-care use. Med Care1996;34:924-30.
- McCrone P, Darbishire L, Ridsdale L, Seed P. The economic cost of chronic fatigue and chronic fatigue syndrome in UK primary care. Psychol Med2003;33:253-61.
- Department of Health. A report of the CFS/ME working group: report to the chief medical officer of an independent working group. DH, 2002.
- National Institute for Health and Clinical Excellence. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management (CG53 NIfHaCECG). NICE, 2007.
- Euba R, Chalder T, Deale A, Wessely S. A comparison of the characteristics of chronic fatigue syndrome in primary and tertiary care. Br J Psychiatry1996;168:121-
- Raine R, Haines A, Sensky T, Hutchings A, Larkin K, Black N. Systematic review of mental health interventions for patients with common somatic symptoms: can research evidence from secondary care be extrapolated to primary care? BMJ2002;325:1082-5.
- Chambers D, Bagnall AM, Hempel S, Forbes C. Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review. J R Soc Med2006;99:506-20.
- Price JR, Mitchell E, Tidy E, Hunot V. Cognitive behaviour therapy for chronic fatigue syndrome in adults. Cochrane Database Syst Rev2008;(3):CD001027.
- Edmonds M, McGuire H, Price J. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev2004;(3):CD003200.
- Powell P, Bentall RP, Nye FJ, Edwards KHT. Randomised controlled trial of patient education to encourage graded exercise in chronic fatigue syndrome. BMJ2001;322:387-90.
- Mellor-Clark J, Simms-Ellis R, Burton M. National survey of counsellors in primary care: evidence for growing professionalisation. Occasional paper 79. Royal College of General Practitioners, 2001.
- Ridsdale L, Godfrey E, Chalder T, Seed P, King M, Wallace P, et al. Chronic fatigue in general practice: is counselling as good as cognitive behaviour therapy? A UK randomised trial. Br J Gen Pract2001;51:19-24.
PEMBAHASAN
Menjawab 5 W+ 1H :
Korespondensi: AJ Wearden
alison.wearden @ manchester.ac.uk
• Diterima 8 Februari 2010
• Diterima 8 Februari 2010
Penelitian
ini membahas tentang perawatan di rumah swadaya berbasis untuk pasien dalam
perawatan primer dengan sindrom kelelahan kronis, Tujuan Untuk mengevaluasi
efektivitas diantar ke rumah rehabilitasi-pragmatis program kegiatan secara
bertahap meningkat dirancang secara kolaboratif oleh pasien dan terapis-dan
mendukung mendengarkan-pendekatan berdasarkan non-direktif konseling untuk
pasien dalam perawatan primer dengan sindrom kelelahan kronis / myalgic
encephalomyelitis atau ensefalitis (CFS / ME).
Peserta 296
pasien berusia 18 tahun atau lebih dengan CFS / ME (penyakit durasi median
tujuh tahun) didiagnosis dengan menggunakan kriteria Oxford. Intervensi Peserta
secara acak dialokasikan untuk rehabilitasi pragmatis, mendengarkan mendukung,
atau pengobatan dokter umum seperti biasa. Kedua terapi tersebut disampaikan di
rumah dalam 10 sesi selama 18 minggu dengan salah satu dari tiga khusus dewasa
perawat umum yang telah menerima pelatihan empat bulan, termasuk praktek di
bawah pengawasan, dalam setiap intervensi. GP pengobatan seperti biasa tidak
dibatasi kecuali bahwa pasien tidak harus dirujuk untuk terapi psikologis yang
sistematis selama masa pengobatan.
Hasil utama mengukur Hasil klinis yang utama adalah kelelahan dan fungsi fisik pada akhir pengobatan (20 minggu) dan 70 minggu dari perekrutan dibandingkan dengan perlakuan GP seperti biasa. Skor kelelahan yang lebih rendah dan lebih tinggi skor fungsi fisik menunjukkan hasil yang lebih baik.
Hasil utama mengukur Hasil klinis yang utama adalah kelelahan dan fungsi fisik pada akhir pengobatan (20 minggu) dan 70 minggu dari perekrutan dibandingkan dengan perlakuan GP seperti biasa. Skor kelelahan yang lebih rendah dan lebih tinggi skor fungsi fisik menunjukkan hasil yang lebih baik.
Kesimpulan
Untuk pasien dengan CFS / ME dalam perawatan primer, rehabilitasi pragmatis
disampaikan oleh terapis perawat terlatih meningkatkan kelelahan dalam jangka
pendek dibandingkan dengan perlakuan GP tak terbatas seperti biasa, tetapi
efeknya kecil dan tidak signifikan secara statistik pada satu tahun follow up.
Mendengarkan mendukung disampaikan oleh terapis perawat terlatih bukan
merupakan pengobatan yang efektif untuk CFS / ME. Sidang pendaftaran
International Standard acak Nomor Controlled Trial IRCTN74156610.
Pengantar
Pengantar
Pasien
dengan sindrom kelelahan kronis, juga dikenal sebagai myalgic encephalomyelitis
atau ensefalitis myalgic, memiliki gejala utama aa kelelahan yang berlangsung
setidaknya enam bulan dan keparahan yang cukup untuk secara substansial merusak
functioning.1 Diagnosis adalah dengan sejarah dan pengucilan alasan medis dan
psikiatris untuk yang fatigue.2 kronis sindrom kelelahan / encephalomyelitis
myalgic atau ensefalitis (CFS / ME) menyebabkan substansial disability3 dan
memiliki konsekuensi penting bagi kesehatan dan penggunaan expenditure.4 5 Di
Inggris, prevalensi populasi CFS / ME telah diperkirakan 0,2- 0,4% .6 Banyak
pasien dengan CFS / ME tidak mengakses pengobatan, baik karena tidak ada
layanan di daerah mereka atau karena mereka tidak mampu untuk menghadiri
services.6
Pasien dengan CFS / ME dalam
perawatan primer berbeda dari yang terlihat di rumah sakit settings.8
Pengobatan untuk CFS / ME yang efektif dalam perawatan sekunder mungkin kurang
efektif dalam perawatan primer, uji coba sangat pragmatis perawatan untuk
pasien dalam perawatan primer needed.9
Sebuah
tinjauan sistematis percobaan terkontrol pengobatan untuk CFS / ME, termasuk
pendekatan perilaku, farmakologi, dan saling melengkapi, menyimpulkan bahwa ada
bukti bahwa terapi perilaku kognitif dan terapi latihan dinilai adalah
effective.10 Sebuah tinjauan Cochrane terbaru dari terapi perilaku kognitif
untuk orang dewasa dengan CFS / ME menyimpulkan bahwa pendekatan ini efektif
dalam mengurangi kelelahan dinilai pada akhir pengobatan period.11 Sebuah
tinjauan Cochrane terapi latihan dinilai menyimpulkan bahwa beberapa pasien
manfaat dari latihan, tetapi pendekatan ini tidak selalu diterima patients.12
Terapi perilaku kognitif dan terapi latihan dinilai direkomendasikan dalam
pedoman NICE, namun kedua perawatan harus disampaikan oleh spesialis
therapists.