6 VEDLEGG
6.3 Informasjonsskriv til pasientene
Forespørsel til pasienter med fibromyalgi (FM) om deltagelse i en studie for å sammenligne effekt av behandlingsopphold i Norge og varmt klima.
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EFFECT OF A MULTIMODAL TREATMENT PROGRAM IN WARM VERSUS COLD CLIMATE FOR PATIENTS WITH FIBROMYALGIA, A RANDOMIZED
CONTROLLED STUDY.
Anne-Cathrine Clarke-Jenssen PT1, Anne Marit Mengshoel Prof2, Yndis Staalesen Strumse, MD, PhD3 Karin Øien Forseth, MD, PhD.3 1Department of orthopaedics, Oslo University Hospital, Rikshospitalet, 2Department of
Health Sciences, Faculty of Medicine, University of Oslo, 3Section for climate therapy, Oslo University Hospital, Rikshospitalet,
Objective: To study the long-term effect on symptoms and physical function of a 4-weeks multimodal treatment program (MTP) for patients with fibromyalgia (FM), and to ascertain if climatic conditions influence the results.
Methods: A total of 129 Norwegian patients with FM were randomized to an intervention in a warm or a cold climate, or to a control group without any intervention. The MTP consisted of aerobic exercise on land and in warm water, stretching, relaxation and patient education. The participants were evaluated immediately before and after the intervention, and after three and 12 months. Pain measured by tender point count (TPC) and physical function measured by six minutes walking test (6MWT) were chosen to be the main outcome measures of this study. One-way analysis of variance (ANOVA) was used for the between group comparisons and Student T-test for within groups analysis.
Results: Lasting reduction in pain measured by TPC was found in the warm climatic setting only. A mean reduction (SD) by 2 (2.7) tenderpoints (TP) in a warm climatic setting compared to 0.3 (2) TP in a cold climatic setting was found one year after the intervention (p≤0.002). Comparable improvements were found in physical function (6MWT) for the two intervention groups. A mean improvement (SD) of 34 (45) m in cold climatic setting and of 38 (41) m in a warm climatic setting were still present one year after the intervention (p≤0.025). No improvements were found within the control group at any point of time.
Conclusion: This study shows that MTP for patients with FM had a positive long-term effect on pain measured by TPC when given in warm climatic setting and some long term effect on physical function in both warm and cold climatic setting.
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INTRODUCTION
Fibromyalgia is a chronic, generalized pain condition with additional non-specific symptoms as fatigue, sleep disturbance, stiffness, depression, anxiety and cognitive dysfunction (1). The multiple symptoms may have a large negative impact on daily life for patients with FM (2;3). The aetiology and pathogenesis of FM is not yet fully understood, but one important contribution is most likely abnormalities in the central nervous system’s pain processing that leads to central sensitization associated with hypersensitivity and allodynia (4). Fibromyalgia is probably a multidimensional disorder, involving somatic, psychological and social factors (5).
There is at present no cure for FM. But a multidisciplinary approach consisting of both pharmacological and nonpharmacological therapies have shown to improve symptoms and function (6).
The nonpharmacological therapies should include patient education, adjusted aerobic exercise and cognitive behavioural therapy (7).
Norwegian patients with inflammatory rheumatic diseases have been offered a multimodal treatment program in warm climate for decades and some studies have shown positive long term effect of this treatment (8-10). What causes the effect of a rehabilitation program in warm climate is not yet fully understood. Positive effect of exercise therapy for patients with rheumatoid arthritis is well documented (11). The rationale for rehabilitation in warm climatic setting for these patients is that sunny, warm and dry climate relieve symptoms like pain and stiffness in rheumatic patients which again is supposed to enhance the patient’s ability to be more physical active and better tolerate the exercise programme prescribed (10;12). Anecdotally patients with FM like other rheumatic patients report less symptoms in warm climate.
But to our knowledge, there exists no randomized controlled study (RCT) comparing the effect of a rehabilitation program given either in warm and cold climate for patient with FM. Neither did we find any RCT studying possible long term effect of a comprehensive rehabilitation program of four weeks in warm climate for patients with FM.
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Objectives
The aim of this study was to examine the long-term effects on symptoms and physical function in patients with FM after a 4-weeks multimodal treatment program (MTP) in warm climate, a similar program in cold climate or no intervention.
MATERIAL AND METHODS
Design
This was a randomized, controlled study to examine the effect of a comprehensible rehabilitation program under different climatic settings. It was a three-group study where the patients were randomized to a four weeks rehabilitation program in a Mediterranean country (44 patients to Scandinavian Rehab Centre in Antalya in Turkey), to a similar treatment program in Norway (44 patients to Skogli Rehabilitation Centre at Lillehammer), or 44 patients to a control group with no specific intervention.
Sample size was calculated according to Aalen et al. For six-minute walking test (6MWT), a power of 80
%, a minimal clinical difference of 50 m, a SD of 75 m and a significant level of 0,05, we needed 36 patients in each group. Allowing for an attrition rate of 20 %, we included 44 patients in each group. All participants were examined before and after intervention and after three and 12 months. The intervention groups were additionally examined after six and 24 months. The intervention groups were examined at the venues of the rehabilitation immediately before and after intervention. The other tests were carried out at Rikshospitalet, Oslo University Hospital. Three experienced physiotherapists (PT) performed all the physical tests, and the same PT examined the same outcome measure each time.
Material
The patients were recruited from an outpatient’s clinic for rheumatic patients at Martina Hansens Hospital (MHH) in the neighbouring county of Oslo. All patients with FM admitted to the clinic between
4 4 2004 and 2006, a total of 425 patients, received a written invitation to participate in the study. Those who were interested, in all 165 patients, were summoned to a screening test. The patients were consecutively included during spring 2007 according to the inclusion criteria until we reached the pre-calculated number of 132 participants. The patients were randomly assigned by 1:1:1 to the Mediterranean group, the Norwegian group or to a control group. The randomization was undertaken by the Biostatistic Centre at Oslo University Hospital, and the patients were stratified by gender and age. They got the result of the randomization by letter. Nine patients from the Mediterranean group and 17 patients from the Norwegian group withdrew immediately after they got the results of the randomization. Invitations to 100 new patients admitted to the clinic in 2007 were send out to uphold the pre-calculated strength of the study. The interested patients were summoned to a screening test and consecutively randomized 2:1, as there was twice as many patients in Norwegian group that had withdrawn and none from the control group. The screening and randomization continued until we again reached the number of 132 participants. The last participants randomized, were given the results of the randomizing by telephone the next day. During the intervention two patients were excluded because of other medical conditions (inflammatory rheumatic arthritis and venous thrombosis) and one patient were excluded for drug abuse. The total number of participants was 129.
Inclusion
Inclusion criteria were: Fulfilling ACR‘s classification criteria of 1990 for FM (13), being between 18 and 60 years of age, self-sufficient in activity of daily living, capable of participating in light exercise group on land and in warm water and understand written and oral Norwegian. Excluded were those having serious physical or psychiatric diagnoses, having alcohol or drug abuse, being pregnant or breast feeding or receiving more than 50 % disability pension. All participants gave their written consent to the participation.
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Intervention
The treatment program followed international recommendation for non-pharmacological treatment for patients with FM (7) and was designed in close cooperation with experienced physiotherapists. An important issue in this study was to examine whether the climate had an additional effect on the outcomes.
It was thus important that the two treatment groups were given as identical rehabilitation programs as possible. The same physiotherapist conducted the exercise classes and patient education at both venues.
Previous studies have shown that patients with FM have diminished working capacity and experience activity induced pain especially at the beginning of an exercise program (14-16). Thus the patients started at a low level, progressed slowly over time and rested between the exercise classes. The intervention program was given five days a week and lasted for four weeks and took place in the autumn of 2007.
Individual treatment was not given, in contrast to the usual practice at both venues.
6 6 Table 1. The rehabilitation program for both intervention groups
Type of
intervention Frequency of
intervention Content Intensity of
intervention Lead by Walking classes Daily for 45 min. Walking outdoors
on partly uneven
Stretching Daily for 15 min.
after the walking All the main
muscles Without pain PT in charge Exercise groups in
warm water Alternatively 2 or 3 times a week for 45 min.
Emphasis on
aerobic exercise Moderate intensity (slightly
breathless)
Local PT
Exercise groups on
land Alternatively 2 or
3 times a week for
Relaxation groups Two times a week
for 45 min. Hold-relax
technique Local PT
Patient education Once a week The topics were:
Update on FM,
The control group had no intervention the first year, and was treated “as usual”. They were however offered rehabilitation in warm climate the following year as compensation for no intervention the first year.
Climate
The interventions took place in September in Norway and in October in Turkey. The temperature and the weather (sunny/cloudy/rainy) were noted daily at noon by a nurse in Turkey. The Norwegian Meteorological Institute gave the same information on the weather in Norway.
7 7 Table 2. The weather at the rehabilitation venues in the treatment periods
Mean daytime
temperature (SD) Precipitation Number of
sunny days Number of
cloudy days Number of rainy days
Antalya, Turkey 260C (31 - 22) 2mm 25 2 2
Lillehammer, Norway 8,50 C (19 - -1) 53mm 16 5 8
Outcome measures
Outcome measures were chosen for their properties to detect changes in the areas important for these patients, namely pain, non-specific symptoms, physical function and quality of life. Most of the outcome measures are evaluated as valid and reliable for patients with FM and recommended in studies for these patients by the OMERACT 7 (17).
Primary outcome measures
Pain is the main symptom in FM and in a number of clinical studies pain is measured by TPC (18;19). In this study digital TPC was tested according to the description in ACR‘s classification criteria (13). TPC is found to be useful as an outcome measure for pain on patients with FM (20) and it is also found sensitive for change in non-pharmacological studies for these patients (21).
6MWT is a clinically relevant measure of a patient’s functional capacity. The patient covers as many meters as possible in six minutes under the same standardized conditions at every test (22). This test is often used in exercise studies for patients with FM (19). 6MWT is tested for validity, responsiveness and reliability for patient with FM (23;24). To ensure that improvements were not just a learning effect, all patients did a 6MWT at the screening situation (23).
8 8 Secondary outcome measures
Fibromyalgia Impact Questionnaire (FIQ) is a disease specific questionnaire designed to evaluate the health status of patients with FM (25). The first part of the questionnaire measures physical function, work status and overall well-being. The latter part measures the intensity of symptoms the last week including a visual analogue scale of ten centimetres (VAS) for pain. FIQ is scored from 0–80 and the higher score the more impact the disease has on daily life. FIQ is tested for validity and reliability for patients with FM in Sweden (26).
The pain mannequin from Mc Gill’s pain questionnaire was used to evaluate the patients own experience of pain distribution (27;28). The patient was asked to circle painful areas during the last week.
Patients with FM experience pain in both joints and muscles, so when the mannequin was scored, the number of circles around both joints and muscle are counted (e.g. fingers, hand, wrist, underarm, elbow, upper arm and shoulder) on the left and right side and on the front and back of the body. The highest score was thus 70.
Grip Strength was used as the second physical test. Jamar dynamometer is a hand held device to measure grip strength. It is a quick test that gives an exact number in pounds of the patients’ ability to generate hand power. The patient is sitting with 90 degree flexions in the elbow and the assessor supports the dynamometer. The patient grips as hard as he can, and the mean value of three attempts is noted (29).
Grip strength is recommended as outcome measure in studies on patients with FM (30).
Arthritis Self Efficacy Scale Arthritis Self Efficacy Scale (ASES) is a questionnaire designed to measure the perceived self -efficacy on pain, physical function and symptoms in patients with arthritis (31).
The subgroups are scored individually from 10-100, and the higher score, the better self-efficacy. It is tested for validity and reliability for Swedish patients with FM (32).
Short Form Health Survey (SF 36) is a generic questionnaire assessing health related quality of life.
SF 36 have 8 subscores for physical function, role physical, role emotional, vitality, bodily pain, general health, social life and depression, and two total scores for physical and mental scores. The raw score is
9 9 converted through a syntax. The final scores are ranged from 0-100, and the higher score the better quality of life. SF 36 is used in a number of clinical FM studies (33).
Leisure Time Physical Activity Index (LTPAI) is a questionnaire designed to estimate the number of hours of physical activity during leisure time in the last week for patients with FM. The patients note the number of hours they perform light, moderate and strenuous physical activity, and the total hours of physical activity can be calculated. LTPAI is valid and reliable for patients with FM (34).
Hospital Anxiety and Depression Scale (HADS) is a questionnaire that measures self-reported anxiety and depression (35). The two subgroups are scored separately from 0-21. The higher score the more seriously effected the patients are by anxiety or depression. Scores above 11 are considered pathological. HADS has been used in a number of FM clinical trials (33).
Statistics
All data were scanned via Teleform to Access and transported to SPSS, version 18. Descriptive statistics were carried out to calculate demographic data and baseline values. The demographic data are presented with mean and SD. Normally distributed continuous data for baseline values and results are presented with mean and 95 % CI, otherwise as median and 25th -75th centiles. Missing data at the follow up tests were replaced with baseline values according to the principle of intention to treat (36). The comparison within the groups was analysed with Paired-Samples T Test or Two related Samples Test (Wilcoxon) according to the distribution. The comparison between the groups was analysed by one-way analysis of variance (ANOVA) with post hoc test Tukey HSD and the group variable was used as factor.
Ethics
The research committee at Martina Hansen`s Hospital from where the patients were recruited, approved of the study and the invitations to participate in the study were signed by the senior doctor of the Department of rheumatology. The Regional Ethics committee and the Norwegian Social Science/Data Inspectorate approved of the study and written informed consent was obtained from all participants.
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RESULTS
The characteristics of the participants are shown in Table 3. The results of the intervention are shown in Table 4 and 5.
Effect on primary outcome variables:
The group that received intervention in warm climatic setting improved significantly in pain
measured by TPC at three and twelve months compared to the group in cold climatic setting and the control group (p≤0.002).
Both treatment groups improved in physical function (6MWT) at three and twelve months after the intervention compared to the control group (p<0.001).
Effect on secondary outcome variables:
The group that received intervention in warm climatic setting improved significantly in self-reported pain distribution (pain mannequin) at three months (p≤0.002) compared to intervention in cold climate. Pain intensity (VAS pain from FIQ) showed improvement at three months in the warm climate group compared to the control group (p=0.023). Grip strength showed improvement at three months for the group that received treatment in a warm climate compared to the control group (p<0.001), and at 12 months for both treatment groups (p≤0.003). The group in cold climatic setting had improvements in physical activity (LTPAI) three months after intervention compared to both the control group and the warm climate group (p≤0.027), and the ASES functional subscores improved only in this group compared to the control group three months after the intervention (p=0.040).
There were no statistically significant changes found in SF 36, HADS or other subscores of ASES and FIQ in either group. There were no adverse effects at the end of the intervention.
11 11 All patients that completed the rehabilitation program received 56 treatments during the four weeks intervention, a total of 2352 in the Mediterranean group treatments and 2408 in the Norwegian group.
Absence was noted and the main reason for absence was temporary increased pain.
Absence from treatment in the Mediterranean group: 114 of 2352 treatments = 5 % Absence from treatment in the Norwegian group: 208 of 2408 treatments = 9 %
DISCUSSION
The goal of this RCT was to examine the long-term effects on pain and physical function after a comprehensive rehabilitation program in different climatic settings. In this study treatment given in warm climatic setting had positive long term effect on pain measured by TPC up till one year after the intervention compared to both the cold climate group and the control group. Improvements in physical function in the same period were seen in both treatment groups compared to the control group.
Improvement in pain measured by TPC after an intervention in warm climate for patients with FM was found in other studies. Zijlstra et al found in their study a statistically significant improvement in pain measured by TPC compared to the control group after three months (37). Forseth and Mengshoel found in their study of patients with FM a statistically significant reduction three months after a rehabilitation program in warm climate (38). All studies showed that intervention in warm climate resulted in improvements in pain measured by TPC. But whether this improvement was due to the rehabilitation program, the warm climate or a combination was not known. In our study improvements in TPC were also found between the two intervention groups in favour of the warm climate group. As the rehabilitation programs were as identical as practically possible, one might assume that the difference in improvements between the two intervention groups were mainly due to the climatic settings.
If the goal of a rehabilitation program for patients with FM includes reduction of symptoms like pain measured by TPC, treatment in warm climate may be preferable. As pain is regarded as the main symptom
12 1 in FM and there are few pharmacological options to reduce the pain up till now, intervention targeted to improve the pain is of great importance for these patients.
Previous studies have shown that patients with FM experience activity induced pain especially at the beginning of an exercise program (15;16;30). The absence from the exercise classes in this study, were almost twice as high in the Norwegian group than in the Mediterranean group. The main reason for absence was temporary increased pain. The Mediterranean group also showed improvement in physical capacity
Previous studies have shown that patients with FM experience activity induced pain especially at the beginning of an exercise program (15;16;30). The absence from the exercise classes in this study, were almost twice as high in the Norwegian group than in the Mediterranean group. The main reason for absence was temporary increased pain. The Mediterranean group also showed improvement in physical capacity