Medication non-adherence in women with fibromyalgia

M. J. Sewitch1, P. L. Dobkin1, S. Bernatsky2, M. Baron3, M. Starr4, M. Cohen4 and M.-A. Fitzcharles4

Departments of 1Medicine and 2Epidemiology and Biostatistics, McGill University, 3Division of Rheumatology, Jewish General Hospital, McGill University Health Centre and 4Division of Rheumatology, McGill University Health Centre, Montreal, Canada.

Correspondence to: M. J. Sewitch, Division of Clinical Epidemiology, MUHC-The Montreal General Hospital, 1650 Cedar Avenue, Room L10-321.1, Montreal, Quebec, Canada H3G 1A4. E-mail: maida.sewitch{at}mail.mcgill.ca


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Objective. To identify the determinants of medication non-adherence in women with fibromyalgia (FM).

Methods. Participants included 10 rheumatologists and 127 women recruited from tertiary care hospitals and the community. Demographic, clinical and psychosocial characteristics and patient–physician discordance were assessed at the baseline visit. Non-adherence was assessed 2 weeks later. Multivariable generalized estimating equations were used to identify determinants of non-adherence to medication.

Results. The average age of the women was 50.4 (S.D. 10.5) yr and the mean disability score was 60.3 (16.0) yr. Sixty (47.2%) women were non-adherent to medication; 20 (33.3%) of these were intentionally non-adherent, 24 (40.0%) were unintentionally non-adherent, and the remaining subjects were both. Overall non-adherence was predicted by higher patient–physician discordance. Unintentional non-adherence was predicted by community subjects, not being under a rheumatologist’s care, less disease activity, less use of instrumental coping, and higher patient–physician discordance. Intentional non-adherence was predicted by shorter duration under a rheumatologist’s care and higher patient–physician discordance.

Conclusion. The therapeutic relationship, in addition to clinical and psychosocial characteristics, influenced non-adherence to medication.

KEY WORDS: Fibromyalgia, Determinants, Medication, Non-adherence, Women.


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The hallmarks of fibromyalgia (FM) are widespread pain, fatigue and multiple tender points [1]. Treatment includes both pharmacological and non-pharmacological interventions. Efficacy of antidepressants in reducing some of the symptoms in chronic pain conditions including FM, has been demonstrated [2, 3]. Other medications commonly used by patients with FM include anxiolytics, hypnotics, analgesics and agents to relieve gastrointestinal symptoms [4]. To date, no single treatment has been consistently successful [5], and it is not surprising that the majority of FM patients discontinue treatment within 1 yr [6].

Patient adherence in FM is a neglected topic. Patient adherence is defined as the extent to which an individual’s behaviour coincides with medical or health advice [7]. Adherence differs from compliance; compliance implies patient obedience to the physician’s authority [810] whereas adherence signifies that the patient and physician collaborate to improve the patient’s health by integrating the physician’s medical opinion and the patient’s lifestyle, values and preferences for care [1113]. While it might be helpful for clinicians to be able to identify patients who are at greater risk of non-adherence in order to intervene, patient characteristics have not been consistently linked to non-adherence in other chronic illnesses [14, 15]. This failure may be due to the fact that patient non-adherence varies between and within individuals, as well as across time, recommended behaviours and diseases. Moreover, previous work has failed to examine characteristics of the patient–physician relationship as possible determinants of non-adherence.

One model of patient adherence holds that effective patient–physician communication is central to optimizing patient adherence [16]. Higher patient–physician discordance has been associated with unfavourable health outcomes [1722], including general and medication non-adherence [23, 24], and with decreased patient satisfaction, a variable that is consistently associated with poorer adherence [15, 2529]. This theoretical framework has not been tested in FM.

The aim of this prospective study was to identify the determinants of medication non-adherence in women with FM. To fully explore the association between patient–physician discordance and non-adherence, patients’ psychosocial characteristics were assessed as potential confounders and effect modifiers, given that they have previously been related to patient and physician perceptions as well as to non-adherence [14, 16, 3032].


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Physicians
Physicians completed a single questionnaire on demographic variables, their level of training, and their experience treating FM. Following the visit with a participating patient, they completed a 10-item visual analogue scale (VAS) questionnaire pertaining to the office visit.

Participants with FM
Two approaches were used for recruitment. First, a convenience sample of 10 rheumatologists working in hospital or private practice settings were asked to identify patients with FM and to invite them to participate. Second, an advertisement was posted in English and French urban newspapers to recruit women with widespread body pain and fatigue. This approach included a structured telephone screening interview developed by White et al. [33] that has been shown to identify patients most likely to have FM. Women who screened positive during the telephone interview were subsequently examined by a rheumatologist to confirm the FM diagnosis. During this visit, a medical history was taken and tender points were assessed. Eligibility criteria included age of at least 18 yr, a diagnosis of primary FM based on the American College of Rheumatology criteria [34], and fluency in English or French. Patients completed a questionnaire immediately following the office visit, a battery of questionnaires within 72 h after the office visit, and a set of questionnaires 2 weeks later. Women recruited from the community were informed that no treatment would be offered. Written informed consent was obtained. The study protocol was approved by the McGill University Faculty of Medicine Institutional Review Board and by other hospitals not affiliated with McGill University.

Instruments
Patient–Physician Discordance Scale
Patient–physician discordance was assessed at the index visit with the Patient–Physician Discordance Scale (PPDS) [35], a 10-item VAS measure of the degree to which patients and their physicians disagree on health-related information. Scale items assess the patient’s health status (pain, disease activity, functioning, psychological distress and well-being) and aspects of the clinical visit (discussions of the main problem and of personal issues, expectation for medication and for further testing and patient satisfaction). Questionnaires are completed independently by both the patient and the physician; each rates his or her own perceptions and the results are examined for discordance. The PPDS yields an overall measure of discordance as well as three subscales: discordance on (i) symptoms and treatment, (ii) well-being and (iii) communication and satisfaction. In the present study, the two questions pertaining to expectations were deleted because they were not applicable to community-recruited women. Prior to their visit to the study rheumatologist, these women were told that the purpose of the visit was to confirm the FM diagnosis and they would not receive any treatment. Therefore, neither overall discordance nor the symptoms and treatment subscales were analysed. Difference scores on individual PPDS items were calculated in two ways. The first, which was used for descriptive purposes, was calculated as the crude patient–physician difference on a particular item. The second was calculated as the ratio of the patient–physician difference on a particular item to the standard deviation of the eight item ratings of the same patient. These standardized differences account for the possible non-comparability of internal scales of different patients, i.e. a subjective process that transforms the patient’s perception into a rating [37] that might arise from the patient’s lack of experience in using VAS. Standardized scores yield lower values, compared with the crude differences, for patients who show larger variation in ratings, those prone to rate towards the extremes of the VAS. Test–retest reliability ranged between 0.64 and 0.92 [23], and values of Cronbach’s {alpha} on the well-being subscale and the communication and satisfaction subscale were 0.49 and 0.75 respectively.

The following instruments were employed to assess patient characteristics within 72 h after the visit.

Psychological distress
Psychological distress was assessed with the Symptom Checklist-90R, a 90-item self-report measure of distress during the past week [36]. This scale does not yield psychiatric diagnoses. The Global Severity Index (GSI) summary score combines the number and intensity of symptoms, and is reported as a normalized T-score (normative mean score = 50, S.D. = 10). Clinically important distress corresponds to T-scores of 63 and greater. The internal consistency of the GSI in our FM sample was very high, as evidenced by Cronbach’s {alpha} = 0.98.

Social support
An abbreviated version of the Social Support Questionnaire was used [37, 38]. The SSQ-6 consists of two subscales assessing the number of people in the network (SSQ-N) and satisfaction with perceived available support (SSQ-S). The scoring for the SSQ-S subscale ranges from 1 to 6 (higher scores indicate greater satisfaction) and for SSQ-N from 0 to 9 (higher scores reflect a larger network). Test–retest reliability is high [37] and internal consistency in our FM sample was high (Cronbach’s {alpha} > 0.87).

Perceived stress
The Perceived Stress Scale (PSS) is a 10-item measure of stressful situations during the past month. Items are scored on a five-point scale from 0 to 4 [39]; the total score provides a global measurement of the extent to which an individual feels overwhelmed. Total scores range from 0 to 40; higher scores indicate greater perceived stress [39]. Test–retest reliability is good [40] and internal consistency in our sample was high (Cronbach’s {alpha} = 0.85).

Coping style
Coping was assessed using the Coping with Health Injuries and Problems (CHIP) developed by Endler and Parker [41]. The CHIP consists of 32 items: eight items pertain to distraction coping (i.e. they are aimed at avoiding preoccupation with the problem); eight items pertain to palliative coping (i.e. the use of self-help responses to alleviate unpleasantness); eight items pertain to instrumental coping (i.e. task-oriented strategies to deal with the illness); and eight pertain to emotional preoccupation (i.e. focusing on the emotional consequences of the problem). The CHIP has good psychometric properties [42]. In our sample, internal consistency was high (Cronbach’s {alpha}>0.71).

Social desirability
Social desirability was assessed with a five-item self-report measure of the extent to which an individual presents him or herself in a socially accepted manner [43]. Items are rated along a five-point scale from ‘definitely true’ to ‘definitely false’, and then dichotomized at ‘definitely true’ to reduce incorrect classification of social desirability. One-month test–retest reliability is satisfactory [43] and internal consistency was adequate in our sample (Cronbach’s {alpha} = 0.61), which, in part, reflects the small number of items in the scale.

Disability
The Fibromyalgia Impact Questionnaire (FIQ [44]) is a reliable, validated self-administered measure of functioning in the past week. The first 10 items address ability to carry out tasks that require physical strength; these are summed and divided by the number of valid scores to yield one physical functioning score. Two items ask respondents to circle the number of days they felt good, as well as the number of days of missed work. Seven items (e.g. pain, fatigue) are measured on a 100-mm VAS. A total score is created, with higher scores indicating greater disability. Test–retest reliability coefficients for each item ranged from 0.56 to 0.95 [44].

Sexual abuse
Sexual abuse was assessed using a validated self-report questionnaire [45] developed for population-based surveys of sexual and physical abuse [46]. The instrument has been used in studies of chronic pain, including FM [47, 48]. Subjects respond to five questions on episodes of sexual abuse in childhood or adulthood. Sexual abuse referred to any kind of sexual conduct or attempted sexual conduct that was unwanted. Scores range from 0 to 5, indicating the number of items endorsed. In the present study, scores were dichotomized at 0 to reflect no vs any sexual abuse.

Pain
Pain was assessed using the McGill Pain Questionnaire (MPQ) [49], a self-report measure of 78 words that describe the subject’s pain. The MPQ contains 78 descriptive words grouped in 20 subclasses of three to five words. The first word in each subclass is given the value of 1, the next word is given the value of 2, and so forth. The rank values of selected words are summed to obtain a pain rating index. The Present Pain Index (PPI), is a global measure of present pain ranging from 0 = no pain, 1 = mild pain to 5 = excruciating pain. The MPQ is extensively used and has excellent psychometric properties [50].

Covariates
Baseline covariates included patient age, years of education, FM-related disability, number of comorbid conditions, number of months since diagnosis, number of years under a rheumatologist’s care (not applicable, <=1 yr, > 1 yr), psychological distress (dichotomized at T-scores of 63, the cutoff point for clinical distress), perceived stress, social support (dichotomized at the median), sexual abuse (0/1), coping styles and social desirability.

Outcomes
Non-adherence to medication was assessed with a four-item, ordinally scaled validated questionnaire [51]. The time frame of the past 2 weeks was introduced to avoid a recall bias and to examine the time interval from the office visit. Non-adherence to medication in general was assessed rather than adherence to specific agents [52, 53] because the number and types of medications used varied across subjects. Responses to the four questions are indicated in binary fashion (yes/no). Total scores are obtained by summing the positive responses. In our sample of FM patients, internal consistency was adequate (Cronbach’s {alpha} = 0.62). We created three binary indicators of non-adherence. ‘Overall non-adherence’ was equal to 1 if patients answered yes to a least one of the four items, and 0 otherwise. ‘Intentional non-adherence’ was equal to 1 if patients stopped medication in response to feeling better or worse, and 0 otherwise. ‘Unintentional non-adherence’ was equal to 1 if patients were forgetful or careless in taking medication, and 0 otherwise.

Statistical analysis
Descriptive statistics were used to characterize the study population. Social support satisfaction and network size were not normally distributed and were dichotomized at the median values. T-tests and {chi}2 tests were used to compare tertiary care and community participants on continuous and categorical variables respectively. Paired t-tests were employed to compare patient and physician ratings on the eight PPDS items. Bonferroni-correction was used to control for multiple comparisons on patient–physician standardized differences and on medication use.

To identify the predictors of non-adherence, statistical methods for clustered data were used. The generalized estimating equations (GEE) approach [54] accounts for the possibility that patients within physicians’ practices were more alike than patients between practices; it also accounts for the unbalanced structure of the data, i.e. for the fact that the number of patients varied across physicians. The GEE analyses were carried out using the SAS procedure PROC GENMOD (Cary, NC, USA). The compound symmetry, known as exchangeable structure, of the covariance of errors was assumed a priori and validated against alternative structures using the Akaike’s Information Criterion (AIC) [55]. To arrive at the final multivariable models, all variables were initially screened for statistical significance (P<0.05) in separate univariate analyses. All variables that were statistically significant in the simple models were then entered into one multivariable model, and a backward elimination procedure was used to identify the statistically significant independent correlates of adherence. The final model was selected based on the smallest likelihood ratio. Statistical significance was set at P = 0.05. To address the role of coping strategies in moderating the effects of discordance on medication non-adherence, interactions between each coping strategy and the two discordance subscales were examined.


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Physicians
Ten physicians participated in the study (Table 1). Median age was 43.8 yr (interquartile range (IQR) 37.3–57.3) and 7 (70%) were male.


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TABLE 1. Physician characteristics (n = 10)

 
Participants
Of the 182 patients recruited, 178 (97.8%) returned the mail-in survey on patient non-adherence, of whom 137 (77.0%) indicated that they were taking medication. Participants who were taking prescribed medication had statistically significantly higher scores on the FIQ (P = 0.001), PSS (P<0.02) and GSI (P<0.04), indicating that they were more disabled, perceived more stress and had more psychological distress than those not taking medications. Of the 137 women who provided adherence data, 127 (92.7%) also had data on patient–physician discordance and are the subjects of this analysis. Fifty-seven (44.9%) women were recruited from tertiary care and 70 (55.1%) from the community.

Table 2 presents demographic, clinical and psychosocial characteristics of the patients. Mean age was 50.4 yr (S.D. = 10.5) and patients reported having FM for a median of 3 yr (range 0.8–23). Compared with tertiary care women, those from the community had more education (13.4 vs 12.3, P = 0.0506) and lower scores on emotional coping (22.7 vs 27.3, P = 0.0015). No other statistically significant differences were found.


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TABLE 2. Description of the fibromyalgia cohort (n = 127)

 
Discordance
Actual and standardized patient–physician difference scores are presented in Table 3. Physicians’ ratings were lower than patients’ ratings, as indicated by the positive scores, on all items for the crude and standardized difference scores. Statistically significant differences were found for physical functioning, psychological distress, emotional well-being, discussion of the main problem, discussion of personal issues, and patient satisfaction with the visit. Because higher ratings on emotional well-being indicate ‘better’ emotional health, for all items except emotional well-being patients were more concerned in comparison with their physicians.


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TABLE 3. Mean patient–physician differences on the Patient–Physician Discordance Scale: crude and standardized differences

 
Medication use
Of the 127 women in the study, only 4 (3.2%) did not list any medication use in the previous 6 months and 2 (1.6%) indicated some form of monotherapy. The majority of women (81.1%) listed between three and seven medications used in the previous 6 months and 11 (8.7%) women listed between eight and 10 medications. Table 4 presents the medications used; as shown in the second column, antidepressants were the most commonly used medication for all subjects (57.5%). There were no significant differences between tertiary care and community subjects.


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TABLE 4. Medications used by women with fibromyalgia (n = 127)

 
Table 5 presents the data on non-adherence to medication. Nearly half (47.2%) of our sample reported at least one form of non-adherent behaviour. More women from the community were careless in taking their medications than were tertiary care patients (P = 0.0122); there were no other statistically significant differences between community and tertiary care participants. Similar proportions (about one-third) of subjects were intentionally and unintentionally non-adherent.


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TABLE 5. Responses to questions about medication non-adherence in women with fibromyalgia according to recruitment method

 
Predictors of non-adherence to medication
The results of the univariate and multivariate GEE models are presented in Table 6. Odds ratios above 1 indicate an increased risk of non-adherence; those below 1 indicate a decreased risk.


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TABLE 6. Odds ratios (OR) and 95% confidence intervals (CI) for univariate and multivariate generalized estimating equations models for the three indices of non-adherence to medication

 
Overall non-adherence
Overall non-adherence to medication was predicted by higher discordance on communication and satisfaction in both univariate and multivariate models.

Unintentional non-adherence
In the univariate models, community subjects, lower disease activity, less social desirability, less use of instrumental coping, not being under a rheumatologist’s care and higher discordance on communication and satisfaction were associated with increased risks of unintentional non-adherence. In the multivariate model, community subjects, lower disease activity, less use of instrumental coping and higher discordance on communication and satisfaction were associated with higher risks of unintentional non-adherence, while longer duration under a rheumatologist’s care was associated with a decreased risk.

Intentional non-adherence
Univariate analysis identified shorter duration of FM, under a rheumatologist’s care for <=1 yr, no sexual abuse and higher discordance on communication and satisfaction as significant determinants of intentional nonadherence. In multivariate analysis, shorter duration under a rheumatologist’s care and greater discordance on communication and satisfaction increased the risk of intentional non-adherence to medication. Duration of FM and a history of sexual abuse were no longer statistically significant in the presence of other variables.


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
This is the first study, to our knowledge, to examine predictors of medication non-adherence in women with FM. We employed a general measure of medication non-adherence because of the variability in number and type of medications taken by this population. Both tertiary care and community-based subjects were recruited to increase the generalizability of study findings, as not all patients with FM seek specialists’ services [56]. The similarities between the two subgroups allowed us to combine them to address the questions under study.

The majority (81.1%) of participants used between three and seven medications in the previous 6 months. Consistent with the literature [5759], antidepressants were most common. Nearly half reported at least one form of non-adherence behaviour, much like patients with other chronic illnesses [60], including those with other rheumatic diseases [61, 62]. Both forms of non-adherent behaviour were evident in 12.6% of participants. More women from the community were careless compared with those from tertiary care.

Support for the collaborative communication theory of adherence [9] was found in the three prediction models. According to this framework, adherence depends on the patient receiving, understanding and recalling essential information. In the present study, patient–physician discordance on communication and satisfaction predicted overall non-adherence. None of the clinical and few of the psychosocial variables tested entered the final models, suggesting that what transpires during the office visit is critical to medication adherence.

Unintentional non-adherence to medication, defined as being careless or forgetful, was predicted by several variables, including discordance between physicians and patients on communication and satisfaction. More discordance, less use of instrumental coping and not being under a rheumatologist’s care increased the risk of unintentional non-adherence. These findings highlight the importance of the physician–patient relationship for adherence. The inverse association between instrumental coping (action-oriented) and unintentional non-adherence is consistent with the literature regarding this adaptive style of coping in chronic illness [63]; women with FM who used less of this coping style were more careless and forgetful.

Intentional non-adherence is infrequently acknowledged but undoubtedly occurs. In our sample, being under the rheumatologist’s care for <=1 yr and greater discordance on communication and satisfaction were statistically significant predictors of intentional non-adherence. Rather than view this behaviour negatively, it is constructive to think of intentional non-adherence as a rational decision on the part of the patient [64]. If the patient has little experience with FM and is not in agreement with the physician, he or she may rely more on his or her own judgement than on the physician’s recommendation. Furthermore, considering that medications are not uniformly beneficial [65], the fact that 20% of participants stopped taking medications when they felt worse is not surprising.

Collectively, our findings demonstrate the importance of the patient–physician relationship for medication adherence in FM. Often patients with FM encounter scepticism towards their disease [66, 67] and a lack of empathy for their suffering [68]. This may be subtly reflected in the finding that subjects were more satisfied with the office visit (Table 3) than physicians thought they were. Physicians are sometimes frustrated when they are unable to offer effective treatment, a sentiment that may be inadvertently transmitted to the patient and which may, in turn, contribute to the patient’s lack of adherence. Possibly, adherence could be improved if physicians assessed coping, proposed a treatment plan that both the patient and physician view as feasible [69, 70], and enquired about the patient’s satisfaction with the plan during the office visit. Regular follow-up visits provide continuity of care and may further enhance adherence.

Several strengths and limitations of the present study merit discussion. The prospective design allowed us to examine the direction of the link between discordance and non-adherence, although it does not confirm causality. Given that non-adherence occurred in 46% of the cohort and in 60% of patients with high discordance (defined as scores above the median), with 127 patients, this study had 89% power to detect an odds ratio of 2 or more at an alpha level of 0.05. Therefore, the sample size provided adequate statistical power and permitted the use of multivariate analytical techniques to control for measured confounders. The fact that about half of our sample was derived from the community may enhance external validity because not all women with FM seek services in tertiary care settings. Nearly one-third of the tertiary care patients were first-time consults and, thus, were similar to the community sample in that the purpose of the visit was to confirm the diagnosis. Moreover, the majority of tertiary care patients were not followed regularly by the rheumatologist. Nevertheless, the sample is not representative of all individuals with FM, in that men were excluded and women with FM who do not seek medical treatment may be under-represented, as the majority of community-recruited participants had previously sought rheumatology care for FM. Another study limitation is that the effect of specific drugs on non-adherence could not be evaluated, given that the majority (87.8%) of patients received more than one drug and non-adherence was not assessed separately for each medication.

No method of assessing non-adherence to medication is infallible. We selected a self-report measure because self-reported non-adherence correlates well with pill counts [71], electronic monitoring and pharmacy refill records [53], and because less practical methods of assessment may not overcome attempts at concealment [72]. We attempted to reduce deliberate misinformation and recall bias by employing a research assistant who was not attached to the study sites, ensuring confidentiality of responses [73], and assessing non-adherence within a short time interval [74]. Moreover, social desirability, which was found to be similar to levels previously reported in medical and mental health outpatients [43], was included in the model-building stages of medication non-adherence to address the issue of self-report.

Finally, it could be argued that the women examined for study purposes only, i.e. the community subjects, were not patients and the office visit was not a real medical encounter. However, these types of medical encounters are common as rheumatologists often see FM patients in the context of a consultation visit, on a once-only basis. In our study, one-third of tertiary care patients were first-time consults and, therefore, similar to community women in that the purpose of the visit was to confirm the diagnosis of FM. In addition, given that most tertiary care patients were not regularly followed by the examining rheumatologist and 80% of the community subjects had previously consulted a rheumatologist, the distinctions between the two groups are likely to be unimportant.

In conclusion, this study provides insight into medication non-adherence in women with FM. Individual characteristics, coping strategy and features of the therapeutic relationship were shown to affect non-adherence to medication. Women with FM were less likely to take prescribed medications when they disagreed with physicians on communication and satisfaction with the visit. Improving patient–physician communication may improve adherence. Our findings may help clinicians identify patients at higher risk of non-adherence, who may require additional monitoring. Given the unsatisfactory response of many FM patients to current therapy, it is important to know whether the poor response is a result of non-adherence or ineffectiveness of treatment.

The authors have declared no conflicts of interest.


    Acknowledgments
 
This study was made possible by funding from the Canadian Arthritis Society. The following physicians examined patients: Drs Martin Cohen, Mary-Ann Fitzcharles, Michael Starr, Jan Schulz, Murray Baron, Pierre Dagenais, Suzanne Mercille, Anne St-Pierre, Sasha Bernatsky and Harbhajan Kang. Ms Maggy Laurore provided excellent secretarial support. We wish to thank the women with FM who participated in the study, as well as Ms Natalie Dayan and Dr Mirella DeCivita for recruitment and data management throughout the study.


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Submitted 25 February 2003; revised version accepted 23 December 2003.