Characteristics at initial CFS classification
Among all fatigued subjects who came to the clinic over the study period, 90 were identified with CFS (43 of 300 in 1997, 15 of 270 in 1998, 22 of 291 in 1999, and 10 of 217 in 2000). Of these, 65 (72.2%) had at least one follow-up visit and thus were considered in this study. Tables ,,, describe these subjects' characteristics at initial classification. More than three-quarters of our sample self-reported their onset as gradual and only 13.9% reported ever being diagnosed or treated for CFS (Table ). A diagnosis of depression was self-reported by 30.8% of the subjects, but only 16.9% had lifetime major depression disorder according to the DIS. The most prevalent CFS symptom was unrefreshing sleep and the most prevalent non-CFS symptom was problems getting to sleep (Table ). More than 60% were currently employed, and only 16.9% reported unemployment due to the fatiguing illness (Table ). Approximately 20% reported short duration of fatigue (≤ 2 years). Compared with published data for CFS subjects [9
], our sample had a significantly higher mean for the situation-specific fatigue subscale (t
-test p-value = 0.0087) and a significantly lower mean for the subscale indicating fatigue responsiveness to rest or sleep (t
-test p-value = 0.0167).
Demographic characteristics of CFS subjects at initial classification (N = 65)
Clinical characteristics of CFS subjects at initial classification (N = 65)
Symptoms and wellness scores for CFS subjects at initial classification and follow-up
Illness characteristics among CFS subjects at initial classification and among fatigued subjects at follow-up
Of the 65 CFS subjects, 59 (90.8%), 39 (60%), and 24 (36.9%) were followed 1, 2, and 3 years, respectively, after initial classification. Reasons for missing visits included permanent exclusions in the previous visit, refusal to participate, cancellation of clinic appointment, or loss to follow-up (respondent moved or could not be located). Subjects with follow-up visits had shorter duration of illness (median = 6 years vs. 9.1 years, Wilcoxon test p-value = 0.0378), fewer non-CFS symptoms (mean = 4.9 vs. 6.2, t-test p-value = 0.0419) and higher annual income (49.2% vs. 20% above $40,000, χ2 test p-value = 0.0128) than those who were not followed. No differences were found with respect to age, sex, race, education, fatigue severity scores, wellness scores, or number of CFS symptoms.
Using GEE models, it was determined that the mean number of CFS and non-CFS symptoms decreased over time compared with the number of symptoms at initial classification (Table ). Although the prevalence of CFS symptoms also tended to decrease over time, the ranking of symptoms remained the same. At all time points, unrefreshing sleep, muscle pain, post-exertion fatigue, difficulty thinking or memory impairment, and joint pain were the 5 most prevalent symptoms; whereas headaches, tender lymph nodes, and sore throat were the least prevalent symptoms.
Wellness, activities and sleep
Pairwise comparisons between consecutive time periods indicated that wellness scores were higher at the first year compared with initial evaluation (paired t-test p-value = 0.0085) (Table ). No other significant differences were detected.
At initial classification, the median number (interquartile range) of hours spent on work duties, household chores, recreational activities, and sleeping during the week and during the weekend was, respectively, 40 (15–60), 15 (7–20), 0 (0–5.5), 7 (6–8) and 8 (6–9). No significant changes over time were detected.
Only a few fatigued subjects reported that rest relieved fatigue at any follow-up period (Table ). The proportion of subjects reporting that fatigue interfered with social, professional, or educational activities at 1-year follow-up was significantly smaller than at initial classification (McNemar's test p-values = 0.002, 0.0124, 0.0290, respectively). Fatigue severity scores and number of activities affected by fatigue were also significantly reduced at 1-year follow-up (paired t-test p-values = 0.0047, 0.0001, respectively). No other significant differences were detected.
Illness states over time
About one-third of CFS subjects retained the classification after 1 year of follow-up (Table ). At 2 and 3 years follow-up, only 21% of the subjects were classified as having CFS. Most transitioned into a non-CFS state because of insufficient symptoms or fatigue severity, absence of fatigue, or identification of an exclusionary condition. Overall, 23.1% (15 of 65) were eventually diagnosed with permanent exclusions, of which the most common were sleep disorders (i.e. sleep apnea or narcolepsy) (3 of 15), major depressive disorder with melancholia (3 of 15) and inflammatory bowel disease (2 of 15). Female sex, income ≤ $40,000, older age at initial classification, and higher fatigue severity scores were positively associated with the eventual detection of an exclusionary condition (Fisher's exact test p-values = 0.0197, 0.0169, and t-test p-values = 0.0008, 0.0042, respectively). No deaths were observed in this study.
Changes in CFS classification (%)
Table illustrates the pattern of illness states over the 3-year follow-up period. Overall, 56.9% of the subjects (37 of 65) experienced partial or total remission by the end of the follow-up. Among 40 subjects who had 2 consecutive years of follow-up, 22.5% sustained partial remission and 10% sustained total remission. The 4 CFS subjects who sustained total remission had been ill between 0.7 and 19.8 years and ranged in age from 35 to 53 years. There were 3 individuals with gradual and 1 with sudden onset, 2 females, 3 whites, and 1 Hispanic. Only 3 (7.5%) of 40 subjects sustained the CFS classification over two consecutive follow-up visits.
Illness states for CFS subjects at follow-up
Reduced fatigue between visits and treatments used
Thirty-two (54.2%) of 59, 23 (59%) of 39 and 11 (45.8%) of 24 subjects followed at 1, 2, and 3 years, respectively, reported that they felt less fatigued since the last visit. More than half of the subjects reporting reduced fatigued experienced at least 6 periods (53.1%, 65.2%, and 63.6% at 1, 2, and 3 years, respectively) of reduced fatigue. The median duration of the most recent period was 8 days for years 1 and 2, and 30 days for year 3 of follow-up. Fatigue reduction was not significantly associated with remission at the follow-up visit.
Although traditional medicine was the most common treatment among subjects reporting reduced fatigue (100%, 91.7%, and 81.8% at 1, 2, and 3 years, respectively, Table ), only 20% reported using it exclusively. Most subjects reported a combination of traditional medicine, self-help strategies, and complementary and alternative medicine therapies (84.4%, 73.9%, and 63.6% at 1, 2, and 3 years, respectively). More than 35% of the subjects reported use of any complementary and alternative medicine at any point in time and at least 50% of those who used it thought that it reduced their fatigue (Table ). Remission was not associated with any particular treatment.
Treatment use and perception that the treatment was responsible for reduced fatigue at follow-up
Predictors of remission and symptom changes
To determine predictors of remission and symptoms, we considered only the 50 subjects who never developed a permanent exclusion. Sixty-two percent of these subjects ever experienced a partial or total remission. There was no association between the report of ever being diagnosed or treated for CFS and remission (Fisher's exact test p-value = 1.0). Higher fatigue severity scores and larger total number of symptoms were negatively associated with ever experiencing remission. Odds ratios (OR) and 95% confidence intervals (CI) from a multivariate logistic regression model were, respectively, 0.389 (0.156–0.971) and 0.724 (0.533–0.985). Subjects who eventually remitted tended to have fewer symptoms at initial classification but this trend was not statistically significant. Among the 32 subjects with at least two visits, 25% sustained partial remission and 12.5% total remission. By using categories of illness duration of ≤ 2 years, 2.1–10 years, and >10 years, it was found that subjects ill for 2.1–10 years were less likely to sustain remission than subjects ill for ≤ 2 years (OR = 0.107, 95% CI = 0.013–0.88). Subjects ill for >10 years were also less likely to sustain remission than those with shorter duration of illness, but this trend was not statistically significant (OR = 0.625, 95% CI = 0.073–5.350). No other variables were associated with sustained remission.
Few variables at initial classification were univariately associated with the likelihood of reporting individual symptoms (data available from the authors). Unrefreshing sleep was associated with female sex, being white, having higher fatigue severity scores, and being ill for 2.1–10 years when compared with 2 years or less. In a multivariate GEE model for unrefreshing sleep including these variables, being white, fatigue severity, and illness duration remained significant (p-values = 0.0005, 0.0003, 0.0058, respectively). The number of CFS symptoms was positively associated with higher fatigue severity scores (p-value = 0.0043), but the number of non-CFS symptoms was not associated with any variable.