Source: Journal of Behavioral Medicine Preprint Date: December 20, 2008 URL: http://www.springerlink.com/link.asp?id=101595 Longitudinal change in chronic fatigue syndrome: what home-based assessments reveal ---------------------------------------------------------------------------- Fred Friedberg - Stephanie J. Sohl - Department of Psychiatry and Behavioral Science Putnam Hall, South Campus, Stony Brook University, Stony Brook, NY 11794-8790, USA e-mail: fred.friedberg@stonybrook.edu Accepted: November 14, 2008 Published online: 20 December 2008 Abstract The purpose of this 2-year prospective study was to compare standard self- report and ecologically-based outcome measures in patients with chronic fatigue syndrome (CFS). Standard measures assessed physical function, fatigue impact, psychological variables, and global impression of change ratings. Ecological measures included actigraphy, a structured activity record, and an electronic fatigue/energy diary. Results for this high functioning sample (N=75) revealed that self-report global improvement was significantly associated with lower momentary fatigue and fatigue impact, and a higher frequency of standing up (at home), but not with actigraphy or psychological variables. However, actigraphy change was significantly correlated with change in self-report physical function. At follow-up, only a small minority (<20%) scored in the healthy adult range for fatigue impact and physical function. The findings suggest that home-based measures of symptom severity and physical functioning may provide evidence of change (or lack of change) that is important for interpreting standard self-report outcomes in CFS. Keywords Chronic fatigue syndrome - Ecological measures - Actigraphy - Momentary fatigue - Prospective study Reviews of prospective studies in chronic fatigue syndrome (CFS) have reported improvements in varying proportions of patients 1.5-4 years after initial evaluation (Cairns and Hotopf 2005; Joyce et al. 1997; Ross et al. 2004). However, both naturalistic studies (Cairns and Hotopf 2005; Joyce et al. 1997) and behavioral treatment trials (Chambers et al. 2006; Whiting et al. 2001) have relied on standard self-report measures administered in the laboratory environment to infer that patient reports of improvement reflected real-life changes. Thus, it is not known if improvement measured in the research setting indicates home-based illness improvement, e.g., lessened symptoms and increased physical activity, improvements in coping with the illness, e.g., lowered performance expectations (Whiting et al. 2001), or perhaps altered perceptions of illness status (Moss-Morris and Chalder 2003). The broader question is: To what extent are longitudinal changes in standard outcome measures related to real-time changes in symptom severity and functioning (Kazdin 2008)? In particular, perceived improvements in physical functioning may reflect several possibilities with respect to actual activity (Friedberg 1999). For instance, functional improvement may be associated with: (1) increased activity, especially in low function patients if they resume pre-illness pursuits, such as employment, or perhaps, (2) no change in absolute activity level, indicating a possible redirection of activity (e.g., walking outside rather than in the house) considered more functional by subjects or investigators. The purpose of this study was to compare standard self-report and ecologically- based measures in a 2-year naturalistic study in patients with CFS in order to determine if ecological outcomes were consistent with conventionally measured outcomes. Furthermore, the relevance of ecological variables to outcome assessments was assessed. Methods Participants The participants were 75 adults with CFS recruited over a 30 month period (study flow chart in Fig. 1) using radio, TV, and newspaper advertising, announcements in a quarterly wellness newsletter, physician referrals, campus listserv announcements, and talks given by the first author. There were no demographic differences among these sources of recruitment. Candidates were offered $200 compensation for full participation in the 2-year study. All participants signed consent forms in a face-to-face meeting with the research staff during their initial appointment. This study was approved by the Stony Brook University institutional review board. General study requirements included age limitations (18-60 years), English fluency, and wakefulness between 9 AM and 9 PM daily. Prior to the initial visit, a physician's note stating that the patient had a CFS diagnosis was required as well as results of any laboratory tests done within the past 6 months. To screen for medical conditions considered exclusionary of CFS, participants completed past medical history questionnaires and a standardized physical examination was performed. Laboratory tests were not taken unless a potentially exclusionary disorder was suspected. Careful questioning was done for the assessment of symptoms of common exclusionary disorders listed on the screening form including sleep disorders such as sleep apnea and narcolepsy. Height and weight were measured to exclude any subjects with a BMI >40. Participants were diagnosed with CFS by the study physician or physician assistant as supervised by the physician. The diagnosis was based on established criteria for CFS (Fukuda et al. 1994; Reeves et al. 2003) which includes 6 months of medically unexplained, debilitating fatigue plus four out of eight secondary symptoms drawn from these domains: flu-like symptoms, neurocognitive difficulties, and post-exertional malaise. In addition, CFS criteria excluded patients who had identifiable medical (e.g., cancer) or psychiatric (e.g., melancholic depression) conditions that might plausibly explain their fatigue symptoms. Psychiatric exclusions were based on the results of the Structured Clinical Interview for DSM-IV (First et al. 2001) conducted by the first author or his graduate student (D. W. Leung). Participant exclusions, based on definitional criteria for CFS (Fukuda et al. 1994; Reeves et al. 2003), were due to: less than 4/8 secondary symptoms (33.1%), melancholic depression in the past 5 years (31.7%), lifelong fatigue (9.2%), sleep disorder (4.2%), or other identifiable medical conditions associated with significant fatigue (21.8%). The study timeline (Fig. 1) proceeded as follows: 841 telephone screening interviews (all conducted by the first author) yielded 231 candidates (i.e., 27.5% of 841 with a tentative diagnosis of CFS) eligible for the study. Ineligibility was primarily due to the definitional exclusions stated above as well as failure to meet age, language, and wakefulness requirements. Based on the limited demographic data available for ineligible subjects, no significant sex differences were found between ineligible and eligible subjects. Of the eligible participants, 126 (54.5%) agreed to participate. The reasons given for non-participation included: time commitment involved, no treatment offered, embarrassment wearing the electronic devices, and not enough compensation. A final CFS diagnosis was confirmed in 123 (97.6%) of these participants, all of whom completed the baseline assessment. Seventy-five baseline participants (61.0%) also completed the 2-year follow-up assessments. Reasons for participant withdrawal after the initial assessment included: the time commitment involved, major improvement or worsening in their condition, move to an inconvenient location, or scheduling problems around working hours. A series of t-tests revealed no significant differences in demographic variables (age, sex, marital status) or fatigue severity between those who dropped out of the study and those who completed time 1 and time 2 measures. However, employment status was marginally significant (t=-1.90, p=.06), indicating that the higher functioning individuals were more likely to remain in the study. Standard self-report measures Global impression of change scale At the 2-year follow-up assessment, participants' global impression of change in illness was measured on a seven-point rating scale, ranging from 1 (very much worse) to 7 (very much improved; Sharpe et al. 1996). This seven-point scale has shown sensitivity to treatment change in CFS (Prins et al. 2001). Fatigue severity scale (FSS) This measure of the effect of fatigue on functioning is comprised of nine items rated on a Likert-type rating scale (1-7), where one indicates no impairment and seven indicates severe impairment (score range: 1-7). In the initial validation study (Krupp et al. 1989), internal consistency for the FSS was high (alpha>.80) and the scale clearly distinguished between patients and controls. The scale has been recommended for use in CFS (Taylor et al. 2000). Short form-36 physical function subscale (SF-36 PF) Physical functioning was measured with the SF-36PF. Limitations of ill health are measured on a scale of 0 (limited in all activities, including basic self-care) to 100 (no limitations, able to carry out vigorous activities). Test construction studies for the SF-36 (McHorney et al. 1993; McHorney et al. 1994) have shown adequate internal con- sistency for the physical function subscale (alpha=.91 -.94) and substantial differences in scores between patient and non-patient populations. Beck depression inventory - second edition (BDI-II) Depressive symptomatology was measured with the BDI-II (Beck et al. 1996a, b), a 21-item self-report instrument with well-established psychometric properties (Beck et al. 1996a, b). BDI-II scores were corrected by removing the effect of the somatic factor (Storch et al. 2004), which included fatigue-related symptoms, from the total score. The remaining items focus on cognitive and emotional phenomena related to depression. The BDI-II Cognitive-Affective factor (Storch et al. 2004) has shown high internal consistency (alpha=.87) and convergent validity with the two established factors for the State Trait Anxiety Inventory-Trait version (Depression: r=.77 and Anxiety: r=.70, p<.001). Beck anxiety inventory (BAI) Anxiety symptoms were measured with the BAI, a 21-item self-report measure with high internal consistency (alpha=.92) and established and replicated construct validity (He- witt and Norton 1993; Steer et al. 1995). Factor analysis of the BAI yielded a first-order factor labeled anxiety that had salient loadings for all 21-items on the BAI, but only one item on the BDI-II. Catastrophizing subscale (fatigue-related cognitions scale [FRCS]) The catastrophizing subscale of the FRCS (Friedberg and Krupp 1994) contains 10-items with a five-point response format and queries subjects about their cognitive reactions to fatigue symptoms in the past 2 weeks. The subscale items reflect different aspects of catastrophizing about fatigue consistent with the three replicated dimensions of catastrophizing, i.e., magnification, rumination, and helplessness (Sullivan et al. 2001). Adequate internal consistency for the catastrophizing subscale (alpha=.79) was demonstrated in our sample. Ecological measures Electronic diary The electronic diary was a palm pilot computer (Model: Palm Vx, Palm, Inc; Sunnyvale, California) with software (Satellite Forms) specifically designed to record momentary data. The system has been successfully used in many other studies (Aaron et al. 2005; Stone et al. 2004). The palm pilot emitted auditory prompts that were linked to a display of symptom rating scales. A participant-operated stylus was utilized to select a response to each numerical symptom scale. The software recorded the time and date of each entry. To avoid interruptions of important ongoing activities (e.g., business meetings), participants were allowed to enter data in between scheduled prompt times. Off schedule data entry was seldom done, as participants answered 92% of the scheduled prompts, an excellent level of compliance. In order to obtain a representative diurnal sample of fatigue and energy without undue subject burden (Wilson et al. 1994), the palm pilots prompted subjects for 21 days, six times a day every 2 h plus or minus a randomly programmed 1-20 min interval (i.e., Ecological Momentary Assessment; Stone et al. 1999). The first daily prompt occurred within 1 hour of the subject's wakening and the last daily prompt approximately 12 h later. No prompt signals occurred during the subject's reported sleep time. After each prompt, several response-activated screens were displayed, each with a numerical rating scale (0-10). The end point anchors on the numerical scales were 0 (none) and 10 (highest). The scales were labeled 'Fatigue Now' and 'Perceived Energy Now'. Subjects were instructed to record intensity ratings on the 0-10 scale for both of these subjective states. Actigraph The actigraph (Model: MTI, Fort Walton Beach, Florida) was a small, light-weight, cost-efficient activity monitor that could continuously collect data every minute of the day and night for 22 days before memory is completely full (Tryon and Williams 1996). All participants wore the actigraph on a waist belt for a 3-week period (waking hours only) during each assessment. Tryon and Williams (1996) demonstrated both within- and between-device reliability (97.5-99.4%) and validity (coefficients of at least .99) of this actigraph as a monitoring instrument. Actigraphy was intended to assess overall changes in physical activity levels from baseline to follow-up. Activity record (ACTRE) The ACTRE, developed and validated at NIH (Furst et al. 1987; Gerber et al. 1987; Gerber and Furst 1992), is a written log kept by the participant for two consecutive days with data entry scheduled three times a day. The participant indicates by numerical code if he or she was standing, sitting, or lying down while doing identified activities (e.g., sleep, self-care, work). Changes from baseline to follow-up in the frequency of standing, sitting, and lying down were used in this study as a home-based measure of physical functioning potentially related to standard outcomes. Reliability estimates for the ACTRE are not feasible as day to day activities are not predictable. For validity estimates (Furst et al. 1987; Gerber et al. 1987; Gerber and Furst 1992) based on disease activity and function in patients with rheumatological disease, significant correlations were found between the ACTRE disability ratings and other measures of disability. Functional capacity measure Six-minute walking test The six-minute walking test (Butland et al. 1982), an abbreviated behavioral measure of functional capacity, measures the distance walked during a 6-min interval. It is a useful, reproducible, and inexpensive measure of exercise tolerance (Butland et al. 1982). The measure has good test-retest reliability (intraclass correlation=.97; Streiner 1995) when repeated 1 week later. Direct comparisons of the six-minute walking test with cardiopulmonary stress testing have revealed strong correlations (.64 -.70) between distance walked in the six-minute test and V02 Max in patients with primary pulmonary hypertension (Miyamoto et al. 2000) and advanced heart failure (Cahalin et al. 1996). Given that the six-minute walking test has been found to be sensitive to behavioral intervention in CFS (Sharpe et al. 1996), it was intended to serve as an additional activity measure that might be associated with global change ratings. Psychiatric diagnosis Structured Clinical Interview for DSM-IV (SCID; First et al. 2001). The SCID for Axis I was used to establish psychiatric diagnoses at baseline. The professionally administered SCID allows for clinical judgment in the assignment of symptoms to psychiatric or medical categories, a crucial distinction in the assessment symptom overlap between CFS and psychiatric disorders (Friedberg and Jason 1998; Taylor and Jason 1998). Because of the extensive time involved, the SCID was administered for the initial assessment only. Procedure The SCID was administered at baseline only. For both baseline and 2-year follow-up assessments (study period: March 2002 to March 2007), participants completed the following: standardized questionnaires, 6-min walking tests, 21 days of data collection for the actigraph and electronic diary, and 2 days data collection for the Activity Record. Subjects were trained individually on how to use the ecological measures. Data analysis The primary goal of this analysis was to compare standard self-report and ecological measures with respect to outcomes. The unit of analysis was participants. For data analysis, the ecological data included: (a) daily actigraphy counts averaged over 3 weeks; (b) average 3 week momentary ratings of fatigue and energy, and (c) the 2-day frequency of lying down, sitting, and standing up as reported on the Activity Record. Because the number of assessments available for each individual was the same, the averaging of ecological data at each assessment is appropriate (Schwartz and Stone 1998). The outcomes analysis was based on difference scores between the follow-up and baseline assessments. These difference scores were then correlated with each other and with the seven-point global impression of change rating for the 2-year period. The clinical significance of improvements for each participant was also assessed by comparing scores on the SF-36 PF (Ware et al. 2000) and FSS (Krupp et al. 1989) to healthy norms. A hierarchical regression with age and sex entered in step 1 was done to further examine the relationships between any psychological and behavioral variables (predictors) that were significantly associated with global change or activity change measures (criterion variables). This order of entry enabled us to examine the predictive value of fatigue and activity change after controlling for the potentially confounding demographic variables of age and sex (Friedberg et al. 2000; Ray et al. 1997; van der Werf et al. 2002). Given the large number of comparisons, all significance tests were two-tailed using an alpha of .01. Results Baseline assessment Participant characteristics Table 1 presents the baseline values for both demographic variables and the standardized measures of physical function, fatigue impact, and the psychological variables. Participants were predominantly white (93.2%) women in their 30 s and 40 s, moderately educated (75.8% attending at least some college), and married or cohabitating (51.5%). The mean duration of the CFS illness was 8.3 years (SD=6.8; range: 1.1-37 years) and the sample exhibited moderate to high fatigue severity, based on the fatigue severity scale (Krupp et al. 1989) and 3-week averages of momentary fatigue ratings (Friedberg and Sohl 2008). In addition, 69.3% of participants had one or more SCID-based psychiatric diagnoses at one point in their lifetime. The most frequent diagnoses were: major depression (15), alcohol abuse (10) or dependence (3), panic disorder with (2) or without (4) agoraphobia, eating disorders (5), social (3) or specific (2) phobia, and post-traumatic stress disorder (3). Employment status (rated on a five-point scale ranging from full-time worker or student to on disability) revealed that 43.8% of the sample was working full-time, 28.4% were working part-time or half-time, 10.8% were unem- ployed, and 19.2% were on disability. Despite this high employment level for subjects with CFS in comparison to previous studies (Ross et al. 2004), the sample exhibited, on average, moderate physical impairment on the SF-36 PF subscale. The employment status rating appeared to be a reasonable approximation of physical functioning, given that it was significantly correlated with the SF-36 PF (r=.48; p<.0001), 3-week mean actigraphy counts (r=.39; p<.001), and the frequency of lying down on the ACTRE (r=-.54; p<.0001). Baseline to follow-up changes The 24-month follow-up assessment occurred about 2 months later than scheduled. The average interval was 793.1 days (SD=50.8). Global impression of change ratings Most subjects reported relatively modest change in their global ratings at 24 months: 0 were very much improved, 4 were much improved, 25 were somewhat improved, 19 selected no change, 22 were somewhat worse, 3 were much worse, and 2 were very much worse. Global ratings of improvement were significantly associated with 2-year change scores (Table 2) for momentary fatigue (lower), fatigue impact (lower), and frequency of standing up (higher) on the 2-day activity record. However, actigraphy and the 6-min walk distance were not significantly associated with global change. A hierarchical regression analysis revealed that global change was not significantly predicted by any of the significant variables above when controlling for age and sex (F=1.52; p>.20), suggesting that overlapping variance precluded any significant independent predictors. In addition, global outcomes were unrelated to age, sex or illness duration. Activity and symptom measures (Table 2) Although actigraphy was not significantly associated with global change, mean actigraphy counts were significantly correlated with increases in the SF-36 PF subscale. Thus, actigraphy was correlated with a self-report measure of physical functioning that is plausibly related to activity levels. Furthermore, improvement on the 6-min walking test was not significantly correlated with any physical function or symptom variable. Contemporaneous correlations at the 2-year follow-up assessment revealed that the Beck inventories were not significantly associated with self-report employment rating (BAI: r=-.13, p=.32; BDI: r=-.12, p=.33). The BDI was skewed towards lower scores with 57.3% of subjects scoring below the dysphoric range (<12) and 76.1% scoring below the clinically depressed range (<18; Dozois et al. 1998). Clinical significance of outcomes Clinically significant improvement on the FSS over the 2-year study period, defined as a 1-point score reduction (Garssen et al. 2006) or about a one SD change in this cohort, occurred in 19.6% of the sample. In addition, at the 2-year follow-up, only 17.7% and 17.2% of the sample scored in the healthy adult range on the FSS and the SF-36 PF subscale, respectively. Discussion This 2-year longitudinal study in participants with CFS found minor changes on the global impression of change rating for most subjects. Yet significant associations were evidenced between global change ratings and change in self-report fatigue impact and the ecological measures of momentary fatigue and the frequency of standing up. The global change rating, however, was not significantly associated with changes in actigraphy, self-report physical function, or an estimate of functional capacity. By comparison, increased actigraphy counts were significantly correlated with improvement in self-report physical function and increased momentary energy from baseline to follow-up. In addition, at the 2-year assessment, neither depression nor anxiety scores were associated with self-report physical functioning or working status. Global impression of change and outcomes Participant-rated global improvement at the 2-year follow-up was significantly correlated with lessened in vivo fatigue and an increased frequency of standing up. This suggests that the global rating captured, to some degree, important ecological changes indicative of changed symptom severity and physical functioning, i.e., real-time improvement in the participant's home environment. This is noteworthy in the current sample, given the relatively modest changes in global ratings. Yet the considerable overlap between standard self-report and ecological predictors indicated that no independent predictor of global outcomes could be identified. Furthermore, global change was not associated with change in actual activity or self-report physical function over the 2-year study period. Previous studies have sug- gested that CFS patients do not accurately perceive their disease status with respect to sleep disturbance (Majer et al. 2007), neurocognitive deficits, disability, and symptom severity (Moss-Morris and Chalder 2003). Such mis-perceptions might also be invoked to explain the absence of associations between activity level and global change in this study. However, it is not clear that self-report global change, a generic measure, necessarily represents a mis-perception of disease status if objective activity change does not show a corresponding change, as discussed below. Furthermore, subjects in this study did show significant associations over a 2-year period between self-report and objective measures of activity, i.e., SF-36 physical function scores and actigraphy counts that represent overlapping aspects of physical functioning. Thus, their ability to judge functional levels did not seem to be compromised. Given that the majority of subjects were employed at baseline, it may be unrealistic to expect that minor globally rated improvements would substantially increase physical functioning, and by implication real-time physical activity in these already high functioning individuals (Friedberg 1999). In addition, actigraphy counts may not have fully captured new or modified role activities that only partly involved physical movement. Perhaps, rather than doing more physical activity overall, improved subjects may have conducted their activities differently, possibly in a more energy-conserving manner suggestive of improved illness coping (Bleijenberg et al. 2003). Similarly, an important element of cognitive-behavioral (e.g., Deale et al. 1997) and graded exercise (Wallman et al. 2004) interventions in CFS is the use of activity pacing to break up energy-depleting activities, including exercise, into smaller, more manageable tasks so as to avoid the debilitating push-crash cycles that are often reported by these patients (Bleijenberg et al. 2003). Consistent with this activity pacing approach, a recent randomized trial (Jason et al. 2007) of four non-pharmacological interventions in moderately functional (45% full- or part-time employed) CFS patients utilized a central activity pacing component in their coping skills oriented cognitive-behavioral treatment (CBT) condition. In comparison to the other treatment conditions (graded activity CBT, relaxation, and anaerobic exercise), coping skills CBT yielded the greatest overall improvement, including significant gains in SF-36 physical function scores. This intervention, which was intended (behaviorally) to substitute stress-reducing activities for stress-exacerbating activities rather than to increase activity levels per se (as in graded activity CBT), may have resulted in a more sustainable balance between activity and rest (cf. Bleijenberg et al. 2003). By comparison, in other successful randomized trials that used graded activity oriented CBT (Deale et al. 1997; Prins et al. 2001; Sharpe et al. 1996), their largely low functioning subjects with CFS (13-37% employed) may have been more responsive to increasing activity schedules because their baseline activity levels were probably much lower. In fact, a large sample actigraphy study (van der Werf et al. 2000) that compared CFS to healthy controls identified a 'pervasively passive' subgroup of participants with CFS which showed significantly lower levels of daily physical activity and higher disability scores in comparison to moderately and highly active participants in both groups. None of the participants in the healthy control group were categorized as pervasively passive. In the clinical realm, distinguishing high-active and low-active patients with CFS is considered an important pre-treatment assessment which determines whether prescribed activities will initially moderate or increase patients' daily activity levels (Bleijenberg et al. 2003). Clearly, the above use of employment status as a comparative measure of physical functioning across studies is at best an approximation of daily activity and functional level. Yet, in the current study, self-report work status received some level of validation as it was shown to be significantly correlated with both ecological and standard measures of physical functioning. Clinical significance of outcomes Despite the largely working status of this sample, their levels of physical function and fatigue impact showed that only small minorities (<20%) scored in the healthy adult range at the 2-year follow-up. Perhaps their low levels of maladaptive coping and concurrent depressive symptoms allowed these subjects to achieve and maintain relatively high functioning limited largely by the biological aspects of their fatiguing illness. By comparison, concurrent psychiatric comorbidity in CFS (Cairns and Hotopf 2005; Ross et al. 2004) has been associated with greater unemployment and disability. Regarding clinically relevant change, standard self-report measures alone may not reveal if improvements in CFS are related to home-based changes - such as increased activity levels. Thus, home-based measures are desirable and perhaps essential to inform behavioral outcomes research in CFS. This is particularly important in assessing the in vivo efficacy of CBT which is almost entirely based on standard measures (Friedberg and Sohl, in press). As an alternative to the time, expense, and inconvenience of home-based measures, treating clinicians can ask their patients more specific questions about how they have changed when interventions are viewed as successful. For instance, are they coping better with limitations, doing more activities or perhaps utilizing some combination of these behaviors? With such tailored inquiries, clinicians may be able to assess with greater accuracy the effects of their treatments. Limitations Although an important degree of measurement overlap was found between standard self-report measures and ecological assessments, these sets of measures did not precisely match in concept (e.g., global change may or may not imply physical activity change), a possible shortcoming when making such comparisons. In addition, a relatively small number of participants reported major global changes which may limit the strength of the associations with other measures of potential improvement. However, this study sought to determine if the commonly used measures of global change, fatigue impact, physical function, and negative affect could be indicative of real-life changes relevant to illness severity and physical functioning. In turn, such data can inform critical unresolved questions about the nature of improvement, as attributable to illness improvement itself, improved illness coping, measurement limitations, or some combination of these factors (Friedberg 1999; Kazdin 2008; Whiting et al. 2001). A limitation should be noted regarding medical evaluation of subjects which was based largely on medical inter- views without thorough laboratory testing, given its prohibitive expense. With respect to demographics, this sample may not be representative of those subjects with CFS who are generally lower functioning, who sleep during the day, and those who exhibit concurrent psychiatric disorders that affect quality of life and influence outcomes. Whereas our recruitment of higher functioning participants was primarily based on media advertising, previous longitudinal studies (Cairns and Hotopf 2005; Ross et al. 2004) recruited (lower functioning) subjects largely from medical care. Thus, it appears that our sample may have better approximated a community-based illness population of individuals with CFS which typically exhibits less impairment (Jason et al. 1999). Finally, the small percentage of minority subjects suggests that our findings may not generalize to the population of CFS patients which has shown much higher percentages of minorities (Jason et al. 1999). Conclusions In this study, ratings of global improvement were associated with a standard self-report measure of functional improvement (fatigue impact) and with ecological measures of symptom reduction and frequency of standing up, but not with physical activity overall. These findings suggest outcomes reflective of both lessened illness and improved illness coping. It appears that real-time in vivo measures may provide important indications of change (or lack of change) in both symptom severity and physical functioning that may lead to a more complete understanding of outcomes. Thus, these findings suggest that psychosocial assessments in CFS may be enhanced by the inclusion of ecological measures. Acknowledgments We thank Joe Schwartz and Arthur Stone for their time and consultation. This study was supported by NIH grants MH01961-02 and MO1RR10710. Figure Caption Fig. 1. Study flow chart Tables Table 1. Demographic and self-report variables at baseline ------------------------------------------------------------------ Variable Mean or % Standard deviation ------------------------------------------------------------------ Age 41.78 9.86 Female (%) 85.3 SF36PF 53.52 25.56 FSS 5.96 0.94 BAI 14.50 8.85 BDI 16.40 8.28 FRCS 42.21 8.41 ------------------------------------------------------------------ Note: SF36PF = Outcomes Study-Short Form-36 Physical Function Subscale; FSS = Fatigue Severity Scale; BAI = Beck Anxiety Inventory; BDI = Beck Depression Inventory; FRCS = Fatigue-Related Cognitions: Catastrophizing Subscale Table 2. Correlations between change scores for study variables (except Global change) ------------------------------------------------------------------------------------------ 1 2 3 4 5 6 7 8 9 10 11 12 ------------------------------------------------------------------------------------------ 1. Global change - 0.17 -0.14 0.18 -0.39*-0.01 0.09 0.07 0.36* 0.04 -0.39* 0.32 2. BAI - 0.24 -0.09 -0.11 0.21 0.00 0.06 -0.36*-0.38 0.05 -0.13 3. BDI - -0.14 0.45* 0.33* 0.01 -0.21 -0.44*-0.24 0.11 0.01 4. SF36PF - -0.1 -0.32 0.40* 0.30 0.01 0.29 -0.23 0.17 5. FSS - 0.43*-0.05 -0.17 -0.37 -0.43 0.52*-0.42* 6. FRCS - -0.02 -0.03 -0.12 -0.22 0.19 -0.22 7. Mean actigraphy counts - 0.38*-0.15 0.17 -0.27 0.30 8. SD actigraphy counts - 0.21 0.19 -0.1 0.24 9. Frequency of standing up - 0.03 -0.35 0.44* 10. Six-minute walk - -0.28 0.25 11. Momentary fatigue - -0.85** 12. Momentary energy - ------------------------------------------------------------------------------------------ Note: BAI = Beck Anxiety Inventory; BDI = Beck Depression Inventory; SF36PF = Medical Outcomes Study-Short Form-36 Physical Function Subscale; FSS = Fatigue Severity Scale; FRCS = Fatigue-Related Cognitions Scale *p<0.01; **p<0.001 References Aaron, L.A., Turner, J.A., Mancl, L., Brister, H., & Sawchuk, C.N. (2005). 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