Uplifts And Hassles Are Related To Worsening in Chronic Fatigue Syndrome A Prospective Study Part 1

Abstract

Background: Limited published data suggests that the absence of uplifts (minor pleasant events) is associated with clinical worsening in patients with chronic fatigue syndrome (CFS). The current study aimed to assess the relation of illness worsening to the trajectories of social and non-social uplifts and hassles in a six-month prospective study in CFS.

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Methods: Participants were primarily in their 40s, female, white, and ill for over a decade. All participants (N=128) met the criteria for CFS. The interview-based global impression of change rating was used to classify individual outcomes as improved, unchanged, or worsened at six- a six-month follow-up. Uplifts and hassles, both social and non-social, were assessed with the Combined Hassles and Uplifts Scale (CHUS). The CHUS was administered weekly in online diaries over six months. Linear mixed-effect models were utilized to examine linear trends for hassles and uplifts.

Results: No significant differences were found between the three global outcome groups for age, sex, or illness duration; however, work status was significantly lower for the non-improved groups (p<.001). Nonsocial hassles intensity showed an increasing slope for the worsened group (p=.03) and a decreasing slope (p=0.05) for the improved group. For the worsened group, a downward trend was found for the frequency of non-social (p=0.01) uplifts.

Conclusion: Individuals with worsening as compared to improving illness in CFS show significantly different six-month trajectories for weekly hassles and a deficit in uplifts. This may have clinical implications for behavioral intervention.

Background

Psychological uplifts are minor pleasant events, such as completing a rewarding task, that occur in daily life [1]. Although these events appear to be important to well-being [2], they have not been extensively studied. By comparison, minor stressors or “hassles,” such as misplacing things, have received considerably more empirical attention. Hassles have been associated with increased somatic health symptoms, e.g., backaches, and headaches [1], as well as decreases in health and positive mood, whereas uplifts can make a person feel joyful, glad, or satisfied [2]. Uplifts and positive events are correlated with lower fatigue in individuals with chronic fatigue and chronic pain [3, 4].

Uplifts and hassles also appear to have biobehavioral effects. A cross-sectional study of healthy adults [5] suggested that hassles and uplifts significantly and independently predicted changes in inflammation markers (e.g., Interleukin-6 (IL-6)), independent of sociodemographic, biological, and psychological measures, including depressed mood. A later prospective study of over 900 middle-aged adults [6] found that the frequency of daily positive events was associated with lower inflammatory markers (IL-6 and C-reactive Protein) in the overall sample and lower fi fibrinogen among women. Effects were more pronounced for participants in the lowest quartile of positive event frequency, suggesting that lack of positivity in daily life may be particularly consequential for inflammation. Furthermore, interpersonal positive events were more predictive of lower IL-6 overall and lower fi fibrinogen in women than noninterpersonal positive events. The authors concluded that daily positive events may serve a protective role against inflammation, a biological factor that may contribute to the pathophysiology of particular subgroups in chronic fatigue syndrome (CFS) [7].

Apart from biological correlates, several behavioral papers [8] suggest that social interactions may play a  role in determining the magnitude of fatigue experienced by those with chronic pain [9]. Specifically,  investigations of rheumatoid arthritis, osteoarthritis, and fibromyalgia (FM) patients have shown that positive interpersonal events are associated with lower daily fatigue, and negative interpersonal events are correlated with elevated daily fatigue [9, 10]. Furthermore, the impact of hassles may also play a role in negative outcomes. A cross-sectional study [11] comparing newly diagnosed CFS and FM patients to multiple sclerosis and arthritis patients found that the combined CFS and FM group showed a higher frequency and higher emotional impact of daily hassles. This may indicate a need for better coping with hassles and/or positive behavioral changes that may reduce hassles as part of a self-management program [12]. These reported associations between commonly experienced positive and negative events, and fatigue symptoms in chronic pain and chronic fatigue conditions suggest that clinical approaches to potential illness improvement may be enhanced with careful assessments of these interactive phenomena.

Recently, a six-month observational study of a biobehavioral model in CFS [13] found that decreased intensity of behavioral uplifts, as assessed on the Combined Hassles and Uplifts scale (CHUS)[14], was the only significant behavioral predictor of patient-reported global non-improvement. Given this intriguing, if somewhat imprecise finding, perhaps the CHUS measure could be more informative if a greater specific city could be applied to its constructs. For instance, in a study on relationship satisfaction [15],  hassles and uplifts on an abbreviated version of the CHUS were grouped into those dealing with social (e.g., family, friends) and non-social (e.g., job, health) events. Contrary to their hypothesis, non-social uplifts had the strongest positive impact on relationship satisfaction. In CFS, the influence of these minor social and non-social events may shed light on their relative importance in influencing outcomes.

Concerning longer-term outcomes, positive impacts of uplifts have been reported in a one-year prospective study of 130 patients with chronic fatigue syndrome (CFS)[3]. This study found that pleasant activities and/or life events implying moderate or major life changes were associated with significantly improved outcomes, including reduced fatigue and impairment. Similarly, a clinical model of behavioral intervention in CFS [12] suggested therapeutic prescription of uplifting activities and the enhancement of positive coping skills to diminish the impact of hassles and improve outcomes. These clinical research threads may have implications for better-targeted approaches to behavioral management for patients with fatiguing illnesses.

The purpose of the current report was to assess the relationship between the global outcomes of illness worsening and improvement to the trajectories of social and non-social uplifts and hassles in a six-month prospective study in CFS. Although the global outcome rating is frequently used as an important indicator of perceived change in CFS observational and intervention studies [16–18], its relation to potentially influential patterns of uplifts, hassles, and social and non-social events has not been studied. Furthermore, validated weekly assessments, rarely reported in CFS observational studies, may have utility in identifying specific behavioral patterns that may influence outcomes, particularly illness worsening that, in turn, may inform therapeutic management strategies.

Methods

Participants and procedure

This report utilized data from a six-month home-based observational study in 128 CFS patients, detailed elsewhere [13] that examined biobehavioral predictors of global outcomes. Most participants were in their 40s (M age=46.11, SD=11.8), female (87.2%), white (90.3%), unemployed or on disability (67.9%), and ill with CFS for over a decade (M=16.5 years, SD=10.3). Baseline questionnaire scores showed clinically relevant fatigue severity (Fatigue Severity Scale; [19]), impaired physical function (SF-36 Physical Function Subscale; [20]), and elevated autonomic symptoms (COMPASS; [21]. The entire study sample met symptom and impairment criteria for CFS [22], as assessed in a validated phone interview [23] conducted by research nurses (PB, MM) experienced in chronic fatigue and chronic pain assessments.

The primary study protocol [13] (Table 1) classified subjects into improved and non-improved groups with behavioral predictors (e.g., uplifts) based on 26-week means. The current study divided the CFS sample into three outcome groups, i.e., improved, unchanged, and worsened, and created new variables for social and non-social uplifts and hassles. Weekly uplifts and hassles scores drawn from assigned web diaries were utilized in the data analysis as behavioral predictors of outcomes across the three outcome groups, which were treated as response variables in our models.

Nationwide recruitment in the United States began in September 2016 and ended in October 2019. Recruitment methods included study announcements posted on major CFS patient support websites (e.g., Health Rising, SolveME) and in the large private practices of CFS-specialized physicians located in New York and Utah. Without a travel requirement, this home-based study was considered more likely to recruit these under-served patients, particularly those who were disabled and homebound [24]. This study was approved by the Stony Brook University Committee on Research Involving Human Subjects which reviewed and approved the study procedure. All participants provided written informed consent via land mail of signed consent forms. Participants were compensated up to $300 for their participation. The study was pre-registered on ClinicalTrials.gov (NCT02948556).

Measures

Hassles and uplifts. Hassles and uplifts were measured with the Combined Hassles and Uplifts Scale (CHUS)[14]. A 26-week weekly web diary (ScienceTrax, Inc., Macon, Georgia) contained the 53-item CHUS which measures perceived hassles and uplifts. Hassles are defined as "irritants—things that annoy or bother you; that can make you upset or angry." Uplifts are defined as "events that make you feel good;  that can make you joyful, glad, or satisfied." The CHUS yields subscales of frequency and intensity. Hassles and uplifts frequency scores have a potential range of 0 to 53, with the total score indicating how many items were simply endorsed. When endorsing an item, participants are asked to rate how much of a hassle or uplift the specific item was. Items are rated on a 3-point Likert-based scale ranging from 1 (somewhat), 2 (quite a bit), to 3 (a great deal). The average rating of these items yields intensity scores. Participants may rate events as hassles, uplifts, or both. The CHUS has shown good reliability and validity in predicting mood and somatic health outcomes [11, 25]. The measure has high test–retest reliability and a reported Cronbach's alpha of 0.71 [2]. The CHUS alpha for the present study was excellent (α = 0.87).

Based on a prior study of relationship satisfaction [15], the CHUS items were subdivided into ten social (e.g., children, relatives, family obligations, friends) events and 43 non-social (e.g., job, finances, exercise,  health, neighborhood, pets, home maintenance, free time, recreation outside the home) events. The possible range of frequency scores for social events is 0–10 and for non-social events, 0–43. Means and standard deviations for intensity ratings in this study were: social hassles (M=1.37, SD=.04), social uplifts (M=1.72, SD=.03), non-social hassles (M=1.66, SD=.02), and non-social uplifts (M=1.48, SD=.02). Means and standard deviations for frequency totals were: social hassles (M=3.21, SD=0.33),  social uplifts (M=4.26, SD=0.47), non-social hassles (M=15.36, SD=1.45), and non-social uplifts (M=12.40, SD=1.21).

Global Impression of Change. The outcome assessment for overall change was measured with the Patient's Global Impression of Change (PGIC) rating. The PGIC rating, assessed during the six-month follow-up phone interview of each participant, is based on seven levels of change ranging from very much worse to very much improved as it applied to the prior six months. Subjects who selected a PGIC  rating of "very much worse," "much worse," or "somewhat worse" were assigned to the “worsened” subgroup. Individuals with an “unchanged” rating were assigned to the “unchanged” subgroup and participants who selected “very much improved,”“much improved,” or “somewhat improved” were assigned to the “improved” subgroup. The PGIC rating, which provides a generalized view of the patient’s perception of overall change [26, 27], has shown construct validity in CFS studies, including an empirical finding that patient-reported global outcomes of even modest improvement (the most commonly endorsed level in CFS), as opposed to no change or worsening, was associated with significantly improved fatigue (Fatigue Severity Scale) and functioning (SF-36 Physical Function Subscale) in a longterm outcome study [23]. More generally, CFS prospective studies have often relied on the PGIC as a  broad outcome measure of improvement or worsening [16].

Power estimation

Sample size and power calculation issues were addressed in the primary study [13]. 

Data Analysis

Linear mixed effect models were utilized to examine and compare the linear trend of four qualitative types of hassles and uplifts over 26 weeks including social intensity, non-social intensity, social frequency, and non-social frequency. With the assumption that hassles and uplifts exhibit linear trends over time, the week was treated as a continuous variable. It was also hypothesized that patients in different outcome groups (improved vs. unchanged vs. worsened) would exhibit different weekly patterns; thus, an interaction term between week and outcome group was adjusted in our models. No other factors were adjusted in the regression models as this was an exploratory analysis.

Based on Akaike Information Criteria (AIC), the covariance structure to model correlations among longitudinal measurements from the same patient is selected from Compound Symmetry (CS), and fi rstorder autoregressive (AR(1)), Toeplitz (TOEP), and Unstructured (UN). The coefficient of the week, based on linear mixed effect models, was used to characterize the longitudinal pattern of behavioral measurement over 26 weeks. A coefficient>0 suggests an increasing pattern and a coefficient<0 suggests a decreasing pattern. Statistical analysis was performed using SAS 9.4 (SAS Institute Inc., Cary, NC) and the significance level was set at 0.05.

Results

The study sample consisted of 128 participants with global ratings at six-month follow-up of improved (29%; n = 37), unchanged (33%; n = 42) or worsened (38%; n = 49). No significant differences were found between groups for age, sex, or illness duration; however, work status was significantly reduced for the non-improved groups (χ 2 = 819.72 (8); p < .001). Participant completion of weekly web diaries was excellent (95.6%).

Over 26 weeks, the longitudinal profile of intensity of non-social hassles (Fig. 1; Table 2) was significantly different across the 3 groups (p = 0.016). More specifically, the worsened group showed a significantly increasing pattern (weekly change = 0.003, p = 0.033) of non-social hassles intensity (Table 3), while the improved group evidenced a significantly decreasing pattern (weekly change = -0.003, p = 0.05).

The trend slope (Fig. 1; Table 3) for the frequency of social uplifts significantly decreased over time in all three groups as follows: improved (weekly change = -0.02, p = 0.039), unchanged (weekly change = -0.02, p = 0.019), and worsened (weekly change = -0.02, p = 0.003). By comparison, only the worsened group showed a significantly decreasing pattern in the frequency of non-social uplifts (weekly change = -0.07, p = 0.011).

Comparing the trend slope across groups (Fig. 1; Table 3), the improved group and worsened group presented significantly different patterns of change for non-social hassles intensity (improved vs. worsened groups: difference of coefficient of week = -0.006, p = 0.004). No other significant trends were found for uplifts or hassles.

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