Study population characteristics
63 adolescents with CFS/ME were included in the study, with a female:male ratio of 4,2:1 and mean age18 years (Table 1). The number of participants from Oslo University Hospital and from St. Olavs Hospital was 41 and 22, respectively. The distributions of gender and age were not significantly different between the two hospitals (data not shown). Duration of fatigue initial to diagnostic evaluation was 15 months (10-33) (median (Q1-Q3)), and at the time of study enrollment 52 months (36-67) (median (Q1-Q3)). 37 (76%) of the adolescents had a delayed school progression defined as not having completed all compulsory subjects in school at their level. Furthermore, a majority of the adolescents (66%) reported no participation in leisure activities. Four adolescents had recovered after 6, 12 and 36 months, respectively (one unknown) (Table 2).
Generic PedsQL4.0 score for all participants in this study was 50 (17) (mean (SD)) (Table 1). The subscale scores were lowest for the domain school functioning and highest for social functioning. Overall PedsQL-MFS score was 36 (19). The domain general fatigue had the lowest score. There was a strong correlation between generic PedsQL4.0 and overall PedsQL-MFS scores (Pearson`s r =.861, p<.001). The SMFQ sum score was 7 (5) (mean (SD)), whereas 27 % of the participants scored 11 or higher, suggesting a possible treatment-requiring depression. The correlation between SMFQ and generic PedsQL4.0 score showed moderate to strong negative correlation (r = -.544, p < .001).
There were no correlation between duration of fatigue at time of study enrolment and overall score of HRQoL, fatigue level or depressive symptoms (Fig. 1). Adolescents recovered from CFS/ME reported higher HRQoL than those who had not recovered (83 vs. 48, p <.001) (Table 2).
Table 1. Patient characteristics and overall results from PedsQL 4.0, PedsQL-MFS and SMFQ.
|
N
|
%
|
Mean (SD)
|
Median (Q1-Q3)
|
Gender (Female / Male / Undetermined)
|
50/12/1
|
79/19/2
|
|
|
Age at time of enrolment
|
63
|
|
18 (2)
|
|
Duration of fatigue initial to diagnostic evaluation (months) a)
|
48
|
|
|
15 (10-33)
|
Duration of fatigue at time of enrolment (months)
|
59
|
|
|
52 (36-67)
|
Recovered from CFS/ME (yes/no)
|
4/58
|
6/94
|
|
|
Delayed school progression (yes/no)
|
37/12
|
76/24
|
|
|
Participation in leisure activities (yes/no)
|
21/41
|
34/66
|
|
|
PedsQL4.0:
|
|
|
|
|
Overall HRQoL score (b)(c)
|
63
|
|
50 (17)
|
|
Sub scale scores: Social functioning
|
63
|
|
67 (16)
|
|
Emotional functioning
|
63
|
|
56 (20)
|
|
Physical functioning
|
63
|
|
42 (25)
|
|
School functioning
|
58
|
|
41 (21)
|
|
Psychosocial functioning
|
63
|
|
55 (16)
|
|
PedsQL-MFS:
|
|
|
|
|
Overall Fatigue score (b)
|
62
|
|
36 (19)
|
|
Sub scale scores : Cognitive fatigue
|
62
|
|
41 (25)
|
|
Fatigue related to sleep/rest
|
62
|
|
36 (19)
|
|
General fatigue
|
62
|
|
32 (23)
|
|
|
|
|
|
|
SMFQ (13 items) Sum score (c)
|
63
|
|
7 (5)
|
|
Score <11 / 11 or higher
|
46/17
|
73/27
|
|
|
a)Not available data from 15 participants, b) Pearson`s correlation = .861, p<.001 between generic PedsQL4.0 and overall PedsQL-MFS, c) Pearson`s correlation = -.544, p<.001between generic PedsQL 4.0 and SMFQ sum score.
HRQoL, fatigue and depressive symptoms versus study population characteristics
There was a significant gender difference in generic PedsQL4.0 score where girls scored significantly lower than boys (47 vs 64, p=.003). In subscale scores, girls scored lower than boys for all dimensions (data not shown). There was also a significant gender difference in PedsQL-MFS score where girls scored lower than boys, and a similar result was found in the SMFQ score (Table 2).
Fig. 1. HRQoL-, Fatigue- and SMFQ- scores in relation to Duration of fatigue, n=59. For PedsQL4.0 and
PedsQL-MFS high score is better, for SMFQ low score is better.
School attendance, delayed school progression or participation in leisure activities were not statistically significant associated with SMFQ scores (Table 2). However, both generic PedsQL4.0 and overall PedsQL-MFS scores differed between adolescents having or not having participated in leisure activities or delayed school progression, with higher scores for the adolescents who were able to participate in leisure activities and adolescents with a normal school progression. School attendance initial to diagnostic evaluation showed a similar trend when setting the cut-off at 50% school attendance, although not attaining statistical significance.
Table 2. PedsQL generic and multidimensional fatigue scales and SMFQ sum score related to patient characteristics.
|
PedsQL Generic scale (23 items)
|
PedsQL Multidimentional Fatigue scale (18 items)
|
SMFQ sum score (13 items)
|
N
|
Mean (SD)
|
95%CI for diff
|
N
|
Mean (SD)
|
95%CI for diff
|
N
|
Mean (SD)
|
95%CI for diff
|
Gender: Girls Boys
|
50 12
|
47 (16) 64 (20)
|
(-27; -6)
|
49 12
|
33 (16) 51 (24)
|
(-30; -7)
|
50 12
|
8 (5) 4 (3)
|
(2 – 6)
|
Age: <16 16+
|
10 53
|
57 (17) 49 (17)
|
(-4 – 20)
|
10 52
|
46 (13) 34 (20)
|
(-2; -24)
|
10 53
|
6 (3) 8 (6)
|
(-4 – 0)
|
Status at response time: Not recovered from CFS/ME Recovered from CFS/ME
|
58 4
|
48 (16) 83 (13)
|
(19 – 51)
|
57 4
|
33 (16) 78 (15)
|
(-61; -28)
|
58 4
|
8 (5) 3 (4)
|
(0 – 10)
|
Is your school progression delayed: Yes No
|
37 12
|
49 (16) 65 (18)
|
(-27; -4)
|
37 12
|
34 (19) 52 (21)
|
(-31; -6)
|
37 12
|
8 (5) 5 (6)
|
(-1 – 6)
|
School attendance initial to diagnosis: <50% 50% or more
|
39 9
|
50 (18) 61 (21)
|
(-25 – 2)
|
38 9
|
36 (19) 50 (25)
|
(-29 – 1)
|
39 9
|
8 (5) 6 (5)
|
(-2 – 6)
|
Do you participate in leisure activity: Yes No
|
21 41
|
59 (17) 46 (16)
|
(4 – 22)
|
21 40
|
46 (19) 31 (18)
|
(5 – 24)
|
21 41
|
6 (4) 9 (5)
|
(-5 – 0)
|
Two-sided Independent Samples T-test. Difference in N is due to one undetermined which gender, and that participation with questionnaire was higher than participation in interview.
HRQoL versus selected factors initial to diagnosis, by the time of diagnosis or at follow-up
To further explore factors positively or negatively associated with HRQoL, 34 variables collected from patients and patient journals were selected and divided into three groups; initial to diagnosis, by the time of diagnosis and at follow-up period. Factors significantly associated with generic PedsQL4.0 or subscale scores are shown in Table 3.
Looking at the possible association between HRQoL and factors being present initial to the diagnose CFS/ME, we found that school attendance < 50% or using medications were associated with lower HRQoL in PedsQL subscales, but not with generic PedsQL4.0.
All adolescents had a physician involved in diagnostic evaluation. Beyond that, there were differences regarding the type of health personell involved. Our analysis show that when either an occupational therapist, a physical therapist or a clinical nutritionist were involved, this was positively assossiated with the PedsQL4.0 subscale emotional functioning, but not with other subscales or generic score.
For the follow-up period, we found four factors associated with HRQoL. Teacher follow-up at school was positively associated with generic PedsQL 4.0 (55 vs 41, CI (0.08 – 29)), and with the subscale scores for emotional and psychosocial functioning. Participation in leisure activity was positively associated with generic PedsQL4.0 (59 vs 46, CI (4 – 22)) and with the subscale scores for physical, social, school and psychosocial functioning. Been to rehabilitation stay was negatively associated with generic PedsQL4.0 (43 vs 57, CI (-24;-3)) and with subscale scores for emotional, social and psychosocial functioning. Delayed school progression was negatively associated with generic PedsQL4.0 (49 vs 65, CI (-27;-4)) and with subscale scores for physical, social, school and psychosocial functioning. We also found that possible clinical significant depression (SMFQ score equal to or greater than 11) was negatively associated with generic HRQoL (CI (-27;-10)) and with all dimensions.
(insert Table 3 approximately here)
Multivariate analysis: HRQoL versus selected factors in a regression model
Multiple linear regression analysis was performed to predict HRQoL based on the four variables from follow-up, identified from bivariate analyses and with the most significant positive or negative association. Dependent variable generic PedsQL 4.0 was normally distributed. 48 participants had responded to all predictor variables. Predictor variables correlated with HRQoL (Pearson`s r > .300 except from follow up from teacher r .290) (Table 4).
Table 4: Multiple Linear regression - predictors to HRQoL in adolescents diagnosed with CFS/ME
N=48
|
Beta coefficient
|
(95%CI)
|
β
|
p
|
Constant
Gender (a)
Follow-up from teacher (b)(c)
Delayed school progression (d)
Participation in leisure activity (e)
Been to rehabilitation stay (f)
|
50
10
10
-10
8
-8
|
(34 – 66)
(-1 – 21)
(-3 – 23)
(-21 – 1)
(-2 – 18)
(-18 – 2)
|
.230
.200
-.249
.211
-.212
|
.000
.079
.121
.051
.114
.104
|
- a) female =0, male =1), b) follow-up from teacher no =0, yes =1, c) follow-up from teacher,
correlation coefficient to HRQoL .290 (<.3). d) school delay no=0, yes =, 1, e) participate in
leisure activity no=0, yes =1, f) been to rehabilitation stay no=0, yes =1.
Model summary: Adj R² .319, F Change 5.399, Sig (ANOVA) p = .001.
The results from the multiple regression analysis confirmed the assossiations from bivariate analyses. The regression model was significant at the level p = .001, explaining 32 % of the variance. Follow-up from teacher and participation in leisure activities were positively associated with HRQoL, while negative associations came from delayed school progression, and having been to a rehabilitation stay. The regression coefficient for delayed school progression was -10 (β -.249), and for follow-up from school teacher 10 (β .200), indicating clinical relevance. We also looked at the multiple linear regression analyses without the four participants who reported recovery. The predictors was distributed similarly in the regression model, and with similar results.
Based on the difference in bivariate analyses between participants with and without depressive symptoms, we looked at the multiple regression analysis if excluding the group of ten participants with depressive symptoms. With n=38 participants the distribution of the predictors was still the same, but with regression coefficient for delayed school progression at -14 (β -.378), and follow-up from teacher 10 (β .162). Participation in leisure activity, β .260, and been to rehabilitation stay, β -.143. Hence the model explained 23 % of the variance (p = .019).