3.1. Patient characteristics at baseline
Seventy-one percent were males, and the mean age was 43 years (Table 1). Half had more than primary school as the highest level of education. Eighty-three percent received opioid agonist therapy, and 42 % had injected substances in the last 30 days leading up to the health assessment. The mean values of the FSS-9 items varied from 4.43 to 5.38 at baseline (Table 2). For the VAFS, the mean value was 5.19 at baseline. The FSS-9 and VAFS variables were slightly left-skewed (skewness ranged from –1.14 to –0.29) and tended towards a flattened distribution (kurtosis ranged from –1.39 to –0.09).
Table 1: Baseline characteristics of patients (numbers (n) and percentages (%)).
|
N = 655
|
Age (years), n (%)
|
|
|
18-29
|
81 (12)
|
|
30-39
|
185 (28)
|
|
40-49
|
207 (32)
|
|
50-59
|
147 (22)
|
|
≥ 60
|
35 (5)
|
|
Mean (SD)
|
43 (11)
|
Gender, n (%)
|
|
|
Male
|
462 (71)
|
|
Female
|
193 (29)
|
Highest educational level, n (%)
|
|
|
Not completed primary school
|
40 (6)
|
|
Completed primary school (9 years)
|
286 (44)
|
|
Completed high school (12 years)
|
260 (40)
|
|
≤ 3 years of college or university
|
57 (9)
|
|
> 3 years of college and university
|
12 (2)
|
Receiving opioid agonist therapy (OAT), n (%)
|
542 (83)
|
OAT opioid, n (%):
|
|
|
Methadone
|
212 (39)
|
|
Buprenorphine*
|
323 (60)
|
|
Long-acting morphine sulfate
|
7 (1)
|
Housing situation the past 30 days, n (%)
|
|
|
Owned or rented housing
|
518 (79)
|
|
Temporary residence (homeless shelter, with family or friends)
|
156 (24)
|
|
Living on street
|
27 (4)
|
|
Prison
|
7 (1)
|
|
Other
|
27 (4)
|
Ever injected substances, n (%)
|
573 (94)
|
Injected substances the past 30 days, n (%)
|
257 (42)
|
|
|
|
|
* Buprenorphine includes buprenorphine, buprenorphine-naloxone, and buprenorphine depot.
OAT: Opioid agonist therapy; SD: Standard Deviation
Table 2: Descriptive information of the Nine-item Fatigue Severity Scale (FSS-9) and Visual Analog Fatigue Scale (VAFS) at baseline (FSS-9: N = 654, VAFS: N = 655).
|
Mean
|
SD
|
Median
|
IQR
|
Skewness (SE)
|
Kurtosis (SE)
|
Variance
|
FSS-9 items:
I1: My motivation is lower when I am fatigued
|
5.38
|
2.04
|
6.00
|
5.00-7.00
|
-1.14 (0.10)
|
-0.09 (0.19)
|
4.16
|
I2: Exercise brings on my fatigue
|
4.73
|
2.12
|
5.00
|
3.00-7.00
|
-0.54 (0.10)
|
-1.11 (0.19)
|
4.49
|
I3: I am easily fatigued
|
4.54
|
2.15
|
5.00
|
3.00-7.00
|
-0.42 (0.10)
|
-1.24 (0.19)
|
4.60
|
I4: Fatigue interferes with my physical functioning
|
4.95
|
2.07
|
6.00
|
3.00-7.00
|
-0.74 (0.10)
|
-0.81 (0.19)
|
4.27
|
I5: Fatigue causes frequent problems for me
|
4.43
|
2.22
|
5.00
|
2.00-7.00
|
-0.31 (0.10)
|
-1.39 (0.19)
|
4.91
|
I6: My fatigue prevents sustained physical functioning
|
4.62
|
2.19
|
5.00
|
2.00-7.00
|
-0.48 (0.10)
|
-1.22 (0.19)
|
4.79
|
I7: Fatigue interferes with carrying out certain duties and responsibilities
|
5.00
|
2.14
|
6.00
|
4.00-7.00
|
-0.84 (0.10)
|
-0.75 (0.19)
|
4.56
|
I8: Fatigue is among my three most disabling symptoms
|
4.64
|
2.34
|
5.00
|
2.00-7.00
|
-0.50 (0.10)
|
-1.35 (0.19)
|
5.48
|
I9: Fatigue interferes with my work, family, or social life
|
4.85
|
2.17
|
5.00
|
3.00-7.00
|
-0.69 (0.10)
|
-0.95 (0.19)
|
4.72
|
VAFS
|
5.19
|
2.65
|
5.00
|
3.00-7.00
|
-0.29 (0.10)
|
-0.78 (0.19)
|
7.04
|
|
|
|
|
|
|
|
|
|
|
FSS: Fatigue Severity Scale; I: Item; IQR: Interquartile range (25-75 percentiles); SD: Standard Deviation; SE: Standard Error.
Legend: Table 2 displays descriptive information of the FSS-9 and VAFS at baseline. The FSS-9 was answered on a Likert scale from 1 (no fatigue) to 7 (worst fatigue). The VAFS was answered by placing a mark on a line from 0 (no fatigue) to 10 (worst fatigue)). The items in bold represent the FSS-3 items.
3.2.1 Internal consistency of the FSS-9 and the FSS-3 with added VAFS
The nine-item Fatigue Severity Scale’s Cronbach’s α was 0.94 at baseline and 0.93 at the second health assessment (Additional file 3). For the FSS-3, retaining items 5–7 from the FSS-9, Cronbach’s α was 0.87 at baseline and 0.84 at the second health assessment. The internal consistency was not substantially affected when we added the VAFS to the FSS-9 and FSS-3 at baseline (FSS-9 plus VAFS: α = 0.94; FSS-3 plus VAFS: α = 0.87), and at the second health assessment (FSS-9 plus VAFS: α = 0.93, FSS-3 plus VAFS: α = 0.85).
3.2.2 Longitudinal confirmatory factor analysis for evaluating the fit of the FSS-9 and FSS-3 with added VAFS
The results from the CFAs comparing the fit of items in the FSS-9 and FSS-3 with and without added VAFS at baseline and at the second health assessment are shown in Table 3. At baseline, the unidimensional model with unique factor loadings, residuals, and intercept values resulted in a borderline fitted model, with a Comparative Fit Index and Tucker Lewis Index below the suggested levels and a Root Mean Square Error of Approximation point estimate just at the level of a poor fit for the FSS-9. The modification index showed that the estimation of the residual covariance between items 2 and 3 improved the model with the best result (Δχ2 = 80.1, degree of freedom (df) = 1, P < .001). The factor loadings for the nine items of the FSS-9 in this model were (ranged from items 1 to 9): 0.66, 0.74, 0.77, 0.78, 0.85, 0.79, 0.84, 0.84, and 0.84. The FSS-3 showed a well-fitted model. The FSS-9 and FSS-3 were highly correlated with r = 0.95, P < 0.001, giving 90 % explained variance after estimating factor scores. The VAFS, together with the FSS-9 and FSS-3, respectively, gave identical results. The correlations with VAFS were r = 0.70, P < .001 (FSS-9) and r = 0.68, P < .001 (FSS-3). We obtained relatively similar results for the factor models at the second health assessment for both the FSS-9 and FSS-3 with and without the VAFS. The full FSS-9 version showed the factor loadings to be (ranged from items 1 to 9) 0.59, 0.66, 0.75, 0.69, 0.84, 0.74, 0.85, 0.80, and 0.79. The longitudinal CFA model based on the FSS-3 supported time-invariant equal factor loadings and equal residuals between the baseline and the second health assessment (Figure 1). The correlation between the models at baseline and at the second measurement was r = 0.52, P < 0.001. A small reduction in the model fit was found if the intercept values were constrained to be equal within each measured item between health assessments. However, this simpler model was still a well-fitted model.
Table 3: Confirmatory factor analysis results at baseline and at the second health assessment
|
χ2
|
df
|
P
|
|
CFI
|
TLI
|
RMSEA
|
|
|
|
|
|
|
|
εa
|
εa 90%CI
|
εa p<.05
|
Time 1 (baseline)
|
|
|
|
|
|
|
|
|
|
FSS-9
|
212.90
|
27
|
<0.001
|
|
0.93
|
0.90
|
0.10
|
0.09, 0.12
|
0.00
|
FSS-9 ResCov
|
132.80
|
26
|
<0.001
|
|
0.96
|
0.94
|
0.08
|
0.07, 0.09
|
0.00
|
FSS-9 ResCov + VAFS
|
151.33
|
34
|
<0.001
|
|
0.96
|
0.95
|
0.07
|
0.06, 0.09
|
0.00
|
FSS-3
|
0.48
|
2
|
0.788
|
|
1.00
|
1.00
|
0.00
|
0.00, 0.05
|
0.95
|
FSS-3 + VAFS
|
4.42
|
4
|
0.352
|
|
1.00
|
1.00
|
0.01
|
0.00, 0.06
|
0.87
|
Time 2 (second health assessment)
|
|
|
|
|
|
|
|
|
FSS-9
|
108.14
|
27
|
<0.001
|
|
0.90
|
0.86
|
0.12
|
0.10, 0.14
|
0.00
|
FSS-9 ResCov
|
50.16
|
26
|
0.003
|
|
0.97
|
0.96
|
0.06
|
0.04, 0.10
|
0.18
|
FSS-9 ResCov + VAFS
|
65.44
|
34
|
<0.001
|
|
0.96
|
0.95
|
0.06
|
0.04, 0.09
|
0.15
|
FSS-3
|
4.20
|
2
|
0.122
|
|
0.99
|
0.98
|
0.07
|
0.00, 0.17
|
0.27
|
FSS-3 + VAFS
|
5.37
|
4
|
0.252
|
|
1.00
|
0.99
|
0.04
|
0.00, 0.11
|
0.50
|
Time 1-2
|
|
|
|
|
|
|
|
|
|
FSS-3 0
|
13.33
|
8
|
0.101
|
|
0.99
|
0.99
|
0.03
|
0.00, 0.06
|
0.83
|
FSS-3 1
|
14.47
|
10
|
0.153
|
|
1.00
|
0.99
|
0.03
|
0.00, 0.05
|
0.92
|
FSS-3 2
|
15.48
|
13
|
0.278
|
|
1.00
|
1.00
|
0.02
|
0.00, 0.04
|
0.98
|
FSS-3 3
|
23.35
|
16
|
0.105
|
|
0.99
|
0.99
|
0.03
|
0.00, 0.05
|
0.96
|
Legend: CFI: Comparative Fit Index; TLI: Tucker Lewis Index; VAFS: Visual Analog Fatigue Scale; FSS-9: Nine-item Fatigue Severity Scale; FSS-3: Three-item Fatigue Severity Scale; εa: Root Mean Square Error of Approximation (RMSEA); εa P<.05: Probability of close fit (RMSEA = .05); ResCov: Residual covariance between items 2 and 3 estimated; SD: Standard deviation.
0 free factor loadings, intercepts, and residuals within and from baseline (time 1) to the second health assessment (time 2)
1 equal factor loadings from baseline (time 1) to the second health assessment (time 2): Wald test of constraints: 0.77, P = .682
2 and equal residuals within each indicator from baseline (time 1) to the second health assessment (time 2): Wald test of constraints: 1.25, P = .682
3 and equal intercepts within each indicator from baseline (time 1) to the second health assessment (time 2): Wald test of constraints: 8.61, P = .035
The table shows the confirmatory factor analysis results with variance and model fit of the FSS-9, FSS-9 with ResCov, FSS-9 plus VAFS, FSS-9 with ResCov plus VAFS, FSS-3, and FSS-3 plus VAFS at baseline (Time 1) and at the second health assessment (Time 2). For the FSS-3, a longitudinal confirmatory factor analysis was shown in the period from baseline to the second health assessment (Time 1-2). The mean time interval between baseline and the second health assessment was 11.6 months (SD: 4.2).
3.2.3 Linear mixed model analysis for evaluating changes in the FSS-9 and the FSS-3 sum scores with added VAFS between the annual health assessments
The linear mixed model analysis showed considerable intra-individual clustering for the FSS-9 and FSS-3 with added VAFS, and for the separate items (Table 4). However, the intraclass correlation coefficient estimated variations of 0.18 to 0.52, and these showed more variation over time in some variables than in others. The random slope and covariance between the intercept and the slope were statistically non-significant for all models. This indicated an equal linear change from baseline at the individual level. The re-estimated linear random intercept fixed slope models showed a small increase in the items 1–4, while no similar change was found in the other items. A mean change was also found in the VAFS variable.
Table 4: Linear mixed model analysis results for the FSS-9, the FSS-3 and the Visual analog Fatigue Scale (VAFS)
|
Fixed effects
|
|
Random effects
|
|
|
|
Baseline
|
|
Change
|
|
Residual
|
Intercept
|
Slope
|
Covi,s
|
|
ICC
|
|
I
|
P
|
|
S
|
P
|
|
σ2e
|
P
|
σ2i
|
P
|
σ2s
|
P
|
σ2is
|
P
|
|
|
FSS-9 a
|
4.76
|
***
|
|
0.01
|
|
|
1.46
|
***
|
1.61
|
***
|
0.00
|
|
-0.02
|
|
|
.52
|
FSS-3 b
|
4.64
|
***
|
|
0.00
|
|
|
2.07
|
***
|
1.64
|
***
|
0.00
|
|
-0.01
|
|
|
.44
|
Item 1
|
5.35
|
***
|
|
0.02
|
*
|
|
2.52
|
|
1.53
|
***
|
0.00
|
|
-0.04
|
|
|
.38
|
Item 2
|
4.71
|
***
|
|
0.03
|
**
|
|
2.95
|
***
|
1.41
|
***
|
0.00
|
|
-0.03
|
|
|
.32
|
Item 3
|
4.51
|
***
|
|
0.03
|
**
|
|
2.40
|
***
|
2.13
|
***
|
0.00
|
|
-0.02
|
|
|
.47
|
Item 4
|
4.90
|
***
|
|
0.03
|
**
|
|
3.43
|
***
|
0.73
|
*
|
0.00
|
|
-0.04
|
|
|
.18
|
Item 5 sv
|
4.38
|
***
|
|
0.02
|
|
|
2.99
|
***
|
1.84
|
***
|
0.00
|
|
-0.02
|
|
|
.38
|
Item 6 sv
|
4.57
|
***
|
|
-0.01
|
|
|
3.18
|
***
|
1.60
|
***
|
0.00
|
|
-0.01
|
|
|
.34
|
Item 7 sv
|
4.97
|
***
|
|
0.00
|
|
|
2.92
|
***
|
1.62
|
***
|
0.00
|
|
-0.02
|
|
|
.36
|
Item 8
|
4.60
|
***
|
|
0.02
|
|
|
2.92
|
***
|
2.50
|
***
|
0.00
|
|
-0.02
|
|
|
.46
|
Item 9
|
4.82
|
***
|
|
-0.01
|
|
|
2.90
|
***
|
1.90
|
***
|
0.00
|
|
-0.00
|
|
|
.40
|
VAFS
|
5.14
|
***
|
|
0.02
|
*
|
|
4.73
|
***
|
2.27
|
***
|
0.00
|
|
-0.02
|
|
|
.33
|
Legend: Covi,s, Covariance between intercept and slope; ICC: Intraclass Correlation Coefficient of between on total variance; I: Intercept (baseline); S: Slope (change); σ2: variance (residual, intercept and slope); σ2i,s: Covariance between intercept and slope
* P < .05 ** P < .01 *** P < .001.
a FSS-9: Nine-item Fatigue Severity Scale;
b FSS-3: Three-item Fatigue Severity Scale;
sv Items included in the FSS-3;
The table shows the linear mixed model analyses, including the fixed effects, the random effects, and the ICC of the FSS-3, FSS-9, VAFS, and the single items of the FSS-9. The random effects show the residual, the slope, and the covariance between the intercept and slope.