A total of 1566 patients were screened and 1520 patients were included in the analysis. The reasons for exclusion were: age below 18, no cancer diagnosis, and missing ESAS sleep. Table 1 represents the demographic and clinical characteristics of all patients, patients with ESAS sleep>/=4, and less than 4. Seventy percent of the patients were women. Most common cancer diagnoses included breast (42%) or gastrointestinal (14%); close to one-third of the patients (32%) had metastatic disease. The median (IQR) for SD was 5(3–7). Figure 1 shows the frequency and percentage for SD scores from the ESAS. Of 1520 patients, 1300 patients (86%) reported ESAS sleep score as 2 or higher, 971 patients 4 or higher (64%), and 447 patients 7 or higher (29%). However, only 164 of 1520 patients (11%) reported sleep as the primary or secondary concern on the MYCaW for seeking the IO consultation. The primary concern listed for consultation included integrative approach and overall health (316, 21%), diet advice (232, 15%), pain (221, 14%), stress/anxiety, depression, relaxation (152,10%), neuropathy (144, 10%), natural product information (108, 7%), fatigue (78, 5%) and others such as dry mouth, exercise, hot flashes, appetite loss, memory, nausea and spirituality.
Table 1
Demographic and Clinical Differences of Patients with Sleep Disturbances in Patients Referred for an Ambulatory Integrative Medicine Consultation
Characteristic
|
ESAS 0–10
|
ESAS (SD) < 41
|
ESAS (SD) ≥ 41
|
P-value
|
N = 1520
|
N = 549
|
N = 971
|
Age, Mean (SD)
|
56.64 (12.88)
|
57.39 (13.21)
|
55.64 (12.88)
|
0.012
|
Gender, N (%)
|
|
|
|
0.073
|
Female
|
1067 (70.2)
|
370 (67.4)
|
697 (71.78)
|
|
Male
|
453(29.8)
|
179 (32.6)
|
274(28.22)
|
|
BMI, N (%)
|
|
|
|
0.102
|
< 25
|
607 (41.41)
|
233 (43.71)
|
374 (40.09)
|
|
25–30
|
449 (30.63)
|
164 (30.77)
|
285 (30.55)
|
|
30–35
|
242 (16.51)
|
89 (16.7)
|
153 (16.4)
|
|
> 35
|
168 (11.46)
|
47 (8.82)
|
121 (12.97)
|
|
Cancer, N (%)
|
|
|
|
0.2
|
Breast
|
638 (42.08)
|
223 (40.77)
|
415 (42.83)
|
|
Central Nervous System
|
42 (2.77)
|
19 (3.47)
|
23 (2.37)
|
|
Endocrine
|
40 (2.64)
|
12 (2.19)
|
28 (2.89)
|
|
Gastrointestinal
|
206 (13.59)
|
82 (14.99)
|
124 (12.8)
|
|
Genitourinary
|
151 (9.96)
|
61 (11.15)
|
90 (9.29)
|
|
Gynecologic
|
77 (5.08)
|
27 (4.94)
|
50 (5.16)
|
|
Head/neck
|
110 (7.26)
|
44 (8.04)
|
66 (6.81)
|
|
Heme
|
113 (7.45)
|
30 (5.48)
|
83 (8.57)
|
|
Others
|
13 (0.86)
|
5 (0.91)
|
8 (0.83)
|
|
Sarcoma
|
3 (22.11)
|
16 (2.93)
|
16 (1.65)
|
|
Skin
|
31 (2.04)
|
9 (1.65)
|
22 (2.27)
|
|
Thoracic
|
63 (4.16)
|
19 (3.47)
|
44 (4.54)
|
|
Metastasis, N (%)
|
|
|
0.36
|
No
|
1021 (68.39)
|
360 (66.91)
|
661 (69.21)
|
|
Yes
|
472 (31.61)
|
178 (33.09)
|
294 (30.79)
|
|
Opioid Use*, N (%)
|
|
|
|
0.003
|
No
|
521 (58.21)
|
205 (64.87)
|
316 (54.58)
|
|
Yes
|
374 (41.79)
|
111 (35.13)
|
263 (45.42)
|
|
Steroid Use*, N (%)
|
|
|
|
0.55
|
No
|
7 (88)
|
281 (88.92)
|
507 (87.56)
|
|
Yes
|
107 (11.96)
|
35 (11.08)
|
72 (12.44)
|
|
Stimulant use*, N (%)
|
|
|
|
0.175
|
No
|
862 (96.31)
|
308 (97.47)
|
554 (95.68)
|
|
Yes
|
33 (3.69)
|
8 (2.53)
|
25 (4.32)
|
|
Benzodiazepine use*, N (%)
|
|
|
|
0.001
|
No
|
748 (83.58)
|
281 (88.92)
|
467 (80.66)
|
|
yes
|
147 (16.42)
|
35 (11.08)
|
112 (19.34)
|
|
1 ESAS (SD) < or ≥ 4 = Edmonton Symptom Assessment Scale - sleep disturbance score less than 4 or equal to or greater than 4 |
*Data not available for all patients |
Comparing patients reporting clinically significant SD (ESAS sleep ≥ 4) to those who did not revealed that patients with SD tended to be younger than those without SD (SD = 55.6 vs. No SD = 57.9 years, p = 0.012) (Table 1). Opioid use was also significantly higher in the cohort with clinically significant SD compared to those without clinically significant SD (45.4 vs. 35.1, p = 0.003). There were no other demographic or medical characteristic differences between those with and without clinically meaningful SD. Table 2 shows that the symptom burden was higher in the group with ESAS sleep ≥ 4.
Table 2
Symptom Burden of Patients with Sleep Disturbance
ESAS Variable
|
ESAS 0–10
|
ESAS (SD) < 41
|
ESAS (SD) ≥ 41
|
|
N = 1520
Median (IQR)
|
N = 549
Median (IQR)
|
N = 971
Median (IQR)
|
Anxiety
|
3 (1,5)
|
1 (0,3)
|
3.5 (1,6)
|
Depression
|
1 (0,4)
|
0 (0,2)
|
2 (0,5)
|
Drowsiness
|
2 (0,5)
|
1 (0,3)
|
3 (1,5)
|
Fatigue
|
5 (2,7)
|
3 (1,5)
|
5 (3,7)
|
Memory
|
3 (2,5)
|
2 (1,4)
|
4 (2,6)
|
Nausea
|
0 (0,2)
|
0 (0,0)
|
0 (0,3)
|
Numbness &Tingling
|
0 (0,2)
|
1 (0,3)
|
2 (0,6)
|
Hot Flashes
|
0 (0,4)
|
0 (0,2)
|
1 (0,5)
|
Pain
|
3 (1,6)
|
2 (0,4)
|
4 (1,6)
|
Well-being
|
4 (2,6)
|
2 (1,4)
|
5 (3,6)
|
Shortness of Breath
|
0 (0,2)
|
1 (0,1)
|
1 (0,3)
|
Spiritual Pain
|
0 (0,2)
|
0 (0,1)
|
0 (0,3)
|
Appetite
|
3 (0,5)
|
1 (0,3)
|
4 (1,5)
|
Financial distress
|
0(0,2)
|
1 (0,3)
|
3 (0,5)
|
Dry mouth
|
1 (0,4)
|
3 (1,5)
|
5 (3,7)
|
PHSa
|
15 (9,24)
|
10 (5,16)
|
19 (12,26)
|
PSSb
|
4 (1,8)
|
2 (0,5)
|
6 (2,10)
|
GDSc
|
24 (14,36)
|
14 (8,24)
|
29 (21,41)
|
PROMIS PHd
|
13 (11,15)
|
15 (13,17)
|
12 (10,15)
|
PROMIS MHe
|
13 (11,15)
|
14 (12,16)
|
12 (10,14)
|
1 ESAS (SD) < or ≥ 4 = Edmonton Symptom Assessment Scale - sleep disturbance score less than 4 or equal to or greater than 4 |
aPHS equals the sum of pain, fatigue, nausea, drowsiness, appetite, and shortness of breath scores (total 0–60); bPSS equals the sum of depression and anxiety scores (total 0–20); cGDS equals the sum of pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, sense of well-being, and shortness of breath scores (total 0–90). |
PROMIS10 scores includes a physical health (PROMIS PHd) scale (4–20) and mental health (PROMIS MHe) subscale (4–20). Higher scores represent better mental, physical or global health. |
Abbreviations: ESAS, Edmonton Symptom Assessment Scale; PHS, physical distress score; PSS, psychological distress score; GDS, global distress score. |
Table 3 shows univariate logistic regression analyses of factors associated with clinically significant SD, revealing that all ESAS symptoms, PROMIS, age, BMI, and opioid use were associated with SD. Multivariate analysis of the significant variables revealed ESAS fatigue (adjusted OR 1.16; CI 1.07–1.26, p < 0.01), ESAS pain (adjusted OR 1.07; CI 1.00-1.15, p < 0.05), ESAS hot flashes (adjusted OR 1.14; CI 1.07–1.22, p < 0.001), well-being (adjusted OR 1.33; CI 1.22–1.46, p < 0.001), and PSS (Psychological distress – the sum of ESAS anxiety and depression) (adjusted OR 1.16; CI 1.01–1.11, P < 0.01) remained as factors independently associated with clinically significant SD. Age, BMI, opioid use, symptoms such as nausea, numbness and tingling, shortness of breath were not significant in multivariate model (NB: PHS, GDS, PROMIS PH and PROMIS MH were not included in the final analysis as they are a combination of other variables or overlap significantly).
Table 3
Univariate and Multivariate Models for Factors Associated With Sleep Disturbances
Covariates
|
Univariate
|
|
Multivariate
|
|
Odds Ratio (95% CI)
|
p-value
|
Adjusted Odds Ratio (95% CI)
|
p-value
|
Age
|
0.99 (0.98-1.00)
|
0.012
|
1.00 (0.99–1.01)
|
0.9
|
Gender
|
|
|
NA
|
NA
|
Women vs men
|
0.81 (0.65–1.02)
|
0.073
|
Body mass index
|
|
|
|
|
Overweight 25-29.9 vs Normal Weight
|
1.08 (0.84–1.39)
|
0.537
|
NA
|
NA
|
Obese 30–35 vs Normal Weight
|
1.07 (0.79–1.46)
|
0.663
|
Moderate risk obesity > 35 vs Normal Weight
|
1.60 (1.10–2.33)
|
0.013
|
1.08 (0.60–1.93)
|
0.794
|
Metastasis
|
|
|
|
|
Metastatic vs Non-Metastatic
|
0.90 (0.72–1.13)
|
0.359
|
NA
|
NA
|
Opioid use
|
1.54 (1.16–2.04)
|
0.003
|
0.921 (0.63–1.34)
|
0.67
|
Steroid use
|
1.14 (0.74–1.75)
|
0.549
|
NA
|
NA
|
Stimulant use
|
1.74 (0.77–3.90)
|
0.18
|
ESAS
|
|
|
|
|
Anxiety
|
1.29 (1.24–1.35)
|
< 0.001
|
NA
|
NA
|
Depression
|
1.34 (1.27–1.41)
|
< 0.001
|
Drowsiness
|
1.31 (1.25–1.38)
|
< 0.001
|
Fatigue
|
1.33 (1.27–1.39)
|
< 0.001
|
1.16 (1.07–1.26)
|
0.01
|
Nausea
|
1.21 (1.14–1.28)
|
< 0.001
|
0.97 (0.89–1.07)
|
0.59
|
Numbness & Tingling
|
1.13 (1.09–1.17)
|
< 0.001
|
1.03 (0.97–1.10)
|
0.29
|
Hot Flashes
|
1.22 (1.17–1.27)
|
< 0.001
|
1.14 (1.07–1.22)
|
0.01
|
Pain
|
1.23 (1.18–1.28)
|
< 0.001
|
1.07 (1.00-1.15)
|
0.05
|
Well-being
|
1.47 (1.39–1.55)
|
< 0.001
|
1.33 (1.12–1.46)
|
0.01
|
Shortness of Breath
|
1.22 (1.15–1.29)
|
< 0.001
|
0.96 (0.87–1.06)
|
0.41
|
Spiritual Pain
|
1.34 (1.25–1.43)
|
< 0.001
|
1.10 (0.97–1.23)
|
0.12
|
PSSa
|
1.18 (1.1–1.21)
|
< 0.001
|
1.06 (1.01–1.11)
|
0.01
|
PHSb
|
1.10 (1.0-1.11)
|
< 0.001
|
NA
|
NA
|
GDSc
|
1.08 (1.07–1.09)
|
< 0.001
|
NA
|
NA
|
PROMIS-PHd
|
0.80 (0.77–0.83)
|
< 0.001
|
NA
|
NA
|
PROMIS-MHe
|
0.79 (0.76–0.82)
|
< 0.001
|
aPSS is the sum of depression and anxiety scores (total 0–20) |
bPHS equals the sum of pain, fatigue, nausea, drowsiness, appetite, and shortness of breath scores (total 0–60) |
cGDS equals the sum of pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, sense of well-being, and shortness of breath scores (total 0–90). PROMIS10 scores includes a physical health (PROMIS PHd) scale (4–20) and mental health (PROMIS MHe) subscale (4–20). Higher scores represent better mental, physical or global health. Abbreviations: ESAS, Edmonton Symptom Assessment Scale; PSS, psychological distress score; GDS, global distress score; PROMIS-PH – physical health; PROMIS-MH – mental health.
|
Of 971 patients with ESAS SD ≥ 4, 495 patients used IO services on follow up. As a part of their IO treatment plan, integrative clinical services utilized by patients reporting SD included acupuncture 35% (n = 175), oncology massage 15% ((n = 75), health psychology 5% (n = 24) and meditation 1% (n = 6).