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SLEEP BREATHING PHYSIOLOGY AND DISORDERS •ORIGINAL ARTICLE
New-onset insomnia among cancer patients undergoing
chemotherapy: prevalence, risk factors, and its correlation
with other symptoms
Huong Thi Xuan Hoang
1,2
&Alex Molassiotis
1
&Choi Wan Chan
1
&Thi Huong Nguyen
3
&Van Liep Nguyen
2
Received: 14 December 2018 /Revised: 26 March 2019 /Accepted: 30 March 2019
#Springer Nature Switzerland AG 2019
Abstract
Study objectives Although insomnia is common among cancer patients, its prevalence remains variable, and its risk factors and
correlation with other cancer-related symptoms are not fully explored in the literature. This study aims to determine the preva-
lence and severity of insomnia as well as risk factors and sleep-related symptom clusters in a sample of cancer patients.
Methods A cross-sectional survey was conducted collecting data from 213 cancer patients undergoing chemotherapy (age =
53.1 ± 11.3 years, 60% female). Insomnia was measured using the Insomnia Severity Index, a sleep log, and Actigraph, while
symptoms were assessed using the Memorial Symptom Assessment Scale and the Hospital Anxiety and Depression Scale.
Quality of life was measured with the Functional Assessment of Cancer Therapy—General.
Results Of the participants, 42.8% reported insomnia, with 31.9% of those with insomnia reporting severe insomnia. Insomnia
occurrence and severity were not correlated with the participants’characteristics, cancer-related or treatment-related factors, only
with the participants’anxiety/depression scores. Principal component analysis showed that insomnia, depression, and anxiety
formed a symptom cluster (p< 0.001). There was no difference between sleep parameters measured by Actigraphy in insomnia
and non-insomnia participants.
Conclusion This study demonstrated that the prevalence of insomnia was high and indicated a symptom cluster of insomnia,
depression, and anxiety. Therefore, interventions to reduce this symptom cluster may benefit cancer patients who are trying to
manage these symptoms.
Keywords Insomnia .Depression .Anxiety .Symptom cluster .Cancer .Chemotherapy .Quality of life .Actigraph
Introduction
Insomnia is common among patients undergoing chemother-
apy treatment [1,2]. Previous studies have revealed a wide
range of insomnia prevalence in cancer patients from 8.95 to
93.3% [3–6]. Insomnia can be categorized as either a symp-
tom or a disease [7]. When being categorized as a symptom,
insomnia can be detected by using questionnaires such as the
Insomnia Severity Index and Pittsburgh Sleep Quality Index.
In this study, insomnia is categorized as a symptom based on
an Insomnia Severity Index (ISI) score of 15 or above.
Insomnia generates adverse health problems. Short-term
consequences include somatic problems and psychological
and social issues, while the long-term consequences are more
severe and include cardiovascular disease, obesity, and cancer
[8]. Studies indicated that people with insomnia have a high
risk of developing a wide range of cancers [8–11]. Results of a
recent study stated that insomnia could damage DNA and
lower the body’s ability to repair this, possibly increasing the
risk of developing cancer [12]. Insomnia is a major problem
and significantly associated with poorer quality of life among
cancer patients [13–15]. Furthermore, short sleep duration is
The institutions where work was performed:
1. Vietnam National Cancer Hospital, 43 Quan Su St., Hoan Kiem
district, Hanoi, Vietnam
2. Bach Mai Hospital, 78 Giai Phong St., Dong Da district, Hanoi,
Vietnam
3. Hanoi Oncology Hospital, 42A Thanh Nhan, Hanoi, Vietnam
*Alex Molassiotis
alex.molasiotis@polyu.edu.hk
1
School of Nursing, The Hong Kong Polytechnic University, 11 Yuk
Choi Rd, Hung Hom, Kowloon, Hong Kong SAR
2
Faculty of Nursing, Phenikaa University, Hanoi, Vietnam
3
Hanoi Medical College, Hanoi, Vietnam
Sleep and Breathing
https://doi.org/10.1007/s11325-019-01839-x
associated with mortality in cancer patients [16]. However,
this condition often goes unrecognized because patients do
not report their sleep difficulties [17]. Also, this condition
has received little attention by clinicians and researchers [13,
18–21].
The lack of using standardized questionnaires has resulted in
a wide range of insomnia prevalence in the literature. In addi-
tion, most studies are conducted on small sample sizes with
diverse participant characteristics, which can lead to the inabil-
ity to conduct subgroup analysis and identify potential risk
factors of insomnia [17]. Moreover, few studies have included
an objective measurement to explore specific impaired sleep
patterns or quantify insomnia among participants [13,17].
Although a variety of factors are associated with the develop-
ment of insomnia in cancer patients (e.g., gender, age, cancer
treatments, unpleasant symptoms), mixed results were shown
across studies regarding risk factors and only a limited number
of studies have been conducted to determine if insomnia affects
individuals undergoing chemotherapy [22]. Therefore, more
studies are needed to clarify these gaps in the literature.
Recent studies indicated that insomnia correlates with other
symptoms to form a Bsymptom cluster^(SC). A symptom clus-
ter has been defined as at least two symptoms co-occurring,
being clinically meaningful together, and relating to each other
[23,24]. Different sleep-related symptom clusters (SCs) in can-
cer patients have been reported in the literature, including fa-
tigue, depression, and insomnia [4,13,25]; pain, fatigue, and
insomnia [26–28]; pain, depression, and insomnia in prostate
cancer patients [29]; and depression, anxiety, pain, and insom-
nia in breast cancer patients receiving aromatase inhibitors [30].
However, the correlation between insomnia and other symp-
toms is not fully investigated due to limitations of previous
studies, including not using validated questionnaires to measure
insomnia [4,13,25,26,28,31] and measuring a limited num-
berofsymptoms[4,13,25,26,28,31]. Moreover, the use of
small sample sizes [25,26,28,31] and investigating insomnia
on specific cancer diagnoses limits our ability to generalize
sleep-related SCs in cancer patients [26,28–31].
The objective of this study was to provide evidence of the
prevalence of insomnia with its severity in cancer patients
undergoing chemotherapy, objectively quantify insomnia
among participants, clarify possible risk factors for insomnia,
determine how insomnia impacts the participants' quality of
life, and identify sleep-related symptom clusters.
Methods
Participants
This cross-sectional survey included cancer patients from three
large cancer hospitals in Hanoi, Vietnam, including Vietnam
National Cancer Institution, Bachmai Hospital, and Hanoi
Oncology Hospital. Patients with any cancer diagnosis were
invited if they were undergoing chemotherapy in the participat-
ing hospitals between May and July 2017 using convenience
sampling method. The inclusion criteria were age 20–84 years
old and having a Karnofsky Performance Index ≥80. Patients
were excluded if they had cognitive impairments or psychiatric
disorder (based on clinical records or clinician opinion) as these
conditions would prohibit completion of the questionnaires or
adhere with Actigraph use requirements, history of insomnia
before the diagnosis of cancer (based on clinical records or as
reported by patient) as the study aimed to capture new-onset
insomnia related to cancer and its treatment time, and presence
of a sleep disorder other than insomnia and receiving insomnia
treatment for at least 1 month prior to the study.
Procedures
Data were collected by the principal researcher and two re-
search assistants. Potential participants were approached and
invited to the study on the first day they were admitted to the
hospital. The purpose of the study was explained to them.
Participants who agreed to participate were informed of the
procedures in detail and were provided with the study informa-
tion sheet. Each participant signed the consent form.
Afterwards, they were given the questionnaires to complete.
Before they were discharged from the hospital, the principal
researcher gave them the actigraphy and explained how to use
it. The study obtained ethical approval from the Human Subject
Ethics Board, The Hong Kong Polytechnic University (Hong
Kong SAR), and Hanoi School of Public Health (Vietnam).
Measurements
Insomnia
The Insomnia Severity Index (ISI), a sleep log, and Actigraph
were used to assess insomnia. The ISI is a self-reported question-
naire consisting of seven items. A score of 15 and above indicat-
ed the patient had insomnia; the insomnia severity is interpreted
as follows: moderate insomnia (ISI score of 15 to 21) and severe
insomnia (ISI score of 22 to 28) [32]. This instrument has been
validated and translated into Vietnamese [33]. In this study, the
ISI had high reliability, with Cronbach’sα= 0.92.
Actigraph The wGT3X-BT was used to collect the following
data:
&Total sleep time (TST): the period measured from sleep
onset during nighttime to the final awakening.
&True sleep time (TuST): the period that patient actually
sleeps.
&Wake after sleep onset (WASO): a period of time spent
awake after the sleep onset, calculated by TST minus TuST.
Sleep Breath
&Mid-sleep awakening: the number of awakenings during a
sleep period.
&Sleep efficiency: calculated by dividing TuST (at night) by
TST (at night) multiplied by 100%.
The data were collected in 1-min epochs and scored with
the ActiLife6 version 6.13.3 software using the Cole-Kripker
algorithm, and the sampling rate was 30 Hz. Patients were
asked to wear the Actigraph for three consecutive nights
[34]. This device has been validated in measuring sleep pa-
rameters with Actiwatch 2 (a device that has been validated
previously) among 49 adults in Hong Kong; results from the
study indicated that Actigraph wGT3X-BT could measure
sleep parameters similarly to Actiwatch 2 (Spearman correla-
tions ranging from 0.74 to 0.90) [35].
A sleep log was used to calculate sleep onset and sleep
efficiency in the study participants. The components of the
sleep logs were:
&The time that individuals went to bed
&The time that individuals got out of bed
&Time the Actigraph was removed from the participants’
wrist
&Number of night awakenings
The sleep log helped in identifying misclassified sleep or
wake during the recordings (e.g., motionless activities such as
watching a movie, sitting in a car, which are scored as sleep).
Therefore, participants were asked to complete a 3-day sleep
log during the time they wore the Actigraph.
Other symptom assessments
The validated Vietnamese version of The Memorial Symptom
Assessment Scale (MSAS) (α= 0.79) was used to measure 32
symptoms (Long NH, 2010, Factors related to postoperative
symptoms among patients undergoing abdominal surgery.
Burapha University, unpublished MSc thesis). In this study,
the internal consistency was reported to be high, with the
overall scale having α= 0.92, the psychological subscale
α= 0.80, and the physical subscale α=0.83.
The Vietnamese version of the Hospital Anxiety and
Depression Scale (HADS) was used to measure depression
and anxiety (Long NH, 2010, unpublished MSc thesis). This
scale has seven items measuring anxiety and seven items mea-
suring depression over the past week. In the current study, the
Cronbach’s alpha for the scale was 0.87, for the anxiety sub-
scale was 0.86, and for the depression subscale was 0.76.
Quality of life
The Vietnamese version of Functional Assessment of
Cancer Therapy-General (FACT-G) was used in this
study to assess the quality of life in participants [36].
The questionnaire consists of 27 items and has four sub-
scales: The physical well-being (PWB), the social/family
well-being (SWB), the emotional well-being (EWB), and
the functional well-being (FWB). In this study, the
Cronbach’s alpha for the scale was 0.89 and for the
EBW subscales was 0.78, for the FWB was 0.82, for
the PWB was 0.81, and for the SWB was 0.82.
Data analysis
Data were analyzed using SPSS 20.0. Between-group com-
parisons were performed using Ttests and one-way
ANOVA for continuous variables and χ
2
test for categori-
cal variables. Spearman’scorrelationswereusedtoassess
the association between insomnia and other variables.
Symptom clusters were identified by using principal com-
ponent analysis (PCA). The statistical significance level
was set at p<0.05.
Results
There were 224 patients included in the study; 11 patients
withdrew from the study during the time they wore the
Actigraph, leaving a final sample of 213 participants.
Figure 1depicts the flow of the study’s participant recruit-
ment. The mean age of patients was 53.1 ± 11.3 (min 21,
max 80), with 60% being female. Nearly one-third of the
participants were diagnosed with breast cancer. The vast
majority of the sample was in cancer stage 2 (n= 66,
31%) and stage 3 (n= 62, 29.1%). More details are shown
in Table 1.
Prevalence and severity of insomnia
There were 42.8% of participants (n= 91) reporting insomnia.
Among the participants reporting insomnia, 68.1% reported
moderate insomnia and 31.9% reported severe insomnia.
Risk factors for insomnia
There was no difference between the average ISI score and
insomnia occurrence regarding different gender, age groups,
cancer diagnoses, cancer stages, and chemotherapy regimens
(all p> 0.05). Patients with depression had a significantly
higher ISI score and greater insomnia prevalence than patients
with no depression (mean score = 15.4 vs. 11.36; 60.4% vs.
39.6%, respectively, both p< 0.01), and patients with anxiety
had a higher ISI score and greater insomnia prevalence than
those with no anxiety (mean score = 15.24 vs. 11.61; 63.7%
vs. 36.3%, respectively, both p<0.001) (Table 2). Insomnia
Sleep Breath
occurrence was correlated with anxiety (r= 0.30; p< 0.01)
and depression (r=0.27; p<0.01).
Symptom clusters analysis
Before performing PCA, we excluded the MSAS item of
BDifficulty sleeping^and included the scores for ISI, anxiety,
and depression. PCA was thus conducted on 34 items with
varimax rotation. We determined SCs based on four dimen-
sions: symptom frequency, symptom severity, symptom dis-
tress, and total symptom score. The results showed that across
the insomnia symptom dimensions, anxiety, depression, and
depressive symptoms (worrying, feeling sad) formed a clear
SC (Table 3).
Among participants with insomnia, there were 44 partici-
pants (48.4%) reporting the sleep-related SC and 47 partici-
pants (51.6%) reporting insomnia only. Among participants
reporting the sleep-related symptom cluster, 21 patients
(47.7%) reported three symptoms (insomnia, depression, and
anxiety) and 23 patients (52.7%) reported two symptoms (in-
somnia and depression/anxiety).
The impact of insomnia and sleep-related symptom
cluster on participants' quality of life
Participants experiencing the sleep-related SC had significant-
ly lower QOL scores in comparison with non-insomnia pa-
tients and participants reporting insomnia only (all p<0.001).
They also had worse scores than those without insomnia or
those reporting insomnia only regarding emotional, function-
al, and physical well-being. Participants reporting insomnia
only had significantly poorer scores in comparison with non-
insomnia participants regarding functional well-being
(p< 0.05) (Tables 4and 5).
Sleep parameters measured by Actigraph and sleep
log
According to the results from Actigraphy, insomnia patients
slept 363.75 min (≈6 h) per night on average, and their sleep
efficiency was 89%. Furthermore, their average WASO was
44.2 min with 1.4 times on average being awakened. In com-
parison, the results measured by the participants’sleep log
Fig. 1 Flowchart of study
recruitment
Sleep Breath
reported that these same participants slept 354.82 min (≈6h)
and woke up 1.8 times on average per night.
The results also indicated that there was no significant dif-
ference in sleep parameters measured by Actigraph or sleep
log in terms of TST, TuST, SE, and the number of night awak-
enings and WASO between insomnia and non-insomnia par-
ticipants (Table 6).
Discussion
In the general population, insomnia is one of the most common
sleep disorders with a prevalence that is approximately 10 to
20% [37,38]. The findings of this study showed a high preva-
lence of new-onset complaints of insomnia among cancer pa-
tients undergoing chemotherapy which is double that of the
general population. This prevalence in our study is higher than
previous studies which also used ISI to measure insomnia in
cancer patients [5,29,39]. The difference can be explained by
the characteristics of the samples used. More specifically, Morris
et al. [39] recruited participants who contacted a cancer care
helpline and this could create a selection bias [3]. Davis et al.
[5] recruited advanced cancer patients who participated in a
palliative medicine program and did not report the type of cancer
treatment the participants received [8]. However, two studies
conducted in breast cancer patients and prostate cancer patients
indicated that the chemotherapy period was associated with
more insomnia severity than other times, which is in line with
our findings [3,40]. Furthermore, our sample was drawn from
Vietnamese hospitals, where patients are often treated in over-
crowded clinics, and patients often have to travel long distances
from other regions to attend for treatment in Hanoi. Hence, we
can conclude that the peri-chemotherapy time is a stressful time
that is strongly linked with the development of insomnia com-
plaints in cancer patients as a relatively high percentage of che-
motherapy patients have moderate to severe insomnia complaints.
We did not find a significant difference in insomnia frequen-
cy and severity rates between male and female participants,
participants in different age groups and different cancer diag-
noses or cancer stages (although breast cancer patients and
those receiving taxanes had numerically higher percentage of
insomnia complaints in our sample). These findings are differ-
ent from some of the existing literature. Gender and age were
identified as predisposing factors for insomnia in cancer pa-
tients as well as in the general population [21,41].
Nevertheless, these findings are in line with some recent studies
in cancer patients, whereby there was no significant difference
in insomnia rates between males and females and participants in
different age groups [1,15,39,42,43]. Several large-scale
studies, however, found significant differences in insomnia
prevalence between lung/breast cancer patients compared to
other cancer diagnoses [4,44]. Some potential reasons for the
differences may include the antiemetic drugs used (i.e., dexa-
methasone), tumor biology, and side effects from chemotherapy
(i.e., menopause) [4,44]. In addition, we found participants
reporting depression and/or anxiety had significantly higher
insomnia rates than those with no depression and anxiety.
Table 1 Demographic and clinical characteristics of the participants
(N=213)
Number Percent
Age group
≤45 54 25.4
46–60 104 48.8
>60 55 25.8
Marital status
Single 13 6.1
Married 189 88.7
Divorced/widowed 11 5.1
Hospital
Hospital A 74 34.7
Hospital B 45 21.1
Hospital C 94 44.1
Occupation
Unemployed 30 14.1
Retired 51 23.9
Laborer 80 37.6
Officer 12 5.6
Teacher 11 5.2
Others (medical staff, engineer, freelancer) 29 13.6
Education
Primary school 18 8.5
High school or part of 145 68.1
College or part of 28 13.1
University or higher 22 10.3
Comorbidity
None 177 83.1
Diabetes 7 3.3
Hypertension 13 6.1
Hypertension and diabetes 3 1.4
Degenerative spine 5 2.3
Others (adiposis hepatica, gout, dyslipidemia) 8 3.8
Cancer diagnosis
Breast cancer 59 27.7
Gynecologic cancer 24 11.3
Lung/bronchial cancer 41 19.2
Gastrointestinal cancer 38 17.8
Non-Hodgkin’s lymphoma 30 14.1
Laryngeal cancer 3 1.4
Nasopharyngeal cancer 12 5.6
Brain cancer 2 0.9
Urinary system cancer 4 1.9
Cancer stage
12813.1
26631.0
36229.1
45726.8
Surgical debulking
Optimal 121 56.8
Suboptimal 20 9.4
No information/no surgery 72 33.8
Chemotherapy Regimen
Taxanes 10 2 47.9
Cyclophosphamide and doxorubicin 50 23.5
Oxaliplatin 23 10.8
Gemcitabine 18 8.5
Others (vinorelbine, rituximab, trastuzumab) 20 9.4
Sleep Breath
Studies in the literature also showed consistently that patients
with depression experience insomnia, and insomnia is also a
risk factor for developing depression and anxiety [45]. Anxiety
brings more difficulty in falling asleep resulting in less restor-
ative sleep and nightmares, while depression has been linked to
difficulties maintaining sleep and unwanted early waking up in
the morning as well as nightmares [46,47]. Therefore, the rate
and severity of insomnia may be related to the participants’
distressing symptoms and not only to the participant’scharac-
teristics and cancer diagnosis or treatment variables.
In our study, participants with the sleep-related SC had a
significantly worse global QOL score as well as other subscale
scores (except for the SWB) than those without insomnia, or
those reporting insomnia only. The sleep-related SC seemed to
contribute to lower physical and FWB and poorer EWB of the
patients. The consistent results from previous studies also support
our findings of how insomnia impacts on patients’quality of life
[13–15,19,48,49]. Insomnia caused cancer patients to be less
able to cope with stress and carry on with their daily activities and
had greater difficulty dealing with emotional problems [14,15],
which impaired them physically and emotionally [48,49].
This survey identified insomnia, anxiety, depression, and
depressive symptoms (worrying and feeling sad) all forming a
SC. Since worrying and feeling sad are symptoms of
Table 2 Insomnia Severity Index (ISI) score classification by the demographic and clinical characteristics of the sample
Number ISI score (mean) SD p(for mean score) Insomnia
participant, n=91(%)
p(for insomnia
occurrence)
Gender 0.98 0.54
Male 84 13.3 7.4 36 (39.6%)
Female 129 13.3 6.6 55 (60.4%)
Age groups 0.34 0.058
≤45 55 12.8 6.2 17 (18.7%)
46–60 104 13.0 7.2 45 (49.5%)
> 60 54 14.5 7.3 29 (31.9%)
Cancer diagnosis 0.54 0.26
Breast cancer 59 13.14 6.7 24 (26.4%)
Gynecologic cancer 24 13.92 6.14 11 (12.1%)
Lung/bronchial cancer 41 13.54 7.4 18 (19.8%)
Gastrointestinal cancer 38 11.5 6.47 11 (12.1%)
Non-Hodgkin’s lymphoma 30 14.27 7.82 14 (15.4%)
Laryngeal cancer 3 13.2 6.5 0 (0%)
Nasopharyngeal cancer 12 14.32 7.2 10 (10.9)
Brain cancer 2 12.5 6.7 0 (0%)
Urinary system cancer 4 14.12 7.1 3 (3.3%)
Chemotherapy regiment 0.81 0.87
Taxanes 102 12.85 7.08 43 (47.3%)
Cyclophosphamide and doxorubicin 50 13.62 0.07 20 (22%)
Oxaliplatin 23 13.96 6.49 10 (11%)
Gemcitabine 18 12.83 7.39 8 (8.8%)
Others 20 14.6 7.3 10 (11%)
Cancer stage 0.65 0.81
1 28 12.9 6.2 12 (13.2%)
2 66 13.0 7.2 28 (30.8%)
3 62 14.5 7.3 29 (31.9%)
4 57 13.3 7.0 22 (24.2%)
Depression p< 0.0001 p< 0.0001
No depression 110 11.36 6.3 36 (39.6%)
Depression 103 15.4 7.1 55 (60.4%)
Anxiety p< 0.0001 0.001
No anxiety 113 11.61 7.07 33 (36.3%)
Anxiety 103 15.24 6.50 58 (63.7%)
Sleep Breath
depression [50], we conclude that insomnia, anxiety, and de-
pression form a clear and concrete SC. Previous studies in
different cancer populations also reported similar findings
[51,52]. Results from a systematic review further suggested
a bidirectional relationship between insomnia, depression, and
anxiety [53]. However, previous studies used non-specific
scales to measure symptoms [52] or identified symptom clus-
ters on one dimension of the symptom experience (severity)
[51,53]. It is interesting to see that the correlations between
the three symptoms were low in the correlational analysis,
suggesting that other factors, not examined in this study,
may be part of this relation. However, the strength of this
relationship became moderate-to-strong in the SC analysis.
Hence, anxiety and depression are clearly part of insomnia,
but perhaps not the only parts. This supports the use of selec-
tive serotonin reuptake inhibitors (SSRIs) as an option to im-
prove sleep in this population when anxiety and/or depression
are present, balancing well the possible beneficial effect over
side effects and polypharmacy. However, as SSRIs have mul-
tiple side effects, can be addictive, and there are other factors
contributing to insomnia in cancer patients who often experi-
ence a high symptom burden, they have a place in the man-
agement of insomnia in select patients but should not be con-
sidered as the drug of choice in this population. To our knowl-
edge, our study is the first study to date using standardized
measurements to assess insomnia, depression, and anxiety and
identify SCs based on different dimensions of the symptom
experience that give more concrete evidence that insomnia,
anxiety, and depression form a SC.
The results also demonstrated there was no difference be-
tween sleep parameters measured by Actigraph between in-
somnia and non-insomnia participants. The average true sleep
time for both insomnia and non-insomnia participants was
greater than 6 h per night, and the sleep efficiently was nearly
90%. Interestingly, we found that insomnia participants slept
more than non-insomnia participants (although the difference
was not significant) but they seemed to have lower sleep effi-
ciency and tended to wake up more often. Using both objec-
tive and subjective measurements are being recommended to
evaluate multiple sleep parameters of insomnia [34,54].
However, our study indicates the sleep parameters between
insomnia and non-insomnia participants are related to pa-
tients’experience of insomnia, and how their perceived sleep
quality impacts on their lives rather thanobjective quantifiable
sleep parameters, which cannot incorporate patient percep-
tions. A study also found insomnia frequency is related to
patients’perception about sleep, but not the result from objec-
tive measurements [55].
Recent studies further reported a difference between the
participants perceptionof sleep quality and objective measure-
ments [56,57]. A study by Siberfarb et al. indicated that per-
ceptions of Bpoor^or Bgood^sleep were associated with the
Table 3 Identifying symptom clusters by MSAS, ISI, anxiety, and depression score
Symptom occurrence Symptom severity Symptom distress Total symptom score
SC components rSC components rSC components rSC components r
Anxiety
Depression
Insomnia
Worrying
Feeling sad
0.72
0.77
0.63
0.45
0.4
Anxiety
Depression
Insomnia
Worrying
Feeling sad
0.7
0.78
0.62
0.5
0.44
Anxiety
Depression
Insomnia
0.79
0.61
0.61
Anxiety
Depression
Insomnia
Worrying
0.64
0.73
0.62
0.44
KMO 0.86 0.86 0.87 0.84
χ
2
2339.44 2413.48 2506.89 3358.06
p<0.001 <0.001 <0.001 <0.001
Table 4 Participants’quality of life (QOL) and subscales score. The higher score indicates worse emotional well-being while higher score indicates
better functional/ physical/social well-being and overall QOL
Participants reporting
insomnia only (n=44)
(mean, SD)
Participants reporting the
sleep-related symptom
cluster (n= 47) (mean, SD)
Non-insomnia participants
(n= 122) (mean, SD)
Emotional well-being (EWB) score 9.48 ± 6.12 14.04 ± 5.07 9.1 ± 5.68
Functional well-being (FWB) score 15.52 ± 5.56 11.55 ± 4.32 17.94 ± 6.06
Physical well-being (PWB) score 17.88 ± 5 .76 12.81 ± 4.59 19.73 ± 5.68
Social/family well-being (SWB) score 20.99 ± 6.83 19.35 ± 4.25 21.28 ± 5.87
QOL score 70.06 ± 15.6 53.2 ± 10.37 75.15 ± 16.86
Sleep Breath
amount of delta sleep (the deepest form of sleep) but not with
other objective sleep parameters in cancer patients [58]. This
condition may also be explained by Bthe sleep discrepancy^
referring to underestimation of the total sleep time and over-
estimation of the sleep latency, and wakening after sleep onset
in insomnia patients [59]. Sleep experts define this sleep dis-
crepancy as Bparadoxical insomnia,^experienced by up to
50% of insomnia patients [60]. Considering the above evi-
dence, Actigraphy can measure sleep parameters but it does
not measure the sleep quality as perceived by the patients, and
the latter informs the patient’ssatisfactionwithsleep,aspart
of the experience of insomnia. Furthermore, patients’satisfac-
tion with sleep may impact on their psychological states (anx-
iety/depression) and their quality of life, relating to the co-
occurrence of sleep-related symptoms.
The use of a large sample size, multi-site data collection,
sample diagnostic heterogeneity, and measuring insomnia
both subjectively and objectively are strengths of this study.
However, due to limitations inherent in cross-sectional sur-
veys, the study cannot point out which symptom (anxiety,
depression, and insomnia) occurred first nor how they influ-
ence each other or how these symptoms change over the tra-
jectory of the illness. Our suggestion regarding the lack of
difference between sleep parameters measured objectively be-
tween insomnia and non-insomnia participants should be
interpreted with caution, as participants were required to wear
Actigraph for three nights only, which is relatively short time
and may easily be affected by intra-night variability among
patients. A longer Actigraph measurement may potentially
correlate better with subjective measurements.
In addition, not measuring day time napping is also a lim-
itation of this study. Changes in sleep architecture and mal-
adaptive sleep behavior include prolonged bedtime and day-
time napping that are considered as perpetuating factors con-
tributing to the maintenance of insomnia. Cancer patients, in
Table 5 The impact of insomnia to participants’quality of life (QOL)
(1) (2) Mean difference (1)–(2) Std. error p
Emotional well-being score Non-insomnia participants Participants reporting insomnia only −0.38 0.99 0.70
Participants reporting sleep-related SC −4.94 0.99 < 0.001
Participants reporting insomnia only Participants reporting sleep-related SC −4.56 1.18 < 0.001
Functional well-being score Non-insomnia participants Participants reporting insomnia only 2.4 0.98 < 0.05
Participants reporting sleep-related SC 6.3 0.96 < 0.001
Participants reporting insomnia only Participants reporting sleep-related SC 3.96 1.17 < 0.001
Physical well-being score Non-insomnia participants Participants reporting insomnia only 1.84 0.96 0.057
Participants reporting sleep-related SC 6.92 0.94 < 0.001
Participants reporting insomnia only Participants reporting sleep-related SC 5.1 1.15 < 0.001
Social well-being score Non-insomnia participants Participants reporting insomnia only 0.29 1.01 0.78
Participants reporting sleep-related SC 1.9 0.9 0.054
Participants reporting insomnia only Participants reporting sleep-related SC 1.6 1.21 0.178
Overall QOL score Non-insomnia participants Participants reporting insomnia only 5.09 2.7 0.061
Participants reporting sleep-related SC 21.9 2.6 < 0.001
Participants reporting insomnia only Participants reporting sleep-related SC 16.85 3.2 < 0.001
Table 6 Measuring sleep parameters in patients with insomnia and non-
insomnia
Number Mean (min) SD p
Actigraph
Average true sleep 0.7
Non-insomnia 111 360.01 71.14
Insomnia 84 363.75 85.50
Average total night sleep 0.4
Non-insomnia 111 397.63 74.89
Insomnia 84 407.95 91.51
Average midnight awakenings Time 0.3
Non-insomnia 111 1.25 1.12
Insomnia 84 1.40 1.1
Sleep efficiency 0.9
Non-insomnia 111 91% 8%
Insomnia 84 89% 5%
Waking up after sleep onset 0.7
Non-insomnia 111 37.62 27.46
Insomnia 84 44.20 23.1
Sleep log
Average total sleep time 0.2
Non-insomnia 86 376.39 86.59
Insomnia 56 354.82 120.33
Average midnight awakenings Time 0.54
Non-insomnia 86 1.7 1.15
Insomnia 56 1.83 1.39
Sleep Breath
an attempt to cope with sleeplessness, might try the above
sleep behaviors, but as these become habits, insomnia persists
for long term [21]. In addition, individuals with persistent
insomnia, possibly including those with cancer, tend to en-
gage in sleep-interfering activities in their bedroom for staying
awake rather than inducing sleep (e.g., watching TV, listening
to music, eating, working or reading in bed or the bedroom).
These behaviors tend to weaken the association between cer-
tain normally sleep-inducing stimuli (bed, bedtime, and bed-
room) and sleep [32]. Furthermore, sleep efficiency in our
study may be misrepresented, as there are inherent weak-
nesses in its measurement when there is no standardized time
in bed. Finally, as ISI measures sleep complaints in the past
2 weeks and diagnostic criteria for insomnia disorder require
at least 3 months of sleep complaints [61], the insomnia rates
reported in this study may not meet the full diagnostic criteria
of chronic insomnia.
The results of the study confirm the high prevalence of
insomnia among cancer patients undergoing chemotherapy.
In addition, insomnia and sleep-related SCs significantly re-
duced the patient’s quality of life. Approximately half of the
insomnia burden in the sample was accounted for by the sleep-
related SC while the other half was experienced only insom-
nia. This finding suggests that insomnia is driven both by
shared and unique mechanisms. The results from this study
also indicate that insomnia is a subjective symptom, and the
patients’perception of insomnia or quality of sleep may differ
from the actual objectively measured insomnia severity they
experience. The results highlight a high unmet need in this
population requiring interventions to help patients manage
these symptoms.
Acknowledgments We would like to thank all the participants for their
voluntary contribution to the study. We would like to thank Dr. Nguyen
Thi Hoai Nga, Dr. Le Thanh Duc, Dr. Nguyen Trung Kien, Ms. Quach
Thi Viet Huong, and Ms. Le Thi Tuyen from Vietnam national Cancer
Hospital; Mr. Nguyen Cong Binh, Dr. Le Thi Le Quyen, Dr. Nguyen
Trong Hieu, Dr. Le Thu Ha, Ms. Nguyen Phuong Thao, and Ms.
Nguyen Hong Van from Hanoi Oncology Hospital; Prof. Mai Trong
Khoa and Dr. Nguyen Van Thai from The Nuclear Medicine and
Oncology Center of Bach Mai hospital for their great assistant during
the data collection. We are also thankful to Dr. Paul Lee from the
School of Nursing, The Hong Kong Polytechnic University for providing
the Actigraph devices and helping us analyze data from Actigraph.
Compliance with ethical standards
The study obtained ethical approval from the Human Subject Ethics
Board, The Hong Kong Polytechnic University (Hong Kong SAR), and
Hanoi School of Public Health (Vietnam).
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical approval All procedures performed in this study were in accor-
dance with the ethical standards of the institutional and/or national re-
search committee and with the 1964 Helsinki declaration and its later
amendments or comparable ethical standards. Informed consent was ob-
tained from all individual participants included in the study.
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