Prevalence of Insomnia in an Oncology Patient Population: An Irish Tertiary Referral Center Experience

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  • 1 Department of Medical Oncology, Mater Misericordiae University Hospital, Dublin, Ireland;
  • | 2 Department of Medical Oncology, St. James’s Hospital, Dublin, Ireland;
  • | 3 Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York;
  • | 4 Trinity College Medical School, Dublin, Ireland; and
  • | 5 Department of Psychological Oncology Medicine, St. James’s University Hospital, Dublin, Ireland.

Background: The NCCN Guidelines for Survivorship recommend dedicated sleep assessment. Reported insomnia prevalence in the general Irish population is 6% to 15%. Reported insomnia prevalence internationally among new/recently diagnosed patients with cancer varies from 30.9% to 54.3%. Insomnia prevalence has not been previously quantified in an Irish oncology cohort. Methods: A 40-item questionnaire was prospectively administered to ambulatory patients with cancer aged ≥18 years. Prespecified criteria to define insomnia syndrome combined those of the International Classification of Sleep Disorders, version 1, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The Hospital Anxiety and Depression Scale-Depression/Anxiety (HADS-D/A) was used to screen for potential confounding variables. Results: The response rate to the questionnaire was 87% (294/337). The predominant respondent age group was 55 to 64 years (26%; 77/294), 70.7% were female (208/294), and the most common cancer subtypes were breast (37.4%), colorectal (12.9%), and lung (12.2%). A total of 62% (183/294) of patients reported sleep disturbance after diagnosis, 63% (115/183) reported moderate/severe distress related to this disturbance, and 37% (61/183) reported a significant impact on physical function. Although 33% (98/294) met insomnia syndrome criteria, only 34% (33/98) of these patients had a preexisting history of sleep disturbance. Female sex, age <65 years, cancer subtype, alcohol consumption, and HADS-D/A ≥11 were associated with statistically significant higher odds ratios (OR) of insomnia syndrome. Multivariate analysis identified breast cancer (OR, 3.17; P=.01), age <65 years (OR, 1.8; P=.03), and alcohol consumption (OR, 2.3; P=.005) as independent predictors of insomnia syndrome. Conclusions: Insomnia syndrome prevalence in this cohort is comparable to that reported previously and supports dedicated sleep assessment. This study identifies potentially modifiable risk factors for insomnia and demonstrates additional utility of the HADS score in identifying patients at risk.

Background

The WHO estimates that by 2020, 15.5 million people will experience cancer and global cancer deaths will increase from 7.1 million in 2002 to 11.5 million in 2030.1 Both insomnia and depression often develop as associated psychologic comorbidities and can become chronic issues even in the event of remission. Insomnia is more common among patients with cancer than among the general population2 and those with nonmalignant medical conditions.3,4 Insomnia is a significant independent predictor of reduced patient functioning when function 3 months prior to diagnosis is compared with function 8 weeks postdiagnosis,5 regardless of cancer site or stage. Quantification of insomnia syndrome is important from a morbidity and quality-of-life perspective, but also because of potential interaction with mortality.6 Among the general population, emerging epidemiologic data suggest higher rates of all-cause mortality for individuals with shortened duration of sleep.711 Insomnia is equally associated with higher mortality rates among cardiology patients12,13 and poorer prognosis among patients with chronic diseases.14 In addition, increased standardized incidence rates of liver and lung cancer have been noted among patients with newly diagnosed sleep disorders.15

Although sleep disturbance is commonly reported among patients with cancer,16 data regarding exact prevalence of insomnia syndrome distinct from sleep disturbance are more limited. One of the challenges in interpreting the literature is poor differentiation between symptoms of insomnia and insomnia syndrome. A variety of screening tools have been used across heterogeneous patient groups17 (supplemental Appendix 1 and eTable 1; available with this article at JNCCN.org), and often long-term follow-up data are not available.

Reported insomnia prevalence among patients newly diagnosed with or recently treated for cancer varies from 30.9% to 54.3%.1822 Similarly high rates of insomnia symptoms, 23% to 44%,2327 have been identified up to 5 years after initiation of adjuvant therapy for cancer, and insomnia continues to remain a significant issue among long-term survivors (>5 years),28,29 illustrating the chronicity of this sleep disturbance. Sleep disturbance has been reported in nearly 50% of patients with advanced cancer30 and is associated with increased pain, depression, anxiety, and a worse sense of well-being.31 At a practical level, patients may be reluctant to report their symptoms due to the belief that sleep disturbance is a natural consequence of their diagnosis, and medical staff may be reluctant to pose relevant questions due to lack of expertise in managing these symptoms. Despite this, 25% to 50% of all psychotropic prescriptions written for patients who have cancer are for hypnotics.32,33

To our knowledge, insomnia prevalence has not previously been quantified in an Irish oncology cohort. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Survivorship34 recommend dedicated sleep assessment, reflecting acknowledgment of the increased insomnia prevalence among patients with cancer, and its association with increased symptom distress scores. The Irish Sleep Apnoea Trust reports that insomnia affects 6% to 15% of the general Irish population; a multinational European study in the general population that included Ireland reported a rate of 7% of severe insomnia, with higher rates among women than men.35

Methods

We conducted a prospective nonblinded questionnaire-based study over a 6-month period from June to December 2014 at a single tertiary-level Irish hospital, in collaboration with the psycho-oncology service to ensure that any significant mental health issues identified through study participation were dealt with in a sensitive and expeditious manner.

Institutional ethical board approval was obtained and a 40-item questionnaire (supplemental eAppendix 1) was prospectively administered to ambulatory patients with cancer attending either the oncology day ward or the outpatient clinic. Inclusion criteria were confirmed cancer diagnosis, age ≥18 years, ability to read and complete a questionnaire, and capacity to provide informed consent. All eligible patients were invited to participate. After providing consent, participants completed a self-report questionnaire encompassing demographic and clinical data, patient-reported functional status,36,37 and the Hospital Anxiety and Depression Scale (HADS).38 Inpatients were excluded from this study. The primary study endpoint was assessment of the prevalence of insomnia syndrome among the ambulatory patient cohort. Secondary endpoints included investigation of predisposing, precipitating, and perpetuating factors for insomnia syndrome.

Data Reduction

Our prespecified criteria for insomnia syndrome combines those of the International Classification of Sleep Disorders, version 1,39 and the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition; DSM-IV)40 and were described by Savard and Morin17 in their comprehensive review of insomnia among patients with cancer. The 4 criteria used were (1) difficulty initiating sleep or difficulty maintaining sleep, (2) sleep disturbance occurring ≥3 nights per week, (3) sleep disturbance causing significant impairment of daytime functioning or severe distress, and (4) sleep disturbance present ≥1 month. Patients who met all 4 criteria were coded as having insomnia syndrome. Impact on daytime functioning and distress was self-reported and not objectively assessed. Those who met some but not all 4 criteria were coded as having insomnia symptoms.

Assessments

The 40-item questionnaire (supplemental eAppendix 1) was designed to incorporate the sleep-related components of the Hamilton Depression Rating Scale,41 quantify duration and nature of sleep disturbance, evaluate sleep hygiene in the context of well-described precipitating and perpetuating factors for sleep disturbance,17 and evaluate patients’ experiences of inquiries regarding sleep disturbance and preferences for intervention.

The Patient-Reported Functional Status (PRFS) is a patient-completed measure of performance status that represents the activities/function domain of the Patient-Generated Subjective Global Assessment (PG-SGA) measure.37,42 It is based on the ECOG scale but is expressed in lay terms.36,43 In contrast to the ECOG scale, it is a 5-point scale in which 0 is “normal with no limitations,” 1 is “not my normal self, but able to be up and about with fairly normal activities,” 2 is “not feeling up to most things, but in bed or chair less than half the day,” 3 is “able to do little activity and spend most of the day in bed or chair,” and 4 is “pretty much bedridden, rarely out of bed.”

HADS38 was used to screen for depression (HADS-D) and anxiety (HADS-A) as potential confounding variables. This measure is frequently used among patients with cancer because it is characterized by an absence of somatic symptoms that may be attributable to either medical or psychiatric conditions. HADS is a 14-item questionnaire and each item has a Likert response scale. Final scores are cumulative, with higher scores suggestive of a case. The cutoff value used for cases was a score of ≥11, consistent with the original authors’ description of the scale and with an indication of moderate severity of either anxiety or depression. We are aware that lower values have been suggested in some more recent literature.44 We used this scale to assess for anxiety and depression as 2 separate variables, as proposed by its original authors, rather than a combined score, which has been proposed elsewhere.44 The validity of separating the 2 subscales in patients with cancer was confirmed in 568 patients by Moorey et al45; use of HADS to detect anxiety and depressive states separately in a 2-factor model has also been found to be invariant across sex or disease phase among patients with cancer.46

Data Analysis

All patients who accepted and at least partially completed the questionnaire were included for the purpose of data analysis. To explore clinical and demographic factors potentially associated with insomnia syndrome, we first performed univariate logistical regression analysis on factors such as sex, age, alcohol consumption, HADS-D and HADS-A scores, cancer subtypes, smoking status, caffeine and corticosteroid use, and surgery. All variables that had a P value of <.05 were then entered into a multivariate logistical regression model to identify potential independent predictors of insomnia syndrome.

Results

Demographic and Clinical Characteristics

Of the 337 patients invited to participate, 87% consented to study inclusion (n=294); 12 declined without explanation, 15 were too unwell to participate, 8 declined due to lack of appropriate reading aids, 4 declined due to language difficulties, and 4 declined due to time constraints.

Table 1 lists the baseline demographics, cancer subtype, and treatment modalities received by our patient cohort. The predominant respondent age group was 55 to 64 years (n=77; 26%), and 70.7% (n=208) of respondents were female. Consistent with an ambulatory patient cohort, 81.3% (n=239) of patients had a self-reported performance status36 of 0 to 1. Breast, colorectal, and lung were the most common cancer subtypes represented. Most respondents (n=245; 83.3%) were receiving active chemotherapy, slightly more than one-half (56.6%) had undergone oncologic surgery, and 17% (n=50) had been hospitalized in the month prior to completion of our questionnaire.

Table 1.

Patient Demographic and Clinical Characteristics

Table 1.

Insomnia Syndrome

A total of 62% (n=183) of patients reported sleep disturbance after their diagnosis; of these, 37% (n=67) reported a significant impact on physical function and 63% (n=115) reported moderate to severe distress relating to this disturbance. Concerningly, 19% (n=34) indicated that their sleep disturbance had impacted their ability to tolerate further treatment and 24% (n=44) felt it had impacted their cognition.

Among the entire cohort, 33% (n=98) of patients met all 4 prespecified criteria for insomnia syndrome (ie, they reported difficulty initiating sleep or difficulty maintaining sleep, sleep disturbance occurring ≥3 nights per week, sleep disturbance causing significant impairment of daytime functioning or severe distress, and sleep disturbance present ≥1 month). Only 34% (n=33) of patients who met insomnia syndrome criteria had any preexisting history of sleep disturbance. Of the patients who did not meet insomnia syndrome criteria, 45% (n=89) had ≥1 of the 4 critical diagnostic symptoms: 69 had 1 symptom, 19 had 2 symptoms, and 1 patient had 3 symptoms.

Among the entire cohort, 6% (n=18) of patients had a HADS score of ≥11, with 10 of these patients having both HADS-D and HADS-A ≥11. The patients with a HADS score of ≥11 were contacted individually regarding potential referral to psycho-oncology based on patient preference, in addition to further clinical assessment; 3 were already attending psycho-oncology, 3 requested referral, and 12 patients declined referral. Patients’ treating physicians were informed of high HADS-D/A scores so that these patients’ psychologic status could be more closely monitored with additional opportunities for referral if required.

By univariate analysis, female sex, age <65 years, cancer subtype, alcohol consumption, and HADS-D/A score ≥11 were associated with statistically significant higher odds ratios of insomnia syndrome (Table 2). Multivariate analysis demonstrated 3 independent predictors of insomnia syndrome: breast cancer (odds ratio [OR], 3.17; P =.01), age <65 years (OR, 1.8; P=.03), and alcohol consumption (OR, 2.3; P=.005) (Table 3).

Table 2.

Univariate Analysis

Table 2.
Table 3.

Multivariate Analysis

Table 3.

Sleep Hygiene

Alcohol consumption, low level of physical activity, high caffeine intake, and electronic stimulus prior to going to bed are all recognized as factors that impact sleep negatively.47

At the time of study, 67.4% (n=198) of patients reported alcohol consumption; 36 patients did not complete further questions regarding regularity of alcohol consumption. Of those who did respond to more detailed questions regarding alcohol consumption, 76% (n=196) reported alcohol consumption no more than once per week and 24% (n=62) more than once per week. Overall, 12% (n=34) of all respondents had used alcohol on occasion as a sleep aid and 45% (n=132) of patients were unaware that alcohol consumption could impact sleep. Notably, among the 98 patients with insomnia syndrome, 80% (n=79) reported alcohol consumption at the time of study participation.

A total of 81.3% (n=239) of the entire study population self-reported a performance status of 0 to 1, and consequently it is unsurprising that more than one-half (54%; n=159) of the patients reported physical activity lasting at least 30 minutes more than once per week. A minority of patients in the entire study population engaged in meditation (7%; n=22), yoga (6%; n=19), mindfulness (5%; n=14), Pilates (2%; n=5), and acupuncture (1%; n=3).

Of the 98 patients with insomnia syndrome, 98% (n=79) drank caffeine in some form every day, and significantly more than one-half reported drinking caffeine-containing beverages after 6:00 pm; 9.8% (n=10) reported drinking caffeine after 10:00 pm.

In terms of electronic stimuli, in the hour before bed, 85% (n=84) of patients with insomnia syndrome watched television and 89% (n=87) reported either television or computer use.

Previous Inquiry and Preferences for Intervention

Among all respondents, 62% (n=182) thought that cancer management should incorporate sleep assessment, but only 34% (n=100) recalled having such an assessment. Of the patients who recalled previous inquiries about sleep disturbance, 27% had been asked by their oncologist, which was comparable to the 27% who reported similar inquiries from their general practitioner. Other patients reported being questioned by the oncology nurse (18%), palliative care team (15%), and palliative care nurses (5%). Regarding preferred intervention, respondents were asked to indicate on a Likert scale their degree of comfort with a variety of interventions; a score of 10 indicated that patients would be extremely comfortable with the relevant intervention, whereas a score of 1 implied indifference. Written information (mean score, 5.96; 95% CI, 5.52–6.41), mindfulness therapy (mean score, 4.87; 95% CI, 4.43–5.32), and a once-off lecture on sleep management (mean score, 4.82; 95%, CI, 4.38–5.26) were favored over pharmacologic intervention (ie, sleeping tablets) (mean score, 4.58; 95% CI, 4.16–5.00). Respondents allocated a mean score of 3.92 (95% CI, 3.52–4.32) to an individual session with a psychiatrist/psychologist and a mean score of 4.12 (95% CI, 3.71–4.52) to cognitive behavioral therapy (CBT). A series of lectures or group workshops on sleep management were the least popular, with mean scores of 3.57 (95% CI, 3.20–3.95) and 3.54 (95% CI, 3.16–3.92), respectively. This pattern of patient preference is further corroborated by evaluating the frequency distribution of the scores allocated to each of the interventions (supplemental eTable 2).

Discussion

Insomnia is a significant problem for patients with cancer at all stages of their treatment trajectory, with an impact on multiple functional domains and a deleterious effect on overall quality of life.48 Improving sleep outcomes is significantly related to improvements in quality of life and reduced daytime fatigue.49 Data also suggest an association between rest/activity cycles and both response to treatment and overall survival.6

Insomnia incidence in this Irish cohort of patients with cancer was more than twice that of the general population. It was comparable to findings reported elsewhere and would justify dedicated sleep assessment.24 One-third of our patient cohort met criteria for insomnia syndrome and most had no preexisting history of sleep disorder, suggesting causality with both their diagnosis and treatment. Similar to the findings of Palesh et al50 among 826 patients attending oncology private practice groups in the United States, younger age and female sex represent significant risk factors for insomnia syndrome in our Irish cohort. Both these factors and cancer subtype are obviously nonmodifiable but should lower the threshold of clinical vigilance to screen for significant sleep disorders. Two-thirds of patients in our study drank alcohol no more than once per week; concerningly, >10% of these patients had occasionally used alcohol as a sleep aid and nearly half were unaware it could impact sleep patterns detrimentally. Alcohol consumption is a modifiable risk factor that independently predicts insomnia syndrome in our patient cohort.

Insomnia is often described as existing within a symptom cluster with close association to anxiety, depression, and fatigue.5154 Preexisting psychologic morbidity is also a consideration, particularly among patients with breast cancer.55,56 In our cohort, HAD score of ≥11 increased the OR of insomnia syndrome, demonstrating additional utility of this scale. It also allowed us to identify and expeditiously refer these patients to our psycho-oncology colleagues.

One limitation of our study was that although our questionnaire integrated components of previously validated scales, the questionnaire itself has not been externally validated. Equally, our study used a point prevalence self-reported questionnaire without objective measures of sleep disturbance and insomnia. Polysomnography is considered the gold standard for measurement, but it is cumbersome for patients who have cancer, and consequently is used in few studies.54,57 Our study also relied on self-report of impact of sleep disturbance on both physical and cognitive function.

Pharmacologic intervention in the form of hypnotics is the most commonly prescribed intervention for insomnia58 yet more specific data in terms of efficacy among patients with cancer is required.59 In our cohort, patient preference was for nonpharmacologic interventions ranging from written information, to mindfulness therapy, to once-off lectures and CBT. In noncancer groups, CBT for insomnia (CBT-I) consisting of 4 key components—sleep restriction, stimulus control, cognitive restructuring, and relaxation training—is the most effective and durable treatment for insomnia. It has also been validated among patients with cancer in several randomized trials.49,6063

In the current setting of restricted resources, alternative strategies to individual CBT-I need to be evaluated. Group therapy as compared with individual CBT has been shown to be effective in patients without cancer both as an early intervention and for chronic insomnia.64,65 Equally, computer-based interventions,66 telephone-based consultations,67 and self-help strategies68 have all demonstrated efficacy in noncancer populations. Data in patients with cancer are more limited but remain encouraging and potentially more immediately applicable. Ritterband et al69 investigated the feasibility of an internet-based CBT tool, and reported that the intervention group had greater improvements in insomnia severity, sleep efficiency, sleep onset latency, and sleep quality compared with the control group. Savard et al70 demonstrated the feasibility of a self-help program for treating insomnia comorbid with cancer, with statistically and clinically meaningful improvements in numerous sleep variables and overall quality of life. The investigators subsequently conducted a 3-arm randomized controlled trial comparing video-based CBT versus professionally delivered CBT versus no treatment in 242 patients with breast cancer.71 Although face-to-face delivery was associated with superior remission rates and improvements in overall insomnia severity, both CBT groups reported clinically meaningful improvements in sleep variables compared with the control group. Less resource-intensive models of CBT-I delivery represent an important option, particularly in centers without dedicated psycho-oncology services, and require further exploration.

Sleep hygiene is considered ineffective as monotherapy, but does promote behaviors that facilitate sleep in an attempt to limit those that contribute to insomnia.61 In the trial by Dirksen and Epstein,61 the control group received sleep education and information on sleep hygiene. Even addressing sleep disturbances at this low level of complexity seemed to produce meaningful improvements in sleep patterns. Our cohort demonstrated lack of awareness regarding sleep hygiene and exhibited behaviors that have the potential to perpetuate sleep disturbance and ultimately promote the development of insomnia. They also reported willingness to receive written information regarding this topic, which represents a relatively low-cost opportunity for intervention in the absence of dedicated CBT-I programs that remain the gold standard.

Conclusions

It is essential that the long-term goal of research on sleep disturbances in patients with cancer focuses on treatment approaches that will improve quality of life both during treatment and after completion.48 Of particular importance were our findings that the study patients reported being amenable to questioning regarding their sleep patterns, and that most thought that cancer care should incorporate dedicated sleep assessment. Based on results of this study, we are developing a patient education leaflet on sleep management for distribution in all major Irish oncology centers that will incorporate and reinforce our findings.

See page 1738 for related commentary.

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    Dirksen SR, Epstein DR. Efficacy of an insomnia intervention on fatigue, mood and quality of life in breast cancer survivors. J Adv Nurs 2008;61:664675.

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    Berger AM, Kuhn BR, Farr LA, et al. . One-year outcomes of a behavioral therapy intervention trial on sleep quality and cancer-related fatigue. J Clin Oncol 2009;27:60336040.

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    Fiorentino L, McQuaid JR, Liu L, et al. . Individual cognitive behavioral therapy for insomnia in breast cancer survivors: a randomized controlled crossover pilot study. Nat Sci Sleep 2010;2:18.

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    Jansson M, Linton SJ. Cognitive-behavioral group therapy as an early intervention for insomnia: a randomized controlled trial. J Occup Rehabil 2005;15:177190.

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    Verbeek IH, Konings GM, Aldenkamp AP, et al. . Cognitive behavioral treatment in clinically referred chronic insomniacs: group versus individual treatment. Behav Sleep Med 2006;4:135151.

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    Vincent N, Lewycky S. Logging on for better sleep: RCT of the effectiveness of online treatment for insomnia. Sleep 2009;32:807815.

  • 67.

    Bastien CH, Morin CM, Ouellet MC, et al. . Cognitive-behavioral therapy for insomnia: comparison of individual therapy, group therapy, and telephone consultations. J Consult Clin Psychol 2004;72:653659.

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    Mimeault V, Morin CM. Self-help treatment for insomnia: bibliotherapy with and without professional guidance. J Consult Clin Psychol 1999;67:511519.

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    Ritterband LM, Bailey ET, Thorndike FP, et al. . Initial evaluation of an Internet intervention to improve the sleep of cancer survivors with insomnia. Psychooncology 2012;21:695705.

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    Savard J, Villa J, Simard S, et al. . Feasibility of a self-help treatment for insomnia comorbid with cancer. Psychooncology 2011;20:10131019.

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    Savard J, Ivers H, Savard MH, et al. . Is a video-based cognitive behavioral therapy for insomnia as efficacious as a professionally administered treatment in breast cancer? Results of a randomized controlled trial. Sleep (Basel) 2014;37:13051314.

    • Crossref
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Submitted October 14, 2019; accepted for publication June 26, 2020.

Author contributions: Study concept and design: Harrold, Idris, Keegan, Collier, Kingston, O’Dwyer, Cuffe. Patient psycho-oncology support during the study: Collier, Kingston, O’Dwyer. Data collection: Harrold, Idris, Keegan, Corrigan, M. O’Donnell, Lim, Duffy, Cuffe. Data analysis and interpretation: Harrold, Idris, Keegan, Corrigan, Teo, Cuffe. Manuscript preparation: All authors. Critical review: Harrold, Idris, Keegan, Teo, D.M. O’Donnell, Kennedy, Sukor, Grant, Gallagher, Collier, Kingston, O’Dwyer, Cuffe.

Previous presentation: This study was presented as a poster at ESMO 2016 Congress; October 7–11, 2016; Copenhagen, Denmark (Ann Oncol 2016;27[Suppl]:Abstract 4209), and as an oral presentation at the 2016 Irish Society of Medical Oncology Meeting; January 30; Dublin, Ireland.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Disclaimer: All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration. All participants signed informed consent prior to their inclusion in this study.

Correspondence: Emily C. Harrold, MD, Department of Medical Oncology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland. Email: emilyharrold@mater.ie

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    Savard J, Ivers H, Savard MH, et al. . Is a video-based cognitive behavioral therapy for insomnia as efficacious as a professionally administered treatment in breast cancer? Results of a randomized controlled trial. Sleep (Basel) 2014;37:13051314.

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    • Export Citation
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