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Sleep-Wake Functioning Along the Cancer Continuum: Focus Group Results From the Patient-Reported Outcomes Measurement Information System (PROMIS™)
Abstract
Cancer and its treatments disturb sleep-wake functioning; however, there is little information available on the characteristics and consequences of sleep problems associated with cancer. As part of an effort to improve measurement of sleep-wake functioning, we explored the scope of difficulties with sleep in a diverse group of patients diagnosed with cancer.
We conducted 10 focus groups with patients recruited from the Duke University tumor registry and oncology/hematology clinics. Separate groups were held with patients scheduled to begin or currently undergoing treatment for breast, prostate, lung, colorectal, hematological, and other cancer types and with patients who were in posttreatment follow-up. The content of the focus group discussions was transcribed and analyzed for major themes by independent coders.
Participants not only reported causes of sleep disturbance common in other populations, such as pain and restless legs, but they also reported causes that may be unique to cancer populations, including abnormal dreams, anxiety about cancer diagnosis and recurrence, night sweats, and problems with sleep positioning. Many participants felt that sleep problems reduced their productivity, concentration, social interactions, and overall quality of life. Many also shared beliefs about the increased importance of sleep when fighting cancer.
The findings underscore the need for interventions that minimize the negative impact of cancer and its treatments on sleep. This study will inform efforts now underway to develop a patient-reported measure of sleep-wake functioning that reflects the breadth of concepts considered important by patients with cancer.
... sleep constructs -sleep disturbance (ie, trouble sleeping, poor sleep quality) and sleep-related impairment (ie, daytime fatigue, cognitive and behavioral issues). 2 In this paper, we focus on the PROMIS sleep disturbance measure, particularly the 8b short form. 3 The PROMIS measures of sleep disturbance have been used to understand symptoms associated with diseases (eg, cancer, multiple sclerosis) and injuries 4,5 and to evaluate intervention effects on sleep. [6][7][8][9][10] Therefore, it is important to continue gathering validity evidence for these measures. ...
... Patients themselves might also contribute to the underassessment of sleep disturbances. Despite many patients expressing concerns about sleep, these problems are not always discussed with health professions during oncology appointments [93]. Patients do not usually report their sleep problems to health professions because in general it is seen as less significant than the cancer [94]. ...
Patients with advanced cancer experience multiple symptoms, with fluctuating intensity and severity during the disease. They use several medications, including opioids, which may affect sleep. Sleep disturbance is common in cancer patients, decreases the tolerability of other symptoms, and impairs quality of life. Despite its high prevalence and negative impact, poor sleep quality often remains unrecognized and undertreated. Given that sleep is an essential aspect of health-related quality of life, it is important to extend both the knowledge base and awareness among health care providers in this field to improve patient care. In this narrative review, we provide recommendations on sleep assessment in patients with advanced cancer and highlight cancer-related factors that contribute to insomnia. We also present direct implications for health care providers working in palliative care and for future research.
... Qualitative Methods-Several studies utilized qualitative methods to examine sleep in patients with PCa. Flynn et al. used focus groups to discuss sleep issues contributing to sleep-wake functioning in patients with multiple cancers, including PCa. 85 Factors contributing to poor sleep included anxiety, as well as physical factors (e.g., hot flashes, restless legs, bowel control or urination). Consequences of poor sleep included daytime sleepiness/tiredness and fatigue. ...
Objective/Background
To examine the impact of prostate cancer (PCa) on sleep health for patients and caregivers. We hypothesized that sleep disturbances and poor sleep quality would be prevalent among patients with PCa and their caregivers.
Patients/Methods
A systematic literature search was conducted according to the Preferred Reporting Items for a Systematic Review and Meta-analysis guidelines. To be eligible for this systematic review, studies had to include: (1) patients diagnosed with PCa and/or their caregivers; and (2) objective or subjective data on sleep. 2,431 articles were identified from the search. After duplicates were removed, 1,577 abstracts were screened for eligibility, and 315 underwent full-text review.
Results and Conclusions
Overall, 83 articles met inclusion criteria and were included in the qualitative synthesis. The majority of papers included patients with PCa (98%), who varied widely in their treatment stage. Only 3 studies reported on sleep among caregivers of patients with PCa. Most studies were designed to address a different issue and examined sleep as a secondary endpoint. Commonly used instruments included the Insomnia Severity Index and European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaires (EORTC-QLQ). Overall, patients with PCa reported a variety of sleep issues, including insomnia and general sleep difficulties. Both physical and psychological barriers to sleep are reported in this population. There was common use of hypnotic medications, yet few studies of behavioral interventions to improve sleep for patients with PCa or their caregivers. Many different sleep issues are reported by patients with PCa and caregivers with diverse sleep measurement methods and surveys. Future research may develop consensus on validated sleep assessment tools for use in PCa clinical care and research to promote facilitate comparison of sleep across PCa treatment stages. Also, future research is needed on behavioral interventions to improve sleep among this population.
... Poor sleep quality and irregular sleep habits are also associated with the development of chronic diseases, including stroke, cancer, diabetes mellitus [7,8], and with overall mortality [9]. Sleep disturbances also affect quality of life and have consequences on work productivity [10], fatigue [11], trouble keeping up with social activities, and mood disturbance [12]. ...
Purpose:
Sleep quality in relation to anatomic site among colorectal cancer (CRC) patients is not well understood, though discerning the relationship could contribute to improved survivorship care.
Methods:
We ascertained sleep quality (Pittsburgh Sleep Quality Index) and other personal characteristics within an ongoing population-based study of CRC patients identified through a cancer registry (N = 1453). Differences in sleep quality by CRC site were analyzed using chi-square and ANOVA tests. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of tumor site with sleep quality concerns, adjusting for patient attributes and time since diagnosis.
Results:
Sleeping problems were reported by 70% of CRC patients. Overall, participants with rectal (vs. colon) cancer were more likely (OR (95% CI)) to report general trouble sleeping (1.58 (1.19, 2.10)). Rectal cancer patients were also more likely than colon cancer patients to report changes in sleep patterns after cancer diagnosis (1.38 (1.05, 1.80)), and trouble sleeping specifically due to getting up to use the bathroom (1.53 (1.20, 1.96)) or pain (1.58 (1.15, 2.17)), but were less likely to report trouble sleeping specifically due to issues with breathing/coughing/snoring (0.51 (0.27, 0.99)).
Conclusion:
Overall, rectal cancer patients were more likely to have sleep complications compared to colon cancer patients. This suggests sleep-focused survivorship care may be adapted according to CRC site to ensure patients receive appropriate support.
... Hematopoetik kök hücre nakli (HKHN) yapılan hasta sayısının artmasıyla birlikte erken ve geç dönem komplikasyonlarda da artış görülmeye başlamıştır. Bu komplikasyonlar hastalarda sosyal, ekonomik, fizyolojik ve psikolojik sorunlara yol açabilmektedir (1)(2)(3). HKHN yapılan hastalarda görülen önemli sorunlardan birisi de uyku kalitesinin bozulmasıdır. Nakil sonrası hastaların önemli bir kısmının uyku sorunları yaşadığını ve özellikle nakilden sonraki ilk 100 günde görüldüğünü belirten çalışmalar vardır (4-6). ...
Objective:Hematopoietic stem cell transplantation (HSCT) might have early and late complications. One of the major problem is sleep disturbances. The aim of this study is to evaluate sleep quality of the patients who are undergoing hematopoietic stem cell transplantation, prevent the problems that may be faced according to outcome of the research and determine the nursing approaches in order to prevent for problems.Materials and Methods:This prospective study was performed in the adult bone marrow transplantation unit. The study sample consisted of 59 patients. The Pittsburg Sleep Quality index (PSQI) form was completed by the researchers. For statistical analysis, IBM SPSS Statistics 22 program used.Results:A total of 59 patients 44.1% were female, 55.9% were male. According to the distribution of PSQI total scores on the administration day 42.4%, first week 50.8% on the second week 50.8% of the patients had poor sleep quality. After the discharge, PSQI total scores indicated that at the first week 32.2%, second week 27.1% and the third week 25.4% of the patients had poor sleep quality. During the hospitalization period poor sleep quality significantly increased.Conclusion:It was observed that sleep quality was significantly impaired during the period of HSCT. For this reason, it is important to get information on the history of sleep quality and clinical follow-up by nurses when transplant patients are admitted to the clinic. Improving the care plan for the nurses on the sleep problems can positively affect the quality of life of the patients.
... pain, fatigue, emotional distress, physical function, social functioning) that are relevant across chronic illnesses including cancer [3]. These study instruments are available either on paper or electronically (ePROs) and have been validated in patients with cancer [2][3][4][5][6]. PROMIS assessments are ideal to assess HRQL as they are designed to have a low response burden for patients without sacrificing precision and quality for brevity [3]. ...
Objective
The Patient-Reported Outcomes Measurement Information System (PROMIS®) Network has developed a comprehensive repository of electronic patient reported outcomes measures (ePROs) of major symptom domains that have been validated in cancer patients. Their use for patients with gynecologic cancer has been understudied. Our objective was to establish feasibility and acceptability of PROMIS ePRO integration in a gynecologic oncology outpatient clinic and assess if it can help identify severely symptomatic patients and increase referral to supportive services.
Methods
English-speaking patients with a confirmed history of gynecologic cancer completed PROMIS ePROs on iPads in the waiting area of an outpatient gynecologic oncology clinic. Symptom scores were calculated for each respondent and grouped using documented severity thresholds. Response data was compared with clinicopathologic characteristics across symptom domains. Severely symptomatic patients were offered referral to ancillary services and asked to complete post-exposure surveys assessing acceptability of the ePRO.
Results
Of the 336 patients who completed ePROs, 35% had active disease and 19% had experienced at least one disease recurrence. Sixty-nine percent of the cohort demonstrated moderate to severe physical dysfunction (60%), pain (36%), fatigue (28%), anxiety (9%), depression (8%), and sexual dysfunction (32%). Thirty-nine (12%) severely symptomatic patients were referred to services such as psychiatry, palliative care, pain management, social work or integrative oncology care. Most survey respondents identified the ePROs as helpful (78%) and easy to complete (92%).
Conclusions
Outpatient PROMIS ePRO administration is feasible and acceptable to gynecologic oncology patients and can help identify severely symptomatic patients for referral to ancillary support services.
... Savard [8,9] and Fiorentino [10] both reported that 30-50% of all cancer patients report sleep disturbance as a problem related to nocturia, night sweat and pain. If the sleep is disturbed, it will also have a broad, negative impact on cognitive and physiological functions [11,12]. Patients quality of life (QoL) may therefore be severely affected [13]. ...
... Savard [8,9] and Fiorentino [10] both reported that 30-50% of all cancer patients report sleep disturbance as a problem related to nocturia, night sweat and pain. If the sleep is disturbed, it will also have a broad, negative impact on cognitive and physiological functions [11,12]. Patients quality of life (QoL) may therefore be severely affected [13]. ...
Purpose: Cancer patients may experience simultaneous effects of the disease, as well as side effects from the treatment. These factors may all contribute to sleep disturbances. This study explores sleep disruption among cancer patients who undergo systemic adjuvant or palliative oncological treatment. Methods: Patient-reported data was collected using three questionnaires. The Medical Outcomes Study Sleep Scale, the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire as well as study-specific open-ended questions. The patients responded at the initial onset of treatment alternatively when changing to a new line of treatment as well as three months later. The analysis was performed using "Svenssons' method" for paired ordered categorical data. Results: Seventy-two (80%) of the ninety patients responded. Of these, 82% (n=59) reported having insufficient sleep at baseline and 86% (n=62) at follow-up. Health-related quality of life was affected in 92% (n=66) of the patients with a wide variation (Range variation of 0.22). The main causes of sleep disturbance reported at baseline were the disease itself and anxiety. At follow-up the main causes were anxiety and nocturia. The level of anxiety as a self-reported cause of sleeping disturbances in the open-ended questions were similar both before treatment and at follow up due to coping strategies established by the patients. Conclusion: Insufficient sleep is a problem for the cancer patients in this study. The perception of sleep showed a heterogeneous pattern. The cancer treatment does not seem to further worsen the perception of the sleep disturbance. As sleep disturbance is a problem this should be of concern in the clinical care for the cancer patients and an individualized approach should be used.
... Quality bad and very bad was reported by 40.4% of patients. In a survey by Flynn et al. (2010), participants expressed concerns about the importance of sleep to fight cancer. They often felt apprehensive about the potential negative impact that poor sleep could have on their health, fearing that this may contribute to a higher risk of recurrence and progression of cancer. ...
Objective: to evaluate the sleep pattern in cancer patients undergoing gastrointestinal oncological surgery and relate it to the dimensions of quality of life. Method: cross-sectional study with quantitative approach performed with 114 patients. Sociodemographic and clinical instruments, the Pittsburg Sleep Quality Index (PSQI) and the European Organization for Research and Treatment of Cancer Quality of the Questionnaire Core 30 (EORTC QLQ-C30) were used. Results: most patients were male, aged between 50 and 60 years, retired, married, with incomplete primary school. Cancer in colorectal portion was predominant, postoperative period up to two months and time of diagnosis up to six months. The pain, the time of surgery and the time of diagnosis were predictive for sleep disorders, negatively influencing the quality of sleep. Correlations between the PSQI and the EORTC-QLC-C30 were significant for all dimensions of functional scales and the Global Scale of Symptoms (GSS). The higher the score of functional scales of EORTC-QLC-C30 and GSS, the better quality of life, while a high PSQI score indicates worse sleep quality. Individuals who experienced pain had higher PSQI scores indicating worse quality of sleep. Moreover, the shorter the time of the surgery and the time of diagnosis, the greater the PSQI score, that is, poor sleep pattern. Conclusion: the care of cancer patients requires awareness from the nursing staff about the symptoms generated by the treatment, with the purpose that the survival in face of this disease may come along with good quality of life.
KEYWORDS: Oncologic nursing. Sleep disorders. Quality of life. Gastrointestinal neoplasms.
... Eleven PROMIS measures (Anger, Anxiety, Depression, Fatigue, Pain Behavior, Pain Interference, Physical Function, Sleep Disturbance, Sleep-Related Impairment, Satisfaction with Social Role Participation (Sat-SR), and Ability to Participate with Social Roles and Activities (Ability-SR) [12][13][14][15][16][17][18][19]) were administered by CAT in a clinical setting at up to three time points (appointments at baseline, one month post-baseline, and three months post-baseline) to 417 study patient-participants who had back pain and/or depression. Details of this study have been described previously [20,21]. ...
Purpose:
To evaluate the degree to which applying alternative stopping rules would reduce response burden while maintaining score precision in the context of computer adaptive testing (CAT).
Data:
Analyses were conducted on secondary data comprised of CATs administered in a clinical setting at multiple time points (baseline and up to two follow ups) to 417 study participants who had back pain (51.3%) and/or depression (47.0%). Participant mean age was 51.3 years (SD = 17.2) and ranged from 18 to 86. Participants tended to be white (84.7%), relatively well educated (77% with at least some college), female (63.9%), and married or living in a committed relationship (57.4%). The unit of analysis was individual assessment histories (i.e., CAT item response histories) from the parent study. Data were first aggregated across all individuals, domains, and time points in an omnibus dataset of assessment histories and then were disaggregated by measure for domain-specific analyses. Finally, assessment histories within a "clinically relevant range" (score ≥ 1 SD from the mean in direction of poorer health) were analyzed separately to explore score level-specific findings.
Method:
Two different sets of CAT administration rules were compared. The original CAT (CATORIG) rules required at least four and no more than 12 items be administered. If the score standard error (SE) reached a value < 3 points (T score metric) before 12 items were administered, the CAT was stopped. We simulated applying alternative stopping rules (CATALT), removing the requirement that a minimum four items be administered, and stopped a CAT if responses to the first two items were both associated with best health, if the SE was < 3, if SE change < 0.1 (T score metric), or if 12 items were administered. We then compared score fidelity and response burden, defined as number of items administered, between CATORIG and CATALT.
Results:
CATORIG and CATALT scores varied little, especially within the clinically relevant range, and response burden was substantially lower under CATALT (e.g., 41.2% savings in omnibus dataset).
Conclusions:
Alternate stopping rules result in substantial reductions in response burden with minimal sacrifice in score precision.
... Jansen's et al. [16] longitudinal study on QoL in CRC patients revealed that patients \60 years of age reported elevated levels of insomnia 1 year after diagnosis, while insomnia remained a consistent complaint over the 10-year followup, especially among younger patients. Although, however, several demographic and disease parameters and psychological distress symptoms have been determined as predictors or correlates of sleep difficulties in CRC [8,9], little is known about the complex interplay between the background psychological profile, personality variables, and psychological distress as predictors of disturbed sleep in CRC patients. ...
Sleep disturbances are common in cancer patients, but little is known about the complex interplay between the background psychological profile, coping with health stressors capacities and psychological distress in the formation of sleep difficulties in colorectal cancer.
To study the course and to identify psychological predictors of sleep difficulties in early non-metastatic colorectal cancer patients over a one-year period.
In this 1-year prospective study, we assessed in 84 early non-metastatic colorectal cancer patients the association of psychological distress (SCL-90-R), sense of coherence (SOC-29), and defense styles (Defense Style Questionnaire) with sleep difficulties (SCL-90-R) in multiple regression models. Eighty-two patients with breast cancer and 50 patients with cancer of unknown primary site served as disease controls, and 84 matched for age and sex alleged healthy individuals served as healthy controls.
Colorectal cancer patients presented more sleep difficulties compared to healthy participants but fewer than patients with breast cancer and cancer of unknown primary site. Colorectal cancer patients' trouble falling asleep (p = 0.033) and wakening up early in the morning (p < 0.001) deteriorated over time. Sleep that was restless or disturbed was independently associated with low SOC (p = 0.046) and maladaptive defenses (p = 0.008). Anxiety symptoms (p < 0.001) predicted deterioration in trouble falling asleep, while depressive symptoms (p = 0.022) and self-sacrificing defense style (p = 0.049) predicted deterioration in wakening up early in the morning.
Psychological parameters and coping with health stressors capacities are independently associated with sleep difficulties in colorectal cancer patients, indicating the need for psychological interventions aiming at improving adjustment to the disease.
... Patients undergoing the demanding and stressful experience of HSCT commonly experience psychological distress, including both depression and anxiety. [9][10][11][12] It is already known that depression and anxiety are associated with disrupted sleep, [13][14][15][16][17][18] but this link has not been studied in HSCT recipients. We therefore examined the extent to which greater psychological distress, including symptoms of anxiety and depression, may be linked with poor sleep. ...
The present study examined changes in sleep quality following hematopoietic stem cell transplantation (HSCT) and investigated associations with biobehavioral factors. Individuals undergoing HSCT for hematologic malignancies (N=228) completed measures of sleep quality and psychological symptoms pre-transplant and 1, 3, 6 and 12 months post transplant. Circulating inflammatory cytokines (IL-6, TNF-α) were also assessed. Sleep quality was poorest at 1 month post transplant, improving and remaining relatively stable after 3 months post transplant. However, approximately half of participants continued to experience significant sleep disturbance at 6 and 12 months post transplant. Mixed-effects linear regression models indicated that depression and anxiety were associated with poorer sleep quality, while psychological well-being was associated with better sleep. Higher circulating levels of IL-6 were also linked with poorer sleep. Subject-level fixed effects models demonstrated that among individual participants, changes in depression, anxiety and psychological well-being were associated with corresponding changes in sleep after covarying for the effects of time since transplant. Sleep disturbance was most severe when depression and anxiety were greatest and psychological well-being was lowest. Findings indicate that sleep disturbance is a persistent problem during the year following HSCT. Patients experiencing depression or anxiety and those with elevated inflammation may be at particular risk for poor sleep.Bone Marrow Transplantation advance online publication, 18 August 2014; doi:10.1038/bmt.2014.179.
... Sleep disturbance is highly prevalent in breast cancer patients, i.e., 23-61% [2][3][4]. Frequent reports of decreased sleep maintenance, increased daytime sleepiness, and poor quality sleep are documented before patients undergo chemotherapy [5], and increased symptom burden (e.g., concentration problems and pain) during treatment compounds prolonged sleep disturbance [6]. Sleep disturbance is also associated with greater fatigue severity [7,8] and may, at least indirectly, contribute to dose reduction or delay in treatment via its association with fatigue, pain, and/ or depression [9,10]. ...
This study's purpose was twofold: (1) to establish adherence rates to a behavioral therapy (BT) sleep intervention and (2) to identify psychological and physical symptom predictors of adherence to the intervention in women undergoing breast cancer chemotherapy.
A randomized controlled trial began 48 h before the first of four chemotherapy treatments. Women with stages I-IIIA breast cancer (n = 113) received a BT sleep intervention composed of stimulus control, modified sleep restriction (MSR), relaxation therapy (RT), and sleep hygiene counseling components. A BT plan was developed by a research nurse and each participant, reinforced on day 8, and repeated for chemotherapy cycles 2, 3, and 4. Adherence to the BT plan was measured daily; total adherence score was computed at each chemotherapy cycle by combining adherence estimates of all BT plan components. Psychological and physical symptoms over the past 7 days were measured 2 days prior to and 7 days after each chemotherapy treatment.
Total adherence rates to the BT plan were 51-52% at all four treatments but adherence varied by component. Sleep disturbance, pain, and anxiety significantly decreased whereas depression significantly increased across chemotherapy. Structural equation modeling revealed a good model fit with decreasing sleep disturbances (0.409) and increasing depression (-0.711) contributing to lower total adherence rates. Increasing depression predicted lower MSR adherence (-0.203) and decreasing sleep disturbances predicted lower RT adherence (1.220).
Sleep disturbance and depression significantly impacted adherence rates during chemotherapy. Results warrant attention when promoting adherence to BT sleep interventions during chemotherapy treatment.
The Helping to End Addiction Long-termSM Initiative (NIH HEAL InitiativeSM) is an aggressive trans-NIH effort to speed solutions to stem the national opioid public health crisis, including through improved pain management. Toward this end, the NIH HEAL Initiative launched a common data element (CDE) program to ensure that NIH-funded clinical pain research studies would collect data in a standardized way.
NIH HEAL Initiative staff launched a process to determine which pain-related core domains should be assessed by every clinical pain study and what questionnaires are required to ensure that the data is collected uniformly.
The process involved multiple literature reviews, and consultation with experts inside and outside of NIH and the investigators conducting studies funded by the initiative.
Ultimately, nine core pain domains, and questionnaires to measure them, were chosen for studies examining acute pain and chronic pain in adults and pediatric populations. These were augmented with dozens of study-specific supplemental questionnaires to enable uniform data-collection methods of outcomes outside of the core domains.
The selection of core domains will ensure that valuable clinical pain data generated by the initiative is standardized, useable for secondary data analysis, and useful for guiding future research, clinical practice decisions, and policymaking.
Perspective: The NIH HEAL Initiative launched a common data element program to ensure that NIH-funded clinical pain research studies would collect data in a standardized way. Nine core pain domains and questionnaires to measure them were chosen for studies examining acute pain and chronic pain in adults and pediatric populations.
Background:
Cancer patients who undergo allogeneic hematopoietic stem cell transplantation are among the most medically fragile patient populations with extreme demands for caregivers. Indeed, with earlier hospital discharges, the demands placed on caregivers continue to intensify. Moreover, an increased number of allogeneic hematopoietic stem cell transplantations are being performed worldwide, and this expensive procedure has significant economic consequences. Thus, the health and well-being of family caregivers have attracted widespread attention. Mobile health technology has been shown to deliver flexible, and time- and cost-sparing interventions to support family caregivers across the care trajectory.
Objective:
This protocol aims to leverage technology to deliver a novel caregiver-facing mobile health intervention named Roadmap 2.0. We will evaluate the effectiveness of Roadmap 2.0 in family caregivers of patients undergoing hematopoietic stem cell transplantation.
Methods:
The Roadmap 2.0 intervention will consist of a mobile randomized trial comparing a positive psychology intervention arm with a control arm in family caregiver-patient dyads. The primary outcome will be caregiver health-related quality of life, as assessed by the PROMIS Global Health scale at day 120 post-transplant. Secondary outcomes will include other PROMIS caregiver- and patient-reported outcomes, including companionship, self-efficacy for managing symptoms, self-efficacy for managing daily activities, positive affect and well-being, sleep disturbance, depression, and anxiety. Semistructured qualitative interviews will be conducted among participants at the completion of the study. We will also measure objective physiological markers (eg, sleep, activity, heart rate) through wearable wrist sensors and health care utilization data through electronic health records.
Results:
We plan to enroll 166 family caregiver-patient dyads for the full data analysis. The study has received Institutional Review Board approval as well as Code Review and Information Assurance approval from our health information technology services. Owing to the COVID-19 pandemic, the study has been briefly put on hold. However, recruitment began in August 2020. We have converted all recruitment, enrollment, and onboarding processes to be conducted remotely through video telehealth. Consent will be obtained electronically through the Roadmap 2.0 app.
Conclusions:
This mobile randomized trial will determine if positive psychology-based activities delivered through mobile health technology can improve caregiver health-related quality of life over a 16-week study period. This study will provide additional data on the effects of wearable wrist sensors on caregiver and patient self-report outcomes.
Trial registration:
ClinicalTrials.gov NCT04094844; https://www.clinicaltrials.gov/ct2/show/NCT04094844.
International registered report identifier (irrid):
PRR1-10.2196/19288.
Background
Difficulty sleeping is a common symptom for patients living with cancer that significantly affects their lives. However, although sleep disorders are common, it is an overlooked problem in cancer care.
Purpose
This study assessed the prevalence of sleep disturbances among patients living with cancer, and assessed the adequacy of sleep assessment and intervention for patients from both nurses' and patients' perspectives.
Method
Descriptive, cross-sectional and correlational design was used in this study. A convenience sample of 129 patients with cancer and 113 registered nurses working with cancer patients was recruited. A structured face-to-face interview was used to complete the patients' questionnaires and a self-administered questionnaire was given to nurses.
Findings
The majority of patients with cancer reported having poor sleep quality (69.8%). About 86.7% (n=98) of nurses reported that they have never screened patients with cancer for any sleep problems, and 76.7% (n=99) of the patients reported that they have never been assessed for sleep problems by the nursing staff during hospitalisation. Only 8% of patients with cancer who reported having problems sleeping to a nurse received interventions to promote better sleep.
Conclusion
Assessment of sleep disturbances in patients with cancer should be unified using a comprehensive reliable valid instrument, as well as providing evidence-based interventions according to patient's need. A written policy should be introduced to encourage sleep documentation and to make sleep care for patients part of routine nursing care.
Objective:
To identify patient characteristics associated with sleep disturbance and worsening of sleep in individuals diagnosed with localized colorectal cancer and assess heterogeneity in these relationships.
Methods:
Data were from the MY-Health study, a community-based observational study of adults diagnosed with cancer. Patient-Reported Outcomes Measurement Information System® Sleep Disturbance, Anxiety, Depression, Fatigue, and Pain Interference measures were administered. Participants self-reported demographics, comorbidities, and treatment information. Regression mixture and multiple regression models were used to evaluate the relationship between sleep disturbance and patient characteristics cross-sectionally at an average of 10 months after diagnosis (n = 613) as well as change in sleep disturbance over a 6-month period (n = 361).
Results:
Pain, anxiety, fatigue, and the existence of multiple comorbid conditions had statistically significant relationships with sleep disturbance (B = 0.09, 0.22, 0.29, and 1.53, respectively; P < 0.05). Retirement (B = -2.49) was associated with sleep quality in the cross-sectional model. Worsening anxiety (B = 0.14) and fatigue (B = 0.20) were associated with worsening sleep disturbance, and more severe sleep disturbance 10 months after diagnosis (B = -0.21) was associated with improvement in sleep quality after diagnosis (P < 0.05). No evidence of latent subgroups of patients (heterogeneity) was present.
Conclusions:
Pain, anxiety, fatigue, employment, and comorbid conditions were associated with sleep disturbance, but regression coefficients were small (< |2.5|). Results suggest that screening for anxiety, depression, fatigue, or pain is not sufficient for identifying sleep disturbance. Given the negative consequences of sleep disturbance, sleep disturbance screening may be warranted.
Background:
In 2009, the Army Pain Management Task Force was chartered. On the basis of their findings, the Department of Defense recommended a comprehensive pain management strategy that included development of a standardized pain assessment system that would collect patient-reported outcomes data to inform the patient-provider clinical encounter. The result was the Pain Assessment Screening Tool and Outcomes Registry (PASTOR). The purpose of this study was to assess the validity and response burden of the patient-reported outcome measures in PASTOR.
Methods:
Data for analyses were collected from 681 individuals who completed PASTOR at baseline and follow-up as part of their routine clinical care. The survey tool included self-report measures of pain severity and pain interference (measured using the National Institutes of Health Patient-Reported Outcome Measurement Information System [PROMIS] and the Defense and Veterans Pain Rating scale). PROMIS measures of pain correlates also were administered. Validation analyses included estimation of score associations among measures, comparison of scores of known groups, responsiveness, ceiling and floor effects, and response burden.
Results:
Results of psychometric testing provided substantial evidence for the validity of PASTOR self-report measures in this population. Expected associations among scores largely supported the concurrent validity of the measures. Scores effectively distinguished among respondents on the basis of their self-reported impressions of general health. PROMIS measures were administered using computer adaptive testing and each, on average, required less than 1 minute to administer. Statistical and graphical analyses demonstrated the responsiveness of PASTOR measures over time.
To document the use of aromasticks to facilitate sleep in a cancer centre in the UK. Sleep disturbance is a common problem amongst patients diagnosed with cancer. Essential oils may be inhaled by means of an aromastick (a personal inhaler device containing essential oils) as a means of improving sleep.
A prospective audit of aromasticks given to help facilitate sleep. Sixty-five aromasticks were given out over a 13 week period. 94% of patients reported that they did use their aromastick to help them sleep and 92% reported that they would continue to do so. An improvement of at least one point on a Likert scale measuring sleep quality was shown by 64% of patients following the use of an aromastick. Bergamot (Citrus bergamia) and sandalwood (Santalum austrocaladonicum); and frankincense (Boswellia carterii), mandarin (Citrus reticulata) and lavender (Lavandula angustifolia) were the essential oils used in the two blends chosen by patients.
Insomnia, poor sleep quality and short sleep durations are the most common problems seen in cancer patients. More studies are needed about sleep disorders in cancer patients. In our study, we aimed to investigate the prevalence of sleep disorders and the impact of these problems on the quality of life in cancer patients. Pittsburgh Sleep Quality Index (PSQI) was given to a total of 314 patients. The psychometric evaluation of the Turkish version of PSQI in cancer patients revealed that 127 (40.4%) patients had global PSQI scores >5, indicating poor sleep quality. There was no statistically significant relationship between PSQI scores and sexuality, marital status, cancer stage and chemotherapy type (P > 0.05); while the patients with bone and visceral metastasis had much lower PSQI scores (P = 0.006). Patients with Eastern Cooperative Oncology Group performance scores of 3 or more had also significantly lower PSQI scores (P = 0.02). In conclusion, PSQI questionnaire may be used to evaluate the sleep disorders in cancer patients. Consistent use of multi-item measures such as PSQI with established reliability and validity would improve our understanding of difficulties experienced by cancer patients with chronic insomnia.
© 2015 John Wiley & Sons Ltd.
Although sleep is vital to all human functioning and poor sleep is a known problem in cancer, it is unclear whether the overall prevalence of the various types of sleep disorders in cancer is known. The purpose of this systematic literature review was to evaluate if the prevalence of sleep disorders could be ascertained from the current body of literature regarding sleep in cancer. This was a critical and systematic review of peer-reviewed, English-language, original articles published from 1980 through 15 October 2013, identified using electronic search engines, a set of key words, and prespecified inclusion and exclusion criteria. Information from 254 full-text, English-language articles was abstracted onto a paper checklist by one reviewer, with a second reviewer randomly verifying 50% (k = 99%). All abstracted data were entered into an electronic database, verified for accuracy, and analyzed using descriptive statistics and frequencies in SPSS (v.20) (North Castle, NY). Studies of sleep and cancer focus on specific types of symptoms of poor sleep, and there are no published prevalence studies that focus on underlying sleep disorders. Challenging the current paradigm of the way sleep is studied in cancer could produce better clinical screening tools for use in oncology clinics leading to better triaging of patients with sleep complaints to sleep specialists, and overall improvement in sleep quality.
Sleep disorders and insomnia are more prevalent in patients with cancer than in the normal population. Sleep disorders consist of delayed sleep latency, waking episodes after sleep onset, unrefreshing sleep, reduced quality of sleep, and reduced sleep efficiency. Sleep disorders cluster with pain, fatigue, depression, anxiety, and vasomotor symptoms, depending on stage of disease, treatment, and comorbidities. Premorbid sleep problems and shift work have been associated with a higher prevalence of cancer; in fact, shift work has been labeled a carcinogen. Treatment for insomnia includes cognitive behavioral therapy with sleep hygiene, bright-light therapy, exercise, yoga, melatonin, and hypnotic medications. Unfortunately, there are few randomized trials in cancer-related sleep disorders such that most recommendations particularly for hypnotics are based on treatment for primary insomnia. In this article, insomnia is reviewed as a predisposing factor to cancer, prior to and during treatment, in cancer survivorship and in advanced cancer. Recommendations for treatment are based on low-quality evidence but are also reviewed.
Sleep disorders, including insomnia and excessive sleepiness, affect a significant proportion of patients with cancer and survivors, often in combination with fatigue, anxiety, and depression. Improvements in sleep lead to improvements in fatigue, mood, and quality of life. This section of the NCCN Guidelines for Survivorship provides screening, diagnosis, and management recommendations for sleep disorders in survivors. Management includes combinations of sleep hygiene education, physical activity, psychosocial interventions, and pharmacologic treatments.
Sleep disturbances are among the most distressing symptoms in cancer: they often co-occur with fatigue, pain and psychological distress. Despite the negative impact on quality of life, patients rarely seek help for managing their sleep disturbances. This paper presents the results of a multicentre observational study on patients' attitudes towards their sleep problems. The study also investigates symptom correlates. Patients responded to a semi-structured interview and completed the following questionnaires: Pittsburgh Sleep Quality Index; Brief Fatigue Inventory; Hospital Anxiety and Depression Scale; and European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life QLQ-C30 Questionnaire (QLQ-C30). Four hundred and three cancer patients were enrolled in the study. Bad sleepers constituted 66% of the sample. Thirty-eight per cent of them had not turned to any professional to solve their sleep disturbances because they had various beliefs about the importance of the problem and the possibility to be treated. The main correlates of sleep disturbances were psychological distress, reduced physical functioning and reduced overall quality of life. In conclusion, there is a need to sensitise patients to actively search for a solution to their sleep disturbances so they can be solved along with other co-occurring symptoms. Doctors could also be encouraged to dedicate more attention to routinely asking cancer patients about eventual sleep disturbances.
Although lung cancer is perceived as a dire diagnosis, increases in the 5-year survival rate of individuals with non-small cell lung cancer (NSCLC) have been reported. Survivors, however, continue to be excessively burdened with symptoms such as respiratory distress which interfere with functioning and quality of life. While exercise and physical activity are strongly recommended, NSCLC survivors may be reluctant to participate due to actual or anticipated shortness of breath exacerbated with movement.
This quasi-experimental, intervention-only pilot study aimed to determine the effects of an 8-week standardized yoga protocol for Stage I–IIIa NSCLC survivors (n=9). The protocol was developed within the Viniyoga (Hatha) tradition with respiratory experts. Breathing ease, dyspnea, oxygen saturation, and respiratory function were explored in relationship to yoga practice (45-minute sessions once per week and home practice) using repeated-measures analysis. Number of participants reporting dyspnea ranged from 25 to 50% prior to practice with no significant increase during sessions, and moderate decreases noted at times. Oxygen saturation remained high and vital signs stable; forced expiratory volume in 1 second (FEV 1 ) values increased significantly over the 14-week study period (p<0.0001). Yoga, with an emphasis on postures coordinated with breathing and meditation practices, offers a potentially feasible and beneficial option that requires further study in this population.
To evaluate the measurement invariance of 6 self-report measures selected for an ongoing longitudinal study of individuals with spinal cord injury, muscular dystrophy, postpolio syndrome, and multiple sclerosis.
Participants completed and returned by mail surveys that included the targeted self-report measures. Ordinal logistic regressions methods were applied to evaluate items for differential item functioning (DIF) by diagnosis and age range.
Community.
Participants (N=2479) who had 1 of the 4 target diagnoses.
None.
Six short-form measures from the Patient-Reported Outcome Measurement Information System (PROMIS) were administered to participants to measure fatigue, pain interference, satisfaction with social roles, sleep disturbance, sleep-related impairment, and depression.
One item of 1 measure (fatigue) exhibited DIF by diagnosis based on a published standard for meaningful DIF. However, scores corrected for this DIF were highly correlated with uncorrected scores (r>.999). No DIF by age range was found for any of the measures.
Study findings support the use of the selected PROMIS short forms for comparing symptoms and quality of life indicators across different diagnoses and age ranges.
Cancer-related fatigue is an important clinical problem. It is common, distressing, and often difficult to treat. There is a role for drug treatment of cancer-related fatigue, but no consensus has been reached on which drugs are useful. This systematic review and meta-analysis aims to review the available evidence and make recommendations for practice and research.
We searched the Cochrane register of controlled trials (through the second quarter 2007), Medline (January 1, 1966, through August 1, 2007), and EMBASE (January 1, 1980, through August 1, 2007) by use of a predetermined list of search terms. Cochrane Collaboration meta-analysis review methodology was used for this study. The change in fatigue score on the instrument used in each study and other outcomes of interest (adverse events and withdrawal rates) were compared between treatment and control arms by use of the standardized mean difference (SMD) with 95% confidence intervals (CIs). All statistical tests were two-sided.
We identified 27 eligible trials of drug treatments for cancer-related fatigue (with a total of 6746 participants). The overall effect size for all drug classes was small. A meta-analysis of two studies (n = 264 patients) indicated that methylphenidate (a psychostimulant) was superior to placebo (standardized mean difference [SMD] in change in fatigue score = -0.30, 95% confidence interval [CI] = -0.54 to -0.05; P = .02) for treating cancer-related fatigue. A meta-analysis of 10 studies (n = 2226 patients) evaluating erythropoietin in anemic cancer patients who were undergoing chemotherapy indicated that erythropoietin was superior to placebo (SMD = -0.30, 95% CI = -0.46 to -0.29; P = .008). Among anemic patients (four studies with n = 964 patients), improvement in fatigue was associated with darbepoetin treatment compared with placebo treatment (SMD = -0.13, 95% CI = -0.27 to 0.00; P = .05). Progestational steroids and paroxetine were no better than placebo in the treatment of cancer-related fatigue.
There is some evidence that treatment of cancer-related fatigue with methylphenidate appears to be effective. More robust evidence indicates that treatment with hematopoietic agents appears to relieve cancer-related fatigue caused by chemotherapy-induced anemia. Further confirmatory trials are required for both observations.
This multi-institutional sleep study involved two phases aimed at investigating sleep alterations in patients with any stage of breast and lung cancer. The first phase of this study used an 82-item, 20-minute telephone survey to elicit information regarding the impact of sleep disturbances on a convenience sample of 150 patients. Of these patients, 44% reported a sleep problem during the month before the interview. Significant relations included these: report of sleep problems prediagnosis over the past month (x = 5.82; p = 0.02), duration of sleep medication use and frequency of sleep problem (r = 0.58; p = 0.05), age and severity of sleep problems (r = 0.38; p = 0.05), and frequency and severity of the sleep problem over the past month (r = 0.21; p < 0.10). Communication with health care providers occurred in 16.6% of patients reporting a sleep disturbance. The second phase of this study explored the type, frequency, and severity of sleep problems and perceptions of causation, support, and methods of coping with the sleep problem. A qualitative approach to the problem was used in this phase. A one-time telephone interview of 42 patients, derived from a convenience sample, revealed a 45% prevalence of sleep problems a month before the interview. A qualitative analysis of the responses suggested that sleep problems are related to experiences of other symptoms and perceptions of cancer and treatment. Content analysis of the responses identified the following categories: figuring out the reason, seeking help, seeking support and relation to the overall cancer experience.
To estimate the prevalence of insomnia, describe clinical characteristics of sleep difficulties, assess the influence of cancer on the insomnia course, and identify potential risk factors involved in the development of insomnia among women who had received radiotherapy for non metastatic breast cancer.
A sample of 300 consecutive women who had been treated with radiotherapy for non metastatic breast cancer first completed an insomnia screening questionnaire. Participants who reported sleep difficulties were subsequently interviewed over the phone to evaluate further the nature, severity, duration, and course of their insomnia.
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Nineteen percent (n=56) of the participants met diagnostic criteria for an insomnia syndrome. In most cases (95%), insomnia was chronic. The onset of insomnia followed the breast cancer diagnosis in 33% of the patients and 58% of the patients reported that cancer either caused or aggravated their sleep difficulties. Factors associated with an increased risk for insomnia were sick leave, unemployment, widowhood, lumpectomy, chemotherapy, and a less severe cancer stage at diagnosis. Among women with insomnia symptoms, the risk to meet diagnostic criteria for an insomnia syndrome was higher in those who were separated and had a university degree.
Insomnia is a prevalent and often chronic problem in breast cancer patients. Although it is not always a direct consequence of cancer, pre-existing sleep difficulties are often aggravated by cancer. It is therefore important to better screen breast cancer patients with insomnia and offer them an appropriate treatment.
To provide an overview of normal sleep, describe common sleep disorders, and discuss underlying sleep regulatory processes and how cancer, cancer treatment, and associated patient responses may adversely affect sleep.
Published peer-reviewed articles and textbooks.
The duration, structure, and timing of sleep have a profound impact on health, well-being, and performance. Patients with cancer may be at risk for disturbances in sleeping and waking resulting from disease- and nondisease-related circumstances that interfere with normal sleep regulation, including demographic, lifestyle, psychological, and disease- and treatment-related factors.
Patients with cancer are at high risk for sleep-wake disturbances.
An understanding of normal sleep, sleep pathology, and the factors that can precipitate sleep disturbance provides a context for nurses to interpret sleep complaints in their patients, evaluate responses to sleep-promoting interventions, and guide decision making regarding referrals.
While many of the multiple symptoms that cancer patients have are due to the disease, it is increasingly recognized that pain, fatigue, sleep disturbance, cognitive dysfunction and affective symptoms are treatment related, and may lead to treatment delays or premature treatment termination. This symptom burden, a subjective counterpart of tumor burden, causes significant distress. Progress in understanding the mechanisms that underlie these symptoms may lead to new therapies for symptom control. Recently, some of these symptoms have been related to the actions of certain cytokines that produce a constellation of symptoms and behavioral signs when given exogenously to both humans and animals. The cytokine-induced sickness behavior that occurs in animals after the administration of infectious or inflammatory agents or certain proinflammatory cytokines has much in common with the symptoms experienced by cancer patients. Accordingly, we propose that cancer-related symptom clusters share common cytokine-based neuroimmunologic mechanisms. In this review, we provide evidence from clinical and animal studies that correlate the altered cytokine profile with cancer-related symptoms. We also propose that the expression of coexisting symptoms is linked to the deregulated activity of nuclear factor-kappa B, the transcription factor responsible for the production of cytokines and mediators of the inflammatory responses due to cancer and/or cancer treatment. These concepts open exciting new avenues for translational research in the pathophysiology and treatment of cancer-related symptoms.
Cross-sectional studies suggest that clinical insomnia is associated with immune downregulation. However, there is a definite need for experimental studies on this question. The goal of this randomized controlled study was to assess the effect of an 8-week cognitive-behavioral therapy (CBT) for chronic insomnia on immune functioning of breast cancer survivors. Previous analyses of this study showed that CBT was associated with improved sleep and quality of life, and reduced psychological distress.
Fifty-seven women with chronic insomnia secondary to breast cancer were randomly assigned to CBT (n = 27) or to a waiting-list control condition (WLC; n = 30). Peripheral-blood samples were taken at baseline and post-treatment (and postwaiting for WLC patients), as well as at 3-, 6-, and 12-month follow-up for immune measures, including enumeration of blood cell counts (ie, WBCs, monocytes, lymphocytes, CD3+, CD4+, CD8+, and CD16+/CD56+) and cytokine production (ie, interleukin-1-beta [IL-1beta] and interferon gamma [IFN-gamma]).
Patients treated with CBT had higher secretion of IFN-gamma and lower increase of lymphocytes at post-treatment compared with control patients. Pooled data from both treated groups indicated significantly increased levels of IFN-gamma and IL-1beta from pre- to post-treatment. In addition, significant changes in WBCs, lymphocytes, and IFN-gamma were found at follow-up compared with post-treatment.
This study provides some support to the hypothesis of a causal relationship between clinical insomnia and immune functioning. Future studies are needed to investigate the clinical impact of such immune alterations.
Disturbed sleep is observed in association with acute and chronic pain, and some data suggest that disturbed and shortened sleep enhances pain. We report the first data showing, in healthy, pain-free, individuals, that modest reductions of sleep time and specific loss of rapid eye movement (REM) sleep produces hyperalgesia the following morning.
Two repeated-measures design protocols were conducted: (1) a sleep-loss protocol with 8 hours time-in-bed, 4 hours time-in-bed, and 0 hours time-in-bed conditions and (2) a REM sleep-loss protocol with 8 hours time-in-bed, 2 hours time-in-bed, REM deprivation, and non-REM yoked-control conditions.
The studies were conducted in an academic hospital sleep laboratory.
Healthy pain-free normal sleepers, 7 in the sleep-loss protocol and 6 in the REM sleep-loss protocol, participated.
Finger-withdrawal latency to a radiant heat stimulus tested at 10:30 AM and 2:30 PM and the Multiple Sleep Latency Test conducted at 10:00 AM, noon, 2:00 PM, and 4:00 PM were measured.
Finger-withdrawal latency was shortened by 25% after 4 hours of time in bed the previous night relative to 8 hours of time in bed (p < .05), and REM sleep deprivation relative to a non-REM yoked-control sleep-interruption condition shortened finger-withdrawal latency by 32% (p < .02).
These studies showed that the loss of 4 hours of sleep and specific REM sleep loss are hyperalgesic the following day. These findings imply that pharmacologic treatments and clinical conditions that reduce sleep and REM sleep time may increase pain.
To provide an overview of the evidence that supports a role for the proinflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in the etiology of cancer chemotherapy-related symptoms.
Electronic nursing, psychology, and medicine databases; online meeting abstracts; and personal experimental observations.
Substantial evidence implicates the proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6 in the etiology of chemotherapy-related anorexia, cachexia, anemia, pain, sleep disturbance, fatigue, and depression.
Further investigation into the role of these cytokines in the genesis of chemotherapy-related symptoms is warranted. The development of appropriate animal models likely will be key to understanding the relationship among cancer chemotherapy, proinflammatory cytokines, and symptoms.
Nurses traditionally have been leaders in symptom management. The symptoms experienced by patients undergoing chemotherapy have a profound negative impact on quality of life and patients' ability to receive prescribed treatments. An understanding of potential mechanisms underlying the physiologic and behavioral consequences of chemotherapy administration will aid nurses in the development of interventions to effectively manage chemotherapy-related symptoms.
Download the 2014 revision to Putting Evidence Into Practice interventions for fatigue for free at https://cjon.ons.org/file/13991/download by Mitchell et al., CJON, 18(6, Suppl.), 38-58.
Cancer-related fatigue has a significant impact on patients' physical and psychosocial functioning, symptom distress, and quality of life, yet it remains under-recognized and undertreated. The Oncology Nursing Society's Putting Evidence Into Practice initiative sought to improve patient outcomes relative to this important problem by critically examining and summarizing the evidence base for interventions to prevent and manage fatigue during and following treatment. This article critically reviews and summarizes the available empirical evidence regarding interventions for cancer-related fatigue. In addition to offering patients and clinicians a tool to facilitate effective management of the distressing symptom, this evidence-based review identifies gaps in knowledge and research opportunities.
Sleep disorders, such as difficulty falling asleep, problems maintaining sleep, poor sleep efficiency, early awakening, and excessive daytime sleepiness, are prevalent in patients with cancer. Such problems can become chronic in some patients, persisting for many months or years after completion of cancer therapy. For patients with cancer, sleep is potentially affected by a variety of factors, including the biochemical changes associated with the process of neoplastic growth and anticancer treatments, and symptoms that frequently accompany cancer, such as pain, fatigue, and depression.
Fatigue is highly prevalent and persistent in patients with cancer and cancer survivors. Although cancer-related fatigue and cancer-related sleep disorders are distinct, a strong interrelationship exists between these symptoms, and a strong possibility exists that they may be reciprocally related. The majority of studies that have assessed both sleep and fatigue in patients with cancer provide evidence supporting a strong correlation between cancer-related fatigue and various sleep parameters, including poor sleep quality, disrupted initiation and maintenance of sleep, nighttime awakening, restless sleep, and excessive daytime sleepiness.
This paper reviews the data from these studies with a view toward suggesting further research that could advance our scientific understanding both of potential interrelationships between sleep disturbance and cancer-related fatigue and of clinical interventions to help with both fatigue and sleep disturbance.
Disclosure of potential conflicts of interest is found at the end of this article.
Cancer-related fatigue (CRF) is one of the most prevalent symptoms patients with cancer experience, both during and after treatment. CRF is pervasive and affects patients' quality of life considerably. It is important, therefore, to understand the underlying pathophysiology of CRF in order to develop useful strategies for prevention and treatment. At present, the etiology of CRF is poorly understood and the relative contributions of the neoplastic disease, various forms of cancer therapy, and comorbid conditions (e.g., anemia, cachexia, sleep disorders, depression) remain unclear. In any individual, the etiology of CRF probably involves the dysregulation of several physiological and biochemical systems. Mechanisms proposed as underlying CRF include 5-HT neurotransmitter dysregulation, vagal afferent activation, alterations in muscle and ATP metabolism, hypothalamic–pituitary–adrenal axis dysfunction, circadian rhythm disruption, and cytokine dysregulation. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is a characteristic, in particular chronic fatigue syndrome and exercise-induced fatigue. The mechanisms that lead to fatigue in these conditions provide a theoretical basis for future research into the complex etiology of this distressing and debilitating symptom. An understanding of relevant mechanisms may offer potential routes for its prevention and treatment in patients with cancer.
Disclosure of potential conflicts of interest is found at the end of this article.
To examine the relationships among pain, fatigue, insomnia, and gender while controlling for age, comorbidities, and stage of cancer in patients newly diagnosed with lung cancer within 56 days of receiving chemotherapy.
Secondary data analysis.
Accrual from four sites: two clinical community oncology programs and two comprehensive cancer centers.
80 patients newly diagnosed with lung cancer.
Analysis from baseline observation of a randomized clinical intervention trial. Multinomial log-linear modeling was performed to explain the relationships among pain, fatigue, insomnia, and gender.
Pain, fatigue, insomnia, and gender.
For all people with lung cancer, fatigue (97%) and pain (69%) were the most frequently occurring symptoms; insomnia occurred 51% of the time. A model containing all main effects (two-way interactions of pain and fatigue, pain and insomnia, and insomnia and gender; and the three-way interaction of pain, fatigue, and insomnia, along with three covariates [age, comorbidities, and stage of cancer]) was a good fit to the data. Parameter estimates indicated that a statistically significant effect from the model was the three-way interaction of pain, fatigue, and insomnia. Gender did not make a difference. Age, comorbidities, and stage of cancer were not significant covariates.
For people newly diagnosed with lung cancer undergoing chemotherapy, multiple symptoms occur simultaneously rather than in isolation; a symptom cluster exists, consisting of pain, fatigue, and insomnia; and no relationship was found among gender, pain, fatigue, and insomnia.
By understanding this symptom cluster, healthcare providers can target specific troublesome symptoms to optimize symptom management and achieve the delivery of high-quality cancer care.
We present a two-stage method for obtaining both phase and object estimates from phase-diversity time series data. In the first stage, the phases are estimated for each time frame using the limited memory BFGS method. In the second stage, an algorithm that incorporates a nonnegativity constraint as well as prior knowledge of data noise statistics is used to obtain an estimate of the object being observed. The approach is tested on real phase-diversity data with 32 time frames, and a comparison is made between it and a previously developed approach. Also, the image deblurring algorithm in stage two is tested against other standard methods and is shown to be the best for our problem.
Six patients seeking treatment for chronic insomnia participated in two focus groups as a first stage of questionnaire design. Despite the low attendance at the groups, the results are presented because they offer an illuminating insight into the experience of insomnia.
The participants reported major disruption to their daytime activities, especially in terms of safety and reliability, which could affect their life choices and, they believed, could affect their health. They did not feel understood by others, especially doctors, and wanted better information about insomnia and its management. The study also highlighted practical problems involved in running focus groups as well as ethical considerations that arise when conducting research with current patients. These issues are discussed along with the implications of the research, which raise questions about the role of sleep in maintaining lifestyle balance.
Further research with a larger and more varied group is recommended in order to consolidate the findings and it is suggested that further reflection is necessary to determine the extent to which sleep is a legitimate concern for occupational therapists.
Many individual risk factors for insomnia have been identified for women with a history of breast cancer. We assessed the relative importance of a wide range of risk factors for insomnia in this population.
Two thousand six hundred and forty-five women < or =4 years post-treatment for Stage I (> or =1 cm)-IIIA breast cancer provided data on cancer-related variables, personal characteristics, health behaviors, physical health/symptoms, psychosocial variables, and the Women's Health Initiative-Insomnia Rating Scale (WHI-IRS; scores > or =9 indicate clinically significant insomnia).
Thirty-nine per cent had elevated WHI-IRS scores. In binary logistic regression, the variance in high/low insomnia group status accounted for by each risk factor category was: cancer-specific variables, 0.4% (n.s.); personal characteristics, 0.9% (n.s.); health behaviors, 0.6% (n.s.); physical health/symptoms, 13.4% (p<0.001); and, psychosocial factors, 11.4% (p<0.001). Insomnia was associated with worse depressive (OR = 1.32) and vasomotor symptoms (particularly night sweats) (OR = 1.57).
Various cancer-specific, demographic, health behavior, physical health, and psychosocial factors have been previously reported as risk factors for insomnia in breast cancer. In our study (which was powered for simultaneous examination of a variety of variables), cancer-specific, health behavior, and other patient variables were not significant risk factors when in the presence of physical health and psychosocial variables. Only worse depressive and vasomotor symptoms were meaningful predictors.
The purpose of this study was to examine patterns of circadian activity rhythms and their relationship with fatigue, anxiety/depression, and demographic/medical variables in women receiving breast cancer adjuvant therapy treatments (Tx) at three times within a randomized clinical trial (RCT) designed to improve sleep and modify fatigue.
A RCT enrolled 219 women with stage I-IIIA breast cancer who were randomized 2 days prior to starting chemotherapy to a behavioral therapy sleep intervention or healthy eating control group. All cases with available data (n = 190) were included in a descriptive, correlational, repeated measures analysis. Activity data were collected continuously by wrist actigraphy for 7 days at three times: the start (Tx 1), continuation (Tx 3), and recovery (30 days after last Tx) of chemotherapy. Circadian activity rhythm parameters were generated using Action4 software (Ambulatory Monitoring, Inc.). Measures collected simultaneously included Piper Fatigue Scale, Hospital Anxiety and Depression Scale, and demographic/medical variables.
Circadian activity rhythm parameters at three times in both groups were disrupted compared to healthy adults, but similar to values of cancer patients. Significant changes in mesor, amplitude, peak activity, and 24 h autocorrelation values were found over time in both groups. The intervention group's amplitude and circadian quotient values were significantly more robust. More robust activity rhythms were associated with lower fatigue, depressive symptoms, body mass index, and higher performance status in both groups.
Disrupted patterns of circadian activity rhythms were prevalent and associated with distressing fatigue and depressive symptoms during chemotherapy and at recovery. The intervention resulted in more robust rhythms.
Common medical problems are often associated with abnormalities of sleep. Patients with chronic medical disorders often have fewer hours of sleep and less restorative sleep compared to healthy individuals, and this poor sleep may worsen the subjective symptoms of the disorder. Individuals with lung disease often have disturbed sleep related to oxygen desaturations, coughing, or dyspnea. Both obstructive lung disease and restrictive lung diseases are associated with poor quality sleep. Awakenings from sleep are common in untreated or undertreated asthma, and cause sleep disruption. Gastroesophageal reflux is a major cause of disrupted sleep due to awakenings from heartburn, dyspepsia, acid brash, coughing, or choking. Patients with chronic renal disease commonly have sleep complaints often due to insomnia, insufficient sleep, sleep apnea, or restless legs syndrome. Complaints related to sleep are very common in patients with fibromyalgia and other causes of chronic pain. Sleep disruption increases the sensation of pain and decreases quality of life. Patients with infectious diseases, including acute viral illnesses, HIV-related disease, and Lyme disease, may have significant problems with insomnia and hypersomnolence. Women with menopause have from insomnia, sleep-disordered breathing, restless legs syndrome, or fibromyalgia. Patients with cancer or receiving cancer therapy are often bothered by insomnia or other sleep disturbances that affect quality of life and daytime energy. The objective of this article is to review frequently encountered medical conditions and examine their impact on sleep, and to review frequent sleep-related problems associated with these common medical conditions.
Fatigue is a common symptom in cancer patients receiving active treatment. There are a limited number of reviews evaluating interventions for fatigue during active treatment, and they are restricted to patients with advanced cancer, or to patients during radiotherapy. To date there is no systematic review on psychosocial interventions for fatigue during cancer treatment.
To evaluate if psychosocial interventions are effective in reducing fatigue in cancer patients receiving active treatment for cancer, and which types of psychosocial interventions are the most effective.
In September 2008 we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), PUBMED, MEDLINE, EMBASE, CINAHL and PsycINFO, and checked the reference lists.
Randomised controlled trials (RCTs) were included which evaluated psychosocial interventions in adult cancer patients during treatment, with fatigue as an outcome measure.
Three review authors independently extracted data from the selected studies, and assessed the methodological quality using several quality rating scales and additional criteria.
Twenty-seven studies met the inclusion criteria with a total of 3324 participants, and seven studies reported significant effects of the psychosocial intervention on fatigue. In three studies the effect was maintained at follow-up. The quality of the studies was generally moderate. Effect sizes varied between 0.17 to 1.07.The effectiveness of interventions specific for fatigue was significantly higher (80%) compared to interventions not specific for fatigue (14%). In five studies the interventions were specifically focused on fatigue, with four being effective. The five interventions were brief, consisting of three individual sessions, provided by (oncology) nurses. In general, during these interventions participants were educated about fatigue, were taught in self-care or coping techniques, and learned activity management.Of the remaining 22 studies only three were effective in reducing fatigue, and these interventions had a more general approach. These interventions were aimed at psychological distress, mood and physical symptoms, and varied strongly in duration and content.
There is limited evidence that psychosocial interventions during cancer treatment are effective in reducing fatigue. At present, psychosocial interventions specifically for fatigue are a promising type of intervention. However, there is no solid evidence for the effectiveness of interventions not specific for fatigue. Most aspects of the included studies were heterogeneous, and therefore it could not be established which other types of interventions, or elements were essential in reducing fatigue.
During the past decade, the critical role of sleep in health and disease has been underscored by research that further defines the relationship between sleep and myriad physiologic and psychological functions as well as quality of life. For many years, there was little exploration of the significance of sleep and sleep disorders in cancer patients; however, the past decade has seen a steady growth of inquiry in this area. These investigations have demonstrated the high frequency and significance of sleep disturbance as a symptom in cancer patients. They have also explored the complex interaction between sleep and other common cancer symptoms, most notably fatigue, depression, and pain, and have identified risk factors associated with the development of sleep problems in this population. Although treatment studies lag behind, reports of effective psychological and behavioral interventions for insomnia in cancer patients are increasing. Several studies are addressing pharmacotherapeutic intervention for hot flashes as a potential source of sleep disturbance. Other sleep disorders, most notably obstructive sleep apnea, also occur with some regularity in cancer patients.
This article reviews the evidence on the diagnosis, epidemiology, etiology, and treatment of insomnia in the context of cancer and proposes several areas for future research. Clinical and diagnostic features of insomnia are described and prevalence estimates of insomnia complaints in cancer patients are summarized. Then, potential etiologic factors (ie, predisposing, precipitating, and perpetuating factors) and consequences of insomnia (ie, psychologic, behavioral, and health impact) in the context of cancer are discussed. Finally, pharmacologic and psychologic treatments previously shown effective to treat insomnia in healthy individuals are discussed as valuable treatment options for cancer patients as well. Because long-term use of hypnotic medications is associated with some risks (eg, dependence), it is argued that psychologic interventions (eg, stimulus control, sleep restriction, cognitive therapy) are the treatment of choice for sleep disturbances in the context of cancer, especially when it has reached a chronic course. However, the efficacy of these treatments has yet to be verified specifically in cancer patients.
Sleep difficulty is a prominent concern of cancer patients, yet there has been no large study of the prevalence and nature of sleep disturbance in cancer patients. This cross-sectional survey study examined: (a) the prevalence of reported sleep problems in patients attending six clinics at a regional cancer centre; (b) sleep problem prevalence in relation to cancer treatment; and (c) the nature of reported insomnia (type, duration, and associated factors). For three months, all patients attending clinics for breast, gastrointestinal, genitourinary, gynecologic, lung, and non-melanoma skin cancers were offered a brief sleep questionnaire. Response rate was 87%; the final sample size was 982. Mean age of respondents was 64.9 years (SD 12.5). The most prevalent problems were excessive fatigue (44% of patients), leg restlessness (41%). insomnia (31%), and excessive sleepiness (28%). Chi square tests showed significant variation among clinics in the prevalence of most sleep problems. The lung clinic had the highest or second-highest prevalence of problems. The breast clinic had a high prevalence of insomnia and fatigue. Recent cancer treatment was associated with excessive fatigue and hypersomnolence. Insomnia commonly involved multiple awakenings (76% of cases) and duration > or = 6 months (75% of cases). In 48% of cases, insomnia onset was reported to occur around the time of cancer diagnosis (falling within the period 6 months pre-diagnosis to 18 months post-diagnosis). The most frequently identified contributors to insomnia were thoughts, concerns, and pain/discomfort. In a multivariate logistic regression analysis, variables associated with increased odds of insomnia were fatigue, age (inverse relationship), leg restlessness, sedative/hypnotic use, low or variable mood, dreams, concerns, and recent cancer surgery. This study provides new information about sleep-related phenomena in cancer patients, information which will be useful in planning supportive care services for cancer patients.
The focus of this pilot study was to examine issues of criterion validity and detection of insomnia utilizing a single item from the Zung Self-Rating Depression Scale (ZSDS) as a means to rapidly screen cancer patients in ambulatory oncology clinics. In our previous work, we have demonstrated the usefulness of other single items for screening purposes, such as for fatigue. The sleep item reads "I have trouble sleeping through the night" and is rated on a 4-point Likert scale ranging from "none or little of the time" to "most or all of the time." Fifty-two oncology patients were administered the ZSDS and further evaluated with the Pittsburgh Sleep Quality Index (PSQI). The sensitivity and specificity of various cutoffs on the ZSDS sleep item were investigated as predictors of the PSQI. Results revealed that the ZSDS single-item screen has poor sensitivity and specificity for detecting insomnia in cancer patients, and that the relationship between insomnia and depression is more complicated than anticipated. The use of this single item, or perhaps any single item, as a means of screening for sleep disturbances in cancer patients may be problematic. A better understanding of insomnia and its measurement are worthwhile areas of study.
This review includes research findings from sleep-related studies on specific types of cancers, on specific types of treatment protocols, and on persons with end-stage cancer regardless of treatment protocol. Since treatment protocols have evolved in the past decade, literature since 1990 is emphasized. We conclude that researchers should design studies that attend to prior sleep history, gender, type of cancer and treatment modalities, and the specific type of sleep problems experienced over the course of diagnosis, treatment, and recovery. More research is also needed to understand sleep problems in children with cancer and sleep problems in family caregivers. Research is also needed on effective pharmacological and non-pharmacological interventions. Daytime functioning, daytime sleepiness, and altered circadian rhythms should be considered salient outcomes in addition to severity of cancer-related fatigue. Clinicians should consider whether a patient's sleep problem has been chronic and unrelated to cancer, or precipitated by diagnosis and treatment. The specific type of sleep problem should be ascertained so that appropriate interventions can be prescribed. Appropriate interventions can include either pharmacological medication or behavioral strategies, and each has the potential to promote restorative sleep and thereby improve the patient's quality of life, daytime functioning, and well-being.
Approximately 30% of breast cancer survivors report persistent fatigue of unknown origin. We have previously shown that cancer-related fatigue is associated with alterations in immunological parameters and serum cortisol levels in breast cancer survivors. The current study examined the diurnal rhythm of salivary cortisol in fatigued and non-fatigued breast cancer survivors. Salivary cortisol measures were obtained from breast cancer survivors with persistent fatigue (n=13) and a control group of non-fatigued survivors (n=16). Participants collected saliva samples upon awakening and at 1200, 1700, and 2200 h on two consecutive days. Diurnal cortisol slope for each day was determined by linear regression of log-transformed cortisol values on collection time and analyzed using multi-level modeling. Fatigued breast cancer survivors had a significantly flatter cortisol slope than non-fatigued survivors, with a less rapid decline in cortisol levels in the evening hours. At the individual patient level, survivors who reported the highest levels of fatigue also had the flattest cortisol slopes. Group differences remained significant in analyses controlling for demographic and medical factors, daily health behaviors, and other potential confounds (e.g. depressed mood, body mass index). Results suggest a subtle dysregulation in hypothalamic-pituitary-adrenal axis functioning in breast cancer survivors with persistent fatigue.
To test whether sleep disturbance mediates the effect of pain on fatigue.
Cross-sectional.
Radiation therapy clinic, oncology ambulatory clinic, and inpatient oncology unit in an urban teaching hospital.
84 patients with cancer with multiple primary diagnoses who were experiencing pain. Fifty-three percent were female and 92% were Caucasian, with a mean age of 54 years.
All participants completed a symptom questionnaire that included the Brief Pain Inventory-Short Form, the Pittsburgh Sleep Quality Index, and the fatigue subscale of the Profile of Mood States questionnaire. Multistage linear regression was used to test a mediation model.
Fatigue, pain, and sleep disturbance.
Mediation analyses indicate that pain influences fatigue directly as well as indirectly by its effect on sleep. About 20% (adjusted R2 = 0.20) of the variation in fatigue is explained by pain. Thirty-five percent of the variance in fatigue explained by pain was accounted for by the mediation pathway.
Some of the effect of pain on fatigue is mediated by sleep disturbance, but pain has a direct effect on fatigue as well.
Although the relationship can be explained only partially by the commonsense point of view that people who are in pain lose sleep and naturally report more fatigue, this finding is important and leads to a potential intervention opportunity. Strategies to improve sleep by better pain management may contribute to decreased fatigue.
Chronic insomnia is highly prevalent in cancer patients. Cognitive-behavioral therapy (CBT) is considered the treatment of choice for chronic primary insomnia. However, no randomized controlled study has been conducted on its efficacy for insomnia secondary to cancer. Using a randomized controlled design, this study conducted among breast cancer survivors evaluated the effect of CBT on sleep, assessed both subjectively and objectively, and on hypnotic medication use, psychological distress, and quality of life.
Fifty-seven women with insomnia caused or aggravated by breast cancer were randomly assigned to CBT (n = 27) or a waiting-list control condition (n = 30). The treatment consisted of eight weekly sessions administered in a group and combined the use of stimulus control, sleep restriction, cognitive therapy, sleep hygiene, and fatigue management. Follow-up evaluations were carried out 3, 6, and 12 months after the treatment.
Participants who received the insomnia treatment had significantly better subjective sleep indices (daily sleep diary, Insomnia Severity Index), a lower frequency of medicated nights, lower levels of depression and anxiety, and greater global quality of life at post-treatment compared with participants of the control group after their waiting period. Results were more equivocal on polysomnographic indices. Therapeutic effects were well maintained up to 12 months after the intervention and generally were clinically significant.
This study supports the efficacy of CBT for insomnia secondary to breast cancer.
This study identified the psychosocial problems that 752 patients from 3 states who had been diagnosed with 1 of the 10 most commonly occurring cancers indicated concerned them the most. Approximately 1 year after being diagnosed with cancer, 68.1% of patients were concerned with their illness returning, and more than half were concerned with developing a disease recurrence (59.8%) or had fears regarding the future (57.7%). In addition to these psychological problems focused on fear, approximately two-thirds (67.1%) of patients were concerned about a physical health problem, fatigue, and loss of strength. Two other physical health problems that concerned more than two-fifths of patients were sleep difficulties (47.9%) and sexual dysfunction (41.2%). More problems were reported by younger survivors (ages 18-54 yrs), women, nonwhites, those who were not married, and those with a household income of less than 20,000 US dollars a year. Those patients currently in treatment for cancer reported on average significantly more problems (P < 0.001) and on average had a higher Cancer Problems in Living Scale (CPILS) total score (P < 0.001) compared with those not currently in treatment. In a comparison of respondents with one of the four most common cancers, the most concerns regarding problems in living and highest mean CPILS scores were reported by those diagnosed with lung cancer, followed by survivors of breast cancer, colorectal cancer, and prostate cancer.
In recent years, sleep disturbances and the health-related quality of life (QOL) experienced by adults with cancer, during and after cancer treatment, have received increasing attention in the scientific literature. The purpose of this paper was to systematically review current methodological approaches to the study of sleep disturbances and QOL in adults with cancer. Databases were searched to identify longitudinal studies of adults with cancer that measured sleep disturbances and QOL in the past 10 years. The review was focused in five primary areas: trends in publication, measurement of sleep and QOL, study design, changes in sleep disturbances and QOL, and the level of this evidence. Of the 40 studies that met the authors' criteria for inclusion, 75% were descriptive in design and 25% were intervention studies. Studies on sleep and QOL among cancer patients have become more common since 2000, include a range of sample sizes and settings, use a variety of measures of sleep and QOL, and examine patients undergoing many types of cancer therapies. No programs of research have been developed in sleep disturbances and QOL in adults with cancer. The 'evidence' that can be drawn from such studies is obviously weak. Current approaches usually describe changes over time, but have not described whether a relationship exists between sleep disturbances and QOL in adults with cancer. Directions for future research are suggested.
The aim of this study was to evaluate whether diagnostic criteria for cancer-related fatigue syndrome (CRFS) could be rigorously applied to cancer inpatients, and to explore the relationship between subjective fatigue and objective measures of physical activity, sleep, and circadian rhythm. Female cancer patients (n=25) and a comparison group of subjects without cancer (n=25) were studied. Study participants completed a structured interview for CRFS and questionnaires relating to fatigue, psychological symptoms, and quality of life (QoL). Wrist actigraphs worn for 72 hours were used as an objective measure of activity, sleep, and circadian rhythm. Compared to controls, cancer patients were more fatigued, had worse sleep quality, more disrupted circadian rhythms, lower daytime activity levels, and worse QoL. After exclusion of subjects with "probable" mood disorders, the prevalence of CRFS was 56%. Fatigue severity among the cancer patients was significantly correlated with low QoL, depression, constipation, and decreased self-reported physical functioning. It can be concluded that the diagnostic criteria for CRFS can be applied to cancer inpatients but strict application requires a rigorous assessment of psychiatric comorbidity. Despite cancer inpatients having greater impairments of sleep and circadian rhythm, it was found that fatigue severity did not appear to be related to these impairments.
To present expert consensus recommendations for a standard set of research assessments in insomnia, reporting standards for these assessments, and recommendations for future research.
N/A.
N/A.
An expert panel of 25 researchers reviewed the available literature on insomnia research assessments. Preliminary recommendations were reviewed and discussed at a meeting on March 10-11, 2005. These recommendations were further refined during writing of the current paper. The resulting key recommendations for standard research assessment of insomnia disorders include definitions/diagnosis of insomnia and comorbid conditions; measures of sleep and insomnia, including qualitative insomnia measures, diary, polysomnography, and actigraphy; and measures of the waking correlates and consequences of insomnia disorders, such as fatigue, sleepiness, mood, performance, and quality of life.
Adoption of a standard research assessment of insomnia disorders will facilitate comparisons among different studies and advance the state of knowledge. These recommendations are not intended to be static but must be periodically revised to accommodate further developments and evidence in the field.
Little attention has been paid to sleep disturbance experienced by advanced cancer patients. The purpose of the present study was to investigate longitudinal change in sleep disturbance and to identify factors that associated with and predicted sleep disturbance among 209 consecutive terminally ill cancer patients. Patients were assessed twice for sleep disturbance by one item of the structured clinical interview for assessing depression, once at the time of their registration with a palliative care unit (PCU) (baseline) and again at the time of their PCU admission (follow-up), and possible associated medical and psychosocial factors were evaluated. The proportions of patients with obvious sleep disturbance at baseline and follow-up were 15.3 and 25.9%, respectively. Sixty-seven percent of the subjects showed some sleep status changes, including both aggravation and improvement, between baseline and follow-up. Being younger, having diarrhea and living alone were significantly associated with sleep disturbance at baseline, and the increase of psychological distress was the only significant predictive factor for sleep disturbance at follow-up. These findings suggest that psychological distress is a possible key cause of sleep disturbance and management of psychological distress may be one promising strategy for prevention of sleep disturbance among advanced cancer patients.
Cytokine-induced sickness behavior was recognized within a few years of the cloning and expression of interferon-alpha, IL-1 and IL-2, which occurred around the time that the first issue of Brain, Behavior, and Immunity was published in 1987. Phase I clinical trials established that injection of recombinant cytokines into cancer patients led to a variety of psychological disturbances. It was subsequently shown that physiological concentrations of proinflammatory cytokines that occur after infection act in the brain to induce common symptoms of sickness, such as loss of appetite, sleepiness, withdrawal from normal social activities, fever, aching joints and fatigue. This syndrome was defined as sickness behavior and is now recognized to be part of a motivational system that reorganizes the organism's priorities to facilitate recovery from the infection. Cytokines convey to the brain that an infection has occurred in the periphery, and this action of cytokines can occur via the traditional endocrine route via the blood or by direct neural transmission via the afferent vagus nerve. The finding that sickness behavior occurs in all mammals and birds indicates that communication between the immune system and brain has been evolutionarily conserved and forms an important physiological adaptive response that favors survival of the organism during infections. The fact that cytokines act in the brain to induce physiological adaptations that promote survival has led to the hypothesis that inappropriate, prolonged activation of the innate immune system may be involved in a number of pathological disturbances in the brain, ranging from Alzheimer's disease to stroke. Conversely, the newly-defined role of cytokines in a wide variety of systemic co-morbid conditions, ranging from chronic heart failure to obesity, may begin to explain changes in the mental state of these subjects. Indeed, the newest findings of cytokine actions in the brain offer some of the first clues about the pathophysiology of certain mental health disorders, including depression. The time is ripe to begin to move these fundamental discoveries in mice to man and some of the pharmacological tools are already available to antagonize the detrimental actions of cytokines.
Chronic insomnia affects approximately one quarter of cancer patients. Non-pharmacologic interventions are the treatment of choice for chronic insomnia, yet they are rarely offered to people with cancer. The study question was how to make these interventions available to cancer patients. Twenty-six cancer patients who had sleep difficulty participated in focus groups or one-to-one interviews. The key questions included: What would be the best way for you to find out about a service for insomnia treatment? What would make it easy/difficult for you to participate? Transcripts were examined independently by three readers who identified participants' answers to the questions, as well as themes that emerged from participants' reflections on their experience with cancer and sleep difficulty. The readers then worked together to reach consensus on a final classification system for describing the content of patients' responses. Participants provided many practical answers to our specific questions. In addition, the following themes emerged: sleep difficulty needs greater recognition by health professionals; patients wish to receive more information about sleep and sleep difficulty; and that although patients perceive sleep as being important, they are reluctant to report sleep problems to doctors. Furthermore, participants recommended that the assessment and treatment of sleep difficulty be integrated into the health care system while considering the cancer-treatment status and energy level of patients.
Fatigue is one of the most common and distressing side effects of cancer and its treatment and may persist long after successful treatment completion. Emerging evidence suggests that inflammatory processes may be involved in cancer-related fatigue both during and after treatment. In this review, we consider the evidence for an association between inflammation and fatigue in cancer patients and survivors. Further, we identify potential mechanisms for persistent inflammation, focusing on the HPA axis. Risk factors and treatments for cancer-related fatigue are also discussed.
Impairments in health, function, and quality of life (QOL) are a central feature of insomnia, yet insomnia treatment is targeted solely to improving problems falling and staying asleep. It is not even known if the nonsleep deficits improve with current treatment. We hypothesized that therapy that improves sleep also improves these nonsleep difficulties and carried out this review to test that hypothesis.
A literature search identified the health, function, and QOL deficits of insomnia patients. A second search determined the effect of insomnia treatments on those problems, capturing randomized controlled treatment trials in insomnia patients that included relevant measures.
Insomnia patients report a variety of symptoms, including daytime sleepiness, fatigue, cognitive impairment, symptoms of depression, anxiety, health decrements, and impairment in social and occupational function. However, the reported deficits are generally not paralleled by objective evidence of impairment. Nineteen treatment studies reported measures related to these deficits. At least one treatment (eszopiclone [5 studies], zopiclone [2 studies], progressive muscle relaxation [2], zolpidem [2], multi-component cognitive-behavioral therapy [1], doxepin [1], valerian/hops [1], and stimulus control [1]) led to a significant improvement compared with placebo in at least one of these measures in 14/20 studies.
Treatment can improve the perceived health, function, and QOL of insomnia patients. This potential improvement signals the need to shift the attention of research and clinical practice to include aspects other than sleep difficulties and move towards defining successful therapy as not only improving sleep but also eliminating deficits in health, function, and QOL.
To determine the efficacy of a cognitive-behavioral intervention for treating insomnia in breast cancer survivors.
Randomized controlled trial.
University and medical center settings.
72 women at least three months after primary treatment for breast cancer with sleep-onset or sleep maintenance insomnia at least three nights per week for at least three months as determined through daily sleep diaries.
Random assignment to a multicomponent intervention (stimulus control instructions, sleep restriction, and sleep education and hygiene) or a single-component control group (sleep education and hygiene).
Sleep-onset latency, wake after sleep onset, total sleep time, time in bed, sleep efficiency, and sleep quality.
After the intervention, both groups improved on sleep-onset latency, wake after sleep onset, total sleep time, time in bed, sleep efficiency, and sleep quality based on daily sleep diaries. A between-group difference existed for time in bed. Wrist actigraph data showed significant pre- to postintervention changes for sleep-onset latency, wake after sleep onset, total sleep time, and time in bed. When compared to the control group, the multicomponent intervention group rated overall sleep as more improved.
A nonpharmacologic intervention is effective in the treatment of insomnia in breast cancer survivors.
Breast cancer survivors can benefit from a cognitive-behavioral intervention for chronic insomnia. Sleep education and hygiene, a less complex treatment than a multicomponent intervention, also is effective in treating insomnia.
Insomnia is the most common sleep disorder in the industrialized world. A variety of precipitating events have been identified, but when it becomes a persistent problem, maladaptive patterns become established, thereby, perpetuating the sleep disturbance. Individuals with insomnia have impaired next-day functioning, which impacts their quality of life and places them at increased risk of motor vehicle accidents. Insomnia is commonly associated with chronic medical conditions, as well as an increased incidence of mental disorders. Despite considerable scientific advances in both the understanding and treatment, insomnia continues to be inadequately identified and treated, with < 15% of those with severe insomnia receiving appropriate treatment. The mainstay of treatment for insomnia is cognitive-behavioral therapy, along with judicious use of hypnotic agents.
Cancer-related fatigue is reported by patients to be the most distressing and persistent symptom experienced during and after treatment. Unrelieved fatigue often accompanies other symptoms and leads to decreased physical functioning and lower health-related quality of life. Various factors, including daytime sleepiness and sleep disturbances, have been reported to influence perceptions of fatigue. This article shares current knowledge about the relationships among cancer-related fatigue, sleep disturbances, and daytime sleepiness, and makes recommendations for routine screening, assessment, and interventions to modify fatigue through optimizing sleep quality in adult cancer patients. Evidence is reviewed for nonpharmacologic and pharmacologic interventions for optimizing sleep quality in patients with acute or chronic insomnia secondary to medical illnesses, including cancer. A summary of interventions is presented that focuses on optimizing sleep quality in attempt to lower fatigue. These interventions may be helpful for adult cancer patients experiencing insomnia but will require further testing to establish their efficacy in this population. Recommendations for research are provided, including the need to increase knowledge on the relationships among fatigue, sleep disturbances, daytime sleepiness, and other symptoms in various disease sites, stages, and treatments of cancer and the need for further testing of the measurements used for the evaluation of sleep quality in clinical practice and research.
Twenty years of research on cytokine-induced sickness behavior
- Dantzer
Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain
Behav Immun. 2007; 21:153-160. [PubMed: 17088043]
Impaired sleep and rhythms in persons with cancer
- Lee