To (a) evaluate the feasibility (recruitment and retention, instrumentation, and intervention administration) and effectiveness of a brief behavioral Caregivers Sleep Intervention (CASI) that addressed the specific needs and sleep goals of family caregivers of persons with cancer, and (b) determine the effectiveness of  CASI in improving caregivers’ sleep quality, depressive symptoms, and quality of life

The Caregivers Sleep Intervention (CASI) had two sessions. The initial CASI session (week 2 of the study) lasted one hour and provided knowledge, guided participants in self-assessment of maladaptive habits affecting their sleep quality, and assisted participants to develop personal sleep and relaxation goals. In study week 5, a second one-hour CASI session (booster) reviewed the information provided in the initial session and rated personal sleep and relaxation goal achievement. Topics covered were (a) the importance of sleep and sleep \"myth busting,\" (b) stimulus control: environmental affects on sleep, (c) sleep hygiene: planning for sleep, and (d) relaxation techniques to promote sleep. Attention control participants were given the “back health” control condition at study weeks 2 and 5, with data collection at baseline, three and five weeks, and two, three, and four months postbaseline.

• The sample included 30 participants.
• Mean age of participants was 53 years, with a range of 21–85 years.
• The sample was 63% female and 37% male.
• To be included in the study, participants had to be age 21 or older, be identified as a family caregiver living with a person with advanced cancer, and have reported difficulty initiating and/or maintaining sleep or nonrestorative sleep for at least one month, with no major diagnosis of depressive disorder or preexisting sleep disorder other than insomnia.
• The sample was 80% Caucasian, 10% African American, and 10% Hispanic.
• The relationships of the caregiver to the patient were spouse/partner (57%), adult children (30%), and other (13%).
• Hours of caregiving ranged from 2 to 24 hours, with an average of 17 hours.

• Single site
• Outpatient setting
• Central Texas

End-of-life care

A repeated measures experimental design was used.

• Pittsburgh Sleep Quality Index (PSQI) was used to measure caregivers’ sleep quality.  
• An actigraph sleep watch was used to measure sleep patterns (latency, duration, efficacy, and wake after sleep onset).
• Sleep Center for Epidemiological Studies–Depression Scale (CES-D) was used to measure current and immediate past symptoms of depressions.CES-D has demonstrated good reliability at α 0.85 in previous studies.
• Caregivers Quality of Life Index–Cancer (CQOLC) was used to measure caregiver quality of life. Contextual factors, including caregiver demographic characteristics, patient demographic characteristics, and sleep arrangements, were collected on a demographic sheet.
   

Feasibility: In terms of recruitment, caregivers were difficult to identify and recruit from the community setting but were enthusiastic once identified. In terms of retention, 35 recruited caregivers who met the inclusion criteria were consented and remained in the study through the final data collection.

CASI effectiveness: Sleep duration and efficiency were consistently strongly negatively correlated with caregiver depressive symptoms and quality of life over time. Overall sleep quality and sleep latency were consistently strongly positively correlated with caregiver depressive symptoms over time.

Caregivers’ quality-of-life scores showed improvement across groups. No significant differences or patterns of change were seen between or within groups. All study participants showed improvement in self-reported sleep quality during the study. Caregivers in the CASI intervention group reported greater improvement in overall sleep quality than did the attention control group caregivers at each time point  (CASI group: baseline, M 7.9 [3]; week 5, M 7.2 [3]; month 2, M 6 [3]; month 3, M 5.5 [3]; and month 4, M 5.4 [3]. Control group: baseline, M 7.9 [5]; week 5, M 7.6 [5]; month 2, M 8.4 [5]; month 3, M 7 [5]; and month 4, M 10.3 [6]). Significant differences were seen in caregiver self-reported sleep latency at week 5 (t = 2.29, p = 0.02) and in overall sleep quality then did attention control caregivers at month 4 (t = 2.40, p = 0.03).  

Actigraph data comparisons between groups showed significant differences in sleep latency scores at two months (t = - 2.57, p = 0.02) and duration scores at four months (t = 2.0, p = 0.05).

The CASI intervention group was significantly different from the control group in sleep latency at the end of four months. Sleep latency is defined as the amount of time it takes to fall asleep. Although this is only one aspect of sleep difficulties, it does show that CASI can be effective.

• The sample was small, with less than 100 participants.
• Risk of bias existed because there was no random assignment.
• The researchers had difficulty identifying subjects for recruitment from the community setting. 
• The sample had limited ethnic diversity.

Sleeping difficulty for caregivers of patients with advanced cancer who are not currently receiving hospice care is an important focus for nursing research because the area is understudied. One-to-one attention from a nurse and goal setting are powerful strategies that healthcare providers can use with family caregivers that can impact sleep improvements and reduction of depressive symptoms. The feasibility of a CASI intervention study is promising with some needed changes to the attention control group that were outlined in this study. The steady improvement in overall sleep quality of caregivers in the CASI intervention group demonstrated the possibilities of success in a future study.

The Yoga of Awareness Program included eight weekly, 120-minute, sessions, including gentle yoga postures, breathing exercises, meditation, didactic presentations, and group interchange. Patients were also encouraged to practice at home.

• The sample was comprised of 13 women with metastatic breast cancer.
• Mean age was 59 years (range 44–75).
• Eleven of 13 patients were Caucasian.

Duke Pain Prevention Program and Treatment Program Office

The study used an exploratory, pre-/post design; no control group was used.

• Brief daily diary using a visual analog scale (VAS) during two pre- weeks and the last two intervention weeks
• Focus group feedback

Those who withdrew had lower fatigue, which was interpreted as less motivation to participate. No significant change occurred in fatigue intercept (slope was not reported). There was a trend in which increased yoga practice was associated with decreased fatigue (p = 0.07). Lagged analysis showed that increased practice was predictive of decreased fatigue the next day. Participants reported that the program was successful to manage fatigue (mean = 7.6).

• The study lacked a control group.
• The study had a small sample size.
• Single-item daily measures were used.
• There was 28% attrition:  3 preintervention and 5 during the intervention.

No adverse events were reported. The intervention was led by a certified yoga instructor.

The study evaluated the effects of a yoga intervention on menopausal symptoms among breast cancer survivors.

Patients were randomized to the yoga intervention or a wait-list control group. The intervention consisted of eight weekly, 120-minute, group classes led by a certified yoga instructor. Classes were videotaped and reviewed. Sessions involved 40 minutes of stretching poses, 10 minutes of breathing techniques, 25 minutes of meditation, 20 minutes of study of pertinent topics, and 25 minutes of group discussion. CD recordings were provided for home practice. Application of concepts to daily life were assigned weekly. Assessments were performed at baseline, posttreatment, and three months postintervention. Wait-list controls were reminded about the assessments they needed. Patients kept daily diaries to rate hot flashes and daily use of yoga.

• The study was comprised of 37 women with a mean age of 54.4 years. 
• Patients were an average of 4.9 years since diagnosis.
• All patients had breast cancer, and 40.5% were stage IA.
• Of the patients, 70.3% had prior chemotherapy, 13.5% were on tamoxifen during the study, 75.7% were married or partnered, 81.1% were Caucasian, and 80.3% had college or graduate level education.
• Patients had no hormone therapy within three months.
• Many patients were on antidepressants.
• Of the patients, 50.5% were receiving aromatase inhibitors known to increase hot flashes.

The study was performed in outpatient clinics at Duke University.

• Patients were undergoing the late effects and survivorship phase of care.
• The study has clinical applicability for late effects and survivorship.

The study was a randomized, controlled trial.

• Patients kept daily hot flash and yoga use diaries. Hot flashes were scored on a 0-to-9 numeric scale.
• In addition, a questionnaire assessed the perceived credibility of the intervention.

Those in the yoga group had a significantly better decline in hot flash frequency, severity, joint pain, fatigue, and sleep disturbance (p < 0.002). Patients in the control group had significantly better decline in the degree to which they were bothered by symptoms (p < 0.0001). There was no difference in night sweats. Mean yoga practice time spent in use of techniques was associated with less fatigue (p = 0.032). Yoga daily participation ranged from 7.3 to 64.6 minutes. There was a 76% completion rate in the yoga group.

The findings suggested a potential benefit of a group yoga and support intervention for some symptoms in breast cancer survivors.

• The study had a small sample size.
• The study had no blinding or attentional control.
• It is unclear if the benefits were derived from the yoga activities or the group activities provided. 
• There was a relatively high drop-out rate, raising the question of the practicality of the intervention as designed. 
• The sample included patients with high education levels and current marriage or partnership support.
• Measurement of symptoms was not clearly described, and scoring was unclear.

The findings suggested that yoga and support activities provided in a group setting may help patients with symptoms of hot flashes, sleep deprivation, and fatigue. There was no apparent effect on night sweats.  

To examine the efficacy of two doses of venlafaxine:  37.5 mg (low-dose study) or 75 mg (high-dose study) to treat hot flashes after breast cancer.

Women were scheduled for 14 weekly visits. Weeks 1 and 2 provided baseline information, and weeks 3 to 14 included six weeks of treatment and six weeks of placebo.

Outcomes were hot flash (frequency, severity, and bother), hot flash impact on daily life, negative effect, fatigue, sleep, and quality of life (QOL).

The sample was comprised of breast cancer survivors:  57 in the low-dose study and 20 in the high-dose study.

University cancer clinics in the southeastern and midwestern United States

Patients were undergoing the long-term follow-up phase of care.

The study included two randomized, double-blind, placebo-controlled, crossover trials.

• Adherence was measured by capsule counts and weekly written verification.
• Sternal skin conductance monitor
• Electronic event markers and written diaries used for self-reporting hot flashes
• Profile of Mood States–Short Form (POMS-SF)
• Positive and Negative Affect Scale (PANAS)
• Center for Epidemiologic Studies Depression Scale (CESD)
• Diagnostic and Statistical Manual of Mental Disorders (DSM)
• Hamilton Rating Scale–Depression (HRSD)
• Pittsburgh Sleep Quality Index (PSQI) 
• Medical Outcomes Survey (MOS)

Venlafaxine resulted in modest decreases in hot flashes, but only hot flash interference improved differentially at the higher dose. The timing of the effect of venlafaxine on hot flashes varied by dose.

Only women with a 50% or greater decrease in physiologic hot flashes experienced significant improvement in fatigue, sleep quality, and QOL. Although side effects were mild, most patients discontinued venlafaxine long-term.

• The sample was racially and ethnically homogeneous.
• The study had a small sample size.
• Treatment time was limited.
• The study lacked pharmacogenetic data.
• In assessing hot flashes, subjective hot flash measures are prone to placebo effects, and subjective hot flash measures and secondary outcome measures may both be subject to a positive reporting bias.
• A study psychologist verified the absence of depressive symptoms, which could confound data if present.
• Trained study nurses are required.

To pilot test the acceptability of a DVD platform to deliver a newly created cognitive-behavioral hot flash intervention and estimate its efficacy.

Participants viewed a DVD consisting of video clips demonstrating the intervention, which included one cognitive activity (distraction) and two behaviors (remain still, breathe). The video clips demonstrated the intervention during three situations:  resting at home, during housework, and in a work environment. Participants were asked to practice the intervention for one week. Outcomes measured were hot flash occurrence, severity, bother, mood disturbance, affect, hot flash disruption, and sleep disturbances.

• The sample was comprised of 49 women (26 at site 1 and 23 at site 2), with 40 completing all aspects of the study.
• Women with any stage of breast cancer or at high risk for disease were included.
• Mean age was 54.42 years, and all women were 21 years or older and experiencing hot flashes (93% were postmenopausal).
• Of the women, 75% were Caucasian.

The study was conducted at outpatient cancer clinics serving rural and urban areas in the midwestern and southeastern United States.

Patients were undergoing the long-term follow-up phase of care.

This was a nonrandomized, pre/post-test pilot study design.

• Center for Epidemiologic Studies Depression Scale (CESD)
• Profile of Mood States–Short Form (POMS-SF)
• Positive and Negative Affect Schedule (PANAS)
• Biolog®3991
• Hot flash severity and bother numeric rating scales
• Hot Flash-Related Daily Interference Scale (HFRDIS)
• Pittsburgh Sleep Quality Index (PSQI)
• Actiwatch®

The DVD was an accepted and feasible intervention delivery method. Although statistically significant improvement in hot flash parameters was observed, changes were equal to about a 10% change. The 10% reduction in hot flashes affected related outcomes, with the HFRDIS improving in all participants and CESD scores improving in the subset that reported the worst hot flash severity. No change in affect or sleep was noted.

• The unblinded, single-group design allows for placebo effect.
• The study had a small sample size.
• There was difficulty quantifying the frequency of intervention use; therefore, the variable was not included in the analyses.
• Drawbacks to using a DVD include the one-way nature of instruction and limited opportunity for participants to ask questions.

Examination of venlafaxine at two doses for efficacy in relation to physiologic and self-reported hot flashes and other outcomes

• Study duration: 14 weeks 
• Low-dose arm:  6 weeks at 37.5 mgof venlafaxine daily 
• High-dose arm: consisted of 1 week of 37.5 mg of venlafaxine daily, 4 weeks of 75 mg daily, and one week of 37.5 mg daily
• Weeks 1 and 2 provided baseline data 
• Weeks 3–14 included 6 weeks of treatment and 6 weeks of placebo

• Breast cancer survivors  recruited between 2000–2004 with follow up continuing through 2005 
• Must have been postmenopausal or using an approved method of birth control
• Low-dose study (n = 64, cancer clinics in the Southeast)
• High-dose study (n = 20, cancer clinics in the Midwest)

Outpatient cancer clinics

Randomized, double-blind, placebo-controlled crossover trial

A psychologist verified absence of depressive symptoms using two measures: Structured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders and the 17-item Hamilton rating scale depression. Adherence to the treatment was assessed using capsule counts and weekly written verification. Physiologic hot flash frequency was evaluated using weekly 24-hour ambulatory sterna skin conductance monitoring and self-reported hot flash diaries. Weekly blood pressure monitoring and other tools were used for side effect monitoring.

Venlafaxine resulted in modest hot flash reduction, but only hot flash interference improved differentially at the higher dose. Timing of effects varied by dose. Only women who experienced a greater than 50% decrease in physiologic hot flashes also experienced a significant improvement in fatigue, sleep quality, and QOL. Although side effects were mild, most patients discontinued venlafaxine long term.

A placebo effect occurred for self-report of hot flashes but not for physiologic hot flashes in the high- and low-dose arms.

Main study limitations:

• Racially and ethnically homogeneous samples
• Limited treatment time
• Small sample size
• Lack of pharmacogenetic data. Also limitations regarding
• Assessing hot flashes with self-reporting is subject to placebo effects

Each study intervention lasted for 14 weeks. The low-dose study treatment required patients to take 37.5 mg/day of venlafaxine. The high-dose treatment required patients to take venlafaxine at 37.5 mg/day for one week, followed by 75 mg/day for four weeks, followed by 37.5 mg/day for one week. Women were scheduled for 14 weekly visits. Weeks 1 and 2 provided baseline information, and weeks 3–14 consisted of six weeks of treatment (T1–T6) and six weeks of placebo (P1–P6). Trained nurses visited patients in the clinic, at home, or in their workplace to maintain consistent follow-up. Patients were telephoned 1, 6, and 12 months after completing the weekly visits to assess continued venlafaxine use.

• The study included 77 breast cancer survivors.
• Low-dose study group
  • Mean age = 50.5 years, mainly non-Hispanic whites (91%), married (81%), and working full-time (60%).
  • Mostly stage II or less at diagnosis (96%), and had received radiation (68%), chemotherapy (70%), or both (51%).
  • 51% were taking endocrine therapy.
• High-dose study group:
  • Mean age = 53 years, mostly non-Hispanic whites (90%), married (53%), and working full-time (63%)
  • Mostly stage II or less at diagnosis (94%), taking endocrine therapy (63%), had received radiation (58%), chemotherapy (63%), or both (38%).
• Patients were excluded if they used tamoxifen or aromatase inhibitor for less than six weeks, were taking antidepressants, received hot flash treatment within the past four weeks, or were pregnant or lactating.

The study was conducted in university cancer clinics in the southeast (low-dose study) and midwest (high-dose study) United States.

Active treatment

Randomized, Double-blind, placebo-controlled, crossover trials:

1. Low-dose study (N=57)
2. High-dose study (N=20)

Profile of Mood States–Short Form (fatigue subscale)

Overall fatigue did not improve with the venlafaxine treatment when compared with the placebo. However, a subgroup of 15 women who received venlafaxine and had a 50% or greater decrease in physiologic hot flashes experienced a significant improvement in fatigue from baseline to six weeks compared to the placebo group (p = 0.007).

Homogenous sample in respect to race and ethnicity Small sample size Limited treatment time Lack of pharmacogenetic data (i.e. did not evaluate genetic polymorphisms in patients which may have explained observed response to venlafaxine treatment

To evaluate long-term effects of completed decongestive therapy (CDT) on lower-extremity lymphedema 

Patients who had been treated for lower-extremity lymphedema secondary to melanoma treatment from January 2006 to July 2009 were invited to participate in reevaluation. Patients participated in a interview and measurement of limb circumference. Treatment that had been provided included initial phase 1 treatment (five consecutive days of manual lymph drainage [MLD], compression bandaging, and exercises with bandages) and phase 2 maintenance treatment (skin care, supporting garments, low-stretch bandages, and a set of 10-minute exercises to be done at home). During active phases, patients completed comprehensive assessment via chart items developed by the Italian Lymphedema Association, including demographic and disease data and quality-of-life items rated by patients on a visual analog scale.

• The sample (N = 12) was 25% male and 75% female.
• All patients had melanoma that had been previously treated in the past one to four years, at least one lymph node removed from the groin area, and unilateral secondary lymphedema diagnosed by lymphoscintigraphy.
• Participants were excluded if they had complete decongestive therapy within the previous six months.

The study was conducted at a single-site, outpatient setting in Italy.

• Patients were in the long-term follow-up phase of care.
• This study has clinical applicability for late effects and survivorship.

A retrospective analysis and follow-up design was used.

• Limb circumference measurements were taken.
• In-depth interview (IDI) questionnaire history (IDI not defined) and quality-of-life information were obtained.

Findings showed that from baseline to the end of initial active treatment with CDT, the percent change in limb volume was –34%, and from baseline to the reevaluation for was –17% (p = 0.05). Patients with higher body mass index (BMI) reported significantly lower quality-of-life results (p < 0.05). Sixty percent of patients reported good compliance with the use of garments, bandages, and exercises.

The study provided limited information about longer-term outcomes of patients with lymphedema secondary to melanoma.

• The small sample (N < 30) and other study method questions limit utility of findings.
• The study had no comparison or controls.
• Procedures stated that all interviews and measurements were done by the same therapist, who was blinded to all prior measures; however, the authors did not explain how this was accomplished.
• Time from initial treatment was highly variable at one to four years.
• How the percent change at the reevaluation was significantly lower than baseline, when prior change that was greater was not significant, is unclear.

Study findings provided minimal information about the longer-term results from CDT for lower-limb lymphedema in patients who had melanoma. Information about management of lower-extremity lymphedema and long-range outcomes related to lymphedema and management approaches is limited. Further research in these areas is needed.

To test the hypothesis that patients who receive a vapor-heated (VH) fibrin sealant in the inguinal wound following inguinal lymphadenectomy in conjunction with treatment of a vulvar neoplasm would experience a 25% reduction in the incidence of grade 2 and 3 lymphedema of the lower extremity compared to control patients

Patients were randomized to the investigational or control arm of the study. In the investigational arm (FS), VH fibrin sealant was applied to the inguinal wound base. In the control arm (SC), the closure of the wound was performed without application of the fibrin sealant. Patients were assessed prior to treatment and postoperatively at the time of drain removal, at six weeks, and at three and six months.

• The study sample (N = 137) was comprised of female patients with a vulvar malignancy.
• Patients were randomized to the FS arm (n = 70) or the SC arm (n = 67).
• Median age in the FS arm was 61 years, with a range of 30–90 years; median age in the SC arm was 57 years, with a range of 33–87 years.
• All patients were undergoing a radical vulvectomy or hemivulvectomy with either an ipsilateral or bilateral inguinal lymphadenectomy.

The study was conducted at multiple Gynecologic Oncology Group member institutions across the United States.

The study used a randomized phase III trial design.

• Circumference was measured to determine leg lymphedema.
• Surgical complications were measured, including vulvar wound separation, inguinal wound separation, grading of infection or cellulitis, and grading of seroma or lymphocyst.
• Duration of drain and drain output in the 24 hours prior to drain discontinuation also were evaluated.

The incidence of grade 2 and 3 lymphedema was 67% in the SC arm and 60% in the FS arm (p = 0.4779). The incidence of lymphedema was strongly associated with inguinal infection (p = 0.0165). No statistically significant difference was found in duration of drains or drain output or incidence of inguinal infections, wound breakdowns, or seromas. The FS arm experienced an increased incidence of vulvar infections (p = 0.0098).

VH fibrin sealant in inguinal lymphadenectomies does not reduce leg lymphedema and may increase the risk for complications in the vulvar wound.

• The sample size in each group was small, with less than 100 participants.
• Follow-up for circumferential measurement occurred only through six months.
• The protocol prescribed 10–15 lb of pressure over the wound bed after the VH fibrin sealant had been applied, but the exact location and amount of pressure over the wound was not monitored.

Future trials should be designed to evaluate surgical techniques and postoperative care that would decrease wound breakdowns and complications while monitoring for variables that may be related to increased incidence of swelling or lymphedema in patients with vulvar cancer.

The mindfulness-based stress reduction (MBSR) meditation program included relaxation, meditation, gentle yoga, and daily practice. Patients attended eight sessions and received a 52-page booklet with weekly instructions plus an audiotape of the meditations. Outcomes were sleep, mood, stress, and fatigue.

• The sample was comprised of 63 patients (49 women, 14 men).
• Mean age was 54 years (range 32–78).
• Patients had mixed cancer diagnoses and stages.

• Outpatient
• Canada

Patients were undergoing the long-term follow-up phase of care.

The study used a prospective, repeated measures, quasiexperimental, feasibility design with one group.

Pittsburgh Sleep Quality Index (PSQI)

At pretreatment, 91% of the sample had a PSQI of 5 or more and 51% had a score of 10 or more. At posttreatment, 27% reported a PSQI of greater than 10. Sleep disturbance was significantly reduced, and subjective sleep quality was improved.

• The study lacked a control or comparison group; also, only a subjective sleep measurement was used. The relative importance of different components of the intervention is not known.
• Training in delivering the intervention is needed.
• Cost is incurred for a space for the class and for an instructor.