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Husebo, A.M., Dyrstad, S.M., Mjaaland, I., Soreide, J.A., & Bru, E. (2014). Effects of scheduled exercise on cancer-related fatigue in women with early breast cancer. The Scientific World Journal, 2014, 271828. 

Study Purpose

To compare the effects of a scheduled, home-based exercise intervention to the effects of advising patients to exercise on fatigue, physical fitness, and physical activity level

Intervention Characteristics/Basic Study Process

Patients who had surgical treatment and were receiving adjuvant chemotherapy for breast cancer were randomly assigned to the scheduled exercise or control comparison groups. The intervention combined resistance and aerobic exercise with resistance bands and strength training three times per week along with 30 minutes of brisk walking daily. Those in the experimental group received motivational phone calls every two weeks. Patients in the control group were advised to continue their regular activity levels and had one follow-up phone call. Study measures were obtained at baseline, prior to chemotherapy, 8–24 weeks at the end of chemotherapy, and about six months after completing chemotherapy.

Sample Characteristics

  • N = 54
  • MEAN AGE = 52.2 years (SD = 9.3 years)
  • FEMALES: 100%
  • KEY DISEASE CHARACTERISTICS: 88.4% of patients had stage I or II disease; 80.6% had college-level education;  81% were living with a partner, and about one half were employed full or part-time.

Setting

  • SITE: Single-site  
  • SETTING TYPE: Outpatient  
  • LOCATION: Norway

Phase of Care and Clinical Applications

  • PHASE OF CARE: Multiple phases of care

Study Design

Randomized controlled trial (RCT)

Measurement Instruments/Methods

  • Schwartz Cancer Fatigue Scale (SCFS-6)
  • International Physical Activity Questionnaire (IPAQ)
  • Six-Minute Walk Test (6MWT)
  • Exercise diary

Results

Fatigue scores increased significantly from baseline to the end of chemotherapy for all patients (p = .003) with no difference between groups. Fatigue returned to baseline levels after the end of chemotherapy with no difference between groups. A similar pattern was shown for all patients in physical fitness. There were no differences between groups in mean levels of physical activity per week, though there was a slight trend toward more exercise in the intervention group.

Conclusions

There were no additional effects of a scheduled home exercise program to reduce fatigue compared to individuals who were simply encouraged to maintain appropriate exercise levels.

Limitations

  • Small sample (< 100)
  • Risk of bias (no blinding)
  • Risk of bias (no appropriate attentional control condition)
  • Subject withdrawals ≥ 10%

Nursing Implications

Study findings show a pattern of fatigue such that fatigue increases significantly during chemotherapy and then declines after the end of treatment. Both groups of patients in this study performed exercise at general recommended levels, which likely accounts for the lack of differences in fatigue found. These results suggest that patients do not necessarily need to have scheduled approaches to exercise, and that encouraging patients to maintain at least moderate exercise levels can be effective. Nurses can encourage patients to maintain exercise and choose approaches that they prefer in order to maintain motivation for regular activity.

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Hurlow, A., Bennett, M.I., Robb, K.A., Johnson, M.I., Simpson, K.H., & Oxberry, S.G. (2012). Transcutaneous electric nerve stimulation (TENS) for cancer pain in adults. Cochrane Database of Systematic Reviews, 3, CD006276.

Purpose

To review and summarize the evidence regarding the effect of transcutaneous electric nerve stimulation (TENS) for management of cancer-related pain

The type of study is systematic review.

Search Strategy

Databases searched were MEDLINE, CINAHL, PEDro, AMED, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials.

An extensive listing of search terms per database are provided.

Studies were included in the review if they evaluated TENS-administered monophasic or biphasic pulsed electrical currents, reported on participants 18 years or older, and were randomized controlled trials (RCTs) not involving active treatment control.

Studies reporting on percutaneous interventions were excluded.

Literature Evaluated

The total of four references were retrieved.

The Jadad scale was used for evaluation as well as the Cochrane risk of bias tool.

Sample Characteristics

Three studies were included in the review; two studies were added to prior review of two studies.

Sample range across studies was 15–49, with a total of 68 patients included in the review.

Results

Results were inconclusive due to lack of suitable RCTs for inclusion. One study indicated that bone pain may improve with TENS, but this was not well designed and underpowered. Two studies showed no significant difference with TENS.

Conclusions

No conclusions regarding the effectiveness of TENS can be made.

Limitations

  • The review included few studies with variable quality.
  • Studies were underpowered.

Nursing Implications

There is insufficient evidence to determine whether TENS is effective for management of pain in patients with cancer.

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Hunter, M. S., Coventry, S., Hamed, H., Fentiman, I., & Grunfeld, E. A. (2009). Evaluation of a group cognitive behavioural intervention for women suffering from menopausal symptoms following breast cancer treatment. Psycho-Oncology, 18, 560–563.

Study Purpose

To evaluate a group cognitive-behavioral intervention to alleviate menopausal symptoms (hot flushes [HF] and/or night sweats [NS]) in women who have had treatment for breast cancer.

Intervention Characteristics/Basic Study Process

Following a two-week daily diary assessment, patients were offered six 90-minute weekly sessions of group cognitive-behavioral therapy (CBT). CBT included:  information and discussion about menopausal symptoms; monitoring and modifying stimulants that precipitate symptoms; relaxation and paced breathing; and techniques to reduce stress and manage HF, NS, and sleep. The primary outcome measures were HF frequency and HF problem rating. Secondary outcomes included scores on the Women’s Health Questionnaire (WHQ) and scores pertaining to health-related quality of life (HRQOL) as measured by the SF-36®. Beliefs about HF were monitored to examine the effects of CBT. 

Sample Characteristics

  • The study was comprised of 17 women receiving group CBT.
  • Mean age was 53.7 years (range 46–65).
  • Of the patients, 12 (71%) had undergone breast-conserving surgery; 3 (18%), modified radical mastectomy; 9 (53%), chemotherapy; 14 (82%), radiotherapy; and 12 (71%) were taking adjuvant hormonal therapies (11 were taking tamoxifen; 1 was taking anastrozole).
  • At diagnosis, seven patients (41%) were premenopausal, six (35%) were in the early or late transition stage of menopause, and four (24%) were in the early or late postmenopausal stage.
  • Average time since diagnosis was 23.2 months.
  • Average duration of HF and NS was 2.1 years.
  • Patients were treated in groups (of six, six, and five members); 12 women (59%) attended all six sessions, three women attended five sessions, and two attended three sessions. The majority (83%) completed all assessments.

Setting

  • Multisite
  • Outpatient
  • Clinic staff recruited patients by using a database at two breast units in London, England.

Phase of Care and Clinical Applications

  • Patients were undergoing the transition phase of care:  after initial treatment and completion of chemotherapy and/or radiotherapy and with or without hormone replacement therapy.
  • The study has clinical applicability for late effects and survivorship.

Study Design

The study was a single-group, exploratory trial with pre- and posttreatment assessment after six weeks and three months.

Measurement Instruments/Methods

  • Hot Flush Frequency and Problem Rating Scale (HFRS) 
  • WHQ
  • Hot Flush Beliefs Scale (HFBS)
  • SF-36® HRQOL ratings
  • Daily diaries
     

Results

  • Weekly frequency of HF and NS was reduced from 75.7 to 46.9 (p < 0.03) at the posttreatment measure to 38.3 (p < 0.02) at the three-month follow-up. This change represents a 38% reduction at posttreatment and a 49% reduction at the three-month follow-up.
  • Problem rating was reduced from 6.3 to 3.4 at posttreatment (p < 0.0001) and to 2.6 at follow-up (p < 0.0001).
  • Depressed mood and anxiety significantly decreased from assessment to posttreatment (p < 0.02), and reductions were maintained at the three-month follow-up (p < 0.03).
  • Sleep improved significantly (p < 0.003).
  • Subscales of the SF-36® showed other significant improvements:  emotional role limitation (p < 0.0001), mental health (p < 0.01), energy/vitality (p < 0.0001), and general health (p < 0.003).
  • Total scores on the HFBS decreased significantly, from 28.2 to 22.4 at posttreatment (t = 3.77; df = 16; p < 0.002), and were maintained at 22.7 at follow-up (t = 4.34; df = 16; p < 0.001). These reductions reflected a significant change in beliefs.

Conclusions

  • Results suggest that CBT delivered in groups might offer a viable option for women with troublesome, undertreated, menopausal symptoms following breast cancer treatment, but further controlled trials are needed.
  • CBT is consistent with the preferred treatment of women surveyed.
  • Improvements continued after treatment, which may reflect the skills-learning aspect of CBT. HF and NS decreased, as did depressed mood and anxiety.
  • Sleep improved, as reported by changes in WHQ ratings.
  • Results showed no signficant improvement in specific dimensions of HRQOL, particularly emotional role limitation, energy/vitality, or mental health.

Limitations

  • The study had a small sample size, with less than 30 patients.
  • The study is of limited generalizability.
  • The main limitations of the study were lack of controls for placebo effects, attention, and spontaneous remission.
     

Nursing Implications

Nurses could be trained to conduct structured, interactive, group CBT with individual treatment goals. A randomized, controlled trial is recommended for further investigation.

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Hunter, M.S., Coventry, S., Hamed, H., Fentiman, I., & Grunfeld, E. A. (2009). Evaluation of a group cognitive behavioural intervention for women suffering from menopausal symptoms following breast cancer treatment. Psycho-Oncology, 18, 560–563.

Study Purpose

Primary aim: To evaluate the effectiveness of group cognitive behavioral therapy (CBT) on hot flashes and night sweats in women who have had breast cancer

Secondary aim: To evaluate the effect of group CBT on depressed mood, anxiety, sleep, and quality of life

Intervention Characteristics/Basic Study Process

The intervention consisted of six group sessions using a psychoeducational approach with education regarding hot flushes, relaxation, stress management, and sleep strategies.

The intervention was delivered by a psychologist plus a trainee/intern.

Relaxation and paced breathing were demonstrated and practiced in each session, and participants were given a CD for ongoing use.

Sample Characteristics

  • The sample was comprised of 17 women with breast cancer.
  • Mean age of participants was 53.7 years, with a range of 46–65 years.
  • Average time since diagnosis was 23.2 months; 82% had received chemotherapy and radiation therapy, and 71% were receiving adjuvant hormonal therapies.
  • Mean duration of hot flashes was 2.1 years.
  • Of the sample, 70% were employed and 53% had more than 16 years of education.

Setting

  • Single site (two breast units)
  • Other setting
  • London, England, United Kingdom

Phase of Care and Clinical Applications

  • Transition phase after initial treatment
  • Late effects and survivorship

Study Design

A pre/post-test design was used.

Measurement Instruments/Methods

  • Hot Flush Frequency and Problem Rating Scale (HFRS): Three 10-point Likert-type scales
  • Daily hot flush diaries completed during a two-week assessment and at the end of treatment
  • Women’s Health Questionnaire (WHQ): 36 items to assess mood and sleep
  • Short Form 36 (SF-36): 36 items to assess health-related quality of life
  • Hot Flush Beliefs Scale (HFBS)

Results

Depression and anxiety decreased from baseline to post-treatment (p < 0.006; p < 0.02). Reductions maintained at the three-month follow-up.

Conclusions

Results suggest that group CBT may be an effective option for women who have menopausal symptoms following breast cancer treatment.

Limitations

  • The sample was small.
  • Only 59% of participants completed all six sessions.

Nursing Implications

Participants had a mean duration of hot flushes of more than two years, suggesting that symptoms may have been unrelated to their recent cancer treatment and more associated with menopause.

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Hunter, A., Mahendra, P., Wilson, K., Fields, P., Cook, G., Peniket, A., … Marcus, R. (2009). Treatment of oral mucositis after peripheral blood SCT with ATL-104 mouthwash: Results from a randomized, double-blind, placebo-controlled trial. Bone Marrow Transplantation, 43, 563–569.

Study Purpose

To assess the tolerability of three ATL-104 doses and to assess the efficacy and safety of ATL-104 on mucositis in patients requiring high-dose melphalan or BEAM (carmustine, etoposide, cytarabine, and melphalan) before peripheral blood SCT (PBSCT)

Intervention Characteristics/Basic Study Process

This study included two parts. In the first part, patients were randomized to receive placebo or ATL-104 in doses of 50, 100, or 150 mg orally by mouthwash as a 15 mL total volume swilled in the mouth for 15-30 seconds and then swallowed. ATL-104 is a plant lectin associated with mitogenic activity and epithelial cell growth. Following harvest of PBSCs, patients received study treatment for three days before beginning a course of chemotherapy. For patients receiving BEAM, chemotherapy lasted for six days, whereas patients receiving high-dose melphalan had one day of treatment. PBSCT was administered 1–2 days after completion of chemotherapy, and patients then received three once daily doses of ATL-104. In the second part, patients were randomized to placebo or to one of the three ATL-104 doses.

Sample Characteristics

  • The study reported on 63 patients with a mean age of 53.3 years.
  • The sample had 17 females and 46 males.
  • The majority of patients (60.3%) received high-dose melphalan chemotherapy for multiple myeloma, and 39.7% received BEAM chemotherapy for lymphoma.

Setting

The study was conducted in an inpatient setting in the United Kingdom.

Study Design

  • Part 1 was a randomized, double-blind, placebo-controlled phase IIa dose escalation study.
  • Part 2 was a randomized, double-blind, placebo-controlled parallel group study.

Measurement Instruments/Methods

  • The extent and severity of mucositis was assessed daily from screening until the final assessment, which was performed 28 days after the last dose of ATL-104 or at withdrawal.
  • World Health Organization (WHO) and Western Consortium for Cancer Nursing Research (WCCNR) toxicity scales were used.

Results

Treatment with ATL-104 substantially reduced the median duration of severe oral mucositis compared with placebo (median duration: ATL-104 for two to three days, placebo 10.5 days) (p < 0.001). The effect of ATL-104 on the incidence of severe oral mucositis was inconclusive. Adverse events (AEs) were mild to moderate in intensity with gastrointestinal (GI) AEs being most common.

Conclusions

ALT-104 substantially reduced the duration of severe mucositis and was well tolerated.

Limitations

This study had inconclusive results regarding the incidence of severe mucositis. Further studies with a larger number of patients are needed to establish the effects of ATL-104 on the duration and severity of mucositis. Limited range of ATL-104 doses may be responsible for the lack of dose-response.

Nursing Implications

Mouthwashes are easy to administer; however, adherence is a concern when used preventatively or when the patient has oral discomfort or fatigue. The hospital setting allows for easier monitoring and assistance in promoting adherence. If further studies show a benefit to patients, cost and availability will be influencing factors toward good outcomes.

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Huisman, M., van den Bosch, M.A., Wijlemans, J.W., van Vulpen, M., van der Linden, Y.M., & Verkooijen, H.M. (2012). Effectiveness of reirradiation for painful bone metastases: A systematic review and meta-analysis. International Journal of Radiation Oncology, Biology, Physics, 84, 8–14.

Purpose

STUDY PURPOSE: To assess pain response after reirradiation in patients with painful bone metastases not sufficiently responding to initial radiation therapy or exhibiting recurrent pain after initial response

TYPE OF STUDY: Combined systematic review and meta-analysis

Search Strategy

DATABASES USED: MEDLINE, EMBASE, and Cochrane Collaboration library

KEYWORDS: Radiotherapy, reirradiation, retreatment, bone metastases, palliative treatment

INCLUSION CRITERIA: All types of studies were allowed. Participants received reirradiation at the initial site of radiation for radiation-refractory metastatic bone pain. Both the initial treatment and retreatment consisted of external beam radiation therapy (EBRT). Reported outcomes were reported at least in response to initial reirradiation, and original research data were reported. If eligibility for inclusion could not be decided based on abstract screening, or if the abstract was not available, the full-text article was reviewed. To qualify for the meta-analysis, the study had to meet additional criteria: outcomes were available on an individual patient level, and the size of the study population was 10 patients or more.

EXCLUSION CRITERIA: Languages other than English, German, French, and Dutch

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 707

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Authors were contacted for missing data. Publication quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) method. Data extraction and quality assessment was performed independently by two observers.

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 10 (qualitative synthesis), 7 (meta-analysis)
  • TOTAL PATIENTS INCLUDED IN REVIEW = 440
  • SAMPLE RANGE ACROSS STUDIES: 11%–24% of patients observed received reirradiation, numbering from 4–173 cases
  • KEY SAMPLE CHARACTERISTICS: Sample characteristics were available in two studies. One study (Van Der Linden et al.) reported that 61% of participants were male, 39% were female, the mean age was 65, and the mean Karnofsky Performance Status was 70. In a second study (Hayalshi et al.), it was reported that 57% of participants were male, 43% were female, the median age was 60, and the mean Eastern Cooperative Oncology Group (ECOG) performance status score was 2.5. Primary tumor types were breast (33%), prostate (21%), lung (23%), and other tumor types (23%). Reirradiated sites were localized to the spine (36%), pelvis (38%), proximal long bones (12%), and other locations (14%). Most patients were treated with single-fraction radiotherapy.

Phase of Care and Clinical Applications

PHASE OF CARE: Transitional care after initial treatment

APPLICATIONS: Late-effects, survivorship, and palliative care

Results

In this meta-analysis, 264 out of 440 patients achieved either complete or partial response with an overall response rate of 58%. Sensitivity analysis was not feasible. The complete response rate for reirradiation ranged from 16%–28%, and partial response rates were 28%–45%. Pooling was not appropriate due to the low number of studies. The time to response after reirradiation ranged from three to five weeks.

Conclusions

Approximately 60% of patients derived some benefit from the reirradiation of radiation-refractory bone pain. The time to response was three to five weeks. For those receiving reirradiation in a circumstance in which the end of life is near, this method may not be effective. Remission of pain, however, was reported to last anywhere from 15–22 weeks.

Limitations

Not all studies reported drop-out rates and so an intention to treat analysis was not feasible. If reported, however, drop-out rates ranged from 14%–35%. These rates were attributed to death and symptomatic relief but were not clear, so bias could not be excluded. Further, no randomized, controlled trial has been published on reirradiation treatment for radiation-refractory metastatic bone pain. There is limited evidence on reirradiation effectiveness, study quality is mediocre, and populations are small. Also, the difference in study design, clinical differences between study populations, lack of clinical guidelines for reirradiation, and changes in insight over time contributed to the heterogeneity observed in the included studies. All of these factors again support the need for ongoing investigation of reirradiation for bone metastases and further investigation of palliative care measures to provide optimal relief for patients with painful bone metastases.

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Huisman, M., Verkooijen, H.M., van der Linden, Y.M., van den Bosch, M.A., & van Vulpen, M. (2015). Effectiveness of repeat radiotherapy for painful bone metastases in clinical practice: A 10 year historical cohort study. Clinical Oncology, 27, 472–478. 

Study Purpose

To assess the effectiveness of retreatment with radiotherapy for painful bone metastases

Intervention Characteristics/Basic Study Process

Data were collected from medical records. Only evaluable patients with pain response documentation were included in the analysis. Information from records was used to categorize pain because no numerical pain scores were recorded. For patients with available data, the pain response proportion was calculated. For those with no response data, it was assumed that these were nonresponders for the calculation of a worst-case scenario.

Sample Characteristics

  • N = 247
  • MALES: 57%, FEMALES: 43%
  • KEY DISEASE CHARACTERISTICS: Various tumor types
  • OTHER KEY SAMPLE CHARACTERISTICS: Overall, 56% of patients had multiple bone metastases, and the most frequent sites were spine, pelvis, and hips.

Setting

  • SITE: Single site 
  • SETTING TYPE: Outpatient 
  • LOCATION: Netherlands

Phase of Care and Clinical Applications

  • PHASE OF CARE: Late effects and survivorship
  • APPLICATIONS: Palliative care 

Study Design

Retrospective, descriptive study

Measurement Instruments/Methods

Not applicable

Results

Overall, 66% of evaluable patients indicated responses with decreases in pain. In the worst-case analysis, the overall response rate was 43%. The use of systemic analgesia (overall response [OR] = 0.39, p = 0.037) and prior pain response to radiotherapy (OR = 1.01, p = 0.049) were predictors of response to repeat radiotherapy. Patients who had an initial response were more likely to respond to retreatment, and those having used systemic therapy were less likely to respond. The toxicities experienced were all grades 1 and 2, including nausea and vomiting, fatigue, diarrhea, and skin reactions. In 4% of patients, a pathologic fracture at the retreated site was reported, and one patient developed radiation-induced femoral head necrosis requiring a total hip replacement. For the initial treatment, it was reported that 13% of patients received no pain medication, and 43% had only levels 1 and 2 analgesia according to the World Health Organization analgesic ladder.

Conclusions

The findings of this study suggested that retreatment with radiation therapy for bone metastases can be effective for pain reduction. Prior response to radiation therapy for pain suggested better odds that retreatment would produce a response.

Limitations

  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment) 
  • Unintended interventions or applicable interventions not described that would influence results
  • Measurement/methods not well described
  • Measurement validity/reliability questionable
  • Other limitations/explanation: No information was provided regarding whether any bone modifying agents were used. The initial analgesia used was low, and it was not clear if pain was maximally treated.

Nursing Implications

Patients who have initial pain responses to radiation therapy for bone metastases may benefit from repeat radiotherapy.

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Hui, D., Morgado, M., Chisholm, G., Withers, L., Nguyen, Q., Finch, C., . . . Bruera, E. (2013). High-flow oxygen and bilevel positive airway pressure for persistent dyspnea in patients with advanced cancer: A phase II randomized trial. Journal of Pain and Symptom Management, 46, 463–473. 

Study Purpose

To examine changes in dyspnea through a randomized trial of high-flow oxygen (HFO) and bilevel positive airway pressure (BiPAP) in patients with cancer

Intervention Characteristics/Basic Study Process

Patients were randomized using a computer-generated randomization scheme in a 1:1 ratio to receive either two hours of HFO followed by a washout period and then two hours of BiPAP or two hours of BiPAP followed by a washout period followed by two hours of HFO. Data on dyspnea were collected every 10 minutes after the first intervention for as much as one hour. Patients participated in the second intervention if their dyspnea level was ≥ baseline dyspnea level minus one or  ≥ 3/10 after one hour.

Sample Characteristics

  • N = 30
  • AVERAGE AGE = 61 years (range = 29–79 years)
  • MALES: 47% (n = 14), FEMALES: 53% (n = 16)
  • KEY DISEASE CHARACTERISTICS: Lung 43% (n = 13), head and neck 3% (n = 1), genitourinary 3% (n = 1), gastrointestinal 10% (n = 3), breast 17% (n = 5), other 23% (n = 7); cancer stage metastatic 87% (n = 26) and local 13% (n = 4); causes of dyspnea were pulmonary parenchymal lesions 70% (n = 21), pleural effusions 50% (n = 15), lymphangitic carcinomatosis 7% (n = 2), and other noncancer causes; not already on home supplemental oxygen 70% (n = 21); majority of participants (93%) on supplemental oxygen at the time of enrollment with a median of 3 L per minute and an average oxygen saturation of 95% (SD = 4%). 
  • OTHER KEY SAMPLE CHARACTERISTICS: Inclusion criteria: average intensity of dyspnea at rest over the past week ≥ 3/10 on a numeric rating scale despite the use of supplemental oxygen, life expectancy of more than one week, and English-speaking; exclusion criteria: hemodynamic instability, acute respiratory distress with impending intubation, delirium (Memorial Delirium Assessment Scale > 13/30), Glasgow Coma Scale < 8/15, contraindications to BiPAP, or noncancer-related dyspnea with supplemental home oxygen before hospitalization

Setting

  • SITE: Single site  
  • SETTING TYPE: Inpatient  
  • LOCATION: MD Anderson Cancer Center

Phase of Care and Clinical Applications

  • PHASE OF CARE: End-of-life care
  • APPLICATIONS: Palliative care

Study Design

Randomized, open-label study with a parallel design and an optional second intervention

Measurement Instruments/Methods

  • Numeric Rating Scale (NRS), a measurement of dyspnea on a 0–10 scale
  • Modified Borg Scale (MBS), an assessment scale for dyspnea
  • Global symptom evaluation
  • Memorial Delirium Assessment Scale (MDAS)
  • Glasgow Coma Scale (GCS)

Results

This study found that dyspnea improved with both HFO and BiPAP in a comparison of pre- and post-treatment dyspnea. BiPAP use was associated with an average of a 3.2 dyspnea improvement on the NRS (p = 0.0004) and 1.5 on the MBS (p = 0.13). HFO was associated with an average improvement of 1.9 on the NRS (p = 0.02) and 2.1 on the MBS (p = 0.007). There were no significant differences in dyspnea relief between HFO and BiPAP on the NRS (P = 0.14) or the MBS (P = 0.47). BiPAP use also was associated with average improvements in NRS scores of 3.2 (P = 0.007) and 1.5 on the MBS (P = 0.13).
 
A statistically insignificant decrease in respiratory rate was identified with both devices. BiPAP use was associated with a decrease in heart rate (p = 0.02). HFO was associated with a significant decrease in systolic blood pressure (p = 0.02) and improvements in oxygen saturation (p = 0.003). No adverse effects were noted for either device. The majority of patients reported that HFO (10/13; 17%) and BiPAP (9/10) improved their dyspnea. 

Conclusions

HFO and BiPAP were found to alleviate dyspnea and improve physiologic parameters. The results of this study justify larger randomized, controlled studies to validate these findings. The authors of this study proposed that HFO and BiPAP be examined separately.

Limitations

  • Small sample (< 100)
  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Other limitations/explanation: Multiple statistical comparisons were conducted. Baseline arterial blood gas and a measurement of oxygen saturation while on room air were not conducted.

Nursing Implications

Dyspnea is one of the most common symptoms for patients with cancer. This study shows that HFO and BiPAP may alleviate dyspnea. These devices are safe for patients to use. Larger randomized, controlled clinical trials are needed to confirm the findings of this study.

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Hui, D., Xu, A., Frisbee-Hume, S., Chisholm, G., Morgado, M., Reddy, S., & Bruera, E. (2013). Effects of prophylactic subcutaneous fentanyl on exercise-induced breakthrough dyspnea in cancer patients: A preliminary double-blind, randomized, controlled trial. Journal of Pain and Symptom Management, 47, 209–217. 

Study Purpose

To study the feasibility of a randomized, controlled trial exploring the effects of fentanyl on breakthrough dyspnea, walking distance, vital signs, and adverse events in patients with cancer

Intervention Characteristics/Basic Study Process

Participants performed a baseline 6-Minute Walk Test (6MWT) without any medications followed by a rest period during which their levels of dyspnea were assessed every five minutes for one hour. When dyspnea levels were less than or equal to baseline dyspnea of +1, patients were given either a single dose of subcutaneous fentanyl or a placebo containing 0.9% preservative-free normal saline. Another 6MWT was performed 15 minutes later when the fentanyl was expected to reach its median peak concentration. 
 
Patients and research clinicians were blinded to the study intervention and randomization sequence. A study pharmacist randomly assigned patients to either intervention in a 1:1 ratio using a computer-generated randomization scheme. Participants enrolled in the fentanyl arm received a parenteral fentanyl dose based on a sliding scale intended to achieve 15%–25% of the morphine equivalent daily dose (MEDD) based on the rescue opioids for breakthrough dyspnea. 

Sample Characteristics

  • N = 20  
  • MEDIAN AGE = 55 years (range = 27–75 years) (mean age was 55 years in the fentanyl group 54 years in the placebo group)
  • MALES: 45% (n = 9), FEMALES: 55% (n = 11)
  • KEY DISEASE CHARACTERISTICS: Breast (5), gastrointestinal (1), genitourinary (3), gynecologic (2), lung (4), and sarcoma (5); other diseases were chronic obstructive pulmonary disease, heart failure, asthma, and bronchiectasis
  • OTHER KEY SAMPLE CHARACTERISTICS: Patients were included if they had a cancer diagnosis, were aged 18 years or older, had average intensity breakthrough dyspnea of three or more on a 10-point Numeric Rating Scale, spoke English or Spanish, were ambulatory with or without an assistive device, had a Karnofsky Performance Status of 50% or more, and were on a stable dose of strong opioids with a MEDD of 30–580 mg. Patients were excluded if their dyspnea scores at rest were seven or more out of 10, they used more than 6 L per minute of supplemental oxygen, they experienced delirium (Memorial Delirium Assessment Scale > 13 out of 30), they were allergic to fentanyl, they had history of substance abuse, they had a recent history of coronary artery disease, and if they had uncontrolled tachycardia or hypertension at the time of assessment.

Setting

  • SITE: Single site  
  • SETTING TYPE: Outpatient  
  • LOCATION: Supportive Care Center at the MD Anderson Cancer Center

Phase of Care and Clinical Applications

  • PHASE OF CARE: Multiple phases of care
  • APPLICATIONS: Palliative care

Study Design

Double-blinded, placebo-controlled, randomized trial

Measurement Instruments/Methods

  • Numeric Rating Scale (NRS) to measure dyspnea from 0–10 (0 = no shortness of breath and 10 = worst possible shortness of breath)
  • Borg scale to assess fatigue level
  • Global Symptom Evaluation (GSE) to evaluate change in dyspnea following interventions
  • Edmonton Symptom Assessment Scale (ESAS) and Cancer Dyspnea Scale (CDS) at baseline to assess the quality of dyspnea over the previous few days

Results

This study achieved its primary outcome of a 100% participant retention rate. Baseline levels of dyspnea were higher in the placebo group compared to the fentanyl group. All patients were able to walk the full 6MWT during each walk test. Twelve patients returned to their baseline levels of dyspnea within five minutes of rest, five returned within 10 minutes, and three returned within 15 minutes.
 
Significant improvements in dyspnea scores were observed among participants who received subcutaneous fentanyl (mean was -1.8 at end of test compared to -0.9 at rest before test) as well as Borg scale fatigue scores at the end of the 6MWT (mean was -1.3), 6MWT distance (mean distance 37.2 m, 95% CI = 5.8), and respiratory rate (mean was -2.4; 95% CI = -4.5, -0.3).
 
According to the authors, a statistically insignificant improvement also was observed among patients in the placebo arm in regard to dyspnea scores at the end of the 6MWT, dyspnea scores at rest before the 6MWT, Borg scale fatigue scores at the end of the 6MWT, 6MWT distance, and respiratory rate. There were no significant differences in physiologic measures between baseline and the second 6MWT in either study group. No statistically significant differences in any outcome measures were observed when fentanyl and the placebo were compared. Both were tolerated well. 
 
Six of the 10 patients receiving fentanyl reported improved dyspnea during the second walk test compared to the first walk test while three found no change and one felt worse. Similarly, in the placebo group, eight, one, and one patients (respectively) reported that their dyspnea was improved, was the same, or was worse, respectively. No statistically significant differences were observed between the study interventions (P = 0.78).

Conclusions

The prophylactic administration of subcutaneous fentanyl appears to be a safe and well-tolerated method for reducing dyspnea, fatigue, and respiratory rate while also enhancing physiologic function and activity levels among patients with cancer. However, the generalizability of these findings are limited because of the small sample size.

Limitations

  • Small sample (< 30)
  • Findings not generalizable
  • Intervention expensive, impractical, or training needs
  • Other limitations/explanation: The statistically insignificant improvement of dyspnea and fatigue among patients in the placebo arm was attributable to a placebo effect. According to the authors, a placebo effect within the context of this study may have been caused by a reporting bias, interviewer bias, or period/training effects. This suggests a need for the standardization of patient encounter experience and the stratification of baseline dyspnea levels. Also, routine subcutaneous administration may not be practical, and it requires some degree of training. The authors suggested rapid-onset fentanyl via transmucosal or intranasal routes as more practical alternatives.

Nursing Implications

Given the high, relatively fast enrollment and high completion rates of this study, the authors cite the feasibility of performing a more adequately powered, placebo-controlled, double-blinded, randomized, controlled trial with higher fentanyl doses to establish the prophylactic management of dyspnea with opioids. In addition, it would be beneficial to assess how long opioid effects last, what kinds of patients and cancer types would benefit more, and the most practical and cost-effective route of opioid administration (e.g., subcutaneous, oral).
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Huether, K., Abbott, L., Cullen, L., Cullen, L., & Gaarde, A. (2016). Energy Through Motion©: An evidence-based exercise program to reduce cancer-related fatigue and improve quality of life. Clinical Journal of Oncology Nursing, 20, E60–E70. 

Study Purpose

To implement and evaluate an evidence-based practice change to encourage exercise for fatigue

Intervention Characteristics/Basic Study Process

The Iowa Model of Evidence-Based Practice Change was used to guide implementation and measure impact on patient outcomes and care processes. An intervention to implement physical activity for patients to combat fatigue was selected. Activity kits for patients were developed, and included information on the benefits of physical activity, activity logs, instructions for workouts, as well as strategies to improve sleep, and nutrition. A pedometer and resistance bands were also provided. A nurse made regular connections with patients to encourage physical activity. Fatigue assessment was done at clinic visits at baseline and three months later. Results from the physical activity group were compared to those of patients receiving usual care.

Sample Characteristics

  • N = 45  
  • AGE: Not provided
  • MALES (%): Not provided, FEMALES (%): Not provided

Setting

  • SITE: Single site   
  • SETTING TYPE: Outpatient    
  • LOCATION: Iowa

Phase of Care and Clinical Applications

PHASE OF CARE: Multiple phases of care

Study Design

Prospective cohort comparison

Measurement Instruments/Methods

Brief Fatigue Inventory (BFI)

Results

Patients who received the activity intervention experienced a significant reduction in fatigue (p = 0.0006) and increase in general activity (p = 0.0066).

Conclusions

The intervention to improve physical activity was effective to improve fatigue.

Limitations

  • Small sample (< 100)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment) 
  • Risk of bias (no appropriate attentional control condition)
  • A single DNP was involved in encouraging patients to continue physical activity, so if this type of practice change would be effective without the consistent follow-up of an individual is unclear.

Nursing Implications

The findings showed that the use of the activity kit and follow-up in this study was effective in increasing physical activity and reducing fatigue in patients with cancer.

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