To determine the effect of OHR118 on appetite, early satiety, and nutritional intake in patients with advanced cancer experiencing anorexia or anorexia-cachexia syndrome

Patients received 4.0 ml of OHR118 via subcutaneous injection daily for 28 days. Patients who benefited were offered the option to continue for a total of 56 days.

• The study reported on a sample of 11 patients with cancer experiencing anorexia or anorexia-cachexia syndrome.
• Mean patient age was 63 years, with a range of 18–80 years.
• The sample was 71% male and 29% female.
• Patients were diagnosed with lung, pancreatic, colorectal, gastric, prostate, or head and neck cancer.
• Of the sample, 27% of patients had stage III disease and 73% had stage IV disease.

• The study site was not specified, but the authors were from the Division of Palliative Care at the University of Ottawa, so it appears that the study was Canadian and done at a single site.
• The nature of the intervention would suggest an outpatient setting.

• Patients were undergoing the active treatment, end-of-life, or long-term follow-up phase of care.
• The study has clinical applicability for late effects and survivorship, and end-of-life and palliative care.

• A prospective, observational study design was used.
• Patients were not randomized, nor was there a control group.
• Neither patients nor researchers were blinded.

• Patient-Generated Subjective Global Assessment (PG-SGA)
• Edmonton Symptom Assessment Scale (ESAS)
• Dyspepsia Symptom Severity Index (DSSI)
• Simmonds Functional Assessment (SFA)
• Bodystat 1500 (lean body mass and body composition measurement)
• Harpenden Skinfold Caliper (skinfold thickness measurement)

Eleven patients completed the first 28 days of the study, and 6 completed the second 28 days. Results from the first 28 days demonstrated a statistically significant improvement of appetite (p = 0.01) and depression (p = 0.05) on the ESAS. All other ESAS items did not show a statistically significant improvement. The overall PG-SGA score measuring nutrition (weight loss, nutrition impact symptoms, intake, and functional capacity) was significantly reduced (p = 0.01). The DSSI showed statistically significant results for the items of frequent burping or belching (p = 0.02), feeling full after meals (p = 0.04), and abdominal distention (p = 0.03). The sit-to-stand item on the SFA was statistically significant (p = 0.01) for deterioration of ability.

The authors concluded that OHR118 showed improvements consistent with previous work done in a \"very positive\" larger study in the AIDS population, and that this translates to \"improved patient comfort and quality of life.\"

Of the many values measured with the multiple measurement tools, only the general PG-SGA score, appetite, frequent belching, feeling full after meals, and abdominal distention showed statistically significant improvement. The study did not meet the secondary endpoints of changes in performance status, lean muscle mass, or quality of life.

• The authors concluded that the depression item on the ESAS was significant with a p value of 0.05; however, their preanalysis value of significance had been determined to be less than 0.05. They then went on to state in their discussion that improving appetite would improve depression, which their study demonstrated. The significant findings of decreased depression were challenging to interpret because of the statistical methods used in analysis and should be interpreted with caution.
• Of the initial 21 patients recruited, 10 dropped out, 5 had disease progression or died, 2 had abdominal pain, 1 had a phobia of needles, and 2 refused to continue citing no reason. There was no control group, and it is not clear from the study how patients were recruited.
• The abstract states that eight patients continued to 56 days; however, the manuscript analysis says that six completed the 56 days.
• It is not clear if OHR118 is an approved agent.

This study should be interpreted with caution because it was small, with limited statistically significant results to support the research objective.

To compare the efficacy of nebulized hydromorphone, systemic hydromorphone, and nebulized saline for incident dyspnea in patients with advanced cancer.

On three occasions when patients requested treatment for incident breathlessness, they randomly received one of the following:

• 5 mg of nebulized hydromorphone
• A systemic breakthrough dose of hydromorphone
• 3 mL of nebulized saline and an agent to maintain double blinding.

If patients felt the intervention was not effective, they could ask for additional pharmaceutical interventions. Patients scored breathlessness at 10, 20, 30, and 60 minutes from completion of treatment. Treatment order was randomized.

• The sample was comprised of 20 patients (11 men, 9 women) receiving palliative care.
• Mean age was 69 years (range 48–83). 
• Diagnoses included primary lung cancer or secondary lung pathology, including lung metastases, pleural effusion, or pulmonary emboli.
• To be eligible, patients had to have Mini Mental State Exam (MMSE) results of at least 24 out of 30.
• Thirteen patients were on continuous oxygen.
• Mean baseline total opioid dose in morphine equivalent mg was 82 (range 10–540).

• Inpatient- and community-based hospice service in Brisbane, Australia
• Single site

Patients were undergoing the palliative and end of life phases of care.

The study was a pilot, double-blind, randomized, crossover, controlled trial.

• Perceived intensity of breathlessness was measured on a vertical 100-mm visual analog scale (VAS).
• Pulse rate and peripheral oxygen saturation were measured with a pulse oximeter.
• Respiratory rate was counted by the research nurse over two 30-second intervals.

There were no differences between treatments in improvement scores. Improvement in breathlessness at 10 minutes post intervention completion was seen in each of the treatment conditions. Improvement considered to be clinically significant (≥1 cm on the VAS) was only seen with the nebulized hydromorphone. Respiratory rate improved over time from 10 to 60 minutes (p < 0.05), with no difference between treatments. There were no clear, consistent preferences among patients for any particular intervention.

The results suggest that nebulized saline provides relief of incident breathlessness; its effect is ongoing and does not differ significantly from the effects of nebulized opioid treatments.

• The study was appropriately powered to answer the study questions, but the study had a small sample size.
• A change of 1 cm on the VAS was used as a clinically significant symptom change, in concert with the work of others.
• Further research to define clinically significant differences in patient perception would be beneficial.
• It is not clear if higher doses of hydromorphone might yield differences across groups.
• The authors suggested that improvements in respiratory rates and peripheral oxygen over time likely represent Type I error in this study because the patients had a background of irreversible baseline dyspnea.
• The presence of the research nurse, to specifically administer this protocol, may have had an effect in terms of reassuring patients and confounded the overall results. Similar research having patients self-administer treatments might address this aspect.
• It is unclear if findings represent placebo effects.

To test the effectiveness of progressive muscle relaxation (PMR) and guided imagery as stress-reducing interventions

Patients randomized to usual care had weekly meetings with psychologists. Those randomized to PMR and guided imagery had four supervised sessions and daily self-practice for three weeks. To stimulate imagery, the guided imagery component included auditory, tactile, and olfactory images. The imagery script was accompanied by music. The intervention was tested and measured with biofeedback prior to study use.  Both groups were assessed at baseline and at the end of three weeks. Daily text message reminders were sent to the intervention group to remind them to practice PMR.

• N = 208  
• AGE RANGE: 40-60 years
• MALES: 50%, FEMALES: 50%
• KEY DISEASE CHARACTERISTICS: Breast and prostate cancer
• OTHER KEY SAMPLE CHARACTERISTICS: 49% had university education; 71% were married

• SITE: Multi-site  
• SETTING TYPE: Home    
• LOCATION: Cyprus

• PHASE OF CARE: Active antitumor treatment

• Single, blind. randomized, controlled trial

• Zung self-rating anxiety scale
• Beck Depression Inventory
• Salivary a-amylase and cortisol levels

The group had a decrease in mean anxiety score whereas the control group had an increase in anxiety at three weeks compared to baseline. The difference between groups of this change was significant (p < 0.001).  The same pattern of change between groups was shown for depression (p < 0.001). Salivary amylase and cortisol levels were directly related to anxiety and depression scores (p < 0.001).

PMR and guided imagery were associated with reduced anxiety and depression among patients with breast and prostate cancer during chemotherapy.

• Risk of bias (no appropriate attentional control condition)
• Other limitations/explanation: No information was provided regarding patient adherence to daily PMR practice. No information was provided regarding any medications for anxiety or depression or chemotherapy regimens involved. Very limited demographic information is provided. The manner in which the imagery scenarios and music were provided were not described.

Findings here showed that progressive muscle relaxation and guided imagery were effective in reducing anxiety and depression during chemotherapy treatment. These are very low-risk interventions that can be helpful and can be readily incorporated into standard patient care.

• FINAL NUMBER STUDIES INCLUDED = 4 
• TOTAL PATIENTS INCLUDED IN REVIEW = Not reported
• SAMPLE RANGE ACROSS STUDIES: Not reported
• KEY SAMPLE CHARACTERISTICS: Three studies included patients with solid tumors; one study included breast cancer only.

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Elder care

The relative risk of complete response for patients under 65 is 1.30 (95% CI: 1.19–1.42; p < 0.0001). It is not significantly different from patients over 65 (Q = 0.281, p = 0.596). The relative risk for a complete response for patients over 75 is 1.42 (95% CI: 1.07–1.89; p = 0.02). It is not significantly different from the relative risk for patients under the age of 75 (1.28, 95% CI: 1.19–1.37; Q = 0.49, p = 0.78). The relative risk of a complete response to regimens including aprepitant for patients over 75 is not different for patients under 65 (Q = 0.42, p = 0.81). There was no statistically significant difference in heterogeneity among studies.

Aprepitant is beneficial for patients both over and under age 65.

• Included studies did not use the same chemotherapy regimen.
• Extremely limited demographic data were presented.
• Search did not include major databases.
• No year limits were described in the study.
• Authors did not state how many studies were retrieved.

The addition of aprepitant should be considered in patients, regardless of age, for the management of chemotherapy-induced nausea and vomiting associated with moderate and highly emetogenic chemotherapy.

To scrutinize the evidence of using acupoint stimulation (APS) by any modality on managing adverse events related to anticancer therapies in patients with breast cancer

English databases searched were PubMed, Cochrane library, Embase, the Cumulative Index to Nursing and Allied Health, and PsycINFO.

Chinese databases searched were CNKI, CEPS, and WanFang as well as manual searching.

Search keywords were medical terms of breast cancer (e.g., breast neoplasm, breast carcinoma, breast tumor) combined separately with at least one of the following: acupuncture, acupressure, auricular acupuncture, ear acupuncture, acupuncture points, electroacupuncture, acupoint, transcutaneous electric nerve stimulation,  moxibustion.

Studies were included if they

• Were in English or Chinese language.
• Reported on adults diagnosed with breast cancer at any stage and undergoing treatments such as surgery, radiotherapy, chemotherapy, hormonal therapy, or palliative treatment and experiencing treatment-induced adverse events.
• Utilized an intervention that involved stimulation of acupuncture points by any modality.
• Had at least one clinically related outcome variable, as well as condition-specific outcomes or generic health status outcomes.

Studies were excluded if they were

• Animal studies.
• Case reports and anecdotal evidence.
• Qualitative studies or descriptive surveys.
• Reports available only in abstract form.
• Trials that included diagnosis other than breast cancer unless separate data was available for the breast cancer group.

Initial review involved 843 titles and abstracts and 51 full-text articles. Of those, 26 studies were included in the report.

Study evaluation began with two independent reviewers using a modified Jadad scale, assessing 3 aspects: randomization procedure (2 points); dropout and withdrawal discussion (1 point); and blinding (2 points). Studies were classified as high quality if they attained a score of 3 or higher.

Evaluated literature included 18 randomized controlled trials (RCTs) and eight controlled clinical trials published between 1999 and 2008. Nine trials included conventional acupuncture, 6 included electroacupuncture, 5 included drug injection in acupoints, 3 included self-acupressure, and 3 included acupoint stimulation by wristbands or acumagnet. Eighteen were in English, and 8 were in Chinese.

• The total sample size was 1,548.
• Age range across across studies was 28–76 years.
• Five studies reported the participant’s body mass index, which ranged from 23.1 to 28.8.
• Information on participants’ education, background of acupuncturists, symptom distress before management, and measurement tool reliability was reported in too few studies to provide a meaningful summary.

Nine of the 26 studies were rated as high quality. Adverse effects (outcomes) of the APS included vasomotor syndrome, chemotherapy-induced nausea and vomiting (CINV), post-mastectomy pain, joint symptoms, lymphedema, leukopenia, and adverse events.

Eleven studies investigated CINV and APS with acupoints P6 and ST36. Ten of the CINV studies reported APS significantly improved emesis caused by breast cancer therapy.

The most common outcome evaluated by APS in the studies was CINV. APS was noted to be effective in reducing acute emesis caused by breast cancer therapy. Authors reported that APS is beneficial in the management of CINV, especially in the acute phase.

Healthcare providers should consider using APS as an option for the management of CINV.

To examine the effectiveness of a psychoeducational intervention (PEI) on the symptom cluster of anxiety, breathlessness, and fatigue compared with usual care.

Education on symptom management and coaching on the use of progressive muscle relaxation was delivered to patients one week prior to the start of radiotherapy (RT) and repeated three weeks after beginning RT. Symptom data were collected at four times points:  prior to the intervention and at three, six, and 12 weeks postintervention.

• In total, 140 patients (83% male, 17% female) with lung cancer receiving palliative RT were included.
• Patients were 16 years or older.
• Patients had stage III or IV lung cancer.

• Single site
• Outpatient
• RT unit of a publicly funded hospital in Hong Kong

The study was a randomized, controlled trial using a pre-/posttest design with two groups.

• Breathlessness was assessed using a 100-mm visual analog scale.
• Fatigue was measured with the intensity subscale of the revised Piper Fatigue Scale (PFS), consisting of 23 items. The instrument was translated into Chinese and found to be valid and reliable.
• Anxiety was measured using the Chinese version of the State-Trait Anxiety Inventory (STAI), consisting of 20 items for measuring immediate feelings of apprehension, nervousness, and worry.
• Functional ability was a secondary outcome measure, using the subscale of the Chinese version of the Short Form 36 (SF-36) Health Survey.

A significant difference (p = 0.003) was seen over time on the pattern of change of the symptom cluster between the PEI intervention and the usual care control group. Significant effects on patterns of changes in breathlessness (p = 0.002), fatigue (p = 0.011), anxiety (p = 0.001), and functional ability (p = 0.000) were found.

PEI is an effective treatment for relieving the symptom cluster of anxiety, breathlessness, and fatigue and each of the individually assessed symptoms.

• The study had a small sample size, with less than 100 participants.
• A high attrition rate was due to death.

The study provided evidence to support the symptom cluster of anxiety, breathlessness, and fatigue as interrelated, with assessment and management of those three symptoms as a cluster. Clarification of the nature of their interrelatedness is a potential area of further study. Education and counseling patients through nurses can be helpful in the management of these symptoms.

To assess the feasibility of using relaxation and patient education

Patients were placed in group 1 or 2 (no randomization information provided). Group 1 received training in progressive muscle relaxation (PMR) and guided imagery (GI) using audiotapes daily. Training was provided daily on days 0-5, then patients practiced the techniques daily for two months. Group 2 received two 30-minute patient/parent education sessions on days 0 and 2, focusing on risk assessment, antiemetic use, and meal planning. All subjects completed instruments at baseline (prior to chemotherapy) then daily for seven more days. One and two months after the intervention, anxiety, compliance with PMR and GI (group 1 only), satisfaction with care, and quality of life was assessed. Pulse and blood pressure were reported in the findings but not listed in the procedure. A third group was comprised of 10 historical control cases who matched the characteristics of group 1.

• The study consisted of 20 participants.
• Mean age was 8.6 years with a range of 4–11 years.
• Gender was not reported.
• The majority of children had acute lymphocytic leukemia, and 12 children had osteosarcoma. Remaining diagnoses were not reported.

The study was conducted at a single site hospital in Hong Kong.

All patients were pediatric and in active treatment.

This was a clinical trial with pre- and post-test design.

• The following instruments were used.
  • The Morrow Assessment of Nausea and Emesis (MANE)
  • Chinese version of A-State scale of the State-Trait Anxiety Inventory
  • Play performance scale for children
  • Physiological indices of caloric intake and changes in body weight 
• Use of antiemetics and satisfaction with care (rated on a 4-point Likert-type scale ranging from 0 = unsatisfactory to 3 = extremely satisfactory) were recorded.
• A self-rating of intervention usefulness (rated on a 6-point Likert-type scale ranging from 0 = not at all useful to 5 = extremely useful) was obtained.
• Health diaries were used to record PMR and Gi practice.

At baseline, group 1 had significantly lower anxiety than group 2 (p = 0.032). Group 1 had less vomiting on day 3 compared to the control group (p = 0.036). No significant difference was found in antiemetic use between the intervention and control groups. No significant difference was found in body weight, CINV, antiemetic use, quality of life, or caloric intake between groups 1 and 2. Health diaries indicated that patients practiced PMR three to four times weekly at home with no significant changes in blood pressure or pulse. Patients and parents reported the interventions as moderately useful.

This study was poorly designed, and findings should be used cautiously. Although the authors reported that PMR and education can reduce CINV, no conclusions should be made except that further research is warranted.

• The sample size was small.
• No information was provided about randomization.
• The authors did not report how the historical control cases were identified or what information was collected.
• No discussion was provided on how the intervention was performed in younger children.
• No report was provided on how blood pressure, pulse, body weight, and caloric intake was measured and recorded.
• Whether data was provided by the children or parents was not made clear.
• Parents’ anxiety and satisfaction of care was discussed in the findings but not described in the procedure.
• No discussion of missing data was included.

The quality of this study is too poor to provide any implications for nurses. Well-designed research in this area is needed.

The study aim was to compare the effectiveness of primary prophylaxis with filgrastim and pegfilgrastim to prevent the incidence of febrile neutropenia in Asian patients with cancer undergoing chemotherapy.  

Data analyzed on intent-to-treat basis from January 2008 and August 2009 identified from the pharmacy prescription database. The G-CSF must have been administered at least 24 hours after chemotherapy administration for primary prophylaxis against febrile neutropenia. Crossover between the two G-CSFs was allowed and the patient was assigned to the treatment group according to the G-CSF used with the first cycle.

• 204 total patients were examined
• 81 received filgrastim, and 123 received pegfilgrastim
• Mean age was 56.7 years (SD = 13.1)  in the  filgrastim group and 55.3 (SD = 14.8) years in the pegfilgrastim group.
• Males outnumbered females, 54% to 46%, respectively
• Patients with non-Hodgkin lymphoma  who underwent chemotherapy
• Primary prophylaxis with filgrastim and pegfilgrastim
   

• Single site  
• Setting type was not specified 
• Location was Singapore
   

Active treatment

Single-center, retrospective study

• Primary end point: Incidence of febrile neutropenia defined as temperature 38.3°C or greater and absolute neutrophil count (ANC) less than 500 mcl.     
• Secondary endpoints: Dose delay of more than three days days or dose reduction of 15% or greater  in subsequent chemotherapy cycles
   

During the first cycle of chemotherapy, six (7.4%) and 11 (8.9%) patients developed FN in the filgrastim and pegfilgrastim arms, respectively (p = 0.8). Across all cycles of chemotherapy treatments, the overall incidence of FN in both arms was much higher than in the first cycle. However, the incidence of FN between the filgrastim group and the pegfilgrastim group remained similar (13.6% in the filgrastim arm versus 16.3% in the pegfilgrastim arm; p = 0.69) across all cycles. More patients in the filgrastim arm experienced treatment delays (8.6%) and chemotherapy dose reductions (4.9%) compared to those who were administered pegfilgrastim (incidence of dose delay = 5.7%, p = 0.25; incidence of dose reduction = 3.3%, p = 0.45) during the first cycle. However, these differences were not statistically significant. The cumulative occurrences of dose delays or dose reductions in all cycles were higher among patients who received pegfilgrastim (absolute difference of dose delay = 2.7%, p = 0.71; absolute difference of dose reduction = 0.7%, p = 1.00). Across all cycles, for regimens that possess a FN risk below 20%, a lower incidence of FN was observed in patients who received filgrastim than those who received pegfilgrastim (12.2 versus 21.4%, respectively; p = 0.31). Similar trends also were observed with the cumulative incidence of treatment delay and chemotherapy dose reduction: patients receiving pegfilgrastim were more likely to suffer from the complications of FN. With regards to the chemotherapy regimens that possess FN risk of 20% or greater, the incidence of FN, treatment delays, and dose reductions all were  similar in both treatment arms (absolute difference in the incidence of FN = 5.6%, p = 0.52; absolute difference in the incidence of dose delays = 0.5%, p = 1.00; absolute difference in the incidence of dose reductions = 4.3%, p = 0.46).

There was no statistically significant difference between filgrastim and pegfilgrastim for the primary prophylaxis of febrile neutropenia in Asian patients undergoing chemotherapy. There was no statistically significant difference between filgrastim and pegfilgrastim with regard to the incidence of dose delays or dose reductions.

Retrospective study that relied on the accuracy of the medical records reviewed.

Filgrastim and pegfilgrastim are equally effective to prevent chemotherapy-induced febrile neutropenia and to prevent dose delays and dose reductions in subsequent cycles.

To review the effectiveness of exercise programs on shoulder mobility and lymphoedema in patients with breast cancer after having axillary lymph node dissection as revealed by randomized controlled trials

Databases searched were CINAHL, Ovid Medline, the BritishNursing Index, Proquest, Science Direct, PubMed, Scopus, and the Cochrane Library. Search keywords were breast; cancer, malignancy, neoplasm, or tumour; modified radical mastectomy, radical mastectomy, breast conservation surgery, wide local excision, axillary lymph node dissection, or adjuvant therapy; exercise, training, weight training, stretching exercise, physical activity, rehabilitation or resistance training, aerobic training, strength training, or lifestyle or range of motion exercises; lymphoedema, arm circumference, arm swelling, oedema, range of motion or shoulder mobility, joint movement, or shoulder function. Studies were included in the study if they

• Were published in English
• Were randomized controlled trials
• Included women undergoing breast cancer treatment with axillary lymph node dissection
• Had treatment strategies defined as various types of exercise programs: weight training, aerobic and strengthening exercises, stretching and range of motion exercises.

Studies were excluded if they

• Targeted male participants
• Reported only decongestive therapy involving manual lymphatic drainage, compression garments, or skin care as interventions
• Dealt with patients undergoing sentinel lymph node biopsy.
   

The total number of studies initially reviewed was 325. A quantitative effectiveness review was used with levels of evidence defined by the Joanna Briggs Institute.

• Six studies were included in the report.
• The total sample size across studies was 429 female patients with a range of 27–205.
• Mean age of the sample was less than 60 years.
• Patients were from the United States, Sweden, the Netherlands, Turkey, Canada, and Australia.

Early rather than delayed onset of training did not affect the incidence of postoperative lymphoedema, but early introduction of exercises was valuable in avoiding deterioration in range of shoulder motion.

Nurses have an important role in educating and encouraging patients to practice these exercises to speed up recovery.

The objective of the study is to examine the effectiveness of a psychoeducational intervention (PEI) that combines patient education with progressive muscle relaxation (PMR) in the relief of a symptom cluster of anxiety, breathlessness, and fatigue in patients with advanced lung cancer receiving palliative radiotherapy (RT).

A total of 140 participants were randomized by lucky draw method to either an intervention group or a control group. Participants in the intervention group received a 40-minute educational package consisting of leaflets and discussion on the symptom cluster (breathlessness, anxiety, and fatigue) and self-care management. Coaching of PMR was delivered within one week prior to the beginning of the course of RT and reinforced three weeks after RT commencement. The intervention was delivered by RNs with two years of clinical experience who went through a two-day training session on the materials in the educational package and the practice of PMR. An audiotape in Chinese and educational leaflets were also given, and patients were encouraged to practice PMR daily and as required. Patients in the intervention group were given a telephone reminder at the end of the second week to enhance participation in the week three sessions. Those in the control group only received “usual care,” which was offered to patients in both the intervention and control groups and consisted of a mandatory individual briefing of RT procedures and a five- to seven-minute discussion of side effects focusing on skin care by a therapy radiographer. An optional group talk by an RN and a medical social worker about general care before and/or after the start of RT was also offered. Data were collected by a research assistant (RA) who was blinded to group allocation. Data collection on symptoms was obtained at four time points: prior to intervention (T0), week 3 (T1), week 6 (T2), and week 12 (T3). Patients were also asked to record adherence to the relaxation exercise in a simple health diary (calendar) for 12 consecutive weeks.

• The study reported on 140 patients.
• Patient age was not indicated.
• The sample was 83% male and 17% female.
• Patients had stage 3 or 4 lung cancer and were scheduled to receive palliative RT of an average of 4.3 Gy/fraction. Less than half of the patients (46%) had distant metastasis. Chest and mediastinum were the major sites of RT.
• Patients were eligible for inclusion if they were age 16 or older; had stage 3 or 4 lung cancer and were scheduled to receive palliative RT of an average of 4.3 Gy/fraction; were able to communicate in Chinese; signed informed consent; completed an Abbreviated Mental Test with a score of 8 or above, indicating normal cognitive ability; and had a Karnofsky Performance Status score of 60% or more, indicating self-care capacity.
• Patients with known psychiatric morbidity and/or involvement in other clinical trials were excluded from the study.
• The majority of patients (75%–80%) had no history of practicing relaxation exercise or use of other forms of complementary therapies/support services.

• Patients were undergoing the end-of-life phase of care.
• The study has clinical applicability for end-of-life and palliative care.

A randomized, controlled trial design was used.

• 100 mm visual analog scale (VAS) to measure subjective experience/intensity of breathlessness
• Piper Fatigue Scale (Chinese translation), revised intensity subscale, to measure intensity of fatigue
• State-Trait Anxiety Inventory, A-state scale, to measure intensity of anxiety
• SF-36 Health Survey, functional ability subscale, to measure level of functional ability
• An intervention activity log was recorded at each assessment session (baseline, week 3, week 6, week 12) by a research assistant to assess patients’ general involvement and problems encountered during implementation of the intervention.
• A patient-recorded “health diary” was used to report adherence to relaxation exercise for 12 consecutive weeks.
• Previous experience with psychoeducational interventions was assessed as yes/no.

At baseline, all patients had a low intensity for breathlessness (mean: 15.81; range: 0–100), but low-to-moderate fatigue (mean: 3.41; range: 0–100) and anxiety (mean: 42.04; range: 20–80) intensity scores, and an overall low-to-moderate functional score (mean: 25.14–66.41; range: 0–100). Patients in the control group, however, were noted to have significantly more advanced-stage lung cancer (p < 0.05) than the intervention group. In the intervention group, 94% of participants completed the intervention in full (based on the intervention log), the majority of whom demonstrated high attention and interest. Participants practiced about four to five sessions of PMR per week, and more than 60% both read the leaflets and listened to the audiotape. At all four time periods (T0–T4), significant and moderate positive intercorrelations among breathlessness, fatigue, and anxiety were observed (p < 0.01), thus suggesting a prominent relational effect of the three symptoms when considered as a cluster. Over time (T0–T2), a significant difference in the pattern of change in “composite” outcome (i.e., breathlessness, anxiety, and fatigue considered as a cluster) between the two study groups was observed (p = 0.003). When considered individually, univariate tests also confirmed a significant difference in pattern of symptom changes over time (T0–T2) for breathlessness (p = 0.002), fatigue (p = 0.011), and anxiety (p = 0.001), as well as functional ability (p = 0.000). Due to high attrition rates from death after T3, long-term effect of PEI at week 12 (T4) was not found to have significant difference in the pattern of change in fatigue (p = 0.034).

PEI is effective in the simultaneous relief of breathlessness, fatigue, and anxiety as a symptom cluster. The authors suggest that the total difference in symptom intensity between the intervention and control groups would have otherwise gone unrecognized if each were to be examined separately.

One limitation of the study was the higher attrition rate (due to patient mortality) experienced by the control group (42%) than the intervention group (11%) at T3 and overall attrition (27%) at the end of the 12 weeks. More patients in the control group had more advanced-stage cancer and distant metastasis than in the intervention group, thus indicating a failed randomization process. Also, due to high attrition, the authors advise that findings should be viewed with caution because of missing data. Additionally, information is lacking regarding participants’ perceptions and feelings toward the intervention process and outcomes. Other limitations related to possible confounding population characteristics that could influence symptom management include prior lung cancer treatments (especially if known pulmonary toxins), preexisting interstitial lung disease, tumor locations, and patient ages.

PEI with primarily PMR seems promising as a resource for the relief of low-intensity breathlessness in light of low-to-moderate intensity anxiety and fatigue up to at least six weeks after palliative RT. Long-term effect of PEI on this symptom cluster at 12 weeks is inconclusive. Similarly, more studies are warranted to establish if PEI is effective for higher baseline intensity of breathlessness and/or anxiety and fatigue. Cost-effectiveness of PEI (i.e., cost of material and training of personnel to deliver the intervention) should be weighed against the cost of poor symptom management (i.e., frequency of hospitalization, length of stay, and pharmacologic treatments).