To study the effect of fentanyl in preventing dyspnea before exertion.

Opiate-tolerant patients were given a six-minute walk test for baseline, then later given fentanyl or a placebo, waited 30 minutes, then repeated the six-minute walk test. Study measures were then taken between the two arms.

• N = 20 
• AGE: Average age = 55 years
• MALES: 40%  
• FEMALES: 60%
• CURRENT TREATMENT: Supportive care
• KEY DISEASE CHARACTERISTICS: 90% had metastatic disease. All had some concurrent scheduled medications for SOB besides opiates; 0% were used to taking 66-130 mg of morphine a day. SOB of 3-7 on a scale of 10 at rest.
• OTHER KEY SAMPLE CHARACTERISTICS: Karnofsky level mean was 71. Average fvc = 2.4 L, and fev1 = 1.7 L.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Supportive care clinics

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

Double blind randomized placebo controlled trial comparing baseline six-minute walk test and then a second six-minute walk test (6MWT) effects of placebo versus single dose of fentanyl buccal tablet 30 minutes prior to second walk.

Dyspnea was measured using a modified BORG scale from 0-10, with 10 indicating the worst score. Vital signs of BP: O₂ saturation, heart rate, respiratory rate taken before and after the six-minute walk test. Distance walked per minute was recorded. Lung function was only done at baseline. Neurocognitive testing was done before medication and after the second six-minute walk.

No difference with either arm seen for distance walked or fatigue, or vital signs other then respiratory rate between the first and second 6MWTs (mean change = 2.6, 95% CI [0.4, 4.7]) with a trend toward greater level of dyspnea relief compared with placebo (estimate = 0.25, p = 0.068).

Buccal fentanyl had a significant effect in reducing dyspnea then placebo after 30 minutes, when patients exerted themselves.

• Small sample (< 30)

Nurses caring for patients with dyspnea recognize the need to provide interventions that minimize dyspnea during daily activities, particularly when dyspnea interferes with ADLs and impacts patients' quality of life. Interventions such as prophylactic FBT may enable patients to participate in activities, regain independence, and improve their quality of life without experiencing adverse events such as dizziness, drowsiness, and nausea.

To determine the effect of fan therapy on dyspnea in patients with terminally ill cancer.

Fan therapy consisted of directing a fan to blow air for five minutes across the region innervated by the second/third trigeminal nerve branches. Control was directing a fan to blow air for five minutes to legs. Intervention delivered after a washout period for opioids.

• N = 40   
• AGE: Average age = 69 years
• MALES: 55%  
• FEMALES: 45%
• CURRENT TREATMENT: Had to be getting no cancer treatment
• KEY DISEASE CHARACTERISTICS: Metastatic or locally advanced cancer, ECOG score of 3 or 4
• OTHER KEY SAMPLE CHARACTERISTICS: Dyspnea while sitting or laying at rest, O₂ saturation of 90% or greater

• SITE: Single site
• SETTING TYPE: Inpatient palliative care unit    
• LOCATION: Hospital in Chiba, Japan

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

Randomized controlled trial

ESAS-r (ESAS-revised): used NRS for dyspnea (0-10 scale) (primary measure),  facial temperature, respiratory rate, peripheral O₂ saturation, and heart rate (secondary measures)

Improvement in dyspnea for the treatment arm was seen with mean NRS scores that changed by -1.35 in the treatment arm versus a change of -0.1 in the control arm (p < 0.001) and the number of patients who experienced a greater than one or two-point reduction on their NRS was greater (80%) when compared to the control group (25%). There was also a reduction noted in drowsiness in the treatment group. Significant secondary outcomes included that the mean change in drowsiness on NRS was 0.4 for the treatment group versus -0.45 for control (p = 0.01) and facial temperature was significantly lower after the intervention for the treatment group (reduction of 1.43 degrees C) versus control (reduction of 0.01) (p = 0.003)

The authors conclude that the study presents evidence that fan therapy is effective for the treatment of dyspnea in terminally ill patients with cancer.

• Small sample (< 100)

This study has significant implications for nursing as it provides an intervention for dyspnea that could be wholly within the ability of nurses to deliver and could be taught to families. It is also an intervention with little risk and could offer patients some control.

STUDY PURPOSE: Evaluate the four most commonly used pharmacologic therapy options for the management of breathlessness in patients with advanced cancer and non-cancerous diagnosis

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: Ovid, PubMed, Medline, Cochrane

YEARS INCLUDED: (Overall for all databases) 1950 to 2012

INCLUSION CRITERIA: Randomized controlled trials, controlled clinical trials, and systematic literature reviews and meta-analyses that were published in German or English of patients who experienced continued breathlessness despite treatment for the underlying disease including cancer, COPD, chronic heart failure, ALS, MS, and HIV/AIDS, and received pharmacologic treatment with opioids, benzodiazepines, corticosteroids, or oxygen which the intensity of breathlessness could be measured. 

EXCLUSION CRITERIA: Studies with the use of nebulized or oral steroids as a basic treatment for COPD and studies including oxygen for patients with hypoxic COPD.

TOTAL REFERENCES RETRIEVED: 2,029

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Database search yielded 2,559 reviews; after review for duplicates, the references were 2,029. Two reviewers independently searched and analyzed the title, abstract, and study for inclusion criteria, which left 65 references. The reviewers then conducted a full-text review, leaving seven references which made up the final inclusion along with eight references from experts. The final number of studies included 5 systematic reviews and 10 randomized controlled trials.

FINAL NUMBER STUDIES INCLUDED: 15

TOTAL PATIENTS INCLUDED IN REVIEW: 2,125

SAMPLE RANGE ACROSS STUDIES: Patients with advanced cancer, cancer, CHF, COPD

KEY SAMPLE CHARACTERISTICS: Included nine studies, one systematic review and eight RCT/CCT, on efficacy of opioids. Two studies, one systematic review, and one RCT/CCT on efficacy of benzodiazepines. Four studies (three systematic reviews and one RCT) on efficacy of oxygen.

PHASE OF CARE: Multiple phases of care     

APPLICATIONS: Elder care, palliative care

Results are categorized in three medication groups and oxygen. No results are available for corticosteroids because there were no studies identified. Two reviews for benzodiazepines were conducted. A systematic review of seven studies, including 200 patients in which 6 of the 7 studies did not show efficacy for the use of benzodiazepines for breathlessness (effect size = -0.32 with 95% CI [-0.89, -0.24]). The second review was a RCT comparing temazepam to placebo with no difference in relief of breathlessness between the two groups. The strongest evidence is from the nine reviews (one systematic literature review and eight RCT) for studies using opioids. Significant efficacy was reported from the systematic literature review of 18 RCT and 293 patients with oral/parenteral morphine (effect size = -0.4 with 95%CI [-0.63, 0.17], p = 0.0006). All eight reviews of RCT were positive, with three showing morphine significantly better than placebo and five showing relief of breathlessness. There were four reviews (three systematic reviews and one RCT) for the efficacy of oxygen identified. The three systematic reviews all compared oxygen to room air. Two did not show significant improvement, however, in one study of 702 non-hypoxemic COPD patients, oxygen showed significant improvement of breathlessness (effect size = -0.37 with 95% CI [-0.5, -0.24]). The RCT compared oxygen to room air in 239 patients. Breathlessness was improved in both the morning and evening by 0.9 and 0.7 points, however, there was no significant difference between the two groups.

The review emphasizes the treatment of breathlessness is still a challenge with evidence varying and partly limited. However, opioids are recommended as a first choice for the treatment of breathlessness for patients with cancerous and non-cancerous advanced diseases. Benzodiazepines are recommended as a second choice for the co-existing management of panic symptoms, anxiety, and breathlessness. Oxygen is not proven to be effective in the non-hypoxic patient with cancer and the use of hand-held fans should be offered.

• Limited search
• Limited number of studies included
• The search strategy was not specific, including only studies written in English or German, excluding studies in other languages. Studies with uncontrolled study designs were also excluded.

Findings show that only opioids offer benefit to patients experiencing breathlessness and should be considered as first-line therapy. However, there are several other nursing implications provided by this review. A smaller dose of opioid is effective in relieving breathlessness and, whenever possible, should be started low and go slow. The fear of respiratory depression with the use of opioids is not warranted based on results of several studies. This finding should be communicated to nurses with education provided to patients and families. Although benzodiazepines are commonly used for breathlessness, efficacy has not been established. However, nurses must recognize the benefit of reducing anxiety and possibly allowing for lower doses of opioids. Lastly, the use of hand-held fans producing an air stream across the patient’s midface and over the nasal mucosa is an intervention nurses may easily use to reduce breathlessness.

To evaluate the effects of auricular acupressure on dyspnea intensity, distress, and oxygen saturation in patients with lung cancer with advanced disease.

Patients were randomly assigned to one of three groups: either standard of care, standard of care with auricular acupressure appropriately placed, or standard of care with placebo placement of auricular acupressure (placed on alternate site on ear not associated with lung function). Acupressure was applied with vaccaria segetalis seed taped to portion of ear associated with lung function, according to traditional Chinese medicine by a licensed accupuncturist. Data was collected twice per day for all participants, each time oxygen saturation was measured with pulse oximeter and the participants completed the Cancer Dyspnea Scale tool. Baseline data was collected on day 1, treatment intervention began on day 2, and data was collected on days 2, 3, and 4.

• N = 11   
• AGE: Adults, specific age not stated
• MALES (%): Unknown  
• FEMALES (%): Unknown
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Diagnosis of lung cancer, 36% inpatient and 64% outpatient hospice/palliative care center

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Southern California

• PHASE OF CARE: End-of-life care
• APPLICATIONS:  Elder care, palliative care

Randomized controlled trial; participants randomly assigned to three conditions

Cancer Dyspnea Scale, 12-items assessing three dimensions of dyspnea: effort, anxiety, and discomfort using a five-point Likert-type scale. Level of oxygen saturation was measured via pulse oximeter.

Statistical analysis were used as basis for planning for future research design as true analysis was limited by small sample size. No significant relationship was identified for oxygen saturation between the three groups, statistical analysis suggests that the treatment arm had an effect on the measure of dyspnea effort. Data were also analyzed using non-parametric statistic Friedman two-way ANOVA by ranks; running test once for each of the three groups. The only condition that resulted in statistically significant change over time was the auricular acupressure experimental group (chi-squared = 7 and p = 0.43).

Experiment was conducted as a feasibility study showing that the intervention was well-tolerated, with low subject burden and, therefore, auricular acupressure seems to be a feasible intervention with no negative impact. Since subscale of dyspnea effort showed significant change, larger studies are indicated to validate usefulness of intervention to positively affect symptom of dyspnea in end-stage patients with lung cancer.

• Small sample (< 30)
• Findings not generalizable
• Other limitations/explanation: Feasibility study

Use of auricular acupressure to mitigate sensation of dyspnea in patients with advanced lung cancer needs to be studied further with appropriately sized patient populations to accurately measure effect. Use of auricular acupressure did not appear to have negative effects for this small sample size.

To explore potential factors predicting the response to corticosteroids for dyspnea in patients with advanced cancer.

Measurement variables were recorded at two time points as a part of routine practice for patients who received corticosteroids: baseline (day 1) and in the evening on day 2 after administration of corticosteroids. Patients were followed until one month after administration of corticosteroids and dates of discontinuation or death were recorded. Recommended doses of corticosteroids were betamethasone 2-8 mg per day; dexamethasone 2-8 mg per day, prednisolone 15-60 mg per day, methylprednisolone 10-40 mg per day, and hydrocortisone 50-200 mg per day given orally, IV, or subcutaneously.

• N = 74 patients: 82 enrolled, 6 patients died before day 3, and 2 patients had missing values of numerical rating scale (NRS) of dyspnea on day 3 for unknown reasons.  
• AGE: Mean age = 68 years
• MALES: 53%  
• FEMALES: 47%
• CURRENT TREATMENT: Unknown
• KEY DISEASE CHARACTERISTICS: Patients were included if they had metastatic or locally advanced cancer, were receiving specialized palliative care services, and had a dyspnea intensity of greater than 3 on NRS, worst during the last 24 hours. Patients were excluded if they were unable to communicate verbally due to delirium, dementia, or organic brain disorders; had contraindications to corticosteroids; had dyspnea due to acute exacerbation of underlying non-malignant comorbidities; or were planned or did undergo a thoracentesis during the study period.  
• OTHER KEY SAMPLE CHARACTERISTICS: The following patient characteristics were noted: primary lung tumor (39%), primary tumor of the stomach, colon, or rectum (18%), primary tumor of the uterus and ovary (14%). Other patient characteristics include: metastasis to lung (58%), metastasis to pleura (54%), metastasis to peritoneum (31%), metastasis to liver (30%), and metastasis to brain (8.1%). The majority of patients (84%) had an Eastern Cooperative Oncology Group (ECOG) performance status 3 or 4; 76% had palliative prognostic index (PPI) greater than 6; 64% used supplemental oxygen. Median oxygen flow rate was 2 L per minute and median survival was 26 days.

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: 17 sites in Japan

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

Prospective, observational study

Primary end-point of worst dyspnea by NRS the last 24 hours was on the evening of day 3. NRS format for dyspnea from the Japanese version of the MD Anderson Symptom Inventory (MDSAI) was used. A response to corticosteroids was defined as a priori greater than or equal to one-point reduction in NRS of dyspnea. Secondary endpoints included support team assessment schedule, Japanese version (STAS-J), patient-perceived changes in dyspnea, confusion assessment method, short version (CAM), and memorial delirium assessment scale. Potential predictors of response to corticosteroids were recorded prior to administration of corticosteroids by the treating palliative care physicians. Potential predictors included patient demographics, indicators of general conditions, palliative prognostic score (PaP), laboratory findings and oxygen variables, etiologies of dyspnea and clinical manifestations, physician-predicted response of a six-point Likert-type scale, baseline dyspnea severity, and dose of corticosteroid.  
Survival times were calculated using Kaplan-Meier methods. Paired student t tests were used to compare NRS values of dyspnea before and after the administration of corticosteroids. Patients with missing dyspnea NRS values on day 3 due to severe dyspnea or delirium caused by corticosteroids were classified into a non-responder group and Last Observation Carried Forward method was applied. Frequencies and 95% confidence intervals of the proportion of patients with positive CAM tests and those with MDAS item 9 scores greater than or equal to 1 were calculated. Cohen’s kappa was calculated to explore the agreement between CAM-positive and MDAS item great than or equal to 1. Treatment responses between patients with and without each potential predictor was compared using chi-square tests. A logistic multivariate regression analysis was used to identify independent factors predicting greater than or equal to one-point reduction in dyspnea NRS. An alpha (two sided) and power = 0.8, 28 patients per group was needed to determine differences.

Patients had a 1.9 reduction of mean dyspnea NRS worst after administration of corticosteroids (p < 0.001). 50 patients showed a greater than one-point reduction in NRS worst, and 40 patients showed a greater than two-point reduction. 47 patients perceived their condition to be better. Predictor factors that were associated with greater than or equal to one-point reduction in dyspnea were age 70 years or older (p = 0.008), absence of liver mets (p = 0.001), presence of pleuritis carcinomatosa with small collection of pleural effusions (p = 0.011), and presence of audible wheezes (p = 0.002).  Major airway obstruction (p = 0.088), non-purulent serous secretions (p = 0.088), and absence of liver mets (p = 0.055) were associated with a two-point reduction in NRS. Multivariate analysis showed that independent factors predicting response to corticosteroids were PPI greater than 6 (p = 0.021), baseline NRS of dyspnea greater than or equal to 7 (p = 0.036), and absence of liver mets (p = 0.029).

Corticosteroids improved the majority of patients mean dyspnea NRS score. Patients also perceived that the corticosteroids improved their dyspnea. Caution should be taken to monitor for the development of delirium with starting corticosteroids in this patient population.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Selective outcomes reporting
• Other limitations/explanation: Patients received co-interventions such as palliative treatment; therefore, effects cannot be exclusively attributed to corticosteroids. There was no set protocol about the dose and administration methods of corticosteroids therapy. The validity and inter-rater reliability of detecting etiologies and clinical manifestations were not formally tested. Some predictors were based solely on clinical impression. The sample size was not large enough to identify some predictors, such as major airway obstruction. It is unclear how steroids affect patients who have delirium or the inability to interpret symptoms. The benefits of steroids was measured after only 3 days of treatment. Some patients had treatable causes for their dyspnea, which may have contributed to a decreased dyspnea rating.

Nurses may consider using corticosteroids management of dyspnea in the palliative setting based on certain predictors such as bronchial constriction and no evidence liver mets. Even if patients are cognitively impaired, they may still experience symptoms of dyspnea and should be considered a candidate with alternative means of assessing dyspnea.

To evaluate the differences in the effects of various opioids administered concurrently with corticosteroids on severity of dyspnea in patients with terminal-stage cancer.

This study retrospectively investigated the EHRs of patients with terminal cancer who were hospitalized, received oral or IV corticosteroid treatment with an opiate medication for dyspnea, and died while hospitalized. Patients were excluded if they received invasive interventions, received oral corticosteroids prior to admission, or did not receive both medications concomitantly. The effectiveness of combined opioids and corticosteroids treatment for dyspnea was assessed from the first to last administration using the STAS-J. The effectiveness of combined opioids and corticosteroid treatment for dyspnea was compared with time of corticosteroid initiation and maximum effect against dyspnea, as determined by changes in the evaluation score. Data was recorded daily from initiation to death. Opioid doses were recorded to the point at which max efficacy could be confirmed (responders) and at the time at which the assessment began (nonresponders) and compared between groups.

• N = 20 patients; 49 were screened and 29 did not meet full inclusion criteria  
• AGE: Mean age = 71 years (range = 49-94)
• MALES: 65%  
• FEMALES: 35%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Terminal cancer; primary lesions mainly colon cancer, stomach cancer, or lung cancer. 70% of patients presented with pleural effusions, 25% had lung area metastatic spread, and 15% had lymphangitis carcinomatosis.  
• OTHER KEY SAMPLE CHARACTERISTICS: Median opioid dose 30 mg

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Kasugai Municipal Hospital, Japan

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

Retrospective review

Wilcoxon signed-rank test was used to test the effectiveness of opioids in the terms of changes in the STAS-J score. This tool contains many questions about symptoms. The authors stated they used “only questions concerning effectiveness of combined opioid and corticosteroid treatment and opioid doses. They reported score changes as their measurement of interest, but it is unclear if this was a total STAS-J score or a subscale score. It is uncertain if this tool has been validated using individual questions. Logistic regression analysis was used to compare the opioid doses and responders versus nonresponders. Responders were defined as a patient who the STAS-J score decreased by greater than or equal to 2 points. Nonresponders were defined as a patient whose STAS-J score did not decrease or only decreased by 1 point.

Significant difference in STAS-J score at initiation and lowest STAS-J score (p = 0.0034) for patients currently treated with morphine and corticosteroids. STAS-J scores increased by 2 or more points in 14 patients with concomitant opioid and corticosteroid use. The logistic regression analysis did not show a significant impact of the opioid dose on dyspnea alleviation.

Use of morphine and corticosteroids has the potential to alleviate dyspnea in patients with terminal cancer. More research is needed to determine the efficacy of opioids and corticosteroids in reducing dyspnea.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)  
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Measurement/methods not well described
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: The scale used for measurement of dyspnea is a multi-item scale but the authors used only selected questions and did not validate the reliability of using select questions. It is unclear how selecting questions influenced the total score that is reported.

Nurses may consider combining corticosteroids and opiates for management of dyspnea in terminally ill patients. Nurses need to be aware of the potential adverse reactions associated with both opioids and corticosteroids and educate patients on such. Nursing needs to be aware of the various routes of administration for corticosteroids and opioids.

To determine the feasibility of conducting a randomized trial of dexamethasone in patients with cancer and the estimated efficacy of dexamethasone in the treatment of dyspnea.

Patients were randomly assigned to a 1:1 ratio to receive either dexamethasone 8 mg (two capsules of 4 mg) orally twice a day for four days, then 4 mg given orally twice a days for three days or identical-appearing placebo capsules. After one week, patients received dexamethasone 4 mg orally twice a day for seven days in open-label fashion.

• N = 41 patients; 77 eligible for study, 52 enrolled, 11 became ineligible or declined to continue  
• AGE: Mean age = 63 years (range = 48-78)
• MALES: 39%  
• FEMALES: 61%
• CURRENT TREATMENT: Radiation 
• KEY DISEASE CHARACTERISTICS: A majority of patients (88%) had advanced cancer, with lung cancer being the most common diagnosis (81%). If not primary lung cancer, all had clinical or radiologic evidence of lung involvement.
• OTHER KEY SAMPLE CHARACTERISTICS: Other requirements: average dyspnea of 4 or greater over past week, Karnofsky PS of 40% or greater, undergoing radiation therapy, but not chemotherapy within one week. Exclusions: uncontrolled diabetes, severe anemia, oxygen at less than 90% on greater than 6 L per minute oxygen, megestrol use, delirium, open unhealed wound, recent corticosteroid use for greater than 14 days

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: University of Texas MD Anderson Cancer Center

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

Double-blind, parallel, placebo-controlled, randomized trial

Dyspnea was assessed at baseline, day 4+ or -2, day 7+ or -2, and day 14+ or -2. The Edmonton Symptom Assessment System (ESAS) was used. Dyspnea “now” was assessed using the Modified Dyspnea Borg Scale. The Cancer Dyspnea Scale as well as the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-C30) was used. MicroLoop Spirometer was used at baseline to obtain FEV1, FVC, FEV1/FEV2, peak inspiratory flow, and peak expiratory flow. Patients used the portable Microlife PF 100 Peak Flow Meter daily to measure peak flow and FEV1. A priori was considered that the study was feasible if at least 50% of patient completed the study. Twenty patients per arm provided 80% power to detect an effect size as small as 0.66 within arms with a two-tailed alpha of 0.05. To estimate effect size, the within-arm mean differences between baseline and day 4, 7, and 14 along with the 95% CI for dyspnea was determine and applied the Wilcoxon signed-rank test. The Statistical Analysis System was used for statistical analysis.

Dexamethasone was associated with a significant reduction in ESAS dyspnea NRS of -1.9 (p = 0.01) by day 4 and -1.8 (p = 0.02) by day 7. Placebo was associated with a reduction of -0.7 (p = 0.38) by day 4 and -1.3 (p =  0.03) by day 7. After one week of open-label treatment, both arms had improvement in dyspnea by day 14 (p = 0.01 for dexamethasone, placebo p = 0.004). The dyspnea numeric scale showed similar results by day 14. EORTC showed improvements in dyspnea in the dexamethasone arm by day 4 (p = 0.04). ESAS drowsiness improved in the dexamethasone arm by day 4 (p = 0.03) and day 7 (p = 0.01), but not by day 14; however, baseline drowsiness was higher in the dexamethasone arm. Dexamethasone was well-tolerated with no grade 3 toxicities.

Dexamethasone showed to improve dyspnea with minimal adverse effects. Feasibility of a randomized controlled trial without unacceptable attrition was validated. More testing needs to be completed to determine absolute efficacy.

• Small sample (< 100)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Subject withdrawals ≥ 10%
• Other limitations/explanation: 85% of patients completed week 1 of the study and 71% of patients completed week 2. This study focused on patients who had lung involvement with cancer. The sample size was small and hence the study was not powered to detect differences.  Co-interventions were not defined. The study was not powered to compare dexamethasone to the placebo, so no definitive conclusion can be made regarding the efficacy of dexamethasone compared to the placebo. The study description said patients were stratified into FEV1/FVC groups, but group differences were not reported.

Nurses may consider using corticosteroids management of dyspnea for patients with severe dyspnea when no obvious reversible etiologies and targeted interventions exist. Nurses need to be aware of the potential adverse reactions associated with corticosteroids and educate patients on such. Nurses need to be aware of the various routes of administration for corticosteroids.

To survey the use of dexamethasone on the palliative care wards at this cancer center when prescribed according to the guidelines, to document both the indication for use and any benefit obtained, and to document all side effects incurred.

Consecutive patients started on dexamethasone between April and December 1996 were entered into the survey. The department’s corticosteroid-prescribing policy is as follows: start at moderate dose (8-12 mg per day), wean rapidly to lowest effective dose, monitor closely, prescribe prophylactic nystatin (1 ml four times per day), prescribe prophylactic gastric protectants to all patients with a history of PUD or taking NSAIDs; if no benefit, then discontinue.

• N =106 patients enrolled; by week 6, only 24 patients remained. Only 13 (12.26%) had dyspnea. 
• AGE: Not stated
• MALES (%): Not stated 
• FEMALES (%): Not stated
• CURRENT TREATMENT: Not applicable, other
• KEY DISEASE CHARACTERISTICS: All patients had advanced malignant disease, median survival date of all patients from date of commencement of dexamethasone was 40.5 days.
• OTHER KEY SAMPLE CHARACTERISTICS: Mot common indication for steroids was spinal cord compression (6%), while anorexia (19%), nausea (12%), and low mood (12%) were the most common nonspecific indications. The most common reason for stopping steroids was death or deteriorating condition (48%). Seven patients were taking steroids by the end of eight weeks.

• SITE: Single site   
• SETTING TYPE: Inpatient and outpatient 
• LOCATION: England-Royal Marsden Trust hospitals (London and Surrey)

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

Prospective survey

A performa was used to record the reason for starting steroids, the starting and any subsequent doses, the symptoms being palliated, any side effects, and the reasons for stopping steroids. The performa was updated weekly by the ward doctors or research nurses for a maximum of eight weeks. Following discharge, patients were followed-up in the outpatient clinic or at home by telephone. Symptoms were rated on a four-point scale (ranging from 0 to 3) corresponding to none, mild, moderate, and severe. Symptom responses were subsequently recorded as better (decrease in symptom score), worse (increase in symptom score), or no change compared to baseline. Response over time was shown by documenting the proportion of patients with an improvement in a symptom score from baseline at two specific time points: week 2 and at the last assessment. “Best overall response” relates to the best response documented at any time during the treatment with steroids. Side effects were also documented according to the four-point scale. Specific for dyspnea, 5 of 13 (38.5%) patients reported better, 6 of 13 (46.1%) reported unchanged, and 2 of 13 (15.4%) reported worse.

The most common specific reason for initiating steroids was spinal cord compression (6%), followed by cerebral metastases (4%) and then lymphangitis carcinomatosa (4%). The most common nonspecific indications were anorexia (19%), nausea (12%), and low mood (12%). The median starting dose for specific and non-specific indications was 12 mg and 8 mg respectively. In 96 cases, the median duration use was 21.5 days. The most common reasons for stopping steroids include; death/deterioration (48%), tailed off steroids (16%), and trail of steroids ineffective (9%). The symptoms that appeared to get better with steroids are anorexia (73%), nausea (92%), pain (86%), vomiting (94%), bone pain (100%), and all others (73%). The majority of patients complaining of dyspnea or poor mobility showed no change or worsening of symptoms. The most common side effects were oral candida (23% mild and 11% moderate), bruising/petechiae (16% mild and 10% moderate), and proximal myopathy (10% milk and 13% moderate).

Dexamethasone did not improve the symptom of dyspnea in this study. Thirty-nine percent of patients stated the symptom was better, 46% of patients reported no change, and 15% of patients reported dyspnea worsening with steroid use.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Selective outcomes reporting
• Key sample group differences that could influence results
• Measurement validity/reliability questionable 
• Findings not generalizable
• Questionable protocol fidelity
• Subject withdrawals ≥ 10%
• Other limitations/explanation: This study simply reported the findings by reviewing patients in the palliative care program with advanced cancer. No statistical analysis was used to determine if the intervention was successful or not. There is no demographic information regarding the participants other than they all had advanced cancer (no breakdown of age, male or female). No notation of concomitant intervention, no baseline dyspnea statistics (example, how many patients were severe at baseline?). Unknown if more groups were more likely to respond (example, were severe dyspnea patients more likely to respond than mild?). Comorbidities were not identified. Steroid choice and dose not controlled.

If nurses administer dexamethasone, it is imperative they assess for the s/s of oral candida. Nursing staff needs educated on the importance of nystatin as a prophylactic for oral candida. Nursing should be aware of other potential side effects from dexamethasone such as bruising and proximal myopathy.

To evaluate patient-reported satisfaction with treatment, quality of life (QoL), and dyspnea outcomes for four treatment strategies for malignant pleural effusion.

Four treatment regimens (indwelling pleural catheter [IPC] alone, video-assisted thoracic surgery [VATS] and IPC, bedside chest tube and talc slurry; and VATS with talc poudrage) for malignant pleural effusion (MPE) were evaluated using patient-reported outcome tools. The primary outcome of treatment satisfaction was measured immediately after treatment, as well as two and six weeks post-completion using the Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction (FACIT-TS) tool. Secondary outcomes of improvement in dyspnea and QoL were measured at baseline, two, and six weeks post-treatment. Functional Assessment of Chronic Illness Therapy-Palliative (FACIT-Pal) was used to measure QoL; the London Chest Activity of Daily Living scale was used to measure dyspnea.

• N = 104   
• AGE: Median age = 61, range = 26-89
• MALES: 36%  
• FEMALES: 64%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Confirmed diagnosis of cancer with symptomatic pleural effusion confirmed on chest x-ray included; those with endobronchial obstruction, empyema, allergy to talc, or prior treatment for ipsilateral pleural effusion excluded. 
• OTHER KEY SAMPLE CHARACTERISTICS: Must be able to read and write in English. Lung cancer most common, breast cancer second most common diagnoses

• SITE: Multi-site   
• SETTING TYPE: Inpatient urban hospitals
• LOCATION: Canada

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

Prospective cohort study

Functional Assessment of Chronic Illness Therapy-Palliative (FACIT-Pal) was used to measure health-related QoL; the London Chest Activity of Daily Living scale was used to measure dyspnea; Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction (FACIT-TS) was used to measure treatment satisfaction. Post-treatment pain measured on 0-10 scale, and ECOG performance status measurement was added mid-study.

No statistical difference in patient-reported outcomes was identified when comparing results for each of the four treatment modalities: indwelling pleural catheter (IPC), video assisted thoracic surgery (VATS), chest tube and talc slurry; and VATS talc poudrage. There was a statistically significant trend of improvement in overall FACIT-PAL score (p < 0.0001) and trend in decreasing breathlessness measured with both London Chest Activity Daily Living scale (p = 0.003) and FACIT-Pal shortness of breath score (p = 0.0007) when evaluating all study participants as a whole; there was no statistical difference between groups. Treatment satisfaction at six-week point was highest with VATS plus pleurodesis group and lowest with chest tube group; however, difference was NOT statistically significant.

Each of the treatment options for treating malignant pleural effusions are efficacious in improving health-related QoL and decreasing breathlessness with no statistically significant difference in patient-reported satisfaction when comparing each intervention.

• Risk of bias (sample characteristics)
• Key sample group differences that could influence results
• Measurement validity/reliability questionable
• Other limitations/explanation: The subject accrual period was from 2007 to 2013; variability in individuals performing interventions and setting (some outpatient, some inpatient). Difficulty recruiting from multicultural population due to inability to read/write in English influenced participant selection. Sample size small at 104. London Chest Activity of Daily Living scale reliability and validity only tested with COPD population, not MPE.

Nurses educating individuals living with symptomatic malignant pleural effusions need to understand and share data regarding the experience of other patients; patients will benefit from knowledge that other individuals with MPE report an improvement in health-related QoL and a decrease in breathlessness regardless of MPE treatment option utilized. More research is needed in development of measurement tools for breathlessness in individuals with MPE. Additional studies with larger sample sizes are needed to evaluate treatment of dyspnea in patients with cancer because dyspnea is commonly experienced by individuals with advanced disease.

To test the effects of reflexology on chemotherapy-induced peripheral neuropathy (CIPN), compared to standard care and CIPN education alone, in cancer survivors who have grade II-IV peripheral neuropathy.

Standard care control: All participants received verbal education and a brochure on CIPN at baseline, and standard care. 

Intervention: (a) same CIPN verbal education and brochure; (b) reflexology: rhythmic massaging of the head, neck, feet/toes, and fingers applied by a certified reflexologist or a family member trained by the reflexologist. Duration is 20 minutes, twice per day, for six weeks.

• N = 60 (30 in intervention group; 30 in control group)
• AGE: 58 years
• MALES: 53%  
• FEMALES: 47%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Had (a) grade II-IV (mostly grade II) peripheral neuropathy at baseline and had been referred for a neurology examination by their physician; (b) CIPN duration consistent in 68% of patients; (c) received any chemotherapy regimen (mostly taxane- or oxaliplatin-based) and an average of about seven chemotherapy agents; and (d) any cancer type (mostly breast or gastrointestinal cancers). Cancer treatment status unknown. 
• OTHER KEY SAMPLE CHARACTERISTICS: Nearly all patients (93%) had stopped work due to their present illness. Less than 30% completed secondary school or higher. Most (92%) were married.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Trakya University Balkan Oncology Hospital in Edirne, Turkey

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Elder care, palliative care

Pilot randomized controlled trial

• Measurement time points: baseline (before the intervention), three weeks (midpoint), and six weeks (intervention completion).
• Brief Pain Inventory (BPI)–Patient-reported outcome (PRO) measure of pain severity and pain interference with general activities (e.g., walking, sleep, enjoyment of life).
• European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherpay-Induced Peripheral Neuropathy Form (EORTC QLQ-CIPN20)–PRO measure of sensory, motor, and autonomic CIPN symptoms
• NCI CTCAE v4.0–Physician-graded scale of neurotoxicity.
• Neurologic examination–Conducted by physician (only at baseline and six weeks)

Pain interference (BPI), and CIPN motor and autonomic symptoms (EORTC QLQ-CIPN20) improved from baseline to sixweeks in the reflexology group (p ≤ 0.017); but no difference was found between groups at any time point. In the reflexology group, sensory CIPN (EORTC QLQ-CIPN20) improved from baseline to six weeks (p < 0.001) and was significantly less severe at the six-week time point than the standard care group (p = 0.024). The control group’s pain/CIPN severity scores also decreased (non-significantly) over time.

Although reflexology may provide some benefit and relief for cancer survivors with peripheral neuropathy, this study does not support its efficacy in treating CIPN.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)  
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Selective outcomes reporting
• Measurement/methods not well described
• Measurement validity/reliability questionable 
• Findings not generalizable
• Questionable protocol fidelity
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Patient’s current cancer treatment status was unclear; participants could have had peripheral neuropathy from other causes; not all participants received neurotoxic chemotherapy; other CIPN-influencing factors were not controlled for (e.g., diabetes status, concomitant CIPN treatments); sample and eligibility criteria was poorly described; unclear measurement methods–unclear whether patients were interviewed or individually responded to the questionnaires; if interviewed, unclear if the interviewer was blinded; no results reported for the NCI CTCAE v4.0 measure, neurologic exam, or BPI pain severity items; measurement or control for potential contamination, compensatory intervention (by the patients’ doctors), or issues with fidelity; unclear how family members were trained and checked-off to perform the intervention; unclear how many reflexology sessions were conducted by the reflexologists versus the family members, and whether this number was standardized across participants; unclear how they measured patient/family member’s adherence to the protocol; simple (assumed to be convenience) sampling used; Mann Whitney u and Wilcoxon ranked tests were used instead of a repeated measures ANOVA or other more powerful statistical test.

This study suggests reflexology could help to reduce CIPN severity; however, it had several critical limitations. Further research is needed to rigorously evaluate the effects of reflexology on specific types and symptoms of CIPN (e.g., taxane-induced chronic painful CIPN versus oxaliplatin-induced non-painful CIPN)—controlling for key CIPN-influencing factors such as participants’ phase of chemotherapy treatment; baseline CIPN duration, stability, and severity; functional status; concomitant CIPN treatments (e.g., duloxetine); and peripheral neuropathy-related comorbidities—in diverse populations. Subsequently, research is needed to evaluate the specific doses of and mechanisms by which reflexology reduces and/or prevents CIPN.