To determine whether any of three specific doses of American ginseng help cancer-related fatigue, as well as to evaluate toxicity.

Patients were randomized to receive ginseng doses of 750, 1,000, or 2,000 mg per day or placebo. Doses were given in twice daily dosing over eight weeks. The ginseng used was Wisconsin ginseng that met quality-control requirements for pesticides and contaminants. Specific description of ginsenosides content is described. 

Outcome measures were obtained at baseline, four weeks, and eight weeks. Patients were stratified according to stage of disease, gender, baseline fatigue score, and current treatment. Randomization assignments were computer-generated using a dynamic allocation procedure for distribution of stratification factors.

• In total, 175 patients (66% female) with a history of chronic fatigue completed the study. 
• Mean age across study groups ranged from 58 to 62 years (standard deviation [SD] = 12).
• Patient diagnoses were predominantly breast, colon, and lung cancer.
• Of the patients, 62% had stage III/IV disease.
• Of the patients, 71% had a baseline fatigue score of 4 to 7.
• Of the patients, 65% had previous chemotherapy.
• Of the patients, 57% were receiving current chemotherapy and 18% were receiving current radiotherapy.
• No significant differences existed between groups in demographic, disease, or treatment characteristics.

This was a multisite collaborative trial of the North Central Cancer Treatment group and the Mayo Clinic.

This was a randomized, double-blind, placebo-controlled study.

• Brief Fatigue Inventory (BFI)
• Vitality subscale of the Medical Outcome Scale (MOS) Short Form (SF-36)
• Global Impression of Benefit Scale
• Pittsburgh Sleep Quality Index (PSQI)
• Global Impression of Change
• Linear Analogue Scale
• Toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCI CTCAE)
• Patients completed weekly self reports of toxicities in a symptom experience diary to rate side effects on a 0 to 10 scale, with higher scores indicating greater severity.

• Mean scores for the SF-36 subscale between collective ginseng arms and placebo were not significantly different. A trend was observed for greater positive effects at the highest ginseng dose.
• Analysis of change in fatigue showed a greater effect on fatigue with the highest two dose groups, but this was not statistically significant.
• A trend was observed for greatest effect on quality of life measures at the highest ginseng doses.
• The greatest PSQI improvement over time occurred in the placebo group.
• Patient subjective perception of benefits showed an overall trend of higher benefit in the two highest ginseng dosage groups.
• No significant toxicities were associated with the use of ginseng.

Findings suggest that ginseng at the dose of 750 mg per day did not provide any benefit over that of placebo. At the two highest doses of ginseng, a trend was observed of decreased fatigue compared to placebo.

• The study was powered as a pilot study to evaluate composite ginseng dose groups versus placebo, so dose-related findings were underpowered to show statistical significance. 
• A challenge in studying herbal supplements is the lack of standardization and variability in content affected by growing conditions, so the findings may not be generalizable to use of ginseng grown elsewhere or under different climactic conditions.

The preliminary evidence here suggests that the improvement in patient perception with ginseng versus placebo is that this effect may have broad benefit to patients, even if objective measures of outcomes are nonsignificant. It would be worthwhile to more clearly and definitively evaluate the benefits of ginseng in additional larger, more definitive clinical trials.

To explore the effectiveness of psycho-oncologic interventions for patients and partners on anxiety, depression, psychopathology, and distress

Patients and partners who had been referred for psycho-oncologic service were recruited. Common interventions were psychoeducation, cognitive restructuring, behavior control techniques, guided imagery, relaxation, couples communication training, and other types of counseling in an individualized, nonstandard fashion. Patients and partners were grouped according to propensity scores calculated from variables shown to be significant in regression analysis for outcomes of interest, including gender, age, cancer site, stage of disease, baseline anxiety, and depression. Propensity matched control patients, and partners who did not receive the intervention were identified and used as control comparisons. Analysis was done in groupings according to the level of distress with propensity scores as low-, moderate-, or high-distress.

• N = 66 patients and 45 partners in ITT analysis; 43 patients and 27 partners completed the study  
• MEAN AGE = 57.8 years (SD = 14.2 years) for patients, 56 years (SD = 14.4 years) for partners in the intervention
• MALES: 60.6% for patients, 26.1% for partners; FEMALES: 39.4% for patients, 73.9% for partners
• KEY DISEASE CHARACTERISTICS: Multiple tumor types—hematologic, head and neck, and gastrointestinal most common; 63.6% of patients had stage 3 or 4 disease; 69.5% of partners were involved with stage 3–4 disease
• OTHER KEY SAMPLE CHARACTERISTICS: In most areas, patients in the control group did not have significant differences from those in the treatment groups. However, the majority of patients in the control group were highly educated, with 24% at the university level. Educational characteristics of patients and partners in the intervention group were not reported. Note: Sample characteristics are those who were moderately distressed. All characteristics of the full sample across all groups are not clearly provided.

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

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

• Naturalistic design
  • Quasi-experimental with matched control comparison

• Hospital Anxiety and Depression Scale (HADS)
• Symptom checklist (nine psychological symptoms)
• Global Severity Index for overall psychopathology

Time effects within patient groups showed significant decreases over time in depression and distress (p ≤ .05), but not for anxiety and psychopathology. No group effects were seen on outcomes over time. Among partners, no changes were seen over time and no significant effects of the intervention were seen on outcomes. The same pattern was seen in completer and intent to treat analysis. Pre- and post-intervention data showed that patients had significant declines in anxiety (effect size Cohen’s d = 0.32, p = .01), distress (d = .46, p = .001), and depression (d = 0.52, p = .001) at 12 months, and partners had significant declines in anxiety (d = 0.45, p = .01) and distress (d = .42, p = .02) within the highly distressed group. No significant differences were seen in the less distressed group over time.

Findings suggest that psychotherapeutic interventions can reduce anxiety, distress, and depression among patients and partners who are highly distressed. Little benefit may exist for individuals who are less anxious or distressed at baseline.

• Small sample (less than 100)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Questionable protocol fidelity
• Other limitations/explanation: Distress measurement and definition are not described. The matched controls were not completely described but were highly educated; the education level of the comparison group is unknown. The intervention was not standardized or reviewed for content, so one cannot determine the similarities or dissimilarities of intervention sessions.

Psychotherapeutic interventions may be beneficial for patients and caregivers who are highly distressed. Nurses need to be aware of the overall level of patient and caregiver distress and identify those who are likely to benefit from referral for therapy.

To evaluate the efficacy of an energy and sleep enhancement (EASE) intervention to relieve fatigue and sleep disturbance and improve health-related functional status.    

One hundred fifty-three individuals receiving chemotherapy were randomized to the EASE intervention and 139 were randomized to an attention control intervention. Participants in each group received three telephone sessions taught by a specially trained oncology nurse and a separate written handbook for each assigned intervention. The EASE intervention was based on the common sense model and involved appraisal and representation of symptoms, with a focus on fatigue and sleep disturbance, including communication of individualized strategies for fatigue management and sleep enhancement. The control intervention focused on information about nutrition and a healthy diet. The primary outcomes of fatigue, sleep disturbance, and functional status were measured before chemotherapy, day 4 after first treatment (baseline), and 43 to 46 or 57 to 60 days later (follow-up), depending on the chemotherapy cycle length. Two secondary outcomes, pain and depression, were chosen for evaluation, but not targeted for the intervention, because of an increasing body of evidence linking them to fatigue.

• Two hundred seventy-six patients (83% female and 17% male) receiving chemotherapy were included.
• Mean age was 53.9 years (SD = 12.02).
• The most common cancer diagnoses were breast (55%), lung (17%), lymphoma (8%), and ovarian (6%).
• Of the patients, 90% were Caucasian, 70% were married, 42% were college educated, and 95% were treated with chemotherapy alone.

• Multi-site study conducted at two universities:  one community cancer center and one comprehensive cancer center
• Outpatient
• The intervention was delivered by nurses at Fox Chase Cancer Center, Philadephia, PA
   

Patients were undergoing the active treatment phase of care.

This was a randomized, controlled trial using repeated measures and an attention control.

• Demographic and clinical information form    
• General Fatigue Scale (GFS)
• Profile of Mood States Fatigue subscale (POMS-F)
• Pittsburgh Sleep Quality Index (PSQI)
• Octagonal Basic Motionlogger Actigraph
• Morin Sleep Diary
• Brief Pain Inventory (BPI)
• POMS Depressive symptoms subscale (POMS-D)
• Symptom Checklist (SCL)
• Adapted BPI interference items (SXINT)
• Short Form 12 Health Survey (SF-12)
• Eastern Cooperative Oncology Group (ECOG) Performance Status
   

Fatigue and patient-reported sleep disturbance were moderately elevated in both groups at baseline and follow-up. Actigraphy revealed that the total sleep time was almost eight hours, and sleep efficacy was in the normal range of greater than 85% for both groups at both time points. Physical functioning was diminished and at the same level as a sample with serious illness. Mental functioning was in the normal range. The EASE intervention did not improve fatigue, reduce sleep disturbance, or prevent functional decline during chemotherapy. Both the EASE intervention group and the control group had an increase in fatigue and decline in physical functioning over time. ANOVA revealed no statistically significant group-by-time effects for fatigue, sleep disturbance, or functional status. A positive outcome in both groups was a decrease in the average number of nighttime awakenings over time. Unemployed individuals showed greater benefit from the EASE intervention and reported less pain and symptom interference.

In patients with cancer undergoing chemotherapy, the EASE intervention did not significantly improve fatigue, sleep disturbance, or physical functioning compared to the control group. Potential explanations include high variability or floor effect for fatigue, incorrect timing of measures, insufficient amount or dose of the intervention, and confounding effects of gender. Future research should consider screening for symptom severity and tailoring interventions.

• The ineffectiveness of EASE could be affected by the intervention dose, timing of the measures, and the large number of participants with low symptom severity.
• There was an overrepresentation of patients with breast cancer and underrepresentation of patients with lung cancer.
• Factors that may have affected the outcome included variation in populations, treatments being received, and lack of control over the severity of symptoms.

Future research directions were clearly described in the study, and practice implications included:  many individuals with multiple symptoms during chemotherapy could benefit from effective behavioral interventions conducted over time by skilled nurses. Further research could inform nurses of the most effective management methods to control symptoms.

The energy conservation and activity management (ECAM) intervention consisted of information provision, guidance in formulating and implementing a plan for energy conservation and activity management, and support in appraising the effectiveness of symptom management efforts. The intervention included completing a journal to monitor fatigue, sleep, rest, activity, and other symptoms; listing and prioritizing usual activities; and creating a tailored energy conservation plan. The intervention was delivered by nurse counselors in three telephone sessions that were 15 to 30 minutes in length.

• The study included 396 adults (age range 18–83 years); 85% were women, and most were Caucasian.
• Multiple diagnoses were included, but 71% of participants had breast cancer.
• All participants were initiating treatment with chemotherapy (47%), radiotherapy (44%), or concurrent chemoradiotherapy (9%).

Outpatient services of two large university cancer centers

Patients were undergoing the active treatment phase of care.

The study was a randomized, clinical trial with a repeated-measures design and an attentional control group.

• Profile of Mood States (POMS)
• Schwartz Cancer Fatigue Scale (SCFS)
• General Fatigue Scale (GFS)

• The ECAM intervention had a statistically significant effect in reducing fatigue, but the clinical effect was modest.
• The intervention group experienced significantly less disruption of usual activities compared with the control group, although the intervention was not associated with changes in overall functional status.

Efficacy findings were not confounded by the inability of patients who were in poorer health to complete the data collection process.

• Overrepresentation of women and a breast cancer diagnosis limits the generalizability to men, patients with other diagnoses, and those in poorer health.
• The amount of missing data was substantial. 
• Costs were not addressed.

Minimal training with the intervention materials is needed.

The energy conservation and activity management (ECAM) intervention included completing a journal to monitor fatigue, sleep, rest, activity, and other symptoms; listing and prioritizing usual activities; and creating a tailored energy conservation plan. The intervention was delivered by nurse counselors in three telephone sessions of 15 to 30 minutes in length.

• The study sample included 38 adults in two groups:  radiotherapy (n = 18; mean age = 59.4 years; 70% female; 84% Caucasian) and chemotherapy (n = 20; mean age = 57.4 years; 91% female; 95% Caucasian).
• The control group included 182 adults (mean age = 55.1 years; 58% female; 95% Caucasian).

• Experimental participants were outpatients in a National Cancer Institute–designated cancer center.
• Patients in the control group were from a multi-site study on fatigue measurement.

Patients were undergoing the active treatment phase of care.

• The study used a single group pre-/posttest design.
• A nonequivalent control group from another study was used for posttest comparisons.

Profile of Mood States (POMS) Fatigue scale

• The intervention was well tolerated and acceptable to patients.
• Results showed a trend for the two groups to differ at both points in time, with the control group exhibiting higher fatigue scores than the ECAM group.

• The study had a small sample size.
• The control group was a nonequivalent.
• The population was vulnerable, with many medical problems that can effect adherence.

Minimal training with the intervention materials is needed.

Databases: CINAHL, MEDLINE, PsycLIT, and CANCERLIT

The study evaluated 36 randomized clinical trials (RCTs), seven quasi-experimental trials, five  descriptions, six reviews, and one practice guideline published 1980–2000.

In 22 of 36 RCTS, psychoeducational interventions benefited patients with symptoms of depression.

The evidence dervied from this review supports the benefit of psychoeducational interventions for depression in patients with cancer.

STUDY PURPOSE: To evaluate the effectiveness of opioids in relieving the symptom of dyspnea in people with advanced disease

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 26 in review, 18 in meta-analysis 
• TOTAL PATIENTS INCLUDED IN REVIEW = 276 in meta-analysis
• SAMPLE RANGE ACROSS STUDIES: 6–25
• KEY SAMPLE CHARACTERISTICS: Cancer, chronic obstructive pulmonary disease (COPD), and heart disease were included.

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

Based on change in dyspnea from baseline, no statistically significant difference existed with opioids across seven studies. This evidence showed high heterogeneity and low overall quality. A comparison of post-treatment dyspnea scores in 11 studies showed significant benefit with opioids (standard mean difference [SMD] = –0.28, 95% confidence interval [CI] [–0.5, –0.05], p = 0.02). No significant effects (two studies) existed for nebulized opioids. Six studies were of patients with cancer. A few studies evaluated breathlessness in terms of exercise tolerance only.

The findings show that oral opioids have some benefit for the relief of dyspnea and may have some benefit for short-term improvement in exercise capacity.

• Mostly low quality/high risk of bias studies
• High heterogeneity
• Low sample sizes
• No subgroup quantitative analysis; differences for various patient subgroups were not analyzed.

Oral opioids are of benefit for reducing dyspnea. Nebulized opioids were not shown to be effective.

To assess the efficacy and safety of lubiprostone in the treatment of patients with chronic constipation.

Patients had a washout period, followed by a two-week prerandomization period. Patients were randomized to receive either oral lubiprostone 24-mcg capsules (n = 119) or placebo (n = 118) twice daily with food and at least 8 oz of water. Patients were instructed to keep daily diaries to record their medication administration, use of medication rescues, and occurrences of bowel movements (BMs) (date and time). Study assessments were scheduled after one week (office visits), two weeks (telephone evaluation), four weeks (end-of-treatment office visit), and two weeks following the end of treatment.

• The study reported on a sample of 237 patients who met the Rome II criteria for functional constipation.
• Mean patient age was 46.2 years (SD = 12.13) for the lubiprostone group and 45.4 years (SD = 13.24) for the placebo group.
• The study comprised 104 women and 15 men in the lubiprostone group, and 105 women and 13 men in the placebo group.
• Constipation severity was 3 (SD = 0.82) in the lubiprostone group and 3 (SD = 0.76) in the placebo group. 
• Stool consistency was 2.7 (SD = 0.83) in the lubiprostone group and 2.8 (SD = 0.77) in the placebo group.
• All were normal patients with constipation.

• Multi-site
• United States

This was a randomized, double-blinded, placebo-controlled study.

• Daily BM diary
• Five-point scale of stool consistency
• Five-point scale of stool straining

• Lubiprostone was an effective treatment for chronic constipation, with more than 60% of patients having a spontaneous BM within 24 hours of their first dose.
• Patients taking lubiprostone also experienced significant improvement in spontaneous BM frequency, stool consistency, straining, severity, and abdominal bloating.
• Patients' global treatment effectiveness was significantly higher in the lubiprostone group compared with the placebo group.
• Fewer patients receiving lubiprostone required rescue medication.
• Nausea was the most common adverse side effect reported, occurring in 25 patients in the lubiprostone group compared to five patients in the placebo group.

Lubiprostone was an effective treatment for chronic constipation.

• The sample comprised more women than men.
• Nausea was reported as toxicity to the drug, but also was reported in the placebo group. In addition, nausea may also be seen in patients who have issues with constipation.
• The sample did not include patients specifically with cancer or related opioid-induced constipation. Therefore, applicability to that population is unclear.

Lubiprostone has been shown to be effective in the management of chronic constipation and is used for patients with chronic constipation related to irritable bowel syndrome. However, additional studies are warranted in patients with cancer, as well as the palliative care population, in which patients are receiving chemotherapy agents, antiemetics, and narcotics that contribute to their constipation.

To assess the effect of active manuka honey on the grade and duration of mucositis

Patients were randomly allocated by a computer-generated list of random numbers to be given active manuka honey or placebo (golden syrup) mixed with 2% sodium alginate, which increased the contact time by ensuring that the substance adhered sufficiently to the oral and oropharyngeal mucosa. They were shown the technique and given verbal and written instructions to rinse the mouth with 20 ml of the allocated substance and to swallow it slowly, 4 times per day for the duration of the radiotherapy (4 weeks) and for 2 weeks after treatment (42 days in total). To assess compliance, they were also asked to record daily on a card when they took the substance.

The patients were all to receive 4 weeks (20 fractions) of accelerated radiotherapy at a dose between 50 and 55 Gy. Synchronous or induction chemotherapy, or both, was permitted.

Since both substances in the study are known to be cariogenic in patients being treated by radiotherapy, all patients were seen by the hospital dentist before beginning treatment and were provided with fluoride toothpaste and a soft toothbrush and given written and verbal dental hygiene instructions. 

Inter-rater reliability was measured between assessors and found to be higher using the modified scale.

Weekly assessments of mucositis were undertaken during radiotherapy (four weeks) and every two weeks thereafter until the mucositis resolved. Weight was assessed at each assessment.

Swabs were taken from the throat to assess for bacterial and fungal infections. These were taken at baseline and during and after radiotherapy, and the process was overseen by a microbiologist consultant.

• The sample consisted of 131 patients, with 64 in the experimental arm and 63 in the control arm.
• The experimental arm was 83% male and 17% female. The control arm was 92% male and 8% female. 
• The mean age patients in the experimental arm was 59 years old. The mean age of patients in the control arm was 58 years.
• Patients were drawn from a consecutive sample who had either oral or oropharyngeal cancer.

Patients were recruited from an outpatient clinic at a cancer center in northwest England.

Patients were undergoing the active treatment phase of care.

This was a double-blind, randomized, controlled study. The treatment allocation was by minimization with an allocation probability of 2/3 to the arm that would yield a lower imbalance score.

A modified acute radiation toxicity scale of mucositis by the Radiation Therapy Oncology Group was used.

Primary analysis revealed no significant differences in the incidence of grade 3 mucositis or severity or duration of mucositis between the two groups. 

Ninety-eight percent of the patients managed at least 1 week of the intervention, and 67 patients managed more than 2 weeks. Median compliance was 2 weeks for both groups.

The incidence of pathogenic bacteria in both arms was similar to reported baseline values, which indicated that the levels of bacterial colonization were similar to those of an unirradiated mouth. It also confirms the previous findings that honey has a bacteriostatic effect, which might be the result of its hyperosmolar properties, as golden syrup had a similar effect.

No significant differences were found in either the primary or the secondary outcome measures when honey was compared with placebo. The results of the study did not agree with the findings of other trials.

• Poor compliance affected the potential impact of the intervention. Patients reported problems with the taste and texture of the product and cited the effort required to take them as reason for discontinuation.
• Compliance might have been hampered by the use of the carrier agent (sodium alginate).
• The intervention required too much volume and was too sweet for the subjects to be expected to use it daily.
• A different formulation of honey should be used for future studies, using only the active ingredient and using a more liquid formulation.
• This was a single institution study.
• No measurement for or discussion of the use of opioids for pain control in the results and discussion segment of the report, even though this topic was listed as a secondary outcome.
• The article was poorly written with several grammatical errors that hampered understanding.
• The authors did not specify if chemotherapy was given, and, if so, which drugs, amounts, and durations, all of which can influence the development of mucositis.
• Further research is needed to determine methods that are successful in treating grade 3-4 mucositis during radiotherapy.
• The study was not very practical if the median compliance was only half of the study treatment duration. The patients were to swallow 20 ml of honey 4 times a day for the duration of the study, which was too difficult for the participants to accomplish. This intervention is unlikely to be used in clinical practice.

Well-documented bacteriostatic properties of honey exist; further research needs to be done to determine feasibility in the realm of preventing oral mucositis.

To evaluate the efficacy of various complementary and alternative medicine (CAM) therapies to reduce cancer pain

The type of article is systematic review.

• Databases searched were MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine (AMED), and the Cochrane Library up to August 2005. Investigators also searched reference lists from articles to identify relevant studies.
• Search keywords were cancer, pain and alternative medicine, and neoplasm, as well as terms for major individual CAM therapies.
• Studies were included in the review if they were randomized clinical trials (RCTs) that had a CAM intervention for cancer pain.
• Exclusion criteria were not cited.

The initial search identified 101 articles, of which investigators excluded 85. Investigators included an additional two articles, which were found through manual scans of reference lists. Investigators appraised articles by using the Jadad scale.

• The final sample included 18 studies reporting on 1,499 patients.
• The average sample included less than 100 patients; median sample size was 54 patients.

• Acupuncture: Investigators evaluated three trials, of which one was a high-quality study that used auricular acupuncture to treat 90 patients. Compared to the placebo group, the treatment group had a significant decrease in pain intensity that lasted two months.
• Mind-body interventions: Investigators assessed five trials. Two of these were trials of intermediate quality in which support groups were effective in decreasing pain. Interventions included group supportive psychotherapy, hypnosis, and support groups. Two trials concluded that relaxation and imagery were effective in reducing pain. Researchers obtained no greater relief by adding cognitive behavioral therapy to relaxation or imagery.
• Music: Assessment revealed that the three trials were of poor quality. Results were mixed. Effects measured were of very short duration.
• Herbal mixtures: Two trials examined different herbal supplements. Both trials were of poor quality, and one did not report actual statistical results. Authors could draw no meaningful conclusions from this information.
• Massage therapy: The four trials involving massage therapy had mixed results in terms of efficacy. Most of these trials had very small sample sizes, and none found intervention effects that lasted longer than four weeks.
• Healing touch or Reiki: Two trials involved these interventions. Results did not warrant conclusions about effectiveness.

The result of this systematic review was that none of these interventions can be recommended as effective. The most promising therapies appear to be mind-body interventions. In particular, hypnosis and relaxation might have some effect in decreasing cancer pain. Effect may be limited by cognitive impairment caused by cancer or cancer treatment. Support groups may have some positive effects. Whether these benefits are due to increased patient awareness, with more frequent visits to care providers, better compliance with medication regimens, or as a result of group interaction and social or emotional support is unclear. One study found that benefit occurred only in those patients who were more distressed at baseline. It is possible that effect sizes of therapies may be more discernible among patients with higher pain ratings, demonstrating a floor effect related to the symptom of pain.

• Most trials were of low quality, with missing data and incomplete reporting. This fact made extracting sufficient usable information difficult.
• Few studies in the analysis examined a specific intervention.

Current evidence does not support the efficacy of the cited CAM interventions in the management of pain of patients with cancer. Methodologically strong research that incorporates appropriate attentional and sham controls, sufficient sample sizes, and longer duration of follow-up is needed.