STUDY PURPOSE: To access the effectiveness of acupuncture as a treatment option for hot flashes in patients with breast cancer through a systematic review

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 6
• TOTAL PATIENTS INCLUDED IN REVIEW = 281
• SAMPLE RANGE ACROSS STUDIES: Sample size ranged from 20–72.
• KEY SAMPLE CHARACTERISTICS: Women with breast cancer experiencing hot flashes

PHASE OF CARE: Transition phase after active treatment

Of the six studies that were reviewed, three compared the effects of manual acupuncture with sham acupuncture, one compared the effects of electroacupuncture (EA) with hormone replacement therapy, one compared acupuncture with venlafaxine, and one compared manual acupuncture with relaxation therapy. Of the studies examined, all were randomized, controlled trials. Of the three comparing manual acupuncture with sham, one showed favorable results of acupuncture reducing the frequency of hot flashes, whereas the other two studies failed to do so. The study comparing EA with hormone therapy demonstrated that hormone replacement therapy was more effective in controlling hot flashes than EA. The study comparing acupuncture and venlafaxine showed no difference. When relaxation therapy was compared with acupuncture, no intergroup difference occurred.

This systematic review of six articles using acupuncture to treat hot flashes in women with breast cancer failed to demonstrate that acupuncture was a clearly effective treatment tool. When comparing acupuncture with sham acupuncture, the three studies were not consistent in their findings, with one demonstrating that acupuncture was effective and two that did not. In the additional three studies, acupuncture was not found to be superior to hormone replacement therapy, venlafaxine, or relaxation therapy.

• Limited number of studies included
• High heterogeneity
• The researchers acknowledged that some of the studies had suboptimal data in the primary study reviewed.

This review of randomized studies did not demonstrate that acupuncture was a superior therapy to hormone replacement, venlafaxine, or relaxation therapy in controlling hot flashes in women with breast cancer.

STUDY PURPOSE: To evaluate the effect of acupuncture on hot flashes in men with prostate cancer

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 6 
• TOTAL PATIENTS INCLUDED IN REVIEW = 132
• SAMPLE RANGE ACROSS STUDIES: 7–60 patients diagnosed with and treated for prostate cancer
• KEY SAMPLE CHARACTERISTICS: Multiple treatments for prostate cancer

PHASE OF CARE: Not specified or not applicable
 
APPLICATIONS: Elder care

Five of the six studies included were uncontrolled observational studies. All six studies showed a reduction in the severity and frequency of hot flashes in men with prostate cancer. Some studies reported no follow-up; one study followed patients for 12 months. Mild adverse effects reported included distress, fatigue, hematoma at the insertion site, and a very short (few seconds) increase of vasomotor symptoms.

The researchers concluded that the evidence from these six studies is not convincing to recommend acupuncture as an effective treatment for hot flashes in men treated for prostate cancer. The researchers recommended more research with larger randomized, controlled trials. Mild adverse effects were noted with acupuncture.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• High heterogeneity
• Low sample sizes
• No exclusion criteria stated
• Five studies were uncontrolled observational studies.  
• Some studies did not report any follow-up.

The six studies did not provide convincing evidence that acupuncture is an effective treatment for reducing hot flash frequency and severity in men diagnosed with prostate cancer. More large randomized, clinical trials are need to evaluate the effectiveness of acupuncture. Such studies should include longer periods of follow-up to determine the long-term effectiveness.

To summarize a systematic review of existing evidence regarding the effect of acupuncture on cancer-related pain

Databases searched were MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine Database (AMED), PsycINFO, British Nursing Index, the Cochrane Library, and databases relative to Journal of Korean Society for Acupuncture and Moxibustion and Journal of Korean Oriental Medicine. Investigators performed manual searches of department files and the reference lists of all located articles.

Search keywords were acupuncture, electroacupuncture, cancer, neoplasm, and tumor.

Studies were included if they were

• Published in any language
• Prospective clinical studies that used manual acupuncture, ear acupuncture, or electroacupuncture for the treatment of cancer-related pain in humans.

Studies were excluded if they related to laser acupuncture, acupressure, or moxibustion or used transcutaneous electrical nerve stimulation or other cointerventions that were complementary or alternative medicine modalities; were case series, case reports, or  abstracts with no details about the intervention; and involved acupuncture for postoperative pain in patients with cancer.

Investigators reviewed 29 studies initially and chose 7 for analysis. Two authors, working independently, read all articles in full and extracted data about trial methods, study design, participants, interventions, type of pain, pain outcomes, and adverse effects. Authors used a modified Jadad scale to rate the studies. (The study summary cites rating criteria.) Authors met to reach consensus, and discrepancies were settled by discussion with the third author. The Jadad scale was modified because of the near impossibility of blinding the acupuncturist to the treatment.

• The total sample size was not reported.
• The sample range across studies was 12–92.
• Characteristics of the sample were all cancer types (heterogeneous), neuropathic nociceptive (> 30/100), abdominal, back, and not specified.

• The studies of acupuncture for cancer-related pain were not evidence-based. Visual analog scale and patient’s verbal assessment were the primary pain-related measures. One study used the plasma leucine-enkephalin level as a measure.
• The quality of the included studies was lacking—only three of the seven studies were randomized controlled trials.

Data from this study do not support the use of acupuncture as an effective analgesic adjunctive method for the treatment of cancer pain. Note that 2003 is the most recent date of an article in this systematic review; articles excluded were published 1974–2003.

Appropriately powered randomized controlled trials that investigate the efficacy of acupuncture are needed.

To evaluate if armodafinil versus placebo reduced fatigue and improved quality of life when measured via the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale at baseline and 42 days.

Prior to starting treatment, participants completed several questionnaires rating fatigue and quality of life. The participants were randomly assigned 1:1 to the armodafinil group or placebo group, and questionnaires were completed again at day 22, day 43, and day 56, with the primary end point being day 43, as this was the end of radiation therapy for most patients enrolled. Participants in the armodafinil group received 150 mg daily for eight weeks.

• N = 62   
• AGE RANGE =19–79 years; armodafinil group (median = 56 years), placebo group (median = 54 years)
• MALES: 55.6%, FEMALES: 44.4%
• CURRENT TREATMENT: Chemotherapy, radiation
• KEY DISEASE CHARACTERISTICS: Grade 2–4 glioma, grade 4 most common, receiving 50–60 Gy radiation therapy total
• OTHER KEY SAMPLE CHARACTERISTICS: Karnofsky score greater than 60, ability to read and write in English, no history of major mental illness. The majority of patients were receiving concomitant temozolomide.

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Dana–Farber Cancer Institute, Boston, MA

PHASE OF CARE: Active antitumor treatment

Randomized, placebo-controlled, pilot trial

• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)
• FACT-General (FACT-G)
• Brief Fatigue Inventory (BFI)
• Cancer Fatigue Scale (CFS)
• Beck Depression Inventory (BDI)

No statistically significant findings using any questionnaire were reported between the treatment arm and the placebo arm at any point measured (day 21, 42, or 26).

Based on this study, one can conclude that armodafinil is not effective in reducing fatigue or improving quality of life in this patient population. It would be helpful to know if the FACIT-F questionnaire has been used in this patient population previously with no concurrent interventions.

• Small sample (< 100)
• Risk of bias (no blinding)
• Findings not generalizable

The findings of this study indicate that more education regarding the multiple factors that can cause fatigue in this patient population is needed, as well as tools to measure this fatigue more effectively to better gauge interventions. The study stated that fatigue is reported during radiation therapy in this patient population, but the questionnaires used did not capture that.

To compare the effectiveness of standard fluoroquinolone prophylaxis with fluoroquinolone plus ceftriaxone in the prevention of infection post prostate biopsy

Patients received one of three prophylaxis regimens: (a) 500 mg fluoroquinolone by mouth twice a day for three days, (b) 500 mg fluoroquinolone by mouth twice a day for three days plus 2 g IV ceftriaxone once before biopsy, or (c) 500 mg fluoroquinolone by mouth twice a day for more than seven days plus 2 grams IV ceftriaxone once before biopsy.

• N = 5,577   
• MEAN AGE = 64 years
• AGE RANGE = 18–92 years
• MALES: 100%
• CURRENT TREATMENT: Immunotherapy
• KEY DISEASE CHARACTERISTICS: None described
• OTHER KEY SAMPLE CHARACTERISTICS: N/A

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: South Korea

• PHASE OF CARE: Diagnostic

• Retrospective case review

Infection post prostate biopsy was defined as any of the following: a temperature greater than 38 degrees Celsius, a white blood cell count greater than 12,000/mm³, a urinary tract infection, or acute prostatitis.

A significant decrease of infections was observed post prostate biopsy for patients that received prophylaxis with fluoroquinolone plus ceftriaxone (p < 0.001). One percent of patients who received fluoroquinolone prophylaxis had infectious complications compared to 0.3% of patients who received fluoroquinolone plus ceftriaxone. Patients who received fluoroquinolone prophylaxis for more than seven days had no added reduction of infection compared to patients who received fluoroquinolone prophylaxis for three days.

Infection prophylaxis with fluoroquinolone alone after prostate biopsy may be insufficient because of increasing resistance among pathogens, including Escherichia coli. The addition of 2 grams IV ceftriaxone before prostate biopsy was correlated with a significant reduction in infectious complications at one hospital in South Korea.

• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• Findings not generalizable
• The time frame of the retrospective comparison groups differed by several years (group 1: 2005–2009 versus groups 2 and 3: 2010–2012); thus, other clinical practice variations may have affected the results.
• Patient adherence to oral fluoroquinolone was not assessed.
• For infectious cases to be identified, patients with complications needed to return to the participating hospital. Patients with complications may have gone to other hospitals, affecting results.
• Groups were not assessed for risk factors, so comparison between groups is limited.
• The study was conducted at one hospital, limiting generalizability to other hospitals.
• Observation/reporting time frame for infectious complications after prostate biopsy not defined

Adequate patient education on potential infectious complications is necessary post prostate biopsies. To tailor infection prophylaxis, nurses should consider assessing for individual risk factors for infection (e.g., diabetes, history of organ transplant, etc.) and collect rectal swabs to identify quinolone-resistance organisms.

To examine the effects of nurse-led cognitive-behavior therapy (CBT) on fatigue and quality of life (QOL) experienced by patients with breast cancer who were currently undergoing radiotherapy.

An oncology nurse-led six-week intervention program that included cognitive restructuring, education about breast cancer and medical treatment, relaxation therapy, and rehabilitation exercise was offered to women receiving radiation therapy at a university hospital in Korea. Nurses who led the course attended the beginner’s course of CBT for 36 hours.

• In total, 71 patients (71% female) were included.           
• Age ranged from 25 to 60 years.
• Patients had breast cancer.
• Of the patients, more than half had a partial mastectomy, 93% had no family history of breast cancer, and nearly half had received chemotherapy.

Single site

Patients were undergoing the active antitumor treatment phase of care. 

The study used a quasiexperimental pre-/posttest design with a nonequivalent control group.

• Korean version of the Revised Piper Fatigue Scale (PFS)
• QOL Scale for Korean Patients With Cancer

Levels of fatigue increased in both groups at the posttests. Increases in the levels of fatigue were greater in the control group than in the experimental group. Levels of QOL increased in the experimental group and decreased in the control group.

Nurse-led CBT did not show a significant effect in reducing the levels of cancer-related fatigue, although the increments of fatigue were significantly lower than the control group. Nurse-led CBT was effective in increasing QOL.

• The study had a small sample size, with less than 100 patients.
• The study had a risk of bias due to no blinding.
• Findings were not generalizable
• Intervention expensive, impractical, or training needs.
• Authors mentioned seasonal influence – fatigue is exacerbated in the winter and alleviated in the summer.

There is a role for oncology nurses to lead a structured cognitive-based intervention program to help alleviate cancer-related fatigue in women with breast cancer receiving radiotherapy.

To systematically review randomized, controlled trials that investigated the efficacy of acupressure for the management of symptoms.

Databases searched were CINAHL, MEDLINE, and PubMed.

Search keywords were acupressure, clinical trial, human, and/or randomized.

Studies were included in the review if

• They were randomized, controlled trials published from January 1, 2000 to January 31, 2010
• They were published in English
• They used acupressure as the sole intervention for one group
• There were four or more studies of the efficacy of acupressure for that particular symptom.

Studies were excluded from the review if they

• Had sample sizes of less than 30 patients
• Used auricular or hand pressure, reflexology, shiatsu, and electronic or magnetic devices
• Were unpublished studies and abstracts.

In total, 108 references were screened.

Each experimental study was evaluated for quality using the Cochrane risk of bias (RoB) tool. Articles were evaluated for the presence of each of the six domains, and one point was assigned for each domain present. Scores ranged from zero to six, with higher values indicating higher quality and less risk for bias. All trials were evaluated by two authors, and agreement between them was 100%. A significant likelihood of bias was found in the evaluation.  

Only six randomized, controlled trials included were performed to determine the efficacy of acupressure on the reduction of fatigue and improvement of sleep in adults in various populations. Fatigue and insomnia were grouped together because those investigations were typically studied simultaneously.  
 

• The final number of studies included was 43.
• The total sample size was 5,021 patients across all studies of all symptoms. For studies that specifically focused on fatigue and insomnia, the sample size was 211 patients.
• The sample range across all studies was 36 to 739 for all studies of all symptoms.
• Multiple diagnoses and symptoms were included:  nausea, pregnancy, chemotherapy, radiation, surgery, motion sickness, pain, dysmenorrhea, labor, back pain, fracture, trauma, dyspnea, asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, endstage renal disease (ESRD), and insomnia.

Patients were undergoing the active treatment phase of care.

Only three studies conducted included a measure of fatigue. Six studies concluded that acupressure was effective in improving fatigue and reducing insomnia. Multiple symptoms were discussed in topic areas; findings from other symptom reviews were not included in the summary.

The review did not provide rigorous support for the use of acupressure for the efficacy of symptom management.

• Significant bias existed according to the Cochrane RoB tool. 
• Lack of fidelity to the intervention confounded the results and may have added bias to the studies.

Well-designed randomized, controlled trials are needed to determine the utility and efficacy of acupressure to manage various symptoms in several patient populations. Issues exist when looking at fatigue and insomnia concurrently, such as determining whether fatigue is an intervening variable for insomnia or an outcome variable of insomnia or whether insomnia is an intervening variable for fatigue. A conceptual framework is needed to guide how concurrent or symptom clusters are studied.

To assess the efficacy and safety of an herbal decoction including Astragali Radix in improving appetite and body weight and changing cytokine levels in patients with advanced cancer experiencing anorexia

The herbal decoction consisted of a combination of herbs including Astragali Radix made in the hospital pharmacy every week. The decoction was administered 30 minutes after meals, three times a day for three weeks. The decoction was stopped for treatment refusal, the aggravation of anorexia or weight loss in the midst of therapy, or physician decision. Assessments of appetite were performed at baseline and then weekly until termination of the study. Cytokines were checked at baseline and at the third week.

• The study reported on 11 patients.
• Mean patient age was 59.8 years (range = 42–76 years).
• The sample was 72.7% male and 27.3% female.
• Patients were diagnosed with lung cancer, gastric cancer, or colorectal cancer.
• Use of chemotherapy or radiation therapy was permitted throughout the study period.
• Exclusion criteria included use of tube feedings or parenteral nutrition; simultaneous treatment with adrenal corticosteroids, androgens, progestational agents, or other appetite stimulants; brain metastasis; pregnancy or lactation; and mechanical obstruction of the alimentary tract.

• Single site
• East-West Neomedical Center at Kyung Hee University in Seoul, Republic of Korea

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

A prospective, phase II trial design was used.

Toxicity was assessed as well as tumor response using Recist criteria.

• History and physical exam
• Visual analog scale (VAS) for anorexia
• Body weight
• Skinfold thickness
• Cytokine levels: IL1β, IL-6, TNF-α, and lactate

Primary endpoint: VAS anorexia scores before and after the herbal decoction were significantly improved (p = 0.008). Secondary endpoints: 55% of patients had improvements in both anorexia and body weight at the third week (p = 0.009). The correlation of improvement of anorexia and body weight at the best point was also significantly positive (p = 0.003). The changes in skinfold thickness of the triceps, subscapula, and suprailiac did not significantly change (p = 0.182). The cytokines did not significantly change. Lactate and lactate dehydrogenase (LDH) levels were significantly worse at three weeks. Eight patients were administered the full treatment of the herbal decoction, three patients had the decoction for two weeks, one patient had treatment stopped due to toxicity of concomitant chemotherapy, and two patients had disease progression. Grades 1/2 diarrhea occurred in two patients. Grade 1 dyspepsia occurred in two patients. Grade 1 alanine transaminase abnormality occurred in one patient. Grade 2 neutropenia and grade 2 anemia occurred in two patients who also received concomitant chemotherapy.

This small study demonstrated potential for a combination herbal product to improve anorexia in patients with advanced cancers. Although patients showed significant improvements in anorexia scores and weight gain, cytokine and lactate and LDH values did not improve significantly and in some cases worsened, which is contrary to current thinking regarding the chemical picture of anorexia. Results of this study should be interpreted with caution.

• The study had a small sample size, with less than 30 participants.
• The study was not randomized, so placebo effect cannot be ruled out.
• Cytokines and VAS scores were not evaluated at the same intervals (cytokines were checked at baseline and the third week, and anorexia VAS scores were evaluated at baseline and weekly thereafter). Cytokine changes may have been missed. Changes in anorexia may not have been affected by cytokines.
• The study did not meet its projected accrual number of 30 patients and closed early because of an extended recruitment process. Sample size may have been too small to notice a change in the short period assessed.

Anorexia is a common symptom in patients with cancer. There are some drugs such as corticosteroids and megestrol acetate that can help to control anorexia. Complementary and alternative medicines may help treat cancer-related symptoms. Nurses need to remain knowledgeable about potential medications and complementary agents that may be useful in managing patients’ symptoms.

To test the efficacy of doxepin hydrochloride in reducing radiotherapy-induced oral mucositis pain

Arm 1: Doxepin oral rinse 10 mg/ml x 2.5 ml = 25 mg diluted with sterile or distilled water for a total of 5 ml. Arm 2: Placebo rinse prepared in similar manner with flavored syrup added. Study dose was prepared by unblinded nurse or pharmacist. Blinded personnel administered the rinse. On day 1, the patients swished for one minute, gargled, and spit. On day 2, patients received the opposite rinse. Patients completed symptom questionnaires at set time intervals during the hour following administration and then again at home at two and four hours. No analgesics or oral rinses were allowed 60 minutes prior to and following the study doses. Patients returned the next time their oral pain was ≥ 4/10 and received their second study dose, after which they were unblinded and given the option to continue use of doxepin rinses prn. Patient-reported questionnaires with numerical pain analog scale (0–10) done at BL, 5, 15, 30, 60, 120, and 240 minutes after the rinse on days 1 and 2 to measure pain, taste, stinging or burning, and drowsiness.

• N = 129 
• MEAN AGE = Doxepin-Placebo, 62 years (range = 39–93 years), Placebo-Doxepin, 60 years (range 37–86 years)
• MALES: 80%, FEMALES: 20%
• KEY DISEASE CHARACTERISTICS: Patients 18 years or older with head and neck malignancy currently undergoing radiotherapy, with or without chemotherapy, with a minimum planned dose of 50 Gy, including one third of the oral cavity mucosa using 1.6–2.2 Gy per fraction currently experiencing oral mucositis without infection and mouth pain rated 4 or higher (0–10 scale) and ECOG 0-2.
• OTHER KEY SAMPLE CHARACTERISTICS: No known allergies to doxepin or TCAs, use of TCAs or MAO inhibitors two weeks prior, no active or untreated herpes simplex virus or oral candidiasis, and no untreated narrow angle glaucoma or urinary retention within six weeks of registration. Patients were stratified according to sex, concurrent sensitizing chemotherapy, and age (< vs ≥ 60 years of age). Patients had to receive an oral examination with confirmed oral mucositis and without oral infection to be enrolled. 

• SITE: Multi-site
• SETTING TYPE: Outpatient
• LOCATION: 26 radiation centers in the United States

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care, palliative care

Randomized, double-blind, placebo-controlled, phase III trial with crossover phase followed by continued use of active agent

• Questionnaires were based on the Oral Mucositis Daily Questionnaire and the Oral Mucositis Weekly Questionnaire-Head.  
• CTCAEv.4.0 was used for toxicities.

Primary outcome: AUC for mean mouth and throat pain reduction was greater for doxepin compared with placebo (–4.4 difference p < .001). Crossover data revealed similar findings with –2.3 difference p < .001.

Largest placebo-controlled trial to date for oral mucositis pain with positive results

• Doxepin can cause drowsiness, caused more stinging and burning, and had a worse taste than placebo. Patients may have suspected what arm they were receiving because of these side effects, and it may have affected their decision about continuing with the doxepin rinses rather than efficacy alone. 
• Lack of longitudinal comparison data beyond one or two doses.
• Minimal data was collected in the continuation phase.
• No comparison with magic mouthwash. 
• Further studies are needed to confirm results. Prevention of mucositis was not looked at in this study, which is a much needed indication that should be researched.   

This is a promising option for mucositis pain although there are concerns about how the solution will be made, the cost, the ease of use, the side effects, and adherence to the rinse. Additional questions exist concerning whether or not this data can also be applied to patients receiving chemotherapy or those who have cancers other than head and neck cancer.

To identify and review all relevant data to determine whether lactulose or polyethylene glycol (PEG) is more effective in treating chronic constipation.

Databases searched were Medline, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials. Bibliographies of studies and conference proceedings  were hand searched.

Search keywords were fecal impaction, chronic constipation, delayed bowel movement, obstipation, irregularity, polyethylene glycol, ethylene glycol, PEG, ethylene oxide, PEG 3350, lactulose, and disaccharide.

Studies were included in the review if they

• Were randomized controlled trials comparing the use of lactulose and PEG
• Reported on adult patients or children diagnosed with chronic constipation or fecal impaction.

One hundred three initial references to January 24, 2008, were identified. A final set of 10 trials was included in this review. Studies were evaluated for various sources of bias and overall methodological quality. Trials were conducted in different countries in a variety of settings.

• The 10 trials included a total of 868 participants.
• 322 were adults and 546 were children.

• In most studies, assessment of study quality by investigators yielded highly variable results and little agreement of bias issues.
• In five studies, the overall mean difference in stool frequency per week was 0.65 (95% confidence interval [CI] [0.15, 1.15], p = 0.01) in favor of PEG.
• Among three studies in children, the mean difference in stool frequency per week was 1.57 (95% CI [0.36, 2.77], p = 0.011) in favor of PEG.
• In two studies that measured stool form and consistency, the mean difference was 0.89 (95% CI [0.43, 1.45], p = 0.00015) in favor of PEG.
• In one study of adults and two studies in children, the odds ratio for relief of abdominal pain was 2.09 (95% CI [1.26, 3.44], p = 0.004) in favor of PEG.
• Across three studies, patients on PEG had much less need for additional products to manage constipation (p = 0.000078).

• Findings suggest that PEG may be more useful than lactulose in both children and adults for improvement in constipation; however, the evidence is insufficient to draw firm conclusions because of the small number of studies and degree of heterogeneity found.
• Studies had a number of methodological issues.
• This review involved studies that did not include an oncology population.

One study included a sample of patients on methadone maintenance, which may have some relevance for constipation associated with opioid use.