STUDY PURPOSE: To evaluate what is known about mechanisms of scramble therapy and investigate preliminary evidence regarding efficacy

TYPE OF STUDY: General review/semi-systematic review

• FINAL NUMBER STUDIES INCLUDED = 20
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,200
• SAMPLE RANGE ACROSS STUDIES: 3–226 patients
• KEY SAMPLE CHARACTERISTICS: Four reports involved patients with chemotherapy-induced peripheral neuropathy; seven studies included patients with cancer

PHASE OF CARE: Not specified or not applicable

Most reports showed positive results for pain reduction for various pain syndromes. One double-blind, randomized trial showed no difference between controls and those receiving scrambler therapy for chemotherapy-related peripheral neuropathy.

Scramble therapy may have benefit for management of chronic pain and symptoms of peripheral neuropathy; however, current evidence is limited and weak.

• Limited number of studies included
• No quality evaluation
• Mostly low quality/high risk of bias studies
• Low sample sizes

Scrambler therapy, a neuromodulator approach to pain relief, may have some benefit in the management of chronic pain and peripheral neuropathy; however, current evidence is limited, and study designs have high risk of bias. Given the promising findings with scrambler therapy, additional well-designed research is warranted.

He-Ne wavelength 632.8 nm and output of 10 mW was administered for three minutes five days a week until completion of radiation.
Control group received  oral analgesics, anesthetics, 0.9% saline, and ovidine wash.

Physician was blinded to the type of treatment.
 

Patients with cancer of the oral cavity stages 2–4 receiving radiation 66 Gy in 33 fractions over six weeks

Computer randomization; 25 patients receiving laser treatment, 25 patients in the control group
 
Mean age of study group was 54 years (+/– 1 year); mean age of the control group was 53 years (+/–1 year).
 
Ratio of men to women was 2:1.
 

WHO mucosiis

VAS for pain

Recorded weekly
 

At the end of week 6 of RT, pain rank in the study group significantly decreased (p < 0.001) as compared to the control group (13 versus 38).

Mean pain score in the study group was 2.6 (+/– 0.64); the control group score was 6.68 (+/– 1.44) (p < 0.001).

At the end of radiation,  mucositis grade in the study group was 1.72 (+/–  0.67); the grade was 3.32 (+/–0.09) in the control group  (p < 0.001).

18 patients in the study group had grade 1, and 7 had grade 2 mucositis;
14 patients in the control group had grade 3, and 11 had grade 4.
 

Small sample size, but findings were significant at the end of radiation.

Did not report data during treatment
 

To evaluate the use of natural honey for treatment of radiation mucositis

Patients were randomly assigned to the honey treatment or control group. Patients in the intervention group were instructed to take 20 ml of honey 15 minutes before radiation therapy, 15 minutes after radiation therapy, and at bedtime. On days when they had no radiation treatment, they were to take the same amount of honey 3 times per day. Patients were evaluated at baseline, weekly during treatment, and at 3 and 6 weeks after completion of radiation therapy.

• The study reported on 55 patients with head and neck cancer.
• The mean age of patients was 47.5 years with a range of 35–65 years.
• The sample was 78% male and 22% female.

The study was conducted at a single outpatient site in India.

Patients were undergoing the active antitumor treatment phase of care.

This was a randomized controlled trial.

• The World Health Organization (WHO) mucositis scale was used.
• Body weight was recorded.

The authors reported that honey delayed the onset of severe mucositis in about 80% of the intervention group, while 63% of the control group developed severe mucositis.  Grade 3 mucositis developed in 11 patients in the control group and 5 patients in the study group. No statistical analysis was done.

This study suggests that honey may help to delay the onset of mucositis in patients with head and neck cancer during radiation therapy; however, multiple limitations in this report make it impossible to draw firm conclusions.

• The sample size was small with fewer than 100 patients.
• A risk of bias exists because of the lack of blinding and an appropriate attentional control condition.
• Although the authors reported that patients were receiving chemotherapy and radiation therapy, no information was provided regarding the chemotherapy agents used, any treatment delays, or radiation dose at which mucositis developed. 
• No statistical analysis was done.

 Findings as reported from this study are inconclusive regarding any effect of honey on the development of mucositis.

To evaluate the effectiveness of autologous fat grafting to control pain in patients with persistent postmastectomy pain syndrome (PMPS)

Patients who received lumpectomies and radiation therapy and had severe scar retraction, radiodystrophy, and chronic pain met the definition of PMPS and were considered for the study. Patients who had fat grafting underwent liposuction of the subumbilical area, and the obtained fat was processed and purified. The fat was then injected into the scar area. Study data were obtained at baseline and at one year after the procedure. Patients who had the fat graft procedure were compared to patients who did not receive the procedure.

• N = 92  
• MEAN AGE = 52.5 years (range = 33–68 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer and PMPS; none had chemotherapy, local recurrence, or previous breast surgery other than the initial lumpectomy

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

• PHASE OF CARE: Active antitumor treatment

Prospective trial

• Visual Analog Scale (VAS) for pain

Among those who had the fat graft procedure, there was a mean reduction of 3.1 points for pain compared to a mean reduction of 0.9 points in the comparison group (p ≤ 0.005).

Autologous fat grafting may have reduced PMPS.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Other limitations/explanation: It was not clear if the VAS measurement was of worst pain, average pain, etc., or over what time period it was considered.

Persistent pain as a consequence of surgical treatment for breast cancer is a clinical problem for which the general treatment is pain medication. Nurses need to be aware of this syndrome and educate patients about alternative approaches that may be available for management. Additional well-designed research regarding the efficacy of fat grafting for this population is needed.

To evaluate the tolerability and activity of Kamillosan (chamomile cream) as compared to almond ointment in patients receiving radiation therapy

Patients were assigned to use one product above and the other product below their scar. The physician who evaluated the skin was blinded to which product was used on which side of the scar. The skin product was applied twice a day with the first 30 minutes before external beam radiation therapy and again at bed time. Reactions were noted after every 10 Gy and at two weeks and three months following completion.
 

• The study sample (N = 48) was comprised of female patients with breast cancer.
• Mean age of the sample was 56 years, with a range of 30–79 years.
• Patients received 2 Gy per fraction five times per week to 50 Gy (no break).

The study took place at Helsinki University Central Hospital in Helsinki, Finland.

The study used a quasi-experimental single-blinded design. Patients were used as their own controls

Adverse skin effects were graded on a four-point rating scale, with 0 being no change, 1 light erythema, 2 dark erythema, and 3 moist desquamation. Subjective evaluation was also performed, including symptoms such as pain and itching.
 

Skin changes seemed to appear later in the Kamillosan group; however, a higher proportion of the Kamillosan group developed grade 3 reactions. Overall, differences between groups were not significant. The subjective symptoms, such as itching and pain, were equally uncommon in the two groups. Most patients preferred Kamillosan because of convenience and hygienic preference.
 

Neither of the two agents prevented a skin reaction and every patient developed grade 1 erythema.

• Patients were able to decide which product went above or below the incision, leaving room for error.
• The skin grading scale is not one commonly used, and reliability or sensitivity is unknown.
• The sample size was small, with less than 50 patients.
• Since both products were used on all patients, there was no complete control and the effectiveness of either product could not be determined.
   

To compare the efficacy of sucralfate cream to a control base cream in women receiving postoperative electron beam therapy to their chest wall

Patients were randomized to apply sucralfate containing 7% micronized sucrose sulfate or equivalent base cream on either side of the scar.

N = 44

AGE RANGE = 33–84 years

MEAN AGE = 60 years

FEMALES: 100%

KEY DISEASE CHARACTERISTICS: Breast cancer of the chest wall

OTHER KEY SAMPLE CHARACTERISTICS: 6 MeV electron beam total dose 50 Gy—10 Gy weekly in five fractions. Surface area varied from 11 cm × 11cm–20 cm × 20 cm. The scar was situated horizontally in the middle of the portal image.

• SITE: Single
• LOCATION: Helsinki, Finland

• Quasi-experimental, double-blind design
  • Patients used as own controls

• Adverse effects were graded on a five-point rating scale (0 = no reaction; 1 = light erythema; 2 = dark erythema, area painful; 3 = wet desquamation; 4 = necrosis of the skin).
• Patients were interviewed for their preference of cream.

Grade 1 and 2 reactions appeared later on the areas treated with sucralfate cream. Grade 2 reactions in the entire sample were observed more often at four weeks (p = 0.01) and at five weeks (p > 0.01 but < 0.05). Recovery time of radiation-induced reactions was faster and, after finishing radiation therapy, the grade of skin reaction remained lower with the sucralfate cream than the base cream (p = 0.05).

Sucralfate may be of benefit in reducing severity of radiation dermatitis.

• No information is provided regarding patient compliance.
• What the total dose was when checked weekly is unclear.
• Where the rating scale came from is unclear.
• Small sample size

To find out the influence of rational emotive behavior therapy (REBT) on pain intensity among patients with cancer in India and Iran

The intervention included eight two-hour sessions of REBT characterized as cognitive techniques, imagery techniques, and behavioral techniques. The intervention was given to the experimental group for 45 days (10 sessions), and at the end of the intervention, pain of patients was evaluated again. Empathy, warmth, respect, relationship building, and family dynamics were covered in the first session; personal experience assessment was covered in the second session; counseling and REBT approach were covered in the third session; REBT was covered in the fourth through seventh sessions; and coping with stress was covered in the final session. Workbooks, worksheets, and practice exercises were included in the program. What the intervention actually entailed is not clear.

• N = 88
• AGE = 21–52 years
• MALES, FEMALES: Not described
• KEY DISEASE CHARACTERISTICS: Patients with cancer (no information about disease site or stage)
• OTHER KEY SAMPLE CHARACTERISTICS: None described

• SITE: Multi-site
• SETTING TYPE: Hospital
• LOCATION: India and Iran

• PHASE OF CARE: Multiple phases of care

• RCT

• McGill Pain Questionnaire

Because of errors in the tables, interpreting the findings is difficult. Data in the table are transposed from the information included in the narrative text; this makes interpretation of the information uncertain. The overall reliability of the data is in question.

The authors have asserted that an intervention resulted in reduction in pain perception, as measured by the McGill Pain Questionnaire, in an experimental group receiving REBT when compared with a control group. However, discrepancies in the article make interpretation difficult.

• Small sample (less than 100)
• Measurement validity/reliability questionable
• Other limitations/explanation: Rigor of scientific reporting is questionable.

Nurses are well aware that psychoeducational interventions can affect pain control. This study aims to support that contention. This study does not provide additional strong support in this area because of multiple study limitations.

To evaluate the effects of massage and compression in women with and without arm lymphedema secondary to breast cancer  

Women with clinically diagnosed lymphedema secondary to breast cancer and a convenience sample of women without breast cancer or lymphedema were recruited. Women who wore a compression garment removed it two hours before measurement and massage.  Measurements were taken prior to, mid way through, and at the completion of massage. Women received a therapeutic massage for one hour using the Foldi method of lymphatic drainage provided by a single trained therapist.

• The study reported on 30 female patients.
• The mean age of patients in the breast cancer group was 60 years. The mean age of patients in the nonbreast cancer group was 46 years.
• All patients with breast cancer were at least three months post-completion of any treatment. All of these patients had an interarm volume difference of at least 200 ml by perometry or bioimpedance interarm ratio greater than the standard cutoff for lymphedema.

This was a single-site study conducted in the outpatient setting in Australia.

The study used a pre/post design.

Perometry and bioimpedance techniques were used.

No statistically or clinically significant effect was found between the use of massage and limb volume with either study group.

A single session of lymphatic massage did not reduce lymphedema.

The sample size was small, with fewer than 30 participants.

 Findings suggest that a single session of lymphatic massage does not have any effect on arm volume in women with or without lymphedema.

To evaluate the effects of a psychoeducational program (COPE) on caregivers of patients with cancer

The COPE (Caregivers of Cancer Outpatients' Psycho-Education Support Group Therapy) intervention was provided to caregivers during four weeks. The program included didactic content and supportive interventions in group sessions. Study measures were obtained before and after the intervention. A subgroup was invited to participate in semistructured interviews. Caregivers were placed in one of two groups, one of which was wait-listed and used as a control in the analysis.

• N = 97   
• AGE = 21 years and older
• MALES: 35.1%, FEMALES: 64.9%
• CURRENT TREATMENT: Chemotherapy, radiation 
• KEY DISEASE CHARACTERISTICS: Patients had varied tumor types, and most had advanced disease.
• OTHER KEY SAMPLE CHARACTERISTICS: The majority had provided caregiving for 0–6 months.

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

PHASE OF CARE: Multiple phases of care

Nonrandomized, prospective, parallel group

• Caregiver Quality of Life scale
• Hospital Anxiety and Depression Scale (HADS)

No significant differences existed between study groups in postintervention caregiver quality of life overall or burden subscale scores. Those in the wait-list control group had much better quality of life scores at baseline.

The intervention studied here did not demonstrate an effect on caregiver burden or quality of life.

• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)
• Risk of bias (sample characteristics)
• Key sample group differences that could influence results
• Substantial differences between study groups existed at baseline for quality of life and burden.

The specific psychoeducational program examined here did not demonstrate an effect on caregivers. Several limitations existed.

To determine if psychosocial interventions, led by nurses instead of mental health professionals, for patients newly diagnosed with cancer in Singapore could help ease distress, minor psychiatric morbidity, and psychosocial worry

This quasiexperimental study researched the benefits of a six-month nurse-led psychosocial intervention program for patients with newly diagnosed with cancer receiving chemotherapy. The program consisted of 20- to 30-minute sessions with a nurse and occurred monthly for two visits and bimonthly for two more visits. Participants were offered this intervention along with their treatment. Training of the oncology RNs at the National Cancer Institute in Singapore included personal training by a psychiatrist and a psychologist on psychoeducation for managing stress, sleep hygiene, anxiety, and depression and included resources, deep breathing exercises, muscle relaxation, and inspirational self-talk. Patients also received counseling, supportive therapy, and printed/audio education to encourage practice at home. The RN training also included simulated one-on-one sessions with feedback on performance. Demographic and medical data were collected. Primary outcomes were measured by questionnaires at baseline and at six months.

• N = 63
• AGE = Older than 21 years
• MEDIAN AGE = 51–60 years
• MALES: 35%, FEMALES: 65%
• CURRENT TREATMENT: Chemotherapy

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: National Cancer Institute-Singapore Medical Oncology Clinic

PHASE OF CARE: Active antitumor treatment

• Quasiexperimental study

• Distress Thermometer (DT)
• Hospital Anxiety and Depression Scale (HADS)
• EuroQol EQ-5D
• Data were analyzed using SPSS, version 22.

One hundred twenty-one participants were recruited. Seventy (58%) chose to participate, and the rest received treatment as usual (TAU). Sixty-three (90%) participants completed the four nurse-led sessions and were available at six months for reassessment. No significant demographic difference was reported between the intervention and TAU groups at baseline. No significant demographic difference existed between those followed up with and those lost to follow-up, but those lost to follow-up did have higher anxiety and depression scores at baseline. The intervention group had significantly increased distress, anxiety, and depression scores and lower EQ-5D scores at baseline. The intervention group participants had significantly reduced distress (p = 0.001), anxiety (p < 0.001), and depression (p < 0.001) scores, as well as greatly improved quality of life over time. Participants receiving TAU also showed a decline in anxiety and depression over time, with essentially stable distress scores.

A six-month intervention of psychoeducation, counseling, and behavior technique teaching improved participants’ distress, quality of life, anxiety, and depression.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Questionable protocol fidelity
• Subject withdrawals ≥ 10%