To examine the impact of advanced practice nurse (APN)-administered low-level laser therapy (LLLT) as a stand-alone and complementary treatment for arm volume, symptoms, and quality of life (QOL) in women with breast cancer–related lymphedema

Three interventions were used, including LLLT alone, manual lympatic drainage (MLD) alone, and combined MLD and LLLT. LLLT alone used a RianCorp LTU 904, FAD-approved, class I laser. Grids for the areas to be treated were identified. The laser was applied, and exposure was limited to 20–30 seconds per point in each grid. Time for each session using this procedure was about 20 minutes. MLD alone included treatment that followed international standards. A standard number of strokes was used at each anatomical location. Each MLD session took about 40 minutes. Combined MLD and LLLT included participants receiving 20 minutes of LLLT, followed by 20 minutes of MLD. In addition, compression bandaging was applied after each treatment regardless of group assignment. Baseline and outcome data were collected pretreatment and on the last day of treatment after therapy was concluded.

• N =  46   
• MEAN AGE = 66.6 years (SD = 10.4 years)
• MALES: 0%, FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer survivors with treatment-related lymphedema
• OTHER KEY SAMPLE CHARACTERISTICS:  95.7% Caucasian

• SITE:  Single site 
• SETTING TYPE:  Other 
• LOCATION:  Private medical practice in Florida

• PHASE OF CARE: Late effects and survivorship

• A pilot, randomized clinical trial

• Extracellular fluid with bioelectrical impedance
• Arm volume with circumferential measurement
• Height and weight
• Skin assessment checklist
• Lymphedema Symptom Intensity and Distress Scale-Arm (LSIDS-A)
• Brief Fatigue Inventory (BFI)
• Profile of Mood States-Short Form (POMS)
• Center for Epidemiologic Studies-Depression (CES-D)
• Upper Limb Lymphedema-27 (ULL27)
• Functional Assessment of Cancer Therapy-Breast (FACT-B)

All groups had clinically and statistically significant reduction in volume (p < 0.05); however, no statistically significant between-group differences were found in volume reduction. Treatment-related improvements were noted in symptom burden within all groups; however, no group differences were noted in psychological and physical symptoms or QOL. Skin improvement was noted in each group that received LLLT.

LLLT with compression bandaging may offer a time-saving therapeutic option to conventional MLD.

• Small sample (< 100)
• Risk of bias (no blinding)
• Other limitations/explanation: The dose of each intervention varied by individual patient because current reimbursement does not cover lymphedema therapy once reduction has slowed or stopped.

The study demonstrates that a trained APN could implement lymphedema therapy in clinical practice. LLLT with bandaging may offer a time-saving therapeutic option to conventional MLD. Studies with a larger sample size are needed to compare MLD and LLLT.

To examine potential efficacy of the Flexitouch system (compression garment) for self-care home use in patients with breast cancer who had truncal lymphedema

The system examined includes compression garments for the trunk, chest, and arm and applies variable dynamic pressure to affected areas, controlled by software programming. It uses multi-chambered inflatable and stretchable fabric garments. Patients were fitted for the garments. Patients completed one-hour daily treatments for 10 days. Patient symptoms and cirumferential measurements were done at baseline, after the fifth treatment, and at the end of the study. Patients were trained in use and, after the initial treatment, were instructed in use for home treatment. Research staff observed the first home treatment, then patients completed the rest on their own at home.

• The study sample (N = 12) was comprised of female patients with breast cancer.
• Mean age was 55.3 years, with a range of 43–79 years.
• Patients had an average of 5.4 years since diagnosis and an average of 52.6 months duration of lymphedema.
• Of patients in the study, 75% were married or partnered and 50% were employed full-time.

The study took place in home settings in the United States.

The study has clinical applicability for late effects and survivorship.

The study used a quasi-experimental pre-post design.

• Patients took the Lymphedema Symptom Intensity and Distress Survey-Arm and Trunk (LSIDS-AT).
• Patients took the Functional Assessment Screening Questionnaire.
• Trunk circumference was measured using Gulick II tape.

There were significant reductions in symptoms of truncal heaviness (x² = 15.07, p = 0.0001), swelling (x²=14.73, p = 0.0001), tightness (x² = 12.63, p = 0.0002) and itchiness (x²= 12.0, p = 0.0002). There were no significant changes in truncal measurements; however, there was a general non-significant trend of reduced circumference in all areas measured. There was also significant reduction in difficulty sleeping (p = 0.008).  All significant changes occurred after the fifth treatment and then remained stable at the end of the study. There was a general trend of increasing reports of skin conditions over the course of the study.

The system may be an effective device to relieve lymphedema symptoms with home self-care treatment.

• The sample size was small, with less than 30 participants.
• The study design had a risk of bias because of no control group, no blinding, no random assignment, and no appropriate attentional control condition. Risk of bias (no control group) 
• The study duration was short, and it is not clear what the longer-term effects would be, particularly given the trend of increasing skin condition reporting.

The device may be helpful to reduce symptoms of lymphedema with an approach that patients can use at home for self-care. Larger controlled studies are warranted and longer term use should be evaluated.

To compare the safety and efficacy of a once-daily dose of a new formulation of morphine sulfate—abuse-deterrent, prolonged-release erodible-matrix (ADPREM) morphine sulfate—to the safety and efficacy of a twice-daily dose of standard controlled-release morphine

During a run-in period of three days, clinicians determined each patient's effective dose of the study drug. Throughout the study, immediate-release morphine was available for breakthrough pain. The study drug was titrated to provide a level of pain relief characterized by four or fewer episodes of breakthrough pain per day and a level of pain intensity that was acceptable (this level was undefined). Treatment periods were two weeks long. In a crossover trial, patients received either the study drug, once daily, or controlled-release morphine twice daily. In diaries patients recorded daily all medications used, number of breakthrough episodes, and pain ratings. Clinicians evaluated adverse events.

• The sample was composed of 34 patients.
• Mean patient age was 57.5 years. Age range was 42–81 years.
• Of all patients, 36.8% were female and 63.2% were male.
• The most common cancer types in the sample were lung, breast, and rectal cancer.

• Multisite
• Outpatient
• Italy

Randomized phase 2 double-blind crossover study

• Eleven-point numeric rating scale, to measure pain intensity
• Drug-metabolite concentration in plasma

The pattern of treatment-related adverse events was the same for both treatments. The fixed dose determined during the run-in period was 30–210 mg/day. Authors noted no differences between treatments in regard to breakthrough pain episodes or use of rescue medication. Average pain intensity ratings were similar for both treatments.

The efficacy and side effects associated with a once-daily dose of ADPREM morphine sulfate were similar to those associated with twice-daily doses of controlled-release morphine. Studies that include larger samples are warranted.

• The study had a small sample, with fewer than 100 participants.
• Authors did not provide a standard definition of the term acceptable pain.

For some patients, the ability to control pain by using fewer pills daily may be a significant consideration. This study provides evidence that supports the efficacy and safety of a once-daily ADPREM formulation of morphine.

To determine the proportion of patients who gained at least 1 kg at the end of week 4. Secondary endpoints were the proportion of patients whose appetite or health-related quality of life (HRQOL) improved at week 4.

Patients received the starting dose of 15 mg of mirtazapine orally at bedtime for three days. Thereafter they received 30 mg daily provided they tolerated the medication. Patients were weighed on a mechanical scale and were assessed for appetite change and side effects prior to starting the mirtazapine and at weeks 2, 4, and 8. HQOL was measured at baseline and at weeks 4 and 8. Demographics (age, gender, concurrent medications, disease site, and Eastern Cooperative Oncology Group performance status) were also assessed. Toxicity was assessed at every visit.

• The study reported on 17 patients with metastatic cancer experiencing weight loss.
• Mean patient age was 66 years, with a range of 49–86 years.
• The sample was 53% female and 47% male.
• Cancer types were gastrointestinal, breast, lung, gynecologic, and hematologic.
• Patients experienced weight loss of more than 5% during the previous two months or a score of more than 5 out of 10 on the Edmonton Symptom Assessment Scale.

• Single site
• Outpatient setting
• Princess Margaret Hospital, Toronto, Canada

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

The study was an eight-week, open-label, noncomparative phase II trial.

• Mechanical scale    
• Edmonton Symptom Assessment Scale (ESAS)–appetite
• Functional Assessment of Anorexia/Cachexia Therapy (FAACT)–HQOL

At week 4, 4 of 17 patients (24%) had weight gain of 1 kg or more (range: 1–3.6 kg). One patient maintained weight, and  two patients lost weight. Of the patients who gained weight, all improved by 2 or more points on the ESAS for appetite (range = 2–6 points). One of the responding patients demonstrated improved HQOL by 16 points, and three maintained HQOL. Mirtazapine was well tolerated, but two patients withdrew from the study due to side effects.

Nearly a quarter of patients in this study gained at least 1 kg after four weeks of therapy. Another quarter maintained their weight. While the results of the study indicate that mirtazapine appears to be a potentially useful agent in the management of cancer-related cachexia and anorexia, this study was small, with only four patients in each group.

• The study had a small sample size, with less than 30 participants.
• The study occurred at a single institution.
• The study had a high attrition rate.
• Placebo effect could have contributed to results.
• The study lacked randomization and a control arm.
• The study was also not blinded, and there could have been some placebo effect on the ESAS or FAACT.
• Alternatively, patients recruited to this study had advanced cancer and may have been experiencing a decline in health that pharmacology cannot reverse. Therefore, while encouraging, the study results should be interpreted with caution.

The pathophysiology of cachexia is complex. There is currently no standard treatment for managing cancer-related cachexia. Mirtazapine may be a potential agent useful in the management of cachexia; however, additional research is necessary.

To evaluate the evidence, from controlled clinical trials, relating to the effectiveness of hypnosis for reducing procedure-related pain and distress in pediatric cancer patients

• Databases searched were MEDLINE, EMBASE, Allied and Complementary Medicine Database (AMED), Centralised Information Service for Complementary Medicine (CISCOM), CINAHL, PsycINFO, and the Cochrane Library.
• Searched keywords were neoplasm, tumor, melanoma, cancer, chemotherapy, palliative care, terminal care, and hypnosis.
• Studies were included in investigators' analysis if
  • They were relevant systematic reviews or controlled clinical trials that included outcome measures for pain.
  • They included pediatric patients, with a primary diagnosis of cancer, who were undergoing painful and invasive treatment-related procedures (lumbar puncture, venipuncture, bone marrow aspiration).
  • In the study, hypnosis was used as a specific intervention.
  • Patient- or observer-reported clinical measures of physical pain or anxiety or distress were recorded,
• Studies were excluded if treatment included chemotherapy or if the studies did not include a control group.

• Investigators retrieved nine studies. The studies comprised one systematic review, seven randomized controlled trials, and one nonrandomized controlled trial.
• Authors analyzed eight studies, reviewing design, sample, inclusion criteria, complementary and alternative medicine treatment, control, outcome measure(s), results, methodology, comments, and clinical comments.

• The sample was composed of 313 patients.
• All patients had a diagnosis of cancer and were undergoing a painful procedure. Cancer diagnoses included lymphoblastic leukemia, acute myeloblastic leukemia, and nonmalignant blood disorder.
• None of the studies identified cancer stage. Some studies did not report the percentages of male participants and female participants.
• Authors did not identify the age range of patients.

Using rating scales in the pediatric population is a useful and valid procedure. Some studies included observations of procedure-related behavior, and these observations showed that the intervention yielded some benefit, although the observer's criteria are unspecified. Some studies showed that the level of hypnotizability, as  measured by the Stanford Hypnotic Clinical Scale for Children, was related to analgesic effect, but this finding was invalid. Studies that noted and stratified for the sex of the pediatric patient reported that the child's sex was related to level of distress. Self-hypnosis was not evaluated but has been shown to have an effect on management of symptoms.

Studies reported that using hypnosis as specified had positive effects, resulting in statistically significant reductions in pain and anxiety or distress.

• Most studies had a small sample size.
• Few studies reported the method of randomization.
• The studies did not provide enough information about the duration of the hypnosis session, whether parents were present, and who provided the information about intervention results.

Work remains to be done in this area. Researchers should focus on age, developmental stage, and the association between the sex of the child and the effectiveness of the intervention.

STUDY PURPOSE: To systematically review the research evidence on the effectiveness of hypnosis for chemotherapy-induced nausea and vomiting (CINV)

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 6 (5 of the studies are focused on pediatric patients)
• TOTAL PATIENTS INCLUDED IN REVIEW = 206
• SAMPLE RANGE ACROSS STUDIES: 12-67 patients
• KEY SAMPLE CHARACTERISTICS: Pediatric patients undergoing chemotherapy with anticipated CINV and adult patients with hematologic lymphoma and bone transplantation

• PHASE OF CARE: Active treatment
• APPLICATIONS: Pediatrics, palliative care

All the studies that focused on pediatrics were consistent in that hypnosis was a better treatment option than standard or controlled care. The weighted mean effect sizes indicated that hypnosis was even more effective when followed by therapist contact (D = 0.43) and cognitive behavior therapy (D = 0.18).

Hypnotherapy could be a clinically valuable intervention for anticipatory and acute CINV in children with cancer, but this older systemic review did not show the same results with adults.

Limited number of studies included

Nurses caring for pediatric patients should understand that hypnosis should be part of the toolbox for children who suffer from acute and anticipatory CINV.      

To determine if a 10-week regimen of methylphenidate could alleviate fatigue and improve quality of life in men with prostate cancer being treated with luteinizing hormone-releasing hormone agonists

Subjects were randomized to receive either methylphenidate or a placebo for up to 12 weeks. Methylphenidate was given at a dose of 5 mg daily for two weeks followed by 5 mg twice daily for eight weeks. The dose was tapered back to 5 mg per day for the last two weeks. Patients were contacted by phone at week 2 for reminders to take the medication and to assess drug tolerance. Assessments were done when patients were seen in-clinic at weeks 6, 10, and 12.

• N = 24  
• MEDIAN AGE = 66 years
• MALES: 100%   
• KEY DISEASE CHARACTERISTICS: All patients had prostate cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Baseline assessments suggested a moderate level of fatigue. Significantly more patients in the placebo arm had prior radical prostatectomy.

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Canada

• PHASE OF CARE: Active antitumor treatment

Double-blind, placebo-controlled, randomized trial

• Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) Scale
• Bruera Global Fatigue Severity Scale (BFS)
• Short-Form (36) Health Survey (SF-36)
• The National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE)

FACIT scores improved significantly over the course of the study in all patients, but improvement was only statistically significant in the methylphenidate group (p = .008). The between-group difference in improvement was significant (p = .02). BFS scores also showed improvement in the methylphenidate group over time (p = .0006) but differences between study groups were not statistically significant. One patient discontinued the medication due to side effects.

Methylphenidate was shown in this small study to improve fatigue scores.

• Small sample (< 30)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: There was difficulty in accruing subjects. Accrual was done over four years, and out of 345 eligible men, only 26 were recruited. This raises the question of the practicality and acceptability of this treatment to this group of patients. The Bruera scale is not commonly used, and no full description or reliability information is provided. The study was clearly underpowered.

Methylphenidate may be helpful to some patients in managing fatigue during cancer treatment. Due mostly to sample size limitations, this study does not provide strong evidence for use of methylphenidate in men with prostate cancer.

To assess the efficacy and acceptability of the MC5-A Calmare® device

The Calmare device produces electrical nerve stimulation that is transmitted to nociceptors in order to modulate the pain response. Electrodes were placed on the skin according to the area of pain to be treated. Patients could receive up to a maximum of four treatments per day. Ten 30-minute sessions of the stimulation therapy for two consecutive weeks were delivered Monday through Friday. Pre- and post-treatment assessments were done after the first week and after the tenth day of treatment. Patients continued their usual regimen of analgesics.

• The study reported on a sample of 73 patients.
• Median patient age was 66 years, with a range of 28–87 years.
• The sample was 52% male and 48% female.
• The sample included patient with cancer and noncancer patients as well.
• Of the patients with cancer, 56% had nociceptive pain and 34% had neuropathic pain; most had pain duration greater than three months; and 58% were on strong opioids.

• Single site
• Inpatient and outpatient settings

Patients were undergoing long-term follow-up care.

The study has clinical applicability for end-of-life and palliative care; and elderly care.

A prospective, exploratory, single-group, quasi-experimental design was used.

Numerical rating scale (NRS)

Participants had an overall decrease in pain. Mean value at the beginning of treatment was 5.4 for those with cancer and decreased to 1.4 at the end of the second week (p < 0.0001) and to 2.6 at the two-week poststudy follow-up (p < 0.0001). After the tenth day of treatment, mean value was 2.9 (p < 0.0001), and after the second week of follow-up, the mean one month of treatment pain reduction was 4.0 and 5.2 in patients with cancer and noncancer patients, respectively. No side effects were reported. Among those patients with cancer-related pain, 64% were deemed complete responders, and 7% achieved a partial response. No adverse effects were seen.

This pilot study demonstrated that cutaneous electrostimulation with the MC5-A Calmare® device was effective in chronic pain treatment.

• The sample was small, with less than 100 participants.
• The study had a limited follow-up time frame.

Findings suggest that use of this device may provide benefit as adjunctive treatment for chronic pain control. Further well-designed research is needed to validate findings further.

• FINAL NUMBER STUDIES INCLUDED = 9
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,169
• KEY SAMPLE CHARACTERISTICS: The nine final RCTs were published between 1985 and 2011. Eight of these studies contained a placebo group compared to a group receiving an active drug; one trial compared patients receiving an active drug to patients receiving no treatment. Six studies included multiple cancer types, but three studies reported only patients with breast cancer. Most (83%) of the patients were female, and the mean age of all patients was 54.3 years old. The duration of treatment ranged from 4–12 weeks; attrition was greater than 20% for all but two of the studies. 

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

The three effective antidepressants were mianserin, paroxetine, and fluoxetine. The mianserin group had a lower dropout rate than the placebo group, but with non-significant difference; higher depression response rate. Paroxetine group had higher dropout rate than placebo but with non-significant difference. The fluoxetine group had a significantly higher dropout rate when compared to a placebo. Paroxetine and fluoxetine were not associated with higher depression response rates when compared to a placebo. The evidence for the efficacy and tolerability of different antidepressants remains scarce for cancer-related depression, suggesting a great need for further randomized, controlled trials with placebo controls.

Opening database search dates varied. Heterogeneity among the studies complicated comparisons, causing small sample studies to be left out of at least two analyses. Only nine studies met the final criteria for inclusion, suggesting a need for research addressing the efficacy and tolerability of antidepressant use in patients with cancer and symptoms of depression.

Further research in patients with cancer and depression is needed to determine the best treatment guidelines. Mianserin showed the best results in these studies; however, it was reported that it is not available for sale in the United States. Research using other antidepressant drugs is needed. For example, tricyclic antidepressants and monoamine oxidase inhibitors should be studied. Paroxetine and desipramine did not show promising results in reducing depression in these studies.

To assess if compression pumps decrease lymphedema compared with other treatments and to identify recommended parameters for use of compression pumps

Databases searched were MEDLINE, Ovid, PubMed, CINAHL, Scopus through January 2007, and hand searching from article references. Key search words were breast cancer, lymphedema, pneumatic compression, compression pumps, intermittent compression, and sequential compression. Studies were included in the review if they

• Had participants with upper-extremity lymphedema secondary to breast cancer treatment
• Had participants who received compression pump therapy
• Reported pre- and post-treatment lymphedema measurements.

Exclusion criteria were not specified.

Eighty-five articles were retrieved initially. Studies were categorized using Sackett’s levels of evidence. Additional discussion of study information was done, though specific methods were not described.

• A final sample of eight studies was included.
• The eight studies included a total of 727 breast cancer cases.
• Study samples ranged from 15–227.

Among highest level studies, there were no differences between pneumatic compression and no intervention or compression garments or bandages.

There is no evidence that suggests use of intermittent compression pumps is effective in management of lymphedema or is any better than education about arm care and hygiene. There is no consensus about pressures to be used with compression pumps.
 

• The majority of studies were of low quality and had multiple methodological issues.
• Compression pressures used varied greatly as did duration of treatment.

Findings do not support the use of compression pumps for lymphedema management secondary to breast cancer treatment. There is no information to establish appropriate and safe pressure levels for use.