To compare the analgesic effect of applying magnetic acupressure to the L14 point to that of applying magnetic acupressure to a sham point

Patients were stratified by the number of prior bone marrow aspiration biopsies (BMABs) and randomized to one of two groups. In the first group, a practitioner delivered acupressure to the L14 acupoint (the dorsum of the first interosseus space of the hand). In the second group, a practitioner delivered acupressure to a sham point (the fourth interosseus space of the hand). Two HACI magnetic acupressure suction cups (HMASCs) were applied to the designated area of both the patient's hands for the duration of the BMAB procedure. The same two HMASCs were used on all study patients. All patients received standard local analgesics as ordered by the BMAB provider. The same BMAB provider and acupressure practitioner were used throughout the study. The patient, BMAB provider, and outcome evaluator were blinded to the location of the acupressure. The patient’s pain intensity was measured at baseline and after the BMAB.

• The sample was composed of 77 patients, 37 in the L14 group and 40 in the sham-point group.
• Mean patient age, in both groups, was 57 years (SD = 12.4 years).
• Of all patients, 61% were  male and 39% were female.
• Authors did not cite disease characteristics.
• Of all patients, 82% were Caucasian (authors noted no other races). Of the L14 group, 31% had had more than one BMAB; of the sham-point group, 75% had had more than one BMAB.

• Single site
• Inpatient and outpatient
• Locations associated with the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore
   

Multiple phases of care

Single-center randomized single-blind clinical trial

• Visual analog scale (VAS) of 11 points, to measure baseline pain score and score post-BMAB (The patient was asked to rank the worst pain experienced during BMAB.)    
• Measures of the use of analgesic or anxiolytic medications in the 12 hours preceding the BMAB (Data were gathered by means of questioning patients.)
• Post-BMAB data reflecting patients' opinions about the effectiveness of the acupressure in pain relief
• Measures of acupressure side effects

Authors noted no significant difference in median pain scores between the patients treated at the L14 site versus the sham site (3.0 versus 3.0, p = 0.08, Mann-Whitney test). Eight patients (20%) in the sham-site group experienced severe pain. One patient (2.7%) in the L14 group experienced severe pain (p = 0.03, two-tailed Fisher’s exact test). The unadjusted risk of patients experiencing severe pain in the sham-site group was nine times higher (95% CI 1.07–75.9, p = 0.04). After accounting for age, number of prior BMABs, baseline pain scores, and the number of times the cup fell during the procedure, patients in the sham-site group were more likely to experience severe pain than were those in the L14 group (risk ratio 9.3; 95% CI 1.01–85.6; p = 0.049). The acupressure point was the only statistically significant factor associated with BMAB-related pain.

Magnetic acupressure delivered at L14 may reduce the number of patients who experience severe pain during BMAB.

• The study had a small sample, with fewer than 100 participants.
• Generalizability of findings is limited because data were collected at only one study site and by only one BMAB operator and because one acupressure practitioner delivered the study procedure. In addition, pain was measured after the procedure rather than during the procedure. When this measurement occurred is unclear.

The combination of magnetic acupressure at the L14 site and local anesthetics may reduce severe pain during BMAB. Acupressure is inexpensive, and it requires minimal training to deliver.

To determine the effectiveness, safety, and convenience of acupuncture in decreasing bortezomib-induced peripheral neuropathy (BIPN)

Patients were treated with 10 acupuncture treatments twice a week for two weeks, then once a week for four weeks, and then every other week for four weeks. Patients remained on their prescription PN medications.

• N = 20  
• MEDIAN AGE = 63 years
• AGE RANGE = 49–77 years
• MALES (%): Not stated, FEMALES (%): Not stated
• KEY DISEASE CHARACTERISTICS: Multiple myeloma 
• OTHER KEY SAMPLE CHARACTERISTICS: Patients had received bortezomib 1–83 months ago, had continuing BIPN (grade 2 or greater), and were taking various medications for it, such as gabapentin, narcotics, amitriptyline, pregabalin, and duloxetine.

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: University of Maryland Greenebaum Cancer Center

PHASE OF CARE: Active antitumor treatment

Prospective study

• Clinical total neuropathy score
• Functional Assessment of Cancer Therapy/Gynecologic Oncology Group (FACT/GOG)
• Neurotoxicity questionnaire
• Neuropathy pain scale (NPS)
• Serum cytokines were drawn for correlative studies.

The Clinical Total Neuropathy Score was considered invalid because of reliability and validity issues in this setting. The FACT/GOG Neurotoxicity (Ntx) subscale and NPS scores demonstrated significant decreases in BIPN symptoms. Improvements in buttoning and walking at weeks 10 and 14 (p values < 0.0001) were observed. No differences in nerve conduction evaluations were reported from baseline to the completion of the study. No change in serum biomarkers were reported.

Acupuncture was demonstrated as a safe although inconvenient treatment for BIPN. Patients reported improvements in BIPN symptoms.

• Small sample ( <30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

The intervention produced a decrease in some BIPN symptoms. Acupuncture needs to be administered by a licensed therapist, which may not be a realistic treatment for all patients. A large, randomized trial is indicated for future research.

To evaluate the effect of acupuncture on function and pain in women with aromatase inhibitor associated musculoskeletal symptoms (AIMSS) and the effect of serum hormones and proinflammatory cytokines to help clarify the molecular mechanism of action with the use of acupuncture

Patients were randomized to eight weekly real or sham acupuncture sessions evaluated by the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain visual analog scare (VAS) at baseline and after intervention. Serum hormones and proinflammatory cytokines were measured pre- and post-intervention.

• N = 47  
• AGE = 44–85 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Postmenopausal women with stage 0–III breast cancer that was estrogen-receptor-positive or progesterone-receptor-positive receiving a standard dose of a third-generation aromatase inhibitor for one month or longer and with documented AIMSS. Baseline HAQ-DI or pain using a 100-point VAS of 20 or more
• EXCLUSION CRITERIA: Acupuncture treatment within the past 12 months

• SITE: Multi-site 
• SETTING TYPE: Not specified; outpatient
• LOCATION: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; the University of Maryland Greenebaum Cancer Center

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

• Randomized, controlled double-blind trial

• HAQ-DI
• Pain VAS

No significant difference was seen in HAQ-DI and VAS scores between the groups. A significant reduction of interleukin 17 was seen in both groups after eight weeks, and no significant changes were seen in other hormone/proinflammatory markers in either group. No significant difference were seen in AIMSS between the groups; however, after eight weeks of  treatment, HAQ-DI and VAS scores improved for both groups.

This study does not appear to support acupuncture as a means to reduce musculoskeletal symptoms in patients with breast cancer taking aromatase inhibitors. Sham and real acupuncture seem to improve HAQ-DI and VAS scores and seem to lower baseline, as revealed by a 12-week follow-up after the study. Neither acupuncture nor sham acupuncture produced any adverse effects and seem to be safe as an option for patients with early-stage breast cancer with AIMSS.

• Small sample (less than 100)
• Findings not generalizable
• The sample size limits the ability to generalize findings.
• Acupuncture training is required to perform the intervention.

This study does not support acupuncture over sham acupuncture for the treatment of AIMSS in women with early-stage breast cancer. That being said, acupuncture has helped to improve VAS and HAQ-DI scores, suggesting it as a positive intervention with no side effects for these patients. Education and training in acupuncture would be suggested prior to therapy, but this article suggests that sham acupuncture produces statistically similar results and improves scores.

To explore the interdependence of changes in oxygen uptake, quality of life (QOL), and cancer-related fatigue (CRF) during a four-month exercise intervention

Aerobic exercise capacity was determined by a physician-supervised cardiopulmonary exercise test on an electrically braked cycle ergometer. An initial watt load of 0 watts was increased by 25 watts every three minutes until exhaustion. The results were used at an initial exercise counseling session to individualize exercise plans (i.e., frequency of three to five times per week, intensity, type of exercise, opportunity to participate in a Nordic walking training session once per week). Subjects attended a second counseling session four weeks into the intervention to adjust home-based exercises to fit their conditions. An exercise counselor was available by phone, via email, or in person at any time during the intervention. Assessments were repeated at the end of 16–20 weeks. Self-reported measures of adherence to exercise plans were obtained by diaries.

• N = 101  
• AGE RANGE = 32–85 years
• MALES: 40%, FEMALES: 60%
• KEY DISEASE CHARACTERISTICS: Confirmed cancer diagnosis (any site and stage) within the past three years; during adjuvant, palliative, or postadjuvant therapy (finished within the past 12 months); performance status of 0–II (as ranked by the Eastern Cooperative Oncology Group); exclusion criteria included brain or bone metastasis, uncontrolled hypertension, hemoglobin counts < 8 g/dl, and any condition precluding exercise

• SITE: Multi-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Germany

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

Repeated measures pre- and postintervention

• Aerobic exercise capacity measured by a cardiopulmonary exercise test (CPET) and the peak oxygen consumption (VO2PEAK) 
• QOL measured by the European Organisation for Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 v.3.0)

Subjects were active (i.e., hiking, biking, walking, bicycling) three to six times per week for 60–300 minutes at 60%–100% of individual anaerobic thresholds. At baseline, the groups differed in QOL scores but not CRF or VO2PEAK scores. Subjects with complete data sets had a significant increase in VO2PEAK and QOL scores, and their fatigue decreased significantly over the course of the intervention. No significant effect for diagnosis or time since diagnoses occurred.

A relationship between exercise capacity enhancement, QOL improvement, and fatigue symptom reduction exists during and shortly after cancer treatment.

• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Findings not generalizable
• Questionable protocol fidelity

The data in this study support the role of individualized exercise planning based on baseline exercise capacity with respect to frequency, time, and intensity as well as the importance of patient choice in the type of exercise in which to participate.

To determine the comparative efficacy and safety of gabapentin and amitriptyline as coanalgesics for cancer-related pain

Patients were assigned randomly to receive oral tramadol 150–200 mg and oral gabapentin titrated from 600–1,800 mg daily, or tramadol 150–200 mg and amitriptyline titrated from 25–100 mg daily. Oral morphine or fentanyl transdermal patch were used as rescue medication. At baseline, if patients were on any coanalgesic, they were entered after a washout period. Patients were followed monthly up to six months. Patients were asked to maintain a diary used for assessment of compliance. Once a patient used rescue medication, the patient was excluded from further efficacy assessment, and last pain scores were carried forward.

• N = 76  
• MALES: 53%, FEMALES: 47%
• KEY DISEASE CHARACTERISTICS: Tumor types are not stated. Baseline pain scores were 8.425 on average.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients did not have any disorder of vital organs or bone marrow.

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

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care

• Open-label, two-group, randomized trial

• Visual analog scale (VAS)—scored as 0, 1, or 2 if scores decreased, remained the same, or increased
• Verbal rating scale (VRS)
• Percentage of pain relief (PPR) calculated
• Global pain score calculated as the sum of changes in VAS score, VRS score, and PPR
• MD global impression of efficacy (four-point scale)

For patients receiving gabapentin, pain scores on the VAS reduced significantly between the first and second month (p < .001). The same timing and pattern of pain reduction were shown in the amitriptyline group (p < .001). No significant differences were seen between groups at any study time point. Six patients on gabapentin and eight patients receiving amitriptyline required rescue medication. Thirty percent of patients in the gabapentin group and 42% of patients in the amitriptyline group had adverse events. These were generally mild. More patients receiving amitriptyline experienced postural hypotension (p = .02) and dry mouth (p = .04). Sedation, dizziness, and dyspepsia were the most frequent side effects.

Findings suggest that gabapentin and amitriptyline can be effective as coanalgesics for neuropathic pain.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement validity/reliability questionable
• Findings not generalizable
• Subject withdrawals 10% or more
• Other limitations/explanation: Information regarding any changes in opioid medications or lack of change is not provided. No data regarding compliance are provided. Depending on the timing in which patients who used rescue medication had prior pain scores carried forward, this approach could have overestimated or underestimated results. Opioid dosage information is not provided. The sample did not appear to have any significant comorbid conditions, so applicability among patients with other chronic diseases is unclear.

Findings suggest that either gabapentin or amitriptyline can be effective coanalgesics for neuropathic pain, and professional guidelines generally have suggested consideration of such medication. The side effect profiles of the two drugs studied here were slightly different, so individual patient characteristics and risks need to be considered in medication selection. In this study, patients had no significant other disorders, so if similar results would be seen among patients with comorbid conditions is not clear.

The yoga intervention was a 90-minute, six-week course taught by expert yoga trainers. The course included meditative practices, various postures, guided imagery of cancer cells, positive thought provocation, chanting of various sounds according to the respective patient’s religious beliefs, awareness practices, deep relaxation, and soothing sound vibrations. Control group patients were given supportive counseling and advised to take light exercise.

• The study reported on a sample of 68 women with breast cancer receiving radiotherapy and/or chemotherapy.
• Of these, 58 completed the study: 35 in the yoga intervention group, and 23 in the supportive counseling group.

Three centers in India

A randomized controlled trial design was used.

• Hospital Anxiety and Depression Scale (HADS)
• Perceived Stress Scale
• Alkaline single-cell gel electrophoresis (comet) assay to study cellular DNA damage from peripheral blood

There was significant decrease in anxiety levels in the yoga intervention group (repeated measures ANCOVA, p < 0.001). Yoga intervention decreased anxiety in women with breast cancer receiving radiation therapy.

• The study had a small sample size.
• The study used a convenience sample: Patients may self-select to participate in a study they believe to be effective.
• Start of intervention was not linked to time into radiation treatment and/or administration of chemotherapy.
• Expert yoga trainers were required to administer the yoga courses.

To investigate the impact of early integration of palliative and supportive care on pain management

Patients involved in the palliative care group were seen within two to three weeks of the cancer diagnosis. Services provided by the palliative and supportive care team were individualized, but included comprehensive symptom management, psychosocial, spiritual, and emotional support to patients and families, as well as assistance with treatment choice and coping. Patients in the comparison group received standard care provided by primary specialists. Data were collected from medical records. Patients were interviewed by a pharmacist regarding perception of pain control and pain intensity on a verbal rating scale.

• The study reported on a sample of 1,450 patients.
• Mean patient age was 65.05 years.
• The sample was 56% male and 44% female.
• Of the sample, 81% had metastatic disease. Specific sites were not described.
• A significantly larger percentage of patients receiving palliative care were receiving opioids and strong opioids for pain.

• Multisite
• Inpatient setting
• Italy

The study has clinical applicability for palliative care.

A descriptive, two-group comparison design was used.

Verbal rating scale (five-point)

Use of morphine and oxycodone were higher in the palliative care group (p < 0.0001). Transdermal fentanyl was used more often in the usual care group (p < 0.0001). Results from the interview showed that the percentage of patients with no pain and mild pain were significantly higher in the palliative care group (p < 0.0001). Care model and gender were the only predictive variables for pain outcomes, with male patients reporting lower pain severity (p = 0.003). Type of analgesics used was not a significant predictor of pain scoring results.

Findings suggest that provision of early palliative and supportive care is associated with lower pain severity than provision of standard care. There were significant differences in the types of analgesics used between care models, but this factor was not predictive of measured pain severity.

• The study has baseline sample and group differences of import.  
• The study has risk of bias due to no control group, no blinding, no random assignment, and no appropriate attentional control condition.
• Measurement validity and reliability are questionable.
• Pain was measured at only a single time point.
• Duration of palliative care and time since diagnosis for the entire sample are not described.
• There is limited information about content of standard care as well as overall pain management approaches in all patients.

This study design is associated with multiple limitations and threats to validity, so results cannot be seen as conclusive. Findings do suggest that an integrated care delivery model, incorporating holistic palliative and supportive care that is initiated early in the course of cancer care, may be associated with greater control of cancer-related pain.

To evaluate the efficacy and tolerability of low dose morphine in comparison to standard doses of weak opioids in the treatment of moderate cancer pain in opioid naïve patients

This multicenter, 28-day, open-label randomized controlled study for adults with moderate cancer pain assigned to receive either a weak opioid or low dose of morphine was designed to evaluate the efficacy and tolerability of low dose morphine in comparison to standard doses of weak opioids in the treatment of moderate cancer pain in opioid naïve patients. The weak opioid group received either tramadol or codeine with or without paracetamol. The morphine group received morphine after a three-day titration phase with normal release morphine up to 30 mg per day. The groups were assessed every seven days.

• N = 240   
• AGE = 59–74 years (WO group), 56–74 years (M group)
• MEDIAN AGE = 68 years
• MALES: 57% (WO group), 47.5% (M group); FEMALES: 43% (WO group), 52.5% (M group)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Both solid tumors and hematologic tumors
• OTHER KEY SAMPLE CHARACTERISTICS: Pain intensity, cancer symptoms, Karnofsky score, age, mental capacity

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: 17 Italian oncology centers

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

• Multicenter, 28-day, open-label, randomized controlled study

• Numerical Response Scale (0–10) for pain
• Karnofsky Performance Status Scale, 60% or higher for patient functioning 
• Edmonton Symptom Assessment System (ESAS) used to assess nine symptoms commonly experienced by patients with cancer during the previous 24 hours (validated in the Italian language)

In patients with cancer and moderate pain (4–6 out of 10), low-dose morphine reduced pain intensity significantly compared to weak opioids (tramadol or codeine) with a similarly good tolerability and adverse effects.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Key sample group differences that could influence results
• Long accrual of patients
• Open-label design

This study is has very important patient and nursing implications. By not using step II, weak opioids, we could potentially have better control of our patient’s pain as well as decrease costs by not using some of the more expensive weak opioids. More research is needed to compare the most commonly used strong opioids as first-line medications for pain intensity and adverse effects. Future studies should prospectively determine the morphine equivalent daily doses. These studies may determine that step II opioids are less effective and more costly. Ending step II in the World Health Organization's (WHO) ladder could simplify pain management while giving better pain control in a more efficient manner.

To compare intracerebroventricular (ICV) opioid therapy with either subarachnoid (SA) or epidural (EPI) opioid therapy

DATABASES: AgeLine (1978–1991), Bioethics (1973–1994), BIOSIS (1969–1991), Catline (through 1991), Dissertation Abstract (1966–1991), EMBASE (1974–1991), ERIC (1966–1991), FEDRIP (1966–1991), GPO (1976–1991), Health (1975–1991), NTIS (1964–1991), Psychological Abstracts (1967–1991), Religion Index (1975–2001), Sociological Abstracts (1963), Social Science Research (1972), MEDLINE (1966–2003), CINAHL (1982–2003), and CANCERLIT (1975–2002)

COMMENTS ON LITERATURE USED: Data were extracted from trials and used to compare analgesic efficacy, pharmacologic adverse effects, and catheter and system problems. No controlled trials were identified for these treatments. Data extracted looked at the best available evidence to evaluate the use of these treatments in patients with cancer.

FINAL NUMBER STUDIES INCLUDED: ICV = 13 trials (337 patients); EPI = 31 trials (1,343 patients); SA = 28 trials (722 patients)

TRIALS EVALUATED: No controlled trials were identified for these treatments.

Uncontrolled studies show that neuraxial opioid therapy often is effective for treating cancer pain that has not been controlled by systemic treatment. Long-term use of neuraxial therapy can be complicated by problems with catheters. Some of the therapies are costly. ICV therapy is more costly; however, comparative efficacy, side effects, and system longevity are unknown.

More rigorous reporting of efficacy and complications needs to be done before ICV can be recommended as a first-line therapy.

To obtain feasibility and effect size data for the intervention of true acupuncture on cancer-related fatigue (CRF) in patients receiving radiation therapy.

Participants were randomized to receive acupuncture or sham acupuncture; there were three real intervention assignments for every two sham assignments. Needles were in place for 30 minutes per session, and participants had treatments once or twice per week during the four to six weeks of the trial. Needle placement for true and sham interventions were specifically described in the report.

• In total, 27 females receiving radiation therapy completed the study:  11 were randomized to the sham procedure and 16 were randomized to acupuncture.
• Mean age was 54.1 years (standard deviation = 9.4 years).
• All but one participant had breast cancer.
• Of the sample, 44% had also received chemotherapy (74% of the acupuncture group versus 44% of the sham group).

• Single site
• Magee Womens’ Hospital, Pittsburgh, PA

The study was a double-blind, placebo-controlled, randomized trial.

• The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale was measured at baseline and three, six, and 10 weeks.
• Quality of life (QOL) was measured with the Short Form 36 (SF-36) Health Survey at baseline and six and 10 weeks.
• The Cancer-Related Fatigue Distress Scale (CRFDS) was measured at baseline and six and 10 weeks.
• Confounding variables measured included:  Brief Symptom Inventory (BSI-18) and Center for Epidemiologic Studies Depression Scale (CEDS).

FACIT-F scores in the true acupuncture group improved more over time than those in the sham group, but the differences were not significant. QOL and depression scores improved in both groups over time significantly but were not different between the groups. Observations regarding feasibility during the study included:  there was difficulty getting patients enrolled; changes in staff, staffing, and procedures made protocol use difficult; and due to procedures to maintain blinding and use of sham procedures, therapists felt that there was less needle manipulation possible with the protocol used for true acupuncture and felt it was difficult to determine the actual depth of needle insertion. It was also felt that the sham procedure was actually more than sham, although less than true acupuncture, due to skin and pressure stimulation.

It was concluded that feasibility to conduct this type of trial in a large group of patients was low. Findings of this study did not support the use of acupuncture to reduce fatigue in patients receiving radiation therapy.

• The study had a small sample size.
• It was not clear, or discussed, how many patients in either group received one or two sessions per week during the trial or whether any differences were associated with the frequency of treatment.
• It was noted that the sham/placebo control procedures were inadequate to provide a true control.
• There was no standard care comparison group.
• Improvements in fatigue, QOL, and depression over time may have been associated with increased attention from trial participation rather than any effect from study interventions.
• The study was not sufficiently powered, and the sample size was too small to differentiate between the groups and identify the associated effect size.