RESOURCE TYPE: Evidence-based guideline

Thirty-five systematic reviews, 9 randomized controlled trials, and 19 other studies were used as the evidence base for the guidelines developed.

• Prescribing nonopioid analgesics and adjuvants, topical analgesics—moderate strength of recommendation and intermediate level evidence
• Not prescribing corticosteroids for long-term use

• Limited number of studies involved
• Includes both cancer and noncancer studies
• Incorporates refractory pain approaches with chronic pain evidence

Does not add substantially to the body of evidence or recommendations for chronic cancer-related pain management. Does suggest that effectiveness of long-term pain management should consider aspects such as functional impact and not just reduction in pain severity or other pain-specific outcomes. Provides new information regarding suggested approaches to address potential problems of analgesic abuse and misuse.

To determine the effectiveness of Tong Len meditation on depression, stress, anxiety, and self-perception of quality of life in a population of patients with cancer.

Tong Len meditation (Tibetan meditation practice), a distant healing compassionate act, was used for three months, three times a week for 15-20 minutes on a group of patients with cancer. The evaluation of the results with the POMS and EQ 5 D questionnaires took place after two months, three months, and one month after treatment cessation.

• N = 77
• MEAN AGE = 57.09
• MALES: 6.8%,FEMALES: 93.2%
• KEY DISEASE CHARACTERISTICS: Mostly patients with breast cancer
• THER KEY SAMPLE CHARACTERISTICS: Patients with psychiatric disorders and patients in advance stage or terminal stage of cancer were excluded

• SITE: Single site
• SETTING TYPE: Not specified
• LOCATION: Bologna, Italy

• PHASE OF CARE: Multiple phases of care

• Double-blind randomized, controlled trial

• Profile of Mood States
• EORTC Quality of Life Core 30 questionnaire

Considering the results of Tong Len meditation on depression, there was a significant improvement (p = 0.003) in the treatment group. As far as the other components, there were no significant differences between treatment and control groups. There was a significant increase in levels of vigor and activity in the control group (p = 0.009). In both groups, there was an increase in self-perceived quality of life, possibly due to a “white lab coat\" effect.

Tong Len meditation does not show statistically significant evidence to support scientific efficacy on depression, anxiety, or stress. It does show an improvement in both groups in self-perceived quality of life and an overall psychological gain, which might reflect a positive \"white lab coat\" effect.

• Small sample (less than 100)
• Risk of bias (sample characteristics)
• Intervention expensive, impractical, or training needs

Although Tong Len meditation might be beneficial to patients with cancer, the results of this study should be interpreted with caution due to limitations, including small sample size, non-homogeneity of tumor pathology, and cancer treatment.

To compare the effectiveness of different skin antiseptics in the prevention of catheter-related infection (CRI)

The type of antiseptic used for skin disinfection for catheter care was chosen by the intensive care units of participating hospitals. Maximal sterile precautions for catheter insertion according to guidelines were used. All catheters were nontunneled, and none were used for routine blood sampling. Decisions to remove catheters were at the physicians' discretion and, after removal, catheter tip and peripheral blood cultures were conducted. A one-step procedure of skin cleansing was conducted with 2% chlorhexidine, and a four-step protocol of scrub, rinse, dry, and disinfect was used with other antiseptics. A propensity score was calculated from analysis of covariance to determine the propensity for CRI and was controlled in analysis techniques. In four ICUs, staff switched from a povidone iodine antisepsis to chlorhexidine, and separate analysis of differences in outcomes were analyzed individually (1,368 patients). All suspected cases of CRI were reviewed and determined by a blinded committee.

• N = 3,027
• MEAN AGE = 62.3 years
• MALES: 50.3%, FEMALES: 49.7%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Patient with multiple diseases, including cancer. All were in intensive care units. Over half were on antibiotics, 78% were on ventilators, 10%–14% had an immunodeficiency, and, overall, less than 1%  had neutropenia.

• SITE: Multi-site
• SETTING TYPE: Inpatient
• LOCATION: France

• Prospective cohort comparison

CRI defined as catheter-related bloodstream infection (CRBSI) or the combination of a catheter tip colonization and clinical signs of sepsis with no other cause identified.

The use of chlorhexidine was associated with a decreased risk of CRI (2 per 1,000 catheter days, p = 0.037). The unadjusted incidence of CRI was higher in the povidone iodine group compared to the chlorhexidine group (2.8 versus 2 per 1,000 catheter days, p = 0.001). Overall, CRI risk in the units that switched from povidone iodine to chlorhexidine was lower with chlorhexidine use (hazard ratio [HR] = 0.31, p = 0.005). However, no significant differences in CRBSI existed between groups.

The use of a skin antisepsis with a 2% chlorhexidine alcohol preparation for catheter care may be associated with a lower incidence of CRI.

• Risk of bias (no random assignment) 
• Key sample group differences that could influence results
• No data or control regarding other aspects of catheter care and use existed, which can also affect the development of CRI.
• No information is provided regarding the frequency of dressing changes, etc.
• The various solutions used for skin antisepsis were unclear—both a 2% and 1% chlorhexidine and 5% and 10% povidone iodine solutions were mentioned, but the study does not indicate which patients got which solution, or which solution was associated with which reported result.
• Differentiation of CRI versus CRBSI were unclear, and the association of these with the skin antisepsis used differed.

The use of chlorhexidine skin antisepsis may be associated with a lower incidence of CRI. The evidence has several limitations; however, it is consistent with the body of evidence showing the efficacy of chlorhexidine skin preparation as part of central venous catheter care.

Patients were randomized to receive a placebo or 150 mg per day dose of armodafinil. Armodafinil was taken daily during seven weeks of radiation therapy and then an additional four weeks. There were no dose modifications or drug holidays. If patients could not tolerate the study agent, it was discontinued. Fatigue, cognitive function, and quality of life were assessed at baseline, at the end of RT, and four weeks after RT. Toxicities were evaluated weekly.

• N = 54
• MEDIAN AGE = 59 years (range = 20–79 years)
• MALES: 46%, FEMALES: 54%
• KEY DISEASE CHARACTERISTICS: All patients had brain tumors and were receiving brain irradiation.

• SITE: Multi-site
• SETTING TYPE: Not specified
• LOCATION: North Carolina

PHASE OF CARE: Active antitumor treatment

Double blinded, placebo-controlled, randomized, controlled trial (n = 26 [armodafinil], n = 28 [control])

• Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) subscale
• Brief Fatigue Inventory (BFI)
• Epworth Sleepiness Scale (ESS)
• Functional Assessment of Cancer Therapy–Brain (FACT-B) scale
• Verbal fluency category test
• Hopkins Verbal Learning Test–Revised (HVLT-R)
• Trail Making Test (TMT) parts A and B
• Backwards Digit Span Test

Nine patients dropped out of the study by the end of RT. The most common adverse effects were headache, insomnia, nausea, anxiety, arthralgia, dizziness, dry mouth, sinusitis, and throat and respiratory infections. There were no significant differences in adverse events between the study groups. There were no significant differences between groups in fatigue. In both groups, fatigue increased during treatment and improved following the completion of RT. Neurocognitive measures improved slightly over time in both groups with no significant difference between the groups. Among patients with the most fatigue at baseline, those taking armodafinil showed improvements in fatigue at the end of RT. Armodafinil also did not improve neurocognitive outcomes at the end of RT or at four weeks post RT in the subsets of participants with high or low levels of fatigue at baseline.

Armodafinil was not shown to improve fatigue or cognitive function measures in patients receiving brain irradiation. Armodafinil appeared to show some benefit in improving fatigue among those with high levels of fatigue at baseline.

• Small sample (< 100)
• Findings not generalizable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: The size of the final sample was underpowered. No intent to treat analysis was described. The sample was limited to patients receiving brain irradiation.

The findings did not provide overall support for effectiveness of armodafinil to reduce fatigue in this study although patients with the highest level of fatigue at baseline appeared to have some benefit. Additional research is warranted to determine if there is any benefit of psychostimulants for fatigue and cognitive impairment in patients with brain tumors undergoing radiation therapy.

To determine the effectiveness of Scrambler therapy in patients with chemotherapy-induced peripheral neuropathy (CIPN)

Scrambler therapy involves the use of low-dose electrical stimulation delivered through electrodes placed around patient-reported painful areas. Five sets of electrodes can be placed around a painful area at one time. The goal of this study was to replace pain with no pain and/or lessening of symptoms. Patients were treated daily for up to 10 days.

• N = 37  
• AGE = 33–79 years
• MALES: 32%, FEMALES: 67%
• KEY DISEASE CHARACTERISTICS: Breast, ovarian, colon/rectal, lymphoma, and nine other primary cancers
• OTHER KEY SAMPLE CHARACTERISTICS: Thirteen patients were treated with taxol, eight received carboplatin/ taxol, nine received oxaliplatin, four received cisplatin therapies, and three received vincristine.

• SITE: Not stated/unknown    
• SETTING TYPE: Outpatient  
• LOCATION: USA

PHASE OF CARE: Mutliple phases of care

Prospective, open-label trial

Measurements included numerical analog scales from 0–10 that were part of a neuropathy questionnaire, a global impression of change questionnaire, and the Rydel-Seiffer Tuning Fork to evaluate patient vibratory sense.

Pain scores decreased 53% from baseline to day 10. Numbness decreased 37%, and tingling decreased 44%. Increased quality of life was reported during treatment as well as during the 10-week follow-up period. All of these changes were significant (p < 0.0002). The vibration perception scores measured with the Rydel-Seiffer Tuning Fork also improved.

Although Scrambler therapy demonstrated positive effects in this trial, a large randomized, controlled trial is needed to confirm its efficacy in CIPN. Special training and experienced personnel need to be in place for someone to deliver this therapy. Practicality and cost need to be factored in for this type of intervention.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no random assignment)
• Findings not generalizable
• Only 10 weeks of follow-up
• Thirty-two patients completed the study.
• Findings in solid tumors only and in a small number, making it hard to generalize findings

A large, randomized study is needed for future research. Scrambler therapy is not a very practical treatment, and cost of the treatment was not discussed. Also, specific training is needed to administer it. Currently, insufficient evidence recommends its use.

To evaluate the effectiveness of low-dose dexamethasone (4 mg) given with palonosetron on acute and delayed nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC)

Day 1 (30 minutes before chemotherapy): Administration of palonosetron 0.25 mg and dexamethasone 4 mg intravenously

Days 2 and 3: Dexamethasone 4 mg intramuscularly daily

• N = 26
• MEDIAN AGE = 58 years (range = 42–76 years)
• MALES: 1 (4%), FEMALES: 25 (96%)
• KEY DISEASE CHARACTERISTICS: 100% patients with breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: 54% received epirubicin and cyclophosphamide; 35% received fluorouracil, epirubicin, and cyclophosphamide; and 11% received epirubicin, cyclophosphamide, and trastuzumab. Of the 25 females, 8% were premenopausal and 92% were postmenopausal. 

• SITE: Not stated/unknown  
• SETTING TYPE: Not specified
• LOCATION: Not stated but assumed in Italy since all authors are from Italy

• PHASE OF CARE: Active antitumor treatment

• Observational

Patients were given a diary to record their emesis episodes, nausea and its severity, and use of rescue medication within the first 24 hours and on days 2–5 after chemotherapy. Patients participated in minimum of one chemotherapy course up to a maximum of four chemotherapy courses.

Course 1: 72% of patients had completed response (no emesis, no rescue medication) in the acute phase and complete control (no emesis, no rescue medication, no more than mild nausea) in the delayed phase; 12% had partial response (one emesis, no more than two days of rescue medication) in the acute phase and complete control in the delayed phase; 12% had partial response in the acute phase and partial control (severe nausea no more than two days and needing rescue medication) in the delayed phase; and one patient (4%) did not respond to prophylaxis. Among all chemotherapy courses combined: 72% of the courses showed complete response in the acute phase and complete control in the delayed phase; 8% had partial response in the acute phase and complete control in the delayed phase; 4% had partial response in the acute phase and partial control in the delayed phase; 15% had complete response in the acute phase and partial control in the delayed phase; no control of emesis occurred in one of the courses (1%). No adverse side effects (e.g., constipation, abdominal pain, insomnia, elevated blood glucose levels) were reported.

Low-dose dexamethasone given in conjunction with one dose of palonosetron appears to be effective for the treatment of acute and delayed nausea and vomiting in patients with breast cancer receiving HEC. However, additional research is needed to allow for further comparison of response to variable dexamethasone dosing in conjunction with 5-HT3 for prophylaxis of HEC.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described

Low-dose dexamethasone is an effective treatment for acute and delayed nausea and vomiting with no significant side effects. However, additional research studies are needed to allow for further comparison of response to variable dexamethasone dosing in conjunction with 5-HT3 for prophylaxis of HEC. The authors suggest that patients may experience similar efficacy with an antiemetic regimen that includes lower doses of steroids. Reducing the total dose of steroids has the potential to simultaneously reduce the untoward effects that are known to result from administration of steroids (e.g., altered glucose levels, bone loss, sleep disturbances, mood changes).

The aim of the study was to evaluate the neuroprotective effect of vitamin E in patients treated with cisplatin.

Patients were randomized to either vitamin E 400 mg per day (α-tocopherol) or placebo. The vitamin E (or placebo) was started orally before chemotherapy and continued for three months after completion of cisplatin.

• The study had a total sample of 108 patients. Forty-one were included in the analysis.
• Mean age was 58 years, with a range of 28–74 years.
• Patients had solid tumors and were in generally good health and receiving cisplatin therapy.

The study was conducted at multiple outpatient sites: the National Cancer Institute in Rome and the National Neurologic Institute in Milan, Italy.

The study had a phase III randomized, placebo-controlled trial design.

• Neurologic examination: Standardized history and assessment of pinprick and vibratory sensations, strength, and deep tendon reflexes.              
• Total neuropathy score
• Reidel-Seiffer tuning fork
• Electrophysiologic examination

Neurotoxicity score was significantly lower in patients receiving vitamin E than in the placebo group (mean score of 1.4 versus 4.1; unpaired t test, p < 0.01). Neurotoxicity incidence differed significantly between groups (group 1, 1 of 17 participants; group 2, 10 of 24 participants; p < 0.01). Also, the relative risk of developing signs or symptoms of neurotoxicity was significantly lower in group 1 than group 2 (relative risk of 0.14, 95% confidence interval [0.02, 1],  p < 0.05). At follow-up, compared with baseline, mean sural and sensory median nerve amplitude values were significantly decreased in the control group (p = 0.02 and p = 0.008, respectively), while median nerve amplitude was unchanged and sural nerve amplitude was decreased, but not significantly, in patients receiving Vitamin E.

Vitamin E may be helpful in reducing neurotoxic effects of cisplatin, but larger randomized trials are needed.

• The study was limited by a small sample size (less than 100).
• In addition, a large number of dropouts were reported.

Cisplatin-induced peripheral neuropathy can be painful and also interfere with a patient’s quality of life; however, future research is needed with larger trials before Vitamin E is recommended. Also, drug interactions need to be considered.

This study evaluated the neuroprotective effect of vitamin E in patients with solid tumor malignancy treated with cisplatin chemotherapy.

Patients were randomly assigned to either group 1, which received vitamin E supplementation during cisplatin chemotherapy, or to group 2, which received cisplatin chemotherapy alone. Vitamin E 300 mg per day was administered orally before cisplatin chemotherapy and continued for three months after the suspension of treatment.

• A total sample of 47 patients was recruited. Twenty-seven completed the study.
• Patients had a variety of solid organ malignancies.
• Exclusion criteria included previous chemotherapy treatment or regimens including other neurotoxic drugs.

• Assessment of neuropathic symptoms, pinprick, vibratory sensations, strength, and deep tendon reflexes.
• A follow-up neurologic examination was performed by the same neurologists (not blinded to treatment status) after the three cycles of cisplatin treatment and after the cessation of chemotherapy. Neuropathic signs and symptoms were scored using a questionnaire designed for the detection of sensory disturbances (e.g., paresthesia, pain, and burning in feet or fingers) experienced by patients.
• Nerve conduction velocity and the amplitude of potentials of the sensory median and sural nerves were assessed at baseline and at the end of treatment with vitamin E.
• Plasma levels of vitamin E were measured by gas chromatography-mass spectrometry prior to chemotherapy.

Twenty patients dropped out of the study. Plasma levels of vitamin E were in the normal range and not significantly different between the two groups (8.06 and 7.17 mg/ml, respectively). Twelve of the 14 patients in the control group developed CIPN as compared to 4 of 13 patients who received vitamin E supplementation.

Vitamin E supplementation significantly protects against cisplatin-induced peripheral neuropathy and reduces incidence and intensity of neurologic signs and symptoms.

• The small sample size and differing tumor types included make comparisons difficult.
• The small sample size can also make finding statistically significant results more likely by chance alone.

STUDY PURPOSE: To review current research of free vascularized lymph node transfer (VLNT) for the treatment of lymphedema

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 18
• TOTAL PATIENTS INCLUDED IN REVIEW = 305 patients, 309 limbs and 316 flaps
• SAMPLE RANGE ACROSS STUDIES: Participants aged 13–80 years, 195 upper limbs and 114 lower. Secondary lymphedema was the leading cause of LE. Limb size determination varied. The duration of lymphedema varied from 3 months to 26 years. The average duration of lymphedema was greater than 24 years. Postoperative follow-up ranged from 2 to 132 months. 
• KEY SAMPLE CHARACTERISTICS: Level of evidence studies: 3 were level II, 13 were level III, and 2 were level IV. None of the studies were ranked I or high quality.

PHASE OF CARE: Pre- and postoperative VLNT
 
APPLICATIONS: Elder care

• Outcomes varied because evaluation of reduction was not consistent across studies.  
• Circumferential measurement reduction: Ninety-one percent showed postoperative improvement.  
• Lymphangioscintigraphy/lymphangiography: Sixty percent improved flow with moderate to significant improvement.  
• Patient satisfaction: All but seven patients stated improvement and surgery satisfaction.

The findings suggest that the use of VLNT may be helpful in reducing lymphedema. Larger studies with standardized measurements are needed to create a stronger body of research to fully evaluate this surgical procedure.

• Limited number of studies included
• Low sample sizes
• The need to evaluate same lymphedema types, primary versus secondary, radiation, and no radiation is needed.  
• All lymphedemas are not the same.

Limited evidence supports surgical interventions to manage lymphedema. However, the studies being conducted, although scant, do have potential, but outcomes vary presently.

To compare the clinical outcomes between allogeneic peripheral blood stem cell (PBSC) recipients who did and did not receive matched granulocyte transfusions.

Patients who did not have an ABO matched donor were assigned to a comparison control group, and those with a matched donor were assigned to receive granulocyte transfusions.  Patients received conditioning either with total body irradiation, etoposide and cyclophosphamide or busulfan and cyclophosphamide given over seven days, or the regimen of total body irradiation and cyclophosphamide administered over three days.  Posttransplant granulocyte colony-stimulating factor was given to all patients on day 1 until neutrophil recovery.  No prophylactic antibacterial or antifungal antibiotics were given.  Prophylactic acyclovir was given to prevent herpes simplex infection.  Empiric antibiotic therapy was given for an initial fever of 38.3°C or higher.  Empiric therapy of amphotericin B was given for persistent fever.

• One hundred fifty-one donor-recipient pairs were included.
• Mean age was 44.5 years (range 14–68).
• Of the patients included, 56.3% were male and 43.7% were female.
• The majority of patients had leukemia, myelodysplastic syndrome, myelofibrosis, or aplastic anemia.

• Single site  
• Inpatient  
• United States

Patients were undergoing the active antitumor treatment phase of care. 

This was a prospective two-group study.

• Onset of neutropenia (defined as absolute neutrophil count [ANC] decrease to 500/mm³)
• Recovery (defined as the first day after ANC nadir that ANC increased to 500/mm³ for three consecutive days)
• A febrile day (defined as any day during hospitalization with a temperature of 38.3°C or higher)
• Bacteremia included culture-proven systemic blood infections.

Patients receiving granulocyte transfusion had a mean of 13.2 days of hospitalization, compared to 29.6 days in the control group (p = 0.03).  Patients receiving transfusions had fewer days of severe neutropenia.  This difference was 1.5 days on average (p = 0.0005).  The percentage of patients who developed fever during hospital stay from the start of conditioning to discharge was 82.7% in patients who did not receive granulocytes versus 64.2% in those who received granulocyte transfusions (p = 0.03). There were no other differences between groups in bacteremia or overall survival.

Granulocyte transfusions in this group of patients may have a statistically significant but clinically mild beneficial effect on the duration of neutropenia and hospital stay.

• Risk of bias (no blinding and no random assignment)  
• Unintended interventions or applicable interventions not described that would influence results *

* There was no subgroup analysis between those who may have received empiric treatment for fever as described in the study methods; therefore, it is unclear if such treatment influenced the results.  Sample sizes with results reporting tend to vary throughout the report, so it is unclear if this is related to missing data from the retrospective method.

The findings suggested that granulocyte transfusions may have some benefits for allogeneic stem cell transplant recipients; however, this study did not provide strong support for this intervention due to study limitations.  Because these patients did not receive routine prophylactic antibiotic or antifungal treatment, it is not clear what the clinical role of granulocyte transfusion might be in the setting of more aggressive preventive clinical management.