• FINAL NUMBER STUDIES INCLUDED = 9 
• TOTAL PATIENTS INCLUDED IN REVIEW = 890 patients, 441 assigned to intervention groups and 449 assigned to control groups
• KEY SAMPLE CHARACTERISTICS: The mean age was 59 years (20–91), and 65.6% of patients were women. Cancer diagnoses included multiple myeloma, breast, metastatic breast, colorectal, ovarian, endometrial, and gastrointestinal tract cancers. Chemotherapy included (a) PLD/vincristine/capecitabine; (b) PLD/paclitaxel; (c) PLD 4; (d) capecitabine alone or in combination with cyclophosphamide; (e) capecitabine alone or in combination with cisplatin, or cisplatin with docetaxel; (f) capecitabine; (g) 5-fluorouracil; or (h) capecitabine alone or in combination with cisplatin, or cisplatin and docetaxel.

PHASE OF CARE: Active treatment

Eight studies (two retrospective, two prospective comparative trials, four RCTs) for preventive efficacy and three studies (one RCT and two non-RCTs) for treatment efficacy. Random-effects meta-analysis did not reveal any significant associations between ppx pyridoxine supplementation and HFS development (RR = 0.95%, 95% CI [0.87, 1.05]) or any significant preventive efficacy against HFS in subgroup meta-analyses of study design, chemotherapeutic agents, pyridoxine dose, HFS severity, publication year, or observation period. However, pyridoxine did show significant efficacy in treating HFS (RR = 1.75, 95% CI [1.09, 2.8]) but did not show efficacy in the only RCT (RR = 1.12, 95% CI [0.58, 2.14]).

No evidence to support the use of pyridoxine supplements to prevent HFS during chemotherapy exists.

• Only four RCTs
• Chemotherapeutic agents included PLD or capecitabine

Further nursing research on the alternative uses of topical and oral therapies for HFS is warranted given that no evidence of clinical benefit was revealed.

The objective of this systematic review was to review published data on the efficacy and safety of tunneled indwelling pleural catheters (TIPCs).

Databases searched were MEDLINE, EMBASE, and ISI Web of Science through 2009. A manual search was conducted of reference lists for relevant additional studies.

Search keywords were malignant pleural effusion (MPE), tunneled indwelling pleural catheter (TIPC), and palliative care.

Studies were included if they reported on

• Adult patients
• Patients with MPE
• Patients treated with TIPCs.

Studies with and without control were included.

Studies were excluded if they reported on non-malignant effusions, empyema, chylothoras, long-bore chest tubes, or non-tunneled catheters. Studies in which all patients underwent thorascopy, video-assisted thorascopic surgery (VATS), or pleurodesis were excluded. Studies were excluded if they weren't published in English. Studies without primary data also were excluded.

• A total of 1,011 references were retrieved, which generated 25 eligible reports.
• Data were abstracted independently by two authors, and discrepancies were resolved by discussion and consultation with a third author.
• Abstractors were not blinded to any study details.
• The GRADES system was used for evaluation of quality.
• Case studies and one randomized controlled trial had low-level evidence.

This systematic review pertains to the dyspnea Putting Evidence Into Practice topic in that one outcome of the review evaluated “symptomatic improvement” with emphasis, although not exclusive focus, on dyspnea.
 

• The final number of studies included was 19.
• The total sample size was 1,370 patients.
• The sample range across studies was 8–263.
• The average age was 63 years.
• Of the sample, 50.5% were women.
• Most patients had recurrent MPE with failed thoracentesis or other treatment.
• The majority of the patients had a lung cancer diagnosis, but some also had breast cancer, mesothelioma, and a few other cancers.

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

Symptom relief was variably defined in the studies. Three studies reported symptom improvement without further delineation. One study rated dyspnea improvement on a three-point scale. The remaining studies reported symptomatic relief as “relief of dyspnea” or “improvement in respiratory performance,” “increased exercise tolerance,” “ improvement of pain,” and “catheter was useful.” When combined, 628 of the 657 patients (95.6%) experienced some degree of improvement in their symptoms, although the magnitude of improvement cannot be determined. Serious complications were rare. The most common complications were cellulitis (32 of 935, 3.4%) and obstruction or clogging (33 of 895, 3.7%) or unspecified malfunction of the catheter (11 of 121, 9.1%). The quality of the studies was low, as evaluated by the GRADES system.

Authors suggest that TIPC may improve symptoms for patients with MPE.

Based on the low-quality evidence in the form of the case studies, evidence is insufficient to demonstrate the effectiveness of TIPCs. 

More rigorous studies need to be conducted to establish evidence with respect to dyspnea.

Studies reviewed did not ensure that patients studied had depression or anxiety, so validity of examining impact of Reiki intervention on these problems is questionable. Two of the three studies had high risk of bias. No studies showed a statistically significant benefit.

There is insufficient evidence to evaluate efficacy of Reiki for anxiety and depression.

• Very few studies
• Poor quality studies

The evidence regarding effects of Reiki for anxiety or depression is insufficient to draw any conclusions. If Reiki is to be seen as a serious option for treatment, well-designed research to investigate effects is needed.

• FINAL NUMBER STUDIES INCLUDED = 3
• TOTAL PATIENTS INCLUDED IN REVIEW = 391
• SAMPLE RANGE ACROSS STUDIES: 849–1,840 patients
• KEY SAMPLE CHARACTERISTICS: Two studies included immunosuppressed men and women with cancer and the third investigated immunosuppressed men and women with cancer who had undergone allogeneic hematopoietic cell transplantations (HCTs).

PHASE OF CARE: Active antitumor treatment

A trial comparing voriconazole to liposomal amphotericin B as an empirical treatment for suspected fungal infection in neutropenic patients with cancer in which 6.8% of the patients died showed a significant benefit of using liposomal amphotericin B over voriconazole. No benefits were found between antifungal agents in the other two trials evaluated.

For the empirical treatment of patients with cancer who are immunosuppressed, liposomal amphotericin B is significantly more effective than voriconazole. Voriconazole and fluconazole did not have different outcomes in patients undergoing allogeneic HCT who were given either of these antifungal agents prophylactically. Treatment of aspergillosis comparing voriconazole with amphotericin B was not investigated.

Overall, there were so few trials comparing these antifungal agents (though large sample sizes) that except for one finding, results were inconclusive. These trials also could not be pooled for analysis due to their heterogeneity in study design.

For treatment of suspected fungal infections (neutropenic fever without overt fungal infection), liposomal amphotericin B is recommended. Careful evaluation for side effects of visual disturbances, dyspnea, and hypokalemia is critical.

To provide a consensus statement derived from published articles as well as expert opinion about antiemetic therapy in children younger than 18 years

This resource is a guideline, developed by the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO).

A panel of 23 oncology professionals determined the level of evidence and confidence according to EMSO and MASCC criteria. Between 2004 and June 2009, eight articles were published regarding 5-HT₃ receptor antagonists (RAs) in pediatric populations (two regarding safety issues, four dose-finding or -optimizing studies, and two comparative studies), four articles reported on the NK1 RA aprepitant (one randomized study, two case reports, and one study on the liquid formulation of aprepitant), and two miscellaneous studies looked at the impact of an antiemetic pump and the value of metopimazine when added to ondansetron. Recommendations were classified using the MASCC level of scientific confidence and consensus.

Pertinent information from the published literature from 2004 to June 2009 was retrieved and reviewed for the creation of this guideline.  

Database searched was Medline.

Search keywords were antiemetics, chemotherapy-induced emesis, children, neoplasms, nausea, vomiting, serotonin antagonists, neurokinin 1 receptor antagonists, phenothiazines, butyrophenones, cannabinoids, corticosteroids, and metoclopramide.

No inclusion criteria were identified.

Articles were excluded if they were review articles or addressed emesis not caused by chemotherapy.

• All patients were in active treatment.
• This guideline has application for pediatrics.

• No designated 5-HT₃ RA was recommended. (The MASCC level of confidence was moderate and level of consensus was high. The ESMO level of evidence was II and grade of recommendation was B.)
• No verifiable, high-level evidence-based consensus was possible on the dose of the individual 5-HT₃ RAs.
• Corticosteroids were found to be effective antiemetics for CINV, especially when combined with a 5-HT₃ RA. (The MASCC level of confidence was moderate and level of consensus was high. The ESMO level of evidence was II and grade of recommendation was B.) Safety issues when administering corticosteroids in children must strongly be considered.                                                                                                       
• No recommendations was made regarding ​neurokinin 1 (NK1) RAs, but they showed promising activity. The guideline panel recommended development of more well-designed, three-agent trials testing the addition of a NK1 RA to draw firm conclusions for a recommendation.                                                                       
• The guideline recommended that all pediatric patients receive antiemetic prophylaxis with a combination of a 5-HT₃ RA and dexamethasone for the acute phase of highly emetogenic chemotherapy. (The MASCC level of confidence was moderate and level of consensus was high. The ESMO level of evidence was III and grade of recommendation was B.)                                                                                                          
• For the acute phase of moderately emetogenic chemotherapy, all pediatric patients are recommended to receive antiemetic prophylaxis with a combination of a 5-HT₃ RA and dexamethasone. (The MASCC level of confidence was moderate and level of consensus was high. The ESMO level of evidence was II and grade of recommendation was B.)                                                                                                          
• For the acute phase of low and minimal emetogenic chemotherapy, not enough studies in children have been produced to make a recommendation.

Children receiving chemotherapy should receive a 5-HT₃ RA and dexamethasone for antiemetic prophylaxis both in highly emetogenic and moderately emetogenic chemotherapy. A significant lack of well-designed randomized studies exist to evaluate the problem of chemotherapy-induced emesis in children. Optimal dosing in children and management of delayed and anticipatory CINV in children is not yet clear. Investigation is needed regarding the potential role of NK1 RAs and the 5-HT₃ RAs palonosetron and transdermal granisetron for future consideration in pediatrics.

To determine the role of an neurokinin 1 (NK1) antagonist in multiple-day chemotherapy, in addition to standard of a 5-HT₃ receptor antagonists and dexamethasone

Oral aprepitant 125 mg was given 1 hour before chemotherapy on day 1 and 80 mg oral aprepitant was given daily during chemotherapy and for 2 days after completion of the treatment course. Patients also received 1 mg IV granisetron and 8 mg IV dexamethasone daily prior to chemotherapy. Use and choice of rescue medication was at the discretion of the physician.

• The study reported on 78 participants.
• Mean age was 40, with a range of 18–71 years.
• The sample was 18% female and 82% male.
• The most frequent diagnoses were germ cell cancer and sarcoma. Other diagnoses were myeloma, lymphoma, and thymus cancer.

The setting was a single site in Germany.

Patients were in active treatment.

The study design was a prospective trial.

• The National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 for toxicity assessment was used with nausea rated as yes or no.
• Complete response (CR) was defined as no nausea or vomiting and no use of rescue medication.

• 65.8% had CR in the acute phase.
• 68.4% had CR in the delayed phase.
• 57.9% had CR in the overall phase.
• Preexisting nausea (p < 0.05), pretreatment anxiety (p = 0.0001), and patients with brain metastases (p = 0.04) were associated with lower CR rates.
• No patients discontinued because of adverse events.
• Most common events were hiccups (7.7%), diarrhea, and constipation.

Aprepitant appears to be well-tolerated. CR rates were only slightly above those commonly seen with 5-HT₃ receptor antagonists and dexamethasone.

• No control comparison or blinding with associated risk of bias was used.
• Methods of nausea and vomiting measurement were not clearly stated.
• Use of rescue medications was not stated.
• Definition of nausea as a single yes or no measure is questionable.
• Timing of measures was not stated.

Further well-defined research to fully evaluate multiple drug chemotherapy-induced nausea and vomiting regimens is warranted.

STUDY PURPOSE: To summarize the evidence regarding the effects of calcium and magnesium infusion to prevent peripheral neuropathy associated with oxaliplatin

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 5
• TOTAL PATIENTS INCLUDED IN REVIEW = 694
• SAMPLE RANGE ACROSS STUDIES: 27–353
• KEY SAMPLE CHARACTERISTICS: All were on FOLFOX regimens.

PHASE OF CARE: Active antitumor treatment

Across four studies (640 patients), the relative risk of grade 2 or higher chemotherapy-induced peripheral neuropathy was 0.81; however, the z test for overall effect showed no statistical significance. The largest trial showed no difference between groups.

The findings did not show any benefit of calcium and magnesium infusions for the prevention of oxaliplatin-induced peripheral neuropathy.

• Limited number of studies included
• No quality evaluation
• Low sample sizes
• Two of the five studies had very low sample sizes.

The findings do not support the use of calcium and magnesium infusions to prevent chemotherapy-induced peripheral neuropathy.

To assess the role of an neurokinin 1 (NK1) antagonist in antimetic protection in combination with granisetron and dexamethasone in patients receiving high-dose chemotherapy (HDC)

• Patient undergoing multiple days of HDC received granisetron, dexamethasone, and aprepitant during chemotherapy and two days after the completion of chemotherapy.
• Patients were receiving two HDC regimens for at least two days.
  • Melphalan, 70 mg – 100 mg/m², days 1-4, followed by peripheral blood stem cell translant (PBSCT)
  • Paclitaxel, carboplatin, etoposide, and ifosfamide

• This study consisted of 64 patients.
• Patient mean age was 42.3 with a range of 21–67. The percentage of patients younger than age 35 was 18%.
• The study consisted of 52 male patients (81.2%) and 12 female patients (18.8%).
• Patients had been diagnosed with multiple myeloma (MM) (32.8%), thymic cancinoma (6.3%), testicular cancer (35.9%), sarcoma (23.4%), and unknown primary (1.6%).
• Additionally, 9.4% of patients had received previous gastrointestinal (GI) surgery, 7.8% had a history of alcohol abuse, 7.8% had a history of loss of appetite, 6.3% had preexisting nausea, 1.6% had preexisting dizziness, and 14.1% had anxiety.

This study was conducted at a single site at a university hospital in Halle, Germany.

• All patients were in active treatment.
• The study has clinical application for elderly care.

This was a nonrandomized, single-center, observational trial.

• Complete response (CR) was defined as no vomiting and no use of rescue medications in the overall phase (days 1 until 5 days postchemotherapy).
• Nausea and vomiting were recorded daily on a special documentary chart.  All adverse events were recorded to evaluate the tolerability and were graded according to the common terminology criteria.
• All other drugs administered to the patient during the study were recorded.

• For the overall evaluation phase, the primary endpoint of CR was achieved with 40 (63%) patients.
• For the acute phase (during days of HDC), CR was achieved in 53 patients (83%).
• For the delayed phase (days 1 through 5 after the end of HDC) CR was seen in 45 patients (70%).
• Acute nausea was observed in 13 patients (20%), delayed nausea in 24 patients (24%), and overall nausea in 30 patients (47%).
• At the day of retransfusion of stem cells (second day of delayed phase in all HDC groups), the CR rate was 84% and the rate of nausea was 19%.
• The authors concluded that randomized studies may be necessary to add aprepitant to guidelines.

The study demonstrated a good toxicity profile with the addition of aprepitant to the standard antiemetic regimen, with improvement in the prevention of chemotherapy-induced nausea and vomiting (CINV) during multiday, high-dose regimens.

• The study had a small sample with fewer than 100 patients.
• Tools or scales used to measure nausea were not reported.
• A description of how vomiting and nausea were recorded on the special documentation form was not included.
• The authors did not describe how the nurses were trained to use the form and whether it was only recorded by registered nurses.
• Methodological limitations exist with comparing the results with those only from the current literature.

• The addition of aprepitant to standard antiemetic regimens during multiday HDC administration provides additional protection for both acute and delayed CINV.
• The possible reaction between aprepitant and Ifosfamide was within the reported range of induced encephalopathy (26%, range = 10%–30%).

To investigate the influence of pole walking on arm lymphedema following breast cancer treatment when using a compression sleeve

Pole walking is a walking exercise with the addition of walking poles that simulates the arm motion of cross-country skiing during walking. Subjects participated in pole walking on one occasion for one hour outdoors in a park and on sidewalks for approximately 4 km. Each session was performed similarly and was supervised by the same person. Measurements were made before, immediately after, and 24 hours later.

• The study sample was comprised of female patients aged less than 70 years.
• Arm lymphedema was defined as the affected arm being 5% larger than the contralateral arm, including palpable thickness somewhere in the affected arm compared to the contralateral arm, and the patient's experience of tightness in the affected arm.
• The edema had to be persistent for at least six months.

The study took place at a single site in Sweden.

The study used a pre-post design.

• Both arms were measured with the water displacement method and the contralateral arm was used as a control on each occasion.
• Total arm volume was given in milliliters for both arms.
• Lymphedema absolute volume was calculated as the volume difference between the arms.
• The lymphedema relative volume was calculated in percentage.
• Subjective lymphedema assessments of experience of heaviness and tightness in the affected arm while standing with their arms hanging and no arm sleeve on were used.
• A 100-millimeter visual analog scale used the endpoints ‘‘no discomfort’’ (0 mm) and ‘‘worst imaginable\".

The patients showed no significant difference in total arm volume in the edema arm immediately after pole walking or 24 hours later compared to before walking. Immediately after pole walking, a significant decrease in lymphedema absolute volume and in lymphedema relative volume was found compared to before pole walking. Twenty-four hours later, no differences were found compared to before walking. There were no significant differences in rating of heaviness and tightness on the visual analog scale immediately after pole walking or after 24 hours compared to the rating before pole walking.

A controlled, short-duration pole-walking program can be performed by patients with arm lymphedema using a compression sleeve without deterioration of the arm lymphedema.

• The study had a small sample size (N < 30).
• Out of 42 candidates, 26 participated in the study.
• Participation bias should be advised.

Nurses and clinicians should be aware and encourage women with lymphedema to perform exercises, such as pole walking, which seems not to deteriorate arm lymphedema.

To investigate the effects on intensive pole walking on cardiovascular fitness, subjective assessment, and arm lymphedema in women who were treated for breast cancer

Eight-week exercise period preceded by a two-week control period where subjects were asked not to change anything in daily living. Exercise was self directed 3–5 times/week for 30–60 minutes. Subject pace had to correspond to 70%–80% of estimated maximum heart rate (220-age). Warm up period of 10 minutes included pole walking and light arm exercises. Subjects wore compression garments during exercise and various measurements prestudy, at various intervals, and at the conclusion of the study.

SITE:  Multi-site  

SETTING TYPE:  Outpatient  

LOCATION: Lymphedema unit at Skane University Hospital in Lund and Malmo, Sweden

Quasiexperimental

• Pre-post design: 8 week exercise period preceded by a 2 week control period.
• Arm volume bilateral measurements using the water displacement method and using unaffected arm as a control, cardiovascular fitness was assessed using sub-maximal bicycle ergometer test, which included heart rate monitoring. 
• DASH questionnaire for symptom assessment 
• Visual analogue scale for heainess and tightness in the affected arm
• Two general well-being questions

Statistically significant reduction in total arm volume (p = 0.001), lymphedema absolute volume (p = 0.014), and lymphedema relative volume (p = 0.015), as well as decreased heart rate and rating of tightness in the arms. Both positive and negative influences on well-being were reported.

Moderately intense exercise, such as pole walking, is feasible for patients with breast cancer with lymphedema. Standard precautions and use of compression garments during exercise is advisable. The effects of exercise on cardiovascular health and well-being are consistent with general public. Reduction in arm volume measurements post intervention should be further studied.

• Small sample (< 30)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: Self reported adherence to intervention; measurement of well being and heaviness/tightness in affected arm—subjective assessment—reliability and validity of tools not addressed. Small n value. Further studies are needed.

Patient education