STUDY PURPOSE: To evaluate the effectiveness and safety of ramosetron for chemotherapy-induced nausea and vomiting (CINV) through a systematic review of randomized, controlled trials (RCTs)

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 16
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,083
• SAMPLE RANGE ACROSS STUDIES: Variety of ages and diagnoses
• KEY SAMPLE CHARACTERISTICS: Most cisplatin-based regimens in China, Japan, Taiwan, India, and Korea

PHASE OF CARE: Active antitumor treatment

In the acute phase, ramosetron significantly reduced nausea and acute vomiting compared to other 5HT3RAs. In the delayed phase, difference in complete response of nausea existed between ramosetron and other 5-HT3RAs. No significant differences existed between common adverse reactions.

The study concluded that ramosetron for CINV may be as effective and as tolerable as other 5-HT3RAs, but more well-designed RCTs are needed to confirm the effect of ramosetron on acute or delayed CINV in patients with cancer.

The methodological quality of studies was not high (different dosages, missing data, limited information on MEC or low risk).

Ramosetron may be effective for CINV and as tolerable as other 5HT3RAs. More well-designed RCTs are needed to confirm the effect of ramosetron on acute or delayed CINV.

To investigate whether the use of honey provides protection from the effects of radiation-induced mucositis

Databases searched were PubMed, MEDLINE via OVID, EMBASE, CINAHAL via EBSCO, and Cochrane.

Keywords searched were honey and mucositis or stomatitis.

Studies were included in the review if they

• Were randomized controlled trials that investigated protective effects of honey in patients with head and neck cancer undergoing radiation therapy.
• Used Radiation Therapy Oncology Group (RTOG) or World Health Organization (WHO) criteria to evaluate the severity of radiation mucositis.

Studies were excluded if they

• Were nonhuman clinical trials.
• Were nonrandomized controlled trials.
• Involved patients without diagnoses of head and neck cancer.
• Were trials in which the protective effects of honey were not studied.

A total of 15 references were retrieved. Four trials reported on the protective effects of honey. One of these was nonblinded. The remaining three were randomized examiner-blinded, and these three trials were assessed for overall risk of bias using the Cochrane method. Three of the four studies met the inclusion and exclusion criteria for the meta-analysis.

• The final number of studies included was four human trials, but one trial was excluded because it reported only on pain relief, not the protective effects of honey.   
• The total sample across all studies was 120 patients with 40 in each study.
• Studies involved adults with head and neck cancer receiving radiation therapy. In one study, patients were receiving concurrent chemotherapy and radiation. I all studies, patients with systemic illness or prior chemotherapy were excluded.

All patients were undergoing the active treatment phase of care.

Meta-analysis of the of the three trials reported that honey appeared to have protective effects against radiation-induced mucositis by 80% compared to the control group. Overall relative risk of developing mucositis was almost 80% lower (risk ratio, 0.19; 95% confidence interval, 0.098–0.371) in the honey treatment group than in the control group.

Trials were fairly homogeneous (I² = 0%, p = 0.39), so meta-analysis used a fixed-effects model (Mantel-Haenszel method) to calculate a pooled risk ratio.

• A limited number of trials met the criteria for meta-analysis. Individual studies were weak.
• Two of the studies included had a high risk of bias because of plausible bias in several criteria.
• Patients were not blinded because of the taste of honey. 
• Grade 3 or 4 on the RTOG scale was used as the outcome measure of interest.

Further research is needed to strengthen the current evidence prior to any clinical recommendations for practice. They suggested blinding the assessor in future studies.

The purpose of the study was to Investigate efficacy of secondary antifungal prophylaxis (SAP) .  

Primary antifungal prophylaxis was fluconazole 200 mg PO daily. Patients with documented IFI were treated with intensive antifungal therapy. Two of these had complete response prior to futher treatment of primary disease. Thirty-three patients received prophylaxis with voriconazole, 21 received itraconazole, two received micafungin, and one received amphotericin B. The antifungal prophylaxis continued through time of neutropenia and ended when eradication of residual diseases or initiation of salvage therapy due to failure of SAP.

• 57 patients were included.
• 149 cycles of therapy
• Ages ranged from 14-77 years
• 56% were male, 44% were female
• 21 patients had AML, 23 had ALL, 2 had NHL, and 1 patient had MDS-RAEB
• 70% were in complete remission, 30% identified as uncontrolled disease.
• Medical records for all patients hospitalized for more than two weeks were reviewed.
• 57 patients who received 149 cycles of therapy were included.
   

• Single site  
• Inpatient stem cell transplantation center  
• Tianjin, China
   

Active treatment (i.e., chemotherapy or stem cell transplantation)

Retrospective chart review

• Diagnosis of IFI was according to revised EORTC/MSG criteria: proven cases diagnosed according to pathologic or microbiological evidence.  Probably and possible cases documented by radiological and/or microbiological evidence.
• Response to antifungal treatment graded according to criteria defined by complete response (CR), pratical response (PR), stable disease (SD), or progressive disease (PD).
• Relapse defined as recurrence of fungal lesions in historical foci.
• Breakthrough infection defined as emergence of fungal lesions in other than historical foci.

Median follow-up 120 days (12–1,080) revealed 11 failures of SAP, representing 7.4 per 100 cycles of therapy and cumulative incidence of 24.5% at end of follow-up. Four experienced infection progression, three had infection recurrence, and the other four had breakthrough infection. Of the 11 failures, five occurred in the allo-HSCT and six during chemotherapy. High-dose steroids and neutropenia of more than 14 days were identified as risk factors for SAP failure.

SAP demonstrated high efficacy and can protect further chemotherapy and SCT. Two risk factors, high-dose steroids and neutropenia longer than 14 days, were identified as factors of prophylaxis failure and these patients were deemed to require special consideration.

• Small sample size
• Retrospective study design
   

Based on small sample size and study design, evidence is weak in recommendation for practice. 

STUDY PURPOSE: To evaluate the evidence to determine if a neutropenic diet decreases infection and the mortality rates of patients with cancer at risk for neutropenia

TYPE OF STUDY: Meta-analysis and systematic review

• DATABASES USED: MEDLINE, EMBASE, COCHRANE CENTRAL
• INCLUSION CRITERIA: Randomized, controlled trials and comparative observational studies. A neutropenic diet was any diet that excluded fresh fruits and vegetables, raw meats, and other types of food like soft cheese.
• EXCLUSION CRITERIA: Not specified

• TOTAL REFERENCES RETRIEVED: 537
• EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane risk of bias tool and the Newcastle Ottawa Scale for observational studies. Risk of bias found was related to lack of blinding, which is not always possible in such studies.

• FINAL NUMBER STUDIES INCLUDED = 4 
• TOTAL PATIENTS INCLUDED IN REVIEW = 918
• SAMPLE RANGE ACROSS STUDIES: 19–363 patients
• KEY SAMPLE CHARACTERISTICS: Multiple tumor types, one study of 19 pediatric patients

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

No differences in major infection rates were observed between those on regular diets and those on neutropenic diets. The risk of infection was higher in the neutropenic diet group (risk ratio [RR] = 1.18, p = 0.007), based upon inclusion of a large observational study. When removed, no differences existed between groups. No differences in mortality rates were observed.

The use of a neutropenic diet is not shown to reduce infection or mortality rates among patients with cancer at risk for neutropenia.

• Limited search
• Limited number of studies included

Questions have been raised regarding whether diet restrictions in neutropenic patients should be recommended or whether the focus should be on patient food choices and relaxing diet restrictions to improve nutritional intake and associated quality of life. Larger randomized controlled trials are needed to provide strong evidence in this area.

Patients were randomly allocated to one of three groups:  (a) massage with lavender essential oil and an inert carrier oil, (b) massage with inert carrier oil, or (c) a control group without massage. Patients receiving weekly massages were not told which oils were used. The two massage groups received a standardized, 30-minute back massage weekly for four weeks. Patients in the control group completed the assessment scales weekly during the study period but did not receive massages. Outcomes were anxiety, aromatherapy, massage, pain, palliative care, and sleep.

• The sample was comprised of 42 patients with cancer.
• Median age was 73 years.

• Three specialist palliative care units
• South Thames region, United Kingdom

The study was a randomized, controlled trial.

• Visual analog scale (VAS) of pain intensity
• Modified Tursky Pain Descriptors Scale
• Verran and Snyder-Halpern Sleep Scale (VSH)
• Hospital Anxiety and Depression Scale (HADS)
• Rotterdam Symptom Checklist (RSCL)

No significant long-term benefits of aromatherapy or massage were demonstrated in terms of improving pain control, anxiety, or quality of life (QOL). Sleep scores improved significantly in the massage and the combined massage groups.

• Recruitment to the study was slow.
• Sample sizes were smaller than planned.
• The poor performance status and fatigue experienced by many patients made it difficult for them to complete the questionnaires and attend weekly treatment sessions.
• The study had a relatively high attrition rate (14%).
• Massage therapists were unable to tailor the treatment to individual patients, which may have undermined its true effect.

Participants were randomly allocated to receive weekly massages with either lavender (aromatherapy group), an inert carrier oil (massage group), or no intervention. The two massage groups received a 30-minute back massage weekly for four weeks. Scales were completed the week before the first treatment and in the week after the last massage.

• N = 42
• KEY DISEASE CHARACTERISTICS: Advanced cancer

• SITE: Multi-site
• LOCATION: Palliative care units in the United Kingdom

• A visual analog scale of pain intensity
• A Modified Tursky Pain Descriptors Scale
• The Verran and Snyder-Halpern Sleep Scale
• The Hospital Anxiety and Depression Scale
• The Rotterdam Symptom Checklist

Significant long-term benefits of aromatherapy or massage were not demonstrated for pain, anxiety, or quality of life. A statistically significant reduction in depression scores was present in the massage group.

• RCT but small sample size
• Predominance of women and older age group limit the ability to generalize.
• The measurement interval allows other variables to affect the scores in this population of low performance and fatigued patients.
• Study recruitment took two years.

To evaluate the effects of massage and aromatherapy on pain scores (primary aim), and to improve sleep, reduce anxiety and depression, and improve overall quality of life (secondary aims), in patients with advanced cancer

The intervention was a course of massage therapy with and without an essential oil (aromatherapy). Patients were randomly assigned to one of three groups:

1. Massage with lavender oil
2. Massage with inert oil
3. Control group

• The sample included 42 patients receiving palliative cancer care.
• The aromatherapy group had 16 patients, the massage group had 13 patients, and the control group had 13 patients.

Major hospitals and hospices in the United Kingdom

A randomized controlled trial design was used.

Hospital Anxiety and Depression Scale (HADS)

There were no statistically significant differences between the groups—aromatherapy or massage—in anxiety reduction (p = 0.95–1.0).

• Sample sizes were small.
• The trial demonstrated the difficulty of studying this population. Participants were fatigued, had poor performance statuses, and often could not complete the questionnaires. These factors contributed to the high attrition rate.
• The trial had considerable cost implications in terms of training, nursing time, and equipment.

To determine whether hypnosis, administered before and during a bone marrow procedure, can ameliorate pain and anxiety

Patients were randomized to a group that received standard care or a group that received standard care plus hypnosis just prior to the procedure. Patients learned of their group assignment just before the procedure. In the hypnosis arm, after the local anesthetic was administered, the oncology nurse and physician left the room. A specially trained oncology social worker performed the hypnosis. After 15 minutes, the oncology nurse and physician returned to start the procedure. The social worker continued to deliver the scripted hypnosis until the procedure was completed. In the standard-care arm, the oncology social worker was not present during the procedure. Study outcome measures were obtained immediately before and after the procedure.

• The study was composed of 80 patients with cancer who required bone marrow evaluation.
• In the hypnosis group, mean patient age was 58 years (SD = 14 years); in the standard-care group, mean patient age was 61 years (SD = 14 years).
• The entire sample was 52.5% male and 47.5% female.
• Diagnoses included, among others, leukemia, lymphoma, plasma cell dyscrasias, myelodysplastic syndrome, myleoproliferative disorder, and aplastic anemia.
• Patients were English-speaking, unpaid volunteers undergoing bone marrow aspiration or biopsy. Of all patients, 71% did not take analgesic or anxiolytic medications.

• Single
• Outpatient
• Cancer treatment center associated with Mount Sinai Medical Center, New York City

• Phase of care: diagnostic
• Clinical application: late effects and survivorship

Randomized controlled trial

• Visual analog scales (VASs), to measure pain and anxiety.
  • For pain: Anchors were no pain at the biopsy site versus very severe pain at the biopsy site.
  • For anxiety: Anchors were no anxiety versus very severe anxiety.  
• State-Trait Anxiety Inventory, Trait section, to assess whether the two groups were equivalent in terms of chronic levels of anxiety.
• Blood pressure and heart rate before and after the procedure.
• Patient satisfaction with the visit, assessed by means of a seven-step scale of verbal descriptors: very satisfied, pretty satisfied, somewhat satisfied, neutral, somewhat dissatisfied, pretty dissatisfied, or very dissatisfied.

The pain scores were slightly lower for the hypnosis group; however, the difference was not statistically significant (t(78) = 0.916, ns). The reduction in anxiety was substantially greater in the hypnosis group than in the standard-care group, with nonparametric tests showing that the difference was statistically significant (median test, p = 0.026).

Pre-procedure hypnosis was effective in reducing procedure-related anxiety.

• The study had a small sample, with fewer than 100 participants.
• Assessment of pain experience should encompass sensory and affective components of the experience, differences in hypnotherapists, differences in physicians performing the procedure, and differences in cancer type.
• Hypnosis induction was during the interval between administration of local anesthesia and start of the procedure, a period of 15 minutes. Some questioned whether induction was complete in some cases.
• In-depth training is needed to implement this intervention; in this study, the intervention was implemented by a mental health expert.

Hypnosis may be an effective intervention to reduce procedure-related anxiety. Although not demonstrated in this study, hypnosis has been shown to be effective in reducing procedure-related acute pain. Nurses can advocate for use of hypnosis to benefit appropriate patients. Provision of this intervention requires an appropriately trained and educated provider.

The purpose of the article was to summarize the evidence on the effectiveness of antibiotic-based catheter-lock solutions as compared to heparin-lock solutions to prevent catheter-related blood stream infections (CRBSI) in all patients with long-term intermittent use of central venous catheters (CVCs).

Medline and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched.

Trials that were included were planned as randomized, controlled trials, quasi-randomized trials or systematic reviews/meta-analyses of randomized or quasi-randomized trials, or published as an article. Trials were also included if the effects of one or more preventative antibiotic-based lock solutions were studied in patients with CVCs for intermittent use, and the presentation of sufficient data for calculating risks of CRBSI in the treatment and control group was examined.

No exclusion criteria were specified.
 

Twenty-three total references were retrieved.

Two reviewers independently assessed trial quality using the following components: concealment of allocation, blinding during treatment and at outcome assessment, description of drop-outs, and analysis. Only trial data related to the topic of the review were considered.

The included trials were flawed due to shortcomings that could have introduced bias, as only 2 of 16 trails clearly prevent performance bias and, in eight of those trials, methods of blinding were unclear. Nine  trials had unclear allocation concealment and only one trial performed analysis by intention to treat. Baseline comparability of groups did not differ. Design and methodology of included studies were sufficient to analyze and pool data.
 

• Sixteen studies were included in the final review.
• 1,383 catheter days were included from 532 patients with cancer (261 were children).
• Catheter days across all included studies ranged from 14–80.
• Key sample characteristics were not specified.

• The phase of care was active treatment
• Applications were for late effects, survivorship, and pediatrics

Overall, it could not be determined which antibiotic-based lock solution is most effective in reducing CRBSI. Only two small trials compared different antibiotics head-to-head. In hemodialysis patients, there was a significant benefit in favor of the antibiotic-based solutions in patients with cuffed or tunneled catheters.  In pediatric oncology patients, there was a small but statistically significant benefit of the antibiotic-based lock solutions in the prevention of BSI (not CRBSI). There was an overlap of 42 elderly patients between two trials. Vancomycin-containing lock or flush solutions are effective in reducing the risk of BSI in patients with cancer. One trial also demonstrated a significant reduction of gram-positive CRBSI, using vancomycin flush solutions in pediatric patients with cancer. 

• The studies should be interpreted with caution as all had a small number of patients.
• There was a difference in solutions that were flushed into the bloodstream and lock solutions, and these were not differentiated in this review.  

Although some results seemed promising, these should be interpreted with care, especially in patients with cancer. There was no differentiation made between BSI and CRBSI, which could be complicated in interpreting the results. There also is a small sampling in regard to patients with cancer, as there were only six oncology trials included in the review. There are no real indications that the use of antibiotic-based lock solutions could prevent catheter-related infections, and it is not possible to determine which antibiotic-based lock solution is most effective. There is the risk of bacterial antibiotic resistance when using broad spectrum antibiotics for locking solutions. This should be weighed against the benefit of locking or flushing solutions.

GSH has high affinity for heavy metals, so the researchers postulated that it may reduce the toxic effects of cisplatin. Early clinical studies suggest that GSH provides neuroprotection.

151 women with advanced ovarian cancer were randomized to receive cisplatin with or without GSH 3 g/m² in 200 cc of normal saline or cisplatin and a placebo-infusion of 200 cc of normal saline administered over 20 minutes immediately before cisplatin administration. Randomized in double-blind fashion to cisplatin 100 mg/m² plus 3 g/m² GSH in 200 cc normal saline or a placebo infusion of 200 cc normal saline every three weeks for six cycles. Seventy-seven women received the placebo infusion and 74 received GSH.

151 women with ovarian cancer

Multicenter

The study had a randomized, placebo-controlled, clinical trial with parallel group design.

• Audiograms and neurologic examinations were conducted at baseline and after three and six cycles of chemotherapy.
• Four of 10 centers measured quality of life with the Hospital Anxiety and Depression Scale.
• Anemia, leukopenia, thrombocytopenia, neurohearing, nephrotoxicity, peripheral neuropathy, and nausea and vomiting were assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events and World Health Organization toxicity scales.

The addition of GSH to cisplatin chemotherapy allowed the full six cycles to be administered to more patients (58%) as compared to those who received cisplatin alone (39%). Women in the GSH arm had a statistically significant rise in weight of 2 kg over the study period (p = 0.01). Women in the study who received GSH reported an improvement in quality of life during cisplatin chemotherapy. Significant difference in the reduction of creatinine clearance for GSH treated group as compared to the control group (74% versus 62%). Significant improvement in depression, emesis, peripheral neurotoxicity, hair loss, shortness of breath, and difficulty concentrating as measured by the Hospital Anxiety and Depression scale. Those who received GSH were significantly more able to undertake housekeeping and shopping. The trend was toward a better outcome in GSH-treated group (p = 0.25).

• The study did not clearly identify what the neurologic examination involved.
• The study has substantial between-center differences which may make findings less interpretable.