To determine the efficacy of zinc sulfate supplements in reducing oral mucositis in patients with head and neck cancer

Patients were randomized to receive zinc supplementation or placebo during radiation therapy. Patients received 50 mg zinc sulfate daily at meal times in a syrup form or an identical placebo syrup. All patients received visous Xylocaine^® and analgesics as considered necessary. The primary study end point was to evaluate the frequency of development of greater than grade 2 mucositis and pharyngitis.

• N = 139   
• MEAN AGE = 62 years
• MALES: 86.8%, FEMALES: 13.2%
• KEY DISEASE CHARACTERISTICS: 53% had stage 3–4 disease, 85% were smokers, and 76% used alcohol

• SITE: Single site  
• SETTING TYPE: Not specified   
• LOCATION: Thailand

• PHASE OF CARE: Active antitumor treatment

• Double-blind, placebo-controlled

• National Cancer Institute Common Toxicity Criteria version 2
• Visual analog scale for pain scoring

There was no difference between groups in proportion with greater than grade 2 mucositis. Seventeen percent in the placebo group and 23% in the zinc sulfate group developed grade 3 mucositis. There were no significant group differences in pain severity.

Zinc sulfate supplementation during radiation therapy for head and neck cancer did not produce any benefit in reducing or relieving symptoms of oral mucositis.

• Measurement/methods not well described
• Other limitations/explanation: Timing of pain rating and data used were not well described.

There was no benefit of zinc supplementation for the prevention and management of oral mucositis in this group of patients.

To examine the efficacy and safety of glutamine to reduce vincristine-induced neuropathy in children and adolescents

Patients expected to receive a cumulative dose of 6 mg/m² over a 30-week period were randomized to receive glutamine or placebo. Participants' families were contacted weekly to answer questions and monitor compliance and monitor adverse effects. Study medications were provided in a powder formulation to be mixed in juice for oral administration. Study measures were obtained at baseline, after 21 days, and on day 42 after a wash-out period. Glutamine was given at a dose of 6 g/m² twice daily up to a maximum dose of 10 g.

• N = 49   
• MEDIAN AGE = 11 years
• AGE RANGE = 4–19 years
• MALES: 48.2%, FEMALES: 51.8%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Hematologic malignancies; acute lymphoblastic leukemia was the most common.
• OTHER KEY SAMPLE CHARACTERISTICS: More than 50% were Hispanic.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: New York

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

Double-blind, placebo-controlled, randomized, controlled trial

• Common Terminology Criteria for Adverse Events (CTCAE), version 3.0
• Purdue Pegboard test
• Grip strength
• Symbol Digit Modalities Test
• Pedatric quality of life

Seventy-eight percent developed peripheral neuropathy as defined by CTCAE. There was no correlation between CTCAE and other testing results. A higher number of those receiving placebo had increased CTCAE sensory neuropathy scores compared to those on glutamine (p = 0.02) on day 21. There was no difference between groups on day 42. There were no differences between groups in motor neuropathy scores.

Glutamine had a protective effect for sensory neuropathy in this study. Varied measures for peripheral neuropathy were not correlated, pointing to the need for ongoing research to identify the most valid and reliable measures for assessment.

• Small sample (< 100)
• Baseline sample/group differences of import
• The glutamine group had lower sensory neuropathy scores at baseline.

There have been mixed findings regarding the benefits of glutamine for the prevention of chemotherapy-induced peripheral neuropathy. This study demonstrated some benefit, although limited by sample size. Ongoing research is needed for determination of any potential role of glutamine for the prevention of neuropathy with agents associated with this side effect.

To determine the effect of changing needleless connectors (NC) frequently on central line–associated bloodstream infections (CLABSI) rates

The study was conducted among pediatric bone marrow transplantation (BMT) recipients and the oncology unit population, and was conducted and evaluated in three interrupted times. In time period 1, the healthcare professionals changed needleless connectors (NC) every 96 hours regardless of the infusion of blood products, lipids/total parenteral nutrition (TPN), and IV amphotericin B. In period 2, they changed NC every 24 hours only with blood products and lipids/TPN. In period 3, they changed the NC every 96 hours regardless of infusate. Moreover, they collected data on central venous catheter (CVC) bundle access, which involves hand hygiene and cleaning connectors with alcohol for 15 seconds. In a different general oncology unit, healthcare workers change connectors every 24 hours across all study periods. 

• N = None given, 44 CLABSI episodes    
• AGE = Pediatric, no age specified
• MALES: Not specified, FEMALES: Not specified
• KEY DISEASE CHARACTERISTICS: Stem cell transplantation recipients and patients with cancer 
• OTHER KEY SAMPLE CHARACTERISTICS: Blood product transfusion, lipids transfusion, and infusion of IV liposomal amphotericin B

• SITE: Multi-site    
• SETTING TYPE: Inpatient    
• LOCATION: Boston, MA

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

• Retrospective cohort time series analysis

• Center for Disease Control (CDC) and the National Healthcare Safety Network (NHSN) guidelines for central venous catheter (CVC) care 
• CLABSI rate was number of infections per 1,000 central-line days
• CLABSI defined per National Healthcare Safety Network definitions

According to CDC and NHSN guidelines, NC should be changed every 24 hours, but this study suggests that frequent NC changes may increase the rate of CLABSI.

• Small sample (< 100)
• Risk of bias (sample characteristics)
• Measurement validity/reliability questionable
• Sample size was not described appropriately.
• Method of data collection and measurement for unit adherence to catheter care bundle guidelines was not described.

Nurses should follow CVC access bundle (i.e., hand hygiene, cleaning the NC with alcohol for 15 seconds) while handling CVCs. In addition, organizational policies may help decrease CLABSI and other infections among BMT recipients and patients with cancer as they are at a very high risk of acquiring bloodstream infections. The appropriate frequency of changing all IV line components is unclear. Additional research is needed to establish the evidence base for some infection prevention guidelines.

RESOURCE TYPE: Consensus-based guideline

PHASE OF CARE: Multiple phases of care

Not provided

The influenza vaccine is recommended in patients with active malignancy undergoing chemotherapy, patients with acute leukemia after chemotherapy, and all patients during maintenance treatment. Insufficient evidence exists for acyclovir prophylaxis for preventing herpes simplex virus (HSV), Epstein-Barr virus (EBV), and varicella-zoster virus (VZV) reactivation. The guidelines provide an algorithm for hepatitis B virus (HBV) reactivation prophylaxis, including screening, monitoring, and intervention based on positive HSs antigen and units of HBc DNA identified. Primary antiviral prophylaxis with nucleoside analogues for hepatitis B are effective in reducing risk. The guidelines identify risk factors for HBV reactivation:

• Treatment with anthracyclines
• Treatment with steroids (greater than 10–20 mg daily or equivalent for four weeks or more)
• Treatment with monoclonal antibodies
• Breast cancer or malignant lymphoma

• Limited search documentation

These guideline add to the body of evidence recommending influenza vaccination in patients undergoing cancer treatment. This guideline does not recommend other routine prophylaxis and does provide suggestions regarding specific agents for prophylaxis according to individual patient risk factors based on disease, history, and treatment type.

To quantify immediate and short-term benefits and harms of gabapentin in hospice and palliative care patients

Data recorded at baseline, day 7, and day 21 were obtained from participating sites for patients receiving gabapentin for neuropathic pain. Benefits and harms factors were predefined by an expert committee. Overall benefit was defined as a one-point reduction in the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), and harms were attributed to gabapentin if the day 7 data showed higher CTCAE scores. The Naranjo Scale was used to determine attribution to the drug itself in scores above three.

• N = 127   
• MEDIAN AGE = 68 years
• AGE RANGE = 26–89 years
• MALES: 80%, FEMALES: 20%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: 95.3% of patients had cancer.

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

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

• Prospective cohort

• National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE)
• Charlson Comorbidity Index (CCI)

Data were available at day 21 in 69 patients. Of these, 78% had improvement in their pain and 32% had associated harms. The most frequent harms were somnolence, cognitive disturbance, and fatigue. Twenty-nine patients had medication stopped or dosages reduced. The total number of patients who had benefit without harms was 9.4%. Regression analysis showed higher odds ratio of harm associated with comorbidities (p = 0.013).

Only 9% of palliative care/hospice patients receiving gabapentin had benefit for pain control without any associated harms.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results 
• Measurement validity/reliability questionable
• Subject withdrawals ≥ 10%
• High missing data
• Other interventions used for pain were not accounted for in the analysis, which could have contributed to harms identified

Gabapentin is a common adjuvant pain medication. Findings from this study suggest that relatively few patients achieve benefits without harms. This study has multiple design and reporting limitations; however, it does raise the question of relative benefits of this medication in the hospice/palliative care population. Further well designed research to further evaluation risk/benefits of gabapentin are warranted. Nurses need to be aware of potential harms from various medications and monitor patient responses for appropriate care to identify and reduce harms. Potential for harm from gabapentin may be of greater concern among patients with multiple comorbid conditions.

To determine if a nutritional supplement taken by patients with advanced non-small cell lung cancer receiving paclitaxel with cisplantin/carboplatin chemotherapy can improve body composition, fatigue, health-related quality of life (HRQOL), and overall survival.

The patients were randomized to isocaloric diet or isocaloric diet plus eicosapentaenoic-acid (EPA) supplement ProSure^®.  Evaluations were conducted at baseline, after the first chemotherapy cycle, and after the second chemotherapy cycle.

• N = 92  
• AGE: 44-72 years
• MALES: control group 23 (50%), intervention group 20 (43.5%); FEMALES: control group 23 (50%), intervention group 26 (56.5%)
• KEY DISEASE CHARACTERISTICS: Stage IIIb and IV non-small cell lung cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Life expectancy greater than 12 weeks. All patients receiving chemotherapy with paclitaxel and cisplatin or carboplatin every three weeks for two cycles.

• SITE: Single site    
• SETTING TYPE: Other    
• LOCATION: Mexico

PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trial

• Subject Global Assessment (SGA)
• Bodystat Quadscan 4000 multifrequency
• Food frequency questionnaire (FFQ)
• Supplement intake diaries
• Biochemical analysis
• EORTC Quality of Life Core 30 Questionnaire (EORTC-QLQ-C30)
• EORTC QLQ-LC13
• Common Terminology Criteria for Adverse Events (CATCAE)

The ONS-EPA group exhibited significant differences in weight (p = 0.01) and lean body mass (p = 0.01). Significant improvement was also seen in calorie and protein intake (p <  0.001) when the nutritional supplement was included. The ONS-EPA group also exhibited significant improvement in inflammatory markers between time points (p = 0.02 to p = 0.05). In HRQOL, there was significant improvement in global health status between time points for the ONS-EPA group (p = 0.021). Differences were seen between groups in fatigue (p = 0.04), appetite loss (p = 0.05), and neuropathy (p = 0.05)

In this study, ONS-EPA supplementation appears to be effective in improving nutritional status and decreasing side effects (appetite loss) in patients receiving chemotherapy for non-small cell lung cancer.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Findings not generalizable
• Subject withdrawals of 10% or greater 
• Only patients with non-small cell lung cancer were included.
• There was a high rate of attrition in the control group (6 of 46) due to disease trajectory (worsening condition and death)

More studies need to be done with EPA supplementation in this and other cancers.

To determine the effect of ginger and chamomile capsules on chemotherapy-induced nausea and vomiting (CINV)

• N = 65   
• AGE = 20–60 years 
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Single-day chemotherapy, history of vomiting with previous chemotherapy

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Tehran, Iran

PHASE OF CARE: Active antitumor treatment

Randomized, double-blind clinical trial

VAS for frequency and severity of nausea and vomiting

Ginger and chamomile did not affect the intensity of nausea, whereas both had an effect on the frequency of vomiting (p < 0.0001). Ginger also was shown to be have a statistically significant effect on the frequency of nausea (p = 0.006). Neither had an effect on intensity of nausea.

Ginger and chamomile may have some benefit as adjuncts to antiemetics for the prevention of CINV. Additional research is needed to evaluate these.

• Small sample (< 100)
• Findings not generalizable
• Subject withdrawals ≥ 10%

Ginger may be beneficial in CINV, but ongoing studies are needed.

To compare the efficacy of two medication schemes for the management of pain after gynecologic surgery

Consecutive patients were randomly assigned to two groups. Group 1 received, on the day of surgery, 1 mg morphine/10 kg body mass subcutaneously (SC) every four hours. After surgery Group 1 received 1 g acetaminophen IV every six hours and 500 mg naproxen per rectum every 12 hours daily. Group 2 received 1 mg morphine/10 kg body mass SC every 4 hours, 1 g metamizol IV every 6 hours, and 500 mg naproxen per rectum every 12 hours. For all patients, in instances of pain rated 5 or more, an additional 100 mg of ketoprofen IV was administered. Pain was rated throughout hospitalization.

• The sample was composed of 128 patients.
• Mean patient age was 68 years; the age range of patients was 42–82 years.
• All patients were female.
• All patients underwent operations of category III or IV, a classification indicating extensive tissue injury and significant postoperative acute pain.

• Single site
• Inpatient
• Poland

Randomized parallel group

Numeric pain rating scale of  0–10

• Patients in group 1 had significantly less pain than did the other group (p < 0.05).
• On the operative day, 34% of group 1 patients required rescue medication compared to 52% of patients in group 2.
• By postoperative day 3, 3.12% of group 1 patients required rescue medication compared to 4.69% in group 2.
• During the entire postoperative period, no side effects were associated with either treatment regimen.

For the management of postoperative pain following gynecologic surgery, the combination of morphine, acetaminophen, ketoprofen, and metamizol as used in this study was more effective than the combination of morphine, metamizol, and ketoprofen.

• Authors did not report the anesthesia regimen used.
• Authors did not analyze the demographic differences or other factors, such as type of surgery, that could impact pain scores.

This study describes a perioperative pain management regimen that appears to have decreased the pain of patients who underwent  extensive gynecologic surgery. Note, however, that the more effective regimen did not provide complete control for more than 30% of patients on the day of surgery and for more than 15% on the first postoperative day. This study adds to the growing research regarding  perioperative adjuvant medications for acute pain control.

To study the analgesic effect of honey for mucositis-related pain in patients with head and neck cancer receiving chemotherapy and radiation therapy

Patients were randomized to honey treatment and control groups. Patients were given 20 ml of honey 15 minutes before, 15 minutes after, and six hours after radiation treatment (RT). They were instructed to rinse the honey on the oral mucosa then swallow slowly to smear it on oral and pharyngeal mucosa. All patients also were told to gargle salt soda and benzydamine alternatively every three hours throughout RT and for three months after completion. Pain scores were obtained weekly. As needed, IV antibiotics were given for positive oral cultures, steroids were given for grade 3 mucositis, and gentian violet was applied for moist desquamation.

• N = 69  
• MEAN AGE = 53.4 years
• MALES: 52.2%, FEMALES: 47.8%
• KEY DISEASE CHARACTERISTICS: All participants had locally advanced head and neck cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: In both groups, 72% pf participants had T3, T4, and stage 4A disease. Both groups received a mean RT dose of 69.76 Gy, and the majority received six cycles of cisplatin.

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

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Faces Visual Analog Scale (VAS) for pain (0–10 scale)

In the experimental group, pain scores ranged from 1.83–3.08, and in the control group, scores ranged from 1.36–6.54 across the seven weeks of RT. From week 2 onward, the mean pain score in the experimental group was lower than that of control group (p = 0.000). After RT, mean scores ranged from 1.36–0.36 in patients using honey and from 4.87–1.57 in controls (p < 0.002). Some patients experiened dyspepsia, nausea, and vomiting with honey.

The use of honey was associated with less pain from mucositis in this study.

• Small sample (< 100)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results 
• Measurement validity/reliability questionable
• Other limitations/explanation: There was no mention of any other analgesic use. Compliance with oral protocols was not discussed. No information was provided regarding the use of steroids or antibiotics as outlined in the study protocol.

The findings of this study suggested that honey may be beneficial in reducing pain associated with mucositis caused by chemoradiation therapy in patients with head and neck cancer. Honey is known to have antioxidant and anti-inflammatory properties, which may be helpful for this purpose. Honey is a low-risk intervention, and based on this study's findings, additional well-designed research in larger samples is warranted.

To review the evidence for approaches to prevention and management of radiodermatitis

Databases used were MEDLINE, PubMed, and Cochrane Library. Keywords searched were skin reactions, radiation, radiation adverse effects, erythema, desquamation, and radiodermatitis. Studies were included in the review they

• Were published reports or abstracts from January 1, 2000 to October 1, 2008.
• Reported the method of skin grading.

Studies were excluded from the review if they were letters, comments, editorials, case reports, practice guidelines, systematic reviews, or meta-analyses.
 

The total references retrieved and the quality rating approach were not reported.
 

• Thirty-nine trials were included in the review.
• Patients were receiving radiation therapy.

Patients were undergoing active antitumor treatment.

Washing practice, topical corticosteroids, aloe vera, biafine, hyauronidase-based creams, sucralfate, miscellaneous creams, Amifostine, oral enzymes, pentosifylline, dressings, non-steroidal topical cream, topical colony-stimulating factors supplements, and mode of radiation delivery were reviewed. Other agents studied included beladonna 7CH and a Chinese remedy, lian bai liquid.

There is lack of support for Biafine use. There is some evidence to suggest that topical corticosteroids may be beneficial. Evidence for non-steroidal topical agents is conflicting. Evidence does not support use of Aloe Vera or sucralfate cream. Some evidence to suggest that light-emitting diode, pentoxifylline, sliver-leaf dressings, washing, zinc supplements and intensity-modulated radiation therapy are beneficial.

• The trials were small and had numerous design and reporting limitations.
• Secondary trials evaluated the same agent or treatment, making comparison very difficult.

Further research is needed in this area. Intervention goals, prevention or treatment need to be clear and further work is needed to develop and validate more sensitive assessment tools. Further work is also needed to evaluate differences in risk based on anatomical sites.