To determine if honey swished, held, and swallowed reduced the severity of radiation-induced oral mucositis (ROM)

Honey and placebo gel were provided in 5 mL packets to be taken after salt/bicarbonate oral rinses four times a day after meals and after radiotherapy or approximately the same time on non-treatment days. Participants were to pour the product into their mouth, circulate it for 30 seconds, and swallow. Subjects were instructed not to eat, drink, or rinse their mouth for 30 minutes following swallowing the honey or placebo. Treatment started on the first day of radiation and continued for seven days following the last radiation treatment. Visits to the oral oncology/dentistry department were scheduled weekly until mucositis was resolved. During each visit, an oral examination was done for mucositis severity rating, a brief questionnaire was conducted, and weight was obtained. Unused treatment medication was collected at the last visit to measure compliance.

• N = 81  
• MEAN AGE: Honey arm: 56.8 years, placebo arm: 59.5 years
• MALES: Honey arm: 81%, placebo arm: 84%; FEMALES: Honey arm: 19%, placebo arm: 16%
• KEY DISEASE CHARACTERISTICS: Head and neck cancer—hypopharynx, larynx, nasopharynx, oral cavity, oropharynx
• OTHER KEY SAMPLE CHARACTERISTICS: Radiation therapy of ≥ 50 Gy; 62% had concurrent chemotherapy; Caucasian

• SITE: Multi-site 
• SETTING TYPE: Outpatient 
• LOCATION: Vancouver and Sudbury, Canada

• PHASE OF CARE: Active antitumor treatment

• Double-blind, randomized, placebo-controlled, investigator-initiated

• Sialometry and mucositis severity scales from the Radiation Therapy Oncology Group (RTOG)
• World Health Organization (WHO) Oral Mucositis Scale

There were no differences found between the treatment and placebo arms for any of the three outcome assessment scales of mucositis for quality of life, symptom scores, or sialometry. Both the honey (35%) and placebo (43%) groups had lower than expected rates of ≥ grade 3 mucositis.

The honey, when used as directed in this study, did not significantly decrease the severity of ROM. The treatment and placebo groups were well matched, and the blinding was effective. The dropout rate was high (honey: 57%, placebo: 52%, those receiving concurrent chemotherapy: 59%). Most of the dropouts were related to nausea. Patients receiving radiation only had a dropout rate of 48%. Only 48 patients had complete weekly mucositis assessments.

• Small sample (< 100)
• Subject withdrawals ≥ 10%
• Other limitations/explanation: The initial plan for the study was to enroll 180 subjects. The study was terminated at planned interim analysis when 106 patients had been recruited.

There have been varied outcomes in studies of honey for the treatment of mucositis. Differences in methodology could explain at least part of the variability. In this study, the subjects tolerated the honey poorly because of nausea and gagging, and a couple patients experienced a burning sensation. The authors referenced a study from New Zealand in which a honey mouthwash was used because undiluted honey caused extreme nausea, vomiting, and stinging sensations. Potential reasons for the lack of efficacy seen could be that the mucositis tools may not have had adequate sensitivity to reveal any clinical difference between or the osmotic effect of the honey and placebo. Also, Christian areas like Canada, New Zealand, and Great Britain, where honey does not have any special significance, may differ from Muslim areas that have the Koran’s references to honey’s healing powers.

To assess whether anesthetizing the skin with buffered lidocaine before performing breast lymphoscintigraphy reduces pain

Patients were randomly assigned to the control group without lidocaine or the experimental group in which the procedure was preceded by lidocaine injection. Patients were asked to rate their pain levels before and immediately after injections for the procedure. All patients received two injections and were were masked from knowing whether one of them was lidocaine.

• N = 49   
• MEAN AGE = 61.4 years
• AGE RANGE = 34–87 years
• FEMALES: 100%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Breast cancer

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Rhode Island

• PHASE OF CARE: Diagnostic

• Randomized, controlled trial

• 0–10 numeric pain rating scale

No difference in preprocedure pain levels existed between groups. Those who received lidocaine reported less of an increase in pain postprocedure. No difference in lymph node detection existed between groups.

Administration of local anesthetic prior to breast lymphoscintigraphy was associated with lower pain severity after the procedure.

• Small sample (< 100)
• Risk of bias (no blinding)
• Limited reporting of statistical results and methods

Authors point out that local anesthesia prior to lymphoscintigraphy is not common practice, due to the assumption that any benefit would be outweighed by the pain associated with additional needle sticks. Some patients may feel significant pain during this procedure, and findings from this study suggest an approach to reduce pain with this experience. Authors discuss the findings in terms of the rationale for using a buffered lidocaine solution and implications for practical application and needed lymph node visualization.

To compare the risk of chemotherapy-induced nausea and vomiting (CINV) events for various 5-HT₃ receptor antagonists (RAs) in patients who received moderately (MEC) or highly emetogenic chemotherapy (HEC) by evaluating hospital or emergency department (ED) admissions

Patients with breast cancer who received adjuvant chemotherapy with cyclophosphamide within four months after surgery and patients with lung cancer who were initiated on carboplatin or cisplatin-based chemotherapy within the study time frame (January 1, 2005, through June 20, 2008) were identified using the PharMetrics database. CINV events associated with hospital and ED admissions were extracted using claims with ICD-9-CM codes for nausea, vomiting, or dehydration.  

In each cohort, patients were stratified into two groups, one consisting of patients initiated and maintained on palonosetron as the only 5-HT₃ RA antiemetic, the other with patients who were initiated on one of the older 5-HT₃ RAs and maintained on the same agent or alternated throughout the study duration between the older 5-HT₃ RA and palonosetron, either as single agents or in combinations. The use of aprepitant and dexamethasone was used in both cohorts.

The study consisted of 4,868 patients with breast cancer and 7,106 patients with lung cancer (5,414 treated with carboplatin, 1,692 treated with cisplatin).

The median age in all cohorts ranged from 53–65 years.

The breast cancer cohort was 100% female.

The carboplatin-treated lung cancer cohort was 46.5% female and 53.5% male.

The cisplatin-treated lung cancer cohort was 40.3% female and 59.7% male.

The patients in the breast cancer and carboplatin-treated lung cancer cohorts were considered to be treated with moderately emetogenic chemotherapy (MEC). The cisplatin-lung cancer cohort was considered to be treated with highly emetogenic chemotherapy (HEC). The authors did control for differences in age, Charlson comorbidity index (CCI) score, gender (lung cancer cohorts), cyclophosphamide dose per square meter per cycle (breast cancer cohort), and cisplatin and carboplatin treatment days (lung cancer cohorts).

Site and setting type was not indicated. Data was analyzed using pooled patient information from PharMetrics database.

• Patients were in active treatment.
• This study has application to elderly care.

This was a retrospective data analysis.

• Patient comorbidities for the six-month baseline period prior to the study index date were calculated using the CCI.
• The study population was selected using the PharMetrics database.

Based on the results presented by the authors, patients with breast or lung cancer treated with HEC or MEC, when initiated and maintained on palonosetron throughout chemotherapy, experienced significantly reduced risk of hospital- and ED-associated CINV events compared to patients who received other 5-HT₃ RA-based regimens. In all three cohorts, the p value was < 0.0001. The results of the data analysis do show superiority of palensetron in reducing such events, but a number of variables and limitations may impact the results.

Antiemetic regimens containing palonosetron may be more effective in reducing severe, uncontrolled CINV than other 5-HT₃ agents; however, firm conclusions cannot be drawn because of study design limitations and risks of bias.

• No appropriate control group was included.
• The lead author was a paid consultant to Easai, Inc., the marketer of oalonosetron in the USA. Easai, Inc was also the sponsor of the study. The other authors are employees of Easai, Inc. This has the potential to lead to further selection bias of the patient population.
• A large variable that was unaccounted for was the varying doses of chemotherapy. 
  • The average dose of cyclophosphomide used in the breast cancer cohort was on the lower end of dosing. Cyclophosphomide is typically given in a dose of 300-600 mg/m² as adjuvant therapy to patients with breast cancer depending on the selected regimen. The average dose used in patients in this study was 414 mg.
  • Only 19% of patients treated with cisplatin were treated with guideline recommended triplet antiemetic therapy.
• Though an effort was made to control for comorbid conditions in the cohorts, variables such as differences in chemotherapy doses were not a part of the analysis.

The study is helpful because it was an analysis of a large group of patients. It also seeks to provide meaningful conclusions for patients. Although identifying interventions for the reduction of CINV in patients can aid in quality of life and ability to receive treatment in a timely manner, looking at the significance of CINV reduction in preventing serious events such as ED visits or hospitalizations is also important.

Potential patients were referred to a highly experienced palliative care physiotherapist clinic. Patients were seen by the physiotherapist at three sessions, each lasting as long as 90 minutes. Intervention consisted of breathing retraining, simple relaxation techniques, activity pacing, and psychosocial support.

The study reported on a sample of 30 patients with non-small cell lung cancer, small cell lung cancer, or mesothelioma (pleural effusion excluded) who experienced breathlessness not less than one month after completion of any active treatment; 68 patients were referred, 17 did not fulfill the criteria, 4 declined, and 2 were too ill to treat. Forty-five entered the study, and 15 deteriorated or died before completion. The median age was 71 years; 24 were men, and 6 were women.

The study was conducted in an outpatient clinic in the United Kingdom.

• Uncontrolled study
• Nonrandomized
• Referred patients

Tools completed by the therapist at each visit

• Current Respiratory Symptoms—adapted from two scales (Medical Research Council and Respiratory Symptom Questionnaire); patients were asked to score how often they were breathless, ranging from most or all the time to less than once a week
• Functional Capacity Scale adapted from above tools; patients scored their ability to climb hills or stairs without breathlessness to experiencing breathlessness at rest
• Sputum production scale

Self-assessment tools completed by patients at baseline and following the intervention (four to six weeks)

• Rotterdam symptom checklist
• VAS: breathing at worst and at best in the proceeding 24 hours as well as distress caused by breathlessness (0–10 where 10 = extreme distress)
• Things that improve breathing (in the clinic, patients were taught techniques and coping strategies likely to improve their feeling of breathlessness); the patients were asked to score 20 helpful strategies at baseline and at the last visit on a VAS (1–10 where 10 = extremely helpful).
• Quality-of-life questionnaire
• Therapist recorded patients’ verbatim comments in free narrative form and added own comments.

Statistical analysis of baseline data on 12 patients who were unable to complete the study compared to 30 patients who completed the study showed significantly lower Functional Capacity Scale scores (p = 0.04) at first assessment. For patients who completed the study, a highly significant (p < 0.001) change in frequency of reported breathlessness was found. A decrease existed in reported breathlessness, from 97% reporting it at least once or twice a day, 73% several times a day, and 27% most of the time to 27% experiencing dyspnea several times a day and 3% most of the time at the final visit. A statistically significant change was seen between study entry and completion (p < 0.001) in functional capacity. Overall, 19 improved function, 9 remained stable, and 2 deteriorated.

No change in sputum production was found.

Rotterdam symptom checklist:

Significant changes were seen in the physical distress scores and activity levels (no p value given). Change in psychological distress scores were borderline.

Degree of breathlessness:

Significant improvement (p < 0.001) was found in all three parameters—breathing at best, breathing at worst, and distress caused by breathlessness.

Intervention strategies:

On study entry, patients were asked to score 20 strategies that were likely to improve feelings of breathlessness. Examples of interventions include activity pacing, abdominal breathing, slowing down, relaxation exercises, not worrying, accepting the situation, and positive thinking.

Patients reported that all of the techniques they learned were helpful and improved breathlessness. Patients reported that massage and the use of bronchodilator drugs were not helpful.

Quality of life:

Significant improvements were seen in decrease in time spent lying down (p = 0.02), improved bodily strength (p = 0.03), and increase in things that made patients happy (p = 0.04). Patients reported an increased ability to do things and improved quality of life.

Qualitative data:

The following themes were extracted from the narrative data: difficulty adjusting, issues around death, effects of treatments, and therapies’ impact on daily life.

The study was uncontrolled. A major limitation of the study is that it is a nonrandomized trial of referred patients. Impossible to know are the implied bias in patients who were referred or the true effect of the intervention without a control group. It was based on a prior study, with the time period shortened because of the loss of patients in the earlier study’s sample.

To investigate the effect of hangeshashinto to relieve chemotherapy-induced oral mucositis

Patients were to gargle three times daily with 2.5 g hangeshashinto (TJ-14) in 50 ml of water and rinse the oral cavity for about five seconds. Patients were instructed not to swallow it and not eat or drink anything for 30 minutes. Patients who received the intervention were compared to patients who did not. Measurements were done at baseline and at eight weeks.

• N = 57, only 12 received the intervention  
• MEAN AGE = 59.5 years
• AGE RANGE = 40–75 years
• MALES: 93%, FEMALES: 7%
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Oropharyngeal and hypopharyngeal cancers; total radiation dose of 70 Gy and cisplatin
• OTHER KEY SAMPLE CHARACTERISTICS: The majority of patients had stage IV disease.

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

• Nonrandomized two-group prospective study

• Common Terminology Criteria for Adverse Events (CTCAE)
• Bioimpedance for body composition
• Measurement of food intake

No significant differences in maximum grade of mucositis or daily morphine dose existed. Oral intake and body weight were improved in those who took the hangeshashinto, but no comparative information on this measure from the control group was provided. The radiation completion rate was higher in the treated group (p = 0.045). Twenty-five percent of patients would not continue to use the gargle because of the bitter taste, nausea, vomiting, and refusal to wait 30 minutes before eating.

The findings do not show a benefit of hangeshashinto gargle on mucositis severity or associated pain.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Subject withdrawals ≥ 10%  
• Very few patients actually received the intervention. Little comparative information is provided. The timing of measurement was not clearly reported.

This study did not show the effectiveness of hangeshashinto to prevent or reduce the severity of oral mucositis in patients with head and neck cancer receiving combined radiation and chemotherapy. Multiple report limitations are noted.

To evaluate whether mixing dexamethasone with an oxaliplatin intravenous infusion can reduce venous pain associated with the infusion

Patients receiving either ​capecitabine and oxaliplatin (CapeOX) or S-1 plus oxaliplatin (SOX) chemotherapy were randomly assigned to the experimental or control groups. In the experimental group, 1.65 mg of dexamethasone was mixed with a 5% glucose solution in which 130 mg/m² was dissolved. The resulting mixture was infused over two hours. Those in the control group received the same infusion without the addition of dexamethasone. Patients were evaluated over four treatment cycles.

• N = 48
• MEAN AGE = 66 years (range = 46–81 years)
• MALES: 79%, FEMALES: 21%
• KEY DISEASE CHARACTERISTICS: All patients had colorectal cancers and were receiving regimens containing oxaliplatin.

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Verbal Rating Scale (VRS) for pain
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0

The incidence of grade 2 or greater venous pain based on the CTCAE was 33.3% in patients receiving steroids and 56% in those who did not (based on only 22 patients). The relative risk of venous pain was 0.60 (95% CI, 0.31–1.16).

Patients who received dexamethasone with oxaliplatin tended to experience less venous pain.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement validity/reliability questionable
• Other limitations/explanation: The study was slightly underpowered.

In this study, the incidence of severe venous pain during oxaliplatin infusion was lower with the addition of dexamethasone to the infusion. It has been suggested that mixing dexamethasone may be an option for patients with venous pain or phlebitis caused by chemotherapy. Additional research confirming the efficacy of this approach is needed.

To evaluate the effectiveness of small group neurocognitive training to improve cognitive impairment in patients with brain tumors

Pre- and post-intervention cognitive testing was performed. The 10-week-long intervention consisted of 90-minute weekly group sessions of holistic mnemonic training, which included exercises to train perception, concentration, attention, memory, retentiveness, verbal memory, and creativity.

• A total of 11 patients were enrolled in the study.
• Participants' ages ranged from 23–73 years (median = 50 years).
• The sample was 64% male and 36% female.
• Patients had been diagnosed with glioblastoma multiforme (n = 6) or anaplastic gliomas (n = 5).
• Time since initial diagnosis ranged from 10–42 months (median = 15 months).
• Every participant had received treatment that included surgery, radiation therapy, and adjuvant chemotherapy with temozolomide. One subject also received hydroxyurea and imatinib in addition to temozolomide.
• Three subjects had tumor recurrence 3–28 months prior to study participation; none underwent additional surgery, and further treatment with radiation or chemotherapy was not provided. 
• All subjects were taking antiepileptic medications; however a variety of drugs were used. 
• Subjects varied in professional and educational background, but actual information was not provided.

• Single site
• Outpatient setting
• Vienna, Austria

• Patients were undergoing long-term follow-up.
• The study has applicability for late effects and survivorship.

Pilot study with pre-/post-test design

• Trail Making Test–A (TMT-A)    
• Trail Making Test–B (TMT-B)
• Hopkins Verbal Learning Test (HVLT)
• Controlled Oral Word Association Test (COWAT)

Although comparison of mean group differences found improvement in all neuropsychological tests, separate dependent t-tests revealed statistically significant improvement only in verbal memory total learning (p < 0.05) as measured by the HVLT. Significant improvement was not seen in verbal memory delayed recall (p = 0.11) as measured by the HVLT, psychomotor speed (p = 0.22) as measured by the TMT-A, sustained attention (p = 0.17) as measured by the TMT-B, or verbal fluency (p = 0.29) as measured by the COWAT.

Significant improvement was found in verbal memory (total learning). However, it is not possible to distinguish whether the improvement was a benefit of the intervention or resulted from practice effects associated with the repeated measures occurring 12 weeks from baseline. Additionally, any assumptions regarding effectiveness of the intervention would need to be supported by a larger sample with an appropriate comparison control group.

• The sample was small, with less than 30 participants.
• The lack of a comparison control group or randomization limited the generalizability of results and the feasibility of the intervention.

Although neurocognitive training has been suggested as a potential intervention for cognitive impairment, further studies are needed (including feasibility). Effectiveness of this intervention cannot be established based on this pilot study.

• FINAL NUMBER STUDIES INCLUDED = 30
• TOTAL PATIENTS INCLUDED IN REVIEW = Not reported
• KEY SAMPLE CHARACTERISTICS: Chlorhexidine, benzydamine, sodium bicarbonate, granulocyte macrophage colony-stimulating factor, iseganan, sucralfate, and normal saline were reviewed. No sample characteristics were reported.

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Pediatrics and palliative care

None of the mouth rinses were definitely effective in preventing chemotherapy-induced oral mucositis in children. Normal saline had a preventive effect in patients receiving chemotherapy, radiotherapy, and hematopoietic stem cell transplantation, but other studies have shown less efficacy than chlorhexidine or honey with saline. Benzydamine was less effective than chlorhexidine.

There was limited evidence for agents to prevent or manage oral mucositis in children.

• Few studies for any single agent used
• Few data bases used  
• Limited sample information provided  
• No quality of research evaluation

Mouth rinses are an important component to oral care in the prevention of mucositis in pediatric patients receiving chemotherapy. Nurses need to continue research to develop evidence-based practice guidelines for this debilitating side effect of chemotherapy.

To evaluate the effectiveness of psychotherapeutic and pharmacologic therapy, in depressed patients with cancer, by means of a meta-analysis and systematic review

• Researchers consulted the MEDLINE,^® CINAHL^®, EMBASE, PsycInfo, and Cochrane Collaboration databases. 7,700 references were retrieved.
• Vocabulary terms appropriate to each database were used and are available as a separate file online.
• Inclusion criteria consisted of the following characteristics: Patients were older than 17 years; had a cancer diagnosis at the time of the study; had symptoms of depression that had been measured; were randomized to study groups, to compare the intervention to any control condition; and had elevated symptoms of depression as defined by the authors.
• The study was excluded if eligibility did not include elevated symptoms of depression.

Researchers used the PEDro scale to evaluate study quality.

• 10 studies were included. One was eliminated from the meta-analysis because it was an outlier in the calculated effect size.
• 6 psychotherapy trials involved a total of 1,273 patients. 4 pharmacologic trials included 362 patients.
• Most participants were women, and their mean age was 51.

Multiple phases of care

Across all included trials, Hedges's g = 0.43 (95% CI, 0.48–1.54, p < 0.001) in favor of the intervention. Analysis of effect size at various follow-up periods showed that effect declined over time. Hedges's g effect size at 24 months poststudy entry was 0.19 and was not statistically significant. Follow-up at 18 months still showed a significant effect (g = 0.37, p < 0.001). Overall effect of pharmacologic interventions was g = 0.44 (p < 0.001); of cognitive behavioral therapy, g = 0.83 (p < 0.001); and of problem-solving therapy, g = 0.33 (p < 0.001).

For patients with cancer who had elevated symptoms of depression, psychotherapeutic and pharmacologic interventions were at least moderately effective in reducing symptoms of depression; however, efficacy may decline over time. Comparison of approaches showed that cognitive behavioral therapy had a substantially larger effect than did problem-solving therapy or medications.

Although the heterogeneity in analysis was not high, samples did vary substantially in terms of cancer stage, time elapsed since diagnosis, ethnicity, gender, and sample size.

Antidepressants, problem-solving therapy, and cognitive behavioral therapy were effective in reducing symptoms of depression in patients with cancer who had elevated symptoms of depression. Assessment of the symptoms of depression can identify patients who can benefit from these treatments. Since medication, problem-solving therapy, and cognitive behavioral therapy were efficacious, treatment selection should be based on each patient's characteristics and preferences. It appears that efficacy may diminish over time, pointing to the need for long-term follow-up and management of depression in patients such as those who met the research criteria.

To identify and review clinical practice guidelines (CPGs) related to the assessment and management of physical impairment outcomes of breast cancer and the interventions used to treat the disease. The patient population was patients with breast cancer. 

Relevant health science databases were searched to identify evidence-based CPGs. The CPGs were evaluated using the AGREE II Instrument. The recommendations for updating current guidelines and for future guidelines were developed. Nineteen guidelines were included. Databases used were MEDLINE®, Google, Google Scholar, Physiotherapy Evidence Database (PEDro), Grey Matters and Intuit, CINAHL^®, and Embase (OvidSP). Keywords were breast cancer, rehabilitation, and guidelines. CPGs were included if they focused on breast cancer-related upper-extremity physical impairments, upper-extremity or breast lymphedema, pain, fatigue, chemotherapy-induced peripheral neuropathy (CIPN), cardiotoxicity, or bone health. CPGs also had to be evidence-based recommendations related to weight management in breast cancer, published between 2001–2011 in a peer-reviewed journals or endorsed by a national or multinational government agency or health professional provider group, and available in English. CDPs were excluded if they pertained specifically to metastatic breast cancer. 

• Late effects
• Survivorship

Volume measurements using an opto-electric volumeter (perometer) and bioimpedance spectroscopy are recommended to be used in place of arm circumference measures. The use of compression garments is recommended in the management of lymphedema, but only limited evidence support compression bandaging with manual lymph drainage based on the reviewed guidelines.

High-quality evidence is insufficient to make clinical recommendations in the form of guidelines. There is an urgent need for updating the guidelines on lymphedema. Recommendations include physical therapy beginning the first day after surgery and active stretching exercises after removal of drains. Progressive resistive exercises with light weights within four to six weeks after surgery is also recommended. There is insufficient evidence regarding use of laser treatment and electrical stimulation, and there are published precautions for their use in people with neoplasms. Compression garments and bandaging and complete decongestive therapy are currently recommended.

The AGREE II Instrument fails to assess the quality of evidence supporting the guideline’s recommendations.

The findings from this review have highlighted the importance of conducting more rigorously designed studies related to lymphedema assessment ,measurement, and management. Nurse scientists can play a key role in this needed area.