To report the findings of a feasibility and pilot study using auricular point acupressure for chemotherapy-induced nausea and vomiting (CINV) in a small group of children in Taiwain

• To examine the feasibility of recruiting children with cancer into a larger study
• To assess the feasibility of successfully completing each of the three protocols (standard care, auricular acupressure using sham auricular points [SAP], and auricular acupressure intervention [AAP])
• To analyze the longitudinal CINV data
• To determine the effect size for use in a future study of the efficacy of the intervention.

Subjects were entered into the study for three successive rounds of chemotherapy. Round one was used as the standard care (SC) group and provided baseline data. Subjects were then randomized to one of two treatments: auricular acupressure intervention (AAP) or auricular acupressure using sham points (SAP). In the third cycle, participants were crossed over to the other treatment. Patients had a seed application prior to their round of chemotherapy and seeds remained for seven days. They were instructed to press their acupoints three times a day for three-minute periods. They also were instructed to press the seeds as soon as they felt nausea. Each participant received a booklet with a diary to keep track of stimulation times, sites stimulation, duration, and whether or not the child felt relief. Data was collected prior to chemotherapy administration and daily for seven days.

• The study consisted of 10 participants.
• Mean age of participants was 13.29 years (SD = 3.31).
• The smaple was 60% male and 40% female.
• Cancer diagnoses was 30% leukemia and 70% “other solid tumor.\"

This was a single site study conducted at a large children’s hospital in Taiwan.

All patients were pediatric and in active antitumor treatment.

This was a crossover, randomized design feasibility study.

The study used the Morrow Assessment of Nausea and Emetics (MANE), a 17-item, self-report questionnaire that measures occurrence, duration, and severity of nausea and vomiting. Demographic data was collection from medical chart review. Patients and their parents kept study booklets to record stimulation times, the number of acupoints stimulated, and stimulation duration at each of the acupoints, as well as whether or not the child felt relief from symptoms.

The authors were able to recruit 10 patients from a possible 22, all of whom were able to complete the entire study. Subjects kept the taped seeds on for 88% of the possible treatment days, suggesting the intervention is feasible and acceptable to children and their families.

The SC group reported more nausea overall than either the AAP or SAP groups, with 30% still reporting nausea on day 7. The SAP group reported the same nausea as the SC during the first two days, but declining nausea after day 2, with only 20% still reporting nausea on day 6. The AAP group reported less nausea on day 1, similar nausea on day 2, and no nausea by day 5.  Although analysis did not show statistical significance, the authors described this trend as clinically significant. 

Vomiting followed similar trends with most vomiting in the SC group, followed by SCA, and then AAP, but the difference was not statistically significant.

Because of the small sample size, comparison of the efficacy of the acupuncture intervention group and the sham acupuncture point group is not possible. The intervention group did demonstrate lower occurrence of acute and delayed nausea and shorter duration of nausea, but these results varied.  A larger study using a similar design would be necessary to evaluate this question.

• The sample size was small sample  with fewer than 30 patients.
• A risk of bias exists because of the sample characteristics and the lack of blinding.
• The measurement validity and reliability was questionable.
• The increased presence of research staff may have had a potential psychologic benefit, impacting results.

Acupuncture is an acceptable intervention to children and their parents for CINV. Potential clinical trends toward efficacy exist, but the small sample size limits the ability to draw definitive conclusions regarding its effectiveness.

To investigate the effectiveness of antibiotic and antifungal prophylaxis during intensive chemotherapy for acute leukemia in children and to assess the impact on days of intensive care, changes in antibiotic resistance, and medical cost

Oral ciprofloxacin 300 mg/m² every 12 hours was given when patients became neutropenic and when seven days of neutropenia were expected. Oral voriconazole 4 mg/kg every 12 hours was initiated at the onset of neutropenia in patients with acute myeloid leukemia (AML) and after seven days of neutropenia in patients with acute lymphoblastic leukemia (ALL). IV micafungin was substituted for oriconazole during induction and reinduction chemotherapy. Prophylaxis was discontinued when patients' absolute neutrophil counts recovered to > 100/mcL. Probable invasive fungal infection (IFI) was not included in analysis. Data were analyzed from patients prior to the use of prophylaxis and from patients during the prophylaxis period.

• N = 113  
• MEAN AGE: 4.4 years (range = 0.2–18 years)
• MALES: 40%, FEMALES: 60%
• KEY DISEASE CHARACTERISTICS: AML or ALL

• SITE: Single-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Taiwan

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

Retrospective cohort comparison study

• Bloodstream infection was defined by the isolation of bacteria from blood cultures and clinical signs of systemic infection.
• IFI was diagnosed according to the culture or histology of infected tissue.

In the preprophylaxis period, there were 25 episodes of bloodstream infection among 62 patients, and in the prophylaxis period there were five episodes among 51 patients (p < .01). Preprophylaxis, there were 12 episodes of IFI compared to zero episodes during prophylaxis (p < .01). There were fewer episodes of febrile neutropenia with prophylaxis (p = .01). Ciprofloxacin resistance of E-coli Klebsiella pneumoniae, pseudomonas aeruginosa, and serratia marcescens was significantly reduced during the prophylaxis period. Other gram-negative bacilli did not change with regard to ciprofloxacin resistance between the two periods of time. 39% of patients had hepatotoxicity during prophylaxis with micafungin leading to dose modification in three patients and discontinuation in seven patients. Intensive-care stays due to infection and total cost were significantly lower during the prophylaxis period.

Prophylaxis decreased the occurrence of febrile neutropenia, bloodstream infections, IFI, intensive care length of stay due to infection, and cost for patients with ALL and AML. There was no increase in ciprofloxacin resistance associated with prophylaxis with this agent.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)

This study demonstrates the efficacy of antibiotic and antifungal prophylaxis in children receiving intensive chemotherapy for ALL and AML. There has been limited evidence of prophylaxis use and outcomes in children. Children safely received ciprofloxacin for antibiotic prophylaxis. In this particular study, there was no increase in ciprofloxacin resistant organisms during the time prophylaxis was used; however, analysis was done over a limited period of time and is not seen as conclusive. Continued monitoring for the development of drug resistance is important in organizations providing this type of prophylaxis as a routine. Findings here support the cost effectiveness of prophylaxis, showing lower intensive care stay lengths and overall cost during the time prophylaxis was used.

To evaluate the effect of Shuangbai San on pain relief among patients with liver cancer

Shuangbai San is a traditional Chinese medicine that includes five major herbal components that was prepared for external application. Patients with low level pain (3 or less on an 11-point scale) were randomly assigned to the study intervention or placebo. Two hundred grams of the preparation or placebo was mixed with water and honey to make a paste that was heated in a microwave for three minutes. The mixture was spread on a transparent film, then applied and kept in place around the liver or upper abdomen for six hours for seven days of treatment. Pain scores were measured after one, three, and six hours daily. Quality of life (QOL) was measured pre- and post-treatment.

• N = 133   
• MEAN AGE = 57
• MALES: 86.5%, FEMALES: 13.5%
• CURRENT TREATMENT: Immunotherapy
• KEY DISEASE CHARACTERISTICS: All had primary liver cancer.

• SITE: Multi-site   
• SETTING TYPE: Home    
• LOCATION: China

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

• Double-blind, placebo-controlled randomized trial

• Numeric pain rating scale
• EORTC Cancer Care Quality of Life (EORTC-QLQ-C30) questionnaire

The pain rating scores were significantly lower in the study treatment group at all time points (p < 0.001). Pain scores declined in all. On the EORTC, the intervention group had significant improvement is subscale scores for physical, emotional, fatigue, pain, insomnia, appetite, and global health compared to controls (p < 0.001). These aspects of QOL improved in all study patients. No adverse effects were seen. Only one patient used any analgesic.

Topical application of Shuangbai San was shown to reduce cancer pain and improve aspects of QOL among patients with low-level pain associated with liver cancer.

• Limited availability of the mixture was used.

The traditional Chinese medicine compound Shuangbai San was associated with reduced pain and enhanced QOL among patients with low-level pain from liver cancer. This may hold promise for relief of mild pain. Further testing and application in other types of pain that may be responsive to topical treatment is needed.

Studies were included in the review if they reported on

• Adult patients older than 18 years of age
• Patients with nonhematologic malignancies
• Patients with anorexia or symptoms of anorexia, such as lack of appetite, weight loss, poor performance status, and decreased quality of life.

The review involved only prospective, randomized controlled trials (RCTs; double- and single-blind or unblended and phase III trials). The quality of studies was assessed using the validated scale published by Jadad et al. (1996).

There were 55 studies reviewed that met the eligibility criteria.

Multiple RCTs have been conducted to investigate the safety and efficacy of pharmacologic agents to stimulate appetite. Only two therapeutic interventions for cancer-related anorexia demonstrated enough evidence to support their use in patients with cancer: corticosteroids and progestins. Other studies had mixed outcomes, positive results in only a single randomized trial, or were not placebo-controlled.

There is strong evidence supporting the use of progestins in patients with cancer, of which the most commonly reported drugs were MA and MPA. There was increased weight with both progestins; there was also evidence of a dose-response, but higher doses did not confer any additional benefit with regard to appetite. Metaclopromide is effective for nausea and early satiety but has not been shown to directly stimulate appetite.

The RCTs did not show sufficient evidence to justify the use of dronabinol, EPA, EPO, ghrelin, interferon, melatonin, nandrolone, NSAIDs, or pentoxyfilline in cancer-related anorexia. Cyproheptadine is a weak appetite stimulant, but side effects are limiting.

The optimal dose, start time, and duration of treatment for many appetite stimulants are still unknown. A more systematic approach to research methodology is needed. In addition, uniform outcome measures to better assess the value of various appetite stimulants are needed. These should include subjective ratings of appetite and associated symptoms (e.g.,  early satiety) and objective measures (e.g., food consumed, weight gain, weight loss).

To investigate the effects of providing mouth care education to pediatric patients with cancer on their degree of mucositis

This study was designed to provide mouth care education using written and visual material. Participants were placed in the control group (prior to the start of chemotherapy and and the education intervention) and the research group after intervention. Patients and their mothers were taught an oral care protocol including brushing teeth and gargling with salt water glutamine mouth wash twice daily, then brushing teeth an additional two times per day.

• N = 16    
• AVERAGE AGE = 13.9 years (range = 8–18 years)
• MALES: 31%, FEMALES: 69%
• KEY DISEASE CHARACTERISTICS: Overall, 56% of patients were diagnosed with leukemia or lymphoma, 62.5% were at an advanced stage and in a high-risk group, and 44% were receiving chemotherapy for six days or more.
• OTHER KEY SAMPLE CHARACTERISTICS: In total, 68.75% of participants reported that they received mouth care education from healthcare providers, 75% reported that they received education related to oral mucositis, and 93.75% were irregularly practicing mouth care.

• SITE: Single site
• SETTING TYPE: Inpatient hematology/oncology pediatric clinic    
• LOCATION: A university hospital in Turkey

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

This was a quasi-experimental longitudinal study designed to examine the influence of planned mouth care education on oral mucositis severity and associated pain.

• The data collection tools used were the Child and Parent Information Form (CPIF), World Health Organization (WHO) Oral Mucositis Index (OMI), and the Children’s International Mucositis Evaluation Scale (ChIMES) developed specifically to evaluate mucositis-related symptoms in pediatric patients with cancer.

The difference between the median oral mucositis severity before and after the education intervention was statistically significant according to the OMI (p < 0.05). Actual differences varied across study days. Children indicated that they practiced oral care irregularly. There was a statistically significant difference between the children’s pain scores before and after the program.

Planned mouth care education using written and visual material specifically designed for pediatric patients with cancer beginning on the very first day of diagnosis was helpful as an intervention for pain and mucositis. It also promoted the routine monitoring of each patient’s mouth care practices and assessments of oral mucositis and pain severity using valid and reliable scales at each visit.

• Small sample (< 30)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)  
• Findings not generalizable
• Other limitations/explanation: This study was conducted at one medical center, and there was a time limitation because it was a part of a graduate dissertation project. It was unclear if the information provided regarding the children’s adherence to oral care was gathered from baseline assessments or after the education program. The findings of this study were most applicable to a third-world population with minimal oral hygiene habits.

Nurses have an essential role in providing education and monitoring oral mucositis protocols that can be implemented as part of routine care in a hospital inpatient or infusion clinic setting. The results of this study were favorable in part because of the routine follow-up visits that ensured the effectiveness of the education program. Routine visits were established at the initial visit and included education reinforcement, the promotion of oral care practices, physical assessments, and evaluations of associated pain. These can be supported as interventions for PEP^® pain management. Participants in this study were from a population in which there was little regular oral care as part of regular hygiene habits.

Patients were randomized to receive either 100 mcg subcutaneous octreotide three times per day or 2.5 mg oral diphenoxylate/atropine four times per day.

• The study consisted of 61 patients with grade 2–3 diarrhea associated with pelvic external beam radiation therapy (XRT).
• The octreotide group contained 33 patients, and the diphenoxylate group had 28 patients.
• The sample was balanced for clinical characteristics, including radiation dose.
   

• Investigators recorded the number of days to resolution of diarrhea and the number of days of interruption of radiation therapy.
• Success was defined as a complete response within three days.

• The octreotide group experienced diarrhea resolution in 3.3 days compared with 5.6 in the diphenoxylate group (p = 0.0001).
• The octreotide group experienced 0.45 days of interrupted radiotherapy compared with 1.89 days in the diphenoxylate group (p = 0.003).
• The octreotide group experienced a 61% success rate, while the diphenoxylate group experienced a 14% success rate (p = 0.002).

The sample size was small.

An individualized psychoeducational intervention was delivered in one face-to-face session lasting 20 minutes, followed by two telephone sessions of approximately 10 minutes each. The intervention sessions were delivered at weekly intervals. Participants were also given written materials on fatigue management. The intervention focused on helping patients develop knowledge and skills to engage in self-care behaviors that may decrease fatigue, including increasing mobility/activity, effective use of available energy reserves, and management of sleep disturbances, anxiety, and psychological concerns. The intervention also addressed the predisposing, reinforcing, and enabling factors for self-care, including beliefs, attitudes, and perceptions that might facilitate or hinder a person’s motivation to perform the desired behaviors and use the skills and resources necessary to perform the behaviors and feedback provided by family or health professionals that might influence continuance or discontinuance of the behaviors. Each session was tailored to the patients’ specific needs and circumstances and was designed to target these influencing factors. Scripts and intervention protocols for both the treatment and attentional control groups were provided by the investigators. Efforts to facilitate standardization and quality control in the delivery of the interventions were described.

• The study included 109 women beginning adjuvant chemotherapy for stage I or II breast cancer. 
• Mean age was 49.4 years (range 26–70).
• Approximately 65% had completed post-high school education, and most were from relatively high socioeconomic backgrounds.
• Of the patients, 77.4% were married.
• There were no significant differences between the interventional and control groups for any other medical variables.
• All participants had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 2, and their hemoglobin levels were at least 11.6 g/mL at recruitment.

One of five outpatient chemotherapy/day treatment facilities in a major metropolitan setting

The study was a randomized, controlled trial with an attentional control group and concealment of group allocation. Randomization procedures and attentional control conditions were used explicitly.

• Investigator-Developed Instruments: Fatigue Management Behaviors, Confidence with Managing Fatigue, and numeric rating scales for fatigue
• Revised Piper Fatigue Scale (PFS) 
• Functional Assessment of Cancer Therapy-Fatigue (FACT-F)

The most commonly used self-care actions for fatigue reported at baseline were rest, hydration, relaxation, exercise, and listening to music. Use of these actions remained relatively stable over time, and there were no significant differences in usage between groups. Patients in the intervention group reported a significantly greater mean increase in the number of actions recommended by health professionals compared with patients in the control group. There were notable increases in mean fatigue levels for both groups from time one (start of second cycle of chemotherapy) to time two (immediately after completing the intervention and start of cycle three of chemotherapy), with these higher levels of fatigue persisting at time three (start of cycle four of chemotherapy or day one of radiotherapy for those participants). The increases between baseline and immediate postintervention fatigue scores were significantly greater for the control group when compared with the intervention group for worst fatigue, average fatigue, fatigue severity, fatigue interference, and FACT-F. These differences were not sustained for changes between baseline and times three or four.

The strength of the study was the inclusion of an attentional control group.

• Effects observed in the study reflected improvements on the subjective measures of fatigue experiences rather than for objective measures of fatigue management behavior. The differences may therefore simply reflect patient expectations that they would benefit from the intervention. 
• Measurement time points may have limited the detection of a difference in the fatigue experienced at times three and four.

Psychoeducational interventions were delivered by experienced oncology nurses. Costs were limited to personnel costs and the one-time costs associated with materials development.

The objective of the article is to report on strategies that patients with breathlessness find helpful and provide a review of current evidence about the role of nonpharmacologic interventions in managing dypsnea.

This article reports a secondary analysis of data from a trial in which self-report items were used to assess the impact of dyspnea on daily activities, feelings about breathlessness, and strategies adopted by patients. Authors also review the findings of several systematic reviews of nonpharmacologic interventions for breathlessness involving patients with chronic obstructive pulmonary disease (COPD) as well as lung cancer.

• The article reported on a sample of 144 patients.
• The mean age was 67.9 years (SD = 9.6 years).
• The sample was 60% males and 40% females.
• Patients involved in self-report of strategies all had cancer. 
• Most data from systematic reviews involved primarily patients with COPD.

The multi-site study was conducted in an unspecified setting in Australia.

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

Descriptive

• Author-designed self-report instrument based on an assessment guide developed in the UK
• Likert-type scoring on a 4-point scale

About half of patients reported that breathlessness had some effect on feelings of panic, fear, and anger. Activity modification was the most frequently used strategy.  Cognitive coping strategies were used by 80% of respondents. Other strategies included breathing exercises and environmental modifications. The most helpful strategies related to activity modification. Of those who used coping and breathing exercises, 60% said they were helpful. Breathing retraining was found to be effective but is mainly studied in COPD. Exercise program findings are inconclusive, and interventions to reduce anxiety have had some positive outcomes. Other interventions such as music, distraction, and complementary medicine have insufficient evidence.

Patients in this study reported that activity management was helpful to manage dyspnea.

• Risk of bias (no control group)
• Risk of bias (no blinding) 
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition) 
• Risk of bias (sample characteristics)
• Measurement validity/reliability questionable
• The likert scale used is questionable in terms of lack of differentiation in terms used for degree of effect.
• Findings reported from systematic reviews were mainly from COPD cases, and few included patients with lung cancer. 
• Other cancers were not included.

Findings suggest that educating appropriate patients about activity management can be helpful for them to manage symptoms of dyspnea. Limited evidence exists about the effects of other nonpharmacologic approaches that are effective for patients with cancer.

PURPOSE: Review evidence and provide guidelines for use of natural agents in the prevention and management of oral mucositis in cancer

TYPES OF PATIENTS ADDRESSED: Patients receiving chemotherapy, radiation therapy, or stem cell transplant

RESOURCE TYPE: Evidence-based guideline

PROCESS OF DEVELOPMENT: Systematic review of evidence, quality rating using Hadorn criteria, and level of evidence classified via Somerfield criteria

DATABASES USED: MEDLINE

KEYWORDS: Alternative, complementary, homeopathic, aloe vera, beta carotene, chamomile, chines herbal, folic acid, and numerous other specific natural agents

INCLUSION CRITERIA: Not specified, other than use of a natural agent

EXCLUSION CRITERIA: Not specified

PHASE OF CARE: Active antitumor treatment

APPLICATIONS: Pediatrics

Ninety-nine papers were identified, and, of these, 49 papers were included in the review.

• Glutamine (20 studies)—not recommended for prevention in patients undergoing hematopoietic cell transplantation. For other situations, no guideline was deemed possible.
• Vitamins A  or E (eight studies)—no guideline possible
• Honey (four studies)—no guideline possible. Each study used a different type of honey.
• Zinc (four studies)—no clear recommendation is given, but the committee suggested it may be of benefit for prevention in patients with oral cancer during radiation or chemoradiation therapy.
• Twelve studies of various other agents were reviewed. No guidelines were possible in any of these.

• Many studies were of low quality, and some were more than 10 years old. 
• Hadorn criteria reliability is questionable. 
• For many products, only one study was found.

Findings do not support efficacy of currently studied natural herbal agents and other agents for prevention of oral mucositis. Systemic zinc supplementation may be helpful for patients with oral cancer receiving treatment. Glutamine is not recommended in patients undergoing cell transplant. Further, well-designed research in this area continues to be needed.

STUDY PURPOSE: To assess the efficacy of compound kushen injection (CKI) for bone pain in cancer

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: MEDLINE, Cochrane Collaboration, four Chinese databases, two Korean databases, and one Japanese medical database

KEYWORDS: kushen, yanshu, matrine, and various terms for bone cancer pain

INCLUSION CRITERIA: RCT, adult patients with cancer-related bone pain; patients in the control group were given radiotherapy, opioids, non-steroidal anti-inflammatory drugs, or bisphosphonates

EXCLUSION CRITERIA: Nonrandomized trials

TOTAL REFERENCES RETRIEVED = 170

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Used the GRADES system for quality evaluation

• FINAL NUMBER STUDIES INCLUDED =  7
• SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: 521 total patients; sample size per study not reported
• KEY SAMPLE CHARACTERISTICS: Variety of tumor types

• PHASE OF CARE: Late effects and survivorship     
• APPLICATIONS: Palliative care

All studies were done in China at a single center. Analysis showed that CKI relieved pain when compared to bisphosphonates or radiotherapy (RR 1.25, p < .0001). The quality of all studies included was low, and risk of bias was high. Not all studies examined adverse effects. In four studies, patients who received CKI had less nausea and leukopenia. Analysis showed positive results, indicating publication bias.

CKI may have beneficial effects and reduce cancer-related bone pain. However, the small number of trials and low quality of the evidence is insufficient to show efficacy.

• Small number of studies
• Low quality of studies
• All studies done at the same institution

Evidence is insufficient to determine efficacy of the Chinese herbal medicine kushen.