To analyze the differences between ondansetron and palonosetron in healthcare resource use (i.e., inpatient/outpatient encounters) among patients receiving intraperitoneal (IP) cisplatin

This study reported on a review of an electronic medical record system. Key variables were patient characteristics, chemotherapy regimen, diagnosis, medications, type of 5-HT₃ receptor antagonist (RA), other healthcare resource use, and reasons for use.

• The study reported on 48 patients; however, analysis was based on each IP administration.
• Mean age was 59 years.
• All patients were female.
• The most common cancer diagnosis was ovarian, followed by fallopian tube.
• All patients were receiving IP cisplatin as part of the GOG-172 regimen (six cycles: paclitaxel on day 1 as 24-hour IV infusion (135 mg/m² BSA), IP cisplatin on day 2 (100 mg/m² BSA), hydration on day 3 and discharge, and IP cisplatin (60 mg/m² BSA) on day 8 in the outpatient clinic). 
• Antiemetic coverage was 5-HT₃ RA plus aprepitant and dexamethasone on days 2–3, and aprepitant plus dexamethasone on day 4.
• For breakthrough CINV, prochlorperazine, metoclopramide, diphenhydramide, and lorazepam were prescribed. Patients received dexamethsone on day 1 for fluid retention purposes (not for the control of CINV).

This was a single-site, inpatient and outpatient study conducted in Massachusetts.

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for late effects and survivorship.

This was an observational study (electronic chart review).

The following were recorded.

• CINV-related hospital readmission occurrence    
• Emergency department visits
• Outpatient encounters (clinic visits, telephone calls) occurring within 7 days after cisplatin administration
• CINV-related resource use: events associated with dehydration, hypovolemia, nausea/vomiting, hypokalemia, constipation, shortness of breath, syncope/collapse
   

More CINV-related hospitalizations were found with ondansetron versus palonosetron (5.1% vs. 0%, p = 0.09) with no significant difference in other CINV-related encounters. Palonosetron was always administered as single-day therapy; ondansetron was administered as one-day (27%) or multiday (73%) therapy. No significant differences were found in hospital readministrations, emergency department visits, outpatient visits, or switches to alternate 5-HT₃ RAs between palonosetron and ondansetron. When CINV-related resource use was compared, a trend to more hospitalization was noted in the ondansetron arm, although it was not significant (2 out of 39 in the ondansetron arm versus 0 out of 89 in the palonosetron arm).

Palonosetron was associated with a trend to a lower risk of CINV-related hospital readmission than ondansetron in patients receiving IP cisplatin for gynecological cancers; however, the trend was not statistically significant. The duration of ondansetron therapy might be suboptimal with 27% of patients receiving only one day of therapy during hospital stay.

• No appropriate control group was included.
• Three different data collection periods were used.
• Suboptimal antiemetic intervention was used on day 1 (only dexamethasone for fluid retention purpose).
• Medications taken on an as-need basis and after discharge were not tracked.
• Patients who used healthcare facilities not affiliated with the study institution were not captured.
• Healthcare resource use after 7 days of IP chemo was not assessed. 
• The sample size was small (the study should have had 79 cases in each 5-HT₃ RA arm; however, only 48 patients were included), and the unit of analysis was not each individual patient, but each IP chemotherapy administration.
• Risk factors for CINV were not considered.
• The methodological quality of this study is low.

Because of the design and limitations, this study does not help in building evidence for the conclusion that palonosetron has a lower risk of CINV-related readmission compared to ondansetron.

To report the effects of treatment with zoledronic acid on pain and quality of life outcomes

Patients treated with zoledronic acid monthly for 24 months were observed for 22 months. Quality of life and pain were measured every two months.

• N = 366
• MEAN AGE = 53.7 years (SD = 11 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All patients had breast cancer and radiologic evidence of bone metastases, and 46% had two to five bone lesions. 

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

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

Phase 4, single-arm, open-label, observational study

• European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) BM22 for quality of life
• 100 mm Visual Analog Scale (VAS) for pain severity

VAS scores declined significantly on a monthly basis for the first 22 months (p < 0.05) then returned to baseline levels. Pain-related subscales of the QLQ also declined in the same pattern. There was no significant change in psychosocial aspects of the functional interference scale in the QLQ.

Over a 22-month period, monthly treatment with zoledronic acid reduced pain in women with bone metastases from breast cancer.

• 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
• Other limitations/explanation: No information was provided regarding whether there were any changes in analgesics.

Zoledronic acid is a type of bisphosphonate. Bisphosphonates are effective in reducing pain and skeletal events from bone metastases in patients with cancer. The duration of their effects was shown to be about 22 months in this study.

To determine the feasibility and preliminary efficacy of auricular acupressure as an adjunct for pain treatment

The auricular points selected were individualized and ranged between five and nine points. Vaccaria seeds were taped in place to stimulate the acupoints. An acupoint locator was used to identify points for use. After the seeds were taped to the ear areas, participants were told to press each of the taped acupoints at least three times per day for three minutes, even if they did not have symptoms. Tape remained in place for seven days. Patients were called each day for the collection of data regarding pain and medication use. Each patient received written material about the acupressure technique.

• N = 50
• MEAN AGE = 65.5 years (range = 43–89 years)
• MALES: 46%, FEMALES: 54%
• KEY DISEASE CHARACTERISTICS: All had pain intensities of 3 or more on an 11-point scale; multiple tumor types
• OTHER KEY SAMPLE CHARACTERISTICS: 92% Caucasian; 8% African American; 94% had at least secondary education; 72% were in active treatment

• SITE: Single site  
• SETTING TYPE: Home  
• LOCATION: Taiwan

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

Quasi-experimental

• Brief Pain Inventory (BPI)
• Medication Quanitification Scale (MQS) v3.0
• Adaptation of the Perceived Treatment Efficacy (PTE) assessment in rheumatoid arthritis

Pain severity, worst pain, average pain, and pain interference all declined over time (p < 0.001). Perceived efficacy was not statistically different over time. Average pain was lowest on day 3 and then began to increase. Overall, there was a 58.4% reduction in average pain. In total, 63% of participants took less pain medication than before the treatment, and only 8% were not satisfied with the treatment. Finally, 91% of recruited patients completed the study.

Auricular acupressure as an adjunctive pain treatment may be effective for patients with cancer-related pain. The self-management of auricular acupressure was feasible.

• Small sample (< 100)
• 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)  
• Other limitations/explanation: No information was provided about types of pain or analgesics used. Baseline pain levels were relatively low.

Auricular acupressure may be beneficial as an adjunctive analgesic treatment for patients with cancer-related pain. Patient self-treatment at home for seven days was feasible and well-received. Additional well-designed research of this intervention is warranted, and more research reporting the types of analgesics employed is needed.

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.