To assess effectiveness of a once-a-day fentanyl patch for patients receiving a 72-hour patch that does not last for 72 hours

Patients identified as having end-of-dose failure with a 72-hour fentanyl patch were identified and converted to the once-a-day patch according to manufacturer recommendations. In the evening of the switch day, the new patch was applied immediately after removing the 72-hour patch. Treatment for breakthrough pain was adjusted according to the fentanyl dose, and immediate-release morphine or oxycodone was used for breakthrough pain. If patients were on anti-inflammatories, they remained on this medication. Patients recorded study data daily. Of the patients, 15.6% had the 72-hour patch changed to use every 48 hours. Mean frequency of daily rescue doses for breakthrough pain were analyzed.

• N = 45   
• AGE RANGE: 60–69 years
• MALES: 54.8%, FEMALES: 45.2%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Varied tumor types
• OTHER KEY SAMPLE CHARACTERISTICS: Most were on 25–50 mcg fentanyl per hour.

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

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

• Retrospective cross sectional

• Numeric pain rating scale from patient diaries

Of the patients with suspected end-of-dose failure, 84% were switched to the once-a-day patch. The rest had patches switched at 48 rather than 72 hours. On the last day of the 72-hour patch, mean daily dosing for breakthrough pain was 3.61; on the third day after the switch, the mean daily dosing was 1.18 (p < 0.05). Adverse events occurred in 18% of patients with the new patch, including local skin irritation and sensitivity. Of the patients with shortened interval to 48 hours, three showed a decrease in pain score, two showed no change, and two showed increased scores. After the switch to the once-a-day patch, 61% showed more than a 30% reduction in average pain.

Patients switched to the once-a-day fentanyl patch had a reduction in average pain scores and a reduction in rescue medications needed.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable
• Timing of pain measurement from diaries is not stated.

Differentiating between breakthrough pain and end-of-dose pain medication failure is important. This study suggests that these may not always be well determined. Study findings suggest that a once-a-day fentanyl citrate patch may be more effective for pain control than the usual 72-hour fentanyl matrix, particularly in patients with end-of-dose failure. This study is limited by its design and sample size. Further well-designed research is warranted.

To determine whether biofeedback improves outcomes for patients with pelvic floor dysfunction (PFD), and to assess the relative effectiveness of different types of biofeedback therapy.

Databases searched were CINAHL, Embase, Medline, PsycINFO, Evidence-Based Medicine Reviews (EBMR), and the Cochrane Database. References of retrieved articles also were hand searched.

Search keywords were constipation, anismus, dyssynergia, obstructive defecation, rectocele, rectal intussusception, rectal prolapse, ​and biofeedback.

Studies were included in the review if they

• Were randomized controlled trials (RCTs)
• Reported on adults with PFD
• Included biofeedback as at least one of the treatments studied.

Studies were excluded from the review if they reported on pediatric cases.

The initial searching provided 5,028 references. Study selection and screening for inclusion criteria provided a final set of seven studies. Study quality was evaluated by two reviewers.

• The final sample of seven RCTs included 413 patients.
• Sample sizes ranged from 26 to 109.
• Medical diagnostic information across studies was not provided.

• Three trials compared biofeedback with other interventions such as laxatives, diazepam, and placebo. Meta-analysis showed an odds ratio (OR) of 5.861 (95% confidence interval [CI] [2.175, 15.794], p < 0.001) in favor of biofeedback.
• Four trials compared differences in biofeedback techniques. A meta-analysis of the most widely used technique, electromyogram biofeedback, showed an OR of 6.738 (95% CI [2.194, 15.58], p < 0.001) in favor of biofeedback.

• Results suggest biofeedback is associated with symptomatic relief of constipation; however, the number of studies included was very small and substantial heterogeneity existed across studies.
• Study quality overall was poor.
• Findings are not specific to the oncology population, and whether any of the studies included patients with cancer is not known.

Additional, better-designed studies are needed in this area to determine efficacy. Future studies should compare different biofeedback modalities to identify the most effective approaches.

The study's primary aim was to examine the effect of modafinil on persistent fatigue after treatment. Its secondary aim was to examine the effect of modafinil on cognitive function of patients with breast cancer.

In phase 1, participants were given 200 mg of modafinil daily for four weeks. Participants with a positive response in phase 1 were randomized to phase 2. In phase 2, participants continued to receive 200 mg of modafinil orally once per day or a placebo for four weeks. Repeated measures were completed at baseline (week 0), week 4, and week 8. Participants were stratified by treatment type: chemotherapy, radiation, or both chemotherapy and radiation. 

• The total number of participants was 82, with 76 completing phase 1 and 68 completing phases 1 and 2.
• The median participant age was 54, with a range of 33–83.
• All participants were female.
• All participants had breast cancer and were being treated with surgery and chemotherapy; 87% also received radiation.
• 75% of participants had at least some college education.

The study took place at the University of Rochester Medical Oncology Clinic in New York. 

The study was a prospective, open-label clinical trial.

• The Cognitive Drug Research (CDR) assesses domains of attention and memory, including speed of memory, continuity of attention, quality of episodic and working memory, and power of attention.
• The Brief Fatigue Inventory (BFI) assess fatigue.

Approximately 70% of the participants in the active treatment group had an improvement in continuity of attention from baseline to after treatment (week 8), compared with 52% in the placebo group; however, this difference was not statistically significant (p = 0.19).

In phase 1, modafinil had a significant effect on speed of memory (p = 0.0073) and quality of episodic memory (p = 0.0001). No significant effect in continuity of attention, quality of working memory, or power of attention was observed during this phase.

In phase 2, those who continued modafinil demonstrated significantly greater improvement in cumulative speed of memory (p = 0.029), quality of episodic memory (p = 0.0151), and continuity of attention (p = 0.0101).

Modafinil significantly improved some cognitive functioning, including speed of memory and episodic memory, but failed to demonstrate improvement in working memory.

• Findings were a secondary analysis; cognitive functioning was not the study's primary outcome.
• The study was an open-label trial, and thus participants were not blinded to their assignment.
• The study had a relatively small sample size.
• The majority of participants were an educated group of Caucasian women, limiting generalizability.
• The study did not report if differences existed between the original enrolled sample (n = 82) and those who completed the entire study (n = 68).
• Although not statistically significant, the participants assigned to the modafinil group had a mean age which was five years younger than the placebo group.
• Although the Cognitive Drug Research has been used reliably in other populations, it does not indicate if it has been used in cancer populations.

The objective of this study was to investigate the influence on consciousness of sedative drugs to relieve severe physical distress refractory to standard interventions.

The study was a retrospective review of medical records of 124 consecutive patients admitted to a single palliative care unit between January and December 1999 to evaluate the use of sedation, defined as “a medical procedure to palliate patient symptoms refractory to standard therapy by intentionally dimming consciousness.\" Nocturnal sedation was excluded.

• The study reported on a sample of 63 participants.
• The mean age was 64 years, with a range of 35–87 years.
• Of the sample, 67% were males and 33% were females.
• A key disease characteristic was cancer, with the primary tumor sites being lung (38, 60%) and stomach (7, 11%).
• Symptoms requiring sedation were dyspnea (63%), general malaise/restlessness (40%), pain (25%), agitation (21%), and nausea and vomiting (6%).
• Thirty-five patients (54%) had more than one uncontrollable symptom.

This single-site study was conducted in an inpatient setting in Japan.

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

• Retrospective chart review was conducted to obtain patient characteristics, symptoms, and treatments.
• Statistical analysis of patient data was performed using unpaired t-test.

• Equivalent daily dose (MEDD) of parenteral morphine
• Parenteral equivalent of midazolam (PME)
• Palliative Performance Scale (PPS) (0 = death, 100 = normal)
• Communication Capacity Scale to measure level of consciousness (0 = awake with no drowsiness, 3 = aroused by verbal stimuli, 5 = unarousable by physical stimuli)

• Palliative Performance Scale results were poor in the group before sedation (10 [46%], 20[37%], 30[14%], 40[3%]).
• The longest duration of sedation was 11 days.
• Midazolam was the most frequently administered sedative (98%) by continuous IV infusion (60%) and SQ infusion (35%).
• Between patients receiving sedation and those not requiring sedation, no significant difference was seen in admission duration or level of consciousness day six–day three before death.
• A significant difference in mean CCS only lasted three days prior to death (day two before death CCS 3.3 [SD = 0.8] [p < 0.05], day one before death CCS 3.8 [SD = 0.7] [p < 0.05], day of death CCS 4.7 [SD = 0.6] [p < 0.01]).
• The mean dose of opioid used was greater in the sedated group but only statistically significantly on day two before death (p = 0.04), day one before death (p = 0.03), and day of death (p = 0.08).

This study contributes descriptive information about the use of terminal sedation (midazolam and opioids) for symptom control and the influence sedation has on the level of consciousness during the last days of life. In this study, patients receiving sedation were significantly drowsier and less responsive only during the last three days of life. What is not known from this study, although it is implied, is the degree of symptom control achieved by this intervention.

Limitations of this study included

• Small sample size of less than 100
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias(sample characteristics)
• Selective outcomes reporting
• Questionable measurement validity/reliability
• Nongeneralizable findings
• Limited strength of evidence due to retrospective chart review in single site
• Evidence peripheral to dyspnea relief outcome.

This is helpful, descriptive, and low-level evidence about the use of terminal sedation to control symptoms. No measurement of dyspnea relief was included in the report, although it implies that sedated patients were not in distress.

The objective of the study is to assess the effect of nebulized furosemide (20 mg) on dyspnea uncontrolled by standard therapy in patients with terminal cancer.

Patients inhaled 20 mg of furosemide diluted with 3 ml of normal saline through an ultrasonic nebulizer over 10 minutes.

The study reported on a sample of 15 patients in a palliative care unit with histologic diagnosis of malignant disease and the presence of dyspnea that resists standard treatments.

Uncontrolled, open study

Initial severity of dyspnea was grade 4, assessed with the Hugh-Jones 0–4 classification. Effects were evaluated using the Cancer Dyspnea Scale before treatment and 60 minutes following treatment. Hemoglobin oxygen saturation and heart rate (HR) were measured with a pulse oximeter. Respiratory rate (RR), HR, and arterial blood gas parameters also were determined before and 60 minutes after use of nebulized furosemide. In addition, patients were asked whether they felt relief with the treatment and whether they hoped to continue the treatment.

The study showed that the inhalation of nebulized furosemide alleviated the sensation of dyspnea according to decreased Cancer Dyspnea Scale scores for sense of effort, sense of anxiety, and total dyspnea. However, objective data such as arterial oxygenation (PaO₂), arterial partial pressure of carbon dioxide (PaCO₂), oxygen saturation, HR, and RR did not change with treatment.

The study had several limitations. It was an uncontrolled, open study and, thus, the results may include a placebo effect from the intervention itself. The assessment of dyspnea was conducted on only two occasions—before and after administration of a single dose. Finally, the sample size was small.

Databases searched were MEDLINE, CINAHL, Cochrane Library, CANCERLIT, and PEDro through June 2004 to identify randomized, controlled trials and controlled trials (those with a comparison group but without explicit use of randomization for purposes of group allocation).

To be included in the review, the trials had to have examined the effects of physical exercise after surgery or during or after chemotherapy, radiotherapy, and/or hormonal therapy. Only exercise interventions designed to improve endurance or muscular strength were included.

Studies of relaxing exercises (e.g., yoga or tai-chi) were excluded.

The methodologic quality (using the Delphi criteria list—a set of nine criteria for quality assessment of clinical trials) and substantive results of 34 randomized, controlled trials and controlled trials was examined. Of the 34 studies examined, 22 examined the effectiveness of physical exercise during medical treatment, whereas 12 focused on the period after medical treatment.

Outcomes were fatigue, health-related quality of life, symptom distress, psychological distress, body composition, physical exercise capacity (maximal oxygen consumption [VO₂] max), self-reported exercise/physical activity level, and other physical performance measures, such as walk time. Various physical exercise modalities were used, differing in type (walking, cycling, swimming, resistive exercises, or combined exercises), intensity (with most programs at 50% to 90% of the estimated VO₂ maximum heart rate), frequency (ranging from two times per week to up to two times daily), and duration (ranging from two weeks up to one year). In some studies, the experimental group was compared with a group that received some form of training of a lesser intensity, frequency, and/or duration (e.g., stretching, self-directed exercises, strength exercises, aerobic exercise of a lesser intensity, swimming, behavioral therapy). In other studies, the comparison group did not receive any exercise program or advice, was on a waiting list, or participated in a cross-over trial.

The studies during medical treatment were divided into three subcategories: (1) exercise during breast cancer treatment, (2) exercise during bone marrow and peripheral blood stem cell transplantation, and (3) exercise during medical treatment for mixed solid tumors. The studies after medical treatment were divided into those involving exercise after breast cancer treatment and exercise after medical treatment for other solid tumors. The authors used this strategy to reflect not only differences in cancer diagnosis and the timing of physical exercise programs, but also possible differences in motivation, safety, feasibility and efficacy of exercise. The sample sizes for the intervention groups ranged from 12 to 188 participants.

A clinically significant or statistically significant positive effect of physical activity specifically on fatigue was noted during breast cancer treatment  (three studies) or after breast cancer treatment (two studies), and during treatment (three studies) or after treatment (one study) in a mixed solid tumor population. The median quality criteria score on the Delphi list (range 1–7) was four for studies of exercise during and after cancer treatment. Twenty-five of the trials satisfied more than three criteria on the Delphi criteria list. The most commonly observed methodologic problems were with concealment of treatment allocation, blinding of the outcome assessor, and failure to use an intention-to-treat data analysis strategy.

Overall, the authors concluded that the included trials were of moderate methodologic quality, with a trend toward more methodologic rigor in more recent studies.

The purpose was to assess the effect of calcium and magnesium infusions on incidence of neurotoxicity and clinical outcomes in patients treated in a phase III trial (CAIRO2) with oxaliplatin-based chemotherapy.

Patients who had been treated in an randomized clinical trial for advanced colorectal cancer with either capecitabine, oxaliplatin, and bevacizumab or the same regimen with the addition of cetuximab were retrospectively divided into two groups: those who had received calcium and magnesium infusion at least during the first oxaliplatin cycle and those who did not receive calcium and magnesium during cycle 1. To evaluate the impact on prevention, incidence of neurotoxicity was defined as early (occurring during the first six cycles) or late (present at the last cycle).

• A total sample of 732 participants with colon cancer were enrolled, with men (60%) outnumbering women (40%).
• The mean age of participants was 61.9 years with a range of 27–83 years.

The study was conducted in multiple outpatient facilities in Norway.

• Active treatment
• Late effects

The study was a retrospective analysis of trial data.

• The National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0.
• An evaluation of tumor response with the Response Evaluation Criteria in Solid Tumors (RECIST).

Sample sizes were varied between groups, with 551 having received calcium and magnesium and 181 who did not. Incidence of any grade neurotoxicity was 85% in those who received calcium and magnesium and 92% in those who did not (p = 0.02), and incidence of grade 2 or higher was not significantly different between groups. Early neurotoxicity of any grade occurred more often in those who did not receive calcium and magnesium (91% versus 81%, p = 0.0002). In addition, no significant difference were noted between groups in incidence of grade 2 or higher early toxicity. All grade late neurotoxicity was lower in those who were in the calcium and magnesium group; however, incidence of grade 2or higher late toxicity was no different between groups. No difference was noted in survival or response rates between study groups.

Findings suggest that calcium and magnesium infusion may be helpful in the prevention of neurotoxicity with oxaliplatin; however, findings do not show a clear difference in more severe toxicity of grade 2 or higher.

• Limitations include the retrospective nature of the study with no appropriate control in place.
• The authors define the calcium and magnesium group as getting this infusion with the first cycle of chemotherapy; however, whether or not any of these patients or other patients got any such infusions with later cycles is unclear.
• The only outcome measure is the toxicity grading scale.
• No information is provided regarding total cumulative chemotherapy doses (whether any cycles were not provided, etc.) to evaluate any differences in symptoms according to chemotherapy dosage and cycle completions.

The findings suggest the potential effect of calcium and magnesium infusions in the prevention of neurotoxicity; however, the findings do not show any difference in terms of prevalence of higher grade neurotoxicity. Additional research in this area is needed with more definitive outcome measures.

To evaluate zoledronic acid treatment in patients with advanced cancer and metastases to bone, in regards to safety and effectiveness (as measured by serum value of calcium, concurrent analgesic use, reported bone pain, and pathological bone fractures)

An observational clinical study was conducted that monitored patients with cancer receiving monthly zoledronic acid treatment for 12 months. At each visit, pain status was evaluated using a visual analog scale (VAS), as well as by monitoring prescribed analgesics. Lab values were obtained, and skeletal events (pathological bone fractures, spinal cord compression, or concurrent therapy to palliate bone lesions) were recorded. Monthly doses of zoledronic acid were prescribed and infused according to each disease’s treatment guidelines.

• N = 125  
• AGE RANGE = 47–89 years
• MEAN AGE = 69.2 years
• MALES: 86%, FEMALES: 14%
• KEY DISEASE CHARACTERISTICS: 73.6% had prostate cancer, and 22.4% were diagnosed with multiple myeloma.
• OTHER KEY SAMPLE CHARACTERISTICS: Primarily prescribed for prevention of skeletal events

• SITE: Mulit-site
• SETTING TYPE: Outpatient 
• LOCATION: Slovenia

• PHASE OF CARE: Palliative, end-of-life care
• APPLICATIONS: Elder care, palliative care

• This was an observational, 12-month, multi-center study that monitored patients monthly for 12 months.

At each monthly visit, measurements were taken as follows.

• Analgesic consumption measured and recorded by type prescribed
• Pain status measured on VAS
• Lab values including serum creatinine, calcium, hemoglobin, albumin, alkaline phosphatase, bilirubin, aspartame aminotransferase, alanine aminotransferase, and prostate-specific antigen in patients with prostate cancer
• Skeletal-related events

The percentage of patients on analgesics decreased in the multiple myeloma group from 57%–24%. In the group with prostate cancer, this percentage increased from 70%–88%. Pain VAS scores decreased by 22% in the patients with prostate cancer and by 97% in those with multiple myeloma. Hypocalcemia was recorded in 4% of all participants. Thirty-one skeletal events were reported by 10 patients (rate of 8%).

Zoledronic acid as treatment for patients with multiple myeloma may account for diminished concurrent use of analgesics for the same group over the annual period observed. Patients receiving zoledronic acid treatment concurrently with analgesics experienced a reduction in all types of skeletal events. This does appear to be an effective treatment for patients diagnosed with prostate cancer, specifically in terms of prophylactic treatment with bone metastases, as it has shown a decrease in skeletal events and pathological fractures. It is not effective for palliation of pain symptoms for patients with pancreatic cancer, as analgesic use increased for this group of patients.

• Risk of bias (no control group)
• Risk of bias (no appropriate attentional control condition)
• Excluded patients receiving any cancer therapy other than painkillers

Nurses work with patients to identify and communicate concerns to treatment providers at the earliest possible onset. The results of this study indicate a need for nurses to continue to evaluate, educate, and assist patients to communicate concerns to providers for the purpose of pursuing earliest possible interventions that provide the maximum effectiveness and best possible outcome for quality of care provided and quality of life resulting from that care for each patient. These findings reiterate an area for nursing attention when evaluating patients with pain issues at all stages of disease from initial diagnosis to progression, end-stage, and palliative care.

RESOURCE TYPE: Consensus-based guideline

PROCESS OF DEVELOPMENT: Relevant literature was selected by the authors; not based on a systematic review

Not specified

• Oxygen is not recommended for routine use. It can alleviate dyspnea in patients with hypoxia.
• Opioids are identified as the only pharmacologic agents with sufficient evidence for effectiveness.
• Benzodiazepines can be used in cases of insufficient response to opioids, either alone or in combination with opioids.
• Little evidence for nonpharmacologic interventions exists.
• In assessment, it is important to differentiate between continuous, episodic, breakthrough, or crisis breathlessness and determine exacerbating and relieving factors.
• Treatment of reversible causes should be considered before starting symptomatic treatment.

• No specified systematic review
• Written as mainly consensus-based

Provides very basic recommendations for dyspnea management in patients with advanced disease.

To evaluate the impact of the Urban Zen Initiative (UZI) on quantitative and qualitative measures of the experiences of patients admitted for inpatient oncology care.

The UZI model consists of five focus points:  the physical space surrounding patients, holistic nursing techniques, yoga with trained therapists, a navigator for patients, and audiovisual yoga materials at the bedside. All patients received the intervention; therefore, the investigators collected preintervention information about patients who were receiving standard care prior to the UZI intervention. Preintervention data were the basis of the control comparison. The investigators measured the outcomes immediately after admission and immediately before discharge. 

• The sample was comprised of 163 patients.
• Mean age preintervention was 52.9 years (standard deviation [SD] = 17.3 years). Mean age in the UZI group was 54.4 years (SD = 14.6 years).
• The preintervention group was comprised of 55% males and 45% females. The UZI group was comprised of 49% males and 51% females.
• The investigators did not specify the key disease characteristics.
• Patients were included if they
  • Were admitted to a specific inpatient oncology unit
  • Had a Karnofsky Performance Status (KPS) score greater than 60
  • Had a life expectancy longer than six months
  • Were able to speak English.

• Single site
• Inpatient
• Beth Israel Deaconess Medical Center, New York City

Patients were undergoing the active treatment phase of care.

The study used a quasiexperimental design with historical control groups.

• Profile of Mood States–Brief Form (POMS-BF)    
• EuroQol EQ-5D
• Semistructured qualitative interview
   

• The investigators noted no significant admission or discharge changes based on POMS scores.
• The investigators reported significant changes between groups in regard to tension (p = 0.009), depression (p = 0.03), vigor (p = 0.001), fatigue (p = 0.03), and total mood disturbance (p = 0.008). The scores indicated positive associations with UZI.
• Mobility was significantly different (p = 0.03) between the groups, according to the EQ-5D scores. The EQ-5D demonstrated no significant group-based changes in pain, anxiety, or health state.
• Thirty-three patients participated in qualitative data collection and indicated that the experience included fear and the need for information, caring, and connection. Responses also described the impact of the physical environment on patients' experiences, as well as the impact of yoga on patients' experiences of symptoms. Some patients stated they believed that what they had learned from the UZI could be useful in the future.

UZI may improve components of mood in an inpatient oncology setting. More work is needed to assess the real impact.

• The study had a risk of bias due to lacking an appropriate historical control group.
• Knowing which part of the intervention had the greatest effect was difficult because the UZI has many components.
• Whether the finding of significant pre- and post-UZI differences was based on initial POMS scores or \"change scores\" is unclear. Based on change scores, no intergroup differences existed.  

Providing a multifaceted healing environment, such as the UZI, within inpatient oncology settings could improve mood and perceived health status in patients with cancer. To facilitate the care process, nurses should assess patients' physical spaces; promote relaxation techniques, such as yoga breathing; and support patients.