To assess the effectiveness of and adverse events associated with opioid rotation for the management of cancer-related pain

All consecutive patients who attended the clinics of participating hospitals were eligible. A single opioid conversion table was used by all participants. If a rotation was used because of pain and toxicity, the baseline dosage was reduced by 25%–50% prior to the change. If no toxicity was present, an equivalent dose was used. Pain was assessed days prior to the implementation of the rotation and one week postimplementation. During the week, changes in opioid dosage were allowed and recorded. Patients were followed for 90 days.

• N = 67  
• MEDIAN AGE = 61 years (range 27–91 years)
• MALES: 73.1%, FEMALES: 26.9%
• KEY DISEASE CHARACTERISTICS: Various tumor sites; lung cancer was most prevalent; most had advanced disease
• OTHER KEY SAMPLE CHARACTERISTICS: Pain was nociceptive in 53.6% and mixed or neuropathic in 46.3%

• SITE: Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: Spain

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

Observational

• Numeric Rating Scale (NRS) for average and breakthrough pain
• Number of breakthrough episodes per day
• Common Terminology Criteria for Adverse Events (CTCAE)

About 89.5% of patients had one opioid rotation. The most common drugs used for the rotation were morphine, fentanyl, and transdermal buprenorphine. The most common switch was from fentanyl to morphine. The rotation was effective in 75.4% of patients for reducing average pain and in 57.8% for breakthrough pain. Average pain decreased at day 7 (p < 0.001) by four points, breakthrough intensity decreased by four points (p < 0.001), and the number of breakthrough episodes decreased on average from three to one (p < 0.001). Among patients in whom the rotation was effective, there were no significant differences between pre- and postequivalent doses of opioids. In 10 switches (out of a total of 75), there were no toxicities postrotation at one week. Rotations to methadone appeared to be associated with more postrotation adverse events.

The results of this study suggest that opioid rotation can be effective for pain management and the reduction of opioid-associated toxicities in most patients. Rotations to methadone appeared to be associated with more toxicities than rotations to other medications.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Questionable protocol fidelity
• Other limitations/explanation: Throughout the study period, the total opioid doses were not maintained although there was no overall significant difference in the morphine equivalents found. The study reported results at only one week. There was no information on the length of time patients received opioids prior to the study or the severity of toxicities prior to the rotation. There was no information regarding any potential adjuvant medication use.

In patients with severe cancer-related pain, opioid rotations may be beneficial for improving pain management and addressing opioid-related toxicities. However, the duration of this effect is not clear. These results suggest that switching to methadone might not be the best choice for reducing toxicities.

To assess the safety and efficacy of methylphenidate for cancer-related fatigue. Secondary outcomes included depression, cognition, and adverse effects.

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: PubMed. EMBASE, PsycINFO, Cochrane Collaboration

KEYWORDS: Methylphenidate, dimethylphenidate, Ritalin, cancer, fatigue, asthenia, tiredness, and randomized controlled trial

INCLUSION CRITERIA:  Randomized controlled trials, adults older than 18 years, the trial examined efficacy of methylphenidate on fatigue, and results were sufficient to calculate effect sizes

EXCLUSION CRITERIA: None specified

TOTAL REFERENCES RETRIEVED: N = 374

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The Jadad scale was used for quality assessment.

• N (studies) = 5
• SAMPLE RANGE ACROSS STUDIES: 10–62
• TOTAL PATIENTS INCLUDED IN REVIEW: 198
• KEY SAMPLE CHARACTERISTICS: Three studies included mixed tumor types, one was in prostate, and one was in patients with primary brain tumor.

PHASE OF CARE: Multiple phases of care

Meta-analysis was done with studies grouped according to the measure of fatigue that was used. In studies using the FACT-F (three studies), results showed a favorable effect of methylphenidate with a mean difference of -3.13 and a signficant overall effect (p -0.01). In studies using the BFI, results showed a favorable effect with mean difference of -0.69, but the Z test of overall effect was not significant. Methylphenidate had no effect on depression (two studies) or cognitive impairment (two studies). Studies varied widely in terms of the duration of treatment. Treatment for greater than four weeks was superior compared to placebo. However, treatment for less than four weeks did not show a significant effect compared to placebo. Rates of adverse effects between those getting methylphenidate and those getting a placebo were not significantly different. Those receiving methylphenidate had significantly more vertigo, anxiety, and nausea.

Results suggest that treatment with methylphenidate for at least four weeks is effective in reducing cancer-related fatigue and is not associated with a high rate of adverse effects. Treatment with methylphenidate did not improve depression or cognitive impairment. Use of different methods of measurement of fatigue showed different results.

Few studies were included, and some of these had very small sample sizes. Included studies did not provide sufficient information on relevant concomitant conditions of patients, such as sleep disorders and anxiety. Dosages and dosage increase approaches with methylphenidate varied.

Findings suggest that treatment with methylphenidate for at least four weeks can be helpful in managing cancer-related fatigue. However, the most appropriate dosages are not clear. Patients can experience side effects, and if methylphenidate is used, nurses need to monitor patients for side effects. Further large studies are needed to strengthen evidence related to effects and side effects of methylphenidate.

To determine the incidence of early onset hemorrhagic cystitis (EOHC) and identify the effectiveness of preventive measures upon EOHC

This retrospective study evaluated the effects of hyperhydration, diuresis alkalization, mesna, fluoroquinolone antibiotic prophylaxis, urethral catheterization, and CBI on 158 patients in two centers undergoing BMT regime upon EOHC. EOHC was defined as HC occurring within the 21 days after transplantation.

• N = 158  
• MEAN AGE = 41.9 years
• MALES: 59%, FEMALES: 41%
• KEY DISEASE CHARACTERISTICS: Patients receiving conditioning BMT regimes for either autologous (n = 5) or allogeneic (n = 153) BMT for hematologic malignancies  
• OTHER KEY SAMPLE CHARACTERISTICS: 40% of patients had AML.

• SITE: Multi-site    
• SETTING TYPE: Inpatient    
• LOCATION: Italy

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care

• Retrospective study of patients receiving BMT regimes at two Italian centers

Groups were compared using the Mann-Whitney U test (for continuous variables) and Yates’ correction (for categorical variables). Logistic regression was used to identify factors contributing to the development of EOHC, including gender, age, smoking habits, type of transplantation, stem-cell donor, Cytoxan dose, urethral catheterization, and CBI. A multivariate regression model using a backward stepwise selection algorithm was employed.

Thirty-one patients (all allogeneic transplantations) developed EOHC. Female gender (p = 0.24) and the dose of cytoxan (p = 0.016) were identified as independent risk factors for EOHC. The daily dose of mesna was the only significant measure (p = 0.01) identified between those who developed EOHC (median = 4.463) and those who did not (3.701).

Univariate analysis does not support the current standard, prophylactic catheterization and CBI, for prevention of EOHC. The best practice includes hyperhydration association with diuresis alkalization and mesna infusions.

• Unintended interventions or applicable interventions that would influence results were not described.
• This was a retrospective study.

Nurses caring for patients at risk of HC may need to reassess current standards for prophylactic treatment of HC.

• FINAL NUMBER STUDIES INCLUDED = 13 
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,003
• SAMPLE RANGE ACROSS STUDIES = 16–230 patients
• KEY SAMPLE CHARACTERISTICS: Various tumor types, patients in active treatment undergoing chemotherapy or radiation therapy

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Palliative care

Interventions considered to be BT were healing touch, Reiki, and therapeutic touch. The effect on pain was examined in seven studies. There were some mixed findings, but most showed a reduction in pain over short time periods. Fatigue was assessed in five studies. These demonstrated fatigue reduction post-treatment, but data were conflicting over a longer period of four to eight weeks. Anxiety and depression were examined in seven studies. All but one found a significant reduction in mood disorders, but a study comparing Reiki, sham Reiki, and usual care found no difference between the sham and actual Reiki groups. Most studies were of descriptive or quasi-experimental design; potential confounding variables were not examined, and placebo effects could not be ruled out.

Studies using biofield therapies for relief of pain, anxiety, fatigue, and depression generally showed benefit; however, the evidence is not strong due to the limitations of the studies included.

Low-quality design studies and the short duration of study follow-up

BT therapies have not demonstrated effectiveness in well-designed clinical studies; however, though it is weak, evidence suggests potential benefit. There were no adverse effects of these interventions reported. Biofield therapies are not expensive and are low-risk, so they can be considered in the management of cancer-related symptoms. Well-designed clinical trials are needed to establish efficacy.

To describe the management of moderate to severe dyspnea in patients receiving palliative care

A retrospective study was conducted using the records of patients who were consulted by a palliative care service over a five-year period. Information about medications prescribed was collected for patients who self-reported moderate to severe dyspnea at their initial evaluations by the palliative care service. Follow-up assessments of dyspnea were conducted by the palliative care service within 24 hours of the initial assessment. Data extraction was completed by a physician.

• N = 115  
• MEAN AGE = 64 years (SD = 17 years)
• MALES: 51% (n = 59), FEMALES: 49% (n = 56)
• KEY DISEASE CHARACTERISTICS: Primary diagnoses were cancer (64%, n = 59), heart failure (8%, n = 9), and chronic obstructive pulmonary disease (5%, n = 6). 
• OTHER KEY SAMPLE CHARACTERISTICS: Half of the sample was Caucasian (54%, n = 62). Pneumonia was diagnosed in 34% of patients (n = 39), and 30% of patients (n = 35) had a pleural or pericardial effusion. 

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Urban medical center

• APPLICATIONS: Palliative care

Retrospective chart review of patients with moderate or severe dyspnea

• Charleston Comorbidity Index (CCI) to assess the severity of illness through the classification of comorbidities to predict short- and long-term mortality
• Dosages of opioids were converted into milligrams of oral morphine per day by equianalgesic dosing.
• Plonk’s equation was used to convert methadone to morphine. 
• Dyspnea, pain, and anxiety were measured using a four-point categorical scale based on patient self-reports.
• Data from the chart review included the frequency and dose of opioids and benzodiazepines, age, sex, race, comorbidities, the presence of pneumonia, and pleural or pericardial effusion. 

Most patients reported an improvement in dyspnea within of 24 hours after palliative care service consultation. Most patients with dyspnea received opioids but only the combination of benzodiazepines and opioids was independently associated to improve dyspnea.

• Baseline sample/group differences of import
• Risk of bias (no control group) 
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)  
• Other limitations/explanation: The results were from a retrospective chart review. Conclusions cannot be drawn about the effectiveness of treatment or the causal relationships between medication and improvements in in dyspnea symptoms due to the study’s design. The study acknowledges potential confounding factors including patient factors, procedures, and psychological care that may impact the study’s findings. The results are reflective of the practices of one institution, which may limit generalizability. The population studied may not be generalizable to the broader palliative care population.

Because dyspnea is a common symptom in patients receiving palliative care, the authors conducted a study that reviewed the records of patients with moderate or severe dyspnea. The study found that opioids given with benzodiazepines were associated with improvements in dyspnea. Additional research to determine whether the use of benzodiazepines alone or in combination with opioids is more effective is necessary to to lead to improvements in dyspnea treatments.

To evaluate the effectiveness of preoperative dexamethasone in reducing postoperative nausea, vomiting, and pain after mastectomy

Patients were randomized to receive either IV dexamethasone 8 mg or placebo 60 minutes prior to skin incision. All patients had the same standardized general anesthesia. The same surgical team performed each surgery. Pain was assessed on entry to the recovery room and at 6, 12, and 24 hours postoperatively. Analgesia was ketorolac 30 mg every 8 hours and IV tramadol infusion 50 mg as backup medication. Patients were followed for up to 30 days after surgery.

• The sample was composed of 70 patients.
• In the placebo group, mean patient age was 49.89 years (SD = 10.58 years). In the dexamethasone group, mean patient age was 50.11 years (SD = 12.37 years).
• All patients were female.
• All patients had breast cancer. In each group, more than 90% underwent radical mastectomy with axillary node dissection.

• Single site
• Inpatient
• Guadalajara, Jalisco, Mexico

Double-blinded placebo-controlled randomized trial

• Visual analog scale, to assess pain
• Four-point ordinal scale (0 = no vomiting, 3 = vomiting), to assess postoperative nausea and vomiting

Compared to patients in the placebo group, those receiving dexamethasone had significantly lower pain scale scores immediately after surgery (p = 0.004), at 6 hours (p < 0.0005), and at 12 hours (p = 0.04). Pain score differences between groups were approximately 1 point at these times. Authors noted no differences between groups at 24 hours after surgery. More patients in the placebo group than in the dexamethasone group required analgesics (p = 0.008), and the mean dose of IV tramadol was lower for those who received dexamethasone (p = 0.03). Incidence of nausea and vomiting was lower with dexamethasone; more patients in the placebo group required antiemetics (p = 0.01)

Compared to preoperative administration of placebo, preoperative administration of dexamethasone was associated with less short-term postoperative pain, nausea, and vomiting.

• The study had a small sample size, with fewer than 100 participants.
• Patients with a history of motion sickness and other risk factors for nausea and vomiting were excluded from the study, so patients included were those at lower risk for these problems.
• Authors did not report actual intake of opioid or analgesic.

Findings suggest that preoperative dexamethasone administration can reduce short-term postoperative pain, nausea, and vomiting. In this study patients received specific anesthesia regimens. Findings may not be the same with different anesthetics. Further study in this area should identify optimal management of postoperative symptoms. The administration of a single corticosteroid dose prior to surgery can be a relatively low-risk intervention that seems to improve the patient’s experience.

To analyze risk factors for breakthrough invasive fungal infection (IFI) in patients receiving remission-induction chemotherapy and evaluate effects of echinocandin versus triazole prophylaxis

Data were obtained from patients’ electronic medical records for antifungal use, documented IFI, type of chemotherapy, use of HEPA air filtration, duration of hospitalization, and neutropenia and mortality. Kaplan-Meier curves were used to estimate the probability of remaining IFI free based on prophylaxis strategy. Patient data were used up to IFI diagnosis, loss to follow-up, death, or completion of 120 days post-induction, whichever came first.

• N = 125
• MEDIAN AGE = 64 years
• AGE RANGE = 51–73 years
• MALES: 55%, FEMALES: 45%
• KEY DISEASE CHARACTERISTICS: AML undergoing remission induction. The majority were on cytarabine-based regimens.

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

• PHASE OF CARE: Active antitumor treatment

• Retrospective

• None—no definition of IFI provided

Those receiving echinocandin versus mold active triazole had higher incidence of IFI (0% in the triazole group, 8% in the echinocandin group, p = 0.09). All cause mortality did not differ between groups. Regimens containing clofarabine for induction was also an independent predictor of IFI (p = 0.004). Patients who died within 120 days of beginning induction chemotherapy were more likely to be female, had prior chemotherapy-related AML, had lung disease or infection, or had cardiovascular disease as a comorbid condition. Those receiving echinocandin also had more breakthrough yeast infections.

Findings suggest that primary antifungal prophylaxis during remission induction with echinocandin may be less effective in preventing IFI than prophylaxis with mold-active triazoles.

• Risk of bias (no control group)
• Risk of bias (no random assignment) 
• There were very few fungal infections overall, and a much lower sample size that received echinocandin.

Patients with AML undergoing remission-induction chemotherapy are at high risk for developing IFIs, particularly mold infections. Findings from this study suggest that the class of antifungal prophylaxis agent used influences the patient’s risk of IFI. Nurses should be aware of the potential increased risk for fungal and yeast infections in patients getting echinocandin prophylaxis. Further research in this area is warranted given the limitations of this study.

STUDY PURPOSE: To review the evidence regarding effectiveness of home palliative care services for patients and their caregivers

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: 12 electronice databases were searched up to November 2012—Cochrane Central Register of Controlled Trials (CENTRAL); EMBASE; MEDLINE; Cochrane Pain, Palliative, and Supportive Care (PaPaS) Trials Register; Cochrane Effective Practice and Organisation of Care (EPOC) Trials Register; CINAHL; EURONHEED; PsycINFO; Cochrane Database of Systematic Reviews (CDSR); Database of Abstracts of Reviews of Effectiveness (DARE); Health Technology Assessment (HTA) Database; and NHS Economic Evaluation Database (NHS EED)

KEYWORDS: An extensive listing of search strategies is provided.

INCLUSION CRITERIA: Randomized controlled trials, time series, and pre-post trials; patients older than 18 years and/or their caregivers

EXCLUSION CRITERIA: Services provided in settings other than the home

• FINAL NUMBER STUDIES INCLUDED = 23 (7 included in meta-analysis and 6 included in cost analysis)
• SAMPLE RANGE ACROSS STUDIES: 42–747 in prospective studies; also included large analysis of retrospective data
• KEY SAMPLE CHARACTERISTICS: Advanced disease including noncancer and cancer

PHASE OF CARE: End-of-life care

APPLICATIONS: Palliative care

Strong evidence suggests that home palliative care services increase the likelihood of patients dying at home and decrease symptom burden for patients. Evidence regarding effects for caregivers is conflicting and inconclusive. Evidence regarding cost and cost-effectiveness is insufficient to draw conclusions.

• Most studies were old, and most were done in high-income countries.  
• Most studies had methodologic flaws and relatively high risk of bias.

Findings provide strong evidence that home palliative care services result in increased deaths at home and reduced symptom burden for patients. The effect for informal caregivers is uncertain. Caregiver burden can be higher in situations with more patient symptoms to manage, so one could expect that reducing patient symptom burden could have some benefit for the caregiver.

To compare hydrogel dressing to gentian violet (GV) for healing moist desquamation

Patients were referred after a nurse or radiographer identified moist desquamation. They were randomly assigned to GV or hydrogel. Patients were given instruction on how to apply GV or hydrogel at home and were assessed by radiographers on alternate days until the healing occurred. Tracing of the moist desquamation area on to polythene sheets was done randomly on different days with different patients.

• The study sample (N = 30) was comprised of male (6.3%) and female (93.7%) patients with head and neck or breast cancer.
• Mean age was 61.2 years for the GV group and 57.4 years hydrogel group.
• Median dose was 50 Gy, with a range of 40–64.7 Gy.

The study took place at a single site in the United Kingdom.

The study used a randomized controlled trial design.

• The end point was the time to healing.
• The secondary end point was “area under the curve” of the plot of the median area of moist desquamation against time.
• Tracing of the area of moist desquamation was used as the measure.

• Median healing time was 12 days in the hydrogel group and 30 days in GV group.
• Ten of the 16 patients withdrew from the GV group, citing nonhealing and stinging.
• Three of the 14 patients in the hydrogel group withdrew because of stinging and noncompliance.
• Over the first seven days, there were no differences in the area of moist desquamation.
• Over 14 days, the hydrogel group had a smaller area (p = 0.003), but the area of moist desquamation increased from baseline in both groups.

The study could not support or refute the value of hydrogel dressings.

• The sample size was small, with less than 50 patients.
• There is no standard system to identify moist desquamation.
• Many patients withdrew from the study.
• The study was stopped because of the benefit seen in hydrogel.
• The study had a risk of bias because it was unblinded.
• There was no standard amount of GV applications (several times a day).
• Patients with head and neck cancer often were not nutritionally sound, and patients with breast cancer may not have as many comorbidities.
• No subgroup analysis was done.
• The report did not mention if chemotherapy given.
• Although time to healing was the main end point, no statistical analysis of differences in time to healing could be done.
• There were no standard time points of skin evaluations.

To evaluate the efficacy of primary prophylactic pegfilgrastim compared to on-demand daily G-CSF after treatment with cladribine in patients with hairy-cell leukemia (HCL)

This was a retrospective chart review of 40 patients with HCL (1991–2012) treated with cladribine (0.1 mg/kg per day) for five to seven days either subcutaneously (SC) or IV, receiving a total of 40 courses of therapy treated with filgrastim (300 mcg per day) on demand until the patients' absolute neutrophil counts (ANCs) were > 2.0 x 10⁹ compared to nine courses of therapy with primary pegfilgrastim prophylaxis (6 mg SC for 24 hours after the completion of chemotherapy).

• N = 40 (on-demand filgrastim arm had 31 patients; primary pegfilgrastim prophylaxis arm had nine patients)   
• RANGE AGE = 23–76 years  
• MALES: 80%, FEMALES: 20%
• KEY DISEASE CHARACTERISTICS: HCL diagnosis confirmed by bone marrow biopsy and additional flow cytometry confirmation (after 2004); no significant difference in clinical and laboratory parameters between study populations before therapy including cytopenias, spleen size, ANC, platelet count, hemoglobin count, nadir duration, infections requiring hospitalization, and duration of hospitalization
• OTHER KEY SAMPLE CHARACTERISTICS: The on-demand filgrastim arm included two patients who received three cycles because of relapsed disease, seven patients who were treated with two cycles, and 31 patients who received only one course of therapy. In the primary prophylaxis pegfilgrastim arm, nine consecutive courses were given to nine patients 24 hours after the completion of chemotherapy.

• SITE: Medical centers
• SETTING TYPE: Inpatient  
• LOCATION: Haifa, Israel

• PHASE OF CARE: Active treatment

Retrospective, historical control study of patients with HCL prescribed cladribine determining the effect of IV pegfilgrastim versus filgrastim on neutropenia, hospitalization, 2⁰ FN, severity of infection, and ANC nadir

• The incidence of neutropenia (defined as an ANC < 1.0 x 10⁹ /L)
• Fever (defined as a temperature > 38.2 ^oC)
• Number of days of hospitalization because of FN
• Details of severity of infection
• Number days from the last day of therapy until ANC recovery (defined as an ANC > 1.0 x 10⁹ /L)

The median follow-up was 94 months (range = 12–312 months). No significant difference was found between primary prophylaxis with pegfilgrastim versus on-demand filgrastim for patients with HCL treated with cladribine for the variables of incidence of neutropenia, number days of hospitalization because of FN, severity of infection, or the number of days from the last day therapy till ANC recovery.

This retrospective study demonstrated no difference in the clinical effectiveness of primary pegfilgrastim versus on-demand filgrastim after cladribine therapy for patients with HCL.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Key sample group differences that could influence results
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Findings not generalizable
• Questionable protocol fidelity
• Other limitations/explanation: The majority of patients were in the filgrastim group (n = 31) compared to the pegfilgrastim group (n = 9). There may have been differences between the sites that were not disclosed. The grade of neutropenia not described. There were differences between the study groups (relapsed patients in the filgrastim on-demand arm). There were unknown comorbities in study population. Previous patient chemotherapy exposure was unknown. The details of the types and severity of infections post-treatment were not well-reported or described.

This study demonstrated no difference in the incidence of neutropenia, FN, or infections requiring hospitalization between the use of pegfilgrastim versus filgrastim after treatment with cladribine. Large, prospective, randomized trials need to be conducted to validate this study's results. Nurse-sensitive interventions remain critical in the prevention of infection for patients with HCL and prolonged neutropenia caused by disease and treatment.