The objective of this study was to compare the efficacy of supplemental, oral, and parenteral opioid doses consisting of either 25% or 50% of the equivalent 4-hour opioid dose (i.e., total 24-hour opioid dose divided into 4-hour portions) in patients already receiving opioids on a regular basis.

The study reported on a sample of 33 terminally ill patients with cancer and dyspnea at rest who already were receiving opioids.

The study was conducted in three separate palliative care centers in Quebec, Canada.

The study was a randomized, double-blind, continuous sequential controlled trial.

Dyspnea intensity on the visual analog scale and respiratory rate were measured at baseline, 30, 60, 120, 180, and 240 minutes after dose.

The overall treatment effect, as measured by dyspnea intensity and respiratory frequency, was not significantly different for 25% or 50% of the equivalent four-hour opioid dose. A significant (p < 0.0001) decrease was found in pre- and post-dyspnea intensity. Dyspnea decrease was inverse to baseline dyspnea intensity (i.e., low dyspnea at baseline had greater decrease in dyspnea intensity whereas high dyspnea at baseline had less decrease).

• Authors reported that the sample required one more pair to offer definitive preference in favor of 25% of the four-hour dose.
• The finding was restricted to those already receiving regular opioids.
• The study was properly designed and conducted at multiple sites; however, the sample was limited.

Because 25% and 50% doses had the same effect, a supplementary dose of 25% of the equivalent four-hour opioid dose is recommended to reduce dyspnea for as long as four hours.

To assess the efficacy and safety of an intrathecal (IT) combination of ziconotide and morphine in malignant pain refractory to high doses of oral uploads

Visual anolog scale of pain intensity (VASPI) scores and Karnofsky Performance Status Scale (KPSS) scores were recorded for each patient at the initial visit. An IT catheter was place under fluoroscopy with aseptic technique, with a 1 g dose of cefazolin to prevent infection. Patients continued their long-term oral morphine until the IT infusion started and asked to start a short-acting morphine dose of 10 or 30 mg if needed. VASPI and KPSS scores, vital signs, electrocardiograms (ECGs), and adverse events were evaluated at day 2, day 7, and weekly up to day 28. The ziconotide infusion titration was started at 2.4 micrograms per day and increased by 1.3 micrograms per day at day 7 in patients with a VASPI score greater than 30 at rest. IT morphine dose was calculated based on their daily dose, an oral-IT ratio of 400:1. Increases in IT morphine were based on the oral morphine consumption. Doses were adjusted for adverse events and analgesic effect. The mean VASPI score, mean change in VASPI score, and mean percentage change from baseline to each visit and to the last observation was calculated.

• N = 20   
• AGE = 18 years or older
• MALES: 35%   
• FEMALES: 65%
• KEY DISEASE CHARACTERISTICS: Disseminated cancer with bone metastasis involving vertebral bodies
• OTHER KEY SAMPLE CHARACTERISTICS: Participants had to have pain related to malignancy, prevalently nociceptive pain, a VASPI score greater than 70 mm at rest, or an occurrence of adverse events. Patients were excluded if they showed signs of sepsis or inadequately treated infection; uncontrolled heart failure; second-degree heart block; third-degree heart block; or history of dementia, delirium, hysteria, or untreated affective disorder.
   

• SITE: Single site   
• SETTING TYPE: Inpatient setting   
• LOCATION: Pain Centre at Italy Bari Policlinico Hospital, Bari, Italy

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Late effects and survivorship; end-of-life and palliative care
   

• Prospective, observational study
  • Used repeated measures

• KPSS
• VASPI
• Vital signs: blood pressure, heart rate, respiratory rate, and temperature
• 12-lead ECG
• Adverse events: Coding Symbols for Thesaurus of Adverse Reaction Terms (5^th ed.)
   

Prior to the study, participants had persistent pain for a mean of six months SD = two months) and took a mean daily dose of 320 mg per day (SD = 80 mg) of systemic opioids. The mean VASPI score at rest was 90 mm (SD = 7 mm), with a mean incidental VASPI score of 99 mm (SD = 3 mm), and a mean KPSS of 59 (SD = 10. 4). Patients had severe opioid-related side effects that did not permit an increase in systemic opioids. IT therapy started with morphine 0.82 mg per day (SD = 0.36 mg) with ziconotide 2.4 mcg per day. On day 2, the mean VASPI score at rest decreased to 55 mm (SD = 12 mm), a significant reduction (p < .001). For five patients, an increase in morphine was necessary. On day 7, the mean VASPI at rest was 44 mm (SD = 11 mm), a significant decrease (p < .001). Four patients had an increase in ziconotide daily. On day 28, mean VASPI was 34 (SD = 13), a significant decrease (p < .001). Eighty percent of patients reached the effective dose for morphine and ziconotide within two weeks. Only five patients survived until the third month with good pain control. The maximum dose of ziconotide was 5.2 mcg per day, and the maximum dose of morphine was 2 mg per day. Four patients developing adverse effects attributed them to the study drugs. Changes in serum creatinine kinase levels and vital signs were not significant. No infections correlated with IT catheter placement.

IT therapy with ziconotide and morphine is a helpful strategy in controlling malignancy-related pain refractory to high dose of systemic uploads. Using both drugs appears to have a synergistic effect and may benefit patients with cancer. Lower doses of each drug may be utilized with few adverse events and side effects. However, this study has a few limitations that impair generalizability, may have a potential for bias, and may not have captured the risk to patients being treated longer than a few months.

• Small sample (less than 30)
• No control group or comparison (potential for bias)
• No randomization, no blinding
• Sample size was 20 (less generalizable).
• Only five patients survived to three months.
• Oservation was limited to one month.
• The sample was small and the length of observation was limited, so observable adverse events and complications may have not been observed.

Combination IT ziconotide and morphine in patients with cancer with nociceptive bone pain refractory to systemic opioids may be a helpful strategy for controlling pain. Low doses of ziconotide are required with the use of morphine, as compared to higher doses of ziconotide alone. In turn, less adverse events may be observed with potentially better pain control. When considering drug stability, alternative agents for pain in combination with ziconotide may be considered in place of morphine, as pump refills are required with lower-stability agents.

To determine if a multimodal exercise program for patients during induction chemotherapy is feasible, safe, and beneficial for fatigue, quality of life, and fitness

Patients were randomized to the exercise or usual care groups. Usual care generally included suggestions to walk on a regular basis, without further instruction. Those in the exercise group were approached 4–5 days per week during hospital admission to participate in light-to-moderate–intensity exercise for 30–60 minutes. Exercise sessions included combined aerobic, resistance, and flexibility training. Aerobic intensity was encouraged at an exertion equivalent to 50%–75% of heart-rate reserve. The resistance exercises targeted large muscle groups using resistance bands and free weights. Flexibility was incorporated into each session via static stretching. Exercise sessions were directly supervised by a certified exercise physiologist. Study assessments were completed at baseline, post induction, and within two weeks of discharge, post cycle 2 (4–6 weeks post discharge).

• N = 70 post induction; 63 completed post-consolidation measures.
• MEAN AGE = 57 years (SD = 14.7)
• MALES: 54.3%, FEMALES: 45.7%
• KEY DISEASE CHARACTERISTICS: Patients with acute myeloid leukemia (AML) or relapsed AML receiving induction chemotherapy who were medically cleared for participation
• OTHER KEY SAMPLE CHARACTERISTICS: Participants in the exercise group were slightly older.

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

• PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trial

• European Organization of Research and Treatment of Cancer Core Quality of Life (EORTC QLC-C30)
• Functional Assessment of Cancer Therapy-Fatigue (FACT-F) subscale/BMI
• Maximal oxygen consumption test (VO₂ max test)
• Six-minute walk test (6MWT)
• Grip strength
• Daily exercise diary for control patients

Exercise group participants completed 514.2 minutes of exercise on average during an average admission of 36.5 days. The most common reported reason for not exercising was fatigue. Adherence to exercise sessions was 54%. Control group patients exercised an average of 510.4 minutes over 35.8 days. Participants in both groups demonstrated an improvement in global quality of life. Fatigue scores improved only in the exercise group, with a between group difference of 3.6 points, which was not statistically significant. The six-minute walk improved in both groups but improved significantly more in the exercise group (p = 0.005). No significant adverse event occurred. During over 1,000 patient days of observation, four musculoskeletal events were reported. No differences existed between groups in length of stay or other resource utilization.

This study demonstrated that the provision of an exercise program is feasible for patients during induction chemotherapy and may help manage fatigue in these patients. Patients who participated in the multimodal exercise program demonstrated improved physical fitness.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Given the comparison of mean hours of exercise between study groups, the total amount of physical activity did not appear substantially different between groups, which may have affected the lack of substantial differences in fatigue.

Participation in an exercise program of moderate intensity was shown to be feasible for patients who were hospitalized and receiving induction chemotherapy for AML.

To examine the feasibility (recruitment, retention, and adherence), preliminary efficacy, and safety of a 12-week, home-based exercise program for middle-aged and older acute myeloid leukemia (AML) survivors

• N = 40  
• AVERAGE AGE = 56 years
• MALES: 45%, FEMALES: 55%
• KEY DISEASE CHARACTERISTICS: Acute myeloid leukemia; the average time from diagnosis to study enrollment for all participants was approximately two years.
• OTHER KEY SAMPLE CHARACTERISTICS: Participants were mostly white. The mean body mass index (BMI) 28.25%. Patients had undergone posthematopoietic stem cell transplant.

• SITE: Single-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Home and “health care” gym

• PHASE OF CARE: Transition phase after active treatment
• APPLICATIONS: Elder care  

Phase II randomized controlled trial with an exercise group and a wait-list control group that could cross over to the exercise group at week 12.

• Primary outcome measures included both global quality of life (QOL) and fatigue.
• QOL was measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).  
• Functional Assessment of Cancer Therapy–Fatigue (FACT-F)
• Secondary outcome measures included the Edmonton Symptom Assessment Scale (ESAS).

Recruitment and retention rates were 31% and 91%, respectively. The adherence rate was 28%. The analyses did not suggest statistically significant or clinically important benefits in QOL, fatigue, or physical fitness between groups. There were no adverse events.

Successful recruitment with low adherence and limited effects on clinical outcomes including fatigue.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement/methods not well described
• Other limitations/explanation: The description of the cross-over of patients from the control group is confusing and inconsistently described from the actual protocol.

Further study is needed in this population including how to enhance exercise adherence.

To evaluate the effectiveness of colloidal oatmeal lotion (Aveeno^®), administered TID for at least seven days.

• The study reported on a sample of 10 patients.
• Patients were receiving epidermal growth factor receptor–inhibitor (EGFRI) and tyrosine-kinase inhibitor (TKI) therapy (e.g., cetuximab, erlotinib, panitumumab, sorafenib) and were experiencing cutaneous reactions.

Multiple centers in Washington, DC, and New York, NY

This was an open-label study used to evaluate the rate and quality of response to colloidal oatmeal lotion.

Toxicity was graded as follows.

• Grade 1: asymptomatic, erythematous rash
• Grade 2: rash plus itching
• Grade 3: confluent lesions and tenderness
• Grade 4: deep ulcerations and exfoliative or severe xerosis

• Ten of 11 patients were evaluable.
• Six patients had a complete response and four had a partial response; therefore, the response rate was 100%.
• Responses occurred from six to 10 days after initiation of colloidal oatmeal lotion.

Treatment with colloidal oatmeal lotion appeared to be effective in controlling rash associated with EGFRIs and multiple TKIs. This treatment allowed for the continuation of antineoplastic therapy.

• This was a small, nonrandomized, open-label study.
• The description of the measurement tool or method used to grade rash symptoms was inadequate; reliability and validity were unclear.

To evaluate the short- and long-term effects of ropivacaine wound infiltration on pain after breast cancer surgery

Patients were randomized to receive, prior to surgery, either ropivacaine or normal saline placebo wound infusion. All patients received the same general anesthesia regimen of propofol and sufentanil. At the end of surgery, before skin suturing, the wound was completely infiltrated along the subcutanous and deep layers of the breast and axilla surgical incisions. Infiltration was also done in the second and third intercostal spaces. The ropivacaine group received 3 mg/kg of 0.375% ropivacaine. Pain was assessed every 30 minutes for two hours in the postanesthesia care unit and every six hours for the next 48 hours. Patients completed study questionnaires at baseline and at 3, 6, and 12 months after surgery.

• The sample was composed of 236 patients.
• Mean patient age was 56.5 years.
• All patients were female.
• All patients were undergoing surgery for breast cancer; 45%–52% had breast-conserving surgery with axillary node dissection, and 40%–45% had mastectomy with either axillary or sentinel lymph node dissection.

• Single site
• Multiple settings
• France

Mutliple phases of care

Randomized double-blind placebo-controlled trial

• Visual analog scale (VAS) to assess pain
• Brief Pain Inventory
• Hospital Anxiety and Depression Scale

• During the first 90 minutes, with patients at rest and with movement, VAS pain scores were lower in the group that received ropivacaine (p < 0.001) than in the control group.
• Over the first 48 hours in the ropivacaine group, 73% reported no pain at rest and 53% reported no pain during movement. Over the first 48 hours in the control group, 53% reported no pain at rest and 48% reported no pain during movement (p < 0.001).
• In the first 48 postoperative hours, authors noted no differences between groups in regard to morphine consumption.
• At 3, 6, and 12 postoperative months, authors noted no differences between groups in regard to pain scores.

Surgical wound infusion with ropivacaine resulted in significantly lower acute postoperative pain as measured up to 48 hours after breast cancer surgery. Wound infusion had no effect on longer-term postoperative pain.

Authors did not describe chronic levels of pain at follow-up time points.

Local wound infusion resulted in significantly lower acute postoperative pain after breast cancer surgery. This study adds to the body of evidence that demonstrates the effectiveness of this approach. Nurses can advocate for this approach to help ensure that surgical patients receive effective acute pain management.

STUDY PURPOSE: To examine the efficacy of chemoprotective agents to prevent or limit neurotoxic side effects of cisplatin and related chemotherapy agents

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 20 
• TOTAL PATIENTS INCLUDED IN REVIEW = 2459
• SAMPLE RANGE ACROSS STUDIES: 18–755
• KEY SAMPLE CHARACTERISTICS: Varied tumor types receiving platinum-based chemotherapy

PHASE OF CARE: Active antitumor treatment

There is insufficient high quality evidence to show that any agent is protective against platinum-induced neuropathy. There is some suggestion that amifostine, glutathione, and calcium and magnesium may have some effect.

• Limited number of studies included
• Low sample sizes
• There were few studies per intervention, and very few studies with small sample were included in the meta-analyses.

There is insufficient evidence to show that any agent is truly effective in protecting against neurotoxic effects of platinum-based chemotherapy. There is a continued need for well designed research using appropriate objective as well as subjective measures of neuropathy.

Examine the efficacy of purported chemoprotective agents to prevent or limit neurotoxicity of cisplatin and related agents

TYPE OF STUDY: Combined systematic review and meta-analysis

DATABASES USED: Cochrane Neuromuscular Disease Group Specialized Register, Cochrane Central Register of Controlled Clinical Trials, MEDLINE, EMBASE, LILACS, and CINAHL

KEYWORDS: Extensive list provided in article appendix

INCLUSION CRITERIA: Quasi-randomized or randomized clinical trials whose participants received cisplatin (or related compounds) chemotherapy with or without a potential chemoprotectant and were evaluated zero to six months after completing chemotherapy using quantitative sensory testing (primary) or other measures, including nerve conduction studies or neurologic impairment rating using validated scales (secondary)

TOTAL REFERENCES RETRIEVED: Sixteen randomized trials were evaluated in the initial 2006 review. In the 2010 update, 11 additional randomized trials not among the 2006 review were identified.

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane method of evaluation for risk of bias done by two authors and finalized by consensus

• N (studies) = 6
• SAMPLE RANGE ACROSS STUDIES: 14–242
• TOTAL PATIENTS INCLUDED IN REVIEW: 1,537 participants
• KEY SAMPLE CHARACTERISTICS: Patients who received cisplatin chemotherapy

Cisplatin is considered to have neurotoxic effects, with patients developing sensory neuropathy. Symptoms of pain, numbness, and tingling are observed mostly in the extremities from a distal to proximal distribution. The neuropathy experienced by patients may recover partially or may become permanent. Neuroprotective agents such as acetylcysteine, acetyl-L carnitine, amifostine, calcium and magnesium, growth factors, glutathione, ORG 2766, oxcarbazepine, and vitamin E have been tested. The five newly added randomized controlled trials included three chemoprotective agents not previously described in the 2006 review.

From the data examined in this updated review, inconclusive evidence exists for recommending any neuroprotective agent tested to prevent or limit the neurotoxicity of platinum chemotherapy.

While 1,537 participants were included in the 2010 update, few trials were amenable to meta-analysis. Clinical trials of neuroprotective agents are plagued by issues of study design, including small sample size, unclear randomization and blinding procedures, and lack of quantitative measures, especially conventional QST or electrophysiologic evaluation.

To determine the efficacy of sucralfate mouthwash in the prevention of oral mucositis (OM) in patients receiving fluorouracil (5-FU) chemotherapy

Patients 18 years and older receiving chemotherapy containing 5-FU and calcium folinate were randomized into two groups through a computer-generated list of random numbers. One group received sucralfate suspension mouthwash and the other group received a placebo. Both groups received 10 ml of either sucralfate or placebo mouthwash every six hours for 10 days after the last dose of chemotherapy. Patients were instructed to rinse their mouth with the suspension for at least five minutes and spit it out 30 minutes after meals to ensure prolonged exposure of the mouthwash to the mucosal membranes.

• N = 51   
• AGE = Older than 18 years
• MALES: 15 (sucrafate group), 20 (placebo group); FEMALES: 10 (sucralfate group), 6 (placebo group)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Gastrointestinal cancer (e.g., esophageal, colon, rectal, gastric)

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Imam Khomeini Educational Hospital, Sari, Iran

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics, elder care, palliative care 

• Double-blind, randomized controlled study

• World Health Organization (WHO) grading system for mucositis
• Visual analog scale (VAS) to grade pain intensity

A statistically significant difference in the severity of mucositis was shown between the sucrafate group and placebo group on both day 5 and day 10 (p = 0.005, p < 0.001), respectively. The severity of mucositis in the sucrafate group on day 5 and 10 was grade 0. The majority of patients in the placebo group had a mucositis severity grade 2 on day 5 and day 10. A statistically significant reduction in pain intensity was shown in the sucrafate group versus the placebo group on both day 5 and day 10 (p = 0.004, p = 0.001), respectively.

Sucralfate mouthwash may be more effective than placebo in the prophylaxis of 5-FU–induced OM. A correlation between both the reduction of pain intensity and mucositis severity was shown with the use of the sucralfate mouthwash suspension, further confirming the role of sucralfate in the prophylaxis of OM in patients receiving 5-FU chemotherapy.

• Small sample (< 100)

Sucralfate mouthwash may be effective in reducing the severity and pain intensity of OM in patients receiving 5-FU.

The objective of this study was to compare the effectiveness of bleomycin as a sclerosing agent with povidone-iodine with respect to efficacy, cost, accessibility, safety, ease of administration, and number of doses for complete response.        

Forty participants were assigned into two treatment groups of bleomycin treatment or povidone-iodine treatment via block randomization. A 28Fr. chest tube was placed in all patients at the bedside under local anesthesia with opioids given for pain. The following day, both groups had a sclerosing agent instilled in the chest tube for one hour; bleomycin at 1 mg/kg in 60 mL saline in the study group and povidone-iodine 10%, which was diluted to obtain a final concentration of 2.5% povidone-iodine in the control group. Both groups had 5 mL of 2% lidocaine solution added to the sclerosing agent. In both groups, the chest tubes were clamped for one hour and then connected to water seal. All patients were admitted to the same unit in the hospital and experienced the same post-pleurodesis respiratory and pain management protocols. The chest tube remained in place until output decreased to 200 mL; if high output persisted more than 10 days, a Heimlich valve was placed and patients were discharged from the hospital. Chest x-rays were obtained post-chest tube removal and at 30 days post-procedure to evaluate size of pleural effusions. Pain and dyspnea after drainage ratings were recorded at discharge and at 30 days post-op. 

The sample was comprised of 39 patients.

Key disease characteristics included

• Biopsy- or cytology-proven malignant pleural effusions with a variety of types of cancer
• Effusions previously treated with and showing improvement with thoracenteses but recurrent or symptomatic when entered in study.

Key sample characteristics included

• Symptomatic benefit from thoracenteses
• Chest radiograph confirming lung expansion of 90% or more after therapeutic thoracenteses
• Karnofsky performance status index greater than or equal to 70
• No one with comorbidities that would exclude them from general anesthesia
• No bleeding disorders, massive skin infiltration, or active infectious disease.
   

This single-site study was conducted in the inpatient unit at Valiasr Hospital in Tehran, Iran.

• Patients were undergoing long-term follow-up care.
• The study has clinical applicability for end-of-life and palliative care.
   

The study was a randomized clinical trial.

• Chest tube placement, +/- Heimlich valve    
• Numeric pain scale
• Chest x-ray
• Dyspnea scale (1–10)
   

• According to author reports, the groups were equivalent in demographic variables, but this data was not visible to the reviewer.
• No significant difference was seen between groups with respect to age, duration of thoracostomy, volume of pleural effusion, dyspnea score after drainage, fever, and pleural effusion after drainage, discharge, and one month later.
• Patients in the bleomycin group had significantly lower dyspnea scores at the one-month follow-up time compared to the povidone-iodine group.
• Complete pleurodesis occurred in 79% of the bleomycin group and 75% of the povidone-iodine group, which is not a significant difference in treatment results.

• Bleomycin is more effective at long-term dyspnea management based on one-month follow-up reports.
• No differences were observed between groups based on pain score following procedure, dyspnea at discharge, or reoccurrence of pleural effusion at the one-month follow-up visit. 
• Neither method demonstrated extremely superior results and appear similar in overall effects.

• The study had a small sample size of less than 100 patients.
• Groups were not matched by age and sex.
   

When compared with povidone-iodine, bleomycin offers the advantage of being more effective for dyspnea symptoms one month post-procedure. However, both methods appear similar in terms of pain scores, dyspnea at discharge, and recurrence of pleural effusions at one-month follow-up. For patients with concerns of iodine absorption or side effects, bleomycin would be a comparable sclerosing agent.