STUDY PURPOSE: To assess lidocaine given in different doses in comparison with a placebo, diphenhydramine as a placebo, and active controls (morphine sulfate, ketamine, or amantadine). Mexiletine was compared to an inactive placebo and an active placebo (amitriptyline and gabapentin). Tocainide was used in one trial against carbamazepine. Pain was rated on an 11-point numeric rating scale (NRS). 

DATABASES USED: MEDLINE 1996–2004; EMBASE 1980–2002; CancerLit through December 2002; Cochrane Central Register of Controlled Trials through the second quarter of 2004; System for Information on Grey literature in Europe (SIGLE) and LILACS 1996–2001; hand searches of conference proceedings, textbooks, original articles, and reviews

• FINAL NUMBER STUDIES INCLUDED = 30 
• KEY SAMPLE CHARACTERISTICS: Thirty randomized, double-blind, controlled clinical trials, 16 with IV lidocaine, 12 with mexiletine, one trial with lidocaine plus mexiletine sequentially, and one trial with tocainide. Twenty-one trials were crossover studies, and nine were parallel. Measurement of pain intensity or pain relief was in minutes. All studies used a 0–100 m Visual Analog Scale (VAS) or a 0–10 numeric scale. The mean age was 51.7 years. The median number of participants per trial was 28. Multiple diagnoses were represented.

Intravenous lidocaine and its oral analog mexiletine were more effective than a placebo in decreasing neuropathic pain, were safe, and were as effective as other analgesics. The treatment effect was similar for both drugs. The analgesic effect was clinically important.

More than one half of the 29 trials were of low or fair methodological quality. One third did not adequately describe the method for random allocation, and 80% did not estimate the number of participants needed to have statistical power. However, some of these deficiencies could be because of incomplete reporting. Five trials did not describe exclusion criteria.

There is a need to study specific diseases and patient satisfaction to assess if statistically significant pain relief is clinically meaningful.

To determine the effectiveness of pranayama yoga on fatigue during radiation therapy

Patients were randomized to receive only radiation therapy with routine care or to perform pranayama during radiation therapy. Those in the yoga group performed pranayama morning and evening five days per week for six weeks under supervision. Fatigue was assessed at the beginning and end of radiation therapy.

• N = 160   
• AGE = 57% were younger than 45 years
• FEMALES: 100%
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients were scheduled to receive 50 Gy. All had received chemotherapy and had undergong surgery. Most had stage II or III disease.
• OTHER KEY SAMPLE CHARACTERISTICS: Seventy percent had only mild fatigue at baseline.

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

PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

Cancer fatigue scale

Post-test fatigue scores in the intervention group were lower (p = 0.001), and the intervention group had a significant decline in fatigue score (p = 0.001); however, all scores continued to be in the range of mild fatigue only.

Pranayama may be helpful to prevent or reduce fatigue during treatment with radiation therapy.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Patients had only mild fatigue at all study time points.
• Although postintervention differences were significant with pranayama, clinical relevant is unclear, because fatigue was still only mild.

Participation in yoga during cancer treatment may be helpful to combat symptoms of fatigue. This is a low-risk intervention that nurses can suggest to patients to manage fatigue.

To evaluate once weekly intravenous (IV) amphotericin B lipid complex (ABLC) given at a dose of 7.5 mg/kg as an alternative to posaconazole oral suspension (200 mg three times per day with food) for antifungal prophylaxis in hematopoietic stem cell transplantation (HSCT) recipients.

Patients were randomized to either the ABLC arm (N = 22) or posaconazole arm (N = 24).  All patients were at risk for invasive fungal infection due to intensive chemotherapy for treatment of acute leukemia or lymphoma with a prolonged period of neutropenia expected or they were in the early phase after allogeneic HSCT.  Patients were given ABLC 7.5 mg/kg once weekly over four to six hours or posaconazole oral suspension 200 mg three times daily with a high fat content meal for the duration of neutropenia.  The study evaluated adverse events through the end of prophylaxis and up to two weeks thereafter. Study endpoints were the incidence of invasive fungal infections and drug-related toxicities.  ABLC was discontinued if the creatinine level increased to two times the baseline or greater.  

• Forty patients were included.
• Median age was 56 years (range 21–69) in the ABLC arm and 55 years (range 20–66) in the posaconazole arm.
• All patients in both arms had hematologic malignancies; 100% of those in the ABLC arm and 90% of those in the posaconazole arm received an allogeneic HSCT.  In the ABLC arm, 58% were human leukocyte antigen (HLA)-matched related donors and 42% were matched unrelated donors.  In the posaconazole arm, 63% were HLA-matched related donors and 37% were matched unrelated donors.  
• Duration of prophylaxis was a median of 20 days (range 7–42) in the ABLC arm and 42 days (range 6–42) in the posaconazole arm.

• Single site 
• Inpatient 
• The location was presumed to be MD Anderson Cancer Center (not stated in the article).

Patients were undergoing the active antitumor treatment phase of care.

 This was a prospective, randomized, open-label, single-institution study.

Toxicities were measured using grades 1–4 based on Common Terminology Criteria for Adverse Events (CTCAE) v3.0.  Patient tolerability of the drug was also measured.  Compliance to oral posaconazole and fatty meal intake were measured based on patient diary entries.  Infusion-related toxicity (ABLC) was reported and recorded by the infusion nurse.  Creatinine clearance for ABLC administration was calculated using Cockcroft-Gault formula.  All patients were evaluated for clinical signs and symptoms and radiologic and mycological findings suggestive of invasive fungal infection during the study period (the duration of neutropenia).

Both groups were comparable for the rate of occurrence of neutropenia and its duration, steroid usage, tacrolimus therapy, and tacrolimus blood levels during prophylaxis.  Both groups were comparable for the development of graft-versus-host disease.  Nineteen patients in the ABLC arm and 20 patients in the posaconazole arm developed adverse events, including 18 drug-related events in the ABLC arm (nephrotoxicity, hypokalemia, hypomagnesemia, fever, chills, and headache) and 17 in the posaconazole arm (increase in liver function tests, hypokalemia, hypomagnesemia, nausea, vomiting, and diarrhea).  The discontinuation rate from adverse events was 15 of 19 in the ABLC arm versus 8 of 20 in the posaconazole arm (p = 0.009).  Lower creatinine clearance was noted in the ABLC arm (p = 0.006).  Patients receiving ABLC experienced more chills (p = 0.04).  Median duration of prophylaxis was significantly longer in the posaconazole arm (p = 0.04).  One patient in the ABLC arm developed an invasive fungal infection compared to none in the posaconazole arm.  The study was stopped early because the interim data analysis suggested that there was more than a 70% chance that the nephrotoxicity rate of the ABLC group was greater than 50%.

High weekly doses of IV ABLC may not be appropriate antifungal prophylaxis in allogeneic HSCT recipients due to potential nephrotoxicity, although it could be useful in less complex patients, such as those receiving therapy for leukemia (non-HSCT).  Oral posaconazole can have erratic absorption, but it was shown to be safer than weekly ABLC in this study.  Better prophylaxis is needed in patients who cannot tolerate oral medications.

• Small sample (<100)
• Risk of bias (no control group, no blinding, no appropriate attentional control condition, and sample characteristics*)
• Findings not generalizable*

* The findings are generalizable only to HSCT/hematologic malignancy patients, and only those with hematologic malignancies were included in the sample.

Because posaconazole is such an effective antifungal agent for prophylaxis (reinforced here), nurses must be vigilant in patient education.  Patients must be given instructions to take the drug during or within 20 minutes of a full meal (preferably with high fat content) or liquid nutritional supplement or with an acidic carbonated beverage (i.e., ginger ale).  There are many restrictions, and patient education is key to taking this drug and ensuring its efficacy.

The purpose of the study was to introduce prospective surveillance for nosocomial infections to improve prevention measures and reduce central line-associated blood stream infections (CLABSIs) in patients with hematologic malignancies.

Surveillance was performed for 18 months, after which the incidence rates for CLABSIs were calculated. Ward staff were then presented with the data and trained on measures to reduce CLABSIs according to national and international guidelines. During this time, they also implemented the use of chlorhexidine silver sufadiazine-coated catheters. Surveillance was then conducted for an additional 18 months.

• In total, 268 patients (57% male, 43% female) were included.
• All patients were 18 years or older.
• Patients were undergoing hematopoietic stem cell transplantation (HSCT).
• Patients were studied during neutropenic periods (defined as an absolute white blood count <1x10⁹ cells/L for at least two days).

• Twenty-bed HSCT unit
• The unit had 17 adult beds and 3 pediatric beds, although only adults were included in this study.
• Data from approximately 24 participating national and international centers for bone marrow transplantation from Germany, Switzerland, and Austria were used as a comparator for CLABSI incidence rates.

Active treatment

This was a prospective surveillance (pre/post design) study.

• Incidences (episodes per 100 patients) and incident densities (CLABSIs per 1,000 neutropenic days) were calculated.    
• Incidence densities were compared using the exponential maximum likelihood estimation test.
• Categorical variables were compared using chi-square or Fisher exact test, as appropriate.
• Risk factors were identified using a multivariate analysis with sequential backward stepwise elimination.
   

During the first study period (prior to intervention), CLABSIs occurred at a rate of 24.3 per 1,000 neutropenic days. This rate was notably higher than the median of the comparator group (17.7 per 1,000 neutropenic days) during the same study period. Following intervention, the CLABSI incidence rate dropped to 16.2 per 1,000 neutropenic days, which was below the median of the comparator group (17.7 per 1,000 neutropenic days). The reduction was significant (odds ratio = 0.58; 95% confidence interal [0.34-0.99]).

Strict adherence to hand hygiene and other preventive guidelines when handling central lines in neutropenic patients can have a positive impact on lowering the incidence of CLABSIs.

• The intervention involved educating clinical staff regarding improved preventive measures in handling central lines. The study did not monitor compliance with the new practices, which were multifaceted.  
• The outcome measure of 1,000 neutropenic days did not account for catheter dwell time as the usual CLABSI rate of patient catheter days. In addition to staff training, they also implemented the use of an antimicrobial-impregnated catheter, so it was difficult to determine which of these interventions was truly responsible for the change in results.
   

As part of the intervention, staff education included demonstrating that CLABSI incidence rates at the facility were higher than at comparable centers. This approach provides motivation for changes in nursing practice.

To evaluate the efficacy of HT 7 point acupressure for the treatment of insomnia in patients with cancer as compared to patients with medical illnesses other than cancer.

Patients were included if they reported sleeping disorders lasting at least three months, lacked response to benzodiazepine drugs, reported no chronic pain, and had no current drug therapy inhibiting the induction of sleep. Acupressure devices (H7 insomnia control, Consultream s.as., Como, Italy) were applied to both wrists starting at 10 pm each night for at least two weeks.

• The sample was comprised of 25 patients (32% male, 68% female).
• Median age was 62 years (range 48–75).
• Cancer diagnoses included breast, colorectal, and non-small cell lung cancer.
• Other medical illnesses included anxiety, idiopathic insomnia, and depression.

Not specified

The phase of care was not stated.

The study was a prospective, single-group trial.

• H7 Insomnia Control, Consulteam s.a.s., Como, Italy (intervention instrument)    
• No measure of sleep quality was stated.  
• Duration and pressure of acupressure was not stated.
   

Sleep quality improved in the first 10 days for 15 of 25 patients (60%). A greater number of oncology patients had improvements in sleep quality (79%) than those with other medical illnesses (36%), but this did not represent a statistical difference (no test statistic reported by the authors).

HT 7 improved insomnia in patients with cancer and other medical illnesses.

• The study had a small sample size, with less than 30 patients.
• The study used a convenience sample.
• The description of intervention and measures was inadequate.
• There was no stated measure of sleep quality.
• Chi-square values and other statistical values were not reported by the authors.
• There was no stated control of anxiety or depression in patients with cancer.
• No usual care control group was used.
• There was no stated control of potential confounding factors or medical conditions.
• The article lacked standard components of study reporting.

Further information is needed to accurately draw conclusions regarding the usefulness of acupressure in oncology patients.

Patients were randomized to receive IV L-alanyl-L-gluatime 0.3 g/kg (30 infusions in 5 patients) or 0.4 mg/kg (25 infusions in 5 patients), administered at a rate of 0.1 g/kg body weight/h. The principal endpoint was incidence of mucositis (mean of three highest scores by Objective Mucositis Assessment Score (OMAS) and highest grade on World Health Organization [WHO] scale).

• The sample consisted of 29 patients, 15 in the placebo group and 14 in the treatment group.
• All patients had unresectable head and neck cancer and received cisplatin and fluorouracil (5-FU) followed by concurrent chemotherapy and radiation.
• Patients with severe renal or hepatic insufficiency were excluded from the study. 
• No patients received steroids or antimicrobials prior to the study. No patients received any measure intended to prevent mucositis, although the authors did not indicate what standard oral care included.

The study used a two-step design. Patients were randomized first to different doses of the glutamine intervention, then to placebo (double-blind).

OMAS and WHO grading scale were used.

• OMS values were lower in the treatment group (1.33 in the placebo group versus 0.82 in the glutamine group) (p = 0.044).
• The mean WHO score was lower in the treatment group (2 versus 3) (p = 0.035).
• The OMS and WHO score correlation was significant (r = 0.83, p < 0.0001).
• Nine patients in the placebo group required feeding tubes compared to two patients in the treatment arm (p = 0.020).
• Patients in the treatment arm reported less pain (p = 0.008) and required fewer opioids (p = 0.025).

Measurement using both mucositis scales indicated a significant difference in intensity of mucositis.

• The study sample was small.
• Intensive nutritional support was used in both groups.
• All patients were supplemented with oral formulas containing no glutamine.
• Some question exists regarding whether glutamine can be a fuel for rapidly proliferating tumors; other studies have failed to demonstrate this effect.

• Medroxyprogesterone (MPA) 500 mg twice daily (BID) + celecoxib 200 mg BID + polymeric diet X 6 weeks
• Enteral food supplementation = 20% ​basal metabolic rate (BMR) with meal advice to caregiver and patient advice to engage in regular exercise.

Systemic-immune metabolic syndrome (SIMS) implies dysregulation of psychoneuroimmunoendocrine homeostasis, resulting in cachexia, anorexia, chronic nausea, early satiety, fatigue, tumor fever, cognitive changes, and superinfections (i.e., increased cytokines may increase cachexia-anorexia syndrome [CAS] and mediate anorexia).

The study included 15 adult outpatients with stage IIIb or IV lung adenocarcinoma.

Patients were included if they 

• Had CAS 10% weight loss
• Had anorexia 5/10 or greater
• Had fatigue 5/10 or greater
• Were not currently treated within one month with surgery, radiotherapy, chemotherapy, steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), appetite stimulants, or progestational agents
• Had no bowel obstruction, ascites, endocrine abnormalities, diabetes mellitus, severe anemia, or bleeding.

The study was conducted in a community outpatient setting in Argentina.

The study used a pilot, open-label, uncontrolled convenience sample design.

Weekly measurements included

• Performance status
• Appetite
• Nausea
• Fatigue Numerical Scale (FNS, 0-10)
• Calculations of lean mass (LM), fat mass (FM), total body water (TBW), caloric intake, mid-arm circumference (MAC), caregiver’s report of volume of supplement consumed, blood chemistry, C-reactive protein (CRP), interleukin-10 (IL-10), and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels.

• Thirteen of eighteen participants showed stable or increased weight compared with prestudy (p = 0.0001).
• Of the patients, 100% had a lowered rate of weight loss.
• Less than 20% of patients followed advice to exercise.
• Significant differences were noted in nausea, fatigue, appetite, performance status, and MAC.
• Some improvement trends were observed in body weight index (BWI) (body mass) and LM.
• No significant differences were noted in FM and TBW.

• The study was uncontrolled.
• The study had a small sample size.
• FNS was the only tool used to measure fatigue.
• Cox-2 inhibitor may prevent reduction of IL-10, causing more infectious complications.

Cost of medications, polymeric diet, and cost of cytokine measurements should be considered.

To determine if a structured approach using patient narrative in patients with advanced cancer decreases pain and improves sense of well-being

Patients were randomized into one of three groups: (1) narrative group, (2) questionnaire group, or (3) control group. Patients in the narrative group were asked to write about how cancer affected their lives, calling upon their deepest thoughts, feeling, and fears, and to write for at least 20 minutes once a week. Patients in the questionnaire group were asked to complete a pain questionnaire as an attentional control. Patients in the control group were asked to attend weekly medical follow-up visits and receive usual care. All patients were seen weekly in the clinic for eight weeks. Three weeks after randomization, research personnel called patients to remind them about completing narratives, filling out the questionnaire, and coming to the office for follow-up. Research personnel who collected data were blinded to group assignment. Patients rated their average pain intensity during the prior week in clinic visits. Investigators rated emotional content of the narratives.

• The study reported on 234 patients.
• Mean patient age across groups ranged from 46.2 (SD = 12.6) to 50.2 (SD = 10.5) years.
• The sample was 64% female and 48% male.
• Patients had a broad variety of cancer diagnoses, with breast cancer being the most prevalent (23.5%).
• All patients had a Karnofsky Performance Status score of less than 50%.
• All patients had an average pain intensity score of at least 5 on a 10-point scale, and average baseline intensity was at least 7.2 (SD = 1.8).
• The majority of patients had pain duration of less than six months.

• Single site
• Outpatient setting
• University cancer center in Bogota, Colombia

The study was a randomized, single-blinded, controlled trial.

• Numeric pain rating scale (0–10)
• Seven-point Likert-type scale for well-being

There were no differences between groups in outcomes measured. More than half (53%) of patients in the narrative group completed narratives as requested, 86% of patients in the questionnaire group completed the questionnaire, and 90% of patients in the control group kept all clinic appointments. Twenty patients did not demonstrate any emotional disclosure in narratives. Five patients had strong emotional content of narratives, and these patients had lower pain intensity scores.

Participation in writing narratives as structured in this study did not have any impact on pain or well-being. Only half of the patients fully participated in the narrative writing as designed.

• Methods for qualitative analysis of the emotional content of narratives were not described, and methods to ensure reliability were not stated.
• The observation that most narratives were not very emotional suggests that the impact of actual emotional disclosure cannot be evaluated from this study.

Study findings suggest that having patients write narratives for emotional disclosure to reduce pain is not effective. The apparent lack of actual emotional content in the majority of narratives reviewed in this study suggests that patients need assistance to identify and disclose these aspects of their experience. It is not clear whether patients may have concerns about privacy in terms of what content they provided in this research.

To evaluate the effect of listening to music on acute or chronic cancer pain; to relate the effect of listening to music on analgesic requirements

• Databases searched were the Cochrane Pain, Palliative & Supportive Care Group Trials Register and the Cochrane Central Register of Controlled Trials (Sept. 14, 2004); MEDLINE (1966–Oct. 4, 2004); EMBASE (1980–Sept. 15, 2004); PsycINFO (1985–Sept. 24, 2004); and LILACS (1982–Sept. 8, 2004).
• Search keywords included free text, MeSH, and Emtree terms: music, music therapy, analges*, and pain. The report provides an extensive list of search terms.
• Studies were included if they
  • Were randomized controlled trials.
  • Evaluated the effect of music on acute, chronic neuropathic cancer pain or experimental pain in children or adults.
  • Involved evaluation of pain intensity, pain relief, global improvement, or opioid requirement.
• Studies were excluded if a music intervention was combined with any nonpharmaceutical approach to pain.

• Investigators retrieved 113 studies, 62 of which the investigators excluded.
• Authors assessed study quality by scoring subject assignment, study blinding, dropout rate, and intention-to-treat analysis.

• The final sample included 51 studies.
• The 51 studies comprised 1,867 patients who received a music intervention and 1,796 control patients, who did not.
• Eight studies evaluated the use of music to treat the pain of children and neonates.
• The range of patients in a sample was 11–233. Median sample size was 53.
• Samples included patients with chronic pain, acute pain, postoperative pain, and labor pain.

• Pain intensity: Meta-analysis involved 30 studies that used the same scale of pain intensity. The pooled estimate of effect was a 0.46 reduction on a 0–10 point scale (95% CI = –0.75 through –0.17, not significant). The studies comprised significant heterogeneity, and authors' analysis showed that one study had a major influence on overall effect size. When this study was removed, the effect of music was deleterious, being associated with a pain increase of 0.3.
• Studies of children: In the eight studies of children, four studies did not provide quantitative data. Overall, no effect on pain proved significant, though some positive results were reported.
• Pain relief: Four studies showed that 70% of those who used music had a greater probability of at least a 50% reduction in pain, relative risk (RR) – 1.70 (95% CI 1.21–2.37, p = 0.002).
• Opioid requirement: Thirteen studies evaluated differences in opioid requirements. These studies were of patients who had procedural or postoperative pain. The mean difference (MD) supported use of the music intervention: –1.29, (95% CI –2.22 through –0.37, p = 0.006)
• Authors judged that half the analyzed studies were of low quality. Authors noted a high level of heterogeneity in most subgroup analyses.

Music has limited utility in clinical practice for pain reduction: A music intervention was associated with minimal reduction in pain intensity. A music intervention was associated with a small reduction in opioid use for the treatment of acute pain. The reduction was smaller than that associated with the use of an NSAID or paracetamol.

The analysis provided little support for the effectiveness of music in the reduction of pain: The size of effects is small, and their clinical relevance is unclear. On the other hand, the analysis revealed no negative effects from the music intervention. Clinicians should be aware of the limited utility of music for pain management. Most of the studies in the analysis did not include patients with cancer; however, the highest effect sizes were in the setting of chronic pain, so a music intervention may be relevant to patients with cancer. Use of music along with other nonpharmaceutical and maximal pharmaceutical pain management may be helpful for some patients. Further research in this area would be useful.

To study the efficacy of methylphenidate for relief of depressive symptoms in patients with advanced cancer.

Patients who indicated some depressive symptoms from screening were randomized to receive methylphenidate ranging from 10-45 mg daily for 28 days. Doses were adjusted according to individual patient need and toxicity evaluation according to a protocol established for the study. Patient visits and evaluation occurred at days 0, 2, 7, 14, 21, and 28 either in the clinic or the patients’ homes. Patients who completed at least eight days of involvement were included in intent-to-treat analysis using the last measure carried forward.

• N = 69  
• MEDIAN AGE = 72 years (range = 40-87)
• MALES: 58%,FEMALES: 42%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types. Average Karnofsky score range = 50-70
• OTHER KEY SAMPLE CHARACTERISTICS: About 75% had clinically significant HADS depression scores at baseline, and slightly less than 50% had clinically relevant anxiety scores. All had a life expectance of at least one month.

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

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

• Double blind, randomized, placebo controlled

• Hospital Anxiety and Depression Scale (HADS)
• Edmonton Symptom Assessment Scale (ESAS)

Methylphenidate administration was not significantly better than placebo for symptoms of depression or anxiety and was associated with more adverse events. The evidence regarding efficacy of methylphenidate is inconclusive.

• Small sample (less than 100)
• Other limitations/explanation: Study was underpowered

This study sample was not large enough to enable firm conclusions from this individual study; however, findings did not show a benefit of methylphenidate and showed more adverse events that may be associated with methylphenidate. These results are not supportive for use of methylphenidate in the management of anxiety and depressive symptoms in patients with advanced cancer.