To determine if using antimicrobial-coated central venous catheters (CVCs) is of benefit for patients undergoing stem cell transplantation

Patients were given multilumen polyurethane nontunneled antimicrobial chlorhexidine/silver sulfadiazine-coated CVCs. Transparent occlusive dressings were changed weekly or more frequently as needed. Blood cultures were taken from CVC lumens and peripheral blood on first occurrence of fever or at the discretion of medical staff.  Skin swabs were taken from around the CVC insertion site with dressing changes before local disinfection. Povidone-iodine was used for skin disinfection with dressing changes and before CVC insertion. CVC insertion was stated to be under strict aseptic technique. Patient outcomes were compared to those of historical controls in whom noncoated CVCs were used.

• N = 107
• MEDIAN AGE = 52 years
• AGE RANGE = 20–68 years
• MALES: 57%, FEMALES: 43%
• KEY DISEASE CHARACTERISTICS: All had hematologic malignancies; 47.7% had acute myeloid leukemia.
   

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

• PHASE OF CARE: Active antitumor treatment

• Prospective
  • Comparison to historic controls

• Insertion site infection: positive skin swabs
• Catheter-related blood stream infection: no apparent source other than CVC and blood culture positive with the same microorganism
   

Patients experienced fewer days with fever per 1,000 catheter days with the antimicrobial CVC (p < .001). No significant differences were observed between groups in insertion site inflammation or infection. Significantly fewer patients in the coated CVC group had positive blood cultures (45% versus 36%, p < .05) and peripheral positive blood cultures (p = .005).

 This study provides minimal support that antimicrobial-coated CVCs may be of benefit for patients undergoing stem cell transplantation.

• Risk of bias (no control group) 
• Risk of bias (no blinding)  
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• Selective outcomes reporting
• Measurement/methods not well described  
• Measurement validity/reliability questionable
• Questionable protocol fidelity
• Other limitations/explanation: Whether the exact same approaches for CVC insertion were used in the prospective and historic groups is not clear. Although CVC-related infection clearly was defined, results were not reported in this way, so whether the blood and CVC culture differences were CVC-related infection, as defined, is not clear. No information is provided on whether other methods, such as prophylactic antimicrobial therapy or colony-stimulating factors, were used or differed between groups.

Results do not provide strong supportive evidence for use of chlorhexidine/silver sulfadiazine-coated CVCs because of study limitations.

To summarize all controlled clinical trials on aloe vera preparations to provide evidence for or against its clinical effectiveness.

Databases searched were MEDLINE, EMBASE, Biosis, and Cochrane Library.

Search keywords were complementary medicine, aloe vera, and review. 

Experts working in the area were contacted and asked for published and unpublished controlled clinical trials and their own papers and files. All databases were searched from their inception to May 1998.

Studies were included if they were controlled clinical trials.

Studies were excluded if they were not performed on aloe vera mono-preparation and if they were designed only on a certain pharmacologic constituent of the aloe vera plant.

Data were extracted in a predefined fashion, and the methodologic quality of the study was assessed using the Jadad scoring system.

Ten trials met the inclusion criteria and were included. Three clinical studies were excluded because of not being performed on aloe vera mono-preparation or use of only a constituent of the plant. No unpublished studies were found.

• The study included 740 participants from 10 clinical trials.
• Conditions included were arthritis, asthma, Candida, chronic fatigue syndrome, lupus erythematosus, sports injuries, ulcers, digestive disorders, and various skin conditions.
• Aloe vera was used as as a topical agent in six studies and was administered orally in four studies. Of these studies, two examined topical aloe vera for prevention or mitigation of radiodermatitis.

• In the studies regarding use for radiodermatitis, no difference was reported between the treatment group and the placebo group.
• Aloe vera might be useful in patients after dermabrasion, mild to moderate plaque-type psoriasis, and treatment of initial genital herpes episodes, with shortened time to healing.
• In postoperative gynecology surgery patients with wound complications, standard wound care was superior to aloe vera. It was concluded that evidence regarding would healing was contradictory.
• All studies had methodologic flaws and did not achieve high scores for quality of the study design. Flaws included lack of randomization, lack of blinding, small sample size, lack of intention to treat analysis, and lack of power calculations.
• Trials tended to originate from the same research groups, and independent replications were lacking. As a result, firm conclusions from the review cannot be drawn.
• Oral aloe vera may have had some effect in reducing blood glucose levels in combination with antidiabetic therapy and in influencing lower serum lipids in one study.

No firm conclusions were drawn from the review because of multiple methodologic studies. It was concluded that topical application does not seem to prevent radiation-induced skin damage. No statistical significance findings from studies were reported.

The authors only included abstracts of controlled trials but then drew no conclusions about these findings because they were only abstracts.

More and better clinical trial data are needed to define the clinical effectiveness of this remedy.

To determine the effectiveness of venlafaxine, soy, and a combination of venlafaxine and soy on hot flashes in men with prostate cancer

Participants randomly were assigned to one of four groups: daily placebo pill in the morning plus daily milk powder (20 g per day); daily venlafaxine (75 mg) in the morning plus daily milk powder (20 g per day); daily placebo pill in the morning plus daily soy powder (20 g with 160 mg isoflavones); or daily venlafaxine (75 mg) in the morning plus daily soy powder (20 g with 160 mg isoflavones). Venlafaxine was provided in extended-release capsules. Prior to enrollment, participants completed a seven-day prescreening period. The intervention was administered for 12 weeks. Patients kept a daily log of medications and were contacted via phone at week 2, 4, 8, and 12 to assess toxicities and complete study measures. Patients on venlafaxine were titrated off medication after the end of the study.

• N = 119
• MEAN AGE = 68.5 years
• AGE RANGE = 46–91 years
• MALES: 100%
• KEY DISEASE CHARACTERISTICS: Prostate cancer

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: United States

PHASE OF CARE: Late effects and survivorship

• RCT, double-blind, placebo-controlled, 2 x 2 factorial design

• Daily count of hot flashes
• Hot Flash Symptom Severity Score (HFSSS)
• Functional Assessment of Cancer Therapy-Prostate (FACT-P)
• Body mass index (BMI)

There was no significant difference in sample characteristics between the four groups including severity of disease, BMI, performance status, and type of treatment. Vasomotor symptoms decreased in all arms (p < 0.001). No differences existed between treatment arms at baseline and 4, 8, or 12 weeks. The severity of hot flashes decreased in all arms (p < 0.001). All four arms showed a decrease in the HFSSS (p < 0.001). Toxicities did not differ between groups and were mild. The study was ended by the Data Safety Monitoring Board due to a lack of effect. The placebo group had the largest decrease in HFSSS scores (55%).

In men with prostate cancer, venlafaxine, soy, and a combination of the two were no more effective than a placebo at decreasing the number and severity of hot flashes.

Venlafaxine, soy, and a combination of both are not effective at treating hot flashes in men with prostate cancer.

To determine if administration of palifermin during autologous hematopoietic stem cell transplantation (AHSCT) in children will lower incidence of oral mucositis and shorter duration of hospitalization

Patients received palifermin 60 µg/kg/day IV for the three consecutive days prior to myeloablative conditioning and for the three consecutive days after the end of chemotherapy. All patients received six total doses. Treating physicians were responsible for the decision to administer palifermin. Data were collected using electronic and paper medical charts.

• N = 58  
• AGE RANGE = 6.85–7.96 years
• MALES: 58.3%, FEMALES: 39.2%
• KEY DISEASE CHARACTERISTICS: Brain tumor, solid tumor, lymphoma
• OTHER KEY SAMPLE CHARACTERISTICS: Prior radiation, conditioning regimens (e.g., carboplatin, thiotepa, etoposide)

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: NewYork-Presbyterian Morgan Stanley Children’s Hospital

• APPLICATIONS: Pediatrics

• Retrospective analysis

• World Health Organization (WHO) grading for mucositis

No statistical difference in grades III-IV mucositis (p = 1.0), lower incidence in grades III–IV (p = 0.047) in patients receiving solid tumor regimen, and no difference in length of hospitalization

Palifermin administration did not result in a statistically significant decrease in incidence and grade of oral mucositis, nor did it result in shorter hospitalization.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: Retrospective analysis

High doses of chemotherapy prior to AHSCT causes significant morbidity due to oral mucositis. A larger study is needed to confirm findings of lower incidence of grades III and IV mucositis in the solid tumor regimens.

To compare the effectiveness of oral morphine to that of rapid-onset opioids, intranasal fentanyl spray (INFS), oral transmusocal fentanyl citrate, and fentanyl buccal tablets in the management of breakthrough cancer pain (BTCP)

Databases searched were MEDLINE, EMBASE, and BIOSIS Citation Index. The search was for the period 1996–October 2007. In addition, investigators searched conference proceedings. Pre-published data regarding INFS were included.

Search keywords included the generic and brand names of opioids and combinations of generic and brand names and pain and episodic, breakthrough, transient, flare, incident, exacerbation and transitory, cancer, malignant, tumor, and neoplasia.

Studies were included if they were 

• Randomized controlled trials (RCTs)
• Involved the management of BTCP
• Studies involving adult patients with cancer, with breakthrough pain, who were being treated with opioids for the management of background pain
• Studies that measured pain intensity difference (PID) at specified time points at the start and after the start of the pain episode

The initial review was of 128 abstracts. Assessment of abstracts and full articles, according to inclusion criteria, identified six RCTs for analysis.

• The sample across all studies was composed of 594 patients.
• The range of sample sizes was 77–139 patients.
• Samples included both males and females.
• The range of mean patient age, across all studies, was 53.9 years (SD = 11.3 years) through 62 years (SD = 11.6 years).
• The range of pain intensity at baseline across studies was 5.9–6.9 (SD = 0.2) on a 10-point scale.

PID was measured at various time points across studies. Meta-analysis demonstrated that INFS provided the greatest reduction in pain within 15 minutes, with a 99% probability in all comparisons. Oral morphine was no better than placebo within the first 45 minutes of a breakthrough episode. Oral morphine was only better than placebo after 45 minutes. INFS provided better relief than did buccal fentanyl before 45 minutes and better relief than did oral transmucosal fentanyl citrate for the first 60 minutes.

Findings show that INFS provides better rapid-onset pain relief for BTCP than does oral morphine, transmucosal oral fentanyl, and buccal fentanyl tablets. Oral morphine showed the same level of pain relief as placebo for the first 30 minutes, showing that oral morphine is an inappropriate treatment for BTCP.

All studies involved an initial period in which appropriate dosing of INFS was established for each patient. Effective use of INFS necessitates determination of individualized dose.

To determine the effectiveness of an aerobic and strength training program on neurotoxic symptoms, gait, balance, and quality of life in women with breast cancer treated with taxol

Women with breast cancer treated with taxol were randomized to either a strength/aerobic exercise program, which they performed at home, or to breast cancer education. The program was conducted for 12 weeks. Data were collected at baseline, every four weeks, and then three months postintervention. Education was provided to the control group, occurred at the same intervals as study group assessments, and lasted for 45 minutes. They also received reminder telephone calls every other week for data collection and equalized contact.

• N = 19  
• AGE = 48.8 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients newly diagnosed with stage I–IIIa breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Eight patients had a lumpectomy, six had a mastectomy, and five received neoadjuvant chemotherapy.

• SITE: Single site    
• SETTING TYPE: Outpatient  
• LOCATION: Oncology clinic in the Midwest

PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trial

• Functional Assessment of Cancer Therapy (FACT)-Taxane
• Timed Up and Go Test
• Leisure-Time Exercise Questionnaire
• Symptom Experience Scale

No significant differences existed in results between the groups regarding neurotoxic symptoms, gait or balance, or quality of life. No significant differences existed between groups regarding stage of disease, level of exercise, age, taxol dose, or breast cancer symptoms.

The results indicated that patients randomized to the exercise group experienced a small but insignificant positive effect on neurotoxic symptoms, gait, and balance.

• Small sample (<  30)
• Risk of bias (no blinding)
• Findings not generalizable

Home exercise programs produced a small to moderate positive effect on gait and balance, symptoms, and quality of life. A large, randomized trial with patients receiving neurotoxic chemotherapy will help determine if this can be a positive intervention.

To describe—in accordance with the World Health Organization (WHO) treatment strategy of pain stages—the classification, evaluation, and treatment of chronic cancer pain in adults

The resource is consensus-based, but authors did not delineate the development process.

• Phase of care: multiple phases
• Clinical application: palliative care

Authors did not state any results.

Recommendations adhere to WHO guidelines for stage of pain. Authors provide some recommendations about the management of breakthrough and intractable pain, citing specific dosage suggestions for opioid formulations and coanalgesic drugs used with neuropathic pain. Authors recommend rapid-onset opioids based on transmucosal fentanyl as drugs of choice for the treatment of breakthrough pain. The resource cites sedation as the best option for refractory pain.

The basis of evidence for these recommendations is unclear. The recommendations do not reflect recent research, particularly in the area of intractable pain. The resource is primarily a reiteration of the WHO step-analgesic recommendations, which some of the most current research is challenging.

The resource provides recommendations from a professional group; nurses should keep in mind that the base of evidence regarding these recommendations is unclear.

The objective of this study was to evaluate the effectiveness of four drug classes: opioids, phenothiazines, benzodiazepines, and systemic.

Databases searched were HealthSTAR, MEDLINE, CINAHL, EMBASE, Cochrane Library and Database of Abstracts and Reviews of Effects Issue 2, American Society of Clinical Oncology conference proceedings (1995-2006), Canadian Medical Association Infobase, and National Guidelines Clearing House. Reference lists from relevant articles were searched for additional trials

Search keywords were dyspnea, breathlessness, shortness of breath, respiratory distress, breath and shortness, and breath and difficult combined with terms for pharmacologic agnets, study designs, and publication types.

Inclusion criteria included

• Systematic reviews
• Meta-analyses
• Evidence-based practice guidelines
• Fully published or abstract reports of randomized or nonrandomized controlled studies of opioids, phenothiazines, or benzodiazepines administered by any route involving adult patients with dyspnea
• Subjects with any advanced disease
• Studies involving corticosteroids, only if the primary advanced disease was cancer
• Studies in which one of the outcomes reported was dyspnea, measured by a patient-reported scale.
 

Exclusion criteria included
• Studies in languages other than English
• Stuides eported in letters or editorials.

• The search identified two practice guidelines, three systematic reviews, 23 published randomized controlled trials (RCTs), two abstracts of RCTs, and three published nonrandomized trials, for a total of 33 references.
• The review did not identify the number of excluded items from the initial search. 
• Study quality was evaluated formally using the Jadad scale.

The total sample across  29 trials was 600 patients, with individual sample sizes ranging from 4-101. Trials included involved

• 6 trials of opiods in only patients with cancer
• 10 trials of systemic opioids including patients who did not have cancer
• 7 trials of nebulized opioids including patients with and without cancer
• 4 trials of benzodiazepines
• 2 trials of phenothiazines.
   

• Search sources and criteria were not reported in either of the two practice guidelines. One indicated that both corticosteroids and opioids were options for managing dyspnea but that the evidence was poor. The other, a Finnish guideline, recommended opioids, steroids, and benzodiazepines, but evidence was only cited for opiods.
• Opioids studied included morphine orally, subcutaneously, or via nebulizer; dihydrocodeine; diamorphine; and promethazine with morphine. All but three studies examined the effects of a single dose on dyspnea via use of a visual analogue scale or exercise tolerance.
• In opioid trials involving only patients with cancer, four examined systemic opioids, one used nebulized opiods, and one included both systemic and nebulized administration. One trial used a combination of morphine and midazolam. Systemic opioid studies tended to show significant decrement in mean dyspnea and respiratory rate with morphine. In the trial that included midazolam, more patients on the combined regimen reported relief from dyspnea at 24 and 48 hours and had fewer episodes of breakthrough dyspnea. However, no differences were seen in mean dyspnea scores and exercise tolerance between groups overall.
• Nebulized opioids did not show significant differences compared to systemic morphine in one trial.
• One benzodiazepine trial involved patients with cancer. In trials with other patients, none of the studies demonstrated a significant reduction in dyspnea when compared to placebo.
• No trials were on phenothiazines in patients with cancer. One study showed a benefit with promethazine compared to placebo on dyspnea and exercise tolerance.
• Adverse effects reported across trials included drowsiness, nausea and vomiting, and constipation in opioid trials. Results of opioids on oxygen level were mixed.
• Results of benzodiazepines and phenothiazines on oxygen and carbon dioxide levels were mixed. Drowsiness was the most frequent adverse effect reported with benzodiazepine.

• Overall evidence favors a beneficial effect of systemic opioids on dyspnea and exercise tolerance.
• None of the studies comparing nebulized morphine with placebo or systemic opioids found it to be beneficial. 
• Whether studies with opioids indicate a drug class effect is not clear because only a few drugs have been studied.
• Studies of benzodiazepines did not suggest any benefit.
• Studies of phenothiazines gave conflicting results.
• Overall evidence in this area demonstrate conflicting results, and this systematic review also gives conflicting results and conclusions within the article.
• Most studies had very small sample sizes, and doses, dose schedules, routes, and outcome measures varied greatly, making overall conclusions difficult.
• While the stated purpose of the review was to determine effects within a cancer population, most of the research reviewed was not in this population.
• While use of opioids may be of benefit for patients with cancer in reducing the sensation of dyspnea, this effect needs to be balanced with the adverse effects that can be expected with such treatment, including symptoms of constipation, drowsiness, and nausea and vomiting. Interventions to prevent or manage these effects would also be essential.

This systematic review evaluated the effectiveness of four drug classes (opioids, phenothiazines, benzodiazepines, and systemic corticosteroids) to relieve dyspnea experienced by patients with advanced cancer.

A criterion for inclusion in the review was a controlled trial involving the specified drug classes; however, trials were not limited to cancer except for corticosteroids.

The review identified three systematic reviews (one with meta-analysis), two practice guidelines, and 28 controlled studies.

• Outcomes were dyspnea measured by patient self-report, exercise tolerance, quality of life, and adverse events.
• Data were not pooled for opioid trials because of heterogeneity between trials but was pooled for benzodiazepines and phenothiazines.
• The review identified seven systemic studies that found a statistically significant beneficial effect of opioids on patient-reported breathlessness.
• None of the studies comparing nebulized morphine with placebo found it to be beneficial for relieving dyspnea.
• Controlled trials of benzodiazepines in patients without cancer did not show any benefit for treating dyspnea.
• Only two trials evaluating phenothiazines in patients without cancer were identified and showed conflicting results.

Systemic opioids, administered orally or parenterally, can be used to manage dyspnea in patients with cancer. Oral promethazine also may be used alone or in addition to systemic opioids. Nebulized morphine, prochlorperazine, and benzodiazepines are not recommended for the treatment of dyspnea, and promethazine must not be used parenterally because of the concern for serious tissue damage when administered intravenously.

RESOURCE TYPE: Expert opinion

PROCESS OF DEVELOPMENT: Review of clinical trials results and clinical experience

Currently, limited evidence regarding the effects of interventions for adverse events with immunotherapy exists, and current information is based on initial clinical trial results and personal clinical experience.

Nurses need to be aware of the myriad adverse effects that can occur with immunotherapies, and recognize that many of them can occur long after treatment has concluded. This means that patient teaching and ongoing follow-up to assess for these effects are crucial. Current sources point to the importance of early detection and interventions for the management of adverse effects to prevent more severe negative patient outcomes. As opposed to some other sources, these authors recommend against “knee jerk” implementation of systemic corticosteroids for diarrhea because such treatment may mask the development of severe colitis.