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Bozkurt, M., Palmer, L.J., & Guo, Y. (2016). Effectiveness of decongestive lymphatic therapy in patients with lymphedema resulting from breast cancer treatment regardless of previous lymphedema treatment. The Breast Journal, 23, 154–158.

Study Purpose

To compare the effects of decongestive therapy in patients who did and did not receive previous treatment for lymphedema

Intervention Characteristics/Basic Study Process

Data were obtained retrospectively from medical records. Patient were grouped according to having received lymphedema treatment or not. Patients had undergoing assessment and 4–12 lymphedema treatments for four to six weeks. Consecutive patients referred for lymphedema treatment were included in the analysis. The intervention included MLD and compression, as well as teaching about good skin care, limb exercises, and deep breathing.

Sample Characteristics

  • N = 72   
  • MEAN AGE = 53
  • FEMALES: 100%
  • KEY DISEASE CHARACTERISTICS: Patients with breast cancer with unilateral arm lymphedema who had standard axillary lymph node dissection
  • OTHER KEY SAMPLE CHARACTERISTICS: Two to three years postsurgery for breast cancer

Setting

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

Study Design

Retrospective cohort comparison

Measurement Instruments/Methods

  • Lymphedema defined as a volume increase of greater than 150 ml compared to the ipsilateral arm.
  • Perometer measurement

Results

Both groups had a reduction in limb volume.

Conclusions

Complete decongestive therapy was effective in reducing lymphedema for both patients who had prior treatment for lymphedema and those who did not.

Limitations

  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • Unclear what types of previous treatment were involved

Nursing Implications

The findings add to the body of knowledge that complete decongestive therapy is effective in reducing lymphedema volume whether or not patients had undergone previous treatment for lymphedema.

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Bozcuk, H., Artac, M., Kara, A., Ozdogan, M., Sualp, Y., Topcu, Z., . . . Savas, B. (2006). Does music exposure during chemotherapy improve quality of life in early breast cancer patients? A pilot study. Medical Science Monitor, 12, CR200–CR205.

Intervention Characteristics/Basic Study Process

Patients were exposed to the same kind of music played from a music set located within the chemotherapy unit while their chemotherapies were administered. Music included pieces from the album “Love Songs” by James Galway, distributed by BMG music, 2001 of which were instrumental pieces of international classical music. Patient outcomes were evaluated before and after a baseline cycle of chemotherapy and before and after a chemotherapy cycle with the musical intervention.

Sample Characteristics

  • The sample was comprised of 18 patients with breast cancer receiving adriamycin-containing adjuvant chemotherapy after undergoing modified radical mastectomy (median age = 45.5 years [range 28–60]).
  • The majority of patients had stage II disease (77.8%), and five patients (27.7%) had associated comorbidities (e.g., hypertension, type 2 diabetes mellitus, coronary heart disease).

Setting

Outpatient clinics

Study Design

This was a pilot study.

Measurement Instruments/Methods

European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

Results

The music intervention did not demonstrate improvement in fatigue outcomes.

Limitations

  • The study had a small sample size.
  • The study lacked a control group.

Nursing Implications

Future studies may want to account for personal preferences of the patients for the type of music listened to during chemotherapy.

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Boyden, J.Y., Connor, S.R., Otolorin, L., Nathan, S.D., Fine, P.G., Davis, M.S., & Muir, J.C. (2015). Nebulized medications for the treatment of dyspnea: A literature review. Journal of Aerosol Medicine and Pulmonary Drug Delivery, 28, 1–19. 

Purpose

STUDY PURPOSE: To complete a thorough systematic review of the evidence available in the literature regarding the use of nebulized medications in the treatment of dyspnea in chronic obstructive pulmonary disease (COPD), cancer, interstitial lung disease (ILD), and cystic fibrosis

TYPE OF STUDY: Systematic review

Search Strategy

DATABASES USED: MEDLINE/PubMed, CINAHL, Cochrane, and Google Scholar, as well as a reference list search
 
YEARS INCLUDED: 1989–2013
 
INCLUSION CRITERIA: Research studies, systematic reviews, and meta-analyses; examined the use of nebulized medications for the treatment of cancer, COPD, cystic fibrosis, ILD, or experimentally induced dyspnea; written or translated into the English language; underwent peer review
 
EXCLUSION CRITERIA: Related to asthma; nonsystemic reviews; muscarinic agents and beta-agonists

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 50
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Evidence was graded, but this did not serve as the criteria for further exclusion, as all grades were included. Further exclusion from the initial 50 returned appears to be for relevance. The method was not delineated.

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 39
  • TOTAL PATIENTS INCLUDED IN REVIEW = Not combined for evaluation, not quantified
  • SAMPLE RANGE ACROSS STUDIES: 1–100, also included literature reviews
  • KEY SAMPLE CHARACTERISTICS: Studies varied widely, including studies examining medications, examining medication delivery (jet nebulizers), and reviewed literature reviews. Studies on children as well as adults with a variety of lung illnesses were included.

Phase of Care and Clinical Applications

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Pediatrics, elder care, palliative care

Results

Results delineated by disease populations.

  • Cancer: Findings were mixed with 12 publications supporting use, 8 inconclusive/insignificant, and one recommendation against use. Studied drugs included morphine, fentanyl, hydromorphone, and furosemide. Mixed results existed with both.
  • For COPD: Medications reviewed included opioids and furosemide, again with mixed results. Favorable results were observed with jet nebulizers and fentanyl and furosemide. All morphine studies were negative.
  • IPF: Of seven studies, three were high quality, and all of these were studies that included subjects with multiple diseases, one of which was IPF. Results were mixed (two inconclusive and one positive).
  • Cystic fibrosis: Four studies were included. All were positive, but all had low-quality evidence (case reports).  
  • Healthy: These were studies in which dyspnea was induced experimentally—two reviews; four double-blind, randomized trials of furosemide; and three positive.
  • Terminal/end-stage populations: Three looked at cystic fibrosis, two looked at end-stage ILD/IPF, one at end-stage COPD, and eight at end-stage cancer. None was high-quality. Positive results with various agents existed, but, again, no high-quality studies existed.
  • In all studies, results with morphine were mixed, and there were more positive studies with hydromorphone, fentanyl, and furosemide, but these were not of high quality.

Conclusions

Although many studies evaluated nebulized medications, this review included a wide variety of studies with varied goals, including systemic reviews, evaluation of opioids and furosemide, and delivery via ultrasound versus jet nebulizer across many disease processes and populations. The authors of this review suggested considering the use of nebulized medications on a case-by-case basis. No broader recommendations can be made at this point.

Limitations

  • Mostly low quality/high risk of bias studies
  • High heterogeneity
  • Low sample sizes

Nursing Implications

The oncology nurse should be aware of the use of nebulized medications as a delivery method for dyspnea but that there has not been any high-quality evidence to support the use of any specific medication. Although the delivery method may be more acceptable, the increased cost and lack of evidence do not support its use at this time.

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Boyd, K.J., & Kelly, M. (1997). Oral morphine as symptomatic treatment of dyspnoea in patients with advanced cancer. Palliative Medicine, 11, 277–281.

Study Purpose

To assess the effect of regularly administered extended-release morphine for dyspnea in patients receiving standard hospice care

Intervention Characteristics/Basic Study Process

  • Regular administration of extended-release oral morphine 10 mg twice daily or 30% dose increase for those already on morphine
  • Patients received 15 mg twice-daily metoclopramide for the first five days and a laxative.

Sample Characteristics

  • N = 15 (13 completed 48-hour assessment, 9 completed final assessment)
  • MEAN AGE = 73 years
  • MALES: 7, FEMALES: 8
  • KEY DISEASE CHARACTERISTICS: Patients with cancer in hospice; mixed diagnoses—mostly lung primary or lung metastases, but four also had chronic obstructive pulmonary disease; patients with dyspnea from irreversible causes
  • OTHER KEY SAMPLE CHARACTERISTICS: 13 were opioid-naive, and 2 were opioid-tolerant

Setting

  • Eight patients were at home, and seven were hospice inpatients.

Study Design

  • Open, nonrandomized, uncontrolled

Measurement Instruments/Methods

  • Dyspnea visual analog scale (VAS)
  • Support Team Assessment Schedule
  • Borg Scale
  • Respiratory rate
  • Sedation VAS
  • State-Trait Anxiety Inventory
  • Pain (0–10)
  • Assessments at baseline, 48 hours, and 7–10 days

Results

Decline in dyspnea VAS scores for six patients was not statistically significant (p = 0.06). No clinically significant decline was found in respiratory function. No change was seen in anxiety, but actual scores were not reported. The authors stated that the high incidence of sedation and dizziness was of concern and indicated a need to monitor patients carefully. The authors also stated that the use of immediate-release morphine on an as-needed basis might be effective and cause less sedation.

Conclusions

Although the authors claimed that morphine should be trialed in patients, the evidence from this study does not support that. The problem may be the use of modified-release morphine 10 mg opposed to immediate release.

Limitations

  • The study had a small sample size with attrition.
  • Three patients died, and three asked to withdraw because of side effects.
  • Sedation at 48 hours was the main problem.
  • Two patients who withdrew and two who died reported excessive drowsiness.
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Boyages, J., Kastanias, K., Koelmeyer, L.A., Winch, C.J., Lam, T.C., Sherman, K.A., . . . Mackie, H. (2015). Liposuction for advanced lymphedema: A multidisciplinary approach for complete reduction of arm and leg swelling. Annals of Surgical Oncology, 22, 1263–1270. 

Study Purpose

To evaluate a liposuction surgery and multidisciplinary rehabilitation approach for advanced lymphedema of the upper and lower extremities

Intervention Characteristics/Basic Study Process

Liposuction was performed under general anesthesia following limb exsanguination and tourniquet application. Using specialized Helixed Tri-Port III cannulas (22 and 30 cm long, 4–5 mm wide) connected to a vacuum pump, subcutaneous tissue was removed through multiple small incisions along the limb. Presurgical limb volume determined how much tissue was removed to equalize volume relative to the unaffected limb. Compression garments were applied to the affected limb immediately postsurgery prior to tourniquet release (custom-made 30 mmHg JOBST® Elvarex for arms, or Ready Wraps® [Solaris] for legs). From one week postsurgery, all leg patients wore JOBST Elvarex custom-made compression garments 50–80 mmHg. Initial postsurgical garments were measured using the circumference of the unaffected limb. Subsequent measurements were obtained from the operated limb by a trained garment fitter. Every order consisted of two garments, allowing one to be worn while the other was washed. Throughout follow-up, compression garments alone were used in areas where liposuction was performed. However, decongestive lymphatic therapy was used when indicated in areas where liposuction was not performed (hands or feet) or areas that could not be adequately compressed (shoulder or hip).

Sample Characteristics

  • N = 21 (15 arm and six leg)
  • MEAN AGE = 57.8 years (range = 25–69 years) in arm group; 50.7 years (range = 18–66 years)
  • FEMALES: 100%
  • KEY DISEASE CHARACTERISTICS: Cancer-related secondary lymphedema
  • OTHER KEY SAMPLE CHARACTERISTICS: Cancer-related secondary lymphedema was a more common reason for liposuction (85.7%) than primary (congenital) lymphedema (14.3%) with breast cancer treatment being the most common underlying cause (66.7%). The mean time of longstanding lymphedema was 9.1 years (range = 2–29 years) in the arm group versus 15.5 years (range = 3–42 years) in the leg group. 

Setting

  • SITE: Single site    
  • SETTING TYPE: Multiple settings
  • LOCATION: Australia

Phase of Care and Clinical Applications

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

Study Design

Prospective clinical study, one arm, pre and post measures

Measurement Instruments/Methods

  • Limb volume by tape was calculated using 4 cm truncated cone circumferential measurements
  • Lymph fluid measured by bioimpedance spectroscopy (L-Dex®) measurement
  • Functional and emotional impairment was assessed using the Patient-Specific Functional Scale (PSFS). PSFS is reliable and valid across contexts and sensitive to change in breast cancer survivors, but it was not previously validated for lymphedema.

Results

A significant postliposuction reduction in limb volume was achieved for all patients. The mean preoperative limb difference was 45.1% (range = 23–83), decreasing between two and six weeks postsurgery to 13.2% (range = -2–24), a significant 68.2% reduction (range = 35–104; t[20] = 9.66; p < 0.001). Limb volume difference reduced to 3.8% by six months postsurgery, an 89.6% (range = 38–149) reduction of presurgical volume (t[18] = 9.17; p < 0.001). This near-complete reduction was maintained to 12 months (n = 8), a 97.7% reduction (range = 73–123; t[8] = 5.73; p < 0.001). Mean presurgical limb volume difference was 45.1% (arm 44.2%; leg 47.3%). L-Dex increased four weeks postsurgery to 55 (range = 32–73), reflecting the extracellular fluid associated with postsurgical swelling (t[18] = -2.51; p = 0.02). Functionally, all patients reported improvements on the PSFS index of personally important activities by six months postsurgery (p < 0.01). 

Conclusions

Liposuction was safe and may be an effective option for carefully selected patients with advanced lymphedema. Assessment, treatment, and follow-up by a multidisciplinary team is essential.

Limitations

  • Small sample (< 30)
  • Baseline sample/group differences of import 
  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment) 
  • Risk of bias (no appropriate attentional control condition)  
  • isk of bias (sample characteristics)
 

Nursing Implications

Liposuction is a surgical approach to lymphedema. It should be noted that even with continuous compression therapy, postliposuction, patients’ lymph fluid level was elevated beyond normal. Nurses should continue observing the impact of liposuction on patients’ physiological, functional, and emotional aspects. Nurses should also advise patients according to current evidence.

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Box, R.C., Reul-Hirsch, H.M., Bullock-Saxton, J.E., & Furnival, C.M. (2002). Physiotherapy after breast cancer surgery: Results of a randomised controlled study to minimise lymphoedema. Breast Cancer Research and Treatment, 75(1), 51–64.

Intervention Characteristics/Basic Study Process

The purpose of the study was to evaluate the incidence of lymphedema after axillary dissection to determine the effects of prospective monitoring and early physiotherapy intervention

Sample Characteristics

The study sample (N = 65) was comprised of a treatment group and a control group.

Study Design

The study used a randomized controlled trial design.

Measurement Instruments/Methods

Both arms of patients were measured for circumference, volumetry, and multi-frequency bioimpedance analysis preoperatively and 5 days and 1, 3, 6, 12, and 24 months postoperatively.

Results

A small number of women detected with clinically significant lymphedema (n =12); 91% of women completed measures at two years after surgery. Two women had bilateral surgeries within the first month after enrollment. At 24 months, three times as many women in the control group compared to treatment group showed secondary lymphedema (except for volume criteria). Using volume criteria, a trend toward increased lymphedema in patients with mastectomy complete with breast conservation therapy existed. Hand or arm dominance did not influence lymphedema by these measurements. Logistic regression used to determine risk factors for development of lymphedema included

  • Axillary dissection by level
  • Number of lymph nodes removed
  • Number of lymph nodes affected with disease
  • Wound infection
  • Body mass index
  • Total wound drainage
  • Seroma
  • Age
  • RT
  • Occupation
  • Clinical.

Clinical incidence of lymphedema in the study was 21% at two years.

Conclusions

The study was very well done and well designed.

Limitations

  • The sample size was small; however, the data are useful in that they suggest a preventative approach with ongoing monitoring to prevent and minimize risk in a population with high-risk criteria for development of symptoms.
  • Anecdotal evidence of some specific cases.

Nursing Implications

Nurses should advocate ongoing measurement to detect changes early and intervene.

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Bower, J. E., Garet, D., Sternlieb, B., Ganz, P. A., Irwin, M. R., Olmstead, R., & Greendale, G. (2012). Yoga for persistent fatigue in breast cancer survivors: a randomized controlled trial. Cancer, 118, 3766–3775.

Study Purpose

To examine, relative to a health education control, the feasibility and efficacy of an Iyengar yoga intervention for breast cancer survivors with persistent posttreatment fatigue.

Intervention Characteristics/Basic Study Process

Outcome assessors of the performance tasks were blinded to group assignment. The intervention was briefly but fully described, and then participants were randomly assigned to a group that received a 12-week, Iyengar-based yoga intervention or a group that received 12 weeks of a health education (control group).

Sample Characteristics

  • The sample was comprised of 31 women.
  • Mean age was 54.4 years (standard deviation [SD] = 5.7 years) in the intervention group and 53.3 years (SD = 4 years) in the control group.
  • All participants had stage 0 to II breast cancer.
  • Most participants were white.
  • The range of education was high school completion through graduate degree.
  • Twenty-four participants were completing radiotherapy, 17 were completing chemotherapy, and 22 were receiving hormone therapy.
  • In the intervention group, median time posttreatment was 1.7 years (range 0.7–4.1).
  • Breast cancer survivors with posttreatment fatigue were recruited through multiple mechanisms. Inclusion and exclusion criteria were applied.
  • The original enrollment target was 72 participants; researchers assumed a 20% loss to follow-up. Because of the stringent enrollment plan, the sample size was smaller than expected.
     

Setting

  • Single site
  • Outpatient
  • University of California, Los Angeles
     

Phase of Care and Clinical Applications

  • Patients were undergoing the posttreatment phase of care.
  • The study has clinical applicability for survivorship and late effects and survivorship.

Study Design

The study was a randomized, controlled trial.

Measurement Instruments/Methods

  • Fatigue Symptom Inventory (FSI)
  • Multidimensional Fatigue Symptom Inventory (MFSI), to assess vigor
  • Beck Depression Inventory II (BDI-II)
  • Pittsburgh Sleep Quality Index (PSQI)
  • Perceived Stress Scale (PSS)
  • Timed chair stands and functional reach test, to assess physical performance
  • Medical Outcomes Study (MOS)
     

Results

Relative to the control group, fatigue severity in the intervention group declined significantly (p = 0.032) from baseline to posttreatment and over the three-month follow-up. In addition, relative to the control group, the yoga group had significant (p = 0.011) increases in vigor. Both groups had positive changes in symptoms of depression and perceived stress (p < 0.05). The authors noted no significant changes in sleep or physical performance. 

One adverse protocol-related event occurred:  a participant with a history of back problems experienced a back spasm in yoga class. After evaluation by her physician, she returned to class.

Conclusions

A targeted yoga intervention led to a significant reduction in fatigue and improvement in vigor among breast cancer survivors with persistent fatigue symptoms. This conclusion should be understood in the context of the study:  participants were relatively healthy and without comorbid conditions found in the general population.

Limitations

  • The study had a small sample size, with less than 100 participants.
  • Some participants had been living with cancer for more than five years, which was longer than most in the study had been living with cancer.
  • Because of the context of the study, researchers were unable to use a double-blind design.
  • The study included multiple conditions.
  • The results were not generalizable.

Nursing Implications

This study offered minimal conclusive data in support of the intervention. Preliminary findings indicated that the yoga intervention is feasible and safe and has a positive effect on fatigue. A larger trial that includes participants with common comorbid conditions—a study more representative of the general population of women with breast cancer posttreatment—is warranted. Secondary outcomes included vigor, symptoms of depression, sleep, perceived stress, and physical performance.

Print

Bower, J.E., Bak, K., Berger, A., Breitbart, W., Escalante, C.P., Ganz, P.A., . . . American Society of Clinical Oncology. (2014). Screening, assessment, and management of fatigue in adult survivors of cancer: An American Society of Clinical Oncology clinical practice guideline adaptation. Journal of Clinical Oncology, 32, 1840–1850. 

Purpose & Patient Population

PURPOSE: To present screening, assessment, and treatment procedures for adult survivors of cancer who have completed treatment
 
TYPES OF PATIENTS ADDRESSED: Cancer survivors diagnosed at age 18 or older who completed curative treatment, are considered in remission, or are disease-free and on maintenance therapy.

Type of Resource/Evidence-Based Process

RESOURCE TYPE: Consensus-based guideline  
 
PROCESS OF DEVELOPMENT: Two content experts reviewed and recommended use of pan-Canadian guideline; the ASCO panel suggested use of National Comprehensive Cancer Network (NCCN) articles. The Appraisal of Guidelines for Research and Evaluation (AGREE) II subscale was then used on three articles. Experts issued recommendations based on guidelines and modified based on local context and practice beliefs.
 
DATABASES USED: MEDLINE and Embase
 
KEYWORDS: Fatigue, cancer, survivor, post-treatment, late effects, long-term effects
 
INCLUSION CRITERIA: Cancer survivors diagnosed at age 18 or older who completed curative treatment, are considered in remission, or are disease-free and on maintenance therapy.
 
EXCLUSION CRITERIA: None

Phase of Care and Clinical Applications

PHASE OF CARE: Late effects and survivorship

Results Provided in the Reference

Adapted from three guidelines by multidisciplinary experts using supplementary evidence and clinical experience. Most recommendations listed verbatim but some modified to include updated evidence or current practice beliefs.

Guidelines & Recommendations

Recommendations focused on patients who have completed active treatment or are considered in clinical remission. Treat underlying causes, moderate physical activity after cancer treatment with PT and lymphedema referrals as needed (meta-analysis, systematic review, [randomized controlled trial [RCT]; 10 cited), cognitive behavioral therapy (meta-analysis, RCT, systematic reviews; 6 cited), psychoeducational therapies (systematic, RCT; 3 cited), psychosocial services, mindfulness-based interventions (RCT; 3 cited), yoga (RCT; 2 cited), acupuncture (RCT; 2 cited), psychostimulants/wakefulness agents (limited evidence in patients who are post-treatment disease-free). Additional areas in which research needed include biofield therapies, massage, music therapy, relaxation, Reiki, Qigong, ginseng, and vitamin D.

Limitations

Guidelines were tailored to survivors with current evidence as not all evidence done is survivors.

Nursing Implications

Screening, assessment, and treatment guidelines summarized for use in cancer survivors.

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Bow, E.J., Vanness, D.J., Slavin, M., Cordonnier, C., Cornely, O.A., Marks, D.I., . . . Schlamm, H. (2015). Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients. BMC Infectious Diseases, 15, 128-015-0855-6.

Purpose

STUDY PURPOSE: To compare clinical trials examining outcomes with use of oral antifungal agents for prophylaxis in patients undergoing hematopoietic cell transplantation

TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy

DATABASES USED: Medline EMBASE, Cochrane collaboration
 
KEYWORDS: Fluconazole, itraconazole, posaconazole, voriconazole 
 
INCLUSION CRITERIA: RCTs using head-to-head comparisons of oral antifungal agents, patients undergoing allogeneic HCT

Literature Evaluated

TOTAL REFERENCES RETRIEVED: Not in article
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: No risk of bias evaluation was done.

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 5
  • TOTAL PATIENTS INCLUDED IN REVIEW = 2,147
  • SAMPLE RANGE ACROSS STUDIES: 140–600 patients
  • KEY SAMPLE CHARACTERISTICS: Not provided.

Phase of Care and Clinical Applications

PHASE OF CARE: Transition phase after active treatment

Results

Network meta-analysis using Bayesian statistical techniques were used. Results showed that voriconazole was the agent most likely to reduce incidence of overall probable or proven invasive fungal infection at 180 days post-transplantation. Mold-active agents voriconazole, itraconazole, and posaconazole were overall more likely to be effective than fluconazole as primary antifungal prophylaxis.

Conclusions

Findings suggest that primary antifungal prophylaxis with mold-active agents are more effective for patients undergoing allogeneic HCT.

Limitations

  • Few studies included

Nursing Implications

Primary antifungal prophylaxis with mold-active agents may be preferred to reduce probable or proven invasive fungal infections. Aspergillus tends to predominate invasive fungal infections in this group of patients. There is limited data directly comparing the various mold-active agents.

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Bow, E.J., Laverdiere, M., Lussier, N., Rotstein, C., Cheang, M.S. & Ioannou, S. (2002). Antifungal prophylaxis for severely neutropenic chemotherapy recipients: A meta analysis of randomized-controlled clinical trials. Cancer, 94, 3230–3246.

Purpose

The evaluated treatment was antifungal prophylaxis with azoles (fluconazole, itraconazole, ketoconazole, and miconazole) or an amphotericin B formulation compared with placebo or no prophylaxis controls.

Search Strategy

The search used MEDLINE and EMBASE (1966–2000); additional studies were identified from bibliographies/reference lists of articles, topical reviews, and information from the pharmaceutical industry and investigators in the field.

Literature Evaluated

38 randomized, controlled trials

Sample Characteristics

7,014 patients who received cytotoxic therapy for acute leukemia or hematopoietic stem cell transplantation (HSCT) sufficient to result in neutropenia (an absolute neutrophil count [ANC] of less than 1,000) lasting one week or more.

Results

In severely neutropenic patients (ANC less than 1,000 for a week or more), antifungal prophylaxis reduced the use of:

  • Parenteral antifungal therapy by 43% (prophylaxis success).
  • Superficial fungal infection by 71%.
  • Invasive fungal infection by 56%.
  • Fungal infection-related mortality by 42%.


In subgroup analyses, superficial fungal infections were not reduced for:

  • HSCT recipients overall.
  • Patients receiving low-dose amphotericin B formulations.
  • Patients in a single, small miconazole trial.


However, superficial fungal infections were reduced in HSCT recipients on azoles.

In subgroup analyses, fluconazole was more effective than itraconazole or low-dose amphotericin B formulations to prevent superficial fungal infections.

In subgroup analyses, a reduction in fungal infection-related mortality was not observed in:

  • Pediatric trials.
  • Non-HSCT trials.
  • Trials comparing azoles with polyene controls.
  • Trials comparing low-dose amphotericin B formulations with placebo.
  • Trials with itraconzaole, ketoconazole, or miconazole.


There was a reduction in fungal infection-related mortality in trials using fluconazole for antifungal prophylaxis.
Antifungal prophylaxis did not affect:

  • Overall mortality, except in subsets of HSCT recipients or patients in which the mean duration of neutropenia was longer than two weeks.
  • The incidence of aspergillosis, perhaps because the overall incidence was low (1%) in both groups; therefore, a treatment effect could not be detected.
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