To evaluate the effect of the administration of tranexamic acid (TA) upon blood loss and the need for transfusions in patients undergoing head and neck surgery

Patients undergoing supramajor head and neck surgeries were randomized to receive TA (10 mg/kg) or placebo (normal saline). The patients were stratified a priori based upon their anticipated surgical procedure. The attending anesthesiologist, blinded to the drug, administered 100 ml of solution of normal saline with or without TA (10 mg/kg) during 20 minutes postinduction of anesthesia, and, if the surgery was prolonged, every three hours during the surgery. Blood loss was measured during surgery and postoperatively for the first 24 hours. A transfusion trigger was established.

• N = 219   
• AGE = 51.9 years (TA) and 50.67 (placebo)
• MALES: 77%, FEMALES: 23%
• CURRENT TREATMENT:  Other
• KEY DISEASE CHARACTERISTICS: Resectable squamous cell carcinoma oral cavity
• OTHER KEY SAMPLE CHARACTERISTICS: Undergoing surgical resection and reconstructive procedures

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Tertiary referral cancer center in India

PHASE OF CARE: Active antitumor treatment

Randomized, placebo-controlled, double-blind, prospective study

Gravimetry, blood collection in suction bottles, and visual inspection were used to calculate intraoperative blood loss; postoperative blood loss was calculated with a measure of the blood collected in suction bottles during 24 hours.

Differences in intraoperative blood loss between the groups was not significant (p = 0.22); however, the placebo group demonstrated a significantly greater amount of blood loss postoperatively than the TA group (p = 0.009). This difference, however, did not translate to a significant difference between groups in the number of transfusions (p = 0.51).

The administration of TA in patients undergoing head and neck cancer surgery did not decrease intraoperative blood loss or overall blood loss; although it did reduce postoperative bleeding, this did not translate to a reduction in the number of transfusions.

Nurses must assess perioperative blood loss because it places patients at risk for serious complications. An ongoing need to evaluate measures exists to decrease this risk. 

To evaluate the efficacy of low level laser therapy (LLLT) for the treatment of chemotherapy-induced oral mucositis (OM) in pediatric patients undergoing chemotherapy or stem cell transplant

Children and adolescents with cancer receiving chemotherapy or hematopoietic stem cell transplantation (HSCT) who developed grade II OM were included. OM was scored daily by the same investigator. In the experimental group, the treatment was applied to each OM lesion for five consecutive days. The control group received sham treatments to each OM lesion for five consecutive days also.

• The study reported on 14 patients with an age range of 4.8–12.3 years.
• The sample was 19% female and 81% male.
• The sample had three patients diagnosed with solid tumors, 15 patients with lymphoma/leukemia, and three patients undergoing stem cell transplant.

This was a single site, inpatient study conducted in the Pediatric Oncology Unit of the Hospital de Clinicas de Porto Alegre at Federal University of Rio Grande do Sul, Brazil.

The study was a randomized, placebo-controlled trial.

• The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 2.0 was used.
• One examinator assessed mean, standard deviation, and percentiles for age, localization and grade of mucositis, and mucositis severity daily.

No differences were found in grades of mucositis as a function of the LLLT protocol. Mucositis was diagnosed 5.0 to 7.5 days postchemotherapy. On the seventh day after the diagnosis of mucositis, 1 out of 9 patients in the laser group and 9 out of 12 patients in the sham group had grade II or greater OM (p = 0.029). The mean OM duration in the laser group as compared to the sham group was 3.1 days less (p = 0.004).

LLLT can significantly reduce the duration of chemotherapy-induced OM in children.

• The sample size was small with fewer than 30 patients.
• The study did not evaluate pain or functional impairment.

Laser therapy is effective in treatment of mucositis, but it is very high tech and requires special equipment and highly trained personnel.

The primary purpose of this study was to determine the percentage of patients experiencing febrile neutropenia. A secondary goal was to examine infection-related mortality, all early mortality during chemotherapy, bone pain or musculoskeletal pain, and relative dose intensity.

Medline, EMBASE, Cancerlit, Cochrane, Database of Systematic Reviews,and Cochrane Central Register of Controlled Trials database were reviewed.

Key words include G-CSF, granulocyte–colony-stimulating factor, colony-stimulating factors (CSFs), recombinant G-CSF, lenograstim, filgrastim, pegfilgrastim, and pegylated filgrastim, randomized controlled trials

Inclusion criteria was primary and secondary G-CSF prophylaxis   

Studies were excluded if they encompassed those with granulocyte macrophage–colony-stimulating factor (GM-CSF), RCTs in children, leukemia or multiple myeloma, bone marrow or peripheral blood stem cell transplantation, and studies of established neutropenia or febrile neutropenia.
 

12,128 potentially relevant papers were reviewed.

Cochran’s Q statistic and inconsistency index of Higgins,fixed-effects model, and random effects models.

The Jadad scale was used to evaluate study quality.

17 randomized, controlled trials (RCTs) were included.

The total sample size was 3,493 patients  

The sample across all studies ranged from 31–928

Key characteristics included filgrastim in 10 trials (59%), lenograstim in six trials (35%), and pegfilgrastim in one trial (6%). Eleven trials (65%) involved patients with solid tumors and six (35%) were in patients with lymphoma, including four (24%) limited to older adult patients, eight studies using placebo control, and three that permitted secondary G-CSF in control patients (two prohibited its use and the remaining studies did not specify). Five RCTs prohibited the use of prophylactic antibiotics and three used antibiotic prophylaxis. The remaining did not specify.

Active treatment

Reductions in infection-related and early mortality with G-CSF were seen in patients with solid tumors but not among those with lymphoma.

This analysis and review confirms that primary prophylaxis with G-CSF significantly reduces the risk of febrile neutropenia while sustaining and enhancing chemotherapy dose delivery in patients receiving conventional chemotherapy across a broad range of baseline risk in eligible trials. The most important and previously unreported observation that emerged from this overview is the observed reduction in infection-related (RR = 0.552, p = 0.018) and all-cause (RR = 0.599, p = 0.002) early mortality in patients randomized to receive primary prophylaxis with G-CSF. There were no differences based on whether or not patients also received prophylactic antibiotics or between those receiving G-CSF as primary or secondary prophylaxis. 

• Early mortality was not defined in this analysis.
• Although methods for determination of heterogeneity were discussed, findings regarding heterogeneity were not reported.

To evaluate primary granulocyte colony-stimulating factor (G-CSF) prophylaxis versus a placebo or untreated control group

DATABASES USED: Electronic databases through December 2006: MEDLINE, EMBASE, CANCERLIT, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effect, and Conference Proceedings (American Society of Clinical Oncology and American Society of Hematology). In addition, references from included articles and relevant published reports were hand searched, and references from leaders in the field were solicited. The literature search had no language restrictions.

INCLUSION CRITERIA:

• Eligible studies were those of adult patients with cancer receiving conventional-dose chemotherapy for solid tumors or malignant lymphoma and randomly assigned to primary G-CSF prophylaxis versus a placebo or untreated control group.
• Primary G-CSF prophylaxis refers to G-CSF administration in the first cycle of chemotherapy before the onset of neutropenia, whereas secondary G-CSF prophylaxis is defined as G-CSF prophylaxis started in the chemotherapy cycle after the first episode of febrile neutropenia (FN). Patients may have received prophylactic antibiotics as long as they were permitted equally in both study arms.
• G-CSF must have been administered continuously until neutrophil recovery. Previous studies and guidelines concluded that myeloid growth factors are less effective if administered on the same day as chemotherapy, delayed more than four days following chemotherapy, or delayed until the onset of neutropenia. Therefore, studies were eligible only if the initiation of G-CSF was one to three days after the completion of myelosuppressive chemotherapy in each cycle.
• Studies in which control patients received secondary G-CSF prophylaxis after the first cycle with the same myeloid growth factor were permitted.

EXCLUSION CRITERIA:

• Studies were excluded if they used granulocyte-macrophage colony stimulating factor, were studies of children or patients with leukemia or multiple myeloma, included bone marrow or peripheral blood stem cell transplantation, or represented an economic analysis.
• Studies also were excluded if G-CSF was administered for established neutropenia or FN. Studies of patients receiving dose-dense or dose-escalation chemotherapy were excluded, as were studies that allowed differing drugs, doses, or schedules of chemotherapy or G-CSF in the different study arms.

FINAL NUMBER STUDIES INCLUDED = 17 RCTs of primary prophylactic G-CSF

TOTAL PATIENTS INCLUDED IN REVIEW = 3,493 patients

KEY SAMPLE CHARACTERISTICS:

• Ten studies (59%) used filgrastim, six (35%) used lenograstim, and one (6%) used pegfilgrastim.
• The cancer types consisted of solid tumors in 11 trials (65%) and aggressive non-Hodgkin lymphoma in six RCTs (35%).
• Four RCTs (24%) were limited to elderly patients with lymphoma.
• Eight studies used placebo control.
• At least three trials permitted secondary prophylaxis with G-CSF in control patients, with only two reports explicitly prohibiting this use of G-CSF. Eleven trials failed to specify whether secondary prophylaxis with G-CSF was allowed in controls.
• Prophylactic antibiotics were used in three trials, prohibited in five trials, and not specified in eight trials.

The occurrence of FN was reported as an outcome in 15 trials with 3,182 patients.

• G-CSF reduced the risk of FN by 46%.
• FN occurred one or more times in 39.5% of controls and 22.4% of G-CSF patients, resulting in a weighted summary RR of 0.54 (95% CI, 0.43 to 0.67; P < .0001).
• Filgrastim (RR = 0.61; 95% CI, 0.53 to 0.72) and lenograstim (RR = 0.62; 95% CI, 0.44 to 0.88) had similar efficacy.
• The single pegfilgrastim study demonstrated significantly greater efficacy (RR = 0.08; 95% CI, 0.03 to 0.18) compared with filgrastim and lenograstim (P < .0001).

Infection-related mortality was reported as an outcome in 12 trials including 1,454 control patients and 1,463 patients receiving G-CSF.

• Overall, infection-related mortality was observed in 2.8% of controls and 1.5% of G-CSF patients, for a weighted summary RR of 0.55 (95% CI, 0.34 to 0.90; P = .018).
• Reductions in infection-related mortality with G-CSF were observed among studies of filgrastim (RR = 0.53; 95% CI, 0.30 to 0.92; P = .024). Statistical analysis of the subset of patients who received lenograstim or pegfilgrastim was not possible because the sample size was too low to detect differences.

Early mortality was reported in 13 trials with 3,122 patients.

• Overall, early mortality was observed in 5.7% of control patients and 3.4% of G-CSF patients, resulting in a weighted summary RR of 0.60 (95% CI, 0.43 to 0.83; P = .002).
• Reductions in early mortality with G-CSF were observed among studies of filgrastim (RR = 0.60; 95% CI, 0.41 to 0.89; P = .010) and pegfilgrastim (RR = 0.36; 95% CI, 0.13 to 0.99; P = .047) but not lenograstim (RR = 0.84; 95% CI, 0.38 to 1.83; P = .657).

Relative dose intensity (RDI) was reported as an outcome in 10 trials. The average RDI among control patients in these studies ranged from 71.0%–95.0%, with a mean RDI of 86.7% (median RDI: 88.5%).

• Among G-CSF-treated patients, the average RDI ranged from 91.0%–99.0%, with a mean RDI of 95.1% (median RDI: 95.5%). RDI differences between study arms ranged from 2.8%–20.0%, with average differences of 8.4% (P = .001). None of the 10 G-CSF treatment arms reported an average RDI of less than 90%, whereas 6 of 10 control groups reported a mean RDI of less than 90%, with four control arms averaging an RDI of 85% or less.

Bone or musculoskeletal pain during the course of chemotherapy was reported as an outcome in 14 trials including 3,029 patients.

• Bone pain was reported in 10.4% of controls and 19.6% of G-CSF-treated patients, for a weighted summary RR of 4.023 (95% CI, 2.156 to 7.52; P < .0001).

To investigate the protective effects of glutamine on radiation-induced diarrhea

Patients were divided into two groups. One group received 15 g oral glutamine each day beginning one week prior to radiotherapy and continuing until one week after radiation therapy completion. The other group was given an oral glucose solution.

• The study consisted of 36 patients with a mean age of 66 years.
• The sample was 62% male and 38% female.
• Renal, prostate, bladder, and gynecologic were the most common cancers.
• All were receiving radiation therapy in the range of 45–70 Gy. Some also had received concomitant chemotherapy with 5 fluorouracil (5FU) or cisplatin.

The study was conducted at a single outpatient site in Turkey.

Patients were undergoing the active treatment phase of care.

This was a two-group prospective trial.

• Patient diaries were used. 
• The National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 3.0, for diarrhea was used.
   

No between-group differences were found in overall incidence of diarrhea. None of the patients in the glutamine group developed grade 3–4 diarrhea, compared to 69% of those in the placebo group (p = 0.0000). More patients in the placebo group required loperamide and parenteral supportive therapy.

Findings suggest that oral glutamine may be helpful in the prevention and management of severe radiation-induced diarrhea.

• The sample size was small with fewer than 100 patients.
• A risk of bias exists because no blinding or random assignment was used.
• More patients in the placebo group received 5FU and had rectal cancer. 
• Diarrhea grading depends on patient recall of stool frequency, so reliability and accuracy may be questionable.
• The authors did not clarify how the criteria were applied and what toxicity value was used in analysis, because grading was apparently done twice weekly. 
• A 10% drop-out rate occurred because of a lack of compliance with the oral medication. 
• The glucose solution used as placebo was not well described. The nature of this solution could have worked as an osmotic laxative in the placebo group. 
• The authors did not explain how patients were assigned to study groups.

Findings suggest that oral glutamine may help in the prevention of severe radiation-induced diarrhea. However, study design issues limit the quality of this study. Use of glutamine warrants further investigation in large, well-designed randomized studies.

To determine if patients receiving treatment for cancer experienced less treatment-related fatigue if they participated in a regular committed exercise regimen, compared to those who did not exercise regularly.

Databases searched were CINAHL, MEDLINE, Ovid, and ProQuest between January 2000 and October 2006.

Search keywords were fatigue, cancer, and exercise.

Studies were included in the review if

• The date range was January 2000 to October 2006
• The participants were 18 years or older
• They were written in the English language
• They were published in peer-reviewed nursing and healthcare journals
• They were quantitative or qualitative studies.

Two unpublished doctoral dissertations were also included.

Initially, 400 articles addressing the topics of fatigue, cancer, and exercise were found. When the inclusion criteria were applied, 10 studies were included. Levels of evidence presented were established using the Priority Symptom Management (PRISM) system developed by the Oncology Nursing Society.  No meta-analysis was performed due to differing definitions and methods of measurement of fatigue across studies.  All studies demonstrated strong levels of evidence of PRISM level I or II. Brief summaries of study design, exercise regimen, outcomes, limitations, level of evidence, and study recommendations were provided. Studies were identified within two major categories: home-based exercise interventions and out-of-home exercise interventions.

• There were 523 total participants across 10 studies.
• Sample sizes of studies ranged from 12 to 108 participants.

The majority of studies (eight of 10) used home-based exercise interventions.

Eight of the studies had findings that supported exercise during treatment to reduce fatigue.  In the two studies that did not show differences in fatigue, one had a very small sample size and one showed poor patient adherence to the exercise regimen.

Exercise was generally well tolerated by participants, and there were no adverse events associated with exercise.

Components of the regimens that were found to be beneficial were

• Ease of treatment (home-based, use of own equipment, etc.)
• Interest in treatment (allowing patients to choose an aerobic activity of interest to them, such as biking, walking, swimming, etc.)
• Inclusion of a daily diary to record frequency and intensity of exercise, as well as other symptoms
• Design of a program based upon a physician’s assessment of individual abilities
• Participation in a group exercise program provided support and increased motivation.

Theoretical foundations of studies were reviewed. These included

• Transtheoretical Model
• Roy’s Adaptation Theory
• Adherence
• Multidimensional conceptual framework interrelating psychosocial and physiologic dimensions of fatigue.

The evidence suggested that an individualized exercise program should be included in the treatment of patients receiving chemotherapy and/or radiation therapy. Studies have not shown any adverse effects, such as increased fatigue or falls, as a result of exercise. Studies retrieved were limited to four types of cancer: multiple myeloma, breast, lung, and prostate. Studies reviewed encompassed both early and late stages of disease.

Common limitations found among the studies reviewed included

• Lack of a universal definition of fatigue
• Lack of a universal instrument or method to measure fatigue and evaluate the effectiveness of interventions.

Use of common definitions and methods of measurement of outcome variables is needed to further advance this area of study. Evidence supports the inclusion of scheduled exercise in the care plan of patients undergoing cancer treatment. It was noted that approximately 50% of healthy Americans have been shown to have difficulty initiating and maintaining an exercise program for more than three months. This suggests that individuals with cancer are likely to need professional support to begin and maintain an exercise program. Nurses’ awareness of the role of exercise can enable better education that benefits patients.

To compare the safety and efficacy of pegfilgrastim and filgrastim in patients being treated with intensive chemotherapy for malignant lymphoma

Patient receiving CHASE(R) chemotherapy were randomized to receive either a single dose of pegfilgrastim or daily doses of filgrastim starting on day 4 after the completion of therapy. The primary endpoint was the duration of severe neutropenia.

• N = 111 randomized, 109 treated, 107 evaluable   
• MEDIAN AGE = 61 years (pegfilgrastim group), 60.5 years (filgrastim group)
• MALES: 66% (pegfilgrastim), 57.4% (filgrastim); FEMALES: 34% (pegfilgrastim), 42.6% (filgrastim)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Pegfilgrastim: 94.3% (non-Hodgkin lymphoma [NHL]), 5.7% (Hodgkin lymphoma [HL]); filgrastim: 92.6% NHL, 7.4% HL
• OTHER KEY SAMPLE CHARACTERISTICS: Bone marrow involvement in 11.3% of the pegfilgrastim group and 9.3% of the filgrastim group; radiotherapy prior to current regimen in 13.2% of the pegfilgrastim group and 11.1% of the filgrastim group

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Japanese Cancer Centers

• PHASE OF CARE: Active antitumor treatment

• Multicenter, randomized, double-blind, phase-III trial

The primary endpoint was the duration of severe neutropenia. Secondary endpoints were the duration of neutropenia and the incidence of febrile neutropenia.

The mean duration of severe neutropenia in patients receiving pegfilgrastim was 4.5 days (SD = 1.2) and 4.7 days (SD = 1.3) in the filgrastim group (p < 0.001). This demonstrated that noninferiority of pegfilgrastim compared to filgrastim. The neutrophil count peaked on the day after the start of the study drug administration for pegfilgrastim and on day 5 for filgrastim. The peak of the nadir was between days 8 and 10 for both groups and then returned to ≥ 1.0 x 10^9/L by day 16 in all patients. The mean duration of neutropenia was 5.2 (SD = 1.3) days for pegfilgrastim and 5.1 (SD = 1.3) days for filgrastim. The mean neutrophil count at nadir was 0.013 (SD = 0.026) x 10^9/L in the pegfilgrastim group and 0.017 (SD = 0.055) x 10^9/L in the filgrastim group. The incidence of febrile neutropenia was 56.6% in the pegfilgrastim group and 55.6% in the filgrastim group.

In respect to both primary and secondary endpoints, noninferiority was proven. While not an endpoint of the study, the adverse effects were very similar as well.

• Risk of bias (no control group)

Education about neutropenia, the duration of neutropenia, and the risk of febrile neutropenia as well as the importance of a granulocyte–colony-stimulating factor (G-CSF), whether filgrastim or pegfilgrastim, is important. In addition, nurses should provide education on the side effects of both medications.

To determine whether short-term and low-dose prednisolone reduces aromatase inhibitor (AI)–induced arthralgias in patients with breast cancer

Prednisolone 5 mg was administered to women once daily in the morning for one week.

• The study reported on a sample of 27 patients.
• Mean patient age was 62.8 years, with a range of 51–81 years.
• All patients were hormone receptor–positive women with breast cancer.
• Of the sample, 25 were taking anastrazole, and 2 were taking letrozole; 68% had finger pain, and 29% had knee joint pain.

• Multisite
• Outpatient setting
• Japan

Patients were undergoing active antitumor treatment.

The study was a prospective intervention clinical trial.

• Questionnaire for assessment of arthralgia symptoms (no mention of validation); symptoms were measured at one week, one month, and two months.
• A visual analog scale also was used to measure percentage of relief.

Joint symptoms improved in 67% of patients immediately after prednisolone, 63% continued to report relief at one month, and 52% at two months. Thirty percent of patients reported an improvement in daily life at one week and one month and 26% at two months.

Results suggest that a low dose of 5 mg of prednisolone given for one week at the initiation of AI therapy can relieve arthralgias in some patients.

• The study had a small sample, with less than 30 participants.     
• The study had baseline sample/group differences of import (two patients on letrozole and others on anastrozole).     
• The study had risk of bias due to no control group.
• Measurement/methods were not well described.  
• Measurement validity/reliability were questionable.
• Adverse effects were not delineated.

While this study suggests that AI-related pain can be reduced in patients with breast cancer using prednisolone, randomized controlled trials are needed that reflect longer follow-up and adverse event monitoring. Insufficient evidence exists to recommend practice implementation.

To provide a guideline for the use of antimicrobial prophylaxis for patients in an allogeneic bone marrow transplantation setting.

This was classified as a guideline of evidence-based medicine criteria.  The author used a table to rate available evidence-based articles about antimicrobial prophylaxis in allogeneic bone marrow transplant recipients.

• The phase of care was active treatment surrounding hematopoietic stem cell transplantation (HSCT).
  • Pre-engraftment occurred until day 30.
  • Post-engraftment occurred from days 30 to 100.
  • Late post-engraftment occurred after more than 100 days.

Evidence was rated using this table.   

Category, Grade                        Definition

Strength of Recommendation
A             Good evidence to support a recommendation for use (strongly recommended)
B             Moderate evidence to support a recommendation for use (generally recommended)   
C             Poor evidence to support a recommendation (optional)
D             Moderate evidence to support a recommendation against use (generally not recommended)
E             Good evidence to support a recommendation against use (never recommended)

Quality of Evidence
I                Evidence from at least one well-executed randomized, controlled trial
II               Evidence from at least one well-designed clinical trial without randomization; cohort or
                     case-controlled analytic studies (preferable from more than one center); multiple time-series    
                     studies; or dramatic results from uncontrolled experiments
III              Evidence from opinions of respected authorities based on clinical experience, descriptive
                      studies, or reports of expert committees.

Bacterial

Al:  Fluoroquinolones should be used for antibacterial prophylaxis.
BII:  Pneumococcus prophylaxis should be used for any patient with active chronic graft-versus-host disease and for the remainder of the patient's life following splenectomy.
BIII:  Patients already receiving Pneumocystis carinii pneumonia (PCP)-prophylaxis with trimethoprim/sulfamethoxazole (TMP-SMZ) should have additional prophylaxis based on the epidemiology for the area and patterns of resistance.
DI:  Anti-infectious prophylaxis with intravenous immunoglobulins should be used.

Cytomegalovirus

Preventing Exposure

AIII:  All patients being considered for allogeneic stem cell transplant should have anti-cytomegalovirus (CMV) IgG-antibody testing.  This is recommended to establish the risk for reactivation (de novo infection).
BIII:  CMV-negative transplant candidates and patients should not share drinking cups or eating utensils that have been used by others.  If a patient who is CMV-negative is in a monogamous relationship, his/her partner is advised to be CMV-serotested. If his/her partner is positive or the patient is not in a monogamous relationship, condom use during sexual contact is recommended.
Al:  Transplant recipients who are CMV-seronegative should receive blood products from donors who have also tested negative. When blood banks lack CMV-negative donors, only leukocyte-depleted red cells and thrombocytes should be issued to this group.
DI:  CMV prophylaxis should use preparations of human immunoglobulin for CMV-negative matched related donors.

Preventing Disease and Reactivation

BIII:  For a CMV-positive recipient, most transplant physicians recommend a CMV-positive donor.
Al:  Any patient at risk for CMV disease should be screened for pp65 antigenemia or nucleic acid using real-time polymerase chain reaction (PCR) at least weekly after transplant from days 10 to 100.
Al:  Patients should begin pre-emptive therapy following one positive pp65 or two consecutive PCR results.  Pre-emptive therapy is advised for two weeks, followed by another two weeks of maintenance therapy.
AI:  In a pre-emptive setting, if the patient has resistance to ganciclovir, switching to foscarnet is recommended.
AI:  The recommendation for herpes simplex virus (HSV) reactivation in IgG-positive patients is acyclovir.  Acyclovir therapy should begin between the start of conditioning therapy and day 1 after the transplant and should continue until day 30 after stem cell transplantation.
Al:  The recommendation of drugs for prophylaxis or therapy of CMV are ganciclovir and foscarnet.  (Cidofovir has a BII recommendation.)
EI:  High-dose acyclovir and valacyclovir should be used to prevent CMV.
El:  Human immunoglobulins should be used for prophylaxis or therapy of CMV.

Herpes Simplex Virus

Preventing Exposure

AIII:  Serum tests for anti-HSV serostatus are mandatory.

Preventing Reactivation

AI:  Acyclovir should be used for standard reactivation prophylaxis, beginning between the start of conditioning therapy and day 1 posttransplant and continuing to day 30 following stem cell transplant.
CI:  Evidence is lacking for the use of acyclovir prophylaxis increased to 100 days or more.
BIII:  If repeated reactivation is present after 30 days of prophylaxis, continued therapy is recommended.
EIII:  Acyclovir is not recommended for continued HSV prophylaxis at times when gancyclovir or foscarnet is used for CMV therapy or prophylaxis because gancyclovir and foscarnet are effective against HSV in vitro.
CIII:  The effectiveness of valacyclovir and famciclovir in preventing HSV reactivation lacks the support of trials, but they are presumed effective.

Varicella-Zoster Virus

AIII:  All patients being considered for stem cell transplant should avoid contact with those suspected of active varicella-zoster virus (VZV) infection or reactivation.
BIII:  Those living with or in close contact with a transplant patient should be vaccinated before transplant.
AIII:  To prevent nosocomial spread, transplant patients with overt VZV disease are to be isolated until all lesions are crusted.
CIII:  Long-term acyclovir prophylaxis is not effective for prevention.

Epstein-Barr Virus

AIII:  Seronegative transplant candidates and patients with Epstein-Barr virus (EBV) should not share drinking cups or eating utensils that have been used by others.  If a patient negative for EBV is in a monogamous relationship, his/her partner is advised to be EBV-serotested.  If his/her partner is positive or the patient is not in a monogamous relationship, condom use during sexual contact is recommended.

Community Respiratory Virus

AIII:  Exposure prophylaxis is critical in avoiding respiratory syncytial virus, influenza, parainfluenza, and adenovirus.
BII:  Those living with or working on units with transplant patients should be vaccinated for influenza.
BIII:  Patients should receive a two-week course of amantadine or rimantadine for chemoprophylaxis if vaccination occurred during an influenza outbreak.

Yeasts

CIII:  Foods at risk for allowing fungi to colonize in the gastrointestinal (GI) tract should be restricted.
AIII:  Hand washing and disinfecting by personnel should be performed to prevent GI-colonizing fungi from reaching patients at risk.
Al:  It is recommended to take fluconazole 400 mg/day IV or orally  to prevent yeast infections in allogeneic stem cell recipients while they are neutropenic.  
BI:  One study found itraconazole superior to fluconazole but noted that GI side effects can limit oral use.
EII:  Itraconazole is not recommended for yeast prophylaxis because of interactions with metabolism of busulfan.   
EI:  Itraconazole is not recommended for yeast prophylaxis because of interactions with metabolism of cyclophosphamide.

Molds

AII:  Stem cell transplant candidates and patients must avoid construction, renovation, or other areas with dust exposure.
AII:  Use of air conditioning with high-efficiency particulate absorption filtration or laminar air flow in transplant units reduces mold spore presence in the air and mortality related to fungal invasion.
BIII:  Transplant patients should wear appropriate fitting masks when traveling through or to areas off the transplant unit.
BII:  No drug demonstrates effectiveness for the primary prophylaxis of aspergillosis following bone marrow transplant.      
DII:  Itraconazole capsules are limited based on low bioavailability.
AI:  For patients with acute leukemia, itraconazole solution reduced the incidence of invasive aspergillosis if plasma levels were greater than 500 ng/mL.
AIII:  Secondary prophylaxis with a drug having systemic effectiveness was recommended despite a lack of trial evidence.

Pneumocystis jiroveci (formerly Pneumocystis carinii)

BIII:  Stem cell recipients are not to have contact with patients with known PCP.
AII:  TMP-SMZ prophylaxis should be used for all allogeneic transplant patients beginning at engraftment until the completion of immunosuppressive therapy or when chronic graft-versus-host disease is resolved.  
AII:  Dapsone or aerosolized pentacarinate should be used when TMP-SMZ is contraindicated or when the patient does not tolerate it.  Higher breakthrough rates are noted with these alternate drugs.

Toxoplasmosis

AIII:  Allograft recipient candidates should be tested for Toxoplasma gondii antibodies to identify risk for reactivation.  Education should include ways to avoid exposure.
CIII:  Toxoplasma prophylaxis at the time of acute graft-versus-host disease or secondary prophylaxis following history of toxoplasmosis should be performed.

Food

BIII:  Foods with a risk of fungi, bacteria, or other contamination should be eliminated during and following stem cell transplant, and safer alternatives should be used (e.g., pasteurized cheese instead of unpasteurized cheese).

Vaccination After Stem Cell Transplant

AIII:  Immunity against specific pathogens should be analyzed one year after allogeneic transplant with reimmunization with inactivated vaccine or toxoids.

The article also states that stem cell transplant recipients are not to receive live-attenuated virus vaccination during the two years after transplant.  No rating was provided for this “strictly contraindicated” recommendation.

• Some clinical trials during the 1990s did not specify allograft recipients for inclusion, so patients undergoing allograft and autologous stem cell transplants may have been included.
• Placebo studies are rare for this area of study, so most trials compared an old medication with a new one.
• Advances in allogeneic stem cell transplantation over the past 15 years make comparisons of patients who received growth factor stimulation after transplant and those who did not, which is problematic.
   

Specific recommendations with strong evidence, AI and EI, should be included in nursing practice guidelines with recommendations for and against practice, respectively.  Other recommendations should not be included until higher evidence from trials can be demonstrated or included in the “Evidence Not Established” category. 

To investigate the feasibility and effects of a multimodal intervention for fatigue compared to home-based aerobic exercise

Individuals selected which intervention they wanted—home exercise or the multimodal intervention. The multimodal intervention included psychoeducation, including mindfulness-based techniques, sleep education regarding sleep hygiene, restriction and stimulus control, eurythmy therapy involving mind-body exercises, and medicine-oriented painting therapy. Those in the exercise group were asked to carry out 30-minute sessions three to five times weekly. Those in the multimodal group had 225 minutes of activity once weekly over 10 weeks, led by specialists in that therapy. Baseline and follow-up study measures were obtained within three weeks prior to starting the study and within three weeks after completion.

• N = 28 
• MEAN AGE = 57 years
• MALES: 0.5%, FEMALES: 99.5%
• KEY DISEASE CHARACTERISTICS: All had breast cancer. On average, patients were three years out from initial diagnosis and treatment.
• OTHER KEY SAMPLE CHARACTERISTICS: Approximately half were employed. All had a fatigue score of at least four and had fatigue for at least six months.

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

• PHASE OF CARE: Late effects and survivorship

• Observational two-group pilot study

• Cancer Fatigue Scale (CFS-D) (scale of affective, physical, and cognitive fatigue)
• Pittsburgh Sleep Quality Index (PSQI)
• Satisfaction with intervention on five-point Likert scale

Those in the multimodal group showed a significant reduction in physical fatigue (p = .0342, mean change = -2.1). Those in the multimodal group had a significant improvement in global sleep quality (p = .041, mean change = -2.0).

A multicomponent intervention was seen to be feasible and had a positive impact on rating of physical fatigue and global sleep quality.

• Small sample (< 30)
• 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)
• Other limitations/explanation: Adherence to home-based exercise is not known.

A holistic multicomponent approach to manage patient fatigue and sleep disruption may have greater benefit than interventions that only incorporate exercise. Further research is needed to determine what type and intervention components are most effective.