To review prospective comparative studies that address infection prevention for high-risk patients undergoing chemotherapy and stem cell transplant recipients to evaluate the evidence for best practice and assess for mortality.

Databases searched were CENTRAL (the Cochrane Library issue 4, 2006), PubMed (1966–2008), and LILACS (1982–2006). Unpublished trials that were presented at the following conferences were also queried: American Society of Hematology (2001–2006), American Society of Clinical Oncology (1995–2006), and European Society for Medical Oncology (2002–2006). The references lists from all included studies were reviewed to identify additional studies. 

Keywords searched were not provided by the authors.

Studies were included if they 

• Were prospective comparative studies that included patients with cancer in the hospital or outpatients who were receiving chemotherapy for solid tumors.
• Reported hematological malignancies.
• Reported stem cell transplant recipients.  
• Compared an intervention to placebo, no treatment, or another intervention, as well as all environmental measures, barrier precautions, and other nonpharmacological measures used for the prevention of infectious diseases.

Studies were excluded if they were nonrandomized studies that compared patients with different types of cancer or compared different treatment protocols (i.e. stem cell transplant versus chemotherapy) or if they assessed pharmacological interventions, such as antimicrobial prophylaxis and mouth rinse preparations, unless these interventions were applied together or as a control for the infection-control interventions.

Forty studies were included.

Method of Study Evaluation

Prevention of infection measures used in the studies were identified and grouped together: control of air quality (air filtration), protective isolation, and suppression of the endogenous flora (antibiotics). Subgroup analyses were performed for two major outcomes: all-cause mortality at 100 days and documented infections.

• The total sample size was 40 studies; the sample range across studies was 45 to 3900.
• Twenty-six studies in the analysis studied protective isolation, 11 assessed outpatient versus inpatient care, and three evaluated other random interventions.  
• Twenty-nine studies assessed patients with acute leukemia, six included patients with other hematologic malignancies, and 22 included hematopoietic stem cell transplant (HSCT) recipients exclusively.
• No study included patients with solid tumors at low risk for infection.

The primary outcome, all-cause mortality, was assessed at 30 days, 100 days, and at the longest follow-up reported in each study. Secondary outcomes included the rate and types of infections (including bacteremia), the need for hospitalization and length of hospital stay, the length of the febrile period, infection-related mortality, bacterial and fungal colonization, and antibiotic and antifungal treatment.

• Protective isolation, including control of air quality, barrier isolation, and endogenous suppression due to antibiotics, were shown to significantly reduce mortality (relative risk [RR] = 0.79; 95% confidence interval [CI] [0.72, 0.87]).
• Antibiotic prophylaxis was the main component mediating the beneficial effect of isolation interventions. Improved survival was only shown when antibiotic and antifungal prophylaxis was used with air quality control or barrier isolation (RR = 0.66; 95% CI [0.55, 0.79] in studies with prophylaxis compared with RR = 0.93; 95% CI [0.75, 1.15] in studies without prophylaxis).
• Protective isolation with prophylactic antibiotics also significantly reduced infection, whereas control of air quality or barrier isolation alone did not.
• Control of air quality did not significantly reduce mold infections.  Outpatient mortality was also significantly lower than inpatient mortality (RR = 0.72; 95% CI [0.55, 0.95]).

A combination of air quality control, barrier isolation, and prophylactic antibiotics is estimated to reduce 30-day all-cause mortality by 40% in high-risk cancer patients, including allogeneic or autologous HSCT recipients and patients with acute leukemia. Prophylactic antibiotic use is the most significant preventive strategy; air quality control and barrier isolation did not show an independent contribution, and their use should be reserved for patients at highest risk of infection. Survival significantly improved with outpatient management, which included the use of prophylactic antibiotics without environmental controls.

The reduced mortality seen in outpatient management may be due to

• Selection bias (healthier patients are able to remain outpatient)
• Decreased risk of infection from hospital pathogens
• Use of antibiotic prophylaxis.

There is no evidence that any of these preventive strategies (air quality control, barrier isolation, or prophylactic antibiotics) are necessary or appropriate for low-risk cancer patients with solid tumors.

To evaluate the effectiveness of a three-week educational intervention on patients' levels of fatigue

The intervention was comprised of a printed educational package that contained basic information about fatigue with three face-to-face two-hour sessions once a week that were tailored to the specific needs of the patient groups. The control group received no educational sessions. They did receive standard face-to-face care provided by a healthcare provider in an outpatient clinic. Study measures were obtained at baseline, immediately after the intervention, and at three months.

• N = 160 (81 control group; 79 intervention group)  
• MEAN AGE = 55.3 years (SD = 25–77 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTIC: Early-stage breast cancer 
• OTHER KEY SAMPLE CHARACTERISTICS: Fatigue score was > 2.5 on a 0–10 numeric rating scale. Most subjects were university/college-educated, married/partnered, lived with someone, and were employed.

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Norway, university-based breast cancer clinic

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care  

Randomized, controlled trial

• Demographic questionnaire
• Clinical questionnaire
• Numeric rating scale (Fatigue)
• Fatigue Questionnaire (FQ)
• Lee Fatigue Scale (LFS)

This study demonstrated no statistically significant differences between groups or within groups for any fatigue measures.

More research is needed to identify important variables that might affect the experience of fatigue as well as the effectiveness of the type of psychoeducational interventions in women with breast cancer.

A standardized psychoeducational intervention alone may not be sufficient to affect the experience of fatigue among women with breast cancer. Nurses can use the critique of the methods and instruments used and learn about reasons for withdrawing/not completing interventions/evaluations by research subjects to apply to future studies.

RESOURCE TYPE: Evidence-based guideline

PHASE OF CARE: Active antitumor treatment

Recommends a threshold of 10,000 mcl for prophylactic platelet transfusions in patients undergoing therapy for acute leukemia. It is noted that higher levels may be necessary in newborns or patients with signs of hemorrhage and those undergoing invasive procedures. The same threshold is suggested for individuals with solid tumors, except for those receiving aggressive therapy for bladder tumors. In this case, a threshold of 20,000 mcl is recommended. It is suggested that counts of 40,000–50,000 mcl should be sufficient for major invasive procedures in the absence of coagulation abnormality. For minor procedures such as bone marrow biopsy, a platelet level of 20,000 should be adequate for safety.

The overall threshold suggested for most patient situations for prophylactic platelet transfusion is 10,000 mcl.

In areas such as solid tumors, there is limited evidence.

This guideline provides information about administration of platelets for prevention of bleeding and recommended thresholds for prophylactic transfusions.

The purpose of the study was to determine if central venous catheters (CVCs) impregnated with rifampicin and miconazole would decrease growth of bacteria and lead to a decline in catheter-related bloodstream infections as well as the complications associated with them.

Hospitalized adults (aged 18–80 years) who required a CVC for at least two days and were undergoing their first venous catheterization were included in this study. A triple lumen polyurethane CVC supersaturated with rifampicin andmiconazole was compared with the standard version. A segment of the catheter was cultured to evaluate catheter colonization. Catheter colonization was defined as growth of 15 or more colony-forming units detected on a catheter segment by the semi-quantitative roll-plate technique. Catheter-related local infection was defined as a colonized catheter accompanied by at least one of the following criteria: redness, induration/swelling, purulent secretion, and/or pain.

• The total sample included 223 participants.
• The mean age was 61 years (range = 21–80)
• Male participants made up 69% of the sample; female participants made up 31%.
• Participants were hospitalized surgical patients requiring a CVC (84 patients [38%] with oncological diagnoses.
• Overall catheter indwelling time was 6.7 days (SD = 3.2) in the control group and 7.5 days (SD = 4.7) in the intervention group. However, long-term indwelling  (more than seven days) was significantly higher in the intervention group (10.8 days [SD = 4.9], median = 9 days, n = 46) than in the control group (9.2 days [SD = 2.9], median = 8 years, n = 48) (p = 0.029).

Single inpatient setting in Germany.

Active treatment

Prospective-controlled, non-blinded, randomized clinical trial.

• Microbiologic evaluation
• Swab samples taken from the catheter connectors (hub) and the skin at the site of catheter insertion
• Cultures of  the IV part of the catheter.
• After removal of the catheter, ex vivo activity of the antimicrobial catheters was measured as the mean diameter of inhibition towards Staphylococcus epidermidis RP62A.

Compared to the standard device, modified CVCs showed significantly lower catheter colonization as well as catheter-related infection during short-term (less than seven days, p = 0.001), as well as during long-term (seven days or more, p = 0.001). In the control group,38 (36.3%) of the 105 standard CVCs were colonized. In the intervention group, 6 of 118 loaded CVCs were colonized (5.1%). The colonization rate in the oncology subgroup did not differ greatly from the rate of the patients without cancer (39% versus 34.4%, p = 0.629); however, the catheter-related infection rate was significantly higher in patients with cancer. The catheter-related infection rate of oncologic patients was reduced from 26.8% to 2.3% using the loaded CVC, indicating its pronounced efficacy in preventing catheter-related infection in patients with cancer (p < 0.001). The main covariate for catheter colonization was colonization of the skin at the catheter site (p = 0.001), underscoring the importance of hygienic site care.

Use of an impregnated antimicrobial catheter in patients with cancer has the potential to decrease the risk of catheter-related bloodstream infections and the associated complications.

• Only 38% of the patients in this study had an oncologic diagnosis (n = 84)
• All of the patients were surgical patients.

CVCs impregnated with rifampicin and miconazole may decrease the risk of catheter-related infections and appear to exert their antimicrobial effect for more than four weeks. Additional study is needed to evaluate these catheters in a general oncology population with a larger sample. Skin colonization was associated with increased risk of catheter colonization, emphasizing the importance of meticulous site care.

This study was designed to evaluate interventions targeted to occur at the point when treatment is ending—a time when distress and concerns are known to increase. It also targets younger women; as some studies report, younger women are at greater risk for psychological distress and face different challenges than older women do.

Women with breast cancer were assigned to a three-arm clinical trial. In the two active arms, the women received either an educational intervention, which provided information about their disease and treatment, or information about nutrition, featuring a low-fat, high-fruit-and-vegetable-eating pattern. Both active treatment arms received four group sessions, meeting once per month for four consecutive months. Sessions were led by professionals, and interactions between participants were kept to a minimum. The control arm was standard medical care. Random assignment assessments occurred at baseline, then 4 months, and 13 months later (corresponding to immediate post-intervention and nine months post-intervention.)

• N = 252
• AGE: 50 years and younger
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS:  Diagnosis of stage 0, I, or II breast cancer with no more than 10 positive lymph nodes
• OTHER KEY SAMPLE CHARACTERISTICS: Within two months of completing nonhormonal adjuvant therapy

• SITE: Multi-site
• LOCATION: Recruited from oncology clinics and medical offices in a single state

• RCT

• Depressive symptoms were assessed using a 10-item version of the CESDS.
• Health-related quality of life was assessed using the SF-36 from the Medical Outcome Studies.
• Mediating measures also were assessed including intrusive thoughts, self-efficacy, cancer concerns, self-concept, and coping.

At the 13th-month assessment, participants in the nutrition arm reported significantly fewer depressive symptoms, and in the education arm, marginally fewer depressive symptoms were reported than in the control arm. The difference between the two active treatment arms was not significant. The mediating factors also were identified as contributing by enhancing self-efficacy expectations, reducing some concerns regarding morbidity and mortality, lessening intrusive thoughts about illness, and buffering self-concept perceptions.

• Compliance with treatment sessions was higher in the nutrition arm than in the education arm.
• The trial focused on early-stage disease; if generalizability exists in patients with advanced disease is not known.
• The sample was composed largely of Caucasian, middle-class women in one state. 
• The sample size was adequate, but little diversity of the sample limits generalizability. 
• The difference between the two treatment arms was not significant.

To describe the five-year follow-up results of the use of liposuction for arm lymphedema after breast cancer treatment

Patients who had chronic arm lymphedema who were compliant with use of compression garments were referred for liposuction surgery. Study questionnaires and limb volume measures were performed pre- and postoperatively. Limb volume was measured at 2 and 4 weeks postoperatively and at 3 months, 6 months, and yearly for 5 years. Specific liposuction technique was described. Patients had a custom-made pressure garment applied at the time of the surgery.  All received 5-day courses of antibiotics, analgesia, and limb elevation. Patients were discharged on day 4.

• The study reported on 12 patients who were followed for one year. Only two patients were available for follow up in the fifth year.
• The mean age of patients was 48 years with a range of 38–60 years.
• The sample was 100% female.
• All of the patients had breast cancer. Lymphedema developed at an average of one year after initial surgery, and mean duration was 7 years.
• Eleven of the patients received axillary dissection, while one developed lymphedema after subsequent thyroidectomy. 
• Most of the patients had received adjuvant radiation or chemotherapy.

The study was conducted at a single site, inpatient and outpatient setting, in the United Kingdom.

• Patients were undergoing long-term, follow-up care.
• The study has clinical applicability for late effects and survivorship.

This study involved prospective analysis.

• The Hospital Anxiety and Depression Scale (HADS) was used.
• A visual analog scale (VAS) was used to measure overall well being.
• Arm volume was measured using conal measurement at 4-cm intervals.

No surgical complications occurred. The mean percent reduction in arm volume after surgery was 84%. At one year after surgery, the mean volume difference between operated and unaffected arms was 29 ml. At two years, a mean volume ratio of the operated to nonoperated arm of 0.98 was found, demonstrating that volumes were virtually the same.  In 11 patients, postoperative anxiety scores declined (p = 0.049). Researchers noted that ongoing compliance with use of compression garments was essential to continued effect.

Findings suggest that liposuction and ongoing use of compression garments may be a promising approach to manage upper extremity lymphedema in patients after surgery for breast cancer.

• The sample size was small with fewer than 30 participants.
• No comparison or control group was included; however, these results are shown in patients who had prior unsuccessful standard treatments for lymphedma.

Further research into this intervention is needed to further validate these findings in comparison with other approaches.  Liposuction may have some benefit for patients with lymphedema that is not adequately controlled by other means.  The procedure for this application is very specific and requires specific surgical training in this technique.

To clinically evaluate upper ipilateral limb function and the impact of certain post-surgical consequences arising after invasive or breast-conserving surgery for early breast cancer, by intervening, or not intervening, with an early rehabilitation program

Group A received reoperative information verbally; did not begin physiotherapy during hospitalization. Group B received preoperative information in written form; treated by a dedicated physiotherapist during hospitalization from the day following surgery until the hospital discharge. One physiotherapy session per day, with each session lasting for 30–40 minutes. The exercises were initially focused on deep breathing, relaxation, stretching of the neck muscles, and then on elevation, abduction, external and internal rotation of the shoulder, flexion and extension of the elbows in a neutral position. The patients were instructed on how to position their shoulder-arm in bed and how to carry out exercises at home after discharge. The patients were given an exhaustive brochure containing pictures and explanations of the exercises to carry out at home. All patients were assessed at 15–30, 60, and 180 days after surgery. 

SITE:  Single site  

SETTING TYPE:  Inpatient  

LOCATION: Rome, Italy

PHASE OF CARE: Transition phase after active treatment

Two-group cohort comparison

• Shoulder-arm mobility, upper limb function, presence of lymphedema, prescription of outpatient physiotherapy
• Constant and Murley Score for mobility
• Arm circumference measures

Although no differences were identified between two groups in the outcome assessment, statistically significant differences (p <  0.05), in favor of Group B, were encountered at the 180-day follow-up visit, including shoulder-arm mobility, upper limb function (p < 0.001), and presence of lymphedema (p = 0.036).

The early assisted mobilization (beginning on the first postoperative day) and home rehabilitation, in conjunction with written information on precautionary hygienic measures to observe, play a crucial role in reducing the occurrence of postoperative side-effects of the upper limb.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias(sample characteristics)
• Other limitations/explanation: limited follow-up duration, retrospective first follow-up visit in Group A

The study findings suggest that nurses should be aware of early rehabilitation (e.g., early assisted mobilization right after the surgery) and home exercises rehabilitation as well as written/educational information may play a critical role to prevent postoperative side-effects in patients with breast cancer. Studies with rigorous design are warranted to further evaluate the study intervention.

STUDY PURPOSE: To review the evidence for use of oral glutamine to prevent treatment-related mucositis in adult patients with cancer

• DATABASES USED: MEDLINE
• KEYWORDS: glutamine; cancer; mucositis; esophagitis; stomatitis
• INCLUSION CRITERIA: Prospective or retrospective design, evaluating the use of oral glutamine for prevention
• EXCLUSION CRITERIA: Pediatric patients, use of glutamine as treatment for mucositis, combining with other interventions, lack of a control or comparison arm

• FINAL NUMBER STUDIES INCLUDED = 15 studies; only data from 11 studies are discussed.
• TOTAL PATIENTS INCLUDED IN REVIEW = Sample sizes and other study details are not provided.
• SAMPLE RANGE ACROSS STUDIES: 21–326 patients
• KEY SAMPLE CHARACTERISTICS: Patients with varied tumor types and treatments

PHASE OF CARE: Active antitumor treatment

Seven studies reported actual mucositis outcomes. Other studies measured outcomes such as weight change or time to onset but not mucositis grades. Various methods of mucositis grading were used. In seven studies, statistical significance of differences observed was not reported. In 10 of 11 studies, the percent of patients with grade 3 mucositis was lower with oral glutamine. In two studies, grade 4 mucositis incidence was lower with glutamine, and in two studies, it was higher with glutamine. Duration of mucositis and time to development findings were inconsistent. Dosage and timing of glutamine varied across studies.

The results of this systematic review are insufficient to provide strong support for the efficacy of oral glutamine for the prevention of oral mucositis.

The authors stated that the study samples were small. High heterogeneity in terms of tumor types and treatments were involved, and no subgroup analysis was done.

The findings do not show a strong evidence of efficacy of oral glutamine to prevent oral mucositis in patients with cancer undergoing a variety of treatments. Oral glutamine did not, however, demonstrate adverse effects, and some evidence suggests that the severity of mucositis might be lower with glutamine. The effect dose and timing of oral glutamine for various patients and treatment types is unclear.

To study the effect of using streptokinase in pleurodesis for the management of multiloculated malignant pleural effusion (MPE)

Patients were randomly assigned to either the treatment group, which received streptokinase 250,000 IU into pleural space via a thoracostomy tube, or the control group, which received 50 ml of saline at 24, 36, 48, and 60 hours post tube placement. Data were collected regarding volume of pleural drainage, chest computerized tomography (CT) images before and after treatment, dyspnea before and after treatment, and recurrence rate of effusion. Coagulation profiles were assessed prior to administering streptokinase, and all patients had a chest CT to locate the largest locule of fluid. A 20 Fr chest tube was placed and connected to an underwater seal at a continuous suction of -20 cm H₂O. For both groups, daily pleural drainage at 48 and 72 hours were measured. After the third day, a CT thorax was taken and read by one radiologist. On the fourth day, pleurodesis was performed using 4 g of sterile talc. On the fifth day, the chest tubes were removed. Patients that continued to be dyspneic (oxygen dependent) were not discharged from the hospital, and nondyspneic patients were discharged (n = 29) and later evaluated in regard to whether or not they required a repeat pleural catheterization within 30 days because of the redevelopment of dyspnea.

• N = 40   
• MEAN AGE = 57.8 years
• MALES: 60%, FEMALES: 40%
• CURRENT TREATMENT: Immunotherapy
• KEY DISEASE CHARACTERISTICS: All had multiloculated MPE; 40% had diagnosis of lung cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Other cancer diagnoses included breast, colon, ovarian, lymphoma, and others.

• SITE: Not stated/unknown   
• SETTING TYPE: Not specified    
• LOCATION: Istanbul, Turkey

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care 

• Randomized, double-blind, placebo-controlled trial

Measurements were given as mean and standard deviations, and the two groups were compared using the Mann-Whitney U test. The chi-square test was used to compare the improvement scores of the groups via CT evaluation, dyspnea scores, and recurrence rate. SPSS, version 15.0, was also used.

The differences between drainage volumes between groups was statistically significant. Mean drainage volumes for the intervention group versus the control was 493/248 at 24–48 hours, 446/198 at 48–72 hours, and 939/446 overall (p <  0.001). Dyspnea symptoms (defined as oxygen dependent) improved in 90% of the fibrinolytic group and 55% of the control group (p = 0.03). Post discharge of 29 nondyspneic (nonoxygen dependent) patients, 11% of fibrinolytic group had recurrence versus 45% of the control group (p = 0.07). A thorax CT demonstrated a 40% or greater improvement in 85% of the fibrinolytic group and 35% of the control group (p = 0.001).

The treatment group receiving streptokinase via a chest tube prior to pleurodesis had greater improvement in symptoms of dyspnea, greater reduction in volume of MPE, and a lower rate of effusion recurrence.

• Small sample (< 100)
• Measurement/methods not well described

The use of fibrinolytic agents for management of MPE prior to pleurodesis may improve outcomes for reducing dyspnea and reducing recurrence post-pleurodesis leading to enhanced patient quality of life. Additional large-scale studies are indicated for validation. Having a basic understanding of pathophysiology and rationale is important for self-knowledge, patient monitoring, and education in settings using fibrinolytic therapy to treat MPE.

To determine the feasibility of conducting a larger trial to investigate effectiveness with use of compression stockings to prevent leg lymphedema after vulval cancer

Fourteen patients undergoing inguinofemoral lymphadenectomy were randomized to either the best supportive care (control group) or best supportive care plus the use of graduated compression stockings for six months. Patients were seen preoperatively and followed at four weeks, three months, and six months after surgery. Patients were asked to wear treatment stockings during the daytime for six months once mobile beginning no later than three days after surgery. Expected compliance with stockings was 10 hours per day for 180 days.

• The sample was comprised of 14 female patients with vulvar cancer undergoing inguinofemoral lymphadenectomy.
• Median age was 71.5 years with a range of 41–87 years.
• Mean body mass index was 29.4 with a range from 20.432.4.

• Single site
• Inpatient and outpatient
• Northern Gynaecological Oncology Centre, a tertiary referral center cover northeastern England

The study was a randomized controlled feasibility design.

Lower-limb volume was calculated just above the ankle to at least 4 cm below the perineum. Circumference of the limb was measured using an ordinary tape measure at 4 cm intervals commencing approximately 2 cm from the lateral malleolus. The Nottingham Health Profile was used.

Eleven of 14 patients complied with the entire visit schedule. Two patients in the study group had travel hardship and one patient was frail and therefore dropped off. Three patients in the control group failed to comply. Patients in the control group showed greater increase in mean leg volume while those in the treatment arm showed better performance based on leg symptoms and clinical examination.

Prophylactic use of stockings is feasible.

• The sample size was small (N < 30).
• The study was unblinded.

Although a small sample, quality-of-life measurements were equal in both groups. Further studies are needed to evaluate the role of compression garments in prevention of lower-extremity lymphedema.