To determine the feasibility and acceptability of mindfulness-based stress reduction to manage the symptoms of fatigue, anxiety, and depression in women with metastatic breast cancer

An eight-week mindfulness-based (Kabat Zinn) stress reduction course was taught by a trained, experienced instructor. The sessions in weeks 1 and 8 were two and a half hours, and week 2–7 sessions were two hours. Week 6 included a day of mindfulness of four and a half hours. Home practice with CDs 30 minutes a day was recommended. Sessions were done in a group setting.

• N = 19  
• AGE RANGE = 37–65 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Metastatic breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Mean years since metastatic breast cancer diagnosis was 2.76; Eastern Cooperative Oncology Group (ECOG) Performance scores 0–2; stable disease; life expectancy at least six months

• SITE: Single site  
• SETTING TYPE: Outpatient    
• LOCATION: Community oncology center, United Kingdom

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

Mixed method design using qualitative and quantitative data with repeated measures

Qualitative data consisted of interviews one to two weeks prior to the course and four months after the course. Quantitative data consisted of four questionnaires delivered at five time points: the Brief Fatigue Inventory (BFI), the Hospital Anxiety and Depression Scale (HADS), the EuroQol Quality of Life-5 Dimensions, and the Toronto Mindfulness Scale (TMS) at baseline and at weeks 4, 8, 15, and 24. Quantitative data consisted of one questionnaire at two time points: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) at baseline and at week 24.

A group mindfulness-based stress reduction intervention appeared feasible for patients with stable advanced cancer. However, the intervention as used here was time intensive. This type of intervention may be helpful in dealing with some symptoms in patients with advanced disease.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Cost to train mindfulness instructors; time commitment for patients; repeated measures design raises the question of potential testing effect as the same instruments were used repeatedly; no control comparison or attention control study design, so it is impossible to tell how much of the changes seen in anxiety and depression were due to the group interaction rather than the intervention

There is an opportunity to study mindfulness-based stress reduction in patients with metastatic breast cancer and other patients with advanced disease. This study showed that this may be feasible; however, recruitment was difficult, and patients identified barriers related to severity of illness, time commitment, and travel to attend sessions.

To investigate the impact of Pilates exercise on physical parameters, as well as on fatigue, depression and quality of life among women with breast cancer.

Patients selected for participation were randomly assigned to a home exercise program or to the hospital exercise program. Those in the hospital program performed Pilates exercise for one hour per day three times a week for eight weeks. All patients were given an instructional booklet showing pictures of the exercise program as well as information about lymphedema prevention and activities of daily living. All patients were instructed to perform these exercises once daily at home and to walking 20 to 30 minutes per day, three days a week. Assessments were performed prior to the intervention and eight weeks after the exercise program.

• The sample was comprised of 42 participants.
• Mean age was 49.13 years.
• All participants were female.
• Of the participants, 98% had a total mastectomy.
• There was an average of 38 months since diagnosis of breast cancer.
• All patients had completed treatment.
• Forty percent had adjuvant treatment.

• Single site
• Outpatient
• Turkey

The phase of care was late effects and survivorship.

This was a prospective, randomized two-group, pre-/post study.

• Six-minute walk test
• Modified sit-and-reach test (for flexibility)
• Brief Fatigue Inventory (BFI)
• Beck Depression Inventory (BDI)
• European Organization for Research and Treatment of Cancer QOL scale (EORTC) quality of life QOL scale
   

• Almost 50% of the initial sample assigned to home exercise failed to complete the study due to lack of interest, difficulty commuting to the hospital, or medical problems.
• The hospital exercise group showed significant improvement in the six-minute walk test (p = 0.00), depression scores (p = 0.01), and functional aspects on the QOL scale (p = 0.04).
• The only difference between groups was seen in the six-minute walk test, with hospital exercise patients showing improvement and others showing a decline.

Supervised Pilates exercise appears to have positive effects on depression and physical functioning. There was no effect seen on fatigue. A substantial number of those on a home exercise program failed to complete the study, and findings and comparisons are limited by the small sample size.

• The study had a small sample size, with less than 100 participants.
• Baseline sample/group differences were of import.
• The study had risks of bias due to no control group, no blinding, no appropriate attentional control condition, and the sample characteristics.
• The intervention was expensive, impractical, and required training.
• Only women with breast cancer were studied, so findings may not apply to other types of patients. The home exercise intervention was not well described, and apparently consisted of just the booklet and a recommendation to do exercises. The fact that so many patients in the home exercise did not complete the study raises the question of the practicality and ability to maintain patient interest in this approach. Patients in the hospital exercise group had higher baseline fatigue and depression scores and may have had greater opportunity for improvement. Patients in the hospital exercise group did this in a group setting; related social support may have influenced results.

This study provides some evidence that exercise can be of benefit to patients in managing depression. The study has multiple limitations.

To evaluate the protective effects of Na-sucrose octasulfate (NaSOS) on radiation-induced skin damage in patients with head and neck cancer.

Each patient was his or her own control. NaSOS was applied on one side, and the placebo was applied to the other. It was started on day 1 of radiation therapy (RT) treatment. The gel was applied twice a day during RT and for two weeks after.
 

• The sample was comprised of 60 patients (20 females, 40 males).
• Mean age was 60 years (range 21–81).
• Patients had head and neck cancer.
• Megavoltage was 4 to 6 MV.
• There were two opposing lateral portals with separate anterior low neck portals, 2 Gy per fraction, to a total dose of 50 to 70 Gy. Mean total dose was 59.7 Gy.

Norway

The study used a quasiexperimental, double-blind, vehicle-controlled design. Each patient was his or her own control.

• Assessments were performed at initiation and weekly.
• European Organisation for Research and Treatment of cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) acute skin reaction scoring system was used for skin reactions and for pain and itching on both sides.

• The mean skin reaction grade was higher where the placebo was used (p = 0.02).
• There were no differences between groups in other variables or the timing of skin reaction development.
   

There was no significant protective effect with use of NaSOS.

• The authors did not specify who performed evaluations, and there was no interrater reliability.
• There was no log for validation of compliance with study protocol.
• Other skin care regimens are uncertain.
• The study had a relatively small sample size.

STUDY PURPOSE: To review findings of 10 systematic reviews of clinical trials of erythropoietic-stimulating agents (ESAs) in the five-year period spanning 2004–2008.

TYPE OF STUDY: Systematic review

TOTAL REFERENCES RETRIEVED: 10

• FINAL NUMBER OF STUDIES INCLUDED = 10
• TOTAL PATIENTS INCLUDED IN REVIEW =  86,374
• SAMPLE RANGE ACROSS STUDIES: 1,949–21,378
• KEY SAMPLE CHARACTERISTICS: Inference that all patients included in reviews were patients with cancer, but report did not actually specify

PHASE OF CARE: Active treatment

10 reviews of effects of ESA treatment on symptoms and quality of life (QOL) were reviewed.

• (From authors) Overall evidence from studies seem to support  a symptom and QOL benefit from ESA treatment, which is unlikely to be due to chance alone.
• (From reviewer) Quality of studies presented in review, variability of instruments and ESAs used to measure variables of interest, missing data, and lack of description of sample populations in studies limits sufficient evidence for empirical benefit from ESA treatment in patients with cancer

• Focus of review was on patient-reported symptoms and QOL outcomes versus all risks (safety, survival, thrombosis) and benefits (transfusion use, hematologic response) of ESA use.
• Not all of the studies reviewed were placebo controlled or double blinded.
• Increased risk of placebo effect when outcome of interest is patient self-report.
• Many studies failed to report metrics needed for a more detailed analysis.
• Substantial loss of data and lack of documentation of how missing data were handled.
• Timing and conditions under which symptoms and QOL were measured were not described in many studies.

• Focus future studies on description of conditions for the safe use of ESAs.
• Determine empirically derived cutoff above which ESA therapy is contraindicated.
• Conduct detailed analysis of secondary data sources (meta-analysis).
• Need for inclusion of patient perspective of benefits and harms of ESA therapy.
• Development of patient education materials about relative risks and benefits of ESA use or lack thereof.

Patient were randomized to receive sucralfate or placebo, delivered in an oral suspension with identical appearance, taste, and consistency. Patients received six 1-gram doses daily at regular intervals beginning on day one of radiation therapy (RT) and throughout RT, including weekends.

• The study reported on 44 patients with head and neck cancer; 23 received sucralfate and 21 received placebo.
• Mean age of the sample was 55 years with a range of 34–72 years.
• Patients were receiving RT covering at least one-third of the oral mucosa to a minimum dose of 60 Gy.
• Patients were not receiving chemotherapy.

The study was conducted between December 1996 and December 1997.

This was a prospective, randomized, double-blind, placebo-controlled trial.

• Patients received baseline oral examinations and questionnaires with drug- and oral mucositis-related questions.
• The Vander Schueren et al. scoring system was used to assess for mucositis.
• World Health Organization (WHO) criteria for oral and topical analgesics were used.
• Patients underwent biopsy on the 20th day of RT.

• Compliance in the sucralfate group ranged from 3–6 times per day with a median of 5. Patients in the placebo group had a 4–6 times per day compliance rate with a median of 5 (p = 0.21).
• Mean mucositis scores on the 20th day of RT were 2 in the sucralfate group versus 4 in the placebo group (p = 0.0002).
• Pain and dysphagia were reported less frequently in the sucralfate group, but the difference was not significant.
• Patients in the sucralfate group had decreased altered vascular calibration, altered vascular permeability, and leukocyte emigration.

Sucralfate is low in cost, is easily administered, and had a similar compliance rate.

• The sample size was small.
• Compliance rates raise questions.

To research the evidence regarding the use of mold-active versus fluconazole prophylaxis in hematopoietic stem cell transplantation (HSCT) recipients.

Databases searched were Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials.  The authors also searched ClinicalTrials.gov, study reference lists via handsearching, Web of Science, and abstracts from the American Society of Clinical Oncology annual meetings for the past two years.

Search keywords were fluconazole, aspergillus or mycoses, prevention or prophylaxis, neoplasm, stem cell transplantation, and neutropenia.

Sources were included if they

• Were randomized, controlled trials comparing mold-active to fluconazole prophylaxis.
• Included randomization between fluconazole and any mold-active agent.
• Included patients of any age undergoing chemotherapy or HSCT.

Sources were excluded if more than one systemic prophylactic antifungal agent was given in a single study arm; pre-emptive or empiric therapy or antifungal treatment was reported; and if they did not report primary or secondary outcomes of invasive fungal infection (IFI) proven or probable, IFI-related mortality, all cause mortality, and adverse events.

Nine hundred eighty-four references were retrieved. Risk of bias was evaluated using definitions derived from the Cochrane Handbook for Systematic Reviews of Interventions.

• The final number of studies included was 20, with 5,725 total patients. Sample sizes per study ranged from 24 to 882.
• All participants had hematologic malignancies or had received allogeneic or autologous HSCT.
• Age ranged from 6 months to 82 years.
• Fifty percent were multi-center studies.
• Children were included in four trials.

• The phase of care was active antitumor treatment.
• The application was for pediatrics.

Study regimens included amphotericin B formulations, micafungin, posaconazole, voriconazole, and itraconazole. 

The majority of studies did not provide adequate information on randomization and allocation concealment. Six of 20 studies completed intention-to-treat analysis. 

Mold-active prophylaxis compared to fluconazole significantly reduced the risk of IFI (relative risk [RR] = 0.71; 95% confidence interval [CI], [0.52, 0.98]; p = 0.03). Mold-active prophylaxis decreased the risk of aspergillus infection (RR = 0.53; 95% CI [0.37, 0.75]) and IFI-related mortality (RR = 0.67; 95% CI [0.47, 0.96]); however, it did not influence overall mortality. Use of mold-active agents was associated with more adverse events leading to discontinuation of antifungal prophylaxis (RR = 1.95; 95% CI [1.24, 3.07]; p = 0.004). Types of adverse events are not described.

Prophylaxis with mold-active agents compared with fluconazole prophylaxis significantly reduced the number of proven and probable IFI and aspergillus infections in these types of patients. However, these agents were also associated with increased adverse events that necessitated stopping antifungal prophylaxis. Findings also suggested that use of mold-active agents did not affect overall mortality, although use did affect IFI-related mortality. Fluconazole is generally less expensive than some mold-active agents, and amphotericin B is not available in an oral form. Further study of the relative benefits and harms with various approaches for antifungal prophylaxis in this group of patients is warranted, and additional study is needed to better understand the full role of antifungal prophylaxis in overall survival in these patients.

Many studies had design issues regarding the description of randomization and lack of blinding. The types of adverse events observed were not provided, and clinical severity leading to study discontinuation are not described. The prophylaxis endpoint of included studies varied—some were based on absolute neutrophil count (ANC), and some were simply time-limited. ANC endpoints varied across studies. It is unclear if all studies involved primary prophylaxis or included secondary prophylaxis.

Findings suggested that antifungal prophylaxis with agents, such as amphotericin B, micafungin, posaconazole, voriconazole, and itraconazole, appears to be more effective in the prevention of invasive fungal infection and aspergillus infection than routine prophylaxis with fluconazole; however, these agents were also associated with a much greater risk of adverse events. Selection of approach for antifungal prophylaxis necessitates weighing the risks and benefits of both approaches for individual patients. Findings suggest that this type of comparison for secondary prophylaxis is worth evaluating as well.

STUDY PURPOSE: To examine the effectiveness of lysine analogues in the prevention of bleeding related to hematological disorders

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 3 (7 total, but 3 had not been completed and were not included and one was excluded because of flaws in the study)
• TOTAL PATIENTS INCLUDED IN REVIEW = 86
• KEY SAMPLE CHARACTERISTICS: Adults with acute leukemia receiving chemotherapy

PHASE OF CARE: Active antitumor treatment

Three studies located have not been concluded but may show promise in future analysis. However, the three studies included in the update of this review compared the lysine analogue to placebo. No significant results related to the risk of bleeding were found. All the studies reported a decrease in platelet transfusions given, but no meta-analysis could be performed.

No certain findings existed following this systematic review. Whether TXA or EACA decrease the risk of bleeding or the use of platelet transfusions, or increase the risk of developing a clot, is unclear. Whether they cause adverse events is also unclear.

• Limited number of studies included
• Low sample sizes
• Risk of bias because of lack of study methodology reporting
• Low quality evidence

At this time, not enough evidence supports the use of TXA and EACA in adult patients with acute leukemia receiving chemotherapy.

STUDY PURPOSE: To determine the effectiveness and safety of prophylactic granulocyte transfusions in people with neutropenia or disorders of neutrophil functions

TYPE OF STUDY: Meta-analysis and systematic review

• DATABASES USED: MEDLINE, EMBASE, CINAHL, Cochrane Collaboration, LILACS, KoreasMed, PakMediNet, IndMED, Transfusion Evidence Library, and sites for ongoing research
• INCLUSION CRITERIA: Randomized, controlled trials or quasirandomized, controlled trials comparing patients receiving granulocyte transfusions to those not receiving granulocyte transfusions
• EXCLUSION CRITERIA: Neonates

• TOTAL REFERENCES RETRIEVED: 2,188
• EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Risk of bias according to Cochrane Handbook for Systematic Reviews of Interventions

• FINAL NUMBER STUDIES INCLUDED = 11 
• SAMPLE RANGE ACROSS STUDIES: 18–225 patients
• KEY SAMPLE CHARACTERISTICS: Patients with hematologic malignancies undergoing hematopoietic cell transplantation (HCT)

PHASE OF CARE: Active antitumor treatment

No differences in mortalit existed between those receiving and not receiving granulocyte transfusions. Three of five studies showed slightly lower number of days on antibiotics for those receiving prophylactic granulocyte transfusions. Granulocyte transfusion dosages varied. A decreased number of people receiving intermediate dosing had bacteremia and fungemia (609 patients—risk ratio [RR] = 0.45, 95% confidence interval [CI] [0.30, 0.65]). Not all endpoints could be evaluated because of varied outcomes reporting methods.

Insufficient evidence exists to detect differences in all-cause or infection-related mortality, adverse events, or duration of fever or antibiotic use between those who did and did not receive prophylactic granulocyte transfusions.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• High heterogeneity
• Highly variable dosages, frequency, and methods of granulocyte harvesting

Very limited evidence suggests the efficacy of prophylactic granulocyte transfusions for the prevention of infection in patients with cancer. The review suggests that the use of the intervention be regarded as investigational. Appropriate dosages and frequency of transfusion are unclear.

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Pediatrics, elder care

There was no difference in the risk of bleeding in patients with thrombocytopenia secondary to myelosuppressive chemotherapy or HSCT when using the standard trigger of 10 x 10⁹/L for prophylactic transfusions compared with higher thresholds (20 x 10⁹/L or 30 x 10⁹/L). There was evidence that using the standard trigger of 10 x 10⁹/L for prophylactic transfusions led to a decreased number of platelet transfusions when compared with higher thresholds.

Based on this review, there is no evidence to recommend that the standard trigger for prophylactic platelet transfusions be increased from 10 x 10⁹/L to either 20 x 10⁹/L or 30 x 10⁹/L.

The validity of the studies were compromised as the participants and their doctors were not blinded to the study arm. In addition, the treatment effect was not precise.

There is evidence that the current standard for platelet transfusion may be safely maintained. The sequelae of decreased number of infusions may help to preserve the supply and potentially decrease the incidence of reactions.

STUDY PURPOSE: To determine the most effective use of platelet transfusion in order to prevent bleeding in hematologic patients receiving chemotherapy or stem cell transplantation

TOTAL REFERENCES RETRIEVED: 4,434 records screened

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two independent authors did the initial screening of all citations and abstracts. The third author was utilized for disagreements among reviewing authors. A study eligibility form was developed to assist with assessment of relevance. Data extraction was performed by two authors using guidelines by the Cochrane Collaboration. Using the Cochrane Handbook, two review authors assessed all studies for a possible risk of bias, which included information about the design, conduct, and analysis of trials.

PHASE OF CARE: Transition phase after active treatment
 
APPLICATIONS: Pediatrics, elder care

This review was intended to examine several questions looking at the endpoint objective of determining the best use of platelet transfusions for the prevention of bleeding in patients with hematological diseases receiving myelosuppressive chemotherapy or stem cell transplants. The review did not provide any new evidence for changing the current practice of prophylactic threshold of 10 x 10⁹/L to prevent bleeding. The point of using a lower dose of platelets was identified and should be used in order to preserve the platelet supply as well as to prevent alloimmunization in patients. The findings of this review suggest the need for more studies.

Some of the studies were identified as having flaws in validity due to not describing methodology in the study. One study examined also had a small sample size.

Direct-care nurses are at the frontline in administrating these products and monitoring for bleeding and possible reactions. In many centers and hospitals, providers may be rotating through the service and may not realize the recommended threshold, thus exposing patients to unnecessary transfusions and usage of the current supply.