To determine the feasibility of using electroencephalography (EEG) biofeedback (neurofeedback) and identify its potential effects on cognitive impairment, sleep quality, fatigue, and psychological symptoms.

Neurofeedback was provided using an EEG system that detects and alerts the brain of phase changes to increase brain flexibility and resilience. Single EEG sensors, placed at the left C3 and right C4 for each brain hemisphere, analyze EEG activity for identification of phase state changes in the brain. During the session, the patient listened to music while sitting quietly; brief interruptions of the music signal alerted the patient that the software detected phase changes and was providing the brain feedback. No patient response or action was required because it is believed that the brain uses the feedback for its own self-organization without conscious action. Patients had twice weekly sessions for 10 weeks. Assessments were performed prior to beginning the sessions and during the fourth, seventh, and tenth week of sessions.

• The study included 23 Caucasian women with a median age of 56 years (range 43–70).
• All patients were breast cancer survivors with self-reported cognitive impairment since diagnosis.
• Median time since last chemotherapy was 24 months (range 9–59).
• Of the patients, 26% were taking antidepressants and 39% were taking sleep medication.

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

The study has clinical applicability for late effects and survivorship.

The study used a feasibility quasiexperimental design.

• Functional Assessment of Cancer Therapy–Cognitive Function (FACT-C)
• Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F)
• Pittsburgh Sleep Quality Index (PSQI)
• Brief Symptom Inventory (BSI)

Significant symptom presence and dysfunction were reported by this sample at baseline, as compared to normative data. Baseline comparisons to normative sample showed significant differences from the norms in all measures, indicating significant dysfunction. FACT, FACIT, and PSQI scores improved over time, although not at a constant rate over longitudinal time points. At study conclusion, symptom report of dysfunction no longer differed significantly from normative populations on three of four FACT-C subscales, FACIT, and PSQI. The proportion of patients using sleep medications declined from 39% to 17% by study conclusion. No adverse effects of the intervention were identified.

EEG neurofeedback was shown to be feasible and potentially beneficial for improving cognitive function, sleep, and fatigue in breast cancer survivors.

• The study had a small sample size, with less than 30 patients.
• The study had risks of bias due to no control group, no blinding, and no random assignment.
• Unintended interventions or applicable interventions were not described that would influence the results.
• The intervention was expensive, impractical, or required training.
• Findings were not generalizable.
• This intervention requires specialized equipment, training, and setting to provide EEG feedback sessions.
• It was not stated whether patients were receiving any other interventions aimed at these symptoms.
• Cognitive function was measured only with self-report instruments with repeated measures design; thus, self-reported improvements may be because of testing effects.
• No objective cognitive function instruments were used to determine cognitive impairment at time of baseline or improvement in cognitive function over time.
• The sample was a homogenous group of patients, potentially limiting generalizability to other patient groups.

This study reported a potentially promising intervention that may have a positive effect on several symptoms experienced by breast cancer survivors. Additional well-designed clinical trials are needed to assess the efficacy of this approach.

To determine the efficacy and safety of loading dose IV ibandronate in women with metastatic breast cancer and bone metastases

Ibandronate 6 mg per day was administered for 15 minutes on days 1, 2, and 3 of the study, and patients were followed up until day 14 of the study. Pain was assessed by visual analog scale (VAS) and functional performance index on days 1, 7, and 14. Patients were supplied with a pain diary and instructed to record at the same time each evening. Assessments for opioid use were performed using the Morphine Equivalent Daily Dose (MEDD) index.

• N = 13   
• AGE = 18 years or older
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Painful bone metastases

• SITE: Multi-site 
• SETTING TYPE: Outpatient 
• LOCATION: Turkey

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

• Phase II, open- label, single-arm study for women with breast cancer and painful bone metastases

• VAS
• Karnofsky Performance Scale Index
• Patient diary
• MEDD
• Lab tests (e.g., red and white cell counts, thrombocyte and neutrophil count, hemoglobin and hematocrit levels, alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glut, total protein, blood urea nitrogen, Cr, Mg, Ph, Ca, CrCl)

Pain intensity decreased on days 7 and 14 versus day 1 using the VAS. Mean Karnofsky index score increased (80.8 [SD = 13.1] and 80.8 [SD = 13.2] on days 7 and 14 versus 77.7 [SD = 11.7] on day 1; p < 0.005 on both days).

This study demonstrates the short-term safety of an intensive ibandronate dosing schedule as indicated by the good tolerability profile and lack of effect on safety parameters including hematology, blood chemistry, and urine analysis. Intensive ibandronate therapy provides a well-tolerated alternative treatment option to analgesic use for patients requiring rapid relief of moderate to severe metastatic bone pain, particularly patients experiencing breakthrough or opioid-resistant pain.

• Small sample (less than 30)

Ibandronate therapy provides alternative pain relief to patients with breast cancer who have bone metastases and, thus, should improve quality of life with good tolerance and no renal safety concerns.

• Patients were given a tetracaine gel consisting of tetracaine HCL 1.5%, miconazole 2%, ethanol 5%, glycerin 10%, saccharin 0.6%, water 65.3%, starch 15%, tween 20.5%, and flavor 0.5%.
• Patients were instructed to apply the gel on oral mucosa after using mouthwash and 30 minutes before and after meals, approximately six times per day. Gel use was continued until resolution of pain.
• Patients were placed into two groups for statistical analysis: no pain relief (grade 1) or presence of pain relief (grade 2, 3, and 4).

• The studied consisted of 50 patients with head and neck cancer.
• Median age was 61  years with a range of 28–73.
• Patients were receiving external beam radiation therapy (XRT) and had oral mucositis of grade 2 or more. Twenty-two patients (44%) had grade 2 mucositis, and 28 patients (56%) had grade 3 or more mucositis.

The study was conducted between July 2000 and December 2003.

This was a prospective, descriptive study.

• Patients were given a questionnaire to evaluate the effectiveness of the gel using a 1–4 verbal subjective scale with grade 1 = no pain relief and grade 4 = highest grade of pain relief.
• The feasibility and toxicity profile of the tetracaine gel in reducing oral pain were evaluated after a week of gel administration.
• Other indirect parameters included the necessity of drug administration, gastrostomy-tube or parental infusion, weight loss, and interruption of XRT.
• The radiation oncologist used the Radiation Therapy Oncology Group-European Organization for Research and Treatment of Cancer (RTOG-EORTC) scale to evaluate results and determined other supportive therapy.

• A majority of patients (79.2%) reported a reduction in oral cavity pain, and 82.9% reported no side effect. Most patients (71%) had no difficulty in gel application. Some patients reported unpleasant taste (12%) and interference with food taste (39%).
• Planned XRT was less interrupted, although this was difficult to evaluate because of the lack of a control group.

• The study did not include a control group.
• The sample size was small.

To evaluate if discontinuing systematic VRE surveillance and contact isolation of colonized patients affects the incidence of vancomycin-resistant enterococcus (VRE) faecium bacteremia

• N = 2,319   
• AGE = 5–94 years
• MALES: 58/59%, FEMALES: 42/41%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Hematologic malignancies: leukemia, lymphoma, BMT
• OTHER KEY SAMPLE CHARACTERISTICS: Underlying malignancies were ALL/AML, CML/MDS/MPD, HL/NHL/CLL, and plasma cell malignancies. No significant differences existed in either group.

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Buffalo, NY

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

Prospective nonrandomized observational study comparing the incidence of VRE faecium bacteremia in colonized patients with hematologic malignancies during the period of active surveillance/contact precautions versus no active surveillance/contact precautions

Comparing study periods, no significant difference existed in incidence of VRE bacteremia, MRSA bacteremia, and C-diff. Antibiotic utilization was not significantly different between study periods. Levofloxacin prophylaxis had no affect on the incidence of VRE bacteremia. Daily chlorhexidine bathing showed no effect on VRE colonization/bacteremia. No significant difference existed in aggregate antibiotic use and incidence of bacteremia ≤ 30 days prior between study periods. Nursing hours/patient day was not significantly different during study periods. No significant difference existed in patient demographics, patients per service, or underlying hematologic malignancies between study groups/periods.

In a single-site institution (with sporadic molecular epidemiology of VRE faecium in patients with hematologic malignancies), the incidence of VRE faecium bacteremia was not significantly different comparing study periods—active surveillance/contact precaution per institutional policy and after discontinuation of policy. Incidence of MRSA bacteremia and C-Diff remained stable.

• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• Findings not generalizable
• Single-site study
• Only hematologic malignancies, not generalizable to other cancer types
• Predictive ability limited because of different sequential groups rather than the same group with time matched controls
• Nursing hours/day does not clearly estimate care burden/nurse/patient ratio
• Rates of colonization comparing groups not provided
• Treatment phase or types not collected comparing groups
• Lack of data on compliance with hand hygiene and lack of molecular epidemiologic data on VRE isolates from the second study period
• Role of active surveillance and contact precautions was not examined in clonal outbreaks, so the study may not be applicable to other patient populations with cancer or in outbreaks with different molecular data

A single-site study revealed that VRE bacteremia incidence in hematologic malignancy inpatients was not affected by VRE surveillance/contact precautions. Nursing practice measured as hours/patient day was not an effective measure for influencing nursing-sensitive infection-related outcomes. Larger multisite trials that include nursing-sensitive measures are needed to identify the most effective practices essential to prevent/control VRE bacteremia in high-risk patients.

To provide information about patterns of granulocyte colony-stimulating factors (G-CSF) use in Spanish oncology clinical practice and to compare neutropenia-related outcomes in patients treated daily with G-CSF with patients receiving nondaily G-CSF (pegfilgrastim)

Medical records were reviewed for data collection and analysis of outcomes in patients who received pegfilgrastim compared to those who received daily G-CSF.

• N = 391 patients from 34 participating centers 
• AGE: Older than 18 years
• MALES: 46.4% in daily G-CSF group, 31.8% in pegfilgrastim group  
• KEY DISEASE CHARACTERISTICS: Solid tumors excluding breast
• OTHER KEY SAMPLE CHARACTERISTICS: Had chemotherapy with at least one concomitant G-CSF administration more than two months prior; 79.3% had stage 3 or 4 disease

• SITE: Multi-site
• SETTING TYPE: Outpatient
• LOCATION: Spain

• PHASE OF CARE: Active treatment

• Retrospective, multi-center, observational
  • Each investigator reviewed the most recent charts of five patients treated with daily G-CSF and of another five most recently treated with pegfilgrastim.

• Percentage of patients with grade 3 or 4 neutropenia (absolute neutrophil count [ANC], .0 x 10⁹/L) and incidence of febrile neutropenia (FN), defined as ANC 0.5 x 10⁹/L and temperature 38°C or higher during the same day
• Percentage of patients experiencing dose delays (more than three days during any cycle) and dose reductions (less than 84% of planned dose)
• Percentage of patients with dose intensity was 85% or higher (defined as 85% or more of planned dose for all agents in regimen and three days or less of dose delay)
• FN-related hospitalizations and response to chemotherapy—complete, partial, or nonresponse per physician’s criterion

In the multivariate analysis following adjustment for possible confounding factors, a significantly higher risk (OR 1.73, 95% CI 1.004–2.97) of severe neutropenia was associated with daily G-CF versus pegfIlgrastim. The patient group receiving daily G-CSF had a 73% higher probability of grade 3 or 4 neutropenia. Patients receiving daily G-CSF experienced a greater number of dose reductions (38.4% versus 31/6%, p = 0.116) and delays (54.7% versus 41.7%, p = 0.013). Chemotherapy dose intensity of less than 85% also was greater in the daily G-CSF group (39.4% versus 28.9%,p = 0.030). Response rates also were lower in the daily G-CSF group. Complete responses were 17% for daily G-CSF versus 26.4% for the pegfilgrastim group (p = 0.028) and partial response was 41.2% for daily G-CSF versus 52% for the pegfilgrastim group (p = 0.009), again demonstrating better response in the pegfilgrastim group. The two main adverse reactions reported were bone pain and asthenia, with a higher incidence noted in the daily G-CSF group (6.2% versus 1.7%, p = 0.025). Patients receiving at least five days of daily G-CSF, versus those who received fewer than five days, experienced better outcomes.

G-CSF and pegfilgrastim can reduce the incidence and adverse outcomes of treatment-related neutropenia. If G-CSF is stopped prematurely, the efficacy is compromised. This study demonstrates that G-CSF often is initiated later than recommended following chemotherapy, and patients receive fewer days per cycle than required for optimum efficacy.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable

Daily G-CSF and pegfilgrastim are used prophylactically to reduce grade 3 or 4 neutropenia, incidence of FN, dose delays and reductions, and FN-related hospitalizations, and to increase response to chemotherapy, measured as complete, partial, or nonresponse per physician’s criterion. Suboptimal dosing is more prevalent with daily G-CSF because of starting later than recommended following myelosuppressive chemotherapy and stopping too early.

To test the feasibility of providing a psychoeducational intervention for people with head and neck cancer.

The NuCare coping strategies program used a self-study book and audiocassette designed to enhance personal control and teach emotional and instrumental coping responses. It consisted of training in problem solving, relaxation, coping skills, goal setting, communication, social support, and lifestyle factors. Three participants chose to receive it in a small group format, 33 chose one-on-one sessions with a therapist, and 23 chose a home format with no therapist. The outcomes measured were quality of life (QOL), anxiety, and depression.

• The study was comprised of 66 patients with head and neck cancer; 59 completed the program and 50 gave outcome data.
• No age, gender, race, or ethnicity demographics were provided.

The study was conducted at the head and neck oncology outpatient clinic of the Montreal Jewish General Hospital, Quebec, Canada.

Patients were undergoing the active treatment phase of care and were evaluated at baseline and three-month follow-up.

This was a prospective, nonrandomized, one-group, feasibility study.

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLC-C30) was used to measure QOL and sleep.

Patients reported improvement in physical and social functioning and global QOL, sleep disturbance, fatigue, and depressive symptoms.

• Patients were able to choose which format was used.
• The pilot study was not designed to test the effectiveness of the intervention.
• Special training of the research nurse was required.
• There was no cost to patients.

Participants were offered the Nucare coping strategies program (teaches people to cope with cancer, based on the McGill Model of Nursing) in one of three formats:  small group; one on one; and one on one with therapy (home version with materials).  There was no control arm.  Data were taken at baseline and two and three months following the intervention outcome.  Participants chose the study arm.

• Fifty-nine participants completed the study, and there were outcomes data for 50.
• Gender, race, and income were not described. 
• Participants had head and neck cancer.

This was a nonrandomized, no control pilot, feasibility study for delivery in which participants wanted the intervention.

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

Fatigue was improved in 17 (38%) patients overall, and improvement was equal in self (home) to that seen with the use of a therapist.

• Only one cancer group was studied.
• There were costs associated with the use of a therapist.

The objective of this study was to compare the efficacy of supplemental, oral, and parenteral opioid doses consisting of either 25% or 50% of the equivalent 4-hour opioid dose (i.e., total 24-hour opioid dose divided into 4-hour portions) in patients already receiving opioids on a regular basis.

The study reported on a sample of 33 terminally ill patients with cancer and dyspnea at rest who already were receiving opioids.

The study was conducted in three separate palliative care centers in Quebec, Canada.

The study was a randomized, double-blind, continuous sequential controlled trial.

Dyspnea intensity on the visual analog scale and respiratory rate were measured at baseline, 30, 60, 120, 180, and 240 minutes after dose.

The overall treatment effect, as measured by dyspnea intensity and respiratory frequency, was not significantly different for 25% or 50% of the equivalent four-hour opioid dose. A significant (p < 0.0001) decrease was found in pre- and post-dyspnea intensity. Dyspnea decrease was inverse to baseline dyspnea intensity (i.e., low dyspnea at baseline had greater decrease in dyspnea intensity whereas high dyspnea at baseline had less decrease).

• Authors reported that the sample required one more pair to offer definitive preference in favor of 25% of the four-hour dose.
• The finding was restricted to those already receiving regular opioids.
• The study was properly designed and conducted at multiple sites; however, the sample was limited.

Because 25% and 50% doses had the same effect, a supplementary dose of 25% of the equivalent four-hour opioid dose is recommended to reduce dyspnea for as long as four hours.

To assess the efficacy and safety of an intrathecal (IT) combination of ziconotide and morphine in malignant pain refractory to high doses of oral uploads

Visual anolog scale of pain intensity (VASPI) scores and Karnofsky Performance Status Scale (KPSS) scores were recorded for each patient at the initial visit. An IT catheter was place under fluoroscopy with aseptic technique, with a 1 g dose of cefazolin to prevent infection. Patients continued their long-term oral morphine until the IT infusion started and asked to start a short-acting morphine dose of 10 or 30 mg if needed. VASPI and KPSS scores, vital signs, electrocardiograms (ECGs), and adverse events were evaluated at day 2, day 7, and weekly up to day 28. The ziconotide infusion titration was started at 2.4 micrograms per day and increased by 1.3 micrograms per day at day 7 in patients with a VASPI score greater than 30 at rest. IT morphine dose was calculated based on their daily dose, an oral-IT ratio of 400:1. Increases in IT morphine were based on the oral morphine consumption. Doses were adjusted for adverse events and analgesic effect. The mean VASPI score, mean change in VASPI score, and mean percentage change from baseline to each visit and to the last observation was calculated.

• N = 20   
• AGE = 18 years or older
• MALES: 35%   
• FEMALES: 65%
• KEY DISEASE CHARACTERISTICS: Disseminated cancer with bone metastasis involving vertebral bodies
• OTHER KEY SAMPLE CHARACTERISTICS: Participants had to have pain related to malignancy, prevalently nociceptive pain, a VASPI score greater than 70 mm at rest, or an occurrence of adverse events. Patients were excluded if they showed signs of sepsis or inadequately treated infection; uncontrolled heart failure; second-degree heart block; third-degree heart block; or history of dementia, delirium, hysteria, or untreated affective disorder.
   

• SITE: Single site   
• SETTING TYPE: Inpatient setting   
• LOCATION: Pain Centre at Italy Bari Policlinico Hospital, Bari, Italy

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Late effects and survivorship; end-of-life and palliative care
   

• Prospective, observational study
  • Used repeated measures

• KPSS
• VASPI
• Vital signs: blood pressure, heart rate, respiratory rate, and temperature
• 12-lead ECG
• Adverse events: Coding Symbols for Thesaurus of Adverse Reaction Terms (5^th ed.)
   

Prior to the study, participants had persistent pain for a mean of six months SD = two months) and took a mean daily dose of 320 mg per day (SD = 80 mg) of systemic opioids. The mean VASPI score at rest was 90 mm (SD = 7 mm), with a mean incidental VASPI score of 99 mm (SD = 3 mm), and a mean KPSS of 59 (SD = 10. 4). Patients had severe opioid-related side effects that did not permit an increase in systemic opioids. IT therapy started with morphine 0.82 mg per day (SD = 0.36 mg) with ziconotide 2.4 mcg per day. On day 2, the mean VASPI score at rest decreased to 55 mm (SD = 12 mm), a significant reduction (p < .001). For five patients, an increase in morphine was necessary. On day 7, the mean VASPI at rest was 44 mm (SD = 11 mm), a significant decrease (p < .001). Four patients had an increase in ziconotide daily. On day 28, mean VASPI was 34 (SD = 13), a significant decrease (p < .001). Eighty percent of patients reached the effective dose for morphine and ziconotide within two weeks. Only five patients survived until the third month with good pain control. The maximum dose of ziconotide was 5.2 mcg per day, and the maximum dose of morphine was 2 mg per day. Four patients developing adverse effects attributed them to the study drugs. Changes in serum creatinine kinase levels and vital signs were not significant. No infections correlated with IT catheter placement.

IT therapy with ziconotide and morphine is a helpful strategy in controlling malignancy-related pain refractory to high dose of systemic uploads. Using both drugs appears to have a synergistic effect and may benefit patients with cancer. Lower doses of each drug may be utilized with few adverse events and side effects. However, this study has a few limitations that impair generalizability, may have a potential for bias, and may not have captured the risk to patients being treated longer than a few months.

• Small sample (less than 30)
• No control group or comparison (potential for bias)
• No randomization, no blinding
• Sample size was 20 (less generalizable).
• Only five patients survived to three months.
• Oservation was limited to one month.
• The sample was small and the length of observation was limited, so observable adverse events and complications may have not been observed.

Combination IT ziconotide and morphine in patients with cancer with nociceptive bone pain refractory to systemic opioids may be a helpful strategy for controlling pain. Low doses of ziconotide are required with the use of morphine, as compared to higher doses of ziconotide alone. In turn, less adverse events may be observed with potentially better pain control. When considering drug stability, alternative agents for pain in combination with ziconotide may be considered in place of morphine, as pump refills are required with lower-stability agents.

To determine if a multimodal exercise program for patients during induction chemotherapy is feasible, safe, and beneficial for fatigue, quality of life, and fitness

Patients were randomized to the exercise or usual care groups. Usual care generally included suggestions to walk on a regular basis, without further instruction. Those in the exercise group were approached 4–5 days per week during hospital admission to participate in light-to-moderate–intensity exercise for 30–60 minutes. Exercise sessions included combined aerobic, resistance, and flexibility training. Aerobic intensity was encouraged at an exertion equivalent to 50%–75% of heart-rate reserve. The resistance exercises targeted large muscle groups using resistance bands and free weights. Flexibility was incorporated into each session via static stretching. Exercise sessions were directly supervised by a certified exercise physiologist. Study assessments were completed at baseline, post induction, and within two weeks of discharge, post cycle 2 (4–6 weeks post discharge).

• N = 70 post induction; 63 completed post-consolidation measures.
• MEAN AGE = 57 years (SD = 14.7)
• MALES: 54.3%, FEMALES: 45.7%
• KEY DISEASE CHARACTERISTICS: Patients with acute myeloid leukemia (AML) or relapsed AML receiving induction chemotherapy who were medically cleared for participation
• OTHER KEY SAMPLE CHARACTERISTICS: Participants in the exercise group were slightly older.

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

• PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trial

• European Organization of Research and Treatment of Cancer Core Quality of Life (EORTC QLC-C30)
• Functional Assessment of Cancer Therapy-Fatigue (FACT-F) subscale/BMI
• Maximal oxygen consumption test (VO₂ max test)
• Six-minute walk test (6MWT)
• Grip strength
• Daily exercise diary for control patients

Exercise group participants completed 514.2 minutes of exercise on average during an average admission of 36.5 days. The most common reported reason for not exercising was fatigue. Adherence to exercise sessions was 54%. Control group patients exercised an average of 510.4 minutes over 35.8 days. Participants in both groups demonstrated an improvement in global quality of life. Fatigue scores improved only in the exercise group, with a between group difference of 3.6 points, which was not statistically significant. The six-minute walk improved in both groups but improved significantly more in the exercise group (p = 0.005). No significant adverse event occurred. During over 1,000 patient days of observation, four musculoskeletal events were reported. No differences existed between groups in length of stay or other resource utilization.

This study demonstrated that the provision of an exercise program is feasible for patients during induction chemotherapy and may help manage fatigue in these patients. Patients who participated in the multimodal exercise program demonstrated improved physical fitness.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Given the comparison of mean hours of exercise between study groups, the total amount of physical activity did not appear substantially different between groups, which may have affected the lack of substantial differences in fatigue.

Participation in an exercise program of moderate intensity was shown to be feasible for patients who were hospitalized and receiving induction chemotherapy for AML.