To test the hypothesis that an exercise program for aerobic endurance, sensorimotor training, and strength training would improve neuromuscular function, improve balance control, and reduce peripheral neuropathy side effects in patients with lymphoma

Patients were randomly assigned to the training intervention or control group. The training intervention was provided twice weekly for 36 weeks under the supervision of a certified sport therapist or physiotherapist. Aerobic endurance training was done on a treadmill or bicycle dynamometer for 10–20 minutes. Four postural stabilization tasks were carried out with increasing task difficulty and surface instability. Resistance exercises with a theraband were included for strength training. Study measures were obtained prior to chemotherapy and after 12, 24, and 36 weeks. Both groups were asked to maintain a weekly diary of physical activities.

• N = 56  
• MEAN AGE = 46 years (range = 19–73 years)
• MALES: 77%, FEMALES: 23%
• KEY DISEASE CHARACTERISTICS: Patients with Hodgkin disease, multiple myeloma, or non-Hodgkin lymphoma
• OTHER KEY SAMPLE CHARACTERISTICS: At baseline, before the intervention, 37 patients had already begun treatment with neurotoxic drugs, and nine patients had symptoms of peripheral neuropathy.

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

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Tuning fork evaluation of sensitivity
• Activity level diary
• Pressure displacement measurement for balance
• Subjective global assessment questionnaire for side effects monitoring

During the first 12 weeks, there were significant differences between the groups in aspects of quality of life; however, there was no difference between the groups after 36 weeks. The incidence of reduced peripheral deep sensitivity was lower in the intervention group compared to the control group (p = 0.002), and this symptom diminished in 87.5% of those in the intervention group. No symptoms declined in the control group. Those in the intervention group had a greater improvement in time to regain balance than those in the control group, but this difference was not significant. There were differences between groups in various aspects of balance control and ability to complete attempts for balance control.

The training intervention provided here demonstrated some benefits for reductions in peripheral neuropathy symptoms and some aspects of balance control.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Measurement/methods not well described
• Other limitations/explanation: The specific method of measurement of quality of life was not stated even though quality of life was the primary outcome of this study. The individual, specific sensory-motor measurements were difficult to interpret in terms of overall comprehensive effect because aspects of measurement varied in their results and data presentation.

Sensory-motor training may be beneficial for reducing symptoms of peripheral neuropathy and improving at-risk patients’ balance and motor function. Additional, well designed research studies with larger samples are warranted.

To determine if continuous wound infusion of a local anesthetic reduces postoperative pain, opioid consumption, and chronic pain compared to standard piritramide intravenous infusion

Patients scheduled for primary breast reconstruction with a tissue expander or for prophylactic mastectomy were randomized preoperatively to receive the local anesthetic wound infusion or standard intravenous analgesia. All subjects had the same anesthesia for the procedure. A fenestrated wound catheter was placed into the wound cavity in the experimental group. A continuous infusion of 0.25% levobupivacaine at 2 ml per hour was provided and the catheter was removed after 50 hours. Control patients were on a continuous IV infusion with piritramide, metoclopramide, and metamizole after surgery for 24 hours. An IV bolus of rescue analgesia was provided to patients in both groups as needed. Pain data were obtained by nursing staff in the recovery room at three, six, and nine hours after surgery and then every eight hours for three days. Three months after surgery, pain was assessed. Opioid consumption after surgery and alertness were evaluated.

• N = 60  
• MEAN AGE = 47.8 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer surgery
• OTHER KEY SAMPLE CHARACTERISTICS: American Society of Anesthesiologists score for the surgical procedure was not significantly different between groups

• SITE: Single-site    
• SETTING TYPE: Inpatient    
• LOCATION: Slovenia

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Visual Analog Scale (VAS) for pain – median scores of all measures on the day of surgery and the first day postoperatively were used.

There were no local signs of complications where wound catheters were inserted and no differences between groups in postoperative complications. Consumption of piritramide in the first 24 hours after surgery was lower in the experimental group (p < .0001). Alertness six hours after surgery was higher in the experimental group (p < .0001). Patients in the experimental group reported less nausea and consumed less metoclopramide (p < .0001). Three months after surgery in the treatment and control groups, pain was reported in 16.7% and 50% of patients, respectively (p = .01).

The findings showed that continuous wound infusion of local anesthetic after primary breast reconstruction reduced pain immediately after surgery and for the first postoperative day.

• Small sample (< 100)
• Risk of bias (no blinding)

Continuous local anesthetic wound infusion postoperatively was associated with reduced short-term postoperative pain and less chronic pain after breast reconstruction. Similar findings have been seen with other types of surgical procedures. Nurses can advocate for consideration of this approach for acute pain management in surgical cases.

The three-week inpatient rehabilitation included exercise, manual lymph drainage, and massage; some patients also received group counseling, progressive muscle relaxation, and balneotherapy (carbon dioxide bath and mud therapy). The aim of carbon dioxide baths is to increase peripheral blood flow while mud packs increase tissue temperature. Measures were obtained two weeks preadmission, at the end of treatment, and six months later.

• The sample was comprised of 149 women with breast cancer who were 3 to 72 months postsurgery.
• Mean age was 57 years (standard deviation = 10.5 years; range 32–82 years).
• Of the patients, 70% had lymphedema.

Rehabilitation center and spa in Austria

The study used a pre-/posttest design.

• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) 
• Hospital Anxiety and Depression Scale (HADS)
• CA15-3 tumor markers
• German Illness-Coping Questionnaire

Patients received a median of 61 treatments. Of the patients, 22% dropped out at follow-up. There was a significant decrease in fatigue (p < 0.001) from pre- to posttest (effect size [ES] = .38) and pretest to six-month follow-up (ES = .38).

Fatigue improvement was greater for those with greater lymphedema.

• The study lacked a control group.
• The measure of fatigue was limited.
• The study was very heterogeneous in terms of type of treatment and time since treatment.
• No data were provided regarding cost or whether service was free.

STUDY PURPOSE: The purpose of this article was to review published literature on impact resistance training (RT) in adults with cancer.

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: Clinical Trial Register, Cochrane Trial Register, MEDLINE, and EMBASE

KEYWORDS: cancer, resistance training, muscle function, muscle strength, body mass, fatigue

INCLUSION CRITERIA: RCT comparing RT with an exercise or non-exercise control group in adult patients with cancer. Evaluation and report on strength, body composition, or fatigue comparing RT to no exercise, usual care, or alternative treatment.

EXCLUSION CRITERIA: Single RT intervention, intervention less than six weeks, recommendation of interventions with no further detail, indirectly or poorly documented RT, clinical co-intervention not applied to control, concomitant aerobic endurance training not applied to control

TOTAL REFERENCES RETRIEVED = 261

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Assessed by Jadad score (randomization, double-blinding, follow-up, intention to treat). Scores higher than two considered.

• FINAL NUMBER STUDIES INCLUDED = 14
• SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: Total patients = 1,323 (594 RT and 555 control, 174 aerobic endurance not included in meta-analysis); studies collecting fatigue = 437
• KEY SAMPLE CHARACTERISTICS: 72% women, 57% breast cancer, 21% prostate cancer, 7% head and neck cancer, 14% any cancer. Six studies during cancer treatment, eight after completion. Mean age range = 47–75 years. Nine studies recruited only women.

PHASE OF CARE: Multiple phases of care

Four studies provided FACT-fatigue data. Improvement was seen in pooled fatigue scores (p = .05; WMD 1.86; CI -.03–3.75). Individually, two studies showed significant improvement. The therapeutic dose necessary to reduce fatigue was unable to be determined. No significant difference was seen in participant characteristics. No significant side effects were reported.

Low-to-moderate intensity RT may improve cancer-related fatigue described as muscle fatigue within 15–20 repetitions.

• Heterogeneity between treatment stage, cancer type, and type of RT intervention
• Not all studies measure fatigue data
• Limited to English-only and three databases

RT may have benefits for fatigue with a certain subset of patients with cancer with low risk for side effects. Further studies are needed to establish dose and to validate improvement for certain populations.

After 7–14 days of baseline assessment, patients were randomized to treatment with cannabis extract (CE) (standardized for 2.5 mg of delta-9-tetrahydrocannabinol [THC] and 1 mg of cannabinoid) or THC (2.5 mg), or placebo.

Assessments were performed every two weeks during clinic visits at screening, and patients maintained a diary at weeks two, four, and six.

• The study reported on 243 randomly assigned adult patients with advanced cancer.
• Patients had cancer-related anorexia-cachexia syndrome, weight loss of more than 5% over six months, and an Eastern Cooperative Oncology Group performance status of 2 or less.
• A total of 164 patients completed treatment.

The study was conducted in 30 centers in Germany, Switzerland, and the Netherlands.

A multicenter, phase III, randomized, double-blind, placebo-controlled, parallel study design was used.

• Appetite was measured using a visual analog scale (VAS), with 0 mm indicating the worst and 100 mm indicating the best; appetite values were calculated as the mean of daily appetite scores for the seven days of week two in each biweekly period.
• Patients’ estimation of food intake was measured daily using a VAS.
• Mood was assessed using a VAS monitored daily.
• Nausea was assessed using a VAS monitored daily.
• Quality of life (QOL) was assessed using questions on global health status and QOL on the European Organization for Research and Treatment Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) transformed into a single functional scale ranging from 0–100.

No differences between groups were noted at baseline in terms of age, sex, weight loss, performance status, antineoplastic treatment, appetite, or QOL. Intent-to-treat analysis showed no significant differences between the three arms for appetite, QOL, or cannabinoid-related toxicity. An independent data review board recommended termination of recruitment because of insufficient differences between study arms.

Researchers concluded that there was no difference in either appetite or QOL outcomes between the CE, THC, or placebo groups.

• The study lacks a constitutive definition of anorexia.
• Adverse events included nausea, fatigue, pain, anemia, dizziness, dyspnea, diarrhea, and constipation.
• The multicenter design (n = 30) may have contributed to some of the variation in data, although statistical procedures were used to address this limitation, and investigators were trained in outcome measurement procedures.

Successful management of lymphedema relies on early diagnosis. The aim of this study was to demonstrate the effectiveness of a surveillance program that included preoperative limb volume measurement and interval postoperative follow-up to detect and treat subclinical lymphedema. Inconsistent measurements have prevented a surveillance model from becoming an accepted standard of care.

Limb volume measured prior to surgery and at three-month intervals after surgery. If an increase more than 3% in upper-limb volume developed compared with the preoerative volume, a diagnosis of lymphedema was made and a compression garment intervention was prescribed for four weeks. Upon reduction of lymphedema, compression was worn only for strenuous activity, with symptoms of heaviness, or with visible swelling. The compression garment was a lightweight Jobst^® (BSN medical) ready-made 20–30 mm/HG compression sleeve and gauntlet fitted by the physical therapist. Two patients required custom-fitted garments because of arm size. Garments were worn daily and no activity limitations were given. Patients were advised to follow up for repeated measure in one month. At follow-up, when limb volume decreased, as indicated by the measurements, women were advised to only wear compression for strenuous activity with symptoms of heaviness or with visible swelling. Women were reassessed at their next three-month interval surveillance visit for repeated measures, or sooner, if symptoms were exacerbated.

• The sample (N = 196) was comprised of women with newly diagnosed, unilateral, early-stage breast cancer (stage I–III) preoperatively.
• Patients were excluded from the study if they had a previous history of breast cancer, bilateral breast cancer, prior severe trauma, or surgery of the affected upper extremity.
• Patients were included in the study if they had a diagnosis of subclinical lymphedema.
• A volume increase of greater than or equal to 3% in the affected upper extremity was compared with patients' preoperative measurements and with consideration of the contralateral limb volume changes. This is set below the criteria currently outlined in the medical literature to facilitate early treatment of lymphedema before a clinically apparent onset.
• Exclusion from the compression sleeve intervention were swelling because of infection or blood clot (n = 5).

The study used a prospective trial design.

• Bilateral upper-extremity strength, range of motion, and volume were assessed at the preoperative visit and reassessed at 1, 3, 6, 9, 12, and 18 months postoperatively.
• Measurements for both upper extremities were taken in a standard position with the perometer.
• Lymphedema volume was calculated by suing 80% of the total limb length, which was measured from the styloid process of the ulna to the tip of the acromion for standardization.
• Body weight was recorded at each visit to control for weight change.

The time to onset of lymphedema averaged 6.9 months postoperatively. The mean affected limb volume increase was 83 ml at lymphedema onset (p = 0.005) compared with baseline. After the intervention, a statistically significant mean of 48 ml volume decrease was realized (p < 0.001). The mean duration of the intervention was 4.4 weeks. Volume reduction was maintained at an average follow-up of 4.8 months after the intervention. A short trial of compression garments effectively treated subclinical lymphedema. Detection and management of lymphedema at this early stage may prevent the condition from progressing to a chronic, disabling stage and may enable a more cost-effective, conservative intervention. The authors speak of a shift from current practice pattern in favor of a surveillance model. Throughout the surveillance trial, 43 women ages 34–82 years were diagnosed with subclinical lymphedema. An age-matched control group of women without lymphedema was selected from the trial for comparison.

• A perometer is a very costly machine that required training for patients to use, making it unlikely to be replicated.
• Not a randomized control trial.

The results of the study support the continued search for an easy measurement.

To provide a systematic review examining the management of opioid-induced central side effects including sedation, cognitive failure, sleep disturbance and myoclonus

• The literature reviewed included research, case reports, and retrospective chart reviews in an effort to establish evidence levels for practice guidelines and make recommendations for future research and practice. 
• This review is part of a larger review to produce guidelines on the use of opioids in adult patients with cancer pain.

Databases: Medline, EMBASE, Cochrane Library

Keywords: Narcotic, opioid analgesics, opioid, neoplasms, myoclonus, sleep initiation and maintenance disorders, hallucination, sleep disorder, fatigue, delirium, hyperalgesia, sedation, confusion, opioid-induced hyperalgesia, analgesics

Inclusion criteria: Studies were included that were conducted with human, adult patients with chronic cancer pain, contained data on the efficacy of a treatment for an opioid central nervous system adverse effect (e.g., sedation, cognitive impairment, myoclonus, hyperalgaesia, insomnia), and were published in the English language.

Exclusion criteria: Studies were excluded if they were comparing the efficacy or side effects of different opioids, the efficacy or side effects of adjuvant analgaesics, different doses of opioids, or different routes of administration of opioids.
 

A total of 318 manuscripts were screened. Inclusion and exclusion criteria were screened from titles and abstracts; duplication studies were eliminated. No scoring criteria for evidence recommendations were presented, but levels of evidence were presented for each central side effect.

Cognitive failure was evaluated by sedation and psychomotor speed; those studies consisted of two randomized controlled trials, one retrospective chart review, and four case reports. Four studies were focused on the central side effect of delirium, and two randomized controlled trials were focused on psychomotor aspects of cognitive function. Five side effects of opioid therapy were identified: sedation, cognitive impairment, myoclonus, sleep disturbance, and hyperalgesia.

Forty studies were potentially eligible, with a final 26 meeting all inclusion criteria. The final sample of studies included 86 subjects, ranging from case reports of one subject (n = 2), a case report of six subjects (n = 1), a retrospective chart review of 40 subjects (n = 1), and randomized controlled trials of 12–20 subjects (n = 2).

The adult subjects in the studies had varying cancers and were receiving opioid administration for chronic pain in palliative care inpatient and outpatient settings. Ages, education, occupational attainment, and socioeconomic data were not provided across the studies.

This systematic review is applicable in palliative care.

In two similar randomized controlled trials using the same psychomotor test battery, methylphenidate improved verbal and visual memory, arithmetic, and tapping speed as compared to placebo for subjects receiving morphine, whereas IV infusion only improved tapping speed. Delirium was improved by donepezil in 7 of 9 patients as measured by the Clinical Global Impression of Improvement Scale on retrospective chart review, whereas improvements were observed in only 2 of 6 patients with delirium receiving donepezil in a case report series. Atypical antipsycholtics and neuroleptics have also been used to improve delirium that is resistant to donepezil, according to three additional case reports: physostigmine (N = 1), olanzapine (N = 1), and quetiapine (N = 6).                                                                     

Seven studies were identified as related to cognitive impairment: two were randomized controlled, and five were case reports or case series.Three of the case reports combined totaled 12 patients. Two more studies were related to delirium.

The authors weakly recommended the use of methylphenidate for the symptom management of opioid-induced cognitive failure. Other agents lack evidence to make a recommendation.

Further study is warranted with incorporation of cognitive test batteries for multiple cognitive domains.

Limitations include small sample size, use of varying medications as the intervention, outcome focus on delirium as cognitive impairment, and use of case reports and retrospective chart reviews.

To evaluate the significance of a protective environment (PE) on febrile neutropenia and mortality in patients with cancer with chemotherapy-induced neutropenia

The intervention was comprised of engineering and design interventions, incorporating high-efficiency particulate filters, positive air pressure, well-sealed rooms, and infection control routines according to international recommendations for a PE. Outcomes were compared to those of patients admitted prior to the implementation of standard environmental practices.

• N = 371
• MALES: 47%, FEMALES: 53%
• KEY DISEASE CHARACTERISTICS: Acute myeloid leukemia, chronic myeloid leukemia, acute lymphoid leukemia, chronic lymphoid leukemia, multiple myeloma, Hodgkin disease, non-Hodgkin lymphoma, myelodysplastic syndrome, other hematologic malignancies, aplastic anemia, solid tumors
• OTHER KEY SAMPLE CHARACTERISTICS: Risk categories of autologous hematopoietic stem cell transplantation (HSCT), allogeneic HSCT, acute myeloid leukemia, and other diseases

• SITE: Single site 
• SETTING TYPE: Inpatient hospital  
• LOCATION: Brazil

• PHASE OF CARE: Active treatment

• Descriptive cohort

• Cumulative incidence of febrile neutropenia and death were determined by the Kaplan-Meier method.
• The adjusted hazard ratios were computed in a Cox regression model.

Fever occurred in 74.7% of episodes of neutropenia in the PE group and in 86.7% in the control group (p = 0.003). Adjusting for length of neutropenia, risk, category, antibacterial prophylaxis, and central venous catheter use, the PE reduced febrile neutropenia (p = 0.009). The PE also decreased overall mortality (p = 0.001) and 30-day mortality (p = 0.002). Gram-negative bacterial infections were more frequent after the intervention (p = 0.18), while gram-positive bacterial infections were similar (p = 0.85). Fungal infections were more frequent in the control group (p = 0.04).

This study shows the advantages of the PE on reducing febrile neutropenia and mortality among patients with cancer and indicates that multiple infection control interventions significantly can diminish hospital-acquired infections.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Although the study does not delineate what they are, an important part of the intervention is infection control routines. These routines include hand hygiene and the routine use of personal protective equipment. Infection control is essential not only to protect nurses, but also to prevent the transmission of infection from one patient to another, particularly when those patients are at higher risk because of chemotherapy-induced neutropenia, and their importance cannot be overstated.

Databases searched were MEDLINE, EMBASE, and CINAHL (1966–2004). 

Search keywords were [neoplasms] AND [(mucositis OR stomatitis)] AND [limit to (clinical trial OR randomized-controlled trials)]. 

Studies were included in the review if they were

• Published in English.
• Were aimed at the prevention of mucositis in patients undergoing head and neck radiation, chemotherapy, or chemoradiation.

The search yielded 109 publications. Of these, five were not aimed at prevention, 13 were nonrandomized, and 29 did not contain data in a comprehensive form. Seventeen articles stood alone in terms of intervention, and 45 articles included meta-analyses. Studies with zero or infinite odds ratios were omitted because variances could not be calculated with accuracy. Sample sizes ranged from 14–502.

Patients with various cancer diagnoses receiving chemotherapy, radiation therapy, or combination chemoradiotherapy.

Of the 27 interventions identified for the prevention of oral mucositis, meta-analysis could be performed on eight. Four interventions showed a preventive effect on the development or severity of oral mucositis: PTA (polymyxin E, tobramycine, and amphotericin B) lozenges or paste, systemic administration of granulocyte macrophage–colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF), oral cooling, and amifostine.

Of 14 studies (each on a different intervention type), nine showed some positive results; however, methodological flaws (e.g., small sample sizes, lack of double-blind or placebo-controlled designs) prevented those studies from demonstrating effectiveness. One study of benzydamine (Epstein et al., 2001) showed an improved ulcer-free rate and decreased incidence of ulcer and erythema.

Palifermin demonstrated positive results for the prevention of mucositis in patients with hematologic malignancies undergoing autologous stem cell transplantation.

Tooth patches containing 15 mg flurbiprofen or placebo were applied once a day before sleep to the same natural tooth or the upper denture to the buccal side starting one week prior to radiotherapy (RT) until completion of RT. Treatment was discontinued at the first onset of grade 1 ulceration/pseudomembrane formation.

• The sample consisted of 22 patients, 12 in the treatment group and 10 historical controls.
• The median age was 57.7 – 59.2 years.
• Patients had head and neck cancer and were being treated with RT.

Oral Mucositis Assessment Scale (OMAS) and World Health Organization (WHO) scoring systems were used to evaluate mucositis. Oral pain, pain on swallowing, global assessment of eating function score, and oral washings for viability of mucosal epithelial cells and maturation were used.

• No difference was found in severity and duration of pseudomembranous mucositis.
• None of the patients applied the patch for the whole RT course because of development of mucositis.
• The treatment group experienced a later onset (p < 0.05).
• Based on the OMAS, development and degree of mucositis were lower during the first two weeks. This difference was statistically significant (p = 0.007). After three weeks, the difference was not significant. Results according to the WHO scale was similar with all patients scoring at least 2.
• The study showed a slight delay in the development of mucositis with the treatment; however, it was not effective in terms of prevention.
• Pain was significantly higher in the flurbiprofen group only after the second RT week (p = 0.03).

• The study size was small.
• Use of historical control administration may have been too minimal to see effects.