To investigate, critically appraise, and rate the evidence regarding agents used for the prevention of mucositis in children

Databases searched included CINAHL, Cochrane library, Ovid MEDLINE, PubMed, BioMed Central, and other internet-based sources. A total of 19 databases were searched.

Search keywords were mucositis, stomatitis, oral inflammation, mouth mucosal inflammation, prophylaxis, management, and prevent; in addition to keywords to identify children and all types of cancer therapy.

Studies were included in the search if they

• Involved English-speaking children.
• Were clinical trials conducted on the prevention of oral mucositis during cancer therapy.

Studies were excluded if they

• Were not in English
• Did not involve children
• Involved only gastrointestinal mucositis.
• Involved treatment of mucositis rather than prevention.
• Were case studies or pilot studies.
• Were commentaries or letters to the editor.
• Involved sample sizes of less than 20 patients.

• The total number of references retrieved was 16,471.
• The authors evaluated the references using the Canadian Task Force on Preventive Health Care evidence-based guidelines.

• The final number of studies was 27. The sample range across studies was not reported.
• Other than inclusion of pediatric cases, no other characteristics were described.

• Patients were undergoing the active antitumor treatment phase of care.
• The study has clinical applicability for pediatrics.

• The studies involved the following interventions.
  • Oral care protocols (n = 5)
  • Chlorhexidine mouthwash (n = 7) 
  • Benzydamine mouthwash (n = 1)
  • Iseganan mouthwash (n = 1),
  • Granulocyte macrophage-colony stimulating factor (GM-CSF) mouthwash (n = 2)
  • Oral glutamine (n = 2)
  • Enteral glutamine (n = 1)
  • Oral propantheline and cryotherapy (n = 1)
  • Oral cryotherapy (n = 1)
  • Oral sucralfate suspension (n = 1)
  • Prostaglandin E2 tablets (n = 1)
  • Chewing gum (n = 1)
  • Laser therapy (n = 3). 
• Good evidential support was found for the use of oral care protocols. Fair support was found for the use of chlorhexidine with some mixed results.
• Only one article was found that studied benzydamine, CSF, and iseganan. The evidence was deemed insufficient to make a recommendation. 
• Good evidential support was found against the use of sucralfate and prostaglandin E2 tablets.
• Evidence regarding laser use and oral and enteral glutamine were mixed.

The authors concluded that oral care protocols should be used; oral sucralfate suspension, prostaglandin E2, and GM-CSF mouthwash should not be considered based on current evidence; and chlorhexidine (without use as part of an oral care protocol), laser therapy, and glutamine should not be considered because of conflicting evidence.

• No disease or treatment factors were reported or considered in the analysis. 
• Some interventions were evaluated in only one study.
• The quality of the evidence in general was highly variable.
• No information was provided on how the outcome for mucositis was measured in the included studies.
• The authors recommendations suggest no use of a specific intervention if findings were conflicting, which assumes that insufficient evidence of effectiveness is equivalent to ineffectiveness.

Findings provide further support for use of oral care protocols. Results provided no other useful recommendations for preventive therapies but identified the need for further research in this area.

To determine the effects of a supervised group exercise intervention on aerobic capacity, anxiety, depression, and quality of life in patients with advanced lung cancer

The intervention consisted of physical and relaxation training in groups of 10–12 patients provided twice weekly for six weeks. Exercises included cycling and strength training supervised by a physiotherapist. Study assessments were done at baseline and at six weeks.

• N = 71
• MEAN AGE = 66 years (range = 31–88 years)
• MALES: 42.8%, FEMALES: 57.2%
• KEY DISEASE CHARACTERISTICS: All patients had advanced inoperable lung cancer and were receiving chemotherapy. Most were receiving carboplatin-based treatment.
• OTHER KEY SAMPLE CHARACTERISTICS: The majority of participants were employed full- or part-time

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

• PHASE OF CARE: Active antitumor treatment

Quasi-experimental

• Peak VO₂ for aerobic capacity
• 6-Minute Walk Test (6MWT)
• FEV₁
• Functional Assessment of Cancer Therapy (FACT) general and L for quality of life
• Hospital Anxiety and Depression Scale (HADS)

There were significant reductions in anxiety scores (ES 0.21, -0.9 change, p = 0.007). There was no effect on depression scores. Aerobic capacity, functional capacity, and muscle strength improved significantly.

The findings of this study suggest that group exercise sessions may benefit the managing anxiety and increase functional capacity among patients with advanced lung cancer. Changes were statistically significant; however, actual change scores were small. The clinical relevance of these changes is not clear.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Although significant effects were seen, actual changes scores were small, calling into question the actual clinical relevance of findings. There was a withdrawal rate of about 50%, suggesting that this program may not be practical. Patients self-selected to participate in the program, so the sample was potentially biased. The intervention was provided in a group setting, so it is possible that the change in anxiety was related to participating in a group of individuals with the same problems rather than the exercise itself. An analysis of drop-outs showed that baseline functional capacity was significantly higher among those who remained in the program.

The findings of this study suggest that group exercise sessions can improve function and might reduce anxiety among patients with advanced lung cancer. This type of approach may not be feasible or acceptable for patients with very poor baseline functional capabilities. Additional well-designed research in this area would be helpful, and studies should include attentional control conditions to differentiate the affects of group support versus other aspects of the intervention.

To evaluate, postsurgically, the impact of beauty treatments, in combination with routine cancer care, on body image, psychological distress, and coping in patients with breast cancer

Intervention beauty treatments occurred at the hospital during the first week postsurgery. Intervention treatments included manicures, pedicures, makeup, depilation, hairdressing, and massages. The control group received routine medical care. Data collection occurred at baseline (the day before surgery), at six days postsurgery (Time 1), and at three months postsurgery (Time 2).

• The sample was composed of 100 participants; 50 were in the intervention group and 50 were in the control group.
• In the experimental group, 56.7% of participants were between 40 and 60 years old. In the control group, 62.8% of participants were older than 60.
• All participants were female.
• All patients had undergone mastectomy or tumorectomy.

• Single site
• Inpatient
• France

Active treatment

Randomized prospective controlled trial

• French version of the Hospital Anxiety and Depression Scale (HADS), to measure psychological distress.
• Body-Image Questionnaire (BIQ), to measure satisfaction with body image.
• French version of the Mental Adjustment to Cancer (MAC) Scale, to measure coping style. The instrument consists of five subscales: fighting spirit, helplessness and hopelessness, anxious preoccupation, avoidance, and denial.

Depression scores measured by HADS increased significantly over time in both groups (p < 0.001). Anxiety scores measured by HADS decreased significantly over time in both groups (p < 0.001). Investigators noted no significant intergroup difference or interaction effect for both depression and anxiety. Three months after surgery, the intervention group reported higher body-image scores. Patients' perception of helplessness and hopelessness increased over time in the control group but not in the intervention group (p < 0.05).

Overall, this study did not find that beauty treatment had an effect on psychological distress and coping styles.

• The study had a small sample size, with fewer than 100 participants.
• Investigators did not give enough attention to the control group.
• Investigators did not describe randomization procedures. Whether groups were treated sequentially or concurrently is unclear.
• The report presented no justification for the choice of data-collection time points. Patients might have had beauty treatments on their own.
• Investigators did not evaluate the impact that other cancer treatments (chemotherapy or radiation treatment) or other potentially confounding variables may have had on study outcomes.

Cost-effectiveness needs to be examined, particularly given the fact that the investigation yielded no significant findings.

To summarize the literature on calcium phosphate oral rinse for the prevention and treatment of oral mucositis (OM)

• FINAL NUMBER STUDIES INCLUDED = 30
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,392, of which 890 patients received Caphosol
• SAMPLE RANGE ACROSS STUDIES: Across 19 studies of patients undergoing hematopoietic stem cell transplant, 5–154; across 11 studies of patients with head and neck cancers, 11–218
• KEY SAMPLE CHARACTERISTICS: Studies measured grade and duration of OM, pain assessment and medication, total parenteral nutrition, patient satisfaction, treatment compliance, oral infection rates, duration of hospitalization, polyethylene glycol use, and swallowing. Most of the studies were from single centers and involved free Caphosol provided to the hospital. Observational studies were included. The abstracts and conference proceedings did not consistently provide details about standard treatments and study design.  

• PHASE OF CARE: Active antitumor treatment
• CLINICAL APPLICABILITY: Pediatrics

Caphosol was found to reduce OM grade, duration, or both in 24 out of 30 studies. Caphosol was associated with a reduction in OM-associated pain in 14 of 17 studies with more than 30 patients and 6 studies with fewer than 30 subjects. Data regarding nutrition, patient compliance, and length of hospitalization were conflicting, but the majority demonstrated a benefit with Caphosol. Two studies reported potential cost savings with the use of Caphosol. Three studies with 30 patients and three single-center studies with controls of standard mouth care and MuGard^® did not find significant differences in OM grade or duration. Two studies of more than 30 patients did not demonstrate a benefit associated with OM-related pain. One study did not find a significant difference in nausea or dysphasia for Caphosol-treated patients. Three studies failed to demonstrate any differences in length of stay.

The majority of the studies included in the review reported some benefit from Caphosol use. The data demonstrate the opportunity to further study the role of supersaturated calcium phosphate oral rinse in the prevention and treatment of OM.

• The studies were heterogeneous in their design, so data could not be pooled or consolidated.  
• The review was funded by EUSA Pharma.  
• Porterhouse Medical Ltd provided medical writing services and was funded by EUSA Pharma.  
• Only two full-length, peer-reviewed articles were included in this review.  
• At least 12 of the 30 studies included in the review were observational or retrospective studies.  
• The definition of standard oral care was not well defined in all of the studies, so determining the role of Caphosol in the improvements documented is difficult.

The effects from OM remain a significant challenge for patients receiving cancer treatment. Nursing involvement in prospective, randomized, blinded studies could provide the best practice data needed to recommend treatments for OM. The limitations for the studies included in this review are significant and do not provide rigorous scientific support for the use of Caphosol.

To determine the effects of various opioids in treating cancer-related pain

• Databases searched were MEDLINE, EMBASE, the Cochrane Library, National Health Service Centre for Reviews and Dissemination, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Clinical Excellence (NICE).
• Authors did not include search keywords in the report.
• Studies were included if they
  • Were systematic reviews or randomized controlled trials whose results were published in any language.
  • Included more than 20 participants, of whom investigators followed up with 50%.
• Authors did not list exclusion criteria.

Investigators reviewed 34 studies. Investigators used 22 studies as the basis of their report. Investigators evaluated studies by performing a GRADE evaluation of the evidence, using the following criteria: type of evidence, quality, consistency (similarity of results across studies), directness (generalizability), and effect size. Evidence ratings were very low, low, moderate, and high.

• Authors did not specify total sample size.
• The sample included patients with cancer-related pain.

Authors reported results relative to pain, need for rescue analgesia, function, quality of life, patient preference, and adverse events.

Morphine is the standard opioid in the management of moderate to severe cancer pain. Evidence from this study was insufficient to allow authors to compare other opioids to it. Evidence from this study was insufficient to allow conclusions about codeine. Investigators categorized the effectiveness of dihydrocodeine, a newer option for pain control, as unknown. Evidence from this study was insufficient to allow authors to rate the effectiveness of transdermal fentanyl. Hydromorphone may be as effective as morphine or oxycodone and may cause fewer adverse effects. Methadone may be as effective as morphine or oxycodone, for reducing pain, and the two opioids' rates of associated adverse effects are similar. Oxycodone and morphine may be equally effective in reducing pain. Tramadol may be as effective as morphine, but morphine seems to have quicker onset.

Authors deemed all evidence cited in this review to be of very low or low quality.

To evaluate the effectiveness and safety of prucalopride, a 5-HT4 receptor agonist, in patients with chronic constipation.

Patients with self-reported chronic constipation for at least six months could enroll in the study. The 12-week study procedure comprised a two-week placebo run-in period to determine frequency of bowel movements (BMs). Patients with two or fewer spontaneous complete BMs per week were randomized to one of three treatment groups (2-mg prucalopride, 4-mg prucalopride, or placebo), with study medication taken once daily with breakfast for 10 weeks.

• The study reported on a sample of 641 patients.
• Mean patient age was 47.9 years (range 18–95).
• The sample comprised 555 women (87%) and 86 men (13%).
• Patients were aged older than 18 years and had a history of self-reported chronic constipation for six months or less that was not caused by drug use, surgery, or organic disorders of the large intestine.

• Multi-site
• United States

This was a randomized, double-blind, placebo-controlled, parallel-group phase III trial.

• Patient diary
• Patient global assessments
• Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire
• Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire
• Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36)

• Significantly more patients in the prucalopride 2-mg (23.9%) and 4-mg (23.5%) groups reported three or more spontaneous complete BMs per week compared with the placebo group (12.1%) over the 12-week study period (p ≤ 0.01).
• Significantly more patients in the prucalopride 2-mg (42.6%) and 4-mg (46.6%) groups reported an increase from baseline of at least one spontaneous complete BM per week compared with the placebo group (27.5%) over the 12-week study period (p ≤ 0.001).
• Patients in both prucalopride groups had an increased percentage of normal consistency BMs (p ≤ 0.05), had no straining (p ≤ 0.01), used significantly fewer laxatives per week (p ≤ 0.01), used fewer enemas per week (p ≤ 0.05), rated their treatment effectiveness better (p ≤ 0.001), and rated their constipation as less severe (p ≤ 0.001) compared with the placebo group.
• The most common adverse events were headache, nausea, abdominal pain, diarrhea, and flatulence.

Prucalopride 2-mg and 4-mg administration improved the frequency, consistency, and quality of defecation and led to complete bowel evacuation in adults with chronic constipation.

• Patients who had cancer or were receiving opioid therapy were excluded from the study.
• Eighty-seven percent of the participants were women.

Prucalopride (2 mg or 4 mg daily) appeared effective in the treatment of chronic constipation in adults. Research for applicability in patients with cancer is warranted.

A single dose of nebulized morphine-6-glucuronide (M6G) (the active metabolite of morphine) was given to patients with cancer who had breathlessness. Three dose levels were studied:  5, 10, and 20 mg of M6G. The single dose of morphine was inhaled using an Acorn Porta-Neb jet nebulizer over 15 minutes.

• The sample was comprised of nine patients. 
• No patient characteristics were reported other than age (median = 51 years; range 45–77).
• Six patients were already receiving morphine.

• Unknown
• Results were reported from St. Bartholomew Hospital in London, United Kingdom.

This was an open, uncontrolled study that randomized patients to one of three dose levels.

• 100-mm visual analog scale (VAS) and modified Borg scale were used to quantify breathlessness, anxiety, and effort of breathing at pretreatment and at 15, 30, and 60 minutes posttreatment.
• VAS and verbal rating scales were used to assess nausea, drowsiness, and other side effects.

All patients reported a subjective improvement in breathlessness by the VAS and the Borg scale. A significant difference (p = 0.023) in dyspnea VAS was observed with time across all time points. No significant difference existed among the three treatment groups across all time points (p = 0.176), suggesting no difference among the three doses. A significant difference in dyspnea was found between patients. No significant changes existed in anxiety VAS and effort of breathing VAS with time or with dose. Minimal adverse effects were noted.

Nebulized M6G was relatively safe and possibly therapeutic in patients with cancer-related breathlessness.

• A small number of patients were studied.
• The study was reported as a letter to the editor.

A randomized study is planned.

The study used a two-phase, multimodal, cognitive-behavioral therapy (CBT) combined strategy:  (a) over 3 to 10 weeks and (b) over eight weeks; eight weekly sessions lasted 90 minutes.

The purposes were to establish treatment objectives, stimulus control, sleep restriction, coping strategies for fatigue, and reframe maladaptive cognitions.

Outcomes were sleep, mood, fatigue, and global and cognitive quality of life (QOL).

• The sample was comprised of 10 women with nonmetastatic breast cancer (stages I–III).
• Mean age was 54.3 years.
• Women completed chemotherapy and/or radiation therapy.
• All had a diagnosis of chronic insomnia disorder per the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV).
• All had completed high school.

• Single site
• Patients were recruited from the community sleep laboratory and subjects’ homes.
• Quebec, Canada

Patients were undergoing the long-term follow-up phase of care.

The study used a prospective, nonrandomized, repeated measures, quasiexperimental, single-case design comparing each individual over time.

• Insomnia Interview Schedule (ISI) 
• Sleep diary
• Self-report scales
• Polysomnography and breathing parameters

Most women experienced a statistically significant improvement in sleep efficiency and decreased total wake time pre- and posttreatment. Sleep efficiency continued at the six-month follow-up, but total wake time did not. Findings on sleep diaries were corroborated by objective measures.

• The study had a small sample size.
• The sleep diaries were incomplete.
• The potential existed for influence factors, such as intragroup alliance and empathy.
• Sleep improvement may be an effect of time away from cancer therapy.
• A trained psychologist must administer the tests; in addition, cost is incurred by using a sleep laboratory for polysomnography.

Patients received multimodal cognitive-behavioral therapy (CBT) that combined cognitive, behavioral, and educational strategies. Treatment consisted of eight weekly sessions administered in a group of five participants combined with use of stimulus control, sleep restriction, cognitive therapy, sleep hygiene, and fatigue and stress management. The treatment protocol was based on clinical procedures developed by Morin (1993) and adapted by the investigators for the cancer population.

Ten breast cancer survivors participated in this pilot study. 

Patients were included in the study if they

• Completed radiotherapy of chemotherapy for a stage I to III breast cancer at least one month prior to enrollment
• Met the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) diagnostic criteria for a chronic insomnia syndrome.

Patients who regularly used psychotropic medications other than hypnotics were excluded unless the dosage use was stable in the last month and did not increase during the study.  Individuals currently receiving psychotherapy were also excluded.

• Cancer research facility
• Participants were recruited via fliers and pamphlets.

Patients were undergoing the long-term follow-up phase of care.  

This was a single-arm study with no control group.

Multidimensional Fatigue Inventory (MFI)

Nonparametric statistical testing revealed significant improvements in the general and physical subscales of the MFI; there was no significant change between pre- and posttreatment on the mental, activities, and motivation subscales of the MFI. There was no significant change observed from posttreatment through six-month follow-up on the MFI general and physical subscales, suggesting that the treatment gains were sustained over time.

• The study had a small sample size.
• The effect could have potentially occurred as a result of group support rather than the CBT intervention itself.
• Sustained improvements in fatigue may also be a result of a maturation effect wherein fatigue declined as might be expected, with greater distance from treatment.
• Trained personnel were needed to administer the CBT intervention.
• Group treatment had costs.

All patients received DLT divided into two phases. The intensive treatment phase was administered over a one to three-week time period (daily treatment for at least five consecutive days), and the maintenance phase mainly was carried out by the patient and his or her family members at home. Limb volume was measured on days 5, 12, 19, and 195.

• N = 219  
• MEAN AGE = 59.9 years (SD = 14.3 years)
• MALES: 10.1% (most were lower-extremity participants), FEMALES: 89.9% (most were following breast cancer treatment)
• KEY DISEASE CHARACTERISTICS: Patients with upper or lower extremity unilateral lymphedema
• OTHER KEY SAMPLE CHARACTERISTICS: Lymphedema was the primary reason for clinical treatment.

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

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

Observational, prospective, longitudinal cohort study

• Demographic data
• Lymphedema volume was measured using the truncated cone formula.
• Excess limb volume was calculated using the formula (LLV – HLV)/HLV x 100.

Initial intensive lymphedema treatment resulted in a 31% volume reduction, but the benefits were somewhat abolished when volume increased by 16.5% during the six-month maintenance phase. The only independent variable predictive of volume reduction after intensive therapy was the presence of previous intensive DLT. The most frequent adverse events were skin redness (18.4% of patients) and compression marks (42.3% of patients). Blisters requiring that treatment be stopped were uncommon (1.4% of patients).

There is a need for large, randomized trials to identify which components or combinations of components are most effective. There is a need to identify techniques to improve patient outcomes during the maintenance phase in trials for the long-term control of lymphedema.

• Risk of bias (no control group)
• Risk of bias (sample characteristics)
• Findings not generalizable
• Subject withdrawals ≥ 10%

Nurses should be aware of this intervention as a potential treatment for patients with lymphedema, making this an important point of education. The early identification of lymphedema using \"heaviness\" as a descriptor may help refer patients for treatment sooner. The fact that results may diminish after intensive treatment should be considered, and this could point to the importance of adhering to strict maintenance schedules and encouraging physical activity for long-term benefits.