The study included eight (60- to 90-minute) weekly sessions of cognitive therapy (CT), followed by three booster sessions given at three-week intervals. The focus of therapy was aimed at developing an optimistic but realistic attitude toward their situation as opposed to a negative or overly positive attitude. 

Patients were randomly assigned either to the (1) CT group or the (2) waiting list control (WLC) condition.

Outcomes were depression, anxiety, insomnia, fatigue, quality of life (QOL), and immunological measures.

The sample was comprised of 45 Caucasian women with metastatic breast disease (stage IV) with depressive symptoms determined by Hospital Anxiety and Depression Scale–Depression (HADS-D) scores.

The study was conducted at three Canadian cancer clinics.

Patients were undergoing the active treatment phase of care.

The study was a two-group clinical trial with a WLC.

• Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)
• Scale for Suicide Ideation (SSI)
• HADS
• Beck Depression Inventory (BDI)
• Hamilton Depression Rating Scale (HDRS)
• Insomnia Severity Index (ISI)
• Multidimensional Fatigue Inventory (MFI)
• European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C33)
• EORTC Breast Cancer Specific QOL Questionnaire Module (EORTC QLQ-BR23)
• Health Behavior Questionnaire (HBQ)
• List of Life Events (LLE)
• Immunologic Measures included lymphocyte subpopulations, natural killer cell activity, and cytokine secretion.
   

Although the group comparison was statistically significant on the HDRS measure only, comparison of means of other measures (BDI and HADS-D) revealed a reduction in depression scores in the treatment group versus the control group. In pooled group analysis, these gains were sustained. Also, when using the pooled data set only, the authors found decreased anxiety, fatigue, and insomnia symptoms. No treatment effect was found on the immune variables.

The study supports the efficacy of using CT for treating depressive symptoms in women with metastatic breast cancer.
 

• The study had a small homogenous sample.
• Patients were not severely depressed, which left less room for improvement.
• A licensed psychologist trained in CT is required to deliver treatment.

The study included eight weekly 90-minute group sessions of combined behavioral (stimulus control and sleep restriction), cognitive (cognitive restructuring), and educational (sleep hygiene, fatigue, and stress management) strategies.

Outcomes were sleep, medication use, psychological distress, and quality of life (QOL).

Patients were recruited from the community by advertisement.

The sample was comprised of 57 women who had completed radiation and chemotherapy for stage I to III breast cancer and met Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for a chronic insomnia syndrome.

Canada

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

The study was a two-group clinical trial with a wait-list control.

• Insomnia Interview Schedule (IIS)
• Structured Clinical Interview for DSM-IV
• Sleep diary
• Polysomnography
• Insomnia Severity Index (ISI)

Treated patients showed a significantly greater improvement in sleep posttreatment as assessed by self-reported instruments. However, data from polysomnography were not significantly more improved. Treated patients reduced use of sleep medication.

• The sample was homogeneous (i.e., all white), with most being highly educated, and included a self-selected study group.
• The study used a wait-list control.
• A Master’s-level psychologist who has experience in the administration of this treatment protocol must be included.

The cognitive-behavioral therapy (CBT) intervention for insomnia consisted of eight weekly sessions of approximately 90 minutes, offered in groups of four to six patients, and delivered by a clinical psychologist. The treatment protocol was multimodal and combined behavioral (e.g., stimulus control therapy, sleep restriction), cognitive (i.e., cognitive restructuring), and educational (i.e., sleep hygiene, fatigue and stress management) strategies that were described in a treatment manual given to all participants. A booster session was offered to participants one month after the end of treatment. Missed treatment sessions were rescheduled; therefore, all patients received the entire treatment program. Outcomes were evaluated at the conclusion of the intervention, as well as at three, six, and 12 months after the end of treatment.

Fifty-seven women with stage I to III breast cancer who met the diagnostic criteria for a chronic insomnia syndrome (CBT group, n=27; comparison group, n=30) were included.

Diagnostic criteria included

• Difficulty initiating and/or maintaining sleep, whereby sleep-onset latency and/or wake after sleep onset is greater than 30 minutes
• Sleep efficiency (ratio of total sleep time to total time spent in bed) was lower than 85%
• Difficulties occurring for at least six months
• Difficulties causing marked distress or significant impairment in daytime functioning (e.g., fatigue, disturbed mood, performance deficits).

Only patients whose insomnia was judged to be secondary to cancer were included in the study (i.e., those whose sleep difficulties were caused or aggravated by the cancer diagnosis or treatment).  Most of the sample had received prior adjuvant treatment with radiation therapy (85.2%), chemotherapy (37%), or hormone therapy (59.3%).  Slightly more than one-third of the sample was currently receiving hormone therapy (37%).

Exclusion criteria included severe major depression or other serious psychiatric disorder; presence of a sleep disorder other than insomnia (e.g., sleep apnea), presence of another illness affecting the immune system (e.g., human immunodeficiency virus [HIV] infection), and regular use of a psychotropic medication other than hypnotics (e.g., antidepressants) unless the dosage used was stable in the last month and did not increase during the study; and current involvement in psychotherapy.

• Outpatient
• Large academic medical center
• Participants were recruited through flyers and pamphlets, ads placed in local newspapers, and physician referrals.

Patients were undergoing the active treatment phase of care.

This was a randomized, controlled trial, with patients randomly assigned to CBT for insomnia or a wait-list control group.

Multidimensional Fatigue Inventory (MFI)

Analysis of pooled data revealed a statistically significant improvement in fatigue from pre- to posttreatment, with maintenance of this improvement during the 12-month follow-up period.

• The fact that the study sample was primarily Caucasian and well educated and all patients were survivors of breast cancer may limit the generalization of the findings.
• The use of a wait-list control condition did not allow for the control of nonspecific therapeutic elements in the intervention, such as therapist empathy, group support, etc.
• A modest amount of continuing education, as well as access to some instructional materials for patients, are needed to prepare health care professionals to deliver CBT interventions for insomnia.

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 four to six participants and was 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 was adapted by the investigators for the cancer population.

Fifty-seven breast cancer survivors were randomly assigned to a CBT (n=27) or waiting list condition (n=30).

Patients were included in the study if they

• Had 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 Editoin (DSM-IV) diagnostic criteria for a chronic insomnia syndrome.

Patients who regularly used psychotropic medications other than hypnotics (e.g., antidepressants) 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, advertisements placed in local newspapers, and physician referrals.

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

This was a randomized, controlled trial with a waiting list control group and a 12-month follow-up period to assess the short- and long-term effects of the intervention.

Multidimensional Fatigue Inventory (MFI)-French Canadian version to measure fatigue

Pooled analyses within an intent-to-treat framework revealed significant differences between pre- and posttreatment on fatigue (p < 0.001). No significant difference was detected between posttreatment and the three-, six-, and 12-month evaluations of fatigue, suggesting that the clinical improvement relative to the outcome of fatigue was durable.

• Participants were primarily Caucasian and well educated.
• Of the patients, 36% who were interested in the study and had responded to the advertisement screened out or declined to participate once they heard more about the study. This may limit the generalization of the findings.
• Reasons for exclusion included severe psychiatric disorder, not meeting the DSM-IV diagnostic criteria for chronic insomnia, or having insomnia that was not judged to be secondary to cancer (some participants were also screened out due to ongoing cancer treatment).
• Approximately 20% of the individuals judged the study to be too burdensome when they learned the treatment details and declined to be enrolled.
• Use of the waiting list control condition did not allow for the control of nonspecific therapeutic ingredients.
• Trained personnel were needed to administer the CBT intervention.
• Group treatment had costs.

It is not possible to determine whether the improvements in fatigue observed in this study are attributable to the CBT strategies or to other ingredients common to all psychotherapeutic approaches (e.g., therapist empathy, group support). 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.

STUDY PURPOSE: To develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis

TYPE OF STUDY: Systematic review

DATABASES USED: Ovid, MEDLINE

KEYWORDS: Acyclovir, amitriptyline, adhesive, amphotericin B, analgesic, analgesia, antacid, antibiotic, anti-infective, alfentanil, aqua oral, benzocaine, coating agent, clarithromycin, diclosan, doxepin, fentanyl, film, fluconazole, gabapentin, IB-367, hydromorphone, iseganan, kaopectate, ketamine, kefir, lidocaine, local anesthetic, “magic” or “miracle” mouthwash, mouth rinse or mouthwash, mucoadhesive, methadone, morphine, nystatin, patient controlled, polymyxin, povidone-iodine, polyvinylpyrrolidone, protegrin, sucralfate, tetracaine, tetracycline, tobramycin, topical, zilactin, xylocaine. In addition, the brand names of commercial products in these categories also were searched, including Gelclair^®, MuGard^®, and UlcerEase.

INCLUSION CRITERIA: Studies that focused on the use of antimicrobials, coating agents, anesthetics, and analgesics; English studies; published in MEDLINE on or before December 31, 2010; all age groups; and published in a peer-reviewed journal

EXCLUSION CRITERIA: Articles that did not report on effects of an intervention on mucositis, animal or in vitro studies, literature reviews, non-English papers

TOTAL REFERENCES RETRIEVED: 1,384

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Only articles that reported on the effects of an antimicrobial, mucosal coating agent, anesthetic, or analgesic on oral mucositis that met the inclusion criteria described were included in the review. Also, articles did not have any major or minor flaws per Hadorn and levels of evidence were based on the Somerfield criteria. The results were sorted into three classifications: recommendation, suggestion, and no guidelines possible.

FINAL NUMBER STUDIES INCLUDED = 62

SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: Not discussed in the review

KEY SAMPLE CHARACTERISTICS: Included patients actively being treated for head and neck cancers, hematologic cancers, and solid tumors with radiotherapy, chemotherapy, chemoradiotherapy, and high-dose total body irradiation for hematopoietic stem cell transplant

PHASE OF CARE: Active treatment

Recommendations were made against the use of topical antimicrobial agents for the prevention of mucositis, including recommendations against the use of iseganan for mucositis prevention in hematopoietic stem cell transplantation (HSCT) and head and neck radiation therapy (RT) and antimicrobial lozenges for mucositis prevention in head and neck RT. Recommendations were made against the use of sucralfate for the prevention and treatment of oral mucositis due to chemotherapy or RT. Recommendations were made for the use of patient-controlled analgesia with morphine in HSCT, transdermal fentanyl in HSCT and standard-dose chemotherapy treatment, and morphine and doxepin mouth rinse in patients with head and neck cancer undergoing RT. No guidelines were recommended for any of the other agents reviewed due to insufficient or conflicting evidence.

Additional well-designed RCT studies are needed on the prevention and management of oral mucositis. Studies that look at systemic dosing and absorption may be helpful.

Lack of high-level of evidence prevented the development of guidelines in many of the agents reviewed, such as topical anesthetics, antimicrobial agents, and mucosal coating agents.

The recommendations for use in clinical practice were made for the use of patient-controlled analgesia with morphine in patients undergoing HSCT and for transdermal fentanyl in HSCT and standard-dose chemotherapy treatment, and morphine and doxepin mouth rinse in patients with head and neck cancer undergoing RT. Any use of the other agents in this study were not recommended for use in the prevention or treatment of oral mucositis and should be used with caution.

To determine the effectiveness and safety of adding olanzapine to triple antiemetic therapy with aprepitant, palonosetron, and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for patients with primary breast cancer

Forty-five patients with breast cancer who experienced greater than grade 1 nausea or any vomiting after the first cycle of chemotherapy using both epirubicin and cyclophosphamide were included. Low-dose olanzapine (2.5 mg per day) was administered orally from the first day of chemotherapy for four days, and the number of episodes of vomiting, scale of nausea, dietary intake, and somnolence were compared with the symptoms after the first cycle.

• N = 45   
• MEAN AGE = 49.7 (SD = 13 years)
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer receiving 5-flourouracil, epirubicin, and cyclophosfamide (FEC) or epirubicin and cyclophosphamide (EC) therapy in an adjuvant or neoadjuvant setting

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Iwate Medical University Hospital

• PHASE OF CARE: Active antitumor treatment

• Nonrandomized, prospective, phase-II trial without placebo control

• Common Terminology Criteria for Adverse Events
• Clopper-Pearson method
• Excel statistics
• Cochran-Armitage test
• Paired t-test or Dunnett t-test

The nausea was significantly improved by adding olanzapine (p < 0.05). The mean nausea scale and dietary intake were improved by adding olanzapine.

Adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, a steroid, and aprepitant can be effective and is tolerable.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Key sample group differences that could influence results

Patients with breast cancer with highly emetogenic regimens containing both cyclophosphamide and anthracycline treated with triple therapy for resistant nausea could benefit from the addition of low-dose olanzapine.

To determine the benefit of an educational program on arm and shoulder function for patients with breast cancer given prior to surgery and axillary lymph node dissection three months postoperatively

• N = 149  
• AGE ≥ 20 years
• FEMALES: 100%
• OTHER KEY SAMPLE CHARACTERISTICS: Patients with breast cancer were divided into two groups, those receiving axillary lymph node dissections (ALNDs) and those receiving sentinel lymph node dissections (SLNDs). Within these two groups, patients selected to be either in the intervention or the control group. Exclusion criteria included bilateral breast cancer or recurrence.

• SITE: Single site    
• SETTING TYPE: Other    
• LOCATION: Miyagi, Japan

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Assessment of postoperative arm function

This was a longitudinal controlled trial that was not randomized. There was a control group and an intervention group.

• All measurements were taken at hospital admission, one week postoperatively when the drains were removed, one month postoperatively, and at the close of the study three months postoperatively. 
• Arm girth measurements included two points, forearm girth and upper arm girth, and comparison to the unaffected side.
• For grip strength, a standard dynamometer was used, and differences between dominant and nondominant were determined.
• Shoulder range of motion included three planes, flexion, abduction, and horizontal extension. Differences were calculated.
• Subjective Perception of Post-Operative Functional Impairment of the Arm (SPOFIA) given preoperatively
• Disabilities of the Arm, Shoulder, and Hand (DASH)

Patients with training prior to breast cancer surgery and ALND developed grip strength and perceived improved arm function compared to those who did not receive training and education. No lymphedema was assessed after two months postoperatively. The exercises and the type of intervention were not described. The outcomes of the program require additional randomized studies.

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

Patients with breast cancer usually fail to discuss many symptoms in the DASH or SPOFIA assessment tools. If patients are taught to report these symptoms and not to consider them normal or anticipated, particularly right after surgery, nurses might refer rehabilitation earlier.

To determine the effectiveness of triclosan in the management of radiation-induced oral mucositis.

To compare the effectiveness of triclosan mouth rinse with conventional sodium bicarbonate mouth rinse.

The trial group was comprised of 24 patients who were randomly allocated into two groups of 12 patients each. Patients in Group I were administered sodium bicarbonate mouth rinse and constituted the control group. Group II was the study group who was given triclosan mouth rinse. Allocation into arms was done with the help of a random number table.

The patients in the control group were advised to prepare sodium bicarbonate mouth rinse by dissolving 2 g of sodium bicarbonate powder, available with the chemist in lukewarm water. The triclosan mouth rinse used in the study was provided to the patient as a ready-made commercial mouth rinse.

Upon noticing the early signs of oral mucositis, patients were advised to begin using the mouth rinses. They were instructed to swish the mouth three times a day during the rest of the course of radiation treatment and continue the same regimen for six weeks following the completion of radiotherapy.

A weekly follow up of grading and mucositis (WHO grading), evaluation of body weight, food intake, and pain (visual analogue scale) were made during the radiation treatment period and post-radiation treatment period. Acute exacerbation of signs and symptoms, which could be attributed to reaction of the mouthwash, was also monitored during treatment.
 

The study was comprised of 24 patients. The median age in the control group was 65.9 years, and in the study group, the median age was 63.67 years.

Males (%): 29.1 in study group and 20.8 in control group. Females (%): 20.8 in study grup and 29.1 in control group.

Key Disease Characteristics: Histopathologically confirmed cases of oral squamous cell carcinoma, selected for external beam radiotherapy.

Site: Single site

Setting Type: The study was conducted in the radiation oncology department of a regional cancer center, Trivandrum in association with the Department of Oral Medicine and Radiology, Dental College.

Location: The center is locaed in Kerala, India.

Phase of Care: Active treatment

Twenty-four patients who underwent radiation therapy for oral cancer and subsequently developed oral mucositiis were included in the study.

WHO Grading scale for mucositis

Visual analogue scale for pain

Both the groups were statistically identical. All 24 patients in both groups passed through grade 3 mucositis on the last day of radiotherapy. However, 10 patients in the control group and only one patient in the study group entered to grade 4 mucositis. A definite change was noticed in the severity of mucositis, food intake, and weight loss. The control group took more than 45 days to resolve the mucositis, while the study group took only less than 28 days.

No firm conclusions regarding effects of triclosan mouthrinse can be made, due to study limitations.

• Small sample size
• Single institution
• No blinding

The sodium bicarbonate mouthwash was needed to be prepared by the study participants, whereas the triclosan was given to the patients already prepared. This is a definite point that could influence compliance. There is no mention as to who did the oral assessments, one person or several different people. If several, was there consistency between them? Unknown.

There was no mention of compliance measurements of the study participant

Triclosan is used in periodontal therapy as an antibacterial agent; however, further research needs to be done to prove the effectiveness in the management of radiation-induced oral mucositis.

To investigate the efficacy of topical morphine compared to routine therapy (magic mouthwash) in the management of oral mucositis in patients with head and neck cancer

In the study group, 10 ml of morphine sulfate 2% was given every three hours, six times per day for six days while the control group received 10 ml magic mouthwash (240 ml of magnesium hydroxide, 25 ml of 2% viscous lidocaine, and 60 ml of diphenhydramine) on the same schedule. The intervention was initiated when patients with head and neck cancer presented with grade 3 or 4 mucositis from chemotherapy, radiotherapy, or chemoradiotherapy. Patients in both arms were instructed to hold the solution in thier mouths for at least two minutes and to not swallow.

• N = 28  
• MEAN AGE = 49.5 years
• MALES: 36.7%, FEMALES: 63.3%
• KEY DISEASE CHARACTERISTICS: Head and neck cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Adults receiving chemotherapy, radiotherapy, or chemoradiotherapy; World Health Organization (WHO) grade 3 or 4 oral mucositis; no current alcohol or smoking  

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: Omid Oncology Hospital in Isfahan, Iran (April–July 2011)

• PHASE OF CARE: Active antitumor treatment

Randomized, double-blinded, controlled study

• A blinded radiation oncologist graded mucositis according to WHO guidelines at baseline, day 3, and day 6.
• Patients were asked if pain or discomfort was relieved by mouthwash, and if so, for how long (less than one hour, one to two hours, or greater than two hours).
• Patients also were asked to grade their satisfaction with treatment (satisfied, tolerable, or intolerable).

No significant difference in treatments were found on the third day. On day 6, there was a significant reduction in mucositis severity in patients in the morphine arm (p = 0.045). The trend in mucositis change showed a decrease in severity in both arms.

Both morphine and magic mouthwash were effective in reducing mucositis severity. However, topical morphine was more effective, and its results were more satisfactory to patients than the magic mouthwash.

• Small sample (< 30)
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results 
• Other limitations/explanation: This study had a small sample size, and there were not enough patients in the study to make recommendations. There was a single inpatient site, a heterogeneous population, and it was unclear how many different medical oncologists assessed mucositis (inter-rater reliability). This study had a short observation period. It was unclear if mucositis would have improved if saline mouth rinses were used instead of magic mouthwash. The act of performing oral care six times per day might have caused the change in mucositis grade.

More studies in larger populations are needed for this intervention. Its comparison to magic mouthwash was questionable because it is not effective in reducing mucositis severity.

• FINAL NUMBER STUDIES INCLUDED = 8
• TOTAL PATIENTS INCLUDED IN REVIEW = 589
• SAMPLE RANGE ACROSS STUDIES: 33–181
• KEY SAMPLE CHARACTERISTICS: Included patients with hepatitis C. One study in melanoma

PHASE OF CARE: Active antitumor treatment

Analysis showed that antidepressant treatment reduced overall incidence of depressive disorder (OR = 0.42, p < 0.001). Only one trial was done in which patients with a history of depression were excluded.

Prophylactic use of antidepressants was associated with reduced incidence of depression in patients receiving interferon alpha monotherapy.

• There was only one study in patients with cancer.

Depression has been identified as an adverse effect of treatment with interferon alpha. This study showed that pre-emptive treatment with antidepressants can reduce the incidence of this effect. Nurses need to be aware of depression associated with interferon alpha treatment, and assess patients for depression, especially if they have a history of depressive symptoms. Long-term effects in patients with cancer are unknown, since there is limited evidence for this group of patients.