To test the effectiveness of four natural compounds (propolis, aloe vera, calendula, and chamomile) in the prevention of acute mucositis during chemoradiotherapy for head and neck cancer.

The patients were randomized to receive a mixture of the natural ingredients or placebo. All patients received dental and nutritional evaluations and were allowed to use standard supportive care such as baking soda mouth rinses, NSAIDs, opioids, and IV hydration. The placebo had the same volume, color, flavor, and density as the experimental solution. The pharmacist who dispensed the study drugs managed the randomization list. Patients were instructed to rinse with 7 ml four times per day (before each meal and RT) during weekdays and before each meal (three times per day) on weekends. Weekly interviews were conducted along with a physical examination, including visual inspection of the oral cavity and the oropharynx, by a nurse and a radiation oncologist. Body weight, objective mucositis, pain control, and dysphagia were assessed during these visits.

• N = 104   
• AGE: median = 57 years
• MALES (%): 86.45  
• FEMALES (%): 13.55
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Head and neck
• OTHER KEY SAMPLE CHARACTERISTICS: Squamous cell carcinoma of the oral cavity, pharynx, or larynx. Squamous cell carcinoma in the neck of unknown primary. Previously untreated with chemotherapy or radiation therapy for head and neck cancer, good oral intake with no feeding tubes (NG or PEG) at study entry, and ECOG 0-1.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Regina Elena National Cancer Institute, Rome, Italy

PHASE OF CARE: Active anti-tumor treatment

Phase III double-blind randomized placebo controlled; 1:1 experimental versus control

CTCAE, version 3.0, was used for grading mucositis. The Verbal Descriptor Scale was used for assessing pain. Locoregional control and OS were computed with the Kaplan-Meier method from the last day of treatment and comparison was done with the log-rank test (These were included in the secondary endpoints of the study).

No difference was noted between arms.

The prophylactic use of the natural agent combination, propolis, aloe vera, calendula, and chamomile, did not show a benefit versus placebo in the prevention of oral mucositis for patients with head and neck cancer receiving chemoradiotherapy.

This was a well-conducted single-site clinical trial.

Use of natural ingredients for supportive care in oncology is usually preferable to more expensive, hard to access pharmacologic interventions. However, if the evidence does not support their use, even natural ingredients should not be used due to potential increase costs and untoward effects. Nurses play an important role in patient and HCP education about evidence-based interventions.

To evaluate the effect and toleration of transmucosal opioid for painful mucositis affecting swallowing.

Retrospective medical chart review was done for data collection for individuals who had opioid maintenance and received fentanyl pectin nasal spray for incidental mucositis pain. Results in patients were compared at different time points when they did and did not use fentanyl pectin nasal spray for incidental breakthrough pain.

• N: 40   
• AGE: Mean age = 64.08 years, range = 36-80
• MALES: 70%  
• FEMALES: 30%
• CURRENT TREATMENT: Radiation, combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Head and neck cancer, orophyarynx most common site

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

PHASE OF CARE: Active anti-tumor treatment

Retrospective observational

• Oral intake
• Prevalence of breakthrough pain
• Numeric rating scale for pain intensity

After implementation of transmucosal opioid for incidental pain, oral intake improved (p = 0.000). With use of fentanyl pectin nasal spray, intensity of breakthrough pain episodes went from 5.73 (SD = 1.54) to 2.25 (SD = 2.45).

Transmucosal opioids may be helpful in managing incidental pain associated with mucositis, and may facilitate oral nutritional intake.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described

Due to rapid onset, transmucosal opioid use for incidental pain that interferes with swallowing and oral intake in patients with head and neck cancer may be of benefit. Further well-designed research in this area is warranted.

To compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemo rt-induced OM in patients with head and neck cancer.

Sixty locally advanced patients with head and neck cancer treated with high-dose RT concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to two weeks after completion of treatment.

• N: 60   
• AGE: 18-70 years
• MALES (%): 24 and 23  
• FEMALES (%): 6 and 7
• CURRENT TREATMENT: Radiation 
• KEY DISEASE CHARACTERISTICS: Patients with locally advanced head and neck cancer with high-dose radiotherapy and platinum-based chemotherapy 
• OTHER KEY SAMPLE CHARACTERISTICS: Starting similar chemRT regimens; matched

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Chiang Mai UH (CMUH), King Chulalongkom Memorial H (KCMH), Siriraj H (SH) and Udonthani Cancer H (UCH)

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS:  Elder care, palliative care

RCT with two intervention groups

Patients were evaluated by the radiation oncologists at baseline before CCRT, weekly during CCRT, at the end of CCRT, and at four weeks after CCRT. The Oral Mucositis Assessment Scale (OMAS) was used to assess severity of mucositis. Ulceration score was 0 for no lesion, 1 for lesion less than 1 cm², 2 for lesion 1–3 cm², and 3 for lesion more than 3 cm². Erythema score was 0 for no lesion, 1 for mild to moderate erythema, and 3 for severe erythema. Pain score (0–10), all prescribed medications including analgesic, artificial saliva supplement, and anti-infection medications, the need for hospitalization, treatment interruption, and the addition of nutritional support or feeding tube were also recorded. Oral candidiasis assessment was based on the physical examination of pseudomembranous lesions or angular cheilitis in centers except at CMUH center where confirmation by microscopic identification of Candida was used.

Prophylaxis rinsing with benzydamine HCl can be more effective in reducing severity of OM induced by CCRT, when compared to basic care with sodium bicarbonate mouthwash. Median of OMAS scores at weekly assessment during CCRT was lower in benzydamine HCl group compared to control. In both groups, maximum of third quartile of OMAS scores around fifth to seventh week of CCRT. Scores decreased at four weeks after CCRT. Statistically, median for OMAS scores was significantly lower in study group at every week between second and eighth week of CCRT. The corresponding p values for those weeks in chronological order were 0.003, < 0.001, < 0.001, < 0.001, < 0.001, 0.01, and 0.04. Maximum of third quartile of OMAS scores to be around fifth to sixth week in both groups. Maximum OMAS score across whole period of CCRT in benzydamine HCl group was 25, lower than maximum of 37 in sodium bicarbonate group. No significant difference in median of pain scores between two groups during CCRT and at follow-up. Corresponding p values from second to eighth week were 0.88, 0.59, 0.96, 0.73, 0.63, 0.92, and 0.15 and p value at follow-up after CCRT was 0.8. Maximum of third quartile of pain scores at seventh week of CCRT in study group and eighth week in control group. Maximum pain score across period of CCRT was 10 in both groups. Four weeks after CCRT, median of pain score decreased to 2 in both groups. Poor compliance was defined as patients in postoperative CCRT group and in definitive CCRT group who received weekly chemotherapy less than 3 cycles and 4 cycles, respectively. More patients with poor compliance in control group than in study group (i.e., 13 patients versus 10 patients). No differences were found between the two groups. Most patients in both groups need analgesic drugs; 89% in control group and 90% in study group, p value = 1. The most common analgesic drugs used were opioids (syrup morphine/morphine sulfate tablet; MST/morphine sulfate sustain released; kapanol^®), prescribed usage rates were 48% in control group and 33% in study group. For antifungal agents, none in benzydamine HCl group needed them, whereas 19% of patients in sodium bicarbonate group required nystatin oral suspension or clotrimazole tablet. Rate of feeding tube placement was same in both groups during CCRT (i.e., 24 and 22% in the study group and the control group, respectively). Oral retention and compliance for mouthwash products were better in sodium bicarbonate arm than in benzydamine HCl arm. Four patients (6.75%) in study arm could not tolerate full dose of benzydamine HCl due to burning and stinging sensation. For these patients, mouthwash was diluted at 1:1 with water.

Prophylaxis oral rinsing with benzydamine HCl for patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy was superior to sodium bicarbonate mouthwash in terms of alleviating the severity of oral mucositis and encouraging trend for reducing the need of oral antifungal agents use.

• Small sample (< 100)
• Other limitations/explanation: Small study with limitations in descriptive measurement.

Review prophylaxis and acute treatment protocol practices.

The aim of this study was to evaluate the effect of photobiomodulation (PBM) in reducing the incidence and severity of OM in patients undergoing HSCT, comparing two protocols that differ only in session frequency, either daily or three times a week.

PBM applied three times per week versus seven times per week in patients undergoing HSCT

• Patients received three PBM sessions weekly (on Monday, Wednesday, and Friday). PBM was applied using a continuous-wave diode laser (0.24 J total radiant energy per point, 33 points)
• Patients received daily PBM sessions. PBM was applied using the same continuous-wave diode laser at the same settings used for group I (0.24J total radiant energy per point, 33 points)
• There is a slight difference in the power outage of each intervention as well as exposure time.

• N = 99
• AGE: 13 to 71 years
• MALES: 51.5%
• FEMALES: 48.5%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: OM
• OTHER KEY SAMPLE CHARACTERISTICS: Allogeneic HSCT, autologous HSCT

• SITE: Single site    
• SETTING TYPE: Inpatient  (not specifically  identified)
• LOCATION: Porto Alegre Clinical Hospital

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS:  Pediatrics, elder care, palliative care

A retrospective study was to evaluate the preventive effect of PBM applied three times per week versus seven times per week in patients undergoing HSCT.

Differences between groups were evaluated using the chi-square test or Fischer’s exact test for qualitative data and the Mann-Whitney test for quantitative data. Receiver operating characteristic (ROC) curves were constructed to analyze the sensitivity and specificity of quantitative risk factors in predicting the presence or absence of OM. The area under the curve is a measure of test accuracy. The SPSS for Windows software package, version 18.0, was used to perform these statistical analyses. Two-way analysis of variance (ANOVA) was used to compare OM average between groups, and the t test was used to compare the average OM at each point.

PBM was effective in preventing OM in patients undergoing HSCT even when it was applied three times a week. Both PBM protocols were equally efficient in preventing OM (p = 0.34, ANOVA). 

Independent of the PBM protocol used, patients who received allogeneic transplant (p < 0.01, Fischer’s exact test), total body irradiation (TBI, 12 Gy) (p = 0.01, chi-square test), busulfan plus cyclophosphamide (p < 0.01, chi-square test), or methotrexate-containing regimens (p < 0.01, Fischer’s exact test) demonstrated higher OM incidence and severity. Myelosuppression (p < 0.01, Mann-Whitney test) and impaired renal function (p = 0.02, Mann-Whitney test) were also considered risk factors for OM.

The study indicates that PBM is effective in preventing OM in patients undergoing HSCT even when administered three times a week.

• Small sample (< 100)
• Intervention expensive, impractical, or training needs (The cost of bringing in a professional or asking the patient to go to a dental office was a hindrance.)
• Other limitations/explanation: Retrospective nature of the study. Allo versus auto transplant regimens are different treatment paths especially the chemotherapy regimens that could influence toxicities.

OM is frequently seen side effect of patients receiving HSCT, these lesions impact patient quality of life, controlling this condition is extremely important, and developing effective interventions is a high priority in protocol support among patients with cancer.

To evaluate/compare three treatments for oral mucositis: (1) Plantago major extract mouthwash, (2) chlorhexidine 0.12%, and (3) aqueous solution of 5% sodium bicarbonate for  the treatment of oral mucositis in patients with solid tumors. Evaluation points included healing time, pain, oral intake, and quality of life.

Randomized controlled trial (phase 3)

• Group A: Control group, received standard of care which included sodium bicarbonate 5% aqueous solution with an additional dose of sodium bicarbonate 5% aqueous solution. 
• Group B: Experimental group, received sodium bicarbonate 5% aqueous solution plus Plantago major extract
• Group C: Experimental group, received sodium bicarbonate 5% aqueous solution plus chlorhexidine 0.12%

The treatment was 14 days for all groups. All groups received education regarding the management of mucositis, a set of instructions, a diary to record signs and symptoms of mucositis, and instruction for proper storing of the mouthwashes. All participants were instructed to rinse with 8 ml of solution for two minutes every six hours. They were instructed to leave 15 minutes between the two mouthwashes.

• N = 50 (evaluable)   
• AGE: Mean age = 59.5 years (SD = 14.3)
• MALES: 48%  
• FEMALES: 52%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Tumor types: breast (30.6%), colorectal (32.7%), lung (14.3%), gastric (8.2%) and other (14.2%)
• OTHER KEY SAMPLE CHARACTERISTICS: Patients had a mean of 3.6 (SD = 3.2) chemotherapy cycles prior to oral mucositis outbreak. Patients received many different chemotherapy drugs. No participants developed neutropenia.

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

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care, palliative care

Randomized controlled trial; investigators, participants, care providers, and statistician were all blinded.

• WHO mucositis scale
• Visual analogue scale (VAS) for pain intensity
• Intake capacity was captured by asking the participants if they could tolerated liquids only or liquids and solids. 
• European Organizsation for Research and Treatment of Cancer Quality of Life Core 30 Questionnaire (EORTC QLQ-C30)
• CBC (evaluation of neutropenia)
• Patient diary

• Healing time: No statistical difference between groups. The group that used the double 5% sodium bicarbonate solution did have a shorter time to heal by two days, which may be clinically significant. 
• Pain intensity: No significant difference
• Oral intake capacity: No significant difference
• Quality of life: No significant difference

In this small group, there is no advantage in using a chlorhexidine or Plantago major extract mouthwash in comparison to a double sodium bicarbonate solution. The latter is likely less expensive and more readily available

• Small sample (< 100)
• Findings not generalizable
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Not generalizable to those patients who become neutropenic or patients with non-solid tumors. Potentially some bias as there was self-reporting of oral intake versus an objective measure. Attrition rate 16% (failure to follow through with monitoring, interruption of the intervention)

This study does not support the use of Plantago major or chlorhexidine mouthwashes over double doses of sodium bicarbonate 5% aqueous solution.

Primary: To evaluate the use of Zataria multiflora (ZM) extract mouthwash to reduce the incidence and severity of oral mucositis (OM) in adult patients with head and neck cancer undergoing radiation therapy alone or combined radiation and chemotherapy. 

Secondary: The impact of ZM extract mouthwash on the amount of opioid used, the use of anti-inflammatory drug use, antibiotic use, and body weight over the course of therapy

• Double blinded, randomized
• Intervention group: Used a mouthwash containing ZM extract
• Control group: Used a placebo mouthwash with no ZM extract
• Both groups: Oral examination prior to initiation of therapy and then weekly until completion of the last radiation dose. Participants encouraged to use the mouthwash three times daily (after breakfast and lunch and at bedtime) in addition to one half hour prior to each radiation session. Maintained for seven weeks after therapy (data collected only until the end of therapy). Participants instructed to not rinse mouth with water up to one hour after gargling with mouthwash. Participants were also instructed not to smoke or eat hot, spicy, or very cold foods. Oral analgesics and anti-inflammatory medications were given as needed and per standard of care.

• N: 63 patients randomized, 25 in treatment group (16% attrition) and 27 in placebo group (20% attrition)   
• AGE: 57.48 years (SD = 17.98) in treatment group, 64.62 years (SD = 12.75) in placebo group
• MALES: 71%  
• FEMALES: 29%
• CURRENT TREATMENT: Radiation, combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Head and neck cancer (radiation [at least 6000 cGy] planned for the entire oropharynx, nasopharynx, and/or greater than one-third of the oral cavity, a KPS > 70, with or without chemotherapy)
• OTHER KEY SAMPLE CHARACTERISTICS: No prior history of head and neck radiation, no current poor oral hygiene, no active infections of the mouth, no liver or kidney disease, no diabetes, no autoimmune disease or disease that might alter healing

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Iran

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care

Double blinded, randomized, placebo controlled study

• World Health Organization (WHO) mucositis scale
• Oral Mucositis Assessment Scale (OMAS)
• Visual analogue score (VAS) for pain
• Required opioid analgesia (weekly)
• Required anti-inflammatory drugs (weekly)
• Required antibiotics (weekly)
• Weekly body weights

Primary outcomes: 

• The presence and intensity of OM the groups was significantly different using the OMAS for all six weeks of assessment (p < 0.05 [range = 0.002-0.016]) and for weeks 3, 4, and 6 using the WHO OM scale (p < 0.05 [range = 0.009-0.045]) favoring the ZM group. There was a decrease in the incidence of grades 3-4 OM in the ZM group in comparison to the placebo group (24% versus 55.5%).

Secondary outcomes: 

• Pain: The ZM group demonstrated a lower pain score in weeks 2-6
• Weight loss: Less in the ZM group (p = 0.000)
• Required analgesia: Less in the ZM group (p = 0.010)
• Antibiotic use: Less in the ZM group (p = 0.037)

The use of ZM mouthwash positively impacted the incidence and severity of OM in patients with head and neck cancer undergoing head and neck radiation with or without concurrent chemotherapy. In addition, the ZM mouthwash contributed to less use of opioid analgesia, less antibiotic use, and decreased weight loss.

• Small sample (< 100)
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: It is hard to discern how analgesic and anti-inflammatory use was ascertained.

ZM may offer an option for decreasing OM in patients undergoing radiation with or without concurrent chemotherapy in the head and neck cancer population.

PURPOSE: To use sub-antimicrobial doxycycline 50 mg per day on patients with leukemia to reduce the onset and severity of OM

TYPES OF PATIENTS ADDRESSED: Patients with ML or LL

RESOURCE TYPE: Evidence-based guideline

PROCESS OF DEVELOPMENT: Patients aged 15 years and older with specific leukemia (N = 47). Patients had basic oral examination and were taught oral care protocol. A baseline oral examination was done three times per week for three weeks. The strategy of development was to prevent the devastating consequences of OM in patients with leukemia. 

INCLUSION CRITERIA: Aged 15 years or older, male or female

EXCLUSION CRITERIA: Patients using the following medications: acitretin, isotretinoin, or tretinin

• PHASE OF CARE: Diagnostic    
• APPLICATIONS: Palliative care

The low-dose use of doxycycline proved ineffective in the management of OM in patients with acute leukemia during chemotherapy.

Effectiveness unlikely. The intervention with doxycycline lacks effectiveness in the reduction of the severity or onset of OM in patients with leukemia.

The findings are not generalizable; limited to one disease group.

The nursing implication is that continued attention to OM is needed to manage and treat the dose interruption and debilitating nutritional problems associated in patients receiving treatment for cancer.

PURPOSE: Prevention of combination drug therapy-induced OM (stomatitis) This is the second clinical trial supported by Novartis in patients taking combination drug therapy (everolimus and exemestane).

TYPES OF PATIENTS ADDRESSED: Patients with hormone receptor-positive, HER2-negative metastatic breast cancer 

RESOURCE TYPE: Evidence-based guideline

DATABASES USED: PubMed   

INCLUSION CRITERIA: Metastatic breast cancer with hormone receptor-positive, HER2-negative

EXCLUSION CRITERIA: All other types of cancer

PHASE OF CARE: Late effects and survivorship

This is the second clinical trial performed by Novartis to eliminate dose interruption of everolimus tablets in combination therapy for women with hormone receptor-positive, HER2-negative metastatic breast cancer. Twenty-three investigational sites based in the United States participated. The average age of the 92/86 female participants was 61 years. It was a single-arm phase 2 study. The primary endpoint was the incidence of grade 2 or worse OM was significantly reduced by proactive oral care use of alcohol-free dexamethasone oral solution (SWISH).

This is the first and largest OM prevention study completed that combines therapeutic management with proactive patient engagement to reduce the incidence of OM in patients who are postmenopausal and receiving combination pill therapy(everolimus and exemestane) as treatment for hormone receptor-positive, HER2-negative metastatic breast cancer. The use of dexamethasone oral solution for two minutes, four times a day, will stop OM from occurring or reduce the severity. It is used for eight weeks or longer if results are positive.

The primary limitation is it is for only one targeted group and for one target drug. The clinical trial is high strength and high quality. There could not be a control group due to the fact that the investigators did not find it ethical for patients to suffer with OM. Novartis is the manufacture of dexamethasone oral rinse and gives free eight-week supplies.

The nursing implication is to teach an oral care protocol to all patients with cancer and ask for more clinical trials for patients with other types of cancer or receiving other treatments. The SWISH trial found that a commercially available, inexpensive, well tolerated dexamethasone oral rinse is an effective intervention in the prevention of OM in women with HER2-negative metastatic breast cancer treated with everolimus.

• To determine the impact of music therapy sessions on outcomes of pain, depression, anxiety, shortness of breath, and mood
• To understand which patient characteristics and goals and music therapist interventions had an effect on study outcomes

Data was collected on admitted palliative medicine patients receiving music therapy from September 2000 to May 2012. A board-certified music therapist (MT-BC) on the unit conducted music therapy sessions with individual palliative medicine patients and family members present. Multiple goals may have been addressed at a single session, using a variety of live patient-preferred musical interventions. Interventions included six main categories—music listening, verbal/cognitive participation, vocal participation, physical participation, verbal/emotional participation, and music-assisted relaxation. Symptom evaluations from patients included pre- and post-session severity of pain, depression, anxiety and shortness of breath. Data collected on patients included standardized music therapy assessment, elements of standardized music therapy, clinical note, patient related information, patient goals for the session, interventions used by the music therapist, symptom evaluations from patients, behavioral evaluations from the therapist, music used, patient and family member reactions, and narratives.

• N = 239   
• AGE: Average = 60 years; median = 61 years; range = 20-89 years
• MALES: 33.1%  
• FEMALES: 66.9%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: All palliative patients; diagnoses include lung cancer, hematologic cancer, breast cancer, gastrointestinal cancer, gynecologic cancer, ASL, sickle cell disease, cardiovascular, chronic pain/RSD/fibromyalgia, liver disease/cirrhosis, ESRD, AIDS, bowel obstruction, multiple sclerosis 
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were included if they were 18 years or older, having at least one patient-reported rating of pain, depression, anxiety, shortness of breath, or mood before and after the music therapy session.

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: The Cleveland Clinic (Ohio)

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care

This is a retrospective study of data collected on palliative medicine patients admitted from September 2000 to May 2012 who participated in music therapy sessions.

• Patient-reported severity of pain, depression, anxiety, and shortness of breath were all rated on a scale from 0 to 10 that was obtained pre- and post-music session.
• Patient-reported mood rated on a scale from 0 to 4 based on the Rogers Happy/Sad Faces Assessment Tool that was obtained pre- and post-music session.
• Music therapist-reported scores on facial expression, body movement, and vocalization based on a three-point scale before, during, and after the music therapy session based on the Nursing Assessment of Pain Intensity and Riley Infant Pain Scale.

Statistically significant reduction improvement in pre- and post-session mean scores were reported for all measurements (p < 0.001) except body movement (p = 0.16). However, the percentage of patients who achieved the clinical significant threshold ranged from 0.7% to 66.2%. Outcomes with the highest percentage of patients with clinically relevant improvement were mood (66.2%), vocalization (58.7%), and facial expression (55.6%). Only 12.3% of patients experienced any clinically relevant improvement. 96% of participants had an overall positive verbal response to the session versus 4% of participants that experienced an ambivalent or no verbal response. Patients who listed pain, depression, anxiety, shortness of breath, or mood as a goal for music therapy achieved the most improvement in these symptoms. Vocalization seemed to have significantly improved when verbal/emotional intervention was used and when distraction was a goal of music therapy. There was no impact on patient demographic or cancer diagnosis on outcomes.

Music therapy does appear to have a positive effect on symptoms of dyspnea and should be considered as an adjunct to current standard interventions. However, more research is needed to determine the degree of clinical benefit of music therapy in the improvement of dyspnea, as well as its cost-effectiveness and duration effect.

• Risk of bias (no control group)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement validity/reliability questionable
• Other limitations/explanation: Use of observational behavioral data (such as the music therapist-reported outcomes) could be biased as it relies on the therapist’s opinion. Therefore, inter-rater reliability of the rating scales was not assessed to account for multiple interpretations of various patient behaviors. Authors “arbitrarily” decided that a change of 2 points on a 10-point rating scale and a change in 1 point on a 4-point rating scale would be considered clinically relevant improvement of symptoms. The study results do not take into consideration the effects of session interruptions, patients with severe pain or high anxiety, actively dying, or those who had fallen asleep. Study also does not capture cost-effectiveness or duration effect of music therapy.

Music therapy should be considered as an adjunct to current standard interventions for dyspnea.

To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl (FBT) in comparison to immediate-release morphine (IRM) for the relief of episodic breathlessness.

Fentanyl buccal tablets 100 mcg and 2% immediate release morphine are titrated to 1/6th dosing based on their daily oral morphine equivalent (DOME) to start and increase up to 400 mcg fentanyl or 1/6th + 100% of DOME. Patients were to keep a diary of when dyspnea episode started and when medication taken, with various times to record effectiveness and oxygen saturation over one hour. Patients had twice-a-day safety checks by researchers. Actual doses used were 100-200 mcg of fentanyl and 6-36 mg morphine. Patients crossed over after five days (of a 10-day study).

• N = 6 patients completed the study
• AGE: Mean = 58 years old
• MALES: 60%
• FEMALES: 40%
• CURRENT TREATMENT: Palliative care
• KEY DISEASE CHARACTERISTICS: Patients with incurable cancer who had at least one month to live and SOB scores greater than 3 of 10.
• OTHER KEY SAMPLE CHARACTERISTICS: Older than age 18 years and opiate tolerant.

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

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Elder care, palliative care

This is an open-label, randomized, active-controlled (morphine), crossover, phase II trial with an open label dose titration phase.

Oxygen saturation testing was done, stop watch, and a breathlessness scale of 0-10, with 10 being the worst score. Respiratory rate, Glasgow Coma Scale, and Karnofsky level.

The Breathlessness Index Difference (BID) was calculated.  At 10 minutes, the difference was p = 0.051, with mean time to onset of meaningful breathlessness relief was for FBT 12.7 minutes (plus or minus 10 minutes), and, for IRM, 23.6 minutes (plus or minus 15.1 minutes), with a mean difference of 10.9 minutes (95% CI [-24.5, 2.7], p = 0.094) in favor for FBT (FBT-IRM). Time of onset between morphine and fentanyl was a mean difference of 8.4 (95% CI [-18.8, 2.1], p = 0.085), which was not statistically significant.

Fentanyl was found to work quicker then MS, without any difference in side effects or satisfaction with the medications.

• Small sample (< 30)

For many patients, once SOB has started, time to relief can be an important factor in keeping the anxiety factor down. For some, the price of fentanyl outweighs the benefit against morphine as both have tolerated side effects for opiate-tolerant patients.