All participants received four weekly 45-minute sessions of therapeutic massage (MT), healing touch (HT), or presence (P) and four weekly sessions of a standard care control. Credentialed practitioners who were also registered nurses delivered MT and HT. The three interventions all included music, a centering message, and a message to focus on breathing and letting go of extraneous thoughts. The order of the conditions was randomized. MT included a written Swedish massage protocol using massage gel. For HT, the protocol developed by Healing Touch International was used, and touch and nontouch techniques were used. Energy techniques used included centering, unruffling, magnetic unruffling, full-body connection, mind clearing, chelation, and lymphatic drain to modulate the energy field. For P, participants lied on a table listening to relaxing music. An MT or HT therapist sat with the participant during the session. The purpose was to be attentive and caring but to avoid therapy or physical intervention. In the control group, symptoms and vital signs were assessed.

• Of the 230 adults who consented to participate, 164 completed all eight sessions.
• Of those who completed the study, mean age was 54.7 years, 87% were female, 98% were Caucasian, and 68% were married.
• The majority had stage III or IV disease, and 52% had breast cancer.
• Mean time since diagnosis was 17.4 months.
• All participants rated fatigue, pain, anxiety, or nausea as greater than 3 on a scale of 0 to 10.

Patients were from two outpatient chemotherapy clinics in the Midwest.

Patients were undergoing the active treatment phase of care.

This was a randomized, two-period crossover (between one of the interventions and standard care) study.

• Profile of Mood States (POMS) for fatigue
• Blood pressure
• Heart rate
• Respiratory rate
• Pain
• Nausea
• Medication use
• Anxiety
• Mood disturbance
• Satisfaction

Compared to the control group, there was no effect of presence on fatigue. When comparing individual interventions to their matched control periods, the effect of MT on fatigue was close to significance (p = 0.057). HT was found to reduce fatigue (p = 0.028).

There was no clear evidence that one intervention was superior to the other, but MT and HT seemed to be more effective than presence alone or standard care in improving fatigue.

• Interventions also included centering, breathing, and music, which may confound the results.
• The commitment to complete the study was great, and the dropout rate was high.
• Cross-over designs may be more appropriate for healthy participants or those with earlier stage disease.
• The study design was complex. There was no blinding, there was variability in the research assistant and practitioners collecting assessments, and there was variation in the intervention technique.
• A greater number of participants assigned to the presence group dropped out due to treatment preference.
• A registered nurse certified in massage or healing touch therapy is required.

To determine if massage therapy and healing touch were effective in reducing anxiety, mood disturbance, pain, fatigue, and nausea and in improving the relaxation and satisfaction with care of patients receiving chemotherapy treatment

Patients were randomly assigned to one of three groups: therapeutic massage, healing touch, or caring presence. All received four weekly 45-minute sessions of the intervention and four weeks of standard care (control). After four weeks, patients were crossed over to another intervention or the control. Order of the intervention and usual-care control were randomized. Pre- and post-assessments of pain, nausea, and vital signs were done at each session. Assessments of intervention effects were done at the beginning and end of each four-week session. Therapeutic massage was provided in a standardized fashion, using a Swedish massage protocol. Healing touch followed a previously developed protocol incorporating centering, unruffling, magnetic unruffling, full-body connection, mind clearing, chelation, and lymphatic drain. Presence consisted of patients lying down for 45 minutes with relaxing music and the presence of a therapist. The therapist asked patients how they were feeling and if they had any questions. Conversation may or may not have occurred, according to the patient’s preference; the purpose of the therapist was to be attentive but to avoid therapy or physical intervention. The control condition consisted of usual care, which the authors did not describe.

• The study reported on a sample of 164 patients.
• Mean patient age was 57.4 years, with a range of 27–83 years.
• The sample was 87% female and 13% male.
• The most common cancer types were breast, gynecologic or genitourinary, gastrointestinal, hematologic, and lung.
• The majority of patients had stage III or IV disease, and 50% were in the first month of chemotherapy treatment.
• All patients had a score of at least 3 on a 10-point scale of symptom severity. The most frequently reported symptoms were fatigue, pain, anxiety, and nausea.

• Single site
• Outpatient setting

Patients were undergoing the active treatment phase of care.

A randomized, controlled, parallel-group, crossover design was used.

• Symptom rating scales (0–10)
• Brief Pain Inventory
• Brief Nausea Index
• Profile of Mood States
• Satisfaction measure according to a four-point Likert-type scale

• Of those who initially entered the study, 29% dropped out. Half of the dropouts were due to changes in the cancer treatment protocol; half were because patients wanted an intervention different from the one assigned. Those who dropped out had higher pain, nausea, mood disturbance, and fatigue at baseline (p < 0.05) than those who did not.
• Massage and healing touch groups showed immediate post-session reduction of respiratory rate, heart rate, and blood pressure (p < 0.01), and these interventions were more effective (p < 0.01) in achieving these reductions than were control and presence conditions. Massage and healing touch were associated with pre- and post-session reduction in current pain (p < 0.001).
• Over the four-week study period, mood disturbance decreased over time in all patients. Massage therapy, compared to the control condition, was more effective at reducing total mood disturbance (p = 0.004) and anxiety (p = 0.023). Healing touch reduced mood disturbance (p = 0.003) and fatigue (p = 0.028).
• Mean pain scores in all cases declined over time.
• There were no differences between groups in nausea or use of antiemetics.
• There were no differences between groups in overall satisfaction. Massage and healing touch were associated with higher satisfaction with the intervention than was presence (p < 0.0001).

Massage therapy and healing touch were more effective than presence alone or standard care in improving mood, reducing anxiety, pain, and fatigue and in reducing heart rate, blood pressure, and respiratory rate immediately postintervention.

• The control condition may not have provided appropriate attentional control.
• The study had risk of bias due to no blinding.
• The anxiety measure was not a rigorous, valid tool; it was a 10-point scale.
• The study had a large drop-out rate.

Massage therapy and therapeutic touch can be beneficial to patients because the interventions induce physical relaxation and reduce pain, fatigue, and anxiety. In this study, these interventions were more effective in this regard than was therapeutic presence alone. Massage therapy and therapeutic touch are complementary therapies that nurses can consider and advocate for on behalf of patients who may benefit from them.

To review the evidence regarding acupuncture for cancer-related fatigue (CRF).

Databases searched were PRISMA, AMED, CINAHL, EMBASE, MEDLINE, PsycINFO, Cochrane Collaboration, one Chinese, three Japanese, and four Korean databases.

Search keywords were acupuncture therapy or electroacupuncture, cancer, and fatigue. A full listing of search terms used was provided.

Studies were included in the review if they were randomized, controlled trials (RCTs) investigating the effect of acupuncture treatments on CRF.

The exclusion criteria were not specified.

In total, 2,419 references were retrieved. The Cochrane tool was used to assess research method quality.

• The final number of studies included was seven RCTs (548 patients).
• The sample range across studies was not provided.

Of the seven RCTs found for inclusion, four favored acupuncture and three showed no effect. Most studies had serious limitations and methodological flaws. Of the two studies that were of relatively high quality, one showed no benefit over sham acupuncture and one favored the intervention over sham and wait-list control. Three of the four studies that controlled for placebo effect showed no benefit of acupuncture.

The evidence for acupuncture in the management of CRF is ambiguous, conflicting, and inconclusive.

• The review included a small number of studies.
• The included studies were of low quality. 
• Heterogeneity among studies precluded meta-analysis.

Findings showed that evidence is lacking in support of acupuncture for the management of CRF.

To assess the efficacy of two variant cognitive skills training (CST) interventions for the caregivers of patients with lung cancer to improve caregiver distress, self-efficacy, and strain

Following a baseline data collection period, participants (patient-caregiver dyads) were randomly assigned to either CST or a cancer education and support group. Trained research assistants blinded to participant treatment groups collected patient and caregiver assessments via telephone calls immediately after each treatment session and at four months post-study. Fourteen 45-minute, telephone-based sessions with individual dyads using speaker phones occurred over an eight-month period. All study patients continued regular healthcare visits informed by including educational information. Trained, registered nurses adhering to detailed and audiotaped treatment outlines received weekly supervision and evaluation from study psychologists. Dyads in the CST group received information about ways to manage disease symptoms, homework assignments, and a CD focused on stress management. The education and support dyad group received lung cancer disease and treatment information, including hospice and palliative care, in a supportive environment without focus on coping skills training.

• N = 233 dyads  
• MEAN CAREGIVER AGE = 59.3 years
• CAREGIVER MALES: 31%, CAREGIVER FEMALES: 69%
• KEY DISEASE CHARACTERISTICS: Caregivers of patients with a diagnosis of early stage lung cancer (non-small cell lung cancer stages 1–3 or limited stage small-cell lung cancer); median of 207.5 days since patient diagnosis; 81% with history of cancer surgery; more than half with stage 1 non-small cell lung cancer
• OTHER KEY CAREGIVER SAMPLE CHARACTERISTICS: 82% Caucasian; 44% college educated; 64% spousal caregivers living with patient

• SITE: Multi-site    
• SETTING TYPE: Multiple settings  
• LOCATION: Home telephone intervention, North Carolina

• PHASE OF CARE: Multiple phases of care

Randomized, controlled trial with blinding of intervention

• Profile of Mood States–B (POMS-B) measuring six aspects of mood (high Cronbach’s alpha)
• Caregiver Strain Index (CSI) measuring caregiver common stressors (high internal consistency and construct validity)
• Modified Caregiver Self-Efficacy in Symptom Management (CSESM) measuring caregiver perceived ability to help patient manage disease symptoms (high Cronbach’s alpha)

No significant demographic or medical variable differences existed between dyads in the CST and education and support groups. Caregiver outcome measures indicated significant main effects over time for the POMS-B anxiety subscale (p = 0.02) and self-efficacy (p = 0.01). Both intervention groups showed decreases in caregiver anxiety and increases in their self-efficacy to manage patient symptoms although no significant time to intervention occurred with hierarchical linear modeling. An exploratory moderator analysis showed the education and support intervention to most benefit the caregivers of patients with stage 1 cancer. The CST intervention most benefited the caregivers of patients with stage 2 or 3 lung cancer.

CST and education and support intervention improved patient and caregiver anxiety and efficacy although the lack of a nontreatment group prevented specific conclusions about either intervention approach. Influences of time and attention may have affected dyadic outcomes. More research on important intervention aspects and their operation for improved lung cancer clinical practice is needed.

• Risk of bias (no control group)
• Findings not generalizable
• Subject withdrawals ≥ 10% 
• Other limitations/explanation: The distinction between the education provided to the CST group and the education and support group was not clear.

Identifying effective caregiver support interventions to aid in the care of patients with lung cancer remains a priority because of high levels of patient and caregiver distress and low self-efficacy. Additional studies need to include diverse participants, structured protocols for data collection and evaluation, a standard care (control) group, and innovative recruitment and retention methods for caregivers to strengthen the clinical practice evidence for this group of caregivers.

To (a) examine data collected eight weeks following participants’ completion of the intervention to determine whether treatment effects were maintained, and (b) process data to identify factors that might explain variability in response to the intervention 

After providing informed consent, participants were administered baseline measures and then randomly assigned to either a partner-assisted emotional disclosure intervention group or an education/support condition group. The partner-assisted emotional disclosure intervention protocol systematically trained couples in skills designed to help patients disclose their feelings and concerns related to the cancer experience.

Individual couples attended four in-person sessions with a master's-level therapist. Sessions included training in communication skills to help patients express their cancer-related thoughts and feelings and partners to encourage patients’ disclosure and communicate understanding and acceptance. The majority of sessions were devoted to couples’ conversations in which patients were given the opportunity to disclose their cancer-related thoughts and feelings to their partners.

Couples in the cancer education/support condition group attended four in-person sessions that centered on presenting information relevant to living with cancer. The therapists and scheduling sessions were the same as for the disclosure intervention. Couples in this condition group did not receive any training in communication skills, and patients were not encouraged to discuss their thoughts and feelings related to the cancer experience with their partners.

• The sample included 130 couples. 
• Mean age of patients was 59.4 years; mean age of partners was 59.3 years.
• The patient sample was 71% male and 29% female; the partner sample was 29% male and 71% female.
• Patient diagnoses were colorectal cancer (42%), pancreatic cancer (15%), esophageal cancer (11%), and other cancers (32%).
• The majority of patients were Caucasian, had stage IV disease, and had received chemotherapy; half were educated beyond high school.
• The majority of partners were Caucasian and were educated beyond high school (60%).

• Outpatient setting
• Duke University and University of North Carolina Hospitals

• End of life/multiple phases
• End of life; survivorship; sustained intervention effect

A randomized controlled trial design was used.

• Quality of Marriage Index (QMI): study Cronbach’s alpha average for both patients and partners = 0.90    
• Miller Social Intimacy Scale (MSIS): study Cronbach’s alpha average for patients and partners = 0.90
• Profile of Mood States (POMS): study Cronbach’s alpha average for patients and partners = 0.89
• Holding Back From Disclosure Measure: study Cronbach’s alpha for patients only = 0.88
• Positive and Negative Affect Scale (PANAS): noted to have reliability and validity
• Self-Feeling Awareness Scale (SFAS): inter-rater reliability previously established

The study experienced a 27.7% attrition rate due to patient death or declining health or conflicts between study completion and life issues. Analysis occurred according to an intent-to-treat model based on an initial randomized sample of 130 couples. For couples in which the patient initially reported high levels of holding back from discussing cancer-related concerns, the partner-assisted emotional disclosure intervention led to significant improvement in relationship quality (p = 0.002) and intimacy (p = 0.020) over an eight-week follow-up period compared to an education/support control condition. There was no treatment effect on mood. Overall, the benefits of disclosure intervention appeared largest for patients who were high in holding back.

In patients who were more expressive during disclosure sessions, patients and partners were significantly more likely to report increases in relationship quality and intimacy from baseline to post-treatment assessment. When patients reported more negative affect following the disclosure sessions, both patients and partners were significantly more likely to report decreases in psychological distress between baseline and post-treatment assessment.

The intervention showed a positive effect on couples’ relationships over the eight-week follow-up; however, there was no demonstrated effect on affect or mood disturbance for patients or their partners.

• Some couples were unable to complete the four sessions of the intervention due to the face-to-face structure of the intervention.
• The large amount of data collected by telephone contact at eight weeks postintervention may influence the accuracy of data.
• Whether partners were also caregivers for patients at the end of life is unclear. 
• Participants tended to be white, well-educated, heterosexual couples.
• The study's focus on patient emotional disclosure, with limited attention to caregiver disclosure, may affect relationship quality and intimacy issues.

Nurses have a role in assessing patient–partner coping during cancer treatment and referring couples to relevant resources to facilitate physical, spiritual, and psychosocial health of couples. Partner-assisted emotional disclosure in a structured supportive environment may benefit couples when patients have difficulty expressing cancer-related concerns.

To demonstrate the safety and efficacy of fentanyl-pectin nasal spray (FPNS) in the treatment of breakthrough cancer pain

Consenting patients entered an open label-titration phase for determination of effective dose of FPNS. Effective dose was defined as a dose that achieved successful treatment of two breakthrough episodes. In the titration phase, if pain relief was unacceptable at 30 minutes, the patient was able to take his or her previous rescue medication. Doses were sequentially increased up to 800 mcg. Individuals who achieved an effective dose were eligible to continue in the double-blind stage. Patients received randomly assigned separate bottles, identified by number. Patients were instructed to use the bottles in the order designated. Each breakthrough episode was treated with a single dose. Pain that continued to require treatment after 30 minutes was treated with the patient’s usual rescue medication. Electronic diaries were used for data collection. Patients recorded pain intensity and pain relief at 5, 10, 15, 30, 45, and 60 minutes. Adverse events were recorded throughout the study, and visual nasal assessments were performed by the study physician at baseline and at the end of treatment. Maximum study duration was eight weeks.

• Seventy-three patients were in the intent-to-treat analysis.
• Mean patient age was 53.8 years (SD = 1 year).
• Of all patients, 46.9% were female and 53.1% were male.
• The study included multiple tumor types. The most common were lung, breast, reticuloendothelial, and bowel.
• All patients were receiving, on a regular basis, opioids for the treatment of pain. The most common opioids for the treatment of background pain were morphine, fentanyl, oxycodone, and methadone. Of all patients, 26% were taking multiple opioids.

Multisite (26 in the United States and 2 in other countries)

Randomized double-blind placebo-controlled crossover study

• 11-point scale, to measure pain intensity
• Five-point scale, to measure overall satisfaction
• Five-point scale, to measure ease of use
• Five-point scale, to rate nasal symptoms

• Thirteen patients (15.7% of those randomized) withdrew from the study because of lack of efficacy or adverse effects.
• At 5 minutes and sustained over all other time points, the mean pain-intensity score for FPNS-treated episodes was significantly lower  (p = 0.03) than that for placebo-treated episodes. At 5 minutes, 33% of patients reporting on FPNS-treated episodes noted a drop of one point or more. At 10 minutes, 61% of patients reporting on FPNS-treated episodes noted a drop of one point or more; at 30 minutes, 73% noted a drop of one point or more.  
• Of all FPNS-treated episodes, 90.6% did not require additional rescue medication. Of all placebo-treated episodes, 80% did not require additional rescue medication.
• Authors noted significantly lower pain intensity (p < 0.0001) with FPNS at 60 minutes.
• Clinical assessment of each patient's nose revealed no changes.
• In regard to adverse events, authors noted no significant differences between treatments. 
• In an open label extension after study conclusion, 87% of patients chose to continue use of FPNS.

FPNC is effective and well tolerated for treatment of breakthrough cancer pain.

• The study had a small sample size, with fewer than 100 patients.
• Authors noted a high response to placebo.
• The study period was relatively short. Whether nasal complications might occur with long-term treatment with FPNS is unclear.

FPNS is an effective approach to the management of the breakthrough pain of patients with cancer who are taking opiods for relief of background pain. FPNS can be a useful alternative in situations where clinicians want to reduce the number of oral medications. Studies of the use of nasal sprays have been relatively brief, so nurses must remain aware of the need to assess the patient’s nares and related symptoms.

To evaluate the safety and tolerance of fentanyl-pectin nasal spray for cancer-related breakthrough pain

Patients completed an open dose-titration phase for dose determination and then entered a 16-week open label treatment phase. Patients were instructed to administer the effective dose from titration for a maximum of four episodes of breakthrough pain per day. If pain relief was inadequate after 30 minutes, patients could take the prestudy rescue medication. Investigators contacted patients at least weekly to review appropriate use of study medication, to discuss the need for dose adjustment and nasal symptoms, and to review use of rescue medication. Patients also rated nasal symptoms by using a 10-point questionnaire. A physician performed graded nasal assessments at baseline, week 8, and week 16.

• Authors reported that 110 patients completed the entire 16 weeks of the study.
• Authors reported 42,227 breakthrough pain episodes in 403 patients included in the analysis.
• Mean patient age was 53.8 years. The age range was 21–84 years.
• Of all patients, the percentage of females was 46.9% and the percentage of males was 53.1%.
• Authors did not report diagnosis information.
• Of all patients, 59.8 % were on morphine; 31.5%, on fentanyl; and 14.4%, on oxycodone. These drugs were used for the treatment of  background pain.

• Multisite
• Outpatient
• Multiple countries

Open label trial

• Nasal-symptom questionnaire, offering a four-point assesment scale for each of the following: stuffy/blocked nose, runny nose, itching/sneezing, crusting/dryness, burning/discomfort, nose bleeding, cough, postnasal drip, sore throat, and taste disturbance
• Measures of the neeed for rescue medication other than the study drug

• Authors reported that 110 patients completed the full 16-week extension trial.
• Of all patients, 24.6% had treatment-related adverse events. The most common adverse events were dizziness, vomiting, constipation, and somnolence, which occurred in 3.5%–5.2% of patients.
• Doses of fentanyl spray were 100–800 micrograms. Authors did not relate overall dose to adverse events.
• For most patients, the results of nasal examination at the end of the study were normal. Authors observed no consistent pattern in patient-reported nasal symptoms.
• Of the 42,227 breakthrough episodes, 94% did not require additional rescue medication to be resolved.

Fentanyl-pectin nasal spray for cancer-related breakthrough pain appears to be well tolerated over a use period of four months.

The study has a risk of bias due to no appropriate control group.

This study showed that, over a four-month period, patients tolerated the fentanyl-pectin nasal spray well. This study suggests that long-term use is not associated with significant adverse nasal events. Fentanyl-pectin nasal spray used as specified, for the treatment of breakthrough cancer-related pain, was effective for the majority of patients. Fentanyl-pectin nasal spray is a rapidly acting treatment for breakthrough pain that can be particularly helpful to patients who have difficulty with oral intake.

To assess the efficacy and safety of subcutaneous methylnaltrexone in patients with advanced illness and opioid-induced constipation (OIC), and to clarify whether a dose-response relationship could be identified.

Methylnaltrexone was administered in doses of 1 mg, 5 mg, or 12.5 mg subcutaneously; patients were randomized to those dose groups in a ratio of 1:1:1. After 22 patients, the dose range was extended to 20 mg; patients were randomized in a ratio of 1:1:3 to 1-mg, 12.5-mg, or 20-mg dose groups. Patients received study medication if they had no bowel movement for at least two days and had a score of 3 or higher on a 5-point scale assessing constipation-related distress. Patients receiving laxatives had to be on a stable regimen for at least four days and remain on regimen during the study.

During the first week of the study, subcutaneous injections were administered on days 1, 3, and 5. Following the first week of double-blind study, patients received the option for open-label study for a maximum of three weeks. The initial dose was 5 mg subcutaneously as often as every other day. The maximum dose was 15 mg in the first 22 patients and 20 mg for the remaining 11 patients. Dose could be increased or decreased by the investigator.

• The study reported on a sample of 33 adult men and women (39 screened) with advanced illness, including patients with cancer receiving palliative care and chronic opioid therapy for pain.
• Mean patient age was 61 years (range 20-87). 
• Mean body weight was 64 kg.
• Seventy-nine percent of patients were Caucasian.
• Eighty-five percent of patients had a primary diagnosis of cancer.
• Eighty-five percent of patients used laxatives at baseline, 33% used stool softeners or emollients, and 27% used osmotic agents. 
• Patients were included in the study if they were receiving opioids, were stable for two weeks, and remained stable for four weeks; had no bowel movements despite conventional laxative therapy; had a life expectancy of at least four weeks; and had stable vital signs.

Multi-center

This randomized controlled, parallel-group, repeated-dose, dose-ranging trial included a double-blind phase for one week followed by an open-labeled phase for a maximum of three weeks.

• The primary endpoint, laxation response, was a bowel movement within four hours of the initial dose.
• Subjective outcomes were obtained prior to each dose and approximately three hours postdose.
• Constipation severity and distress were graded on a five-point categorical scale.
• The Opioid Withdrawal Scale was a modified Himmelsbach scale.
• Patient satisfaction was assessed on a seven-point scale.
• The severity of opioid adverse events were graded on a four-point categorical scale.

Twenty-two patients completed the blinded phase, and 14 completed the open-label phase.

In the blinded phase, laxation occurred within four hours on day 1 for 1 of 10 patients (10%) in the 1-mg dose group, 3 of 7 patients (43%) in the 5-mg dose group, 6 of 10 patients (60%) in the 12.5-mg dose group, and 2 of 6 patients (33%) in the 20-mg dose group. On day 2, for all dose groups higher than 1 mg, 11 of 23 patients (48%) responded (p = 0.05). There was no dose-response relationship across the three highest doses compared to the 1-mg dose.

The median time to laxation was higher than 48 hours for the 1-mg dose group and 1.72, 0.48, and 6.75 hours in the 5-, 12.5-, and 20-mg dose groups, respectively. The median time to laxation was 1.26 hours for all patients dosed 5 mg or higher, and was statistically significant compared to the 1-mg group (p < 0.0003). The 1-mg dose group required laxative rescue approximately twice as often as other groups. There was no trend in worsening pain control over time.

In the open-label phase, the response rate was from 49% to 64% for patients in dose groups from 5 mg to 12.5 mg. Secondary outcomes were not evaluated because of the small sample size.

Methylnaltrexone doses of 5 mg or higher in patients with advanced illness relieved OIC without decreased analgesia or withdrawal symptoms.

• The sample size was small (fewer than 100 patients).
• The drop-out rate was high: 11 of 22 patients withdrew during the double-blind phase, 4 declined the open-label phase, and 4 withdrew from the open-label phase.

To obtain information about the dose response for analgesia and safety in a population with medical illness and pain that is inadequately controlled by an opioid

Patients were randomly assigned to different-dose groupings of nabiximol or placebo delivered as an oral spray. Study design included a 5- to 14–day baseline period, five weeks of treatment titration, and a poststudy follow-up after two weeks. Patients received a daily call, from a voice recording system, that asked them to grade average pain. Patients continued the use of scheduled opioids and usual analgesics for the treatment of breakthrough pain. Patients who received at least one dose of the study drug were included in intent-to-treat analysis.

• The sample was composed of 263 patients.
• Mean patient age was 58 years. Age range was 20–93 years.
• Of all patients, 51.7% were male and 48.3% were female.
• Patients had active cancer and moderate to severe chronic pain despite opioid titration. Of all patients, 15% had breast cancer, 17.8% had gastrointestinal cancer, 17.8% had lung cancer, 12.2% had prostate cancer, 33.9% had some other cancer, and 3.3% had an unknown type of cancer.
• Patients were excluded if they had a major psychiatric or cardiovascular disorder, epilepsy, or significant renal or hepatic impairment or if they were pregnant, lactating, or used inadequate contraception. Also excluded were those expecting to receive therapies that would change pain and patients who were currently using or had used marijuana, cannabinoid-based medications, or rimonabant within 30 days of study entry and were unwilling to abstain for the duration of the study.

• Multisite
• Eighty-four study centers across North America, Europe, Latin America, and South Africa
   

• Phases of care: multiple phases of care
• Clinical applications: end-of-life care and palliative care
   

Randomized placebo-controlled, graded-dose trial

• Data obtained in response to six daily questions delivered via interactive voice-recording system
• Brief Pain Inventory (Short Form) (BPI-SF)
• European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30) Version 3.0
• Patient Assessment of Constipation Quality of Life (PAC-QOL)
• Montgomery-Asberg Depression Rating Scale (MADRS)
   

• Analysis of continuous responder rate favored the nabiximols groups (P = 0.035). However, this analysis was significant in the lower-dose groups only.
• The adjusted mean change in pain score for the low-dose group favored nabiximols (P = 0.006).
• Post hoc analysis that combed the low- and medium-dose groups showed a treatment difference in favor of nabiximols (P = 0.019). When weekly mean scores of average pain were compared across the groups, the low-dose group showed the greatest reduction, favoring nabiximols (P = 0.024).
• Sleep disruption scores were comparable at baseline for all groups. When evaluated at the end of treatment, the significant treatment effect (P = 0.012) was attributed to the low-dose group (p = 0.003). 
• The EORTC QLQ-C30 showed that nabiximols negatively affected cognitive functioning. In addition, compared to patients using placebo, patients using nabiximols experienced a significant amount of nausea and vomiting (P = 0.019). Authors noted that most nausea and vomiting occurred in the high-dose group (P = 0.0090).
• Of nabiximol-treated patients, 29.5% experienced a serious adverse event. Of placebo-using patients, 24.2% experienced a serious adverse event.

Nabiximols can be beneficial in the treatment of the refractory pain of patients with cancer. This study represents a start in regard to discovering the optimum dose effect and safety of nabiximols. In this study, low to medium doses were associated with the greatest effect.

• The study lacked dose individualization; therefore, the study cannot provide the most accurate picture of analgesic efficacy or side effects.
• The opioid-sparing effect could not be evaluated.
• Investigators might have avoided adverse events by lowering the dose of opioid.
• Reporting regarding sleep disruption could have been stronger if the study had used a validated tool.
• Authors provided no analysis of differences regarding breakthrough pain or total opioid doses between groups.
• According to the authors' power calculations, the study was underpowered and intention-to-treat analysis using last result forward could have had over- or underestimated effects.

This study affects nursing by providing a potential treatment option for patients with opioid-refractory pain. Nurses should be able to recognize opioid-refractory patients. Nurses should be educated regarding this novel cannabinoid treatment, its administration, and its side effects. Nurses should be able to teach patients how to use nabiximols. 

The study was conducted to evaluate the need of patients with breast cancer for neuropsychological rehabilitation after adjuvant chemotherapy. It also sought to determine the effectiveness of differentiated training programs after completion of treatment.

Participants were randomly assigned to one of two intervention groups. Control participants were selected from the “time-out” phase of the study when no training was being offered.

Both intervention groups took part in four one-hour training sessions per week during their inpatient stay. Participants were randomized to one of the following outpatient interventions.

1. Neuropsychiatric Training Group (NPT). A maximum of eight participants met with a specialized occupational therapist to work on improving attention and memory through situations specifically designed to reflect the demands of everyday life. They received practice in compensational strategies and specific techniques to improve their performance in these everyday situations, and reflected on their personal experiences.
2. Computer-based training (PC). Participants received individualized computer-based training with continuous therapeutic supervision. The software addressed specific attention and memory dimensions in eight modules. Following the PC training, participants also received individualized coaching according to their specific impairments.

Measures were completed upon admission to the rehabilitation unit (T1), at the end of in-patient rehabilitation (T2), and six months later on an outpatient basis (T3). 

• The number of participants was 90.
• All participants were female.
• All participants had breast cancer, with an average of 9.01 months since diagnosis and 2.06 months since the conclusion of chemotherapy.
• There were 33 participants in the NPT intervention group, 32 in the PC intervention group, and 25 in the control group.
• The average participant age was 49.19 ± 7.71 years.
• 16.7% of participants had a university degree, with only 3.1% not professionally trained.
• Participants were predominately receving chemotherapy with anthracyclines; most had postoperative localized radiation therapy and adjuvant antihormonal therapy.
• Individuals were exclused from the study if they were older than 64 years; had psychiatric mental health disorders or other cancer, psychiatric, or neurologic problems; or were currently using psychoactive medications.

The study took place at the Tumor Biology Center Rehabilitation Unit in Freiburg, Germany.

The study utilized a randomized, controlled trial.

• Questionnaire of Self-Perceived Deficits in Attention (FEDA) for attention
• Test Battery for Attentional Performance (TAP) for attention
• Digit Span for attention
• Wechsler Memory Scale-Revised for memory
• Rivermead Behavoral Memory Test (RBMT) Immediate and Delayed Story Recall for memory
• Learning and Memory Test (LGT-3) for memory
• Multidimensional Fatigue Inventory (MFI) for mental fatigue, activity, and motivation
• Hospital Anxiety and Depression Scale (HADS) for anxiety and depression
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - 30 (EORTC QLQ-30) for global and functional quality of life. The EORTC QLQ-30 uses six subscales (global, physical, role, cognitive, emotional, social functioning). Scores range from 0–100, with higher scores indicating higher quality of life.

No intervention effects were noted in this study. Significant improvement was noted in 11 of 16 neuropsychiatric parameters for all three groups between T1 and T2. Forty participants (44.4%) maintained at least one cognitive deficit at five months; 19 (21.1%) maintained two or more deficits at T3.

Both intervention groups received similar amounts of training sessions. Eighty-four participants (87.5%) had at least one impaired neuropsychological parameter and 54 (56.2%) had two or more at baseline.

No significant differences in cognitive ability between treatment groups were reported.

• The study lacked a clear description of the PC intervention.
• The use of an inpatient setting and the timing of interventions may have affected the outcome.
• The study did not address practice effects with repeated testing over time.