STUDY PURPOSE: Evaluate benefits of MBSR on psychological distress

TYPE OF STUDY: Meta analysis and systematic review

DATABASES USED: PubMed, EMBASE, and Cochrane Central Register from inception to June 2014

INCLUSION CRITERIA: RCT; comparison of MBSR to usual care; breast cancer; measures psychological outcomes such as anxiety, depression, or stress

EXCLUSION CRITERIA: Other types of cancer; did not use MBSR; unpublished

TOTAL REFERENCES RETRIEVED: 323

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Risk of bias assessment according to the Cochrane handbook. Five studies included were not RCTs, despite this as an inclusion criteria. Only one study showed appropriate randomization and was blinded. Non-RCTs were all high risk of bias.

FINAL NUMBER STUDIES INCLUDED: 8

TOTAL PATIENTS INCLUDED IN REVIEW: 964

SAMPLE RANGE ACROSS STUDIES: 13-336

KEY SAMPLE CHARACTERISTICS: All were women with breast cancer

PHASE OF CARE: Not specified or not applicable

Six studies (536 patients) recorded a significant effect on depression (MD = 5.09, p < 0.00001). Four of these studies were pre-/post-test design studies.  Four studies showed a significant effect on anxiety with MBSR (MD 2.79, p < 0.0001). Four studies investigated long-range results from 1 to 24 months. Two showed sustained effects of MBSR at 12 and 24 months.

MBSR is effective for reducing anxiety and depression among women with breast cancer.

• Limited search
• Limited number of studies included
• Mostly low quality/high risk of bias studies
• Low sample sizes
• It is not clear if all studies used traditional MBSR or the more recently seen shortened version of the intervention. Despite an inclusion criteria of RCT, the majority of studies included were not RCTs.

MBSR can be helpful for patients to reduce anxiety and depression. There is some debate about the best form of delivery and full content of MBSR interventions. Additional research is needed to determine if delivery of the intervention for self care via CD or DVD or via Internet applications is effective. Additional research is also needed to determine if shortened interventions that do not include a retreat are as effective, since the time commitment and cost of a retreat may be prohibitive in some cases.

STUDY PURPOSE: To synthesize the evidence regarding immediate and sustained effects of hypnosis on anxiety in patients with cancer

TYPE OF STUDY: Meta analysis and systematic review

DATABASES USED: Scopus, Medline, PsycINFO, Academic Search Premier, CINAHL, and SDOL

INCLUSION CRITERIA: Hypnosis used as intervention, children or adults with cancer, sufficient data for meta analysis, anxiety was an outcome variable

EXCLUSION CRITERIA: Hypnosis combined with another psychological intervention, comparison of different types of hypnosis

TOTAL REFERENCES RETRIEVED: 1,483

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Assessment of quality based on the Cochrane guidelines for RCTs. 13 studies were RCTs and 7 were quasi-experimental design

FINAL NUMBER STUDIES INCLUDED: 20 

TOTAL PATIENTS INCLUDED IN REVIEW: 878

SAMPLE RANGE ACROSS STUDIES: 25-87

KEY SAMPLE CHARACTERISTICS: The majority of studies were in breast cancer survivors; 6 studies were in children

Across all 20 studies, the immediate effect size was significant in favor of hypnosis (Hedges g = 1.05, p < 0.01). There was also significant heterogeneity. The sustained effect size was also significant in favor of hypnosis (Hedges g = 1.69, p < 0.01) across five studies. Heterogeneity for sustained effects was also significant. Hypnosis was more effective when it combined therapist delivery with self-hypnosis than self-hypnosis only. Higher effect sizes were seen in studies of children, with procedure-related anxiety and studies with RCT design. Analysis suggested publication bias, and showed that smaller studies tended to report more positive results. With adjustment for bias, the effect size was reduced from 1.05 to 0.46.

Hypnosis can be beneficial to manage anxiety among patients with cancer. Therapist delivered alone or in combination with self-hypnosis was more effective than self-hypnosis alone.

• Limited number of studies included
• High heterogeneity
• Low sample sizes
• Varied timing, method of delivery and measurement of outcomes. Sample was too small to do relevant subgroup analyses

Hypnosis may be a helpful intervention to manage anxiety in adults and children with cancer for short- and long-term effects. Therapist involvement was more effective than self-hypnosis alone. For patients with significant anxiety, this may be an intervention to be considered.

To compare the effects of self hypnosis, yoga, and cognitive-based therapy (CBT) on psychological and sleep patient outcomes

Women with non-metastatic breast cancer selected whether they wanted to participate in groups receiving CBT, self hypnosis, or yoga interventions. CBT included six weekly 90 minute group sessions led by trained psychologists. The yoga intervention included six weekly 90 minute group sessions of Hatha yoga and a DVD for use in home practice. Self-hypnosis sessions were 2 hours every two weeks for 12 weeks in small groups. The intervention included tasks and discussions inspired by CBT, with a 15 minute hypnosis exercise at the end of the session. They also received a CD with hypnosis exercises and homework assignments between sessions.

• N = 99   
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer, about 33% participated during treatment with chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: On average, all had at least a high school education

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

PHASE OF CARE: Multiple phases of care

Prospective, non-random, three-group trial

• Hospital Anxiety and Depression Scale
• EORTC-QLQ-C30
• Mental adjustment to cancer scale
• Insomnia Severity Index
• Self-report of frequency of practice of interventions provided

The majority of patient selected the hypnosis intervention. Anxiety and depression declined significantly in the yoga and hypnosis groups (p < 0.05). Fatigue and insomnia declined in the hypnosis group (p < 0.05). Most attended at least five sessions and practiced at least weekly at home. All three interventions showed medium effect sizes for change in anxiety (Cohen’s d range = 0.57-0.77).

Yoga and self-hypnosis group sessions were associated with decline in anxiety and depression. Self-hypnosis was also associated with improvement in sleep and fatigue scores.

• Small sample (< 100)
• Baseline sample/group differences of import         
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Key sample group differences that could influence results
• Intervention expensive, impractical, or training needs
• Other limitations/explanation:  Only the CBT group did not have any material for home practice.  Sizes of the sample groups were vastly different, with only 10 people in the CBT group.  Though not statistically significant, the effect size for CBT was moderate, suggesting lack of significance was due to the small sample.  There was no differentiation between women currently in treatment and those not in treatment which could influence results -The hypnosis intervention included elements of CBT, so it is difficult to determine to what extent this versus the self hypnosis approach had effectiveness.  Provision of self hypnosis requires availability of appropriately trained providers.

Findings suggest that self hypnosis can be helpful to reduce anxiety, depression and insomnia in women with breast cancer.  If relevant resources are available to clinicians this could be a low risk and beneficial activity for symptom management.

To test the effect of painting art therapy, provided by a dedicated professional artist, on quality of life and anxiety and depression levels in patients receiving chemotherapy

Patients receiving treatment at an outpatient chemotherapy unit were recruited into the study for 12 weeks. Patients were classified by their exposure to the Painting Art Therapy Program (PATP). One group had prior exposure the the second did not. The third group were patients who declined participation and they were considered the control group. The study investigator who is an experienced art therapist conducted the therapy. Patients participated in watercolor painting and a discussion about the symbolic nature of the paintings, feelings, and thoughts. The investigator artist provided introduction to watercolor. During the chemotherapy infusion, the patient made watercolor paintings. After completions of the painting, patients discussed the meaning and subject of their painting. Patients in the intervention group were also given painting materials for home practice.

• N = 97 (65 in the PATP group and 32 in the control group)    
• AGE: Mean = 50.6 years (range = 22-73)
• MALES: 35%  
• FEMALES: 56%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: 54% metastatic cancer
• OTHER KEY SAMPLE CHARACTERISTICS: In the intervention group, 26 had prior exposure to PATP and 22 did not. The authors did not define what "prior expose" included.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Antalya, Turkey

PHASE OF CARE: Active anti-tumor treatment

Comparative prospective study

• EORTC-QLQ-C30 questionnaire
• Anxiety and depression scores (HADS)
• Analysis of variance (ANOVA) with Bonferroni correction
• Number of paintings finished by a patient (proxy motivation indicator)

All patients reported liking the PATP to some extent. Change in global quality of life and depression scores differed significantly among the three groups (F = 7.87, p = 0.001; and F = 7.8, p = 0.001).  Correlates of change in depression were participation in PATP (F = 7.75, p < 0.001) and baseline depression scores (F = 17.71, p < 0.001). Predictors of the magnitude of change and change in depression were participation in PATP. Patients who had poorer well being showed better improvements by participating in PATP.  Previous exposure to PATP appeared to diminish the benefit obtained by PATP.

The authors showed improved quality of life and relief from depression in patients with the utilization of PATP. They authors demonstrated that watercolor can be an important form of art therapy in maintaining quality of life in patients with cancer. The application is feasible in the outpatient clinic. Patients demonstrated benefit of PATP in close relationship with basal global quality of life and depression scores. Because art is subjective, other forms of art therapy may target different patients more specifically.

• Small sample (< 100)
• Baseline sample/group differences of import
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results

Art therapy can be an important and feasible intervention for patients on active treatment. Participation in art therapy while receiving chemotherapy treatment can improve quality of life and contribute to decreased depression.

To determine the effect of drawing and writing technique on the anxiety level of children treated for cancer during hospitalization.

A five-day therapeutic program to reduce anxiety of children in treatment for cancer was implemented to understand the effect of continuous therapeutic play. Drawing, writing, and mutual storytelling techniques were pre-arranged in the child’s room. Drawing supplies were given to the children. The State Anxiety Inventory was administered on the first day. Drawing was implemented on the first and third days. Children were asked to draw a picture of a child in the hospital and to write a self-created story with a beginning, a middle, and an end about his or her drawing. Mutual storytelling was implemented on the second and fourth days. While listening to the story of the child, the researcher analyzes the themes and psychological meaning for the child. The researcher responds with a story that is similar but has a more positive ending. On the fifth day, the State Anxiety Inventory is administered for the second time.

• N = 30   
• AGE: Mean = 12.56 years (range = 9-16)
• MALES: 7 (23%)  
• FEMALES: 23 (77%)
• CURRENT TREATMENT: Chemotherapy, combination radiation therapy and chemotherapy
• KEY DISEASE CHARACTERISTICS: Leukemia, solid tumor, lymphoma
• OTHER KEY SAMPLE CHARACTERISTICS: Had received two or more courses of chemotherapy; child and parent consent to participation

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Gazi University, Ankara, Turkey

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Pediatrics

Quasi-experimental (pre- and postintervention evaluations of a single group)

• Descriptive data collection
• State Anxiety Inventory
• Wilcoxon test

The five-day program was evaluated on the first and fifth day. The State Anxiety Inventory mean score (38.63 [SD = 4.38]) for children after the intervention decreased when compared to the mean beginning score (42.63 [SD = 4.64])  (Z = -4.57, p < 0.05). Only 2 of the 30 children wanted to keep the drawings after the intervention.

Drawing and writing and mutual storytelling techniques can be used to reduce the anxiety levels of children in treatment for cancer. The five-day program time interval and intervention could be implemented in future research.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• Other limitations/explanation: No information was provided on who implemented the writing and drawing program, although there is a mention of nursing staff or the "researcher" doing this but it was not made clear who this was and what training he or she had.

Writing and drawing can enable children to express their emotions and fears in an artistic format. Nurses should use these techniques to help uncover the hospitalized child’s anxiety. Training for interpretation and projective techniques in therapeutic communication with children would be helpful in hospital settings.

To examine the effects of yoga on shoulder and arm pain, quality of life (QOL), depression, and physical performance in patients with breast cancer

A 10-week Hatha yoga program was evaluated in this study. Hatha yoga is a mind-body exercise program of breathing exercises, flexibility, and relaxation components. The program in this study was supervised by a certified trainer and the session was taught at a beginner level. Sessions lasted one hour and were offered two days per week. All study participants (intervention and control) received education about cancer, lymphedema, and coping with ADLs. This included a booklet with information on exercises to stimulate lymph circulation. All participants were asked to practice these exercises twice a day.

• N = 42   
• AGE: Mean age = 51.9 years
• FEMALES: 100%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Study participants had completed breast cancer treatment and had no evidence of disease. 
• OTHER KEY SAMPLE CHARACTERISTICS: Study participants had not participated in a regular exercise program in the past six months.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: An academic medical center in Turkey

PHASE OF CARE: Transition phase after active treatment

Randomized controlled trial (RCT) with a usual care control group. Study outcomes were assessed by personnel blinded to the study assignment.

Visual analog scale for pain, European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) questionnaire, Beck Depression Inventory, 6-minute walk test, and evaluation of lymphedema. Measures were completed pre- and post-treatment. Study measures were also completed at 2.5 months post-treatment, but because most of the control group did not show up for their follow-up visit, data for the control group were not included in the analysis.

The two study groups did not differ significantly on demographic characteristics, types of breast cancer treatment, and baseline study measure scores. The yoga group demonstrated a significant improvement in pain severity from baseline to post-treatment for shoulder (p = 0.01) and arm (p = 0.01) pain; however, there was no significant difference between the yoga and control groups in regard to pre- and post-treatment pain. The yoga group’s improvement in pain severity was maintained at 2.5 months post-treatment (p = 0.01). There was no difference in depression, 6-minute walk, and QOL scores between groups from baseline to post-treatment. The yoga group demonstrated significantly improved QOL from baseline to 2.5 months post-treatment for functional (p = 0.01) and symptom (p = 0.03) scores, and improvement in their 6-minute walk time (p = 0.04). No evidence of worsening of lymphedema was found in either study group.

It is unclear if the yoga intervention truly relieved the shoulder and arm pain of the women with breast cancer since the control group also experienced a decrease in pain severity from baseline to 10 weeks. Shoulder and arm pain may normally decrease over time for this patient population. However, the Hatha yoga program appears to be a safe intervention which could be recommended if patients are interested in pursuing it.

• Small sample (< 100)
• Other limitations/explanation: The control group did not complete the 2.5 month follow-up questionnaires, so there is no comparison group for the yoga group findings at this time point.
   

Although Hatha yoga was not found to be more effective than usual care in relieving shoulder and arm pain, it appears to be a safe form of exercise. In addition, women in this study liked it as evident by the 95.5% adherence rate. Nurses should have an understanding of Hatha yoga so, if patients ask about it, they can explain that it is a safe form of exercise but its effectiveness in relieving pain needs to be studied further.

To determine whether performing a preoperative ultrasound-guided transversus abdominis plane block is an effective pain control measure for laparoscopic surgery for colorectal cancer.

After anesthesia induction, the patient received 0.5 ml/kg of either 0.25% bupivacaine or normal saline, depending on their predetermined group assignment. Pain was assessed at rest and when coughing 1 hour after surgery, on post-op day 1, post-op day 2, and post-op day 3.

• N = 55   
• AGE: 20-80 years old
• MALES: 67%  
• FEMALES: 33%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Colorectal cancer 
• OTHER KEY SAMPLE CHARACTERISTICS: Laparoscopic surgery for colorectal cancer pain

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: National Cancer Center, Korea

• PHASE OF CARE: Diagnostic
• APPLICATIONS:  Elder care, palliative care

Randomized, double-blind, placebo-controlled trial

Pain was measured using the numeric rating scale (NRS). Cumulative opioid use was recorded from post-anesthesia recovery, post-op day 1, post-op day 2, and post-op 3.

Insignificant differences between the treatment group and control group exists when comparing post-op pain and opioid use.

When comparing the treatment group and control group, the differences in the postoperative pain assessments was not significant enough to support that receiving a transversus abdominis plane (TAP) block provides superior benefits.

Small sample (< 100)

The purpose of this study was to determine whether performing a preoperative ultrasound-guided transversus abdominis plane block is an effective pain control measure for laparoscopic surgery for colorectal cancer. No differences were seen between the treatment and control group. Based on this study a transversus abdominis plane block requires additional research prior to being recommended in this indication.

To determine if using a different morphine amount in a morphine/bupivacaine combination would be more effective in pain management in patients after a radical mastectomy for breast cancer.

Registered clinical trial with 90 patients allocated to receive 10 ml plain bupivacaine 0.5% plus either 5, 10, or 15 mg morphine diluted with saline 0.9% to 20 ml and topically to mastectomy site prior to closing. The three groups were compared for the following: time to first postoperative analgesia; IV patient-controlled analgesia (PCA) morphine consumption; pain scores; hemodynamics; sedation; adverse events in first postoperative 48 hours; and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scores in first and third postoperative months. Each patient participated in two study phases: an initial two-day treatment phase (48 hours post-op), phase 1, followed by a one- and three-month follow-up, phase 2. All clinical staff and patients were blinded to treatment group assignment.

• N = 90   
• AGE: Mean = 50.8 years (SD = 7.73) (morphine 5 mg: 50.43, SD = 7.84; morphine 10 mg: 49.83, SD = 7.78; morphine 15 mg: 52.13, SD = 7.65)
• FEMALES: 100%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Assiut University, Assiut, Egypt

PHASE OF CARE: Active anti-tumor treatment

Prospective, randomized, double-blind comparative study.

Visual analog scale (VAS), analgesia time, cumulative morphine consumption in first 48 hours, LANSS pain scale

There was a significant difference in analgesia-free time between the three groups. Morphine 15 mg had no patients requiring postoperative analgesics in the first 48 hours compared to 8 patients (27%) in the morphine 10 mg group and 19 patients (63%) in the morphine 5 mg group (p < 0.002). Regarding the time to analgesia use, the morphine 5 mg group was 7.31 hours (SD = 3.12) versus 14 hours (SD = 3.54) in the morphine 10 mg group (p < 0.000).

The morphine 15 mg group had the lowest LANSS recorded score in the first postoperative month when compared to the morphine 5 mg and 10 mg groups (1.1 [SD = 0.37] versus 5.76 [SD = 3.26] versus 4.73 [SD = 2.87], respectively) (p < 0.0001).

The increase in topical morphine (specifically up to 15 mg) in combination with bupivacaine, when compared to lower doses of morphine, has shown a decrease in postmastectomy pain through the reduction of analgesic use within 48 hours after surgery as well as lower LANSS scores within the first postoperative month.

• Small sample (< 100)
• Risk of bias (no control group)

15 mg topical morphine with bupivacaine may decrease postoperative pain and reduce the rate of PMPS.

To compare the efficacy of tetrodotoxin (TTX) to placebo in patients with pain secondary to advanced cancer or treatment related to treatment of advanced cancer.

Patients with moderate to severe cancer pain for at least two weeks or longer were randomized to receive a dose of TTX 30 µg or placebo twice daily at least six hours apart for four consecutive days. Participants were then seen on days 5, 8, and 15 in clinic for safety and efficacy evaluations and then on a weekly basis for evaluation by phone or in clinic until pain returned to baseline level.

• N = 165 (intent to treat, N = 149)
• AGE: 25-84 years
• MALES: 43%  
• FEMALES: 57%
• CURRENT TREATMENT: Not applicable, other
• KEY DISEASE CHARACTERISTICS: Any diagnosis of cancer; wide range of solid and other tumors
• OTHER KEY SAMPLE CHARACTERISTICS: Aged 18 years or older, stable baseline pain score greater or equal to 4/10 (worst pain in past 24 hours based on BPI, no greater than a three-point differed between highest and lowest scores, and no greater than 50% change in opioid analgesic use without addition of new analgesic), and all had a history or analgesics and maintained the regimens of opioids and co-analgesics. Exclusions: Clinically relevant hypoxia or history of CO₂ retention, severe renal impairment, prolonged QTc, plan for initiation of a new anticancer therapy, and female with positive pregnancy test.

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Full-service hospital or private clinic in Canada, Australia, or New Zealand

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Elder care, palliative care

Multi-center, randomized, double-blind, placebo-controlled, parallel-design trial

Brief Pain Inventory form completed, patient diary

Clinical benefit of TTX over placebo with estimate effect size of 16.2% (p = 0.046) after adjustment with Holm method, p value was nominally significant for two primary endpoints but not at the prespecified two-side 5% level.  Average analgesic response was 57.6 days with TTX compared to placebo at 9.9 days; however, when pain was combined with QOL, there was not a statistically significant difference between those treated with TTX and those with placebo.

TTX administration provides a potential option for uncontrolled moderate to severe cancer pain in patients with advanced cancer that is a non-opioid. TTX provides a different approach to pain via the mechanism of action. However, this drug does not come without side effects/potential adverse effects and, while clinical significance has been demonstrated, this is a modest benefit. The pain reduction was only nominally statistically significant and because of statistical penalties for multiplicity, the study is not considered statistically positive. Therefore, additional study is needed to determine the usefulness of TTX for clinical practice, particularly in those who require high doses of opioids to manage their pain.

Other limitations/explanation: Conflict of interest: funded by Wex Pharmaceuticals; several doctors received operational funding, Dr. Hagen received honorarium, and some of the authors are employees or consultants for Wex Pharmaceuticals. Patients could be on existing pain regimens, unsure if fixed dosing or not

Patients would have to receive via subcutaneous injection. In the study, there were no fatalities and seemed to have a favorable benefit/risk profile. Non-opioid option, although mishandling could cause devastating consequences (TTX can cause paralysis and be fatal in high doses). Patients on high doses of opioids are poor candidates for TTX.