CRITICALLY APPRAISED PAPER (CAP) Bower, J. E., Crosswell, A. D., Stanton, A. L., Crespi, C. M., Winston, D., Arevalo, J.,... & Ganz, P. A. (2015). Mindfulness meditation for younger breast cancer survivors: A randomized controlled trial. Cancer, 121, 1231 1240. http://dx.doi.org/10.1002/cncr.29194 CLINICAL BOTTOM LINE: Breast cancer is the most commonly diagnosed cancer in women, with approximately 25% of breast cancer cases occurring premenopause. Women emerging from breast cancer treatments may face multiple challenges, including child-rearing and work responsibilities, and are often overcome by symptoms of anxiety and depression. Currently, very few interventions are available to younger women who are dealing with the psychosocial consequences of their cancer diagnosis, and there is a dire need to develop interventions to promote well-being in women with breast cancer. Mindfulness is a holistic intervention that focuses on the intersection of the body and the mind to promote healing. Mindfulness interventions include activities such as yoga, meditation, mindful walks, and group sessions. Mindfulness has been shown to have positive effects on depression and anxiety for survivors of breast cancer, and this research article adds to this literature. One of the trademarks of occupational therapy is its client-centered and holistic approach to patients preventative care to avoid future harm. This study reminds therapists of the importance of consistency and engagement with support groups and daily mindfulness practice for the best results to occur. This study supports the benefits of integrating mindfulness strategies into the treatment plan of breast cancer survivors as they continue their life, so that they will heal psychologically and physiologically. RESEARCH OBJECTIVE(S) List study objectives. To evaluate the feasibility and efficacy of a mindfulness-based intervention for women who had a breast cancer diagnosis at or before the age of 50. The primary outcomes of interest in this efficacy trial were perceived stress and depressive symptoms. Secondary outcomes included behavioral symptoms, cancer-related distress, and positive psychological processes. Furthermore, the effects on inflammatory activity were assessed in particular, proinflammatory gene expression and associated transcription factors. DESIGN TYPE AND LEVEL OF EVIDENCE: 1
Level I: Single-center, two-armed randomized controlled trial SAMPLE SELECTION How were subjects recruited and selected to participate? Please describe. Participants were recruited through physician referrals, the Internet, and invitations to women who had participated in a previous study led by the researchers. Inclusion Criteria Breast cancer diagnosis of Stage 0, I, II, or III at or before 50 years of age, and a completed local or adjuvant cancer therapy (except hormone therapy) at least in the last 3 months and up to 10 years after treatment Exclusion Criteria Breast cancer recurrence, metastasis, or another cancer diagnosis (excluding nonmelanoma skin cancer); active, uncontrolled medical illness that could influence inflammation; or inability to commit to the intervention schedule SAMPLE CHARACTERISTICS N= (Number of participants taking part in the study) 71 #/ (%) Male 0/(0%) #/ (%) Female 71/(100%) Ethnicity White: 76.05%; African American: 2.8%; Asian: 11.26%; other: 9.86% Disease/disability diagnosis Breast cancer survivors INTERVENTION(S) AND CONTROL GROUPS Add groups if necessary Group 1: Mindfulness intervention Brief description of the intervention How many participants in the group? Where did the intervention take This intervention was based on the Mindful Awareness Practices program at the University of California, Los Angeles. It included information about maintaining health and preventing cancer recurrence. This intervention was tailored to younger survivors through the inclusion of information about maintaining health and preventing cancer recurrence. Thirty-nine participants were randomized to the intervention group. Of these, 38 received the intervention (which was defined as attending two or more classes). Thirty-one participants completed the 3-month follow-up questionnaire. Therefore, 8 participants (20.5%) dropped out from intervention start to 3-month follow-up. Outpatient setting as well as home practice 2
place? Who Delivered? How often? For how long? NR Participants met for six weekly, 2-hr group sessions that included lectures, discussions, and group sessions. Also, participants practiced a mindfulness technique at home, starting at 5 min daily and increasing to 20 min daily by the end of the intervention period. 6 weeks + 3 months follow-up time = 18 weeks total Group 2: Wait-list control Brief description of the intervention How many participants in the group? Where did the intervention take place? Who Delivered? How often? For how long? A wait-list control group allowed the researchers to control for naturally occurring changes in stress and other outcomes over the study period. Those assigned to the control group were offered the opportunity to participate in the intervention (Mindful Awareness Practices classes) after the completion of the 3-month follow-up period. Thirty-two participants were randomized to the wait-list control group. A total of 4 participants (12.5%) were lost to follow-up, which resulted in 28 participants in the control group. NR N/A N/A 6 weeks + 3 months follow-up time = 18 weeks total Intervention Biases: Check yes, no, or NR and explain, if needed. Contamination: NR Comment: Co-intervention: NO Timing: Comment: Comment: The in-person assessments were conducted before and within 1 2 weeks after the intervention, which suggests that not all participants were assessed within the same time frame pre- and postintervention. 3
Site: Comment: Site bias could have resulted from the portion of the intervention that took place in the home. Participants had different homes and varying family sizes, and because of this, the daily mindfulness exercises could have been negatively affected by noise, interruption, or other distraction. Use of different therapists to provide intervention: NR Comment: The article did not comment on the number of therapists who facilitated the Mindful Awareness Practices program. MEASURES AND OUTCOMES Complete for each measure relevant to occupational therapy: Measure 1: Name/type of Blood samples measure used: What outcome To examine genomic and circulating markers of inflammation was measured? Is the measure NR reliable? Is the measure valid? NR When is the Baseline, postintervention, and at the 3-month follow-up assessment measure used? Measure 2: Name/type of measure used: What outcome was measured? Is the measure reliable? Is the measure valid? When is the measure used? Self-report questionnaires The primary and secondary outcomes NR NR Baseline, postintervention, and at the 3-month follow-up assessment Measurement Biases Were the evaluators blind to treatment status? Check yes, no, or NR, and if no, explain. 4
NR Comment: The article does not report whether evaluators were blind to treatment status when examining the blood sample results. Recall or memory bias. Check yes, no, or NR, and if yes, explain. Comment: Recall bias is a possibility in this study, given the nature of the self-report questionnaires. Mental health is a sensitive topic, and, as such, the participants might not have been truthful about the extent of their symptoms. In hoping for a reduction of symptoms after completing the intervention, the participants might have inadvertently recorded their symptoms incorrectly, creating this bias. Others (list and explain): RESULTS List key findings based on study objectives Include statistical significance where appropriate (p<0.05) Include effect size if reported The mindfulness intervention did lead to statistically significant reductions in perceived stress from preintervention to postintervention relative to the wait list (p =.004 for Group Time interaction). Similarly, there was a trend toward improvement of depressive symptoms, although this was not significant (p =.095). The effect sizes for changes in perceived stress and depression were.67 and.54, respectively. At the 3-month follow-up assessment, there was a significant group difference for fear of recurrence (p =.048 for Group Time interaction). Additionally, participants who practiced mindfulness more frequently had lower levels of IL-6 (marker of inflammation in the blood) at the postintervention than participants in the wait-list group (p =.025). The mindfulness intervention also led to significant changes in secondary outcomes. Fatigue (p =.007), subjective sleep disturbance (p =.015), and hot flashes and night sweats (p =.015) showed significant improvements from preintervention to postintervention relative to the control group. Additionally, the secondary outcomes of peace and meaning (p =.001) and positive affect (p =.03) showed a significant increase as a result of the mindfulness intervention. Further analysis of the blood samples, with TELiS promoter-based bioinformatics, found reduced activity of NF-kB (p =.0016), which is a proinflammatory transcription factor. This analysis also showed increased activity of anti-inflammatory glucocorticoid receptors (p =.018). Was this study adequately powered (large enough to show a difference)? Check yes, no, or NR, and if no, explain. NO Comment: The study was not adequately powered; the article admits that a limitation of this study is the relatively small sample size. The authors 5
estimated that a sample size of 40 participants for the intervention group and 30 for the control group was necessary for the study to be adequately powered. By the authors calculation, this study was not adequately powered, because the intervention group ended up with 31 participants and the control group with 28. Were appropriate analytic methods used? Check yes, no, or NR, and if no, explain. Comment: Were statistics appropriately reported (in written or table format)? Check yes or no, and if no, explain. Comment: All statistics were listed in a table format, and those that were relevant to the study discussion were also reported in written format. Was the percent/number of subjects/participants who dropped out of the study reported? Limitations: What are the overall study limitations? Limitations include a relatively small sample size and the short duration of the study. Another limitation of this study is its generalizability. The ethnic characteristics of this study were approximately 76% White, and, as such, the mindfulness intervention might not have the same effect on other ethnic groups. CONCLUSIONS State the authors conclusions related to the research objectives. The authors conclusions were that the mindfulness intervention resulted in significant improvements in perceived stress and a trend toward improvement of depressive symptoms (although not significant). Additionally, the secondary outcomes of fatigue, sleep disturbance, menopausal symptoms, and positive psychological processes showed improvements. The authors also found that the mindfulness intervention reduced inflammatory gene expression and signaling. It is important to note that the relationship between the inflammatory marker, on the one hand, and anxiety and depressive symptoms, on the other, was not necessarily causal, given that there is no way to measure that specifically. However, previous studies have shown them to be correlated, and this study draws that conclusion as well during its analysis. The authors conceded that previous randomized controlled trials on this topic have shown similar results regarding the primary outcomes of this study, but they noted that this study is the first trial to demonstrate the effect of mindfulness in regard to the markers of inflammation. The authors concluded that mindfulness had the above significant effects but that they might have been acute, because persistence of the effects postintervention was less 6
clear. It is unknown why the improvements found postintervention were not sustained at follow-up, except for the outcome of cancer-specific distress. The authors wish to study these nebulous follow-up results further, in a larger sample size and for a longer study duration. It is important for additional studies to examine the implications of this study further, with a larger sample size, to care for the mental health of this population of women who have decades of life after cancer ahead of them. This work is based on the evidence-based literature review completed by Lauren Hastings, OTS, and Sarah-Jeanne Salvy, PhD, faculty advisor, University of Southern California. CAP Worksheet adapted from Critical Review Form Quantitative Studies. Copyright 1998 by M. Law, D. Stewart, N. Pollack, L. Letts, J. Bosch, and M. Westmorland, McMaster University. Used with permission. 7