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Effectiveness of energy healing on Quality of Life: A pragmatic intervention trial in colorectal cancer patients
Accepted Manuscript Title: Effectiveness of energy healing on Quality of Life: A pragmatic intervention trial in colorectal cancer patients Author: Christina Gundgaard Pedersen Helle Johannessen Jacob V.B. Hjelmborg Robert Zachariae PII: DOI: Reference:
S0965-2299(14)00060-0 http://dx.doi.org/doi:10.1016/j.ctim.2014.04.003 YCTIM 1334
To appear in:
Complementary Therapies in Medicine
Received date: Revised date: Accepted date:
23-8-2013 7-3-2014 24-4-2014
Please cite this article as: Pedersen CG, Johannessen H, Hjelmborg JVB, Zachariae R, Effectiveness of energy healing on Quality of Life: a pragmatic intervention trial in colorectal cancer patients., Complementary Therapies in Medicine (2014), http://dx.doi.org/10.1016/j.ctim.2014.04.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title page Effectiveness of energy healing on Quality of Life: a pragmatic intervention trial in colorectal cancer patients.
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Christina Gundgaard Pedersen, Post Doctoral fellow., MSc., PhD1, Helle Johannessen, Professor, mag.scient., PhD2, Jacob v. B. Hjelmborg3, Associate Professor, MSc, PhD, Robert Zachariae,
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Professor, MSc, MDSci 1
Unit of Psychooncology and Health Psychology, Department of Oncology, Aarhus University
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Health, Man and Society, Institute of Public Health, University of Southern Denmark, J.B.
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Winsløws Vej 9B, 5000 Odense C, Denmark
Department of Biostatistics, Institute of Public Health, University of Southern Denmark,
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Hospital & Department of Psychology, Aarhus University, Bartholins Allé 9, 8000 Aarhus C
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J.B.Winsløws Vej 9B, 5000 Odense C, Denmark
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Corresponding author: Christina G. Pedersen, Ph.D., MSc., Post Doc., Unit of Psychooncology and Health Psychology, Department of Oncology, Aarhus University Hospital & Department of Psychology, Aarhus University, Bartholins Allé 9, 8000 Aarhus C, Denmark. E-mail: [email protected] Phone: +45 87 16 58 79.
Financial support was provided by The Danish Council for Strategic Research, Ministry of Science, Innovation and Higher Education (Grant no. 09-065176); Department of Psychology and Behavioral Sciences, University of Aarhus; and the Institute of Clinical Research and Institute of Public Health, University of Southern Denmark. The funding sources had no involvement in the study design, collection, analysis, and interpretation of data, or writing of the paper.
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Abstract Purpose: Our aim was to explore the effectiveness of energy healing, a commonly used complementary and alternative therapy, on well-being in cancer patients while assessing the
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possible influence on the results of participating in a randomized controlled trial.
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Methods: 247 patients treated for colorectal cancer (response rate: 31.5%) were either a)
randomized to healing (RH) or control (RC) or b) had self selected the healing (SH) or control
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condition (SC), and completed questionnaires assessing well-being (QoL, depressive symptoms, mood, and sleep quality), attitude towards complementary and alternative medicine (CAM), and
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faith/spirituality at baseline, 1 week, and 2 months post-intervention. They also indicated, at baseline, whether they considered QoL, depressive symptoms, mood, and sleep quality as important
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outcomes to them.
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Results: Multilevel linear models revealed no overall effect of healing on QoL (p=0.156),
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depressive symptoms (p=0.063), mood (p=0.079), or sleep quality (p=0.346) in the intervention groups (RH, SH) compared with control (SC). Effects of healing on mood were only found for
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patients who had a positive attitude towards CAM and considered the outcome in question as important (SH: Regression coefficient: -8.78; SE: 2.64; CI: -13.96- -3.61; p=0.001, and RH: Regression coefficient -7.45; SE: 2.76; CI: -12.86- -2.04; p=.007). Conclusion: Whereas it is generally assumed that CAMs such as healing have beneficial effects on well-being, our results indicated no overall effectiveness of energy healing on QoL, depressive symptoms, mood, and sleep quality in colorectal cancer patients. Effectiveness of healing on wellbeing was, however, related to factors such as self-selection and a positive attitude towards the treatment.
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Introduction The possible effects of so-called “energy healing” have been the subject of much public and scientific debate (1;2), and energy healing is one of the most prevalently used types of
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complementary and alternative medicine (CAM) among cancer patients (3). Although there is no scientific evidence to support its efficacy against the disease itself, healing is often assumed to have
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a beneficial effect on quality-of-life (QoL). However, only few studies have been conducted of the
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effect of energy healing on cancer-related symptoms and well-being, and - due to limited methodological quality and small sample sizes - the available studies do not allow for reliable
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conclusions (4).
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A systematic review of 8 non-randomized and 9 randomized controlled trials of so-called distant healing concluded that there was “no evidence against the notion that distant healing is more than a
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placebo” (1). This conclusion is supported by further research, e.g. by Pohl and colleagues, who
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conducted a single-blinded randomized trial with 80 patients with advanced cancer to determine the
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influence of ‘laying on of hands’ healing on well-being (5). Although a significant improvement of cancer- or cancer-treatment-related symptoms was found, there were no differences in effect between the self-declared healer and an actor, who provided “sham treatment”.
In line with findings from placebo research, it has been suggested that patients’ beliefs and attitudes are the main factors driving the effects of CAM (6). The convictions and positive expectations believed to be associated with the placebo effect have been found to alter neurochemical patterns, including endogenous opioids and pain-modulating interconnections (7), involving key areas of the brain responsible for physical and psychological pain (anterior cingulate cortex), pleasure (basal nuclei), and movement (striatum) (6). A positive attitude towards massage has, for example, been found to increase the effect of massage on cancer-related fatigue (8). Taken together, however, the 3 Page 3 of 29
available results are inconsistent (9). Another possible moderator could be the religious/spiritual faith of patients. Faith in God or a spiritual power has previously been associated with increased use of both CAM in general and healing in particular (10;11), but no studies so far have sought to
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explore faith as a possible moderator of the effect of healing.
Some researchers have voiced their concern that, although being the Gold Standard in clinical
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research, traditional RCTs may not be externally valid, the main reason being that the results cannot
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be generalized to the general population, which includes people with strong treatment preferences (12-14). A systematic review of 32 medical and psychological studies employing one of two types
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of combined designs (1: randomization into randomization or no-randomization group, or, 2: randomization or self-selection group for those refusing randomization) found, however, that
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outcome differences between randomized and self-selection groups were relatively small and inconsistent in direction (15). The individually perceived relevance of the outcomes assessed may
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be yet another potential moderator. Previous reports of qualitative observations of energy healing
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suggest that healing interventions are highly individualized and the outcomes personalized (16;17).
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A pragmatic research methodology that takes individualization into account and considers the individually perceived importance of the outcomes as a moderator, thus appears relevant. The socalled “Cohort multiple randomized controlled trial design” proposes that a large observational cohort of patients with the condition of interest is recruited, outcomes regularly measured, and participants for intervention trials randomly selected based on the cohort (18). So far, however, no controlled studies have sought to investigate the effectiveness in a pragmatic trial of energy healing in both a randomized and self-selected group of participants to explore if effectiveness depends on individual characteristics associated with self-selection.
Taken together, little is presently known about the effectiveness of healing on well-being among cancer patients and the potential moderators of this effect. Thus, as part of the CCESCAM protocol 4 Page 4 of 29
having the primary purpose of developing guidelines and exploring effect of energy healing on personalized outcomes, our aim was to explore the effectiveness of energy healing on the following secondary outcomes: 1) cancer-related Quality of Life (QoL), 2) depressive symptoms, 3) mood, and 4) sleep quality among patients treated for colorectal cancer while assessing the possible
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influence on the results of participating in a randomized controlled trial. This was done using a
pragmatic trial study design aimed at maximizing internal and external as well as ecological validity
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by randomizing a population-based sample of colorectal patients recruited from two major regions
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in Denmark to two groups: One to be randomized to intervention or control, and one to a group selfselecting the healing or control condition. Based on the results of a pilot study, no main effects of
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healing on any of the secondary outcome measures were anticipated. A number of factors were expected to moderate the effectiveness of energy healing including: 1) a positive attitude towards
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CAM, 2) faith in God or a higher spiritual power, and 3) personal prioritization of the outcome of
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Participants
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Methods
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treatment.
A search in the Danish National Patient Registry identified a total of 783 eligible patients. Eligibility criteria were: 1) primary diagnosis of colorectal cancer, defined as C18- C20, according to the International Classification of Diseases (ICD10), 2) completed treatment for colorectal cancer with
intention to cure with surgery or surgery and chemotherapy or radiotherapy in the Southern or Central Region of Denmark between March 1, 2010, and August 1, 2011, and no current cancer, 3) ≤80 years of age. Exclusion criteria were: 1) mentally and cognitively incapable to participate in the study, 2) poor understanding of the Danish language, or 3) in palliative care or cancer recurrence prior to inclusion.
Procedure 5 Page 5 of 29
The study procedure is shown Figure 1. Using a computerized procedure (Minim: Minimization Program for Allocating Patients to Treatments in Clinical Trials), potential participants were, prior to initial contact, first randomized to two arms: Allocation to treatment based on either selfselection (SSA) or further randomization (RA). After inclusion in the study, participants in the RA
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group were then further allocated to treatment or control based on a second randomization
procedure. The randomization was conducted by the first author, who coordinated the database
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management and had no personal contact with the patients.
Eligible patients were mailed written information about the study, a leaflet containing information
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about the healers in the study, an informed consent form, a pre-paid envelope, and Part 1 of a baseline questionnaire package. The accompanying letter differed, depending whether recipients
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were allocated to the self-selection arm or the randomization arm. Recipients in the self-section arm were informed that they could choose between treatments with energy healing and allocation to the
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control group. Recipients in the randomization arm were informed that they would be randomly
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allocated either to receive energy healing or to be in the control group. Participants not receiving the
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energy healing intervention during the trial were offered one free session with an energy healer after trial completion; this offer was accepted by one participant only. Patients willing to participate were instructed to complete the informed consent form (with an indication of two preferred healers) and the enclosed questionnaire package, and return it in the pre-paid envelope. If an eligible patient had not returned the questionnaire within 2-4 weeks, a reminder call was made. If the patient did not respond, he or she was considered a non-responder.
After having returned the informed consent and the Part 1 of the baseline questionnaire, RA participants were further randomized to either intervention (RH) or control (RC), and patients in the SSA were asked to chose self-selected healing (SH) or self-selected control (SC), resulting in a four-arm design. Part 2 of the baseline questionnaire was mailed out after the second randomization 6 Page 6 of 29
procedure prior to intervention start. Additional questionnaires were mailed to participants 8 and 16 weeks after completing the baseline questionnaire, which corresponded to approx. 1 and 8 weeks post intervention.
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Intervention procedure
Participants in RH and SH received four sessions of energy healing at the healer’s clinic over a 2-
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month period as agreed-upon by each participant-healer pair. Healers were identified and recruited
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through a national association of healers (‘Healer-Ringen’). Additional inclusion criteria were: 1) treatment facilities used solely for the practice of healing, and 2) clinic location within the regions of Central and
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Southern Denmark. A total of 31 healers were included. The energy healing provided was not restricted
to a specific form of energy healing, provided that it was based on a general idea of the healer
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providing some type of energy to the participant by the hands. General conversation between the healer and participant was accepted, but no other form of therapy than energy healing was allowed.
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Potential use of other types of CAM during the trial period was recorded in the follow-up
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questionnaire completed approximately 1 week post-intervention.
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(Insert figure 1 near here)
Measures
Outcome measures
Changes in health-related QoL, i.e. physical/functional, psychological, and social and spiritual wellbeing, were assessed using the Danish version of FACIT-sp (19). Depressive symptoms were measured with the Beck Depression Inventory (BDI-II), a commonly used measure in studies of cancer patients both internationally and in Denmark (20;21). Negative mood was measured using the total score of a Danish version of the Brief 37-item version of Profile of Mood States (POMS) validated with cancer patients (22;23). Subjective sleep quality was measured with one item from
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the Pittsburg Sleep Quality Index (PSQI) (24) which has previously been used in studies of Danish patients (25).
Planned moderator measures
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Clinical data, including date of diagnosis and type of treatments received, together with
demographic data (date of birth and gender) were obtained from The National Patient Register.
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Additional socio-demographic information on municipal of residence, civil status, family structure,
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schooling, vocational training, labor market attachment/(early) retirement, and personal and house hold income were obtained via self-report. Attitude towards complementary and alternative
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medicine (CAM) was measured with one question: “What is your attitude towards alternative therapies: Very negative, negative, neutral, positive or very positive?” Faith in God (yes, a little,
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no), faith in a spiritual power (yes, a little, no), and the experienced influence of that faith on QoL and cancer itself (range: 1: no, 2: a little, 3: some, 4: considerably, 5: very much) was measured
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with 4 separate items used in previous studies (10;11). Personal prioritization of preferred outcome
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was measured with the question: “Which of the following topics do you consider most important to
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you right now? Symptoms following your disease (including treatment-related late-effects), physical activity (including coping with daily activities), quality of life (including general well-being), depressive symptoms, mood, sleep quality, economy, or others?”
Ethics
The study adhered to the ethical requirements of the Helsinki Declaration (26). The study protocol was submitted to the regional Committee of Research Ethics in Southern Denmark, was approved by the Danish Data Protection Agency, and the hypotheses were registered in a clinical trial database (ClinicalTrials.gov; NCT01434264) prior to data collection. Participants randomized to the control group were offered to receive the intervention free of charge after the study was completed.
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Statistical analysis Based on the results of a pilot-study, a total of 125 participants were planned to receive healing and 200 to serve as a control group (www.clinicaltrials.org). Statistical power analysis showed that with the planned sample size, it would be possible to detect a change of one point on the protocol’s
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primary outcome scale, Measure Yourself Concerns and Wellbeing (MYCaW) (27), with a 5%
significance level and a statistical power of 80%. MYCaW was not included as an outcome in the
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present analyses and will be reported elsewhere. The modeling of the longitudinal data was based on
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the expectation that the responses of individuals will be correlated over time, i.e, within-individual dependency (28). The estimated variance and within individual correlation over time was based on the
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pilot-study (www.clinicaltrials.gov; NCT01434264).
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The effects were evaluated using linear mixed models with a corrected level of significance (p=0.05/number of outcomes + 1) (29). All interactions between group, time, and putative
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moderators were included in one model. If an interaction was non-significant for any of the
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dependent measures, it was removed from the analysis. Differences in sample characteristics
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between SH and SC as well as between RH and RC were explored using multiple binary logistic regression analysis. All analyses were conducted using SPSS version 19 and STATA version 12.
Results
A total of 247 (response rate 31.5%) men (N=115/46.6%) and women (N=132/53.4%) participated in the study. Participating patients were younger than non-participants, (mean 64.06 and SD 8.84 years vs. 68.42 and SD 8.99 years; range: 29-80 years; t(687)=6.14; p<.001), and an attrition analysis revealed that participants were more likely than non-responders to be women (χ2(1)= 5,258; p=0.022) and to have received oncological treatments other than surgery (χ2(1)= 12,412; p<0.001) (30). 9 Page 9 of 29
As shown in Table 1, participants in the SH group were characterized by being younger, more prone to have a tertiary degree (< master degree), having unambiguous or ambiguous faith in a higher spiritual power, and a more positive attitude towards CAM, compared to SC (OR range: 0.95 -
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13.10; p: 0.02 - 0.001). At baseline, SH participants also exhibited lower QoL, more depressive
symptoms, more negative mood, and poorer sleep quality, compared to SC (OR range: 0.97 – 1.83;
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p: 0.29 – 0.018). A multiple binary logistic regression adjusting for all significant factors associated
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with SH in the unadjusted analysis revealed that SH only differed from SC with respect to ambiguous faith, (OR: 6.07; CI: 1.61-22.93; p=0.008) and a positive attitude towards alternative
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characteristics were found between RH and RC.
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therapies (OR: 4.03; CI: 1.78-9.12; p=0.001) (data not shown). No differences in participant
As shown in Table 1, the majority of participants considered QoL, physical late effects, and
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physical activity (N range: 73 (29.6%) – 26 (10.5%)) as important outcomes, and to a lesser extent
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“other concerns”, depressive symptoms, mood, sleep quality, and financial concerns (N range: 16
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(6.5%) – 7 (2.8%)). In all, 32 patients (13%) did not respond to this question.
(Insert Table 1 near here)
Effectiveness of energy healing on QoL The multilevel linear models revealed no statistically significant effect of healing on QoL for either of the intervention groups (RH, SH) compared to control (SC) (Regression coefficient: -3.27, SE: 2.30; CI:-7.79-1.25; p=0.156). Figure 2 shows the distribution of means across groups over time (higher score = higher QoL). A subset of participants in the self-selected healing group (SH), who had rated QoL as important, reported a borderline statistically significant improvement in QoL 1, week post-intervention, compared with SC, after adjusting for possible confounders, i.e. attitude 10 Page 10 of 29
towards CAM, spiritual faith, and gender (Regression coefficient: 7.68; SE: 3.03; CI: 1.74-13.62; p=0.011). With an unadjusted p-value, this result would have reached statistical significance (p=
(Insert figure 2 near here)
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Effectiveness of energy healing for depressive symptoms
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0.01).
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No overall between-group differences were found for depressive symptoms over time (Regression coefficient: 1.53, SE: 0.82; CI:-0.08-3.13; p=0.063) (See Figure 3; higher score = more depressive
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symptoms). Adjusting for gender and attitude towards CAM, patients in the SH group showed a tendency to experience fewer depressive symptoms compared to SC at the time of follow up
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(Regression coefficient: -2.13; SE: 0.96; CI: -4.02- -0.25; p=0.027) (corrected p=0.01). Prioritizing depressive symptoms as an important outcome did not appear to influence the association between
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participating in SH (Regression coefficient: -1.57; SE: 0.98; CI: -3.49-0.35; p=0.109), RC
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(Regression coefficient: 0.65; SE: 1.01; CI: -1.32-2.63; p=0.516), or RH (Regression coefficient: -
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0.31; SE: 1.03; CI: -2.33-1.69; p=0.760) and depressive symptoms in the multilevel linear models.
(Insert figure 3 near here)
Effectiveness of energy healing on mood Healing was not found to have an overall influence on mood over time (Regression coefficient: 4.41; SE: 2.51; CI: -9.33-0.52; p=0.079) (See Figure 4; higher score = poorer mood). Exploring the role of possible moderators, a subgroup of patients in the SH (Regression coefficient: -8.78; SE: 2.64; CI: -13.96- -3.61; p=0.001) and RH group (Regression coefficient -7.45; SE: 2.76; CI: -12.86-2.04; p=.007) who had a positive attitude towards CAM and prioritized QoL, mood, and other
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concerns as important outcomes, were found to experience an improvement in mood at the time of follow up compared to SC.
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(Insert figure 4 near here)
Effectiveness of energy healing on subjective sleep quality
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No overall influence was found in the multilevel linear models of healing on subjective sleep
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quality (Regression coefficient: -0.09; SE: 0.10; CI: -0.29-0.10; p=0.346) (See Figure 5; higher score = better sleep quality). Prioritizing sleep quality as an important outcome and having a
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positive attitude towards CAM did not influence the association between allocation to intervention group and subjective sleep quality (SH: Regression coefficient: -0.003; SE: 0.12; CI: -0.24-0.24;
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p=.976; RH: Regression coefficient: -0.04; SE: 0.13; CI: -0.21-0.29; p=.766).
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Discussion
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(Insert figure 5 near here)
In accordance with our hypotheses based on a pilot study, we found no overall effect of randomly allocated or self-selected healing on any of the planned outcomes: Cancer-related QoL, depressive symptoms, mood, and sleep quality. Our results suggest that only patients prioritizing the outcome in question and having a positive attitude towards CAM and faith in a spiritual power are likely to experience benefits related to well-being from healing.
This is the first pragmatic trial of the CAM intervention of energy healing comparing the effects between groups of random allocation or self-selection. A common critique of previous research on healing has been that healing is generally not a standardized treatment but targeted individually and therefore should be studied as such to achieve sufficient ecological validity - that is, by 12 Page 12 of 29
approximating the real-world setting of the treatment examined as much as possible (31). In the present study, our first aim was to accommodate this critique, first by letting all participants choose the healer they preferred and second by providing healing under “real-life conditions” in the practitioners’ own clinics. Third, half of the participants were allowed to self-select the intervention
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or control group taking possible individual characteristics associated with self-choice of healing into
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consideration.
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While our study has several strengths, e.g. using a pragmatic trial study design aimed at maximizing internal and external as well as ecological validity, some limitations should also be taken into
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account. Restricting participants not to use other types of CAM during the trial period with the purpose of maximizing internal validity could be argued to be a potential limitation of ecological
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validity, as some participants could have chosen to use several types of CAM under normal, nontrial circumstances. Another possible limitation could be that attitude towards CAM was measured
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in relation to alternative therapies in general and not with specific reference to the intervention
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investigated. Considering that the present study tested hypotheses related to secondary outcomes,
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the primary outcome being the personalized outcome, MYCaW (27), we chose a rather conservative correction of our alpha-level (29). This approach requires considerably more power to detect significant differences, and the relatively low response- and participation rate in the present study meant weaker power than anticipated. Another caution related to the response rate concerns representativity, and the results may not be entirely generalizable to patients treated for colorectal cancer who are older, male, and have received surgery only.
The present findings are in line with a previous study, finding no effect of healing on mood after 4 sessions (32), but in contrast to a culturally common assumption that although healing may not influence the cancer disease directly, there might be positive effects on well-being (4). In the light of previous research on placebo effects and the role of attitudes and beliefs (6;7), we anticipated 13 Page 13 of 29
that a positive attitude towards CAM and faith in God or higher spiritual power would be associated with a larger effect of energy healing. Also, as previous research has suggested that personalized outcomes may be important (33), we also investigated if effectiveness was influenced by the outcome areas considered to be important by the patient. Consistent with a previous study on the
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role of attitude as a moderator (8) and qualitative observations concerning personalized outcomes (16;17), we found that a positive attitude towards CAM and having prioritized mood or QoL as
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important outcome areas were both associated with a more beneficial effect of healing on mood. A
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positive attitude towards CAM was borderline statistically significantly associated with a beneficial influence of healing on QoL, but only among patients who had self-selected healing, had faith in a
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higher spiritual power, and had prioritized QoL as an important outcome topic for them personally. Likewise, in a select group of patients having a positive attitude towards CAM and having self-
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selected healing, a borderline significant trend was found towards an effect of healing on depressive symptoms. In concordance with previous findings (31;33), our results, thus, suggest that it is
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relevant for future research on QoL and mood to consider whether the outcomes in question are
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considered relevant by the participants.
Taken together, the results of the present study suggest that a healing intervention evaluated in a pragmatic trial attempting to maximize ecological validity, while at the same time attempting to ensure internal validity, did not appear to be an effective way to improve QoL, mood, depressive symptoms, or sleep quality in patients having completed treatment for colon or rectal cancer. A select group of individuals who had prioritized the outcome topic in question and who exhibited belief/faith and a more positive attitude towards CAM did experience an effect on mood. In addition, borderline-significant trends were found in select groups for effects on QoL and depressive symptoms, but not sleep quality. The present study suggests that it may be relevant for future intervention research to consider individually prioritized outcomes, self-selection, belief, and attitude towards treatment. 14 Page 14 of 29
Acknowledgements The project was carried out by the CCESCAM group (www.ccescam.dk). Financial support was provided by The Danish Council for Strategic Research, Ministry of Science, Innovation and
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Higher Education (Grant no. 09-065176); Department of Psychology and Behavioral Sciences, University of Aarhus; and the Institute of Clinical Research and Institute of Public Health,
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University of Southern Denmark. The funding sources had no involvement in the study design,
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collection, analysis, and interpretation of data, or writing of the paper. Participating healers were
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identified by a national Danish association for energy healers (“HealerRingen”).
Conflicts of interest
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None to declare.
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months post-surgery in a nationwide cohort study of Danish women treated for early stage breast-cancer. Breast Cancer Res Treat 2009;113(2):339-55.
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(22) Jensen-Johansen M, Christensen S, Valdimarsdottir H, et al. Effects of an expressive writing intervention on cancer-related distress in Danish breast cancer survivors - results from a
M
nationwide randomized clinical trial. Psychooncology 2012;DOI: 10.1002/pon.3193 [Epub
d
ahead of print].
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(23) Cella D, Jacobsen P, Orav E, et al. A brief POMS measure of distress for cancer patients. J
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Chronic Dis 1987;40(10):939-42.
(24) Buysse D, Reynolds 3rd C, Monk T, et al. The Pittsburg Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193-213.
(25) Colagiuri B, Christensen S, Jensen A, et al. Prevalence and predictors of sleep difficulty in a national cohort of women with primary breast cancer three to four months postsurgery. J Pain Symptom Manage 2011;42(5):710-20.
(26) WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. Avalable at: http://www.wma.net/en/30publications/10policies/b3/index.html (accessed 6 january 2013). World Medical Association. 2008. 18 Page 18 of 29
(27) Paterson C, Thomas K, Manasse A, et al. Measure Yourself Concerns and Wellbeing (MYCaW): an individualised questionnaire for evaluating outcome in cancer support care that includedes complementary therapies. Complement Ther Med 2007;15(1):38-45.
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(28) Diggle P, Heagerty P, Liang K, Zeger S. Analysis of longitudinal data. Second edition ed. Oxford: OUP; 2002.
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(29) Davis C. Secondary endpoints can be validly analyzed, even if the primary endpoint does
us
not provide clear statistical significance. Control Clin Trials 1997;18(6):557-60. (30) Techau M, Lunde A, Pedersen C. Attrition and reasons for saying no to participation in a
an
study on energy healing as cancer rehabilitation. Eur J Integr Med 4(1), 180. 2012.
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(31) Sung L, Feldman BM. N-of-1 trials: innovative methods to evaluate complementary and alternative medicines in pediatric cancer. J Pediatr Hematol Oncol 2006 Apr;28(4):263-6.
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(32) Post-White J, Kinney M, Savik K, et al. Therapeutic massage and healing touch improve
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symptoms in cancer. Integr Cancer Ther 2003;2(4):332-44.
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(33) Paterson C, Britten N. In pursuit of patient-centered outcomes: a qualitative evaluation of the Measure Yourself Medical Outcome Profile. J Health Serv Res Policy 2000;5:27-36.
19 Page 19 of 29
Legends to figures Figure 1: CONSORT Study flow diagram Figure 2: Distribution of mean changes in QoL (19) across groups over time (higher score = higher
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QoL)
Figure 3: Distribution of mean changes in depressive symptoms (20) across groups over time
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(higher score = more depressive symptoms)
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Figure 4: Distribution of mean changes in mood (22; 23) across groups over time (higher score = poorer mood)
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Figure 5: Distribution of mean changes in sleep quality (24) across groups over time (higher score =
Ac ce p
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d
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better sleep quality)
20 Page 20 of 29
Figure 1
Figure 1: CONSORT Study flow diagram
The Danish National Patient Registry: 783 eligible colorectal cancer patients
Randomization arm (RA): N=391
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Self-selection arm: N=392
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Randomization
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Invitation and Part 1 of baseline package Excluded N=94
an
Reminder and information call after 3-7 days
M
Participants N= 247 (response rate 31.5%)
Self-selection of SA
SC N=52
ed
SH N=82
Randomization of RA RH N=58
RC N=55
ce pt
Part 2 of baseline package (N= 229)
RH and SH Healing session 1
Ac
RH and SH Healing session 2
RH and SH Questionnaires (N=127) RH and SH Healing session 3 RH and SH Questionnaires (N=125)
SC and RC Questionnaires 6 weeks after part 2 of baseline package (N=90)
RH and SH Healing session 4
Questionnaires 8 weeks after part 2 of baseline package (N=196)
Questionnaires 16 weeks after part 2 of baseline package (N=191) Page 21 of 29
cr an
us
Figure
M
ed
128 126
pt
124 120 118
Self-selected Control
ce
122
Self-selected Healing
Ac
Quality of Life Mean Score
Mean Changes in Quality of Life
Randomized Control
116
Randomized Healing
114
Baseline
8 Weeks Followup
16 Weeks Followup
Time of Measurement
Page 22 of 29
cr an
us
Figure
M
ed
10
pt
8
4
Self-selected Control
ce
6
Self-selected Healing
Ac
Depressive Symptoms Mean Score
Mean Changes in Depressive Symptoms
2
Randomized Control
0
Randomized Healing
Baseline
8 Weeks Followup
16 Weeks Followup
Time of Measurement
Page 23 of 29
cr an
us
Figure
M
Mean Changes in Mood
ed
30
pt
25 15 10
Self-selected Control
ce
20
Self-selected Healing
Ac
Mood Mean Score
35
Randomized Control
5
Randomized Healing
0
Baseline
8 Weeks Followup
16 Weeks Followup
Time of Measurement
Page 24 of 29
cr an
us
Figure
M
ed
1,4 1,2
pt
1 0,6 0,4
Self-selected Control
ce
0,8
Self-selected Healing
Ac
Subjective Sleep Quality Mean Score
Mean Changes in Subjective Sleep Quality
Randomized Control
0,2
Randomized Healing
0
Baseline
8 Weeks Followup
16 Weeks Followup
Time of Measurement
Page 25 of 29
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Tables
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Table 1: Characteristics associated with self-selected healing and randomized healing conditiona Self-selected Control
Randomized Healing
Randomized Control
N (%) or
N (%) or
N (%) or
N (%) or
Mean (SD)
Mean (SD)
Mean (SD)
Self-selection arm
82 (100)
52 (100)
0 (0.0)
Randomization arm
0 (0.0)
0 (0.0)
62.79 (9.09)
66.46 (7.62)
Self-selected Healingb
Randomized Healingc
OR
(95% CI)
p
OR
(95% CI)
p
0 (0.0)
-
-
-
-
-
-
58 (100)
55 (100)
-
-
-
-
-
-
63.52 (9.39)
64.27 (8.72)
0.95
0.91-0.99
0.020
0.99
0.95-1.03
0.656
1.00
Referent
0.92
0.43-1.99
1.00
Referent
Mean (SD)
d
M
an
Study arm N (%)
Age Mean (SD)
us
Self-selected Healing
ep te
Gender N (%) Female
40 (48.8)
19 (36.5)
38 (64.4)
35 (63.6)
1.00
Referent
Male
42 (51.2)
33 (63.5)
21 (35.6)
20 (36.4)
0.61
0.29-1.23
67 (82.7)
41 (80.4)
42 (72.4)
44 (84.6)
1.00
Referent
4 (4.9)
3 (5.9)
6 (10.3)
2 (3.8)
0.82
0.17-3.83
0.797
3.22
0.62-16.86
0.166
5 (6.2)
4 (7.8)
6 (10.3)
4 (7.7)
0.77
0.19-3.01
0.702
1.61
0.42-6.12
0.485
5 (6.2)
3 (5.9)
4(6.9)
2 (3.8)
1.02
0.23-4.50
0.979
2.15
0.37-12.35
0.392
Lower Secondary General (7 yrs)
10 (12.2
17 (33.3)
11 (19)
6 (11.3)
1.00
Referent
1.00
Referent
Lower Secondary General
10 (12.2)
5 (9.8)
6 (10.3)
3 (5.7)
3.40
0.90-12.83
1.09
0.20-6.01
Married Divorced or separated Widow or widower Single –unmarried Educational level
Ac c
Marital status N (%)
0.166
0.834
N (%)
0.071
0.920 Page 26 of 29
20 (24.4)
13 (25.5)
12 (20.7)
6 (11.3)
Tertiary < Master Degree (14 – 17 yrs)
36 (43.9)
12 (23.5)
25 (43.1)
6 (7.3)
4 (7.8)
4 (6.9)
< 200.000
7 (9.5)
9 (19.1)
200.000-300.000
17 (23)
11 (23.4)
300.000-400.000
14 (18.9)
400.000-500.000
6 (8.1)
500.000-600.000
13 (17.6)
600.000-700.000
4 (5.4)
0.92-7.46
0.072
1.09
0.27-4.41
0.903
35 (66)
5.10
1.84-14.12
0.002
0.39
0.13-1.19
0.099
3 (5.7)
2.55
0.58-11.28
0.217
0.55
0.08-3.59
0.528
1.00
Referent
us
an
Tertiary Master Degree (18 yrs)
2.62
cr
Upper Secondary (11 – 13 yrs)
ip t
(8 – 10 yrs)
6 (12.2)
4 (8.5)
1.00
Referent
13 (26.5)
13 (27.7)
1.99
0.57-6.90
0.280
0.67
0.15-2.93
0.667
9 (19.1)
6 (12.2)
10 (21.3)
2.00
0.55-7.30
0.294
0.40
0.79-2.02
0.268
8 (17)
12 (24.5)
5 (10.6)
0.96
0.23-4.10
0.961
1.60
0.31-8.25
0.574
4 (8.5)
4 (8.2)
7 (14.9)
4.18
0.94-18.61
0.061
0.38
0.07-2.22
0.283
3 (6.4)
1 (2)
4 (8.5)
1.71
0.29-10.30
0.556
0.17
0.01-2.09
0.165
3 (6.4)
7 (14.3)
4 (8.5)
5.57
1.13-27.52
0.035
1.00
0.17-5.99
1.000
34 (41.5)
28 (53.8)
15 (25.4)
22 (40)
1.00
Referent
1.00
Referent
48 (58.5)
24 (46.2)
44 (74.6)
33 (60)
1.65
0.82-3.32
1.91
0.86-4.24
2010/02/01-2010/06/30
22 (26.8)
15 (28.8)
19 (32.2)
9 (16.4)
1.00
Referent
1.00
Referent
2010/07/01-2010/10/30
21 (25.6)
16 (30.8)
13 (22)
18 (32.7)
0.90
0.36-2.25
0.36
0.12-1.06
No Yes
ep te
Additional treatment to surgery, N (%)
13 (17.6)
Ac c
>700.000
d
M
Household annual net income DKr., N (%)
0.162
0.112
Time since surgery, N (%)
0.814
0.063 Page 27 of 29
15 (25.4)
17 (30.9)
2011/03/01-2011/07/29
21 (25.6)
10 (19.2)
12 (20.3)
11 (20)
Quality of Life (QoL), Mean (SD)
118.92 (19.79)
127.17 (16.30)
119.31 (22.08)
122.69 (20.43)
Depressive symptoms (BDI-II), Mean (SD)
8.79 (8.01)
5.85 (5.69)
7.97 (9.10)
30.02 (23.36)
22.10 (15.82)
1.22 (0.79)
0.90 (0.67)
0.41-3.02
0.830
0.44
0.15-1.27
0.130
1.43
0.53-3.89
0.481
0.55
0.17-1.71
0.299
0.97
0.95-0.99
0.018
0.99
0.97-1.01
0.414
7.52 (7.87)
1.07
1.01-1.13
0.029
1.01
0.96-1.05
0.780
28.33 (25.28)
27.23 (21.05)
1.02
1.00-1.04
0.037
1.00
0.99-1.02
0.801
1.10 (0.77)
1.16 (0.66)
1.83
1.10-3.05
0.021
0.89
0.53-1.49
0.653
1.00
Referent
an
M
d
Outcome areas considered important, N (%)
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Subjective sleep quality, Mean (SD)
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11 (21.2)
Mood (POMS), Mean (SD)
1.12
cr
18 (22)
us
2010/11/01-2011/02/28
28 (36.8)
3 (7.3)
14 (27.5)
10 (20.8)
1.00
Referent
Physical activity
8 (10.5)
5 (12.2)
4 (7.8)
9 (18.8)
0.17
0.33-0.88
0.034
0.34
0.81-1.44
0.143
Quality of life
22 (28.9)
15 (12.2)
20 (39.2)
16 (33.3)
0.16
0.40-0.61
0.008
0.96
0.34-2.76
0.942
5 (6.6)
3 (7.3)
2 (3.9)
5 (10.4)
0.18
0.28-1.15
0.070
0.31
0.05-1.93
0.208
5 (6.6)
3 (7.3)
2 (3.9)
2 (4.2)
0.18
0.28-1.15
0.070
0.77
0.09-6.45
0.809
4 (5.3)
4 (9.8)
1 (2)
3 (6.3)
0.11
0.02-0.67
0.017
0.26
0.02-2.85
0.268
0
2 (4.9)
4 (7.8)
1 (2.1)
0.00
0-0
0.999
3.08
0.30-31.98
0.347
4 (5.3)
6 (14.6)
4 (7.8)
2 (4.2)
0.71
0.01-0.41
0.003
1.54
0.23-10.15
0.655
Depressive symptoms Mood Sleep quality Economy Others
Ac c
Physical late effects
Faith in a spiritual Page 28 of 29
24 (31.2)
34 (77.3)
19 (37.3)
25 (51)
1.00
Referent
A little
37 (48.1)
4 (9.1)
19 (37.3)
11 (22.4)
13.10
4.12-41.65
>0.001
2.15
0.83-5.61
0.117
Yes
16 (20.8)
6 (13.6)
13 (25.5)
13 (26.5)
3.78
1.29-11.06
>0.015
1.32
0.50-3.48
0.580
Experienced influence of faith in spiritual power on QoL, Mean (SD)
2.49 (1.38)
2.16 (1.43)
2.50 (1.48)
2.81 (1.58)
1.20
0.81-1.77
0.366
0.87
0.64-1.20
0.410
Experienced influence of faith in spiritual power on cancer, Mean (SD)
2.07 (1.24)
1.84 (1.12)
2.39 (1.46)
2.39 (1.59)
1.18
0.75-1.85
0.479
1.16
0.73-1.38
0.996
27 (33.8)
18 (39.1)
12 (23.5)
10 (20.4)
1.00
Referent
28 (35)
13 (28.3)
21 (41.2)
15 (30.6)
1.44
0.59-3.49
0.425
1.11
0.38-3.25
0.847
25 (31.3)
15 (32.6)
18 (35.3)
24 (49)
1.11
0.46-2.67
0.813
0.63
0.22-1.77
0.375
Experienced influence of faith in God power on QoL
2.66 (1.52)
2.62 (1.41)
2.66 (1.40)
2.97 (1.35)
1.01
0.76-1.36
.0925
0.84
0.61-1.16
0.292
Experienced influence of faith in God power on cancer
2.10 (1.37)
2.16 (1.30)
2.37 (1.36)
2.45 (1.52)
0.97
0.70-1.34
0.857
0.96
0.71-1.30
0.803
Attitude towards alternative therapies
3.72 (0.76)
2.83 (0.77)
3.65 (0.89)
3.45 (1.21)
5.01
2.57-9.75
>0.001
1.20
0.82-1.75
0.348
us
an
M
Ac c
Yes
ep te
A little
d
Faith in God, N (%) No
cr
No
ip t
power, N (%)
aOR
= Odds Ratios. CI = Confidence Interval. Unadjusted OR in bold differ significantly (95% CI) from the reference group (OR = 1.00). self-selected control condition as category of reference cUsing randomized control condition as category of reference bUsing
Page 29 of 29
S0965-2299(14)00060-0 http://dx.doi.org/doi:10.1016/j.ctim.2014.04.003 YCTIM 1334
To appear in:
Complementary Therapies in Medicine
Received date: Revised date: Accepted date:
23-8-2013 7-3-2014 24-4-2014
Please cite this article as: Pedersen CG, Johannessen H, Hjelmborg JVB, Zachariae R, Effectiveness of energy healing on Quality of Life: a pragmatic intervention trial in colorectal cancer patients., Complementary Therapies in Medicine (2014), http://dx.doi.org/10.1016/j.ctim.2014.04.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title page Effectiveness of energy healing on Quality of Life: a pragmatic intervention trial in colorectal cancer patients.
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Christina Gundgaard Pedersen, Post Doctoral fellow., MSc., PhD1, Helle Johannessen, Professor, mag.scient., PhD2, Jacob v. B. Hjelmborg3, Associate Professor, MSc, PhD, Robert Zachariae,
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1
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Professor, MSc, MDSci 1
Unit of Psychooncology and Health Psychology, Department of Oncology, Aarhus University
2
Health, Man and Society, Institute of Public Health, University of Southern Denmark, J.B.
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Winsløws Vej 9B, 5000 Odense C, Denmark
Department of Biostatistics, Institute of Public Health, University of Southern Denmark,
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3
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Hospital & Department of Psychology, Aarhus University, Bartholins Allé 9, 8000 Aarhus C
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J.B.Winsløws Vej 9B, 5000 Odense C, Denmark
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Corresponding author: Christina G. Pedersen, Ph.D., MSc., Post Doc., Unit of Psychooncology and Health Psychology, Department of Oncology, Aarhus University Hospital & Department of Psychology, Aarhus University, Bartholins Allé 9, 8000 Aarhus C, Denmark. E-mail: [email protected] Phone: +45 87 16 58 79.
Financial support was provided by The Danish Council for Strategic Research, Ministry of Science, Innovation and Higher Education (Grant no. 09-065176); Department of Psychology and Behavioral Sciences, University of Aarhus; and the Institute of Clinical Research and Institute of Public Health, University of Southern Denmark. The funding sources had no involvement in the study design, collection, analysis, and interpretation of data, or writing of the paper.
1 Page 1 of 29
Abstract Purpose: Our aim was to explore the effectiveness of energy healing, a commonly used complementary and alternative therapy, on well-being in cancer patients while assessing the
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possible influence on the results of participating in a randomized controlled trial.
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Methods: 247 patients treated for colorectal cancer (response rate: 31.5%) were either a)
randomized to healing (RH) or control (RC) or b) had self selected the healing (SH) or control
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condition (SC), and completed questionnaires assessing well-being (QoL, depressive symptoms, mood, and sleep quality), attitude towards complementary and alternative medicine (CAM), and
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faith/spirituality at baseline, 1 week, and 2 months post-intervention. They also indicated, at baseline, whether they considered QoL, depressive symptoms, mood, and sleep quality as important
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outcomes to them.
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Results: Multilevel linear models revealed no overall effect of healing on QoL (p=0.156),
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depressive symptoms (p=0.063), mood (p=0.079), or sleep quality (p=0.346) in the intervention groups (RH, SH) compared with control (SC). Effects of healing on mood were only found for
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patients who had a positive attitude towards CAM and considered the outcome in question as important (SH: Regression coefficient: -8.78; SE: 2.64; CI: -13.96- -3.61; p=0.001, and RH: Regression coefficient -7.45; SE: 2.76; CI: -12.86- -2.04; p=.007). Conclusion: Whereas it is generally assumed that CAMs such as healing have beneficial effects on well-being, our results indicated no overall effectiveness of energy healing on QoL, depressive symptoms, mood, and sleep quality in colorectal cancer patients. Effectiveness of healing on wellbeing was, however, related to factors such as self-selection and a positive attitude towards the treatment.
2 Page 2 of 29
Introduction The possible effects of so-called “energy healing” have been the subject of much public and scientific debate (1;2), and energy healing is one of the most prevalently used types of
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complementary and alternative medicine (CAM) among cancer patients (3). Although there is no scientific evidence to support its efficacy against the disease itself, healing is often assumed to have
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a beneficial effect on quality-of-life (QoL). However, only few studies have been conducted of the
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effect of energy healing on cancer-related symptoms and well-being, and - due to limited methodological quality and small sample sizes - the available studies do not allow for reliable
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conclusions (4).
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A systematic review of 8 non-randomized and 9 randomized controlled trials of so-called distant healing concluded that there was “no evidence against the notion that distant healing is more than a
d
placebo” (1). This conclusion is supported by further research, e.g. by Pohl and colleagues, who
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conducted a single-blinded randomized trial with 80 patients with advanced cancer to determine the
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influence of ‘laying on of hands’ healing on well-being (5). Although a significant improvement of cancer- or cancer-treatment-related symptoms was found, there were no differences in effect between the self-declared healer and an actor, who provided “sham treatment”.
In line with findings from placebo research, it has been suggested that patients’ beliefs and attitudes are the main factors driving the effects of CAM (6). The convictions and positive expectations believed to be associated with the placebo effect have been found to alter neurochemical patterns, including endogenous opioids and pain-modulating interconnections (7), involving key areas of the brain responsible for physical and psychological pain (anterior cingulate cortex), pleasure (basal nuclei), and movement (striatum) (6). A positive attitude towards massage has, for example, been found to increase the effect of massage on cancer-related fatigue (8). Taken together, however, the 3 Page 3 of 29
available results are inconsistent (9). Another possible moderator could be the religious/spiritual faith of patients. Faith in God or a spiritual power has previously been associated with increased use of both CAM in general and healing in particular (10;11), but no studies so far have sought to
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explore faith as a possible moderator of the effect of healing.
Some researchers have voiced their concern that, although being the Gold Standard in clinical
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research, traditional RCTs may not be externally valid, the main reason being that the results cannot
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be generalized to the general population, which includes people with strong treatment preferences (12-14). A systematic review of 32 medical and psychological studies employing one of two types
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of combined designs (1: randomization into randomization or no-randomization group, or, 2: randomization or self-selection group for those refusing randomization) found, however, that
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outcome differences between randomized and self-selection groups were relatively small and inconsistent in direction (15). The individually perceived relevance of the outcomes assessed may
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be yet another potential moderator. Previous reports of qualitative observations of energy healing
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suggest that healing interventions are highly individualized and the outcomes personalized (16;17).
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A pragmatic research methodology that takes individualization into account and considers the individually perceived importance of the outcomes as a moderator, thus appears relevant. The socalled “Cohort multiple randomized controlled trial design” proposes that a large observational cohort of patients with the condition of interest is recruited, outcomes regularly measured, and participants for intervention trials randomly selected based on the cohort (18). So far, however, no controlled studies have sought to investigate the effectiveness in a pragmatic trial of energy healing in both a randomized and self-selected group of participants to explore if effectiveness depends on individual characteristics associated with self-selection.
Taken together, little is presently known about the effectiveness of healing on well-being among cancer patients and the potential moderators of this effect. Thus, as part of the CCESCAM protocol 4 Page 4 of 29
having the primary purpose of developing guidelines and exploring effect of energy healing on personalized outcomes, our aim was to explore the effectiveness of energy healing on the following secondary outcomes: 1) cancer-related Quality of Life (QoL), 2) depressive symptoms, 3) mood, and 4) sleep quality among patients treated for colorectal cancer while assessing the possible
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influence on the results of participating in a randomized controlled trial. This was done using a
pragmatic trial study design aimed at maximizing internal and external as well as ecological validity
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by randomizing a population-based sample of colorectal patients recruited from two major regions
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in Denmark to two groups: One to be randomized to intervention or control, and one to a group selfselecting the healing or control condition. Based on the results of a pilot study, no main effects of
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healing on any of the secondary outcome measures were anticipated. A number of factors were expected to moderate the effectiveness of energy healing including: 1) a positive attitude towards
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CAM, 2) faith in God or a higher spiritual power, and 3) personal prioritization of the outcome of
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Participants
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Methods
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treatment.
A search in the Danish National Patient Registry identified a total of 783 eligible patients. Eligibility criteria were: 1) primary diagnosis of colorectal cancer, defined as C18- C20, according to the International Classification of Diseases (ICD10), 2) completed treatment for colorectal cancer with
intention to cure with surgery or surgery and chemotherapy or radiotherapy in the Southern or Central Region of Denmark between March 1, 2010, and August 1, 2011, and no current cancer, 3) ≤80 years of age. Exclusion criteria were: 1) mentally and cognitively incapable to participate in the study, 2) poor understanding of the Danish language, or 3) in palliative care or cancer recurrence prior to inclusion.
Procedure 5 Page 5 of 29
The study procedure is shown Figure 1. Using a computerized procedure (Minim: Minimization Program for Allocating Patients to Treatments in Clinical Trials), potential participants were, prior to initial contact, first randomized to two arms: Allocation to treatment based on either selfselection (SSA) or further randomization (RA). After inclusion in the study, participants in the RA
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group were then further allocated to treatment or control based on a second randomization
procedure. The randomization was conducted by the first author, who coordinated the database
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management and had no personal contact with the patients.
Eligible patients were mailed written information about the study, a leaflet containing information
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about the healers in the study, an informed consent form, a pre-paid envelope, and Part 1 of a baseline questionnaire package. The accompanying letter differed, depending whether recipients
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were allocated to the self-selection arm or the randomization arm. Recipients in the self-section arm were informed that they could choose between treatments with energy healing and allocation to the
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control group. Recipients in the randomization arm were informed that they would be randomly
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allocated either to receive energy healing or to be in the control group. Participants not receiving the
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energy healing intervention during the trial were offered one free session with an energy healer after trial completion; this offer was accepted by one participant only. Patients willing to participate were instructed to complete the informed consent form (with an indication of two preferred healers) and the enclosed questionnaire package, and return it in the pre-paid envelope. If an eligible patient had not returned the questionnaire within 2-4 weeks, a reminder call was made. If the patient did not respond, he or she was considered a non-responder.
After having returned the informed consent and the Part 1 of the baseline questionnaire, RA participants were further randomized to either intervention (RH) or control (RC), and patients in the SSA were asked to chose self-selected healing (SH) or self-selected control (SC), resulting in a four-arm design. Part 2 of the baseline questionnaire was mailed out after the second randomization 6 Page 6 of 29
procedure prior to intervention start. Additional questionnaires were mailed to participants 8 and 16 weeks after completing the baseline questionnaire, which corresponded to approx. 1 and 8 weeks post intervention.
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Intervention procedure
Participants in RH and SH received four sessions of energy healing at the healer’s clinic over a 2-
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month period as agreed-upon by each participant-healer pair. Healers were identified and recruited
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through a national association of healers (‘Healer-Ringen’). Additional inclusion criteria were: 1) treatment facilities used solely for the practice of healing, and 2) clinic location within the regions of Central and
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Southern Denmark. A total of 31 healers were included. The energy healing provided was not restricted
to a specific form of energy healing, provided that it was based on a general idea of the healer
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providing some type of energy to the participant by the hands. General conversation between the healer and participant was accepted, but no other form of therapy than energy healing was allowed.
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Potential use of other types of CAM during the trial period was recorded in the follow-up
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questionnaire completed approximately 1 week post-intervention.
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(Insert figure 1 near here)
Measures
Outcome measures
Changes in health-related QoL, i.e. physical/functional, psychological, and social and spiritual wellbeing, were assessed using the Danish version of FACIT-sp (19). Depressive symptoms were measured with the Beck Depression Inventory (BDI-II), a commonly used measure in studies of cancer patients both internationally and in Denmark (20;21). Negative mood was measured using the total score of a Danish version of the Brief 37-item version of Profile of Mood States (POMS) validated with cancer patients (22;23). Subjective sleep quality was measured with one item from
7 Page 7 of 29
the Pittsburg Sleep Quality Index (PSQI) (24) which has previously been used in studies of Danish patients (25).
Planned moderator measures
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Clinical data, including date of diagnosis and type of treatments received, together with
demographic data (date of birth and gender) were obtained from The National Patient Register.
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Additional socio-demographic information on municipal of residence, civil status, family structure,
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schooling, vocational training, labor market attachment/(early) retirement, and personal and house hold income were obtained via self-report. Attitude towards complementary and alternative
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medicine (CAM) was measured with one question: “What is your attitude towards alternative therapies: Very negative, negative, neutral, positive or very positive?” Faith in God (yes, a little,
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no), faith in a spiritual power (yes, a little, no), and the experienced influence of that faith on QoL and cancer itself (range: 1: no, 2: a little, 3: some, 4: considerably, 5: very much) was measured
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with 4 separate items used in previous studies (10;11). Personal prioritization of preferred outcome
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was measured with the question: “Which of the following topics do you consider most important to
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you right now? Symptoms following your disease (including treatment-related late-effects), physical activity (including coping with daily activities), quality of life (including general well-being), depressive symptoms, mood, sleep quality, economy, or others?”
Ethics
The study adhered to the ethical requirements of the Helsinki Declaration (26). The study protocol was submitted to the regional Committee of Research Ethics in Southern Denmark, was approved by the Danish Data Protection Agency, and the hypotheses were registered in a clinical trial database (ClinicalTrials.gov; NCT01434264) prior to data collection. Participants randomized to the control group were offered to receive the intervention free of charge after the study was completed.
8 Page 8 of 29
Statistical analysis Based on the results of a pilot-study, a total of 125 participants were planned to receive healing and 200 to serve as a control group (www.clinicaltrials.org). Statistical power analysis showed that with the planned sample size, it would be possible to detect a change of one point on the protocol’s
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primary outcome scale, Measure Yourself Concerns and Wellbeing (MYCaW) (27), with a 5%
significance level and a statistical power of 80%. MYCaW was not included as an outcome in the
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present analyses and will be reported elsewhere. The modeling of the longitudinal data was based on
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the expectation that the responses of individuals will be correlated over time, i.e, within-individual dependency (28). The estimated variance and within individual correlation over time was based on the
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pilot-study (www.clinicaltrials.gov; NCT01434264).
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The effects were evaluated using linear mixed models with a corrected level of significance (p=0.05/number of outcomes + 1) (29). All interactions between group, time, and putative
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moderators were included in one model. If an interaction was non-significant for any of the
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dependent measures, it was removed from the analysis. Differences in sample characteristics
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between SH and SC as well as between RH and RC were explored using multiple binary logistic regression analysis. All analyses were conducted using SPSS version 19 and STATA version 12.
Results
A total of 247 (response rate 31.5%) men (N=115/46.6%) and women (N=132/53.4%) participated in the study. Participating patients were younger than non-participants, (mean 64.06 and SD 8.84 years vs. 68.42 and SD 8.99 years; range: 29-80 years; t(687)=6.14; p<.001), and an attrition analysis revealed that participants were more likely than non-responders to be women (χ2(1)= 5,258; p=0.022) and to have received oncological treatments other than surgery (χ2(1)= 12,412; p<0.001) (30). 9 Page 9 of 29
As shown in Table 1, participants in the SH group were characterized by being younger, more prone to have a tertiary degree (< master degree), having unambiguous or ambiguous faith in a higher spiritual power, and a more positive attitude towards CAM, compared to SC (OR range: 0.95 -
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13.10; p: 0.02 - 0.001). At baseline, SH participants also exhibited lower QoL, more depressive
symptoms, more negative mood, and poorer sleep quality, compared to SC (OR range: 0.97 – 1.83;
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p: 0.29 – 0.018). A multiple binary logistic regression adjusting for all significant factors associated
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with SH in the unadjusted analysis revealed that SH only differed from SC with respect to ambiguous faith, (OR: 6.07; CI: 1.61-22.93; p=0.008) and a positive attitude towards alternative
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characteristics were found between RH and RC.
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therapies (OR: 4.03; CI: 1.78-9.12; p=0.001) (data not shown). No differences in participant
As shown in Table 1, the majority of participants considered QoL, physical late effects, and
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physical activity (N range: 73 (29.6%) – 26 (10.5%)) as important outcomes, and to a lesser extent
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“other concerns”, depressive symptoms, mood, sleep quality, and financial concerns (N range: 16
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(6.5%) – 7 (2.8%)). In all, 32 patients (13%) did not respond to this question.
(Insert Table 1 near here)
Effectiveness of energy healing on QoL The multilevel linear models revealed no statistically significant effect of healing on QoL for either of the intervention groups (RH, SH) compared to control (SC) (Regression coefficient: -3.27, SE: 2.30; CI:-7.79-1.25; p=0.156). Figure 2 shows the distribution of means across groups over time (higher score = higher QoL). A subset of participants in the self-selected healing group (SH), who had rated QoL as important, reported a borderline statistically significant improvement in QoL 1, week post-intervention, compared with SC, after adjusting for possible confounders, i.e. attitude 10 Page 10 of 29
towards CAM, spiritual faith, and gender (Regression coefficient: 7.68; SE: 3.03; CI: 1.74-13.62; p=0.011). With an unadjusted p-value, this result would have reached statistical significance (p=
(Insert figure 2 near here)
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Effectiveness of energy healing for depressive symptoms
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0.01).
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No overall between-group differences were found for depressive symptoms over time (Regression coefficient: 1.53, SE: 0.82; CI:-0.08-3.13; p=0.063) (See Figure 3; higher score = more depressive
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symptoms). Adjusting for gender and attitude towards CAM, patients in the SH group showed a tendency to experience fewer depressive symptoms compared to SC at the time of follow up
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(Regression coefficient: -2.13; SE: 0.96; CI: -4.02- -0.25; p=0.027) (corrected p=0.01). Prioritizing depressive symptoms as an important outcome did not appear to influence the association between
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participating in SH (Regression coefficient: -1.57; SE: 0.98; CI: -3.49-0.35; p=0.109), RC
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(Regression coefficient: 0.65; SE: 1.01; CI: -1.32-2.63; p=0.516), or RH (Regression coefficient: -
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0.31; SE: 1.03; CI: -2.33-1.69; p=0.760) and depressive symptoms in the multilevel linear models.
(Insert figure 3 near here)
Effectiveness of energy healing on mood Healing was not found to have an overall influence on mood over time (Regression coefficient: 4.41; SE: 2.51; CI: -9.33-0.52; p=0.079) (See Figure 4; higher score = poorer mood). Exploring the role of possible moderators, a subgroup of patients in the SH (Regression coefficient: -8.78; SE: 2.64; CI: -13.96- -3.61; p=0.001) and RH group (Regression coefficient -7.45; SE: 2.76; CI: -12.86-2.04; p=.007) who had a positive attitude towards CAM and prioritized QoL, mood, and other
11 Page 11 of 29
concerns as important outcomes, were found to experience an improvement in mood at the time of follow up compared to SC.
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(Insert figure 4 near here)
Effectiveness of energy healing on subjective sleep quality
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No overall influence was found in the multilevel linear models of healing on subjective sleep
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quality (Regression coefficient: -0.09; SE: 0.10; CI: -0.29-0.10; p=0.346) (See Figure 5; higher score = better sleep quality). Prioritizing sleep quality as an important outcome and having a
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positive attitude towards CAM did not influence the association between allocation to intervention group and subjective sleep quality (SH: Regression coefficient: -0.003; SE: 0.12; CI: -0.24-0.24;
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p=.976; RH: Regression coefficient: -0.04; SE: 0.13; CI: -0.21-0.29; p=.766).
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Discussion
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d
(Insert figure 5 near here)
In accordance with our hypotheses based on a pilot study, we found no overall effect of randomly allocated or self-selected healing on any of the planned outcomes: Cancer-related QoL, depressive symptoms, mood, and sleep quality. Our results suggest that only patients prioritizing the outcome in question and having a positive attitude towards CAM and faith in a spiritual power are likely to experience benefits related to well-being from healing.
This is the first pragmatic trial of the CAM intervention of energy healing comparing the effects between groups of random allocation or self-selection. A common critique of previous research on healing has been that healing is generally not a standardized treatment but targeted individually and therefore should be studied as such to achieve sufficient ecological validity - that is, by 12 Page 12 of 29
approximating the real-world setting of the treatment examined as much as possible (31). In the present study, our first aim was to accommodate this critique, first by letting all participants choose the healer they preferred and second by providing healing under “real-life conditions” in the practitioners’ own clinics. Third, half of the participants were allowed to self-select the intervention
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or control group taking possible individual characteristics associated with self-choice of healing into
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consideration.
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While our study has several strengths, e.g. using a pragmatic trial study design aimed at maximizing internal and external as well as ecological validity, some limitations should also be taken into
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account. Restricting participants not to use other types of CAM during the trial period with the purpose of maximizing internal validity could be argued to be a potential limitation of ecological
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validity, as some participants could have chosen to use several types of CAM under normal, nontrial circumstances. Another possible limitation could be that attitude towards CAM was measured
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in relation to alternative therapies in general and not with specific reference to the intervention
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investigated. Considering that the present study tested hypotheses related to secondary outcomes,
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the primary outcome being the personalized outcome, MYCaW (27), we chose a rather conservative correction of our alpha-level (29). This approach requires considerably more power to detect significant differences, and the relatively low response- and participation rate in the present study meant weaker power than anticipated. Another caution related to the response rate concerns representativity, and the results may not be entirely generalizable to patients treated for colorectal cancer who are older, male, and have received surgery only.
The present findings are in line with a previous study, finding no effect of healing on mood after 4 sessions (32), but in contrast to a culturally common assumption that although healing may not influence the cancer disease directly, there might be positive effects on well-being (4). In the light of previous research on placebo effects and the role of attitudes and beliefs (6;7), we anticipated 13 Page 13 of 29
that a positive attitude towards CAM and faith in God or higher spiritual power would be associated with a larger effect of energy healing. Also, as previous research has suggested that personalized outcomes may be important (33), we also investigated if effectiveness was influenced by the outcome areas considered to be important by the patient. Consistent with a previous study on the
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role of attitude as a moderator (8) and qualitative observations concerning personalized outcomes (16;17), we found that a positive attitude towards CAM and having prioritized mood or QoL as
cr
important outcome areas were both associated with a more beneficial effect of healing on mood. A
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positive attitude towards CAM was borderline statistically significantly associated with a beneficial influence of healing on QoL, but only among patients who had self-selected healing, had faith in a
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higher spiritual power, and had prioritized QoL as an important outcome topic for them personally. Likewise, in a select group of patients having a positive attitude towards CAM and having self-
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selected healing, a borderline significant trend was found towards an effect of healing on depressive symptoms. In concordance with previous findings (31;33), our results, thus, suggest that it is
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relevant for future research on QoL and mood to consider whether the outcomes in question are
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considered relevant by the participants.
Taken together, the results of the present study suggest that a healing intervention evaluated in a pragmatic trial attempting to maximize ecological validity, while at the same time attempting to ensure internal validity, did not appear to be an effective way to improve QoL, mood, depressive symptoms, or sleep quality in patients having completed treatment for colon or rectal cancer. A select group of individuals who had prioritized the outcome topic in question and who exhibited belief/faith and a more positive attitude towards CAM did experience an effect on mood. In addition, borderline-significant trends were found in select groups for effects on QoL and depressive symptoms, but not sleep quality. The present study suggests that it may be relevant for future intervention research to consider individually prioritized outcomes, self-selection, belief, and attitude towards treatment. 14 Page 14 of 29
Acknowledgements The project was carried out by the CCESCAM group (www.ccescam.dk). Financial support was provided by The Danish Council for Strategic Research, Ministry of Science, Innovation and
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Higher Education (Grant no. 09-065176); Department of Psychology and Behavioral Sciences, University of Aarhus; and the Institute of Clinical Research and Institute of Public Health,
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University of Southern Denmark. The funding sources had no involvement in the study design,
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collection, analysis, and interpretation of data, or writing of the paper. Participating healers were
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identified by a national Danish association for energy healers (“HealerRingen”).
Conflicts of interest
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None to declare.
15 Page 15 of 29
References (1) Ernst E. Distant healing - an "update" of a systematic review. Wien Klin Wochenschr
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2003;115(7-8):241-5. (2) Astin J, Harkness E, Ernst E. The efficacy of "Distant Healing": a systematic review of
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randomized trials. Ann Intern Med 2000;132:903-10.
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(3) Molassiotis A, Fernandez-Ortega P, Pud D, et al. Complementary and alternative medicine use in colorectal cancer patients in seven European countries. Complement Ther Med 2005
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Dec;13(4):251-7.
Komplement Med 2011;18:146-54.
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(4) Agdal R, Hjelmborg J, Johannessen H. Energy healing for cancer: A critical review. Forsch
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(5) Pohl G, Seemann H, Zojer N, et al. "Laying on of hands" improves well-being in patients
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with advanced cancer. Support Care Cancer 2007;15:143-51.
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(6) Teixeira M, Guedes C, Barreto P, et al. The placebo effect and homeopathy. Homeopathy 2010;99:119-29.
(7) Benedetti F, Lanotte M, Colloca L. When words are painful: unraveling the mechanisms of the nocebo effect. Neuroscience 2007;147(2):260-71.
(8) Fernández-Lao C, Cantarero-Villanueva I, Díaz-Rodríguez L, et al. Attitudes towards massage modify effects of manual therapy in breast cancer survivors: a randomised clinical trial with crossover design. Eur J Cancer Care 2011;21:233-41. (9) Lewith G, Hyland M, Shaw S. Do attitudes toward and beliefs about complementary medicine affect treatment outcomes? Am J Public Health 2002;92(10):1604-6. 16 Page 16 of 29
(10) Pedersen CG, Christensen S, Jensen AB, et al. In God and CAM we trust. Religious faith and use om complementary and alternative medicine (CAM) in a nationwide cohort of women treated for early breast cancer. J Relig Health 2013;52(3):991-1013.
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(11) Bekke-Hansen S, Pedersen CG, Thygesen K, et al. Faith and use of complementary and alternative medicine among heart attack patients in a secular society. Complement Ther Med
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2012.
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(12) Leykin Y, DeRubeis R, Gallop R, et al. The relation of patients' treatment preferences to outcome in a randomized trial. Behavior Therapy 2007;38:209-17.
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(13) Braver S, Smith M. Maximizing both external and internal validity in longitudinal true experiments with voluntary treatments: The combined modified design. Eval Program Plan
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1996;19:287-300.
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(14) Silverman W, Altman D. Patient' preferences and randised trials. Lancet 1996;347:171-4.
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(15) King M, Nazareth I, Lampe R, et al. Impact of participant and physician intervention
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preferences on randomized trials: A systematic review. JAMA 2005;293(9):1090-9. (16) Ostenfeld-Rosenthal A. Symbolsk healing "embodied". Krop, mening og spiritualitet i danske helbredelsesritualer. Tidsskrift for Forskning i Sygdom og Samfund 2007;6:129-50.
(17) Belusa M. Det gode liv - lykkes det? Kræftpatienters oplevelser hos behandlere der arbejder med healing. University of Southern Denmark; 2009.
(18) Relton C, Torgerson D, O'Cathain A, et al. Rethinking pragmatic randomised controlled trials: introducing the "cohort mulitiple randomised controlled trial" design. BMJ 2010;340:963-7.
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(19) Peterman AH, Fitchett G, Brady MJ, et al. Measuring spiritual well-being in people with cancer: The functional assessment of chronic illness therapy-spiritual well-being scale (FACIT-Sp). Ann Behav Med 2002;24(1):49-58.
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(20) Beck AT SRBG. Manual: Beck depression inventory - second edition. San Antonio TX: The Psychological Corp. Hartcourt og Brace; 1996.
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(21) Christensen S, Zachariae R, Jensen A, et al. Prevalence and risk of depressive symptoms 3-4
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months post-surgery in a nationwide cohort study of Danish women treated for early stage breast-cancer. Breast Cancer Res Treat 2009;113(2):339-55.
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(22) Jensen-Johansen M, Christensen S, Valdimarsdottir H, et al. Effects of an expressive writing intervention on cancer-related distress in Danish breast cancer survivors - results from a
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nationwide randomized clinical trial. Psychooncology 2012;DOI: 10.1002/pon.3193 [Epub
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ahead of print].
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(23) Cella D, Jacobsen P, Orav E, et al. A brief POMS measure of distress for cancer patients. J
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Chronic Dis 1987;40(10):939-42.
(24) Buysse D, Reynolds 3rd C, Monk T, et al. The Pittsburg Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193-213.
(25) Colagiuri B, Christensen S, Jensen A, et al. Prevalence and predictors of sleep difficulty in a national cohort of women with primary breast cancer three to four months postsurgery. J Pain Symptom Manage 2011;42(5):710-20.
(26) WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. Avalable at: http://www.wma.net/en/30publications/10policies/b3/index.html (accessed 6 january 2013). World Medical Association. 2008. 18 Page 18 of 29
(27) Paterson C, Thomas K, Manasse A, et al. Measure Yourself Concerns and Wellbeing (MYCaW): an individualised questionnaire for evaluating outcome in cancer support care that includedes complementary therapies. Complement Ther Med 2007;15(1):38-45.
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(28) Diggle P, Heagerty P, Liang K, Zeger S. Analysis of longitudinal data. Second edition ed. Oxford: OUP; 2002.
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(29) Davis C. Secondary endpoints can be validly analyzed, even if the primary endpoint does
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not provide clear statistical significance. Control Clin Trials 1997;18(6):557-60. (30) Techau M, Lunde A, Pedersen C. Attrition and reasons for saying no to participation in a
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study on energy healing as cancer rehabilitation. Eur J Integr Med 4(1), 180. 2012.
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(31) Sung L, Feldman BM. N-of-1 trials: innovative methods to evaluate complementary and alternative medicines in pediatric cancer. J Pediatr Hematol Oncol 2006 Apr;28(4):263-6.
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(32) Post-White J, Kinney M, Savik K, et al. Therapeutic massage and healing touch improve
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symptoms in cancer. Integr Cancer Ther 2003;2(4):332-44.
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(33) Paterson C, Britten N. In pursuit of patient-centered outcomes: a qualitative evaluation of the Measure Yourself Medical Outcome Profile. J Health Serv Res Policy 2000;5:27-36.
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Legends to figures Figure 1: CONSORT Study flow diagram Figure 2: Distribution of mean changes in QoL (19) across groups over time (higher score = higher
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QoL)
Figure 3: Distribution of mean changes in depressive symptoms (20) across groups over time
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(higher score = more depressive symptoms)
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Figure 4: Distribution of mean changes in mood (22; 23) across groups over time (higher score = poorer mood)
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Figure 5: Distribution of mean changes in sleep quality (24) across groups over time (higher score =
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better sleep quality)
20 Page 20 of 29
Figure 1
Figure 1: CONSORT Study flow diagram
The Danish National Patient Registry: 783 eligible colorectal cancer patients
Randomization arm (RA): N=391
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Self-selection arm: N=392
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Randomization
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Invitation and Part 1 of baseline package Excluded N=94
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Reminder and information call after 3-7 days
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Participants N= 247 (response rate 31.5%)
Self-selection of SA
SC N=52
ed
SH N=82
Randomization of RA RH N=58
RC N=55
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Part 2 of baseline package (N= 229)
RH and SH Healing session 1
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RH and SH Healing session 2
RH and SH Questionnaires (N=127) RH and SH Healing session 3 RH and SH Questionnaires (N=125)
SC and RC Questionnaires 6 weeks after part 2 of baseline package (N=90)
RH and SH Healing session 4
Questionnaires 8 weeks after part 2 of baseline package (N=196)
Questionnaires 16 weeks after part 2 of baseline package (N=191) Page 21 of 29
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Figure
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ed
128 126
pt
124 120 118
Self-selected Control
ce
122
Self-selected Healing
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Quality of Life Mean Score
Mean Changes in Quality of Life
Randomized Control
116
Randomized Healing
114
Baseline
8 Weeks Followup
16 Weeks Followup
Time of Measurement
Page 22 of 29
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Figure
M
ed
10
pt
8
4
Self-selected Control
ce
6
Self-selected Healing
Ac
Depressive Symptoms Mean Score
Mean Changes in Depressive Symptoms
2
Randomized Control
0
Randomized Healing
Baseline
8 Weeks Followup
16 Weeks Followup
Time of Measurement
Page 23 of 29
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Figure
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Mean Changes in Mood
ed
30
pt
25 15 10
Self-selected Control
ce
20
Self-selected Healing
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Mood Mean Score
35
Randomized Control
5
Randomized Healing
0
Baseline
8 Weeks Followup
16 Weeks Followup
Time of Measurement
Page 24 of 29
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Figure
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ed
1,4 1,2
pt
1 0,6 0,4
Self-selected Control
ce
0,8
Self-selected Healing
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Subjective Sleep Quality Mean Score
Mean Changes in Subjective Sleep Quality
Randomized Control
0,2
Randomized Healing
0
Baseline
8 Weeks Followup
16 Weeks Followup
Time of Measurement
Page 25 of 29
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Tables
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Table 1: Characteristics associated with self-selected healing and randomized healing conditiona Self-selected Control
Randomized Healing
Randomized Control
N (%) or
N (%) or
N (%) or
N (%) or
Mean (SD)
Mean (SD)
Mean (SD)
Self-selection arm
82 (100)
52 (100)
0 (0.0)
Randomization arm
0 (0.0)
0 (0.0)
62.79 (9.09)
66.46 (7.62)
Self-selected Healingb
Randomized Healingc
OR
(95% CI)
p
OR
(95% CI)
p
0 (0.0)
-
-
-
-
-
-
58 (100)
55 (100)
-
-
-
-
-
-
63.52 (9.39)
64.27 (8.72)
0.95
0.91-0.99
0.020
0.99
0.95-1.03
0.656
1.00
Referent
0.92
0.43-1.99
1.00
Referent
Mean (SD)
d
M
an
Study arm N (%)
Age Mean (SD)
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Self-selected Healing
ep te
Gender N (%) Female
40 (48.8)
19 (36.5)
38 (64.4)
35 (63.6)
1.00
Referent
Male
42 (51.2)
33 (63.5)
21 (35.6)
20 (36.4)
0.61
0.29-1.23
67 (82.7)
41 (80.4)
42 (72.4)
44 (84.6)
1.00
Referent
4 (4.9)
3 (5.9)
6 (10.3)
2 (3.8)
0.82
0.17-3.83
0.797
3.22
0.62-16.86
0.166
5 (6.2)
4 (7.8)
6 (10.3)
4 (7.7)
0.77
0.19-3.01
0.702
1.61
0.42-6.12
0.485
5 (6.2)
3 (5.9)
4(6.9)
2 (3.8)
1.02
0.23-4.50
0.979
2.15
0.37-12.35
0.392
Lower Secondary General (7 yrs)
10 (12.2
17 (33.3)
11 (19)
6 (11.3)
1.00
Referent
1.00
Referent
Lower Secondary General
10 (12.2)
5 (9.8)
6 (10.3)
3 (5.7)
3.40
0.90-12.83
1.09
0.20-6.01
Married Divorced or separated Widow or widower Single –unmarried Educational level
Ac c
Marital status N (%)
0.166
0.834
N (%)
0.071
0.920 Page 26 of 29
20 (24.4)
13 (25.5)
12 (20.7)
6 (11.3)
Tertiary < Master Degree (14 – 17 yrs)
36 (43.9)
12 (23.5)
25 (43.1)
6 (7.3)
4 (7.8)
4 (6.9)
< 200.000
7 (9.5)
9 (19.1)
200.000-300.000
17 (23)
11 (23.4)
300.000-400.000
14 (18.9)
400.000-500.000
6 (8.1)
500.000-600.000
13 (17.6)
600.000-700.000
4 (5.4)
0.92-7.46
0.072
1.09
0.27-4.41
0.903
35 (66)
5.10
1.84-14.12
0.002
0.39
0.13-1.19
0.099
3 (5.7)
2.55
0.58-11.28
0.217
0.55
0.08-3.59
0.528
1.00
Referent
us
an
Tertiary Master Degree (18 yrs)
2.62
cr
Upper Secondary (11 – 13 yrs)
ip t
(8 – 10 yrs)
6 (12.2)
4 (8.5)
1.00
Referent
13 (26.5)
13 (27.7)
1.99
0.57-6.90
0.280
0.67
0.15-2.93
0.667
9 (19.1)
6 (12.2)
10 (21.3)
2.00
0.55-7.30
0.294
0.40
0.79-2.02
0.268
8 (17)
12 (24.5)
5 (10.6)
0.96
0.23-4.10
0.961
1.60
0.31-8.25
0.574
4 (8.5)
4 (8.2)
7 (14.9)
4.18
0.94-18.61
0.061
0.38
0.07-2.22
0.283
3 (6.4)
1 (2)
4 (8.5)
1.71
0.29-10.30
0.556
0.17
0.01-2.09
0.165
3 (6.4)
7 (14.3)
4 (8.5)
5.57
1.13-27.52
0.035
1.00
0.17-5.99
1.000
34 (41.5)
28 (53.8)
15 (25.4)
22 (40)
1.00
Referent
1.00
Referent
48 (58.5)
24 (46.2)
44 (74.6)
33 (60)
1.65
0.82-3.32
1.91
0.86-4.24
2010/02/01-2010/06/30
22 (26.8)
15 (28.8)
19 (32.2)
9 (16.4)
1.00
Referent
1.00
Referent
2010/07/01-2010/10/30
21 (25.6)
16 (30.8)
13 (22)
18 (32.7)
0.90
0.36-2.25
0.36
0.12-1.06
No Yes
ep te
Additional treatment to surgery, N (%)
13 (17.6)
Ac c
>700.000
d
M
Household annual net income DKr., N (%)
0.162
0.112
Time since surgery, N (%)
0.814
0.063 Page 27 of 29
15 (25.4)
17 (30.9)
2011/03/01-2011/07/29
21 (25.6)
10 (19.2)
12 (20.3)
11 (20)
Quality of Life (QoL), Mean (SD)
118.92 (19.79)
127.17 (16.30)
119.31 (22.08)
122.69 (20.43)
Depressive symptoms (BDI-II), Mean (SD)
8.79 (8.01)
5.85 (5.69)
7.97 (9.10)
30.02 (23.36)
22.10 (15.82)
1.22 (0.79)
0.90 (0.67)
0.41-3.02
0.830
0.44
0.15-1.27
0.130
1.43
0.53-3.89
0.481
0.55
0.17-1.71
0.299
0.97
0.95-0.99
0.018
0.99
0.97-1.01
0.414
7.52 (7.87)
1.07
1.01-1.13
0.029
1.01
0.96-1.05
0.780
28.33 (25.28)
27.23 (21.05)
1.02
1.00-1.04
0.037
1.00
0.99-1.02
0.801
1.10 (0.77)
1.16 (0.66)
1.83
1.10-3.05
0.021
0.89
0.53-1.49
0.653
1.00
Referent
an
M
d
Outcome areas considered important, N (%)
ep te
Subjective sleep quality, Mean (SD)
ip t
11 (21.2)
Mood (POMS), Mean (SD)
1.12
cr
18 (22)
us
2010/11/01-2011/02/28
28 (36.8)
3 (7.3)
14 (27.5)
10 (20.8)
1.00
Referent
Physical activity
8 (10.5)
5 (12.2)
4 (7.8)
9 (18.8)
0.17
0.33-0.88
0.034
0.34
0.81-1.44
0.143
Quality of life
22 (28.9)
15 (12.2)
20 (39.2)
16 (33.3)
0.16
0.40-0.61
0.008
0.96
0.34-2.76
0.942
5 (6.6)
3 (7.3)
2 (3.9)
5 (10.4)
0.18
0.28-1.15
0.070
0.31
0.05-1.93
0.208
5 (6.6)
3 (7.3)
2 (3.9)
2 (4.2)
0.18
0.28-1.15
0.070
0.77
0.09-6.45
0.809
4 (5.3)
4 (9.8)
1 (2)
3 (6.3)
0.11
0.02-0.67
0.017
0.26
0.02-2.85
0.268
0
2 (4.9)
4 (7.8)
1 (2.1)
0.00
0-0
0.999
3.08
0.30-31.98
0.347
4 (5.3)
6 (14.6)
4 (7.8)
2 (4.2)
0.71
0.01-0.41
0.003
1.54
0.23-10.15
0.655
Depressive symptoms Mood Sleep quality Economy Others
Ac c
Physical late effects
Faith in a spiritual Page 28 of 29
24 (31.2)
34 (77.3)
19 (37.3)
25 (51)
1.00
Referent
A little
37 (48.1)
4 (9.1)
19 (37.3)
11 (22.4)
13.10
4.12-41.65
>0.001
2.15
0.83-5.61
0.117
Yes
16 (20.8)
6 (13.6)
13 (25.5)
13 (26.5)
3.78
1.29-11.06
>0.015
1.32
0.50-3.48
0.580
Experienced influence of faith in spiritual power on QoL, Mean (SD)
2.49 (1.38)
2.16 (1.43)
2.50 (1.48)
2.81 (1.58)
1.20
0.81-1.77
0.366
0.87
0.64-1.20
0.410
Experienced influence of faith in spiritual power on cancer, Mean (SD)
2.07 (1.24)
1.84 (1.12)
2.39 (1.46)
2.39 (1.59)
1.18
0.75-1.85
0.479
1.16
0.73-1.38
0.996
27 (33.8)
18 (39.1)
12 (23.5)
10 (20.4)
1.00
Referent
28 (35)
13 (28.3)
21 (41.2)
15 (30.6)
1.44
0.59-3.49
0.425
1.11
0.38-3.25
0.847
25 (31.3)
15 (32.6)
18 (35.3)
24 (49)
1.11
0.46-2.67
0.813
0.63
0.22-1.77
0.375
Experienced influence of faith in God power on QoL
2.66 (1.52)
2.62 (1.41)
2.66 (1.40)
2.97 (1.35)
1.01
0.76-1.36
.0925
0.84
0.61-1.16
0.292
Experienced influence of faith in God power on cancer
2.10 (1.37)
2.16 (1.30)
2.37 (1.36)
2.45 (1.52)
0.97
0.70-1.34
0.857
0.96
0.71-1.30
0.803
Attitude towards alternative therapies
3.72 (0.76)
2.83 (0.77)
3.65 (0.89)
3.45 (1.21)
5.01
2.57-9.75
>0.001
1.20
0.82-1.75
0.348
us
an
M
Ac c
Yes
ep te
A little
d
Faith in God, N (%) No
cr
No
ip t
power, N (%)
aOR
= Odds Ratios. CI = Confidence Interval. Unadjusted OR in bold differ significantly (95% CI) from the reference group (OR = 1.00). self-selected control condition as category of reference cUsing randomized control condition as category of reference bUsing
Page 29 of 29