Influence of patient-clinician relationship style on acupuncture outcomes in functional dyspepsia: A multi-site randomized controlled trial in Korea.

INTRODUCTION: Research suggests that a warm and empathic "patient-centered" patient-clinician relationship produces better clinical outcomes when compared with a more neutral "disease-centered" relationship. Acupuncturists performed both styles of therapy for patients with functional dyspepsia in Korea. METHODS: The present randomized controlled trial assigned patients (n = 73) to identical acupuncture treatment with either patient-centered augmented care or disease-centered limited care. The Korean version of the Nepean Dyspepsia Index (NDI-K) was the primary outcome measure. Secondary outcome measures included Consultation And Relational Empathy (CARE) scale. RESULTS: Both groups showed improvement in NDI-K. Patient-centered augmented acupuncture produced less effective symptom improvement compared to disease-centered limited acupuncture (NDI-K sum score and frequency; P = 0.008 and P = 0.037 respectively). CARE scores were higher for the augmented versus limited group (P = 0.001), supporting the fidelity of the experimentally controlled patient/clinician relationship. There were no significant differences between the groups in any of other secondary outcomes. CONCLUSION: Patients demonstrated greater improvement following acupuncture conducted with a more neutral, "disease-centered" style of relationship. This result is counter to similar research conducted in Western countries and suggests that cultural factors can significantly shape optimum styles of acupuncture therapy. PRACTICE IMPLICATIONS: Clinicians should consider cultural differences when applying acupuncture therapy.

Peppermint Oil Treatment for Irritable Bowel Syndrome: A Randomized Placebo-Controlled Trial.

INTRODUCTION: Peppermint oil is often used to treat irritable bowel syndrome (IBS); however, the overall quality of previous studies is low, and findings have been heterogeneous. This study aimed to compare the effects of peppermint oil vs placebo in relieving IBS symptoms. METHODS: In a 6-week, randomized, double-blind, placebo-controlled trial at a single academic center in the United States, individuals diagnosed with IBS (Rome IV criteria), with moderate to severe symptoms based on the IBS Severity Scoring System (IBS-SSS score ≥175), were randomized to enteric-coated peppermint oil 180 mg 3 times daily vs placebo in a 1:2 ratio. The primary outcome was mean change in IBS-SSS scores from baseline to 6-week endpoint. RESULTS: A modified intent-to-treat analysis revealed that there were substantial mean improvements from baseline to 6-week endpoint in the main outcome measure (IBS-SSS) for both peppermint oil (90.8, SD = 75.3) and placebo (100.3, SD = 99.6). Although the peppermint oil group reported numerically lower improvement than the placebo group, the effect size was small (d = -0.11), and the difference between the groups was not statistically significant (P = 0.97). Similarly, both groups reported substantial improvements on the secondary endpoints; but again, there were no statistically significant differences between the groups on any of the secondary measures. Sensitivity analyses using multiple imputation to replace missing data produced similar results and revealed no significant differences between peppermint oil and placebo on any outcome measure. DISCUSSION: Peppermint oil and placebo both showed clinically meaningful improvement in IBS symptoms. However, there were no significant differences between the groups. Further large, rigorous trials are needed to evaluate the role of peppermint oil for the treatment of IBS.

Open-label versus double-blind placebo treatment in irritable bowel syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Placebo medications, by definition, are composed of inactive ingredients that have no physiological effect on symptoms. Nonetheless, administration of placebo in randomized controlled trials (RCTs) and in clinical settings has been demonstrated to have significant impact on many physical and psychological complaints. Until recently, conventional wisdom has suggested that patients must believe that placebo pills actually contain (or, at least, might possibly contain) active medication in order to elicit a response to placebo. However, several recent RCTs, including patients with irritable bowel syndrome (IBS), chronic low back pain, and episodic migraine, have demonstrated that individuals receiving open-label placebo (OLP) can still experience symptomatic improvement and benefit from honestly described placebo treatment. METHODS AND DESIGN: This paper describes an innovative multidisciplinary trial design (n = 280) that attempts to replicate and expand upon an earlier IBS OLP study. The current study will compare OLP to double-blind placebo (DBP) administration which is made possible by including a nested, double-blind RCT comparing DBP and peppermint oil. The study also examines possible genetic and psychological predictors of OLP and seeks to better understand participants' experiences with OLP and DBP through a series of extensive interviews with a randomly selected subgroup. DISCUSSION: OLP treatment is a novel strategy for ethically harnessing placebo effects. It has potential to re-frame theories of placebo and to influence how physicians can optimize watch-and-wait strategies for common, subjective symptoms. The current study aims to dramatically expand what we know about OLP by comparing, for the first time, OLP and DBP administration. Adopting a unique, multidisciplinary approach, the study also explores genetic, psychological and experiential dimensions of OLP. The paper ends with an extensive discussion of the "culture" of the trial as well as potential mechanisms of OLP and ethical implications. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02802241 . Registered on 14 June 2016.

Active albuterol or placebo, sham acupuncture, or no intervention in asthma.

BACKGROUND: In prospective experimental studies in patients with asthma, it is difficult to determine whether responses to placebo differ from the natural course of physiological changes that occur without any intervention. We compared the effects of a bronchodilator, two placebo interventions, and no intervention on outcomes in patients with asthma. METHODS: In a double-blind, crossover pilot study, we randomly assigned 46 patients with asthma to active treatment with an albuterol inhaler, a placebo inhaler, sham acupuncture, or no intervention. Using a block design, we administered one each of these four interventions in random order during four sequential visits (3 to 7 days apart); this procedure was repeated in two more blocks of visits (for a total of 12 visits by each patient). At each visit, spirometry was performed repeatedly over a period of 2 hours. Maximum forced expiratory volume in 1 second (FEV(1)) was measured, and patients' self-reported improvement ratings were recorded. RESULTS: Among the 39 patients who completed the study, albuterol resulted in a 20% increase in FEV(1), as compared with approximately 7% with each of the other three interventions (P<0.001). However, patients' reports of improvement after the intervention did not differ significantly for the albuterol inhaler (50% improvement), placebo inhaler (45%), or sham acupuncture (46%), but the subjective improvement with all three of these interventions was significantly greater than that with the no-intervention control (21%) (P<0.001). CONCLUSIONS: Although albuterol, but not the two placebo interventions, improved FEV(1) in these patients with asthma, albuterol provided no incremental benefit with respect to the self-reported outcomes. Placebo effects can be clinically meaningful and can rival the effects of active medication in patients with asthma. However, from a clinical-management and research-design perspective, patient self-reports can be unreliable. An assessment of untreated responses in asthma may be essential in evaluating patient-reported outcomes. (Funded by the National Center for Complementary and Alternative Medicine.).

Placebo acupuncture as a form of ritual touch healing: a neurophenomenological model.

Evidence that placebo acupuncture is an effective treatment for chronic pain presents a puzzle: how do placebo needles appearing to patients to penetrate the body, but instead sitting on the skin's surface in the manner of a tactile stimulus, evoke a healing response? Previous accounts of ritual touch healing in which patients often described enhanced touch sensations (including warmth, tingling or flowing sensations) suggest an embodied healing mechanism. In this qualitative study, we asked a subset of patients in a singleblind randomized trial in irritable bowel syndrome to describe their treatment experiences while undergoing placebo treament. Analysis focused on patients' unprompted descriptions of any enhanced touch sensations (e.g., warmth, tingling) and any significance patients assigned to the sensations. We found in 5/6 cases, patients associated sensations including "warmth" and "tingling" with treatment efficacy. The conclusion offers a "neurophenomenological" account of the placebo effect by considering dynamic effects of attentional filtering on early sensory cortices, possibly underlying the phenomenology of placebo acupuncture.

Patient and practitioner influences on the placebo effect in irritable bowel syndrome.

OBJECTIVE: To determine whether placebo responses can be explained by characteristics of the patient, the practitioner, or their interpersonal interaction. METHODS: We performed an analysis of videotape and psychometric data from a clinical trial of patients with irritable bowel syndrome who were treated with placebo acupuncture in either a warm empathic interaction (Augmented, n = 96), a neutral interaction (Limited, n = 97), or a waitlist control (Waitlist, n = 96). We examined the relationships between the placebo response and a) patient personality and demographics; b) treating practitioner; and c) the patient-practitioner interaction as captured on videotape and rated by the Psychotherapy Process Q-Set. RESULTS: Patient extraversion, agreeableness, openness to experience, and female gender were associated with placebo response, but these effects held only in the augmented group. Regression analyses controlling for all other independent variables suggest that only extraversion is an independent predictor of placebo response. There were significant differences between practitioners in outcomes; this effect was twice as large as the effect attributable to treatment group assignment. Videotape analysis indicated that the augmented group fostered a treatment relationship similar to a prototype of an ideal healthcare interaction. CONCLUSIONS: Personality and gender influenced the placebo response, but only in the warm, empathic, augmented group. This suggests that, to the degree a placebo effect is evoked by the patient-practitioner relationship, personality characteristics of the patient will be associated with the placebo response. In addition, practitioners differed markedly in effectiveness, despite standardized interactions. We propose that the quality of the patient-practitioner interaction accounts for the significant difference between the groups in placebo response.

"Maybe I made up the whole thing": placebos and patients' experiences in a randomized controlled trial.

Patients in the placebo arms of randomized controlled trials (RCT) often experience positive changes from baseline. While multiple theories concerning such "placebo effects" exist, peculiarly, none has been informed by actual interviews of patients undergoing placebo treatment. Here, we report on a qualitative study (n = 27) embedded within a RCT (n = 262) in patients with irritable bowel syndrome. Besides identical placebo acupuncture treatment in the RCT, the qualitative study patients also received an additional set of interviews at the beginning, midpoint, and end of the trial. Interviews of the 12 qualitative subjects who underwent and completed placebo treatment were transcribed. We found that patients (1) were persistently concerned with whether they were receiving placebo or genuine treatment; (2) almost never endorsed "expectation" of improvement but spoke of "hope" instead and frequently reported despair; (3) almost all reported improvement ranging from dramatic psychosocial changes to unambiguous, progressive symptom improvement to tentative impressions of benefit; and (4) often worried whether their improvement was due to normal fluctuations or placebo effects. The placebo treatment was a problematic perturbation that provided an opportunity to reconstruct the experiences of the fluctuations of their illness and how it disrupted their everyday life. Immersion in this RCT was a co-mingling of enactment, embodiment and interpretation involving ritual performance and evocative symbols, shifts in bodily sensations, symptoms, mood, daily life behaviors, and social interactions, all accompanied by self-scrutiny and re-appraisal. The placebo effect involved a spectrum of factors and any single theory of placebo--e.g. expectancy, hope, conditioning, anxiety reduction, report bias, symbolic work, narrative and embodiment--provides an inadequate model to explain its salubrious benefits.

A treatment trial of acupuncture in IBS patients.

OBJECTIVES: This study aimed to compare the effects of true and sham acupuncture in relieving symptoms of irritable bowel syndrome (IBS). METHODS: A total of 230 adult IBS patients (75 % females, average age: 38.4 years) were randomly assigned to 3 weeks of true or sham acupuncture (6 treatments) after a 3-week "run-in" with sham acupuncture in an "augmented" or "limited" patient-practitioner interaction. A third arm of the study included a waitlist control group. The primary outcome was the IBS Global Improvement Scale (IBS-GIS) (range: 1 - 7); secondary outcomes included the IBS Symptom Severity Scale (IBS-SSS), the IBS Adequate Relief (IBS-AR), and the IBS Quality of Life (IBS-QOL). RESULTS: Although there was no statistically significant difference between acupuncture and sham acupuncture on the IBS-GIS (41 vs. 32 % , P = 0.25), both groups improved significantly compared with the waitlist control group (37 vs. 4 % , P = 0.001). Similarly, small differences that were not statistically significant favored acupuncture over the other three outcomes: IBS-AR(59 vs. 57 % , P = 0.83), IBS-SSS (31 vs. 21 % , P = 0.18), and IBS-QOL (17 vs. 13 % , P = 0.56). Eliminating responders during the run-in period did not substantively change the results. Side effects were generally mild and only slightly greater in the acupuncture group. CONCLUSIONS: This study did not find evidence to support the superiority of acupuncture compared with sham acupuncture in the treatment of IBS.

Mirror, mirror on the wall: placebo effects that exist only in the eye of the beholder.

Rationale The extent to which placebo effects can be driven exclusively by subjective impressions of improvement in the absence of any independent corroboration is unclear. Methods Thirty-six self-referred patients were treated with a light therapy device intended to rejuvenate facial skin. At each of eight weekly treatments, participants' facial skin was exposed for 40 seconds to pulses of multispectral LED-generated light in the range of 588 nm wavelength at 0.1 J cm(-2). Outcomes were assessed by participants as well as by the treating doctor and by blinded, expert raters. Results Patients reported robust and statistically significant improvements in seven facial features at the conclusion of the 8-week treatment regimen as well as at 1-month follow-up (for all comparisons, P 0.05). Moreover, effect sizes were close to zero and in the opposite direction from improvement (median d = -0.06 for doctor ratings; and for observer ratings, there was only a 46% success rate at identifying post-treatment as compared with pre-treatment photographs). Conclusion The robust placebo responses documented in this trial were confined to the subjective impressions of the patients. Neither the treating doctor nor blinded, expert raters could detect any improvement. Thus, patients can perceive improvement in medical interventions in the absence of any independent corroboration that improvement has occurred. This result is used a heuristic to more clearly define the components of the placebo response.

In the eye of the beholder--skin rejuvenation using a light-emitting diode photomodulation device.

BACKGROUND: A light-emitting diode (LED) photomodulation system can produce pulses of amber light expected to induce structural skin changes and reverse the effects of photoaging. OBJECTIVE: To reproduce the encouraging results already published. METHODS AND MATERIALS: Facial skin was exposed to pulses of 588+/-10-nm-wavelength light from a photomodulation device for 40 seconds once a week for 8 weeks. Photographs, clinical assessment, and a subjective questionnaire were taken at baseline, at the last follow-up, and 1 month after that. Thirty-six patients' pre- and post-treatment photos were arbitrarily scrambled, and 30 independent blinded observers were asked to pick the post-treatment photo. Two time-point comparisons were evaluated. RESULTS: For every facial characteristic studied and for both time-point comparisons, patients reported highly statistically significant improvements. In extremely sharp contrast, neither the physician's assessment nor the independent observers' evaluation indicated any improvement. CONCLUSION: Although subjective findings are comparable between studies, we were unable to reproduce the objective results of efficacy previously reported. Patients genuinely believed that several of their facial features had improved, even though there was no detectable objective change. Our data therefore suggest that the LED photomodulation treatment from the device tested is a placebo.

Tactile acuity in experienced Tai Chi practitioners: evidence for use dependent plasticity as an effect of sensory-attentional training.

The scientific discovery of novel training paradigms has yielded better understanding of basic mechanisms underlying cortical plasticity, learning and development. This study is a first step in evaluating Tai Chi (TC), the Chinese slow-motion meditative exercise, as a training paradigm that, while not engaging in direct tactile stimulus training, elicits enhanced tactile acuity in long-term practitioners. The rationale for this study comes from the fact that, unlike previously studied direct-touch tactile training paradigms, TC practitioners focus specific mental attention on the body's extremities including the fingertips and hands as they perform their slow routine. To determine whether TC is associated with enhanced tactile acuity, experienced adult TC practitioners were recruited and compared to age-gender matched controls. A blinded assessor used a validated method (Van Boven et al. in Neurology 54(12): 2230-2236, 2000) to compare TC practitioners' and controls' ability to discriminate between two different orientations (parallel and horizontal) across different grating widths at the fingertip. Study results showed that TC practitioners' tactile spatial acuity was superior to that of the matched controls (P < 0.04). There was a trend showing TC may have an enhanced effect on older practitioners (P < 0.066), suggesting that TC may slow age related decline in this measure. To the best of our knowledge, this is the first study to evaluate a long-term attentional practice's effects on a perceptual measure. Longitudinal studies are needed to examine whether TC initiates or is merely correlated with perceptual changes and whether it elicits long-term plasticity in primary sensory cortical maps. Further studies should also assess whether related somatosensory attentional practices (such as Yoga, mindfulness meditation and Qigong) achieve similar effects.

Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome.

OBJECTIVE: To investigate whether placebo effects can experimentally be separated into the response to three components-assessment and observation, a therapeutic ritual (placebo treatment), and a supportive patient-practitioner relationship-and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome. To assess the relative magnitude of these components. DESIGN: A six week single blind three arm randomised controlled trial. SETTING: Academic medical centre. PARTICIPANTS: 262 adults (76% women), mean (SD) age 39 (14), diagnosed by Rome II criteria for and with a score of > or =150 on the symptom severity scale. INTERVENTIONS: For three weeks either waiting list (observation), placebo acupuncture alone ("limited"), or placebo acupuncture with a patient-practitioner relationship augmented by warmth, attention, and confidence ("augmented"). At three weeks, half of the patients were randomly assigned to continue in their originally assigned group for an additional three weeks. MAIN OUTCOME MEASURES: Global improvement scale (range 1-7), adequate relief of symptoms, symptom severity score, and quality of life. RESULTS: At three weeks, scores on the global improvement scale were 3.8 (SD 1.0) v 4.3 (SD 1.4) v 5.0 (SD 1.3) for waiting list versus "limited" versus "augmented," respectively (P<0.001 for trend). The proportion of patients reporting adequate relief showed a similar pattern: 28% on waiting list, 44% in limited group, and 62% in augmented group (P<0.001 for trend). The same trend in response existed in symptom severity score (30 (63) v 42 (67) v 82 (89), P<0.001) and quality of life (3.6 (8.1) v 4.1 (9.4) v 9.3 (14.0), P<0.001). All pairwise comparisons between augmented and limited patient-practitioner relationship were significant: global improvement scale (P<0.001), adequate relief of symptoms (P<0.001), symptom severity score (P=0.007), quality of life (P=0.01). Results were similar at six week follow-up. CONCLUSION: Factors contributing to the placebo effect can be progressively combined in a manner resembling a graded dose escalation of component parts. Non-specific effects can produce statistically and clinically significant outcomes and the patient-practitioner relationship is the most robust component. TRIAL REGISTRATION: Clinical Trials NCT00065403.