Search

Hojjat Daniali,1 Mollie A Ruben,2 Per M Aslaksen,3 Charlotte Fiskum,1 Ted J Kaptchuk,4 Magne A Flaten1 1Department of Psychology, Norwegian University of Science and Technology, Trondheim, Norway; 2Department of Psychology, University of Rhode Island, Kingston, RI, USA; 3Department of Psychology, UiT The Arctic University of Norway, Tromsø, Norway; 4Program in Placebo Studies, Beth Israel Deaconess Medical Center/ Harvard Medical School, Boston, MA, USACorrespondence: Hojjat Daniali, Department of Psychology, Norwegian University of Science and Technology, Trondheim, NO-7491, Norway, Email hojjat.daniali@ntnu.noIntroduction: Studies suggest facial expressions of caregivers may be important in placebo effects; however, this has not been systematically tested. This experiment investigated the effects of caregivers’ singular positive nonverbal behaviours (NBs) on pain reports.Methods: Fifty-one males and 53 females (total of 104) participants were randomized to four groups that were displayed positive facial expressions, tone of voice, body movement, or neutral NBs of videotaped experimenters. Subjective reports of pain, stress, arousal, and cardiac activity were obtained in a pre-test, a conditioning phase, and at a post-test. Four minutes of heat pain was induced in each test, and a placebo cream was administered before the conditioning and post-test in all groups.Results: There were no differences between the NB groups in the reduced pain. Males had larger reduction in pain in the post-test, and females had lower arousal than the opposite sex. During the conditioning, females had larger reduction in pain ie, unconditioned pain response (UPR). In females, the UPR predicted the reinforced expectation ie, increase in expectations from conditioning to post-test, and fear of minor pain negatively predicted both the UPR and reinforced expectation.Discussion: Singular NBs of caregiver were weak to enhance placebo effects. Females had lower pain during conditioning, and the UPR amplitude in females was associated with positive expectations. Moreover, for females, fear of minor pain weakened the UPR and expectations of cream.Conclusion: No NB of caregivers is more effective in reducing pain. Caregivers’ NBs are less effective when displayed individually. Males and females may be different in underlying mechanisms of placebo effects.Keywords: placebo effects, subtle factors, nonverbal behaviours, heat pain, experimenter effects, pain report

To observe the effect of Xuefu Zhuyu Decoction ()-containing serum (XFZYD-CS) on endothelial progenitor cell (EPC) tube formation in vitro. Mononuclear cells from rat bone marrow were prepared in a Ficoll density gradient centrifuge. EPCs were separated by the differential attachment method, and observed with inverted microscope for the effect of XFZYD-CS on EPC tube formation. After one day, EPCs exposed to the serum containing 5%, 10% and 15% XFZYD-CS formed typical tubes or vessel networks. The tube formation time was two days ahead of the control group and the size of most tubes in the serum groups was smaller than in the control group. XFZYD-CS could induce EPC angiogenesis and hasten tube formation, especially in capillary vessels. The study provides experimental evidence for the plausibility of Xuefu Zhuyu Decoction in the treatment of ischemic diseases. [ABSTRACT FROM AUTHOR]

Aim: We aim to determine the safety and effectiveness of a standard therapeutic package of Korean medicine for the treatment of unexplained infertility in a cross-section of women who sought treatment at an integrative hospital in Seoul, Korea. Background: Infertility affects more than 1.2 million women in the United States alone. Treatment options for infertility vary, yet the barriers of invasiveness, cost, and access inhibit treatment use for many women. Alternative medical approaches exist for this indication, and sustain certain popularity. Therefore, we systematically studied a standard therapeutic package of Korean medicine to treat unexplained infertility in women. Methods: Female participants included in this observational study met inclusion criteria before receiving a set of treatments including herbal medicine, acupuncture, and moxibustion. A study physician screened each patient in accordance with inclusion criteria, provided study information, and after the patients consented, performed the baseline assessment. Assessments included age, the history of assisted reproductive technology, and duration of infertility. The key outcome measure included the number who achieved pregnancy and any neo-natal morbidity and mortality at follow-up stage for those who got pregnant. Any other adverse events including aggravation of existing symptoms, and the number of dropouts, were recorded. Treatments were supposed to be completed after 6 menstrual cycles between February 2005 and April 2006. Results: One hundred and four (104) women with unexplained infertility were included in this observational study. Participant mean age was 32 years (SD: 2.7), with a range between 26 and 41 years. The median duration of infertility after diagnosis was 33.5 weeks (interquartile range: 20.8-50.3). In total, 41 participants (39.4%) had undergone a mean number of 1.4 (SD: 2.2) assisted reproductive technology treatments prior to joining the study. The number of patients remaining in or achieving pregnancy throughout the 6-month study period was 23 (14 pregnancies), 22.1%. Six (6) participants (4.8%) reported minor adverse events including rash in the face ( n = 1), diarrhea ( n = 2), dizziness ( n = 1), and heartburn ( n = 2). Of the 14 pregnancies, there were 10 normal births, and 4 miscarriages; otherwise, no neonatal morbidity/mortality occurred. According to per protocol analysis, 14 pregnancies out of 23 total were achieved by those who remained for the entire six menstruation cycle treatments, yielding a pregnancy rate of 60.9%. Conclusions: The standard therapeutic package for unexplained infertility in women studied here is safe for infants and the treated women, when administered by licensed professionals. While it remains challenging to have the target population complete a 6-month treatment course, during which most patients have to pay out of pocket, the extent of successfully achieved pregnancy in those who received full treatment provides meaningful outcomes, warranting further attention. A future study that includes subsidized treatment costs, encouraging the appropriate compliance rate, is warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Governments, international agencies and corporations are increasingly investing in traditional herbal medicine research. Yet little literature addresses ethical challenges in this research. In this paper, we apply concepts in a comprehensive ethical framework for clinical research to international traditional herbal medicine research. We examine in detail three key, underappreciated dimensions of the ethical framework in which particularly difficult questions arise for international herbal medicine research: social value, scientific validity and favourable risk-benefit ratio. Significant challenges exist in determining shared concepts of social value, scientific validity and favourable risk-benefit ratio across international research collaborations. However, we argue that collaborative partnership, including democratic deliberation, offers the context and process by which many of the ethical challenges in international herbal medicine research can, and should be, resolved. By 'cross-training' investigators, and investing in safety-monitoring infrastructure, the issues identified by this comprehensive framework can promote ethically sound international herbal medicine research that contributes to global health. [ABSTRACT FROM AUTHOR]

In this, the first of 2 companion papers, we present a framework for viewing t'ai chi as a complex, multicomponent intervention that integrates numerous physical, cognitive, and ritualistic components. We discuss how the richness and complexity of t'ai chi poses challenges related to the traditional distinction between specific versus nonspecific effects, the development and interpretation of valid sham controls, and more generally, to the reductionist causal approach of attributing observed outcomes to single, independent component factors. We also discuss parallels between t'ai chi research and the emerging field of whole systems research, and how t'ai chi research may benefit from the use of an ecologic framework. In a second, companion paper, we discuss additional challenges inherent in defining the t'ai chi intervention itself, and more comprehensively outline the benefits and limitations of commonly used clinical research designs to evaluate the efficacy and safety of t'ai chi. [ABSTRACT FROM AUTHOR]

In a pilot study, we evaluated the clinical and mechanistic effects of two styles of acupuncture, Traditional Chinese Medicine (TCM) and Japanese acupuncture, for the treatment of painful diabetic neuropathy. Out of seven patients enrolled, three received Traditional Chinese acupuncture while four received Japanese style acupuncture. Treatments were delivered once a week for 10 weeks. Acupuncturists were permitted to select the needle interventions. Substantial differences in diagnostic techniques, choice of acupuncture points, and needle manipulation were observed between TCM and Japanese acupuncturists. Clinically, patients allocated to Japanese acupuncture reported decreased neuropathy-associated pain according to the daily pain severity score, while the group allocated to the TCM acupuncture reported minimal effects. Both acupuncture styles, however, lowered pain according to the McGill Short Form Pain Score, The TCM style improved nerve sensation according to quantitative sensory testing while the Japanese style had a more equivocal effect. No evident changes were observed in glucose control or heart rate variability in either group. [ABSTRACT FROM AUTHOR]

Since the early 1970s, acupuncture has been the subject of multiple animal experiments and randomized clinical trials. Our understanding of acupuncture from both the clinical and mechanistic perspectives has, as a result, grown tremendously. Yet the final word on acupuncture as a therapy remains mixed, largely due to the contradictory nature of the evidence. With some exception, what clinical conditions would benefit and how acupuncture physiologically operates remains unclear. The impediment to progress is found in three disjunctions in acupuncture research: (1) the biomedical need to standardize treatments creates uncertainty about whether we are studying acupuncture appropriately; (2) the variability in acupuncture styles creates ambiguity about whether we are studying the right style; and (3) the discrepancy between animal and human studies creates questions about whether we truly understand the underlying mechanism responsible for acupuncture's therapeutic effect. We propose that these disjunctions are best addressed with the use of 'manualized' protocols in clinical trials that are linked with mechanistic studies. Through this approach, we can create a healthy dialogue between the medical and acupuncture communities and recognize the unique physiologic properties that may be found in each acupuncture style. To illustrate how this proposal may fundamentally change acupuncture research, we present diabetic neuropathy as a particularly interesting model because of its complex heterogeneous pathophysiology. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study quantifies and compares patient characteristics in outpatient acupuncture. SETTING/DESIGN: Prospective primary source evidence was gathered at two prominent outpatient acupuncture clinics in Beijing, China (n = 563, n = 233). RESULTS: The most common condition was Bell's palsy, which represented 20.6% and 25.3% of total cases at the two clinics, respectively. The second most common condition was cerebrovascular accident (CVA) rehabilitation. These treatments represented 11.9% and 12.0% of treatments at the two clinics, respectively. Other trends at the clinics included the following: (1) neurologic complaints predominated; (2) doctors see a large number of patients per day; (3) the majority of patients overall were female; while (4) the majority of patients treated for CVAs rehabilitation were male. As cultural and socioeconomic differences in perceptions of acupuncture exist between peoples of different countries, this study also compared patient main complaints in China to available data on acupuncture patients seen in other parts of China, Germany, the United Kingdom, Australia, and the United States. Except for the German clinic data, Western clinic acupuncturists saw more musculoskeletal complaints compared to China, where neurologic complaints predominated. Another significant difference between Asian and Western clinics was the number of patients seen per hour. While acupuncturists were reported to see 1.2 patients per hour in U. S. clinics, acupuncturists at the two Beijing, China, clinics saw 7.0 and 10.4 patients per hour, respectively. CONCLUSION: The main complaints seen in acupuncture outpatient clinics throughout the world likely result from a combination of inherent disease prevalence as well as patients' attitudes toward what acupuncture can treat successfully. Copyright Mary Ann Liebert, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND: We aimed to describe prevailing attitudes and practices of rheumatologists in the United States toward complementary and alternative medicine (CAM) treatments. We wanted to determine whether rheumatologists' perceptions of the efficacy of CAM therapies and their willingness to recommend them relate to their demographic characteristics, geographic location, or clinical practices. METHODS: A National Institutes of Health-sponsored cross-sectional survey of internists and rheumatologists was conducted regarding CAM for treatment of chronic back pain or joint pain. In this study we analyzed responses only from rheumatologists. Response items included participant characteristics and experience with 6 common CAM categories, as defined by the National Institutes of Health. Descriptive statistics were used to describe attitudes to CAM overall and to each CAM category. Composite responses were devised for respondents designating 4 or more of the 6 CAM therapies as 'very' or 'moderately' beneficial or 'very likely' or 'somewhat likely' to recommend. RESULTS: Of 600 rheumatologists who were sent the questionnaire, 345 responded (58%); 80 (23%) were women. Body work had the highest perceived benefit, with 70% of respondents indicating benefit. Acupuncture was perceived as beneficial by 54%. Most were willing to recommend most forms of CAM. Women had significantly higher composite benefit and recommend responses than men. Rheumatologists not born in North America were more likely to perceive benefit of select CAM therapies. CONCLUSIONS: In this national survey of rheumatologists practicing in the United States, we found widespread favorable opinion toward many, but not all, types of CAM. Further research is required to determine to what extent CAM can or should be integrated into the practice of rheumatology in the United States. [ABSTRACT FROM AUTHOR]

Few complementary and alternative medicine (CAM) institutions require their students to undergo substantive training in research literacy and conduct, and well-developed programs to train CAM institution faculty in research are virtually non-existent. As part of a National Center for Complementary and Alternative Medicine (NCCAM) initiative to increase research capacity at CAM institutions, the New England School of Acupuncture (NESA), in collaboration with the Harvard Medical School (HMS) Osher Institute, was awarded a Developmental Center for Research on Complementary and Alternative Medicine (DCRC) grant. This article discusses a number of initiatives that we designed and implemented to train NESA students, faculty members, and alumni in the foundations of clinical research and to stimulate interest in both participating in research and receiving additional research training. Specific initiatives included a 30-hour faculty 'Foundations of Research' course; a year-long course entitled, 'How to Write a Publishable Case Report'; institution of a monthly research seminar series; revision of an already required student research course; and the addition of 2 new student-mentored independent research electives. We discuss successes and challenges encountered in developing and administering these initiatives and the overall impact they have had on research culture and productivity at NESA. [ABSTRACT FROM AUTHOR]

A significant practical, yet perhaps under-appreciated, barrier to a more active role of complementary and alternative medicine (CAM) institutions in research is the organizational infrastructure required for submitting and managing research grants. In this article, we discuss how the New England School of Acupuncture, in collaboration with the Harvard Medical School Osher Institute and with the support of a Developmental Center for Research on Complementary and Alternative Medicine grant awarded by the National Center for Complementary and Alternative Medicine of the National Institutes of Health, developed its grants management infrastructure and increased its research capacity. We highlight initiatives that have been successful, challenges we have encountered, and lessons we learned that may be relevant to other CAM institutions that may wish to develop a research program. [ABSTRACT FROM AUTHOR]

CONTEXT: Outpatient clinical studies of magnet therapy, a complementary therapy commonly used to treat osteoarthritis (OA), have been limited by the absence of a credible placebo control. OBJECTIVE: Our objective was to assess the feasibility and promise of studying static magnetic therapy for knee OA and determine the ability of a new placebo-magnet device to provide concealment of group assignment. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: Academic teaching hospital in Boston. PARTICIPANTS: We enrolled 29 subjects with idiopathic or post-traumatic OA of the knee. INTERVENTIONS: Subjects received either high-strength magnetic (active) or placebo-magnetic (placebo) knee sleeve treatment for 4 hours in a monitored setting and self-treatment 6 hours daily for 6 weeks. MAIN OUTCOME MEASURES: Primary outcomes were change in knee pain as measured by the WOMAC Osteoarthritis Index Pain Subscale at 6 weeks and extent of group concealment at study end. RESULTS: At 4 hours, VAS pain scores (+/- SE) on a 5-item scale (0-500, 500 worst) decreased 79 +/- 18 mm in the active group and 10 +/- 21 mm in the placebo group (P < 0.05). There were no significant differences in any primary or secondary measure of efficacy between the treatment groups at 6 weeks. Despite widespread testing for magnetic properties, at study end, 69% of the active group and 77% of the placebo group (P > 0.2) believed that they had been assigned to the active treatment group. CONCLUSION: Despite our small sample size, magnets showed statistically significant efficacy compared to placebo after 4 hours under rigorously controlled conditions. The sustained efficacy of magnetic therapy for knee osteoarthritis could be assessed in an adequately powered trial utilizing an appropriate control such our new placebo-magnet device. [ABSTRACT FROM AUTHOR]

Importance: Chronic back pain (CBP) is a leading cause of disability. Placebo treatments often provide as much pain relief as bona fide treatments, such as steroid injections. Open-label (honestly prescribed) placebos (OLPs) may relieve CBP without deception, but OLP mechanisms remain poorly understood., Objective: To investigate the long-term efficacy and neurobiological mechanisms of OLP for CBP., Design, Setting, and Participants: A randomized clinical trial of CBP with longitudinal functional magnetic resonance imaging (MRI) comparing OLP with usual care, with 1-year follow-up, was conducted in a university research setting and a community orthopedic clinic. Participants were individuals aged 21 to 70 years with CBP. The trial was conducted from November 2017 to August 2018, with 1-year follow-up completed by November 2019. Data analysis was performed from April 2020 to May 2024. The primary analysis was conducted on an intention-to-treat sample., Interventions: Participants randomized to OLP received a 1-time subcutaneous lumbar saline injection presented as placebo accompanied by information about the power of placebo to relieve pain, alongside their ongoing care. Usual care participants continued their ongoing care., Main Outcomes and Measures: The primary outcome was pain intensity (0-10, with 0 indicating no pain and 10 the most intense) at 1 month posttreatment. Secondary outcomes included pain interference, depression, anxiety, anger, and sleep quality. Functional MRI was performed before and after treatment during evoked and spontaneous back pain., Results: A total of 101 adults (52 [51.4%] females; mean [SD] age, 40.4 [15.4] years) with moderate severity CBP (mean [SD], 4.10 [1.25] intensity; duration, 9.7 [8.5] years) were enrolled. Compared with usual care, OLP reduced CBP intensity posttreatment (relative reduction, 0.61; Hedges g = 0.45; 95% CI, -0.89 to 0.04; P = .02). Through 1-year follow-up, pain relief did not persist, although significant benefits were observed for depression, anger, anxiety, and sleep disruption (Hedges g = 0.3-0.5; all P < .03). Brain responses to evoked back pain for OLP vs usual care increased in rostral anterior cingulate and ventromedial prefrontal cortex and decreased in somatomotor cortices and thalamus. During spontaneous pain, functional connectivity analyses identified OLP vs usual care increases in ventromedial prefrontal cortex connectivity to the rostral ventral medulla, a pain-modulatory brainstem nucleus. No adverse effects of treatment were reported by participants., Conclusions and Relevance: In this randomized clinical trial of OLP vs usual care, a single nondeceptive placebo injection reduced CBP intensity for 1 month posttreatment and provided benefits lasting for at least 1 year posttreatment. Brain mechanisms of OLP in a clinical population overlap with those of deceptive placebos in healthy volunteers, including engagement of prefrontal-brainstem pain modulatory pathways., Trial Registration: ClinicalTrials.gov Identifier: NCT03294148.

Introduction: The concept of acupoints is a key defining feature of acupuncture, yet the scientific basis of acupoints remains unclear. In recent years, there has been an emerging body of animal studies demonstrating an association between cutaneous sensitivity and visceral pathophysiology, through which acupoints over the skin are sensitized in pathologic conditions. Several studies with humans have also been conducted to assess whether the sensitivity of acupoints is distinct in healthy versus clinical populations. However, no systematic review has been conducted to collate and synthesize the status and quality of human studies on this topic. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Literature search was performed by combining variations of search terms related to acupoints and pain sensitivity in PubMed, EMBASE, and Alt HealthWatch (EBSCOHost). Screening of titles and abstracts and review of full-text articles for eligibility were performed by two independent investigators. Using a predefined template, information on subject characteristics, pathologic conditions, names of assessed acupoints, and relevant main findings were extracted from the included studies. The methodological quality of included studies was assessed using a modified Newcastle-Ottawa Scale (NOS) for case-control studies. A quality assessment checklist was also developed by the present authors to examine the quality of reporting of experimental variables that were considered important for evaluating acupoint sensitivity. Results: A total of 3453 studies were identified from the database search, of which 11 met the eligibility criteria to be included in this review. Six studies examined the mechanical sensitivity of body acupoints, and the remaining five studies examined the mechanical sensitivity of auricular points. Overall, findings suggest that the sensitivity of acupoints may be distinct in healthy versus clinical populations. However, there were various potential sources of bias and substantial heterogeneity across included studies in clinical conditions and acupoints. Conclusion: There is at present insufficient evidence to support or refute that acupoints in humans are sensitized in pathologic conditions. There were various methodological issues, including small sample size and poor reporting of experimental design and variables, which limit the ability to draw a definitive conclusion on this topic. It is also largely unclear whether it is the general body regions rather than specific acupoints that may be sensitized, as most studies did not include nonacupoint location(s) for comparison. Thus, further rigorous research is warranted.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Hope is an integral, multi-dimensional part of seeking medical treatment. The aim of this study was to develop a self-report scale, the Hope in Medicine (HIM) scale, to measure different modes of hoping in relation to the course of symptoms, the effects of treatment, and supporting medical research., Method: We examined the psychometric properties of the scale in a sample of 74 allergic rhinitis patients participating in a 2-week randomized-controlled trial comparing open-label placebos (OLP) with treatment as usual (TAU)., Results: The HIM scale had a Cronbach's α of .78. An exploratory factor analysis revealed four factors: realistic hope (i.e., hoping for specific positive outcomes such as improvement in symptoms), transcendent hope (i.e., non-directed hoping that things will turn out positively), utopian hope (i.e., hoping to contribute to greater knowledge), and technoscience hope (i.e., hoping for scientific breakthroughs). Speaking to the convergent validity of the scale, realistic hope was moderately related to treatment expectancies (r = .54); transcendent hope was related to optimism (r = .50), treatment expectancies (r = .37), self-efficacy (r = .36), and inversely correlated with pessimism (r = -.43). Hope subscales predicted neither course of symptoms nor impairment., Conclusion: The HIM scale is a questionnaire with adequate internal consistency allowing to assess four modes of hoping. Preliminary results for its convergent validity are promising. Yet, further validation is needed., Competing Interests: The authors have declared that no competing interests exist.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) includes negative sensations that remain a major chronic problem for cancer survivors. Previous research demonstrated that neurofeedback (a closed-loop brain-computer interface [BCI]) was effective at treating CIPN versus a waitlist control (WLC). The authors' a priori hypothesis was that BCI would be superior to placebo feedback (placebo control [PLC]) and to WLC in alleviating CIPN and that changes in brain activity would predict symptom report., Methods: Randomization to one of three conditions occurred between November 2014 and November 2018. Breast cancer survivors no longer in treatment were assessed at baseline, at the end of 20 treatment sessions, and 1 month later. Auditory and visual rewards were given over 20 sessions based on each patient's ability to modify their own electroencephalographic signals. The Pain Quality Assessment Scale (PQAS) at the end of treatment was the primary outcome, and changes in electroencephalographic signals and 1-month data also were examined., Results: The BCI and PLC groups reported significant symptom reduction. The BCI group demonstrated larger effect size differences from the WLC group than the PLC group (mean change score: BCI vs. WLC, -2.60 vs. 0.38; 95% confidence interval, -3.67, -1.46 [p = .000; effect size, 1.07]; PLC, -2.26; 95% confidence interval, -3.33, -1.19 [p = .001 vs. WLC; effect size, 0.9]). At 1 month, symptoms continued to improve only for the BCI group. Targeted brain changes at the end of treatment predicted symptoms at 1 month for the BCI group only., Conclusions: BCI is a promising treatment for CIPN and may have a longer lasting effect than placebo (nonspecific BCI), which is an important consideration for long-term symptom relief. Although scientifically interesting, the ability to separate real from placebo treatment may not be as important as understanding the placebo effects differently from effects of the intervention., Plain Language Summary: Chemotherapy-induced nerve pain (neuropathy) can be disabling for cancer survivors; however, the way symptoms are felt depends on how the brain interprets the signals from nerves in the body. We determined that the perception of neuropathy can be changed by working directly with the brain. Survivors in our trial played 20 sessions of a type of video game that was designed to change the way the brain processed sensation and movement. In this, our second trial, we again observed significant improvement in symptoms that lasted after the treatment was complete., (© 2023 American Cancer Society.)

Background and Objectives: Although acupuncture is listed as a beneficial treatment for neck/shoulder stiffness, which has increased with the spread of information technology, to date, evidence of its efficacy under double-blind conditions has not been shown. This study aimed to assess whether acupuncture treatment with superficial skin piercing is superior to placebo treatment. Materials and Methods: A randomized, double-blind (practitioner-patient) placebo-controlled trial was performed at a single center with four arms (ISRCTN76896018). Four hundred patients with essential neck/shoulder stiffness were randomly assigned to penetrating needle treatment (acupuncture ritual and skin penetration), skin-touch needle treatment (acupuncture ritual and skin touch), no-touch needle treatment (acupuncture ritual alone), and no-treatment control. Each of the six acupuncturists applied a needle to each of the four acupoints in the neck/shoulder of 50 patients. Results: Each of the three treatments significantly ( p = 0.01) improved neck/shoulder stiffness compared with the no-treatment control immediately and 24 h after treatment. There was a significant improvement in penetrating needle treatment over no-touch needle treatment 24 h later. However, there was no significant difference between the penetrating and skin-touch and skin-touch vs. no-touch. Conclusions: All treatments that received the ritual of acupuncture were better than the no-treatment control. Only genuine acupuncture involves the specific effects of needle insertion into the body. The acupuncture ritual had a significant impact on the subjective improvement of neck/shoulder stiffness; however, improvement with ritual alone versions of placebo acupuncture was not maintained as with superficial skin piercing. Our study provides important evidence of acupuncture efficacy and information regarding inert no-touch placebo control in acupuncture research.

Objective: Randomized controlled trials (RCTs) in epilepsy for drug treatments are plagued by high costs. One potential remedy is to reduce placebo response via better control over regression to the mean (RTM). Here, RTM represents an initial observed seizure rate higher than the long-term average, which gradually settles closer to the average, resulting in apparent response to treatment. This study used simulation to clarify the relationship between eligibility criteria and RTM., Methods: Using a statistically realistic seizure diary simulator, the impact of RTM on placebo response and trial efficacy was explored by varying eligibility criteria for a traditional treatment phase II/III RCT for drug-resistant epilepsy., Results: When the baseline period was included in the eligibility criteria, increasingly larger fractions of RTM were observed (25%-47% vs. 23%-25%). Higher fractions of RTM corresponded with higher expected placebo responses (50% responder rate [RR50]: 2%-9% vs. 0%-8%) and lower statistical efficacy (RR50: 47%-67% vs. 47%-81%). The exclusion of baseline from eligibility criteria was shown to decrease the number of patients needed by roughly 30%., Significance: The manipulation of eligibility criteria for RCTs has a predictable and important impact on RTM, and therefore on placebo response; the difference between drug and placebo was more easily detected. This in turn impacts trial efficacy and therefore cost. This study found dramatic improvements in efficacy and cost when baseline was not included in eligibility., (© 2023 International League Against Epilepsy.)