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Background Previous research has shown that after one month of full dose nightly treatment with zolpidem (priming), subjects with chronic insomnia (CI) switched to intermittent dosing with medication and placebos were able to maintain their treatment responses. This approach to maintenance therapy is referred to as partial reinforcement. The present study sought to assess whether priming is required for partial reinforcement or whether intermittent dosing with placebos (50% placebos and 50% active medication) can, by itself, be used for both acute and extended treatment. Method 55 CI subjects underwent a baseline evaluation (Phase-1) and then were randomized to one of two conditions in Phase-2 of the study: one month of (1) nightly medication use with standard-dose zolpidem (QHS [n = 39]) or (2) intermittent dosing with standard-dose zolpidem and placebos (IDwP [n = 16]). In Phase-3 (three months), the QHS group was re-randomized to either continued QHS full dose treatment (FD/FD) or to IDwP dose treatment (FD/VD). Treatment response rates and Total Wake Time (TWT = [SL + WASO + EMA]) were assessed during each phase of the study. Results In Phase-2, 77% (QHS) and 50% (IDwP) subjects exhibited treatment responses (p = 0.09) where the average change in TWT was similar. In Phase-3, 73% (FD/FD), 57% (FD/VD), and 88% (VD/VD) of subjects exhibited continued treatment responses (p = 0.22) where the average improvement in TWT continued with FD/FD and remained stable for FD/VD and VD/VD (p Conclusion These results suggest that intermittent dosing with placebos can maintain effects but do not allow for the additional clinical gains afforded by continuous treatment.

Vulvodynia, vulvar pain of unknown origin lasting at least 3 months, affects 7% of American women. Dyspareunia, its frequent companion, renders sexual intercourse virtually impossible. Although few therapies are efficacious and rapid pain relief is rarely possible, there have been no sham/placebo-controlled studies of acupuncture for vulvodynia. Aims are to: 1) determine efficacy of acupuncture for vulvodynia, 2) explore duration of the acupuncture effect.In a pretest/posttest randomized controlled, double-blind (practitioner-patient) efficacy trial of a standardized acupuncture protocol, we will randomize 80 participants 1:1 to either penetrating needle or skin-touch placebo needle groups. Both types of needles are designed to blind both the acupuncturist and participant. Participants with vulvodynia will insert and remove a tampon as a standardized stimulus and complete primary measures of vulvar pain (pain intensity) and secondary measures of dyspareunia (Female Sexual Function Index, FSFI dyspareunia subscale score) and sexual function (FSFI total score) pretreatment, after the 10th acupuncture session, and pain measures weekly until return to pretest levels. Upon study completion control group participants will be offered 10 free real acupuncture sessions.This is the first multi-needle multi-session RCT using double-blind acupuncture needles as a reliable sham. We hypothesize that controlling for baseline, at posttest there will be statistically significant less vulvar pain and dyspareunia and more sexual function over five weeks in the penetrating needle group compared to the skin touch placebo group.This study is responsive to the need for efficacious pain management for women with vulvodynia.ClinicalTrials.gov Identifier: NCT03364127.

Background Previous studies have found widespread pain processing alterations in the brain in chronic low back pain (cLBP) patients. We aimed to (1) identify brain regions showing altered amplitude of low-frequency fluctuations (ALFF) using MRI and use these regions to discriminate cLBP patients from healthy controls (HCs) and (2) identify brain regions that are sensitive to cLBP pain intensity changes. Methods We compared ALFF differences by MRI between cLBP subjects (90) and HCs (74), conducted a discriminative analysis to validate the results, and explored structural changes in key brain regions of cLBP. We also compared ALFF changes in cLBP patients after pain-exacerbating manoeuvres. Results ALFF was increased in the post-/precentral gyrus (PoG/PrG), paracentral lobule (PCL)/supplementary motor area (SMA), and anterior cingulate cortex (ACC), and grey matter volume was increased in the left ACC in cLBP patients. PCL/SMA ALFF reliably discriminated cLBP patients from HCs in an independent cohort. cLBP patients showed increased ALFF in the insula, amygdala, hippocampal/parahippocampal gyrus, and thalamus and decreased ALFF in the default mode network (DMN) when their spontaneous low back pain intensity increased after the pain-exacerbating manoeuvre. Conclusions Brain low-frequency oscillations in the PCL, SMA, PoG, PrG, and ACC may be associated with the neuropathology of cLBP. Low-frequency oscillations in the insula, amygdala, hippocampal/parahippocampal gyrus, thalamus, and DMN are sensitive to manoeuvre-induced spontaneous back pain intensity changes.

In chronic pain management and treatment, a positive patient-clinician relationship is associated with higher patient satisfaction and treatment efficacy. In this study, we investigated synchronization of brain activity between patients and clinicians during an experimentally controlled augmented (empathetic) compared to limited (business-like) clinical interaction context. We recorded EEG simultaneously (hyperscanning, 16 dyads, 64 channels per subject) from low back pain patients and acupuncturists during a task with treatment trials (acupuncture) and no-treatment trials in conjunction with evoked cuff pain. EEG data were reconstructed using the algorithm exact LORETA on 17 Regions of Interest (ROIs) defined by our previous fMRI study (Ellingsen et al. 2020) and directed statistical connectivity patterns were obtained by comparing Granger Causality-based estimates for treatment and no-treatment trials (α=0.05, FDR corrected). Patients in the augmented group, compared to the limited group, rated therapeutic alliance and clinician warmth significantly higher. Low back pain intensity decreased after acupuncture treatment, irrespective of clinical context. EEG analysis suggested that in Theta band (linked with empathy for pain in prior EEG studies), inter-brain network density within social mirroring and pain/sensorimotor brain regions was altered when acupuncturists treated evoked pain. The number of significant inter-brain clinician-to-patient connections was higher in the no-treatment condition, while the number of patient-to-clinician connections were greater during treatment trials. Also, the density of patient-to-clinician inter-brain connections increased during treatment relative to no-treatment irrespective of clinical context, yet statistical significance was noted only for the augmented group. Both behavioral and simultaneous brain-to-brain responses across the patient/clinician dyad reflect clinical interaction context. EEG hyperscanning is an ecologically valid approach to identify inter-brain networks whose density and directionality within the dyad is altered by treatment and clinical context, highlighting new brain mechanisms linking therapeutic alliance and chronic pain therapy. Research supported by NIH - National Center for Complementary and Integrative Health, NIH-NIBIB National Institute of Biomedical Imaging and Bioengineering and Korea Institute of Oriental Medicine (KIOM).

While patient/clinician relationships significantly impact pain outcomes, the behavioral and neural mechanisms supporting this phenomenon are unknown. Specifically, the precise role of facial expressions in contributing to analgesia and brain-to-brain communication has not been investigated. In this Hyperscan fMRI study, we explored how pain-related, directional facial communication between patient and clinician engaging in interactive pain treatment is associated with brain concordance. Dyads comprising 20 patients with fibromyalgia and 19 acupuncturists completed two synchronous fMRI scans (two different partners per participant). During fMRI, dyad members saw each other's face through closed-circuit video while interacting. The fMRI scan included a series of moderately painful and minimally/non-painful leg cuff pressure stimuli to the patient while the clinician observed. A separate fMRI scan included clinician-applied and remotely-activated electroacupuncture treatment to the patient while they received moderate cuff pressure pain. In-scanner videos were used for automated individual facial muscle unit (FMU) timeseries extraction. FMU data from pain/observation scans was fed into an interpretable machine learning classifier to determine which FMU's dynamics was most associated with pain. FMUs from the pain/treatment scans were used in conjunction with neural-network causality estimation to investigate directional non-verbal communication and their association with brain-to-brain dynamic fMRI concordance (as reported in Ellingsen et al., 2020). Causality analysis indicated a strong asymmetry in which the patients’ facial expressions elicited a range of facial expressions in clinicians, but not vice-versa. Patient lip movement FMUs were most associated with pain. Interestingly, patient-to-clinician causal influence of these FMUs on similar clinicians’ FMUs was associated with dynamic insula cortex brain-to-brain concordance, demonstrating the key role of this social mirroring and salience processing brain region with respect to facial expression mirroring between patients and clinicians. Supported by the National Institutes of Health, National Center for Complementary and Integrative Health (R61-AT009306), Norwegian Research Council /Marie Sklodowska-Curie Actions (FRICON/COFUND-240553/F20), Neuroimaging Pilot Funding Initiative at the Martinos Center for Biomedical imaging, MGH (R90DA023427), Korea Institute of Oriental Medicine (KIOM), Foundation for the Science of the Therapeutic Encounter, National Center for Research Resources (P41RR14075; CRC 1 UL1 RR025758), Harvard Clinical and Translational Science Center, Martinos Computing facilities, and National Institutes of Health (Grant Nos. S10RR023401, S10RR019307, S10RR019254, and S10RR023043).

Research suggests that a good patient-clinician therapeutic alliance can improve clinical outcomes. In this ongoing, longitudinal study, we applied fMRI hyper-scanning to determine whether behavioral, neural, and clinical variables associated with the therapeutic relationship between chronic pain patients and their clinicians influences clinical outcomes. Ten women with fibromyalgia (mean age=40, SD=10.71, each group N=5) were randomly assigned to either an Augmented (warm/attentive) or Limited (neutral/business-like) interaction style, and were treated with electro-acupuncture for 6 biweekly sessions. Before and after acupuncture therapy, each patient-clinician dyad underwent a simultaneously recorded fMRI hyper-scanning procedure with video connection between two scanners and an evoked cuff pressure pain/treatment paradigm. Clinical outcomes and the quality of the patient-clinician relationship were assessed by questionnaires targeting treatment-related changes in clinical pain levels, therapeutic alliance, trust, and the clinician's warmth and competence. Pooled therapeutic alliance (assessed after treatment sessions 1, 3, and 6; scale 0-50) in the Augmented group (mean=43.17, SD=2.97) was significantly higher than in the Limited group (mean=27.27, SD=10.44; t(8)=3.28, p=0.011). Similarly, clinicians’ warmth, as rated by patients, was significantly higher in the Augmented (mean=4.00, SD=0.0) than in the Limited group (3.02, SD=0.73; t(8)=3.00; p=0.017). Preliminary results show that over all 6 acupuncture treatment sessions, irrespective of group assignments, most patients experienced post-treatment clinical pain relief (p

Chronic low back pain (cLBP) is a prevalent disorder. A growing body of evidence linking the pathology of the reward network to chronic pain suggests that pain sensitization may contribute to cLBP chronification via disruptions of mesocortical and mesolimbic circuits in the reward system. Resting-state (RS) functional magnetic resonance imaging (fMRI) data was acquired from 90 patients with cLBP and 74 matched pain-free controls (HCs) at baseline and after a manipulation for back pain intensification. The ventral tegmental area (VTA) was chosen as a seed region to perform RS functional connectivity (FC) analysis. Baseline rsFC of both the mesocortical (between the VTA and bilateral rostral anterior cingulate cortex (rACC) / and medial prefrontal cortex (mPFC)) and mesolimbic (between the VTA and bilateral hippocampus/parahippocampus) pathways was reduced in patients with cLBP (vs. HCs). In addition, patients exhibiting higher back pain intensity (compared to the relatively lower back pain intensity condition) also showed increases in both mesocortical and mesolimbic connectivity, implicating these pathways in pain downregulation in cLBP. Mediation analysis further isolated the mesolimbic (VTA-hippocampus/ parahippocampus) dysconnectivity as a neural mechanism mediating the association between mechanical pain sensitivity (indexed by P40 pressure) and cLBP severity. In sum, the current study demonstrates deficient mesocorticolimbic connectivity in cLBP, with the mesolimbic dysconnectivity potentially mediating the contribution of pain sensitization to pain chronification. These reward network dysfunctions and purportedly, dopaminergic dysregulations, may help us to identify key brain targets of neuromodulation in the treatment of cLBP.

Despite the high prevalence and socioeconomic impact of chronic low back pain (cLBP), treatments for cLBP are often unsatisfactory, and effectiveness varies widely across patients. Recent neuroimaging studies have demonstrated abnormal resting-state functional connectivity (rsFC) of the default mode, salience, central executive, and sensorimotor networks in chronic pain patients, but their role as predictors of treatment responsiveness has not yet been explored. In this study, we used machine learning approaches to test if pre-treatment rsFC can predict responses to both real and sham acupuncture treatments in cLBP patients. Fifty cLBP patients participated in 4 weeks of either real (N = 24, age = 39.0 ± 12.6, 16 females) or sham acupuncture (N = 26, age = 40.0 ± 13.7, 15 females) treatment in a single-blinded trial, and a resting-state fMRI scan prior to treatment was used in data analysis. Both real and sham acupuncture can produce significant pain reduction, with those receiving real treatment experiencing greater pain relief than those receiving sham treatment. We found that pre-treatment rsFC could predict symptom changes with up to 34% and 29% variances for real and sham treatment, respectively, and the rsFC characteristics that were significantly predictive for real and sham treatment differed. These results suggest a potential way to predict treatment responses and may facilitate the development of treatment plans that optimize time, cost, and available resources.

Objective Children with epilepsy experience cognitive deficits and well-being issues that have detrimental effects on their development. Pharmacotherapy is the standard of care in epilepsy; however, few interventions exist to promote cognitive development and to mitigate disease burden. We aimed to examine the impact of two different modalities of neurofeedback (NFB) on cognitive functioning and quality-of-life (QOL) measurements in children and adolescents with controlled focal epilepsy. The study also explored the effects of NFB on clinical outcomes and electroencephalography (EEG) quantitative analysis. Methods Participants (n = 44) with controlled focal epilepsy were randomized to one of three arms: sensorimotor rhythm (SMR) NFB (n = 15), slow cortical potentials (SCP) NFB (n = 16), or sham NFB (n = 13). All participants received 25 sessions of intervention. The attention switching task (AST), Liverpool Seizure Severity Scale (LSSS), seizure frequency (SF), EEG power spectrum, and coherence were measured at baseline, postintervention, and at 3-month follow-up. Results In children and adolescents with controlled focal epilepsy, SMR training significantly reduced reaction time in the AST (p = 0.006), and this was correlated with the difference of change for theta power on EEG (p = 0.03); only the SMR group showed a significant decrease in beta coherence (p = 0.03). All groups exhibited improvement in QOL (p = Conclusions This study provides the first data on two NFB modalities (SMR and SCP) including cognitive, neurophysiological, and clinical outcomes in pediatric epilepsy. Sensorimotor rhythm NFB improved cognitive functioning, while all the interventions showed improvements in QOL, demonstrating a powerful placebo effect in the sham group.

Summary Objective Little is known about the use of Stress Management and Relaxation Techniques (SMART) in racially diverse inpatients. We hope to identify socioeconomic status (SES) factors, health behavior factors, and clinical factors associated with the use of SMART. Design and main outcome measures We conducted a secondary analysis of baseline data from 623 hospitalized patients enrolled in the Re-Engineered Discharge (RED) clinical trial. We assessed socio-demographic characteristics and use of SMART. We used bivariate and multivariate logistic regression to test the association of SMART with socio-demographic characteristics, health behaviors, and clinical factors. Results A total of 26.6% of participants reported using SMART and 23.6% used mind body techniques. Thirty six percent of work disabled patients, 39% of illicit drug users, and 38% of participants with depressive symptoms used SMART. Patients who both reported illicit drug use and screened positive for depression had significantly increased odds of using SMART [OR = 4.94, 95% CI (1.59, 15.13)]. Compared to non-Hispanic whites, non-Hispanic blacks [0.55 (0.34–0.87)] and Hispanic/other race individuals [0.40 (0.20–0.76)] were less likely to use SMART. Conclusions We found greater utilization of SMART among all racial groups compared to previous national studies. In the inner city inpatient setting, patients with depression, illicit drug use, and work disability reported higher rates of using SMART.

Expectations shape the way we experience the world. In this study, we used fMRI to investigate how positive and negative expectation can change pain experiences in the same cohort of subjects. We first manipulated subjects' treatment expectation of the effectiveness of three inert creams, with one cream labeled "Lidocaine" (positive expectancy), one labeled "Capsaicin" (negative expectancy) and one labeled "Neutral" by surreptitiously decreasing, increasing, or not changing respectively, the intensity of the noxious stimuli administered following cream application. We then used fMRI to investigate the signal changes associated with administration of identical pain stimuli before and after the treatment and control creams. Twenty-four healthy adults completed the study. Results showed that expectancy significantly modulated subjective pain ratings. After controlling for changes in the neutral condition, the subjective pain rating changes evoked by positive and negative expectancies were significantly associated. fMRI results showed that the expectation of an increase in pain induced significant fMRI signal changes in the insula, orbitofrontal cortex, and periaqueductal gray, whereas the expectation of pain relief evoked significant fMRI signal changes in the striatum. No brain regions were identified as common to both "Capsaicin" and "Lidocaine" conditioning. There was also no significant association between the brain response to identical noxious stimuli in the pain matrix evoked by positive and negative expectancies. Our findings suggest that positive and negative expectancies engage different brain networks to modulate our pain experiences, but, overall, these distinct patterns of neural activation result in a correlated placebo and nocebo behavioral response.

Placebos are indispensable controls in randomized clinical trials (RCTs), and placebo responses significantly contribute to routine clinical outcomes. Recent neurophysiological studies reveal neurotransmitter pathways that mediate placebo effects. Evidence that genetic variations in these pathways can modify placebo effects raises the possibility of using genetic screening to identify placebo responders and thereby increase RCT efficacy and improve therapeutic care. Furthermore, the possibility of interaction between placebo and drug molecular pathways warrants consideration in RCT design. The study of genomic effects on placebo response, ‘the placebome’, is in its infancy. Here, we review evidence from placebo studies and RCTs to identify putative genes in the placebome, examine evidence for placebo‐ drug interactions, and discuss implications for RCTs and clinical care.

Objective Investigations of the effect of placebo are often challenging to conduct and interpret. The history of placebo shows that assessment of its clinical significance has a real potential to be biased. We analyze and discuss typical types of bias in studies on placebo. Study Design and Setting A methodological analysis and discussion. Results The inherent nonblinded comparison between placebo and no-treatment is the best research design we have in estimating effects of placebo, both in a clinical and in an experimental setting, but the difference between placebo and no-treatment remains an approximate and fairly crude reflection of the true effect of placebo interventions. A main problem is response bias in trials with outcomes that are based on patients’ reports. Other biases involve differential co-intervention and patient dropouts, publication bias, and outcome reporting bias. Furthermore, extrapolation of results to a clinical settings are challenging because of a lack of clear identification of the causal factors in many clinical trials, and the nonclinical setting and short duration of most laboratory experiments. Conclusions Creative experimental efforts are needed to assess rigorously the clinical significance of placebo interventions and investigate the component elements that may contribute to the therapeutic benefit.

Heavy metal and pesticide contamination has previously been reported in Chinese Herbal Medicines (CHMs), in some cases at potentially toxic levels. This study was conducted to determine general patterns and toxicological significance of heavy metal and pesticide contamination in a broad sample of raw CHMs. Three-hundred-thirty-four samples representing 126 species of CHMs were collected throughout China and examined for arsenic, cadmium, chromium, lead, and mercury. Of the total, 294 samples representing 112 species were also tested for 162 pesticides. At least 1 metal was detected in all 334 samples (100%) and 115 samples (34%) had detectable levels of all metals. Forty-two different pesticides were detected in 108 samples (36.7%), with 1 to 9 pesticides per sample. Contaminant levels were compared to toxicological reference values in the context of different exposure scenarios. According to a likely scenario of CHM consumption, only 3 samples (1%) with heavy metals and 14 samples (5%) with pesticides were found with concentrations that could contribute to elevated background levels of contaminant exposure. According to the most conservative scenario of CHM consumption, 231 samples (69%) with heavy metals and 81 samples (28%) with pesticides had contaminants that could contribute to elevated levels of exposure. Wild collected plants had higher contaminant levels than cultivated samples. Cadmium, chromium, lead, and chlorpyrifos contamination showed weak correlations with geographic location. Based on our assumptions of the likely mode of consumption of raw CHMs, the vast majority (95%) of the 334 samples in this study contained levels of heavy metals or pesticides that would be of negligible concern. However, given the number of samples with detectable contaminants and the range between the more likely and more conservative scenarios of contaminant exposure, more research and monitoring of heavy metals (especially cadmium and chromium) and pesticide residues (especially chlorpyrifos) in raw CHMs are advised.

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.

It is well established that expectation can significantly modulate pain perception. In this study, we combined an expectancy manipulation model and fMRI to investigate how expectation can modulate acupuncture treatment. Forty-eight subjects completed the study. The analysis on two verum acupuncture groups with different expectancy levels indicates that expectancy can significantly influence acupuncture analgesia for experimental pain. Conditioning positive expectation can amplify acupuncture analgesia as detected by subjective pain sensory rating changes and objective fMRI signal changes in response to calibrated noxious stimuli. Diminished positive expectation appeared to inhibit acupuncture analgesia. This modulation effect is spatially specific, inducing analgesia exclusively in regions of the body where expectation is focused. Thus, expectation should be used as an important covariate in future studies evaluating acupuncture efficacy. In addition, we also observed dissociation between subjective reported analgesia and objective fMRI signal changes to calibrated pain on the analysis across all four groups. We hypothesize that as a peripheral-central modulation, acupuncture needle stimulation may inhibit incoming noxious stimuli; while as a top-down modulation, expectancy (placebo) may work through the emotional circuit.

Summary Objectives To investigate neural representation evoked by acupuncture from human somatosensory cortices, especially from primary ( SI ) and secondary ( SII ) somatosensory areas. Design and setting Neuroimaging study – Blood-oxygenation-level-dependent (BOLD) functional MRI was performed during acupuncture on LI4 ( n =12 healthy participants). Sham acupuncture and innocuous tactile stimulation were also applied on the same acupuncture site as control comparisons. Outcome measures Responsive neural substrates were visualized and identified based on both individual and group-level surface activation maps. Results Discrete regions within the precentral gyrus (area 4) and the fundus of the central sulcus (area 3a) were selectively activated during the real acupuncture stimulation. In SII , the activation was extended in a postero-inferior direction to the fundus of the lateral sulcus. Conclusion This specific pattern of acupuncture-related activation indicates that deep tissue stimulation (as seen in area 3a activation) and concurrent processing of sensory stimulation (as seen in activation in SII ) may mediate neural responses to manual acupuncture.

Context Gua Sha , therapeutic surface frictioning that intentionally raises transitory petechiae and ecchymosis, is a traditional East Asian healing technique also known as cao gio , coining, scraping, and spooning. There are case reports in Western literature but no studies on the physiological effects of Gua Sha . Objective To study the microcirculatory effects of Gua Sha on the skin and subcutis in humans to elucidate physiological mechanisms responsible for the clinically observed pain-relieving effect of this treatment Design Laser Doppler imaging (LDI) was used to make sequential measurements of the microcirculation of surface tissue before and after Gua Sha treatment in 11 healthy subjects. The effect of Gua Sha treatment on the microcirculation of surface tissue was expressed as changes from baseline in arbitrary perfusion units (PU). Setting The study was conducted at the Department of Nephrology, Unit of Circulation Research, University Hospital of Essen, Germany. Subjects Subjects were volunteers from the nursing and physician staff of the Kliniken Essen. Intervention A single Gua Sha treatment was applied to an area of each subject's back. Outcome Measures Change in microcirculation was measured in PUs. Change in myalgia was subjectively reported and confirmed by manual palpation. Results Gua Sha caused a fourfold increase in microcirculation PUs at the treated area for the first 7.5 minutes following treatment and a significant increase in surface microcirculation during the entire 25 minutes of the study period following treatment ( P P = .003). Each subject experienced immediate decrease in myalgia in both the site treated, in the related distal control site, and in some cases, other distal sites. Pain relief persisted to some extent up to the follow-up visit. There were no adverse reactions. Conclusion Gua Sha increases microcirculation local to a treated area, and that increase in circulation may play a role in local and distal decrease in myalgia. Decrease in myalgia at sites distal to a treated area is not due to distal increase in microcirculation. There is an unidentified pain-relieving biomechanism associated with Gua Sha .

Summary Context The research results on the relationship between social factors and attitudes toward complementary and alternative medicines (CAMs) and conventional practitioners are equivocal. Some researchers theorize a relationship between social factors and attitudes toward providers, with CAM being more attractive to socially and economically marginalized groups. Objectives To evaluate the relationships between selected sociodemographic factors and attitudes toward CAMs in the general US population. Design A subset of data from a 1997–1998 nationally representative survey was examined using descriptive and univariate analyses. Results Five outcomes exploring preference for CAM or conventional medical practitioners are considered. Age was positively related to favoring one's conventional medical doctor. Subjects who reported using CAM for wellness/prevention reported significantly less confidence in their conventional doctors than individuals who did not report using CAM for wellness/prevention. Those with low income were also significantly less confident in their medical doctors and less satisfied with their conventional medical practitioners than those with higher incomes. Conclusions While more prospective work is needed, this analysis suggests that social factors may be related to practitioner preference. Finding out why these relationships exist is important for the effectiveness of health care.

Wayne PM, Krebs DE, Macklin EA, Schnyer R, Kaptchuk TJ, Parker SW, Scarborough DM, McGibbon CA, Schaechter JD, Stein J, Stason WB. Acupuncture for upper-extremity rehabilitation in chronic stroke: a randomized sham-controlled study. Objective To compare the effects of traditional Chinese acupuncture with sham acupuncture on upper-extremity (UE) function and quality of life (QOL) in patients with chronic hemiparesis from stroke. Design A prospective, sham-controlled, randomized controlled trial (RCT). Setting Patients recruited through a hospital stroke rehabilitation program. Participants Thirty-three subjects who incurred a stroke 0.8 to 24 years previously and had moderate to severe UE functional impairment. Interventions Active acupuncture tailored to traditional Chinese medicine diagnoses, including electroacupuncture, or sham acupuncture. Up to 20 treatment sessions (mean, 16.9) over a mean of 10.5 weeks. Main Outcome Measures UE motor function, spasticity, grip strength, range of motion (ROM), activities of daily living, QOL, and mood. All outcomes were measured at baseline and after treatment. Results Intention-to-treat (ITT) analyses found no statistically significant differences in outcomes between active and sham acupuncture groups. Analyses of protocol-compliant subjects revealed significant improvement in wrist spasticity ( P P P P =.09) and digit ROM ( P =.06). Conclusions Based on ITT analyses, we conclude that acupuncture does not improve UE function or QOL in patients with chronic stroke symptoms. However, gains in UE function observed in protocol-compliant subjects suggest traditional Chinese acupuncture may help patients with chronic stroke symptoms. These results must be interpreted cautiously because of small sample sizes and multiple, unadjusted, post hoc comparisons. A larger, more definitive RCT using a similar design is feasible and warranted.

Wayne PM, Krebs DE, Wolf SL, Gill-Body KM, Scarborough DM, McGibbon CA, Kaptchuk TJ, Parker SW. Can Tai Chi improve vestibulopathic postural control? Arch Phys Med Rehabil 2004;85:142-52. Objectives To evaluate the rationale and scientific support for Tai Chi as an intervention for vestibulopathy and to offer recommendations for future studies. Data sources A computer-aided search, including MEDLINE and Science Citation Index, to identify original Tai Chi studies published in English; relevant references cited in the retrieved articles were also included. Study selection A preliminary screening selected all randomized controlled trials (RCTs), non-RCTs, case-control studies, and case series that included Tai Chi as an intervention and had at least 1 outcome variable relevant to postural stability. Data extraction Authors critically reviewed studies and summarized study designs and outcomes in a summary table. Data synthesis Twenty-four Tai Chi studies met screening criteria. No studies specifically studying Tai Chi for vestibulopathy were found. Collectively, the 24 studies provide sometimes contradictory but generally supportive evidence that Tai Chi may have beneficial effects for balance and postural impairments, especially those associated with aging. Ten RCTs were found, of which 8 provide support that Tai Chi practiced alone, or in combination with other therapies, can reduce risk of falls, and/or impact factors associated with postural control, including improved balance and dynamic stability, increased musculoskeletal strength and flexibility, improved performance of activities of daily living (ADLs), reduced fear of falling, and general improvement in psychologic well-being. Studies using other designs support the results observed in RCTs. Conclusions At present, few data exist to support the contention that Tai Chi specifically targets the impairments, functional limitations, disability, and quality of life associated with peripheral vestibulopathy. There are, however, compelling reasons to further investigate Tai Chi for vestibulopathy, in part because Tai Chi appears useful for a variety of nonvestibulopathy etiologic balance disorders, and is safe. Especially needed are studies that integrate measures of balance relevant to ADLs with other psychologic and cognitive measures; these might help identify specific mechanisms whereby Tai Chi can remedy balance disorders.

Summary Background Acupuncture use remains common in the United States, yet little is known of its utilization by minority and underserved populations. Herein we report first visit data capturing patient profiles, types of conditions presented, and self-reports of their experience and satisfaction with acupuncture accessed at a free care clinic with in a large urban safety net hospital. Methods Sixty-one adult, English-speaking acupuncture patients were given a 20 min survey after their first visit to a free care acupuncture clinic. Results Patients were from 12 different countries. Fifty-six percent of the participants were minorities. Sixty-five percent of respondents were female. Average age was 42.1. Eighty percent were acupuncture naive. Patients’ health complaints were similar to those of other surveyed mainstream patients with 57% reporting musculoskeletal conditions. Ninety-three percent would recommend a friend or family for acupuncture, 97% rating their overall experience with the acupuncture clinic as either very good or good. Conclusions When made available to a diverse population of patients, acupuncture is utilized and perceived to be helpful. In this survey, patients sought treatment for musculoskeletal conditions and were satisfied with their first visit. Future research is warranted.

Objective To assess parental attitudes regarding placebo use in pediatric randomized controlled trials and clinical care. Study design Parents with children under age 18 years living in the US completed and submitted an online survey between September and November 2014. Results Among all 1300 participants, 1000 (76.9%; 538 mothers and 462 fathers) met the study inclusion criteria. The majority of surveyed parents considered the use of placebos acceptable in some pediatric care situations (86%) and some pediatric trials (91.5%), whereas only 5.7% of parents found the use of placebos in children always unacceptable. The clinical use of placebo was considered acceptable by a majority of parents for only 7 (mostly psychological) of the 17 conditions presented. Respondents' judgment about acceptability was influenced by the doctors' opinions about the therapeutic benefits of placebo treatment, the conditions for pediatric placebo use, transparency, safety, and purity of placebos. Conclusion Most surveyed parents accepted the idea of using placebos in pediatric trials and within the clinic for some conditions without the practice of deception and with the creation of guidelines for ethical and safe use. This study suggests a need to reconsider pediatric trial design and clinical therapy in the light of generally positive parental support of appropriate placebo use.

The double-blind randomized controlled trial (RCT) is accepted by medicine as objective scientific methodology that, when ideally performed, produces knowledge untainted by bias. The validity of the RCT rests not just on theoretical arguments, but also on the discrepancy between the RCT and less rigorous evidence (the difference is sometimes considered an objective measure of bias). A brief overview of historical and recent developments in “the discrepancy argument” is presented. The article then examines the possibility that some of this “deviation from truth” may be the result of artifacts introduced by the masked RCT itself. Can an “unbiased” method produce bias? Among the experiments examined are those that augment the methodological stringency of a normal RCT in order to render the experiment less susceptible to subversion by the mind. This methodology, a hypothetical “platinum” standard, can be used to judge the “gold” standard. The concealment in a placebo-controlled RCT seems capable of generating a “masking bias.” Other potential biases, such as “investigator self-selection,” “preference,” and “consent” are also briefly discussed. Such potential distortions indicate that the double-blind RCT may not be objective in the realist sense, but rather is objective in a “softer” disciplinary sense. Some “facts” may not exist independent of the apparatus of their production. © 2001 Elsevier Science Inc. All rights reserved.

Objectifs Le but de cette etude est de determiner s’il existe une reponse au placebo chez les patients deficients intellectuels (DI) d’origine genetique. Ces patients presentent en effet une atteinte des capacites qui semblent cruciales pour susciter une reponse au placebo. Materiel et methodes Nous avons realise une meta-analyse (logiciel CMA) comprenant tous les essais randomises controles contre placebo effectues chez des patients DI d’origine genetique, publies avant avril 2013 (Medline/PubMed, EMBASE, CENTRAL et PsycINFO). Resultats Vingt-deux essais randomises controles contre placebo ont ete inclus dans l’analyse ( n = 721, âge moyen = 17.1 ans, 62 % mâles, duree moyenne = 35 semaines). Il existe une reponse au placebo significative chez les patients DI ( g = 0,468, p = 0,002), a la fois pour les mesures « subjectives » (evaluation par une tierce personne, g = 0,6, p = 0,02) et « objectives » (evaluation directe des capacites du patient, g = 0,4, p = 0,03). Un effet significatif de l’âge ( p = 0,02) a ete observe (reponse au placebo plus forte chez les plus jeunes patients). Conclusions Les patients DI d’origine genetique s’ameliorent sous placebo. Il est important de tenir compte du role du placebo pour optimiser les essais therapeutiques futurs dans la DI d’origine genetique.

Although the placebo in a clinical trial is often considered simply a baseline against which to evaluate the efficacy of a clinical intervention, there is evidence that the magnitude of placebo effect may be a critical factor in determining the results of a trial. This article examines the question of whether devices have enhanced placebo effects and, if so, what the implications may be. While the evidence of an enhanced placebo effect remains rudimentary, it is provocative and therefore worthy of further study. Suggestions are made, therefore, for how such an effect can be investigated without violating the principles of informed consent.

Placebo groups are often included in randomized control trials evaluating drug therapy, yet we know little about the placebo effect. The purpose of our study was to evaluate how the presence of a placebo group in a randomized control trial (RCT) influences the patients' ratings of the efficacy of an active drug therapy and their reporting of its adverse effects. We identified studies published between 1966 and 1994 using MEDLINE. Randomized control trials evaluating acetylsalicylic acid, diclofenac, or indomethacin for the treatment of osteo or rheumatoid arthritis were included in our sample. Two investigators independently extracted data. Fifty-eight treatment arms met our inclusion criteria and were available for analysis. Twenty-five treatment arms evaluated a nonsteroidal antiinflammatory drug (NSAID) in placebo control trials and 33 in comparative trials. Using a logistic regression model to adjust for the differences between the evaluated drugs and between the types of arthritis, we found that patients receiving an NSAID in a placebo control trial were more likely to withdraw due to inefficacy (OR=1.3; 95% CI, 1.0 to 1.6; P=0.04). Using a similar model, withdrawals due to adverse effects were found to be more common when the NSAID was given in trials that did not include a placebo group (OR=1.5; 95% CI, 1.1 to 1.9; P=0.002) as were reports of cutaneous (OR=4.2; 95% CI, 1.7 to 9.9), gastrointestinal (OR=1.6; 95% CI, 1.3 to 2.0), and other types (OR=5.3; 95% CI, 3.8 to 7.4) of adverse effects. Although reports of central nervous system adverse effects were more frequent in the comparative trials, this difference was not significant. Including a placebo group in a RCT changes how patients rate the efficacy and adverse effects of their therapy. Our results highlight the need to consider the placebo effect in the design and analyses of clinical trials.

iobitridol : 5 ; iomeprol : 3 ; iodixanol : 1 ; iopentol : 1 ;iopromide : 1). Three patients had a history of previous reaction. Cutaneous reactions (grade 1) occurred in 10 patients, moderate systemic reactions in 9 and life-threatening in 6. Fifteen patients had biochemical studies, 2 had increased concentrations of histamine and tryptase. Sixteen patients went for skin testing, among them 6 had had biochemical measurements. All of them had negative skin Prick tests to the involved CM. One had a positive Prick test to latex, with positive latex IgE, indicating that latex was responsible for the reaction. Eight (including the 2 patients with increased concentrations of mediators, but no patient with normal values) had positive intradermal tests, with the involved CM diluted 1 :100 (2 patients) ; 1 :10 (5 patients), or with the pure ICM (1 patient). The responsible CM were : ioxaglate : 3 ; iomeprol : 2 ; iodixanol : 1 ; iobitridol : 1 ; iohexol : 1. Three of them had also positive skin tests to 2 other CM, indicating cross reactivity between different CM.

Question: Concealment is integral to placebo-controlled clinical trials and insures that participants remain blind to whether they are receiving real (verum) or dummy (placebo) treatment. While participants are routinely informed about and consent to be randomised to verum or placebo, they are typically never told which treatment they actually received: they are not debriefed to treatment allocation. Participants’ experiences of this aspect of trials have not been well-described. Methods: We therefore conducted an idiographic phenomenological study of four participants’ experiences of being blinded to and then debriefed to placebo allocation in a placebo-controlled clinical trial (conducted in the USA). Four participants in a trial of acupuncture for IBS were interviewed before, during, and after receiving a course of placebo treatments over 6 weeks. During the final interview they were debriefed to placebo allocation. Results: Each participant's experiences of being blinded to and then debriefed to placebo allocation are described in depth using a phenomenological approach based on the Sheffield School. All four thought they had received real acupuncture, and based their belief on a combination of embodied experiences during and after treatments, and their perceptions of their acupuncturists. They were all surprised to be told they had placebo, and did not unquestionably accept this news. Instead, they developed revised explanations that reconciled their lived experiences (of real acupuncture) with the conflicting news (of placebo acupuncture) from the interviewer. Conclusions: Our participants’ experiences of blinding and debriefing were embodied, related to their goals in undertaking the study, and social – embedded in trusting and valued relationships with acupuncturists, told to others outside the study, and described to an interviewer. This work suggests that debriefing to placebo allocation can and should be managed sensitively to facilitate positive outcomes for participants: further research should focus on developing best practice in this area.