Exploring Pain, Quality of Life, and Emotional Well-Being in Patients with Advanced Pancreatic Cancer Practicing Spiritual Meditation: A Pilot Study.

INTRODUCTION: Studies on mind-body approaches in patients with advanced pancreatic ductal adenocarcinoma (PDAC) are rare. We performed a pilot study with follow-up until 1 year to explore changes in pain, quality of life (QoL), stress, and negative emotions in patients with advanced PDAC, who regularly practiced a standardized form of spiritual meditation in addition to standard medical care. METHODS: At baseline and every 2 months for a maximum of 1 year, global pain, QoL (global, SEIQoL, FACT-G), spiritual well-being (FACIT-Sp), perceived stress (PSQ-20), anxiety and depression (HADS), and diurnal cortisol secretion (cortisol slope) were assessed. Changes from baseline were explored by pairwise comparisons of available cases. RESULTS: Twenty participants (11 women, 62 ± 9.9 SD years) participated in the study, of whom 9 patients survived the study year. Pairwise comparisons revealed transient improvements of pain after 4 and 6 months (both p values < 0.05), of global QoL after 4, 6, 8, 10 months (all p values < 0.05), of SeiQoL scores after 4 months (p < 0.05), of FACT-G scores after 6 months (p < 0.05), and of FACIT-Sp scores after 2 and 6 months (both p values < 0.05). Furthermore, overall stress levels (PSQ-20) decreased from baseline to 2, 6, and 8 months (all p values < 0.05), and anxiety declined from baseline to 6 months (p < 0.05). Depression scores and the cortisol slope did not change. CONCLUSION: This pilot study demonstrated the acceptability and feasibility of studies on spiritual meditation in patients with advanced PDAC. Randomized controlled trials are warranted to study the effects of spiritual meditation and other mind-body interventions on pain, QoL, and emotional well-being in this patient population.Bislang gibt es kaum Studien zu Mind-Body-Ansätzen bei Patienten mit fortgeschrittenem duktalem Adenokarzinom der Bauchspeicheldrüse (PDAC). Wir führten eine explorative Pilotstudie mit einer einjährigen Nachbe- obachtungszeit durch, um Veränderungen von Schmerzen, Lebensqualität, Stress und negativen Emotionen bei Patienten mit fortgeschrittenem PDAC zu untersuchen, die zusätzlich zur medizinischen Standardversorgung regelmäßig eine standardisierte Form der spirituellen Meditation praktizierten.Zu Beginn der Studie und alle zwei Monate wurden über einen Zeitraum von maximal einem Jahr die globalen Schmerzen, die Lebensqualität (global, SEIQoL, FACT-G), das psychologische Wohlbefinden (FACIT-Sp), Stress (PSQ-20), Angst und Depression (HADS) sowie die circadiane Cortisolausschüttung (Cortisolabfall) untersucht. Die Änderungen gegenüber dem Ausgangswert wurden mit paarweisen Vergleichen der jeweils verfügbaren Fälle auf Signifikanz getestet.20 Patienten (11 Frauen, 62 ± 9.9 SD Jahre) nahmen an der Studie teil, von denen 9 das Studienjahr überlebten. Paarweise Vergleiche zeigten vorübergehende Verbesserungen der Schmerzen nach 4 und 6 Monaten (beide p-Werte < 0.05), der globalen Lebensqualität nach 4, 6, 8 und 10 Monaten (alle p-Werte < 0.05), der SeiQoL-Werte nach 4 Monaten (p < 0.05), der FACT-G-Werte nach 6 Monaten (p < 0.05) und der FACIT-Sp-Werte nach 2 und 6 Monaten (beide p-Werte < 0.05). Außerdem war der Gesamtstress (PSQ-20) nach 2, 6 und 8 Monaten (alle p-Werte < 0.05) sowie die Ängstlichkeit nach 6 Monaten (p < 0.05) signifikant gesunken. Die Depressionswerte und der circadiane Cortisolabfall änderten sich nicht.Diese Pilotstudie weist auf die Akzeptanz und Durchführbarkeit von Studien zu spiritueller Meditation bei Patienten mit fortgeschrittenem PDAC hin. Randomisierte kontrollierte Studie sollten folgen, um die Effekte von spiritueller Meditation und anderen Mind-Body-Interventionen auf Schmerzen, Lebensqualität und emotionales Wohlbefinden in dieser Patientengruppe zu untersuchen.

Changes in Subjective Time and Self during Meditation.

This study examined the effects of meditative states in experienced meditators on present-moment awareness, subjective time, and self-awareness while assessing meditation-induced changes in heart-rate variability and breathing rate. A sample of 22 experienced meditators who practiced meditation techniques stressing awareness of the present moment (average 20 years of practice) filled out subjective scales pertaining to sense of time and the bodily self and accomplished a metronome task as an operationalization of present-moment awareness before and after a 20 min meditation session (experimental condition) and a 20 min reading session (control condition) according to a within-subject design. A mixed pattern of increased sympathetic and parasympathetic activity was found during meditation regarding heart-rate measures. Breathing intervals were prolonged during meditation. Participants perceived their body boundaries as less salient during meditation than while reading the story; they also felt time passed more quickly and they paid less attention to time during meditation. No significant differences between conditions became apparent for the metronome task. This is probably the first quantitative study to show how the experience of time during a meditation session is altered together with the sense of the bodily self.

Central correlates of placebo effects in nausea differ between men and women.

INTRODUCTION: Despite growing evidence validating placebo effects in nausea, little is known about the underlying cortical mechanisms in women and men. Therefore, the present study examined sex differences and electroencephalography (EEG) characteristics of the placebo effect on nausea. METHODS: On 2 consecutive days, 90 healthy subjects (45 females) were exposed to a nauseating visual stimulus. Nausea was continuously rated on an 11-point numeric rating scale, and 32 EEG channels were recorded. On day 2, subjects were randomly allocated to either placebo treatment or no treatment: the placebo group received sham acupuncture, whereas the control group did not receive any intervention. RESULTS: In contrast to the control group, both sexes in the placebo group showed reduced signs for anticipatory nausea in the EEG, indexed by increased frontal lobe and anterior cingulate activity. Among women, the improvement in perceived nausea in the placebo group was accompanied by decreased activation in the parietal, frontal, and temporal lobes. In contrast, the placebo-related improvement of perceived nausea in men was accompanied by increased activation in the limbic and sublobar (insular) lobes. CONCLUSION: Activation of the parietal lobe in women during the placebo intervention may reflect altered afferent activity from gastric mechanoreceptors during nausea-induced tachyarrhythmia, whereas in men, altered interoceptive signals in the insular cortex might play a role. Thus, the results suggest different cerebral mechanisms underlying the placebo effects in men and women, which could have implications for the treatment of nausea.

Nonpharmacological Interventions for Pediatric Migraine: A Network Meta-analysis.

CONTEXT: Migraine is a common neurologic disorder in children and adolescents. However, a comparison of multiple nonpharmacological treatments is lacking. OBJECTIVE: To examine whether nonpharmacological treatments are more effective than waiting list and whether there are differences between interventions regarding efficacy. DATA SOURCES: Systematic review and network meta-analysis of studies in Medline, Cochrane, Embase, and PsycINFO published through August 5, 2019. STUDY SELECTION: Randomized controlled trials of nonpharmacological treatments in children and adolescents diagnosed with episodic migraine. DATA EXTRACTION: Effect sizes, calculated as standardized mean differences (SMDs) for the primary outcome efficacy, were assessed in a random-effects model. RESULTS: Twelve studies (N = 576) were included. When interventions were classified into groups on the basis of similarity of treatment components, self-administered treatments, biofeedback, relaxation, psychological treatments, and psychological placebos were significantly more effective than waiting list with effect sizes ranging between SMD = 1.14 (95% confidence interval, 0.09 to 2.19) for long-term psychological placebos to SMD = 1.44 (95% confidence interval, 0.26 to 2.62) for short-term self-administered treatments. However, when all interventions were examined individually (ie, 1 node per intervention), none were significantly more effective compared with waiting list, mainly because of lack of statistical power. LIMITATIONS: Because of our focus on pediatric migraine, only a small number of studies could be included. CONCLUSIONS: Our findings reveal that components of nonpharmacological interventions are effective in treating pediatric migraine. Some effects have to be interpreted carefully because they are based on small studies. Future researchers should identify factors associated with individual responses in large, multicentered studies.

The Physical, Psychological, and Social Day-to-Day Experience of Women Living With Endometriosis Compared to Healthy Age-Matched Controls-A Mixed-Methods Study.

Background: Endometriosis is characterized by lesions of endometrial tissue outside the uterus. Chronic pain is considered as main symptom, but challenges can relate to various physical, mental, and social aspects of the women's lives. The aim of our study was to gain a holistic understanding of the everyday reality of women with endometriosis compared to healthy controls. Methods: The total sample comprised 12 hormone-free endometriosis patients (EP) and 11 age-matched healthy women (HC). A mixed-methods design was used comprising semi-structured interviews, standardized questionnaires and a comprehensive diary to assess pain ratings and various mental and physical symptoms over the course of a menstrual cycle. Interviews were recorded, transcribed, and evaluated according to phenomenological analysis using the MAXQDA software. Results: Interviews showed that living with endometriosis was associated with an impairment in everyday life. Physical strains, especially pain, high levels of psychological distress, and social limitations have been reported. Living with endometriosis affected the patients' personality and they "no longer felt like themselves." Physical and psychological symptoms were reported to interfere with social interaction and participation. Evaluation of the standardized questionnaires revealed significant impairments in EP compared to HC in regard to anxiety and depression scores (both p < 0.001; Hospital Anxiety and Depression Scale), mental and physical quality of life (both p < 0.001; Short-Form Health Survey-12), stress ratings (p < 0.001; Patient Health Questionnaire-15) and functional well-being (p < 0.001; Functional Well-being-7). The highest levels of mean pelvic pain and dyschezia were observed in EP during menstruation, but mean pain ratings and dyschezia were increased in EPs compared to HP during the whole cycle. EP reported mental symptoms (e.g., depressed mood or anxiety) mainly during menstruation, while HC did not show any mental symptoms during the cycle. In addition, physical symptoms were elevated during the entire cycle in EPs (all p < 0.01). Discussion: The mixed-methods approach enabled to interpret the interviews, the standardized questionnaires, and the symptom diary in a broader context of everyday life. The symptoms do not appear to act independently, but rather influence each other. This leads to a complex interplay of physical, mental, and social impairments, with pain often being the starting point.

Molecular classification of the placebo effect in nausea.

In this proof-of-concept study, we tested whether placebo effects can be monitored and predicted by plasma proteins. In a randomized controlled design, 90 participants were exposed to a nauseating stimulus on two separate days and were randomly allocated to placebo treatment or no treatment on the second day. Significant placebo effects on nausea, motion sickness, and (in females) gastric activity could be verified. Using label-free tandem mass spectrometry, 74 differentially regulated proteins were identified as correlates of the placebo effect. Gene ontology (GO) enrichment analyses identified acute-phase proteins and microinflammatory proteins to be involved, and the identified GO signatures predicted day-adjusted scores of nausea indices in the placebo group. We also performed GO enrichment analyses of specific plasma proteins predictable by the experimental factors or their interactions and identified 'grooming behavior' as a prominent hit. Finally, Receiver Operator Characteristics (ROC) allowed to identify plasma proteins differentiating placebo responders from non-responders, comprising immunoglobulins and proteins involved in oxidation reduction processes and complement activation. Plasma proteomics is a promising tool to identify molecular correlates and predictors of the placebo effect in humans.

Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis: A Systematic Review and Network Meta-analysis.

Importance: Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments in the pediatric population is lacking. Objective: To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability. Data Sources: Systematic review and network meta-analysis of studies in MEDLINE, Cochrane, Embase, and PsycINFO published through July 2, 2018. Study Selection: Randomized clinical trials of prophylactic pharmacologic treatments in children and adolescents diagnosed as having episodic migraine were included. Abstract, title, and full-text screening were conducted independently by 4 reviewers. Data Extraction and Synthesis: Data extraction was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis network meta-analysis guidelines. Quality was assessed with the Cochrane Risk of Bias tool. Effect sizes, calculated as standardized mean differences for primary outcomes and risk ratios for discontinuation rates, were assessed in a random-effects model. Main Outcomes and Measures: Primary outcomes were efficacy (ie, migraine frequency, number of migraine days, number of headache days, headache frequency, or headache index), safety (ie, treatment discontinuation owing to adverse events), and acceptability (ie, treatment discontinuation for any reason). Results: Twenty-three studies (2217 patients) were eligible for inclusion. Prophylactic pharmacologic treatments included antiepileptics, antidepressants, calcium channel blockers, antihypertensive agents, and food supplements. In the short term (<5 months), propranolol (standard mean difference, 0.60; 95% CI, 0.03-1.17) and topiramate (standard mean difference, 0.59; 95% CI, 0.03-1.15) were significantly more effective than placebo. However, the 95% prediction intervals for these medications contained the null effect. No significant long-term effects for migraine prophylaxis relative to placebo were found for any intervention. Conclusions and Relevance: Prophylactic pharmacologic treatments have little evidence supporting efficacy in pediatric migraine. Future research could (1) identify factors associated with individual responses to pharmacologic prophylaxis, (2) analyze fluctuations of migraine attack frequency over time and determine the most clinically relevant length of probable prophylactic treatment, and (3) identify nonpharmacologic targets for migraine prophylaxis.

Meditation-Induced States, Vagal Tone, and Breathing Activity Are Related to Changes in Auditory Temporal Integration.

This study is based on the relationship between meditation, the present moment, and psychophysiology. We employed the metronome task to operationalize the extension of the present moment. A pre-post longitudinal study was conducted. The performance in the metronome task was compared before and after the interventions (meditation, story). The aim was to assess whether physiological changes (heart, breathing) during meditation influence the temporal-integration (TI) of metronome beats. Mindfulness meditators either meditated (n = 41) or listened to a story (n = 43). The heart and breathing activity were recorded during the intervention and compared to a resting-state condition. By applying path analyses we found that meditation led to an increase of the duration of integration intervals at the slowest metronome frequency (inter-stimulus interval, ISI = 3 s). After meditation, the higher the heart-rate variability (i.e., the root mean square of successive differences, RMSSD), the longer the duration of integration intervals at the fastest frequency (ISI = 0.33 s). Moreover, the higher the breathing rate during meditation, the greater the integration of intervals at ISI = 1 s. These findings add evidence to meditation-induced changes on the TI of metronome beats and the concept of the embodiment of mental functioning.

Dietary Ingredients as an Alternative Approach for Mitigating Chronic Musculoskeletal Pain: Evidence-Based Recommendations for Practice and Research in the Military.

OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons, including pain and related outcomes. This work evaluates current research on dietary ingredients for chronic musculoskeletal pain to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. GRADE was used to determine confidence in the effect estimates. The committee made evidence-informed judgments and recommendations for practice and self-care use. RESULTS: Nineteen eligible dietary ingredients were assessed for quality, efficacy, and safety. Avocado soybean unsaponifiables, capsaicin, curcuma, ginger (as a food source), glucosamine, melatonin, polyunsaturated fatty acids, and vitamin D were conditionally recommended as their benefits outweighed risks, but there was still some uncertainty about the trade-offs. No recommendations were made for boswellia, ginger (as a dietary supplement), rose hip, or s-adenosyl-L-methionine. Recommendations were made against the use of collagen, creatine, devil's claw, l-carnitine, methylsulfonylmethane, pycnogenol, willow bark extract, and vitamin E. Research priorities were developed to address gaps precluding stronger recommendations. CONCLUSIONS: Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients. Until then, providers have the evidence needed to make informed decisions about the safe use of these dietary ingredients, and future research can address existing gaps.

Effectiveness of a placebo intervention on visually induced nausea in women - A randomized controlled pilot study.

OBJECTIVE: Improvement of nausea by placebo interventions has recently been demonstrated in clinical trials and experimental settings. However, many questions regarding placebo effects on nausea remain unanswered. For example, nausea reduction in women could only be achieved when the placebo intervention was "enhanced" by conditioning, while men responded primarily to verbally suggested improvement. It is unclear whether these findings are generalizable or were due to situational variables. In this pilot study, we investigated the effects of sham acupuncture point stimulation and verbal suggestions on visually-induced nausea in a female population. METHODS: In a within-subjects design, 21 healthy female volunteers underwent both a placebo condition and a natural history condition (control condition) in a randomized order on two separate days. On both days, nausea was induced through optokinetic stimulation. On the placebo day, participants received sham acupuncture point stimulation together with positive verbal suggestions of nausea improvement. Expected and perceived nausea severity as well as symptoms of motion sickness were repeatedly assessed. RESULTS: Twenty participants completed both testing days. Participants developed significantly less nausea on the placebo day compared to the control day (p<0.001), and the effect size of placebo-induced nausea reduction was large (partial η2=0.71). Symptoms of motion sickness were also reduced (p=0.003). Expectation of nausea decreased following the placebo intervention as compared to no treatment (p=0.030), indicating successful expectancy manipulation. CONCLUSION: Sham acupuncture point stimulation combined with verbal suggestions induced a significant placebo effect on visually-induced nausea in women.

Influence of a Suggestive Placebo Intervention on Psychobiological Responses to Social Stress: A Randomized Controlled Trial.

We tested the hypothesis that a suggestive placebo intervention can reduce the subjective and neurobiological stress response to psychosocial stress. Fifty-four healthy male subjects with elevated levels of trait anxiety were randomly assigned in a 4:4:1 fashion to receive either no treatment (n = 24), a placebo pill (n = 24), or a herbal drug (n = 6) before undergoing a stress test. We repeatedly measured psychological variables as well as salivary cortisol, alpha-amylase, and heart rate variability prior to and following the stress test. The stressor increased subjective stress and anxiety, salivary cortisol, and alpha-amylase, and decreased heart rate variability (all P < .001). However, no significant differences between subjects receiving placebo or no treatment were found. Subjects receiving placebo showed increased wakefulness during the stress test compared with no-treatment controls (P < .001). Thus, the suggestive placebo intervention increased alertness, but modulated neither subjective stress and anxiety nor the physiological response to psychosocial stress.

To what extent are surgery and invasive procedures effective beyond a placebo response? A systematic review with meta-analysis of randomised, sham controlled trials.

OBJECTIVES: To assess the quantity and quality of randomised, sham-controlled studies of surgery and invasive procedures and estimate the treatment-specific and non-specific effects of those procedures. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched PubMed, EMBASE, CINAHL, CENTRAL (Cochrane Library), PILOTS, PsycInfo, DoD Biomedical Research, clinicaltrials.gov, NLM catalog and NIH Grantee Publications Database from their inception through January 2015. STUDY SELECTION: We included randomised controlled trials of surgery and invasive procedures that penetrated the skin or an orifice and had a parallel sham procedure for comparison. DATA EXTRACTION AND ANALYSIS: Three authors independently extracted data and assessed risk of bias. Studies reporting continuous outcomes were pooled and the standardised mean difference (SMD) with 95% CIs was calculated using a random effects model for difference between true and sham groups. RESULTS: 55 studies (3574 patients) were identified meeting inclusion criteria; 39 provided sufficient data for inclusion in the main analysis (2902 patients). The overall SMD of the continuous primary outcome between treatment/sham-control groups was 0.34 (95% CI 0.20 to 0.49; p<0.00001; I(2)=67%). The SMD for surgery versus sham surgery was non-significant for pain-related conditions (n=15, SMD=0.13, p=0.08), marginally significant for studies on weight loss (n=10, SMD=0.52, p=0.05) and significant for gastroesophageal reflux disorder (GERD) studies (n=5, SMD=0.65, p<0.001) and for other conditions (n=8, SMD=0.44, p=0.004). Mean improvement in sham groups relative to active treatment was larger in pain-related conditions (78%) and obesity (71%) than in GERD (57%) and other conditions (57%), and was smaller in classical-surgery trials (21%) than in endoscopic trials (73%) and those using percutaneous procedures (64%). CONCLUSIONS: The non-specific effects of surgery and other invasive procedures are generally large. Particularly in the field of pain-related conditions, more evidence from randomised placebo-controlled trials is needed to avoid continuation of ineffective treatments.

Psychophysiology of duration estimation in experienced mindfulness meditators and matched controls.

Recent research suggests that bodily signals and interoception are strongly related to our sense of time. Mindfulness meditators train to be aware of their body states and therefore could be more accurate at interval timing. In this study, n = 22 experienced mindfulness meditators and n = 22 matched controls performed both, an acoustic and a visual duration reproduction task of 8, 14, and 20 s intervals, while heart rate and skin conductance were continuously assessed. In addition, participants accomplished a heart beat perception task and two selective attention tasks. Results revealed no differences between meditators and controls with respect to performance in duration reproduction or attentional capacities. Additionally no group difference in heart beat perception scores was found. Across all subjects, correlational analyses revealed several associations between performance in the duration reproduction tasks and psychophysiological changes, the latter being also related to heart beat perception scores. Furthermore, former findings of linearly increasing cardiac periods and decreasing skin conductance levels during the auditory duration estimation task (Meissner and Wittmann, 2011) could be replicated, and these changes could also be observed during a visual duration reproduction task. In contrast to our earlier findings, the heart beat perception test was not related with timing performance. Overall, although experienced meditators did not differ from matched controls with respect to duration reproduction and interoceptive awareness, this study adds significantly to the emerging view that time perception is related to autonomic regulation and awareness of body states.

Sympathetic Arousal during a Touch-Based Healing Ritual Predicts Increased Well-Being.

Objective. There is mounting evidence that more elaborate treatment rituals trigger larger nonspecific effects. The reasons for this remain unclear. In a pilot field study, we investigated the role of psychophysiological changes during a touch-based healing ritual for improvements in subjective well-being. Methods. Heart rate, respiratory rate, and skin conductance levels (SCL) were continuously assessed in 22 subjects before, during, and after a touch-based healing ritual. Participants rated their expectations and subjective well-being was assessed before and after the ritual by the "Short Questionnaire on Current Disposition". Results. Subjective well-being increased significantly from before to after the ritual. The analysis of psychophysiological changes revealed a significant increase in respiratory rate from baseline to ritual, while skin conductance, heart rate, and heart rate variability did not change. Increases in SCL as well as decreases in respiratory rate from baseline to ritual were significantly associated with improvements in subjective well-being. Regression analyses showed increases in SCL to be the only significant predictor of improvements in well-being. Conclusion. Higher sympathetic arousal during a touch-based healing ritual predicted improvements in subjective well-being. Results suggest the occurrence of an anticipatory stress response, that is, a state of enhanced sympathetic activity that is known to precede relaxation.

The use of placebo and non-specific therapies and their relation to basic professional attitudes and the use of complementary therapies among German physicians--a cross-sectional survey.

We aimed to investigate the use of placebos (e.g. saline injections) and non-specific treatments (e.g. vitamin supplements in individuals without a relevant deficiency) among physicians working in private practices in Germany, and how such use is associated with the belief in and the use of complementary and alternative treatments, and basic professional attitudes. A four-page questionnaire was sent to nationwide random samples of general practitioners (GP), internists and orthopaedists working in private practices. The response rate was 46% (935 of 2018). 24% of GPs, 44% of internists and 57% of orthopaedists had neither used pure placebos nor non-specific therapies in the previous 12 months. 11% percent of GPs, 12% of internists and 7% of orthopaedists had exclusively used pure placebos; 30%, 33% and 26%, respectively, had exclusively used non-specific therapies; 35%, 12% and 9% had used both. Age, sex and agreement to the statement that physicians should harness placebo effects were not significantly associated with any pattern of use. Exclusive use of pure placebos was associated with being a GP, being an internist, and having unorthodox professional views. In addition to these three factors, a lower use of CAM therapies and a wish for having more time was associated with the exclusive use of non-specific therapies. Among physicians using both pure placebo and non-specific therapies, heterodox views were also somewhat more pronounced. However, associations were particularly strong for being a GP (Odds ratio 11.6 (95%CI 6.41; 21.3)) and having orthodox views (Odds ratio 0.10 (95%CI 0.06; 0.18)) among this group. In conclusion, the use of placebos and non-specific treatments varies strongly between medical specialties and is associated with basic professional attitudes. The findings support the view that the use of placebos and, in particular, of non-specific therapies is primarily a coping behaviour for difficult and uncertain situations.

Subjective expansion of extended time-spans in experienced meditators.

Experienced meditators typically report that they experience time slowing down in meditation practice as well as in everyday life. Conceptually this phenomenon may be understood through functional states of mindfulness, i.e., by attention regulation, body awareness, emotion regulation, and enhanced memory. However, hardly any systematic empirical work exists regarding the experience of time in meditators. In the current cross-sectional study, we investigated whether 42 experienced mindfulness meditation practitioners (with on average 10 years of experience) showed differences in the experience of time as compared to 42 controls without any meditation experience matched for age, sex, and education. The perception of time was assessed with a battery of psychophysical tasks assessing the accuracy of prospective time judgments in duration discrimination, duration reproduction, and time estimation in the milliseconds to minutes range as well with several psychometric instruments related to subjective time such as the Zimbardo Time Perspective Inventory, the Barratt Impulsivity Scale and the Freiburg Mindfulness Inventory. In addition, subjective time judgments on the current passage of time and retrospective time ranges were assessed. While subjective judgements of time were found to be significantly different between the two groups on several scales, no differences in duration estimates in the psychophysical tasks were detected. Regarding subjective time, mindfulness meditators experienced less time pressure, more time dilation, and a general slower passage of time. Moreover, they felt that the last week and the last month passed more slowly. Overall, although no intergroup differences in psychophysical tasks were detected, the reported findings demonstrate a close association between mindfulness meditation and the subjective feeling of the passage of time captured by psychometric instruments.

Use of placebos and nonspecific and complementary treatments by German physicians--rationale and development of a questionnaire for a nationwide survey.

BACKGROUND: We are performing a nationwide survey in a random sample of German general practitioners (GPs), orthopedists, and internists on the use of placebos and nonspecific as well as complementary treatments and their association with basic professional attitudes. In this article we explain the theoretical considerations behind the study approach and the development of the questionnaire. METHODS: Based on a systematic review of published surveys, own surveys on the topic, and on theoretical considerations we developed a preliminary version of a 4-page questionnaire that was tested for feasibility in a convenience sample of 80 participants of a general medical education event. We also performed cognitive interviews with 8 physicians to investigate whether the questions were understood adequately. RESULTS: The questions on typical placebos and complementary treatments were well understood and easy to answer for participants. Discussions about the phrasing of questions on nonspecific treatments during interview reflected the vagueness of this concept; but this did not seem to create major problems when answering the related questions. The original questions regarding basic professional attitudes partly were not understood in the manner intended. The relevant questions were modified but the interviews suggest that these issues are difficult to grasp in a quantitative survey. CONCLUSION: Our testing procedures suggest that our questionnaire is well-suited to investigate our questions with some limitations regarding the issue of basic professional attitudes.

Differential effectiveness of placebo treatments: a systematic review of migraine prophylaxis.

IMPORTANCE: When analyzing results of randomized clinical trials, the treatment with the greatest specific effect compared with its placebo control is considered to be the most effective one. Although systematic variations of improvements in placebo control groups would have important implications for the interpretation of placebo-controlled trials, the knowledge base on the subject is weak. OBJECTIVE: To investigate whether different types of placebo treatments are associated with different responses using the studies of migraine prophylaxis for this analysis. DESIGN, SETTING, AND PARTICIPANTS: We searched relevant sources through February 2012 and contacted the authors to identify randomized clinical trials on the prophylaxis of migraine with an observation period of at least 8 weeks after randomization that compared an experimental treatment with a placebo control group. We calculated pooled random-effects estimates according to the type of placebo for the proportions of treatment response. We performed meta-regression analyses to identify sources of heterogeneity. In a network meta-analysis, direct and indirect comparisons within and across trials were combined. Additional analyses were performed for continuous outcomes. EXPOSURE: Active migraine treatment and the placebo control conditions. MAIN OUTCOMES AND MEASURES: Proportion of treatment responders, defined as having an attack frequency reduction of at least 50%. Other available outcomes in order of preference included a reduction of 50% or greater in migraine days, the number of headache days, or headache score or a significant improvement as assessed by the patients or their physicians. RESULTS: Of the 102 eligible trials, 23 could not be included in the meta-analyses owing to insufficient data. Sham acupuncture (proportion of responders, 0.38 [95% CI, 0.30-0.47]) and sham surgery (0.58 [0.37-0.77]) were associated with a more pronounced reduction of migraine frequency than oral pharmacological placebos (0.22 [0.17-0.28]) and were the only significant predictors of response in placebo groups in multivariable analyses (P = .005 and P = .001, respectively). Network meta-analysis confirmed that more patients reported response in sham acupuncture groups than in oral pharmacological placebo groups (odds ratio, 1.88 [95% CI, 1.30-2.72]). Corresponding analyses for continuous outcomes showed similar findings. CONCLUSIONS AND RELEVANCE: Sham acupuncture and sham surgery are associated with higher responder ratios than oral pharmacological placebos. Clinicians who treat patients with migraine should be aware that a relevant part of the overall effect they observe in practice might be due to nonspecific effects and that the size of such effects might differ between treatment modalities.

Effects of verbal suggestion on coronary arteries: results of a randomized controlled experimental investigation during coronary angiography.

BACKGROUND: Decrease of chest pain perception under placebo conditions has been frequently observed. The aim of this study was to examine whether placebo-induced chest pain improvement could be the result of changes in coronary blood flow. We, therefore, performed an experiment to investigate whether a verbal suggestion (VS) integrated in a cardiologic procedure has an impact on diameters of coronary arteries. METHODS: A total of 30 chest pain patients with normal diagnostic angiograms were assigned to a VS or a control group (CG). Saline solution was administered intracoronarily to both groups. The VS group received a standardized VS, implying coronary vasodilation. The CG remained without VS. Coronary end points were the changes in percentage diameter stenosis, Minimal lumen diameter and reference diameter of the index coronary segment before and 60 seconds after the administration of saline. Furthermore, changes in hemodynamics, psychological distress, and chest pain perception were recorded. RESULTS: The VS led to coronary vasoconstriction in comparison with CG (change in mean percentage diameter stenosis ± SD 3.2% ± 6.3% vs -1.7% ± 6.8%, P = .062; change in mean minimal lumen diameter ± SD -0.18 ± 0.32 mm vs 0.06 ± 0.23 mm, P = .029, no relevant change in the reference diameter). At the same time, the degree of chest pain perception was significantly reduced in the VS group (-0.7 ± 1.3) compared with the CG (0.3 ± 1.3), P = .024. CONCLUSION: The findings of this study suggest that a VS results in a biological alteration within coronary arteries. Contrary to expectation, the VS led to vasoconstriction, whereas chest pain perception decreased.

Organ-specificity of placebo effects on blood pressure.

There is increasing evidence that verbal suggestions accompanying placebo interventions can alter autonomic functions. The underlying mechanisms of these changes are not well understood. However, previous studies point at the specificity of such effects. The aim of the experiment was to lower blood pressure by a placebo intervention and to investigate the specificity of autonomic changes. Forty-five healthy participants received a single administration of an active drug (a homeopathic remedy), an identically-looking placebo drug, or no drug. Active drugs and placebo drugs were administered in a double-blind design and were accompanied by verbal suggestions of a blood-pressure lowering effect. Systolic and diastolic blood pressure, the electrocardiogram, electrodermal activity, and the electrogastrogram were recorded during 30min before and after the intervention, and changes in situational anxiety were assessed. Results indicated a decrease of systolic blood pressure in the placebo group, as compared to the control group. Diastolic blood pressure levels, heart rate, respiratory sinus arrhythmia, skin conductance, gastric slow-wave frequency and situational anxiety did not change differentially between groups. In conclusion, the reduction in systolic blood pressure following the placebo intervention could not be attributed to stress relief or anxiety reduction. Rather, results suggest that the placebo intervention specifically reduced systolic blood pressure.