Working with patients' treatment expectations - what we can learn from homeopathy.

The usual homeopathic remedy, "globules," does not contain any pharmacologically active ingredient. However, many patients and practitioners report beneficial effects of homeopathic treatment on various health outcomes. Experimental and clinical research of the last two decades analyzing the underlying mechanisms of the placebo effect could explain this phenomenon, with patients' treatment expectations as the predominant mechanism. Treatment expectations can be optimized through various factors, such as prior information, communication, and treatment context. This narrative review analyses how homeopathy successfully utilizes these factors. Subsequently, it is discussed what evidence-based medicine could learn from homeopathic practice to optimize treatment expectations (e.g., using an empathic, patient-centered communication style, deliberately selecting objects in practice rooms, or using clear treatment rituals and salient contextual stimuli) and thereby treatment effectiveness. Homeopathic remedy does not work beyond the placebo effect but is recommended or prescribed as an active treatment by those who believe in it. Thus, practitioners need to understand the manner in which homeopathy (as an example of inert treatment) works and are advised to reintegrate its underlying effective placebo mechanisms into evidence-based medicine. This promises to increase treatment efficacy, tolerability, satisfaction, and compliance with evidence-based treatments, and addresses the desires patients are trying to satisfy in homeopathy in an ethical, fully informed way that is grounded in evidence-based medicine.

Skin Transillumination Improves Peripheral Vein Cannulation by Residents in Neonates: A Randomized Controlled Trial.

INTRODUCTION: Establishing peripheral vein access is challenging for pediatric residents and a painful procedure for neonates. We assessed the efficacy of a red light-emitting diode transilluminator during peripheral vein catheter insertion performed by pediatric residents. METHODS: Patients were stratified by current weight (≤1,500 g, >1,500 g) and randomized to the transillumination or the control group. The first three attempts were performed by pediatric residents, followed by three attempts by a neonatologist. The primary outcome was success at first attempt. Secondary comparisons included time to successful insertion and overall success rates of residents and neonatologists. RESULTS: A total of 559 procedures were analyzed. The success rate at resident's first attempt was 44/93 (47%) with transillumination versus 44/90 (49%) without transillumination (p = 0.88) in the strata ≤1,500 g and 103/188 (55%) with transillumination versus 64/188 (34%) without transillumination in the strata >1,500 g (p < 0.001). The overall success rate for residents was 86% in the transillumination versus 73% in the control group in the strata >1,500 g (p = 0.003) but not different in the strata ≤1,500 g (78/93 [84%] vs. 72/90 [80%], p = 0.57). There was no effect when the experience level of residents exceeded 6 months. Neonatologists' overall success rate and time to successful cannulation did not differ significantly in both weight strata. CONCLUSION: Transillumination improves the first-attempt success rate of peripheral vein cannulation performed by pediatric residents in neonates >1,500 g, while no benefit was found in infants ≤1,500 g.

Elevated perceived stress in university students due to the COVID-19 pandemic: Potential contributing factors in a propensity-score-matched sample.

OBJECTIVE: Onset of the Coronavirus Disease 2019 (COVID) pandemic has increased students' perceived burdens. The current study aimed to examine COVID-related changes and to identify potential factors that contribute to students' stress. METHOD: Adopting a cross-sectional cohort-study design, we examined perceived stress and depressive and anxiety symptoms with a specific focus on the role of study-related variables such as perceived study-related demands, study-related resources, academic procrastination, and stress-enhancing beliefs. Two cohorts (Npre-COVID = 2,175; NCOVID = 959) were recruited at the same university and matched with regard to their propensity score (age, gender, semester). RESULTS: Compared with the pre-COVID cohort, university students in the COVID cohort reported more perceived stress, more depressive and anxiety symptoms, more academic procrastination due to fear of failure, more stress-enhancing beliefs, more distress due to the housing situation, and more perceived study-related challenges (Cohen's d = 0.15-0.45). A stepwise regression analysis identified depressive symptoms, procrastination due to fear of failure, general self-efficacy, increased study demands, perceived difficulties with self-organized learning, distress due to housing, and stress-enhancing beliefs as predictors of perceived stress in the COVID cohort. DISCUSSION: Findings suggest that the switch to online-only education increased the study-related burden for students, primarily due to exams being replaced by a greater amount of regular coursework and imposing demands on self-organized learning. Possibly, stress-enhancing beliefs and procrastination due to fear of failure might have been elevated due to less opportunity for social referencing and lack of felt social support by peer students. CONCLUSION: Experienced increased burden in students during the COVID pandemic was mostly accounted for by a lack of perceived individual resources rather than by an increase in objective study-related demands.

Epidemiology of Pertussis and Pertussis-Related Complications in Adults: A German Claims Data Analysis.

INTRODUCTION: Pertussis is a highly contagious respiratory infection. It affects people of all ages, yet evidence of the impact of pertussis in adults with underlying conditions (UCs) is scarce. This study investigated the incidence and complication rate of pertussis in adult patients with and without UC. METHODS: A retrospective analysis was conducted using routinely collected German claims data between 2015 and 2019. Patients with and without different pneumological, cardiovascular, endocrinological, musculoskeletal, and psychological UCs were matched for incidence estimation. Logistic regression models were used to estimate the risk of pertussis depending on the presence of UCs. Negative binomial models were used to assess complication rates in patients with pertussis and with and without UC. RESULTS: In total, 4383 patients were diagnosed with pertussis during the study period. Patients with any UC had an increased risk for pertussis compared to matched patients without UC (odds ratio [OR] 1.72; 95% confidence interval [CI]1.60-1.84, p < 0.0001). Underlying asthma had the highest risk of pertussis (OR 2.70; 95% CI 2.50-2.91, p < 0.0001), followed by chronic obstructive pulmonary disease (OR 2.35; 95% CI 2.10-2.60, p < 0.0001) and depression (OR 2.08; 95% CI 1.95-2.22, p < 0.0001). Severe complications occurred in 10.8% of the pertussis cohort (13.4% with UC vs. 9.5% without UC). The UC-attributable effect on the risk of severe pertussis-related complications was significantly increased for any UC (incidence rate ratio [IRR] 1.29, 95% CI 1.19-1.39). The severe complication risk was also increased for patients aged 60+ (IRR 1.59, 95% CI 1.46-1.72). CONCLUSION: This study shows that adults with certain UCs have an increased risk for pertussis and are more likely to have complications. These results provide further evidence that pertussis is a relevant and impactful infectious disease in adults with and without certain UC, indicating that these patients need to be considered when developing vaccination recommendations to avoid pertussis and its associated complications. A graphical abstract is available with this article.

The impact of pharmaceutical form and simulated side effects in an open-label-placebo RCT for improving psychological distress in highly stressed students.

Open-label placebo (OLP) may be utilized to reduce psychological distress. Yet, potential contextual effects have not been explored. We investigated the impact of pharmaceutical form and the simulation of side effects in a parallel group RCT (DRKS00030987). A sample of 177 highly stressed university students at risk of depression were randomly assigned by computer generated tables to a 1-week intervention with active or passive OLP nasal spray or passive OLP capsule or a no-treatment control group. After the intervention, groups differed significantly in depressive symptoms but not regarding other outcomes of psychological distress (stress, anxiety, sleep quality, somatization), well-being or treatment expectation. OLP groups benefitted significantly more compared to the no-treatment control group (d = .40), OLP nasal spray groups significantly more than the OLP capsule group (d = .40) and the active OLP group significantly more than the passive OLP groups (d = .42). Interestingly, before intervention, most participants, regardless of group assignment, believed that the OLP capsule would be most beneficial. The effectiveness of OLP treatments seems to be highly influenced by the symptom focus conveyed by the OLP rationale. Moreover, pharmaceutical form and simulation of side effects may modulate efficacy, while explicit treatment expectation seems to play a minor role.

The Hand-Withdrawal-Method - An Adapted and Simplified Method of Limits for Behavioral Heat Pain Assessment.

The method-of-limits (MLI) is an established psychophysical procedure, for example for determining thermal thresholds. The standard MLI relies on fixating the thermode at the stimulation site by means of a strap and requires the participant to terminate the increase in heat by pressing a button. This, however, raises concerns regarding safety and task complexity in specific populations, such as cognitively impaired individuals, people with high fear of pain or young children (< 6 years). In this study, we aimed at developing a simplified version of the commonly used MLI for testing heat pain threshold (HPT) and tolerance (HPTol), and at validating it as a first step in healthy adults. Heating is terminated by withdrawing the hand from the heat probe, thereby ensuring maximum control and safety. For validation, HPTs and HPTols were assessed with the novel "hand-withdrawal-method" (HWM) and compared to the standard MLI, using a within-subject design. Additionally, as one potential research area in which the HWM may be used, we explored expectancy-induced placebo hypoalgesic effects by comparing results of standard MLI with those of HWM. Our data confirm good concordance between the 2 methods. For none of the outcomes significant differences between the 2 methods were found. PERSPECTIVE: In the present study in healthy adults, an adapted simplified and safe method of limits was demonstrated to be equivalent to the standard method-of-limits. This novel behavioral "hand-withdrawal-method" seems promising for future investigations of pain sensitivity and placebo effects, especially for specific populations such as young children.

Alpha-2 Adrenoreceptor Antagonist Yohimbine Potentiates Consolidation of Conditioned Fear.

BACKGROUND: Hyperconsolidation of aversive associations and poor extinction learning have been hypothesized to be crucial in the acquisition of pathological fear. Previous animal and human research points to the potential role of the catecholaminergic system, particularly noradrenaline and dopamine, in acquiring emotional memories. Here, we investigated in a between-participants design with 3 groups whether the noradrenergic alpha-2 adrenoreceptor antagonist yohimbine and the dopaminergic D2-receptor antagonist sulpiride modulate long-term fear conditioning and extinction in humans. METHODS: Fifty-five healthy male students were recruited. The final sample consisted of n = 51 participants who were explicitly aware of the contingencies between conditioned stimuli (CS) and unconditioned stimuli after fear acquisition. The participants were then randomly assigned to 1 of the 3 groups and received either yohimbine (10 mg, n = 17), sulpiride (200 mg, n = 16), or placebo (n = 18) between fear acquisition and extinction. Recall of conditioned (non-extinguished CS+ vs CS-) and extinguished fear (extinguished CS+ vs CS-) was assessed 1 day later, and a 64-channel electroencephalogram was recorded. RESULTS: The yohimbine group showed increased salivary alpha-amylase activity, confirming a successful manipulation of central noradrenergic release. Elevated fear-conditioned bradycardia and larger differential amplitudes of the N170 and late positive potential components in the event-related brain potential indicated that yohimbine treatment (compared with a placebo and sulpiride) enhanced fear recall during day 2. CONCLUSIONS: These results suggest that yohimbine potentiates cardiac and central electrophysiological signatures of fear memory consolidation. They thereby elucidate the key role of noradrenaline in strengthening the consolidation of conditioned fear associations, which may be a key mechanism in the etiology of fear-related disorders.

Even when you know it is a placebo, you experience less sadness: First evidence from an experimental open-label placebo investigation.

BACKGROUND: Recent studies demonstrate substantial effects of deceptive placebo on experimentally induced sadness, even on autonomic activity. Whether deception is necessary, remains to be elucidated. We investigated the effect of an open-label placebo (OLP) treatment, i.e. an openly administered placebo delivered with a convincing rationale for its sadness-protecting effect. METHODS: Eighty-four healthy females were randomized to an OLP group or a no-treatment control group. All participants received the same detailed information about the OLP effect, only the OLP group received an OLP nasal spray. Before and after the OLP intervention, participants underwent a sad mood induction procedure combining self-deprecating statements (Velten's method) and sad music. Sadness was assessed by the Positive and Negative Affect Schedule (PANAS-X). Autonomic activity was measured continuously. RESULTS: Participants in the OLP group reported a significantly attenuated increase in sadness upon mood induction and less sadness after induction compared to the control group (d = 0.79). Regardless of intervention, heart rate decreased during mood inductions with a more pronounced deceleration in the second mood induction. LIMITATIONS: Generalizability is limited due to the selective sample and the reliance on an experimentally controlled mood induction. CONCLUSION: OLP treatment had a beneficial effect on perceived sadness, at least at the subjective level. Hence, deception may not necessarily be required for placebos to modulate experienced sad mood. Investigating the beneficial effects of OLP in (sub-)clinical samples would seem a promising and required next step towards a clinical use of placebo-associated positive treatment expectations.

[Item Reduction to Improve Practicability of Neonatal Pain Assessment Tools - Comparison of NFCSshort and PIPP in Daily Clinical Practice]. / Itemreduktion zur Verbesserung der Praktikabilität neonatologischer Schmerzmesssysteme.

HINTERGRUND: Trotz über 50 psychometrisch validierter Beobachtungsverfahren gibt es bisher keinen Konsens über das praktikabelste Schmerzassessment bei Neugeborenen. Die Items von NFCSshort und PIPP wurden mit der Schmerzeinschätzung der prozedurbeteiligten Behandler verglichen und es wurde evaluiert, ob eine Itemreduktion zu Gunsten der Alltagsanwendung möglich wäre. MATERIAL UND METHODEN: 52 Neugeborene wurden in unserer Beobachtungsstudie einer klinisch indizierten peripheren Venenpunktion unterzogen. Patient und Monitordaten wurden standardisiert auf Video aufgezeichnet. Die Schmerzintensität wurden durch sieben unabhängige Untersucher mittels NFCSshort und PIPP bewertet und hinsichtlich der Variabilität zwischen den Untersuchern verglichen. ERGEBNISSE: Nur vier Items des PIPP (Herzfrequenz, Augenbrauenvorwölbung, zusammengekniffene Augen, betonte Nasolabialfalte) wiesen einen signifikanten Zusammenhang mit der geschätzten Schmerzhaftigkeit der Prozedur auf. Die Items 1 (Gestationsalter), 2 (Wachheitsgrad) und 4 (Sauerstoffsättigung) hatten bei keinem Untersucher Einfluss auf das Schmerzmessergebnis. Die Auswertung des NFCSshort zeigte bei zwei Untersuchern für das Item 1 (Vorwölbung der Augenbrauen) und bei einem Untersucher für das Item 2 (zusammengekniffene Augen) keine Einflüsse auf das Messergebnis. DISKUSSION: Die Ergebnisse der Studie legen eine Kürzung des PIPP um drei Items nahe, da diese keinen Einfluss auf das Schmerzmessergebnis zeigten. Eine Reduktion des PIPP um das Item Gestationsalter erscheint fraglich, da es in weiteren Studien als bedeutsames Item bewertet wurde. Ein Verzicht auf das Item Sauerstoffsättigung geht mit einem geringeren Messaufwand einher. Eine weitere Kürzung der bereits gekürzten Version (NFCSshort) auf weniger als fünf Items ist auf Basis unserer Ergebnisse nicht zu empfehlen. BACKGROUND: Despite more than 50 laboratory-evaluated measurement systems, there is no consensus on the most practicable pain assessment in newborns in daily practice. For this purpose, the items of NFCSshort and PIPP were compared to the pain assesment of the involved medical practitioner. The aim of the study was to evaluate whether an item reduction of the assesments in favor of everyday use is feasible. METHODS: In 52 neonates of a paediatric ward venous blood collection was performed in this observational study. Cameras recorded patients and monitor in a standardized way. The pain intensity was assessed with NFCSshort and PIPP by seven independent observers. The ratings were compared for variability between observers. RESULTS: Of the seven PIPP items, only four were significantly associated with procedural pain assessment for all seven observers (heart rate, brow bulge, eye squeeze, nasolabial furrow). For the NFCSshort, no significant association with procedural pain assessment was found for two observers for the item "brow bulge" and for one observer for the item "eye squeeze". CONCLUSION: The results of the study suggest a possible reduction of the PIPP by three items. Disregarding item 1 (gestational age) appears questionable, since its impact as context variable has been proven repeatedly. The waiver of item 4 (oxygen saturation) is associated with less measuring effort. A further reduction of the already shortened version of the NFCS with ten items (NFCSshort, five items) is not recommended by our results.

Conceptual expansion via novel metaphor processing: An ERP replication and extension study examining individual differences in creativity.

The aims of the present ERP study were twofold. First, to determine whether a previous study on creative cognition could be replicated, and second, to extend these findings by examining individual differences in creativity. Conceptual expansion, a capacity that is central to creativity, was induced via the processing of novel metaphors. Brain activity patterns in relation to these were compared to the processing of literal and nonsense phrases. The previous findings were replicated in that the N400, known for its sensitivity to semantic anomalies, indexed the originality of the phrases, while a post-N400 late component (LC), which is linked to semantic integration processes, indexed the appropriateness of the phrases. Moreover, only the LC was significantly sensitive to individual differences in creativity in the processing of these phrases. Differences at the level of semantic integration processes as well as the structure of knowledge organization are thereby implicated in individual differences in creativity.

Placebo nasal spray protects female participants from experimentally induced sadness and concomitant changes in autonomic arousal.

BACKGROUND: To investigate the powerful placebo effects in antidepressant drug trials and their mechanisms, recent pioneering experimental studies showed that expectation manipulation combined with an active placebo attenuated induced sadness. In the present study, we aimed at extending these findings by assessing the psychophysiological response in addition to mere self-report. METHODS: One hundred and thirteen healthy female students were randomly assigned to a drug expectation group (active placebo, positive treatment expectation), placebo expectation group (active placebo, no treatment expectation), or a no-treatment group (no placebo, no treatment expectation). After placebo intake, sadness was induced by self-deprecating statements using the Velten method combined with sad music, including a rumination phase. Sadness was measured using the Positive and Negative Affect Schedule Expanded Form (PANAS-X). Heart rate and skin conductance were assessed continuously. RESULTS: After mood induction and after rumination, self-reported sadness was significantly lower, and skin conductance level was significantly higher, in the drug expectation group than in the no-treatment group. The mood induction was further accompanied by a heart rate deceleration within all groups. LIMITATIONS: Generalizability is limited by sample selectivity and focusing on sadness as a symptom of depression, exclusively. CONCLUSION: Expectation-induced placebo effects significantly influenced sadness-correlated changes in autonomic arousal, and not only subjectively reported sadness, indicating that placebo effects in the context of affect are not merely due to subjective response bias. The systematic modification of treatment expectation could be utilized in clinical practice to optimize current therapeutic approaches to improve mood regulation.

Pain modulation by your partner: An experimental investigation from a social-affective perspective.

BACKGROUND: Social context such as the relationship between a person experiencing pain and a caregiver has been shown to affect the experience of pain, yet, results are not consistent. Possibly, differential effects of interpersonal relationships are modulated by affective states expressed by social partners. Viewing partner pictures in experimental designs is not only associated with lowered perceived pain intensity, but also affects neural responses. However, the role of affective modulation is not clear. The present study aimed to systematically examine the pain modulating effects of stimuli varying in affect and social content including personal relevance using subjective report and psychophysiological measures of facial and autonomic activity. METHODS: Twenty-nine women underwent a tonic heat pain paradigm with simultaneous picture viewing to investigate the influence of their partners' faces with a neutral facial expression compared to strangers' happy, angry and neutral facial expressions on pain intensity and accompanying psychophysiological parameters (facial activity: corrugator muscle activity, autonomic activity: skin conductance level, heart rate). In addition to perceived partner support and relationship characteristics, the contribution of the affective value (valence, arousal) of the partner faces to the observed pain modulation was examined. RESULTS: Partner and happy faces reduced self-reported pain intensity and corrugator activity, the latter being lowest when viewing partner faces as compared to all other picture categories. As corrugator activity is indexing stimulus unpleasantness and a core feature of the facial pain expression, this physiological pattern matches well with the subjective ratings. Neutral objects, neutral and angry faces had no effect on pain self-report, although angry faces were rated as highly negative. Partner faces also led to increased skin conductance, being an index of motivational activation, and heart rate deceleration, possibly reflecting increased sensory intake. Partner-related pain modulation was primarily related to perceived arousal of the partner's picture, i.e., the intensity of the activation of approach motivation, and pain-related catastrophizing. DISCUSSION: Our results are partially consistent with emotional pain control models, especially regarding the modulatory influence of valence. Within the context of socially adaptive behavior, they particularly underline the social signal value of emotion and attachment figures. Clinically, our results imply that just looking at pictures of one's partner when undergoing acute painful procedures can have a robust hypoalgesic effect.

Burden of Herpes Zoster in Adult Patients with Underlying Conditions: Analysis of German Claims Data, 2007-2018.

INTRODUCTION: Several chronic underlying conditions (UCs) are known to be risk factors for developing herpes zoster (HZ) and to increase the severity of HZ and its risk of recurrence. The aim of this study was to investigate the incidence and recurrence of HZ in adult patients with one or multiple UCs. METHODS: A retrospective cohort study based on claims data representing 13% of the statutory health insurance population from 2007 to 2018 in Germany was performed. Patients aged ≥ 18 years were included when at least one of the following UCs was diagnosed: asthma, chronic heart failure, chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), depression, diabetes mellitus type 1 or 2, and rheumatoid arthritis (RA). Exact matching was used to account for differences in the distribution of age and sex between the case and matched control cohorts. Multi-morbidity was considered in sensitivity analyses by analyzing patients with only one UC. RESULTS: Patients with asthma, CHD, COPD, depression, and RA had, on average, a 30% increased risk of developing acute HZ compared to patients without any UC. RA was found to have the highest odds ratio among these conditions, varying from 1.37 to 1.57 for all age groups. Patients with depression also showed a high risk of developing HZ. Analysis of recurrence indicated that patients with at least one UC in the age groups 18-49 years and 50-59 years had the highest risk for a recurrent HZ. After experiencing a first recurrence, patients, regardless of age group, had a two- to threefold higher risk for a second recurrence. CONCLUSION: This study of representative claims data shows a higher HZ incidence and recurrence frequency in patients with UCs. These results provide relevant information for national health care guidelines and disease management programs.

Shingles is caused by the reactivation of the chickenpox virus and is characterized by a painful skin rash with blisters, commonly occurring on the trunk. Underlying conditions (UCs) are conditions that persist for a long time, require ongoing medical attention, and are rarely completely cured (chronic conditions). UCs can increase the severity, the risk, and the frequency of shingles. Here, data from a large German health care insurance provider was used to investigate whether patients with one or more UCs have a higher risk for getting shingles compared to healthy people. In particular, patients with asthma, chronic heart failure, chronic obstructive pulmonary disease, coronary heart disease, depression, diabetes, and rheumatoid arthritis were investigated. The study shows that patients with asthma, coronary heart disease, chronic obstructive pulmonary disease, depression, and rheumatoid arthritis have, on average, a 30% higher risk of developing shingles, regardless of their age. The risk of developing shingles two or more times is also higher for patients with at least one UC, with those aged 18­59 experiencing an even greater risk. It was found that patients with an UC are more exposed to develop shingles and that younger patients have a higher risk of a recurrent episode. The findings provide important information for the development or adaption of national health care guidelines and shingles vaccination recommendations.

[Measurement of pain-related experiential avoidance: analysis of the Acceptance and Action Questionnaire-II-Pain in patients with chronic pain]. / Messung von schmerzbezogener Erlebensvermeidung: Analyse des Acceptance and Action Questionnaire-II-Pain bei Patienten mit chronischem Schmerz.

INTRODUCTION AND OBJECTIVE: Experiential avoidance is a core process variable in the concept of Acceptance and Commitment Theory (ACT) and has been connected to various disorders. A widely used instrument for the measurement of experiential avoidance is the Acceptance and Action Questionnaire II (AAQ-II). Recently, a pain-specific version for chronic pain patients was introduced in the Netherlands (AAQ-II­P). High scores indicate strong pain-related experiential avoidance. The aim of the current study was to measure pain-related experiential avoidance in a sample of chronic pain patients using the German translation of the AAQ-II­P and to analyze its psychometric qualities. METHODS: After a forward-backward translation procedure of the AAQ-II and adaptation to the pain context, a sample of N = 168 patients from a multidisciplinary pain center answered the German version of the AAQ-II­P. Additional questionnaires were administered to measure specific constructs of interest: chronic pain grade (CPG), pain catastrophizing (PCS), health-related quality of life (SF-12), psychopathology (HADS-D), personality (BFI­K) and mindfulness (KIMS-S). Reliability, factorial validity and construct validity of the AAQ-II­P were identified. RESULTS: The AAQ-II­P had high internal consistency (α = 0.89) and the one-factor solution explained 61% of the total variance. Correlations to personality and mindfulness subscales were low (maxima: r = 0.44 with neuroticism and r = -0.43 with acceptance). High correlations were shown for catastrophizing (r = 0.75), depression (r = 0.73) and anxiety (r = 0.66). Also, there was a substantial correlation to health-related quality of life, specifically the psychological total scale (r = -0.58). DISCUSSION AND CONCLUSION: The German AAQ-II­P has good reliability. Regarding factorial structure and construct validity, it is highly comparable to the original version. Direction and magnitude of the relationship to adjacent constructs mostly measure up to our expectations. Chronic pain patients inclined to pain-related experiential avoidance tend to indicate more pain catastrophizing and show restricted quality of life regarding psychological variables. Apparently, pain-related experiential avoidance can be relevant for popular target variables in psychotherapy.

Pain assessment for cognitively impaired older adults: Do items of available observer tools reflect pain-specific responses?

BACKGROUND: A number of observational tools are available to assess pain in cognitively impaired older adults, however, none of them can yet be regarded as a "gold standard". An international research initiative has created a meta-tool compiling the facial, vocalization and body movement items of the majority of available tools. Objective of this study was to investigate the pain specificity and the validity of these items. METHOD: N = 34 older adults with or without cognitive impairment were videotaped in three different conditions (one reference, two painful conditions) in their nursing homes. They were further asked to self-report their pain in each condition. The occurrence of non-verbal behaviours was coded as present or absent using the items of the meta-tool. RESULTS: The majority of non-verbal behaviours was not pain sensitive as they occurred less than three times across participants and conditions. Of the remaining items, two facial items ("pained expression" and "raising upper lip"), one vocalization item ("using pain-related words") and one body movement item ("guarding") were found to be pain specific and valid. One additional item, the vocalization item "gasping", was pain specific, but not associated with pain self-report, and three additional items, the facial items "frowning" and "narrowing eyes" and the vocalization item "mumbling" were correlated with pain self-report but did not help to separate pain from non-pain conditions. CONCLUSIONS: Systematic evaluation of items of existing observational pain assessment tools under naturalistic conditions seems a promising approach in the process of further investigating and improving tools. SIGNIFICANCE: Only few items stemming from observational pain assessment tools were found to be pain sensitive and specific as well as valid in this study. The investigation of existing tools not only on tool but additionally on item-level can provide helpful insights and thereby can help to improve the original tools and establish a gold standard for nonverbal pain assessment in older adults with cognitive impairments.

Placebo effect in children: the role of expectation and learning.

Classical conditioning and expectations are well-known underlying mechanisms of placebo hypoalgesia. Only little is known about their differential effect in adults, however, and even less in children. Previous studies in children evoked placebo hypoalgesia either with expectations alone or in combination with classical conditioning and revealed conflicting results. Furthermore, these studies investigated children of different ages making it even more difficult to draw conclusions. This study tried to disentangle classical conditioning and expectations by investigating them separately. To examine age effects, n = 172 children (6-9, 10-13, and 14-17 years) as well as n = 32 adults (> = 18 years) were tested using a heat pain paradigm investigating the effectiveness of creams some of which were bogusly introduced as analgesic. In addition to subjective pain intensity ratings, peripheral physiological measures were recorded. Results showed a successful induction of placebo hypoalgesia by both mechanisms for pain ratings and heart rate acceleration. Placebo hypoalgesia was particularly pronounced in children younger than 14 years. Furthermore, placebo hypoalgesia was more marked in children whose mothers raised the expectations. It was also stronger in participants who noticed a strong pain reduction during learning trials. These results encourage the use of placebo effect in clinical practice, particularly for younger children. They underline the relevance of an initial pain reduction and encourage the inclusion of parents in treatment.

Placebo- and Nocebo-Effects in Cognitive Neuroenhancement: When Expectation Shapes Perception.

Objective: The number of students using prescription drugs to improve cognitive performance has increased within the last years. There is first evidence that the expectation to receive a performance-enhancing drug alone can result in improved perceived and actual cognitive performance, suggesting a substantial placebo effect. In addition, expecting a placebo can result in lower perceived and actual cognitive performance, suggesting a nocebo effect. Yet, the underlying mechanisms of these effects remain to be elucidated. The aim of our study was to investigate whether the expectation of receiving a performance-increasing drug or a performance-impairing drug leads to changes in actual and perceived cognitive performance, compared to a control group without expectation manipulation. Methods: A total of N = 75 healthy adults were recruited for an experiment to "try cognitive performance-modulating drugs." A participant's actual cognitive performance (alertness, working memory, sustained attention, and divided attention) using the standardized test of attentional performance (TAP) as well as their performance expectation were assessed. Participants were randomly assigned in equal numbers to either receiving a placebo performance increasing nasal spray ("Modafinil") or a nocebo performance impairing nasal spray ("Vividrin®") or no nasal spray (natural history). After placebo/nocebo nasal spray administration, cognitive performance was reassessed. Subsequent to the second assessment, participants rated their perceived change in cognitive performance, as well as adverse symptoms. Results: Unlike hypothesized, a positive or negative performance expectation did not result in changes in actual performance, corresponding to the induced expectation. Participants in the placebo-Modafinil group rated their perceived change in cognitive performance subsequent to the application of the nasal spray significantly better (d = 1.16) compared to the nocebo-Vividrin® group. Additionally, participants who expected to receive Modafinil felt less tired than participants in the Vividrin® group (d = 0.96). Conclusion: Manipulation of performance expectation affects the perceived change in performance and tiredness, but not the actual cognitive performance in healthy adults. This may explain why college students use such drugs despite their little impact on actual cognitive functioning.

[Applicability of Neonatal Pain Scores depending on Level of Education and Work Experience in Child Care]. / Anwendbarkeit neonataler Schmerzscores in Abhängigkeit von Ausbildungsstand und Berufserfahrung in der Kinderpflege.

INTRODUCTION: In management of pain the nursing staff plays a major role in measuring, preventing and treating pain. The influence of general work experience and experience with newborns was investigated by comparing PIPP and NRS measurements in groups with work experience and student nurses. METHODS: 44 students of the nursing school and 35 members of the staff of 2 university hospitals scored the Premature Infant Pain Profile PIPP - a 7 dimensional measurement tool - for 10 videos of painful procedures on preterm and newborn. The subjective impression of the patients' pain was obtained by a NRS. RESULTS: In contrast to the application of one dimensional measurement tools there were no differences between the groups with different experience levels. Also the work experience with newborn did not seem to influence the total PIPP score. Certainly both groups showed a moderate dispersion of the total values (e. g. Video 1: 10,5 [9-12] vs. 10 [3-11]). In NRS students rated the pain lower than experienced nurses. These results were not significant. CONCLUSION: The application of PIPP by students was equal to the application by experienced nurses. The work experience with newborn did not seem to influence the rating. Certainly both groups showed a moderate dispersion of total values (e. g. Video 1: 10,5 [9-12] vs. 10 [3-11]).

Fear Extinction Recall Modulates Human Frontomedial Theta and Amygdala Activity.

Human functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) studies, as well as animal studies, indicate that the amygdala and frontomedial brain regions are critically involved in conditioned fear and that frontomedial oscillations in the theta range (4-8 Hz) may support communication between these brain regions. However, few studies have used a multimodal approach to probe interactions among these key regions in humans. Here, our goal was to bridge the gap between prior human fMRI, EEG, and animal findings. Using simultaneous EEG-fMRI recordings 24 h after fear conditioning and extinction, conditioned stimuli presented (CS+E, CS-E) and not presented during extinction (CS+N, CS-N) were compared to identify effects specific to extinction versus fear recall. Differential (CS+ vs. CS-) electrodermal, frontomedial theta (EEG) and amygdala responses (fMRI) were reduced for extinguished versus nonextinguished stimuli. Importantly, effects on theta power covaried with effects on amygdala activation. Fear and extinction recall as indicated by theta explained 60% of the variance for the analogous effect in the right amygdala. Our findings show for the first time the interplay of amygdala and frontomedial theta activity during fear and extinction recall in humans and provide insight into neural circuits consistently linked with top-down amygdala modulation in rodents.

Pain-specific Reactions or Indicators of a General Stress Response?: Investigating the Discriminant Validity of 5 Well-established Neonatal Pain Assessment Tools.

OBJECTIVES: There are many neonatal pain assessment tools available. However, systematic psychometric comparisons between tools are lacking, particularly those comparing tools regarding their ability to differentiate between pain and stressful procedures. The aim of the present study was to compare 5 widely used neonatal pain assessment tools: Neonatal Facial Coding System-Revised, Premature Infant Pain Profile-Revised, Neonatal Pain, Agitation and Sedation Scale, Neonatal Infant Pain Scale, and Bernese Pain Scale Neonates. MATERIALS AND METHODS: Two coders applied all pain assessment tools to videos of 42 neonates who were videotaped during a pain and a stressful procedure. RESULTS: Interrater reliability and relative convergent validity were high and internal consistency good to excellent for all 5 assessment tools. All tools discriminated between painful and stressful events. Tools differed regarding their overall effect sizes as well as their items' effect sizes. Behavioral items tended to have larger effect sizes than physiological ones. Yet, effect sizes of items from one behavioral category differed greatly, which may be due to different operationalization of coding schemes. DISCUSSION: Given that the tools investigated in the present study appear to be fairly comparable psychometrically. Aspects of their clinical utility are discussed and ways of improvement identified.