Lack of evidence for predictive utility from resting state fMRI data for individual exposure-based cognitive behavioral therapy outcomes: A machine learning study in two large multi-site samples in anxiety disorders.

Data-based predictions of individual Cognitive Behavioral Therapy (CBT) treatment response are a fundamental step towards precision medicine. Past studies demonstrated only moderate prediction accuracy (i.e. ability to discriminate between responders and non-responders of a given treatment) when using clinical routine data such as demographic and questionnaire data, while neuroimaging data achieved superior prediction accuracy. However, these studies may be considerably biased due to very limited sample sizes and bias-prone methodology. Adequately powered and cross-validated samples are a prerequisite to evaluate predictive performance and to identify the most promising predictors. We therefore analyzed resting state functional magnet resonance imaging (rs-fMRI) data from two large clinical trials to test whether functional neuroimaging data continues to provide good prediction accuracy in much larger samples. Data came from two distinct German multicenter studies on exposure-based CBT for anxiety disorders, the Protect-AD and SpiderVR studies. We separately and independently preprocessed baseline rs-fMRI data from n = 220 patients (Protect-AD) and n = 190 patients (SpiderVR) and extracted a variety of features, including ROI-to-ROI and edge-functional connectivity, sliding-windows, and graph measures. Including these features in sophisticated machine learning pipelines, we found that predictions of individual outcomes never significantly differed from chance level, even when conducting a range of exploratory post-hoc analyses. Moreover, resting state data never provided prediction accuracy beyond the sociodemographic and clinical data. The analyses were independent of each other in terms of selecting methods to process resting state data for prediction input as well as in the used parameters of the machine learning pipelines, corroborating the external validity of the results. These similar findings in two independent studies, analyzed separately, urge caution regarding the interpretation of promising prediction results based on neuroimaging data from small samples and emphasizes that some of the prediction accuracies from previous studies may result from overestimation due to homogeneous data and weak cross-validation schemes. The promise of resting-state neuroimaging data to play an important role in the prediction of CBT treatment outcomes in patients with anxiety disorders remains yet to be delivered.

Study protocol TransTAM: Transdiagnostic research into emotional disorders and cognitive-behavioral therapy of the adaptive mind.

BACKGROUND: Emotional disorders such as depression and anxiety disorders share substantial similarities in their etiology and treatment. In recent decades, these commonalities have been increasingly recognized in classification systems and treatment programs crossing diagnostic boundaries. METHODS: To examine the prospective effects of different transdiagnostic markers on relevant treatment outcomes, we plan to track a minimum of N = 200 patients with emotional disorders during their routine course of cognitive behavioral therapy at two German outpatient clinics. We will collect a wide range of transdiagnostic markers, ranging from basic perceptual processes and self-report measures to complex behavioral and neurobiological indicators, before entering therapy. Symptoms and psychopathological processes will be recorded before entering therapy, between the 20th and 24th therapy session, and at the end of therapy. DISCUSSION: Our results could help to identify transdiagnostic markers with high predictive power, but also provide deeper insights into which patient groups with which symptom clusters are less likely to benefit from therapy, and for what reasons. TRIAL REGISTRATION: The trial was preregistered at the German Clinical Trial Register (DRKS-ID: DRKS00031206; 2023-05-09).

Does subjective social status affect pain thresholds? - an experimental examination.

Past research regarding the relationship between different constructs of social status and different aspects of pain has yielded divergent results. So far, there are few experimental studies to investigate the causal relationship between social status and pain. Therefore, the present study aimed to examine the effect of perceived social status on pain thresholds by experimentally manipulating participants' subjective social status (SSS). 51 female undergraduates were randomly assigned to a low- or high-status condition. Participants' perceived social standing was temporarily elevated (high SSS condition) or reduced (low SSS condition). Before and after experimental manipulation participants' pressure pain thresholds were assessed. The manipulation check confirmed that participants in the low-status condition reported significantly lower SSS than participants in the high-status condition. A linear mixed model revealed a significant group x time interaction for pain thresholds: Whereas participants' pain thresholds in the low SSS condition increased post manipulation, pain thresholds of participants in the high SSS condition decreased post manipulation (ß = 0.22; 95% CI, 0.002 to 0.432; p < .05). Findings suggest that SSS may have a causal effect on pain thresholds. This effect could either be due to a change in pain perception or a change in pain expression. Future research is needed to determine the mediating factors.

The Inventory of Social Expectations in Bereavement: Development and psychometric validation of a new instrument.

Negative expectations concerning social interactions contribute to feelings of loneliness. Since loneliness is one of the most pronounced challenges for bereaved individuals, we investigated grief-specific social expectations and its association with loneliness and grief severity. Initially, we developed an Inventory of Social Expectations in Bereavement (ISEB). Its factorial and psychometric validity was then tested in a bereaved sample (N = 344; 28.3 ± 11.1 years; 74.4% female). A two-factor solution for the scale fit the data best (factor 1: "relationship to others," factor 2: "relationship to the deceased") and demonstrated good psychometric validity. Higher ISEB-levels were associated with higher levels in grief severity and loneliness. The results suggest that individual social expectations affect the experience of loneliness after the loss of a significant other. The ISEB assesses these expectations time-efficiently and provides a basis for therapeutic interventions. Expressing expectations as probabilistic beliefs about the future renders them amenable for corrective experiences in clinical practice.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

Does psychological treatment of major depression reduce cardiac risk biomarkers? An exploratory randomized controlled trial.

BACKGROUND: Depression is associated with an increased risk for cardiovascular disease (CVD). Biological cardiac risk factors are already elevated in depressed patients without existing CVD. The purpose of this exploratory trial was to examine whether treating Major Depression (MD) with cognitive behavioral therapy (CBT) is associated with improvements in cardiac risk biomarkers and whether depressive symptom severity at baseline moderates treatment effects. METHODS: Eighty antidepressant-free patients with MD were randomly assigned to CBT or waiting list (WL). Biological outcomes included long-term recordings (24-h, daytime, nighttime) of heart rate, heart rate variability (HRV), and blood pressure, as well as inflammatory markers such as C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. A sample of 40 age- and sex-matched non-clinical controls was also involved to verify biological alterations in MD at study entry. RESULTS: Compared to WL, CBT was associated with a significant increase in overall HRV, as indexed by the 24-h and daytime HRV triangular index, as well as trend improvements in 24-h low-frequency HRV and daytime systolic blood pressure. Self-rated depressive symptom severity moderated (or tended to moderate) improvements in CBT for 24-h and daytime heart rate and several indices of HRV (especially daytime measures). Inflammatory treatment effects were not observed. CONCLUSIONS: CBT increased overall HRV in patients with MD. Initially more depressed patients showed the most pronounced cardiovascular improvements through CBT. These exploratory findings may provide new insights into the biological effects of psychological treatment against depression and must be confirmed through future research.

Same same, but different: effects of likelihood framing on concerns about a medical disease in patients with somatoform disorders, major depression, and healthy people.

BACKGROUND: Research has shown that patients with somatoform disorders (SFD) have difficulty using medical reassurance (i.e. normal results from diagnostic testing) to revise concerns about being seriously ill. In this brief report, we investigated whether deficits in adequately interpreting the likelihood of a medical disease may contribute to this difficulty, and whether patients' concerns are altered by different likelihood framings. METHODS: Patients with SFD (N = 60), patients with major depression (N = 32), and healthy volunteers (N = 37) were presented with varying likelihoods for the presence of a serious medical disease and were asked how concerned they are about it. The likelihood itself was varied, as was the format in which it was presented (i.e. negative framing focusing on the presence of a disease v. positive framing emphasizing its absence; use of natural frequencies v. percentages). RESULTS: Patients with SFD reported significantly more concern than depressed patients and healthy people in response to low likelihoods (i.e. 1: 100 000 to 1:10), while the groups were similarly concerned for likelihoods ⩾1:5. Across samples, the same mathematical likelihood caused significantly different levels of concern depending on how it was framed, with the lowest degree of concern for a positive framing approach and higher concern for natural frequencies (e.g. 1:100) than for percentages (e.g. 1%). CONCLUSIONS: The results suggest a specific deficit of patients with SFD in interpreting low likelihoods for the presence of a medical disease. Positive framing approaches and the use of percentages rather than natural frequencies can lower the degree of concern.

Measuring dysfunctional interpersonal beliefs: validation of the Interpersonal Cognitive Distortions Scale among a heterogeneous German-speaking sample.

BACKROUND: Dysfunctional interpersonal beliefs (DIBs) are a key symptom domain in numerous mental disorders. Because DIBs exert a strong influence on social experience and behavior, they play an important role in a mental disorder's development and progression. To date, only the Interpersonal Cognitive Distortions Scale (ICDS) captures DIBs independently of specific disorders, populations, or contexts. The present study's aim was to psychometrically evaluate and validate a German translation of the ICDS. METHODS: The ICDS was administered along with indicators of convergent (rejection sensitivity, depressive expectations, interpersonal trust, interpersonal problems, perceived social support), discriminant (self-efficacy, perseverative negative thinking, optimism), and clinical validity (psychopathology, perceived stress, well-being) to a pooled sample incorporating non-clinical (N = 114) and clinical (N = 94) participants. RESULTS: An exploratory factor analysis (EFA) suggested a five-factor solution (factor loadings: .44 to .85). Correlational analyses demonstrated acceptable convergent (ρ = -.29 to -.35, ρ = .27 to .59), suboptimal discriminant (ρ = -.27 to -.38, ρ = .52), and acceptable clinical validity (ρ = -.21, ρ = .36 to .44) at the total-scale level. However, results at the subscale level were mixed and required nuanced interpretation. Likewise, internal consistency was acceptable at the total-scale level (α = .76), but ranged from good to poor at the subscale level (α = .61 to .80). DIBs mediated the negative relationship between mental disorder onset and psychopathology levels. DISCUSSION: Our results imply DIBs' relevance to mental health and related outcomes. When working with the ICDS's German version, we recommend employing only the "insecurity" subscale, as this was the only scale revealing acceptable psychometric properties. Future studies should improve the construct validity of the ICDS (and its subscales), e.g., by adding more items to the respective subscales and further classes of DIBs.

The influence of psychological traits and prior experience on treatment expectations.

BACKGROUND: Placebo and nocebo responses are modulated by the treatment expectations of participants and patients. However, interindividual differences predicting treatment expectations and placebo responses are unclear. In this large-scale pooled analysis, we aim to investigate the influence of psychological traits and prior experiences on treatment expectations. METHODS: This paper analyses data from six different placebo studies (total n = 748). In all studies, participants' sociodemographic information, treatment expectations and prior treatment experiences and traits relating to stress, somatization, depression and anxiety, the Big Five and behavioral inhibition and approach tendencies were assessed using the same established questionnaires. Correlation coefficients and structural equation models were calculated to investigate the relationship between trait variables and expectations. RESULTS: We found small positive correlations between side effect expectations and improvement expectations (r = 0.187), perceived stress (r = 0.154), somatization (r = 0.115), agitation (r = 0.108), anhedonia (r = 0.118), and dysthymia (r = 0.118). In the structural equation model previous experiences emerged as the strongest predictors of improvement (ß = 0.32, p = .005), worsening (ß = -0.24, p = .005) and side effect expectations (ß = 0.47, p = .005). Traits related to positive affect (ß = - 0.09; p = .007) and negative affect (ß = 0.04; p = .014) were associated with side effect expectations. DISCUSSION: This study is the first large analysis to investigate the relationship between traits, prior experiences and treatment expectations. Exploratory analyses indicate that experiences of symptom improvement are associated with improvement and worsening expectations, while previous negative experiences are only related to side effect expectations. Additionally, a proneness to experience negative affect may be a predictor for side effect expectation and thus mediate the occurrence of nocebo responses.

Therapist's warmth and competence increased positive outcome expectations and alliance in an analogue experiment.

Objective: The quality of the therapeutic alliance, treatment motivation, outcome expectations (OE), and specific health behaviour predicts psychotherapy success. Therapists should be able to improve these factors to optimize outcomes. This study investigated the therapist's interpersonal behaviour to optimize alliance, motivation, OE, and health behaviour. Method: A stressed study sample (N = 465) completed an online analogue experiment. We gave participants positive information about psychotherapy effectiveness and varied the therapist's interpersonal behaviour along the dimensions of warmth and competence.Results: High (vs. low) competence and high (vs. low) warmth increased alliance, OE, and help-seeking scores, while high (vs. low) competence increased motivation to do psychotherapy. We found no effects on health behaviour.Conclusion: In contrast to previous correlational analyses, our experimental study supports the causal role of the therapist's warmth and competence and its impact on alliance, motivation, and OE. We discuss approaches for future studies and clinical implications.

Pre-surgery optimization of patients' expectations to improve outcome in heart surgery: Study protocol of the randomized controlled multi-center PSY-HEART-II trial.

The PSY-HEART-I trial indicated that a brief expectation-focused intervention prior to heart surgery improves disability and quality of life 6 months after coronary artery bypass graft surgery (CABG). However, to investigate the clinical utility of such an intervention, a large multi-center trial is needed to generalize the results and their implications for the health care system. The PSY-HEART-II study aims to examine whether a preoperative psychological intervention targeting patients' expectations (EXPECT) can improve outcomes 6 months after CABG (with or without heart valve replacement). EXPECT will be compared to Standard of Care (SOC) and an intervention providing emotional support without targeting expectations (SUPPORT). In a 3-arm multi-center randomized, controlled, prospective trial (RCT), N = 567 patients scheduled for CABG surgery will be randomized to either SOC alone or SOC and EXPECT or SOC and SUPPORT. Patients will be randomized with a fixed unbalanced ratio of 3:3:1 (EXPECT: SUPPORT: SOC) to compare EXPECT to SOC and EXPECT to SUPPORT. Both psychological interventions consist of 2 in-person sessions (à 50 minute), 2 phone consultations (à 20 minute) during the week prior to surgery, and 1 booster phone consultation post-surgery 6 weeks later. Assessment will occur at baseline approx. 3-10 days before surgery, preoperatively the day before surgery, 4-6 days later, and 6 months after surgery. The study's primary end point will be patients' illness-related disability 6 months after surgery. Secondary outcomes will be patients' expectations, subjective illness beliefs, quality of life, length of hospital stay and blood sample parameters (eg, inflammatory parameters such as IL-6, IL-8, CRP). This large multi-center trial has the potential to corroborate and generalize the promising results of the PSY-HEART-I trial for routine care of cardiac surgery patients, and to stimulate revisions of treatment guidelines in heart surgery.

Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression.

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

Determining prognostic variables of treatment outcome in obsessive-compulsive disorder: effectiveness and its predictors in routine clinical care.

The objectives of this study were to investigate the naturalistic effectiveness of routine inpatient treatment for patients with obsessive-compulsive disorder (OCD) and to identify predictors of treatment outcome. A routinely collected data set of 1,596 OCD inpatients (M = 33.9 years, SD = 11.7; 60.4% female) having received evidence-based psychotherapy based on the cognitive-behavioral therapy (CBT) in five German psychotherapeutic clinics was analyzed. Effect sizes (Hedges' g) were calculated for several outcome variables to determine effectiveness. Predictor analyses were performed on a subsample (N = 514; M = 34.3 years, SD = 12.2; 60.3% female). For this purpose, the number of potential predictors was reduced using factor analysis, followed by multiple regression analysis to identify robust predictors. Effect sizes of various outcome variables could be classified as large (g = 1.34 of OCD-symptom change). Predictors of changes in OCD and depressive symptoms were symptom severity at admission and general psychopathological distress. In addition, patients with higher social support and more washing compulsions benefited more from treatment. Subgroup analyses showed a distinct predictor profile of changes in compulsions and obsessions. The results indicate that an evidence-based psychotherapy program for OCD can be effectively implemented in routine inpatient care. In addition to well-established predictors, social support, and washing compulsions in particular were identified as important positive predictors. Specific predictor profiles for changes in obsessions and compulsions are discussed.

Baseline depressive symptoms, personal control, and concern moderate the effects of preoperative psychological interventions: the randomized controlled PSY-HEART trial.

This study examined whether baseline (3-14 days pre-surgery) levels of (i) depressive or (ii) anxiety symptoms and (iii) illness beliefs moderate the effects of additional preoperative interventions before coronary artery bypass graft surgery on (i) depressive or (ii) anxiety symptoms and (iii) illness beliefs 1 day before surgery, 1 week and 6 months after surgery. In the PSY-HEART trial, 115 patients were assessed. They were randomized into one of three groups: 1. receiving standard medical care only (SMC), additional psychological interventions: 2. aiming to optimize patients' expectations (EXPECT), or 3. focusing on emotional support. Patients with a higher baseline level of depressive symptoms receiving a preoperative psychological intervention indicated lower depressive symptoms 6 months after surgery compared to SMC. EXPECT increased personal control and concern levels in patients with low baseline personal control/concern 1 day before surgery. Brief preoperative psychological interventions can improve psychological outcomes in heart surgery patients. Baseline status may moderate these effects. The study has been approved by the medical ethics committee of the Philipps University of Marburg and has been pre-registered at www.clinicaltrials.gov (NCT01407055) on August 1, 2011.

Integrated neuropsychological and cognitive behavioural therapy after acquired brain injury: A pragmatic randomized clinical trial.

After acquired brain injury (ABI) many patients suffer from persistent cognitive and emotional disturbances. The aim of this study was to investigate the treatment outcome of an integrated intervention, combining neuropsychological and cognitive behavioural therapy (nCBT), against waitlist (WL) in outpatients with ABI. Individuals seeking outpatient treatment for cognitive and emotional problems after ABI were randomly allocated to nCBT (n = 27) or WL (n = 29) and completed assessments at baseline, post-treatment/WL and at six-month follow-up. The primary outcome measures were general psychopathology and functional activity in daily life. The nCBT group showed significant improvement for general psychopathology post-treatment when compared to WL. nCBT was also superior to WL regarding the secondary outcomes, i.e., the reduction of negative affect and the improvement of quality of life. No significant differences for functional activity and community integration were observed. Significant pre-post effect sizes ranged between small for functional activity and medium for quality of life. The positive effects were maintained at follow-up. The majority of patients with cognitive and emotional problems after ABI benefit from an integrated approach that offers cognitive remediation and psychotherapy. However, the heterogeneous sequelae of ABI and the moderate sample sizes in clinical trials present a methodological challenge to ABI research.

The effect of patient-centered communication on medication intake: an experimental study.

It is not only crucial to provide patients with information, but also to communicate this information in a way to enable patient participation in health decisions. Experimental studies investigating the association between the communication style of health professionals and patients' health decisions are rare, which limits causal conclusions. This study investigated the effect of a doctor's patient-centered communication style on the likelihood to take a medication.Healthy women (N = 120) were randomly allocated to one of three groups. They either received a medical consultation characterized by a patient-centered communication style (PC group) or by a doctor-centered communication style (DC group) or they received no consultation at all (control group). All participants were told that the study would investigate the effects of a 'concentration-enhancing medication'. Voluntary intake of the medication (a placebo pill) served as behavioral outcome. Participants' self-rated intention to take the medication was measured at three assessment points. Data were analyzed using a Chi-square-test and a mixed analysis of covariance.In each group, 40 participants were analyzed. Following the consultation, groups did not differ regarding the behavioral outcome, but participants' intention to take the medication was higher in the PC group compared with the control group.Our results indicate that patient-centered communication has a beneficial influence on participants' intention to take medication. Future studies should investigate the role of communication in individuals with health conditions that require a specified treatment plan and taking medication over the long-term.

Predicting optimal treatment outcomes using the Personalized Advantage Index for patients with persistent somatic symptoms.

Objective: Because individual patients with persistent somatic symptoms (PSS) respond differently to treatments, a better understanding of the factors that predict therapy outcomes are of high importance. Aggregating a wide selection of information into the treatment-decision process is a challenge for clinicians. Using the Personalized Advantage Index (PAI) this study aims to deal with this. Methods: Data from a multicentre RCT comparing CBT (N = 128) versus CBT enriched with emotion regulation training (ENCERT) (N = 126) for patients diagnosed with somatic symptom disorder were used to identify based on two machine learning approaches predictors of therapy outcomes. The identified predictors were used to calculate the PAI. Results: Five treatment unspecific predictors (pre-treatment somatic symptom severity, depression, symptom disability, health-related quality of life, age) and five treatment specific moderators (global functioning, early childhood traumatic events, gender, health anxiety, emotion regulation skills) were identified. Individuals assigned to their PAI-indicated optimal treatment had significantly lower somatic symptom severity at the end of therapy compared to those randomised to their non-optimal condition. Conclusion: Allowing patients to choose a personalised treatment seems to be meaningful. This could help to improve outcomes for PSS and reduce its high costs to the health care system.

Placebo effects in allergen immunotherapy-An EAACI Task Force Position Paper.

The placebo (Latin "I will please") effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients' expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double-blind, placebo-controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials.

COVID-19 pandemic: Practical considerations on the organization of an allergy clinic-An EAACI/ARIA Position Paper.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has evolved into a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Allergists and other healthcare providers (HCPs) in the field of allergies and associated airway diseases are on the front line, taking care of patients potentially infected with SARS-CoV-2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics. METHOD: The scientific information on COVID-19 was analysed by a literature search in MEDLINE, PubMed, the National and International Guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library, and the internet. RESULTS: Based on the diagnostic and treatment standards developed by EAACI, on international information regarding COVID-19, on guidelines of the World Health Organization (WHO) and other international organizations, and on previous experience, a panel of experts including clinicians, psychologists, IT experts, and basic scientists along with EAACI and the "Allergic Rhinitis and its Impact on Asthma (ARIA)" initiative have developed recommendations for the optimal management of allergy clinics during the current COVID-19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies. CONCLUSIONS: This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients while ensuring the necessary safety measures in the current COVID-19 pandemic.

IL-8 and CRP moderate the effects of preoperative psychological interventions on postoperative long-term outcomes 6 months after CABG surgery - The randomized controlled PSY-HEART trial.

INTRODUCTION: Inflammation has been related to several somatic and psychological disorders and may moderate effects of psychological interventions. In the PSY-HEART trial patients benefitted from preoperative psychological interventions before undergoing coronary artery bypass graft surgery (CABG) and, if necessary, concomitant valvular surgery, compared to standard medical care. In this study we examined whether patients' baseline inflammatory status moderated the intervention effects. MATERIAL AND METHODS: In a prospective three-arm randomized clinical trial with 6-months follow-up, 124 patients scheduled for CABG surgery alone or concomitant with valvular surgery were randomized to (i) standard medical care only (SMC) or two preoperative psychological interventions: (ii) CBT-based optimizing expectations (EXPECT) and an (iii) an active control group focusing on emotional support (SUPPORT). Available baseline CRP- (n = 79), IL-6- (n = 78), IL-8- (n = 78) and TNF-alpha-(n = 80) parameters were considered as potential moderators (CRP as a categorical and continuous moderator). Linear mixed model analyses were calculated to test whether baseline inflammatory levels moderated intervention effects on disability, mental and physical quality of life at 6 months after surgery. RESULTS: IL-8 moderated intervention effects on patients' disability and categorical CRP moderated intervention effects on mental quality of life. Follow-up tests indicated that EXPECT (and in part SUPPORT) led to lower postoperative disability and higher mental quality of life compared to SMC in patients with low baseline inflammatory markers. EXPECT indicated higher mental quality of life compared to SUPPORT in the high CRP subgroup. Patients in the SMC group had higher mental quality of life in the high CRP subgroup compared to the low CRP subgroup. CONCLUSION: Especially for patients with a lower inflammatory baseline status preoperative psychological interventions might be helpful to optimize long-term CABG surgery outcomes.