Emotion-centered versus fact-centered medical information to alleviate pain and anxiety in prostate biopsy: A randomized trial.

BACKGROUND: To test the efficacy of emotion-centered (EC) versus fact-centered (FC) written medical information for prostate biopsy to alleviate pain and anxiety in a randomized controlled trial. METHODS: In a single-center, single-blinded study participants were randomized to receive FC or EC (DRKS00022361; 2020). In the EC, the focus was on possible stress reactions and stress-reducing strategies. Participants were asked to complete questionnaires on the day of MRI acquisition (T0) directly before (T1) and after the procedure (T2). The primary outcome measure was the assessment of worst pain in the last 2 h measured by the adapted brief pain inventory. Secondary outcome measures included state anxiety measured by the state-trait anxiety inventory and the subjective evaluation of the impact of the written medical information at T2. For statistical analysis, mixed models were calculated. RESULTS: Of 137 eligible patients, 108 (79%) could be recruited and were randomized. There was a significant effect for time for the outcome variables pain and anxiety. Regarding the comparison for the primary outcome variable worst pain there was a significantly lower increase from T1 to T2 after FC compared to EC (p < 0.004). The course of anxiety displayed no overall group differences. The FC was evaluated as significantly more helpful regarding stress, pain, and anxiety with moderate effect sizes. CONCLUSIONS: FC was favorable with regard to worst experienced pain, assuming that the brief introduction of emotional issues such as stress and coping in written information might be counterproductive particularly in men not used to these subjects.

[Short paths to diagnosis with artificial intelligence: systematic literature review on diagnostic decision support systems]. / Kurze Wege zur Diagnose mit künstlicher Intelligenz ­ systematische Literaturrecherche zu "diagnostic decision support systems".

BACKGROUND: Rare diseases are often recognized late. Their diagnosis is particularly challenging due to the diversity, complexity and heterogeneity of clinical symptoms. Computer-aided diagnostic aids, often referred to as diagnostic decision support systems (DDSS), are promising tools for shortening the time to diagnosis. Despite initial positive evaluations, DDSS are not yet widely used, partly due to a lack of integration with existing clinical or practice information systems. OBJECTIVE: This article provides an insight into currently existing diagnostic support systems that function without access to electronic patient records and only require information that is easily obtainable. MATERIALS AND METHODS: A systematic literature search identified eight articles on DDSS that can assist in the diagnosis of rare diseases with no need for access to electronic patient records or other information systems in practices and hospitals. The main advantages and disadvantages of the identified rare disease diagnostic support systems were extracted and summarized. RESULTS: Symptom checkers and DDSS based on portrait photos and pain drawings already exist. The degree of maturity of these applications varies. CONCLUSION: DDSS currently still face a number of challenges, such as concerns about data protection and accuracy, and acceptance and awareness continue to be rather low. On the other hand, there is great potential for faster diagnosis, especially for rare diseases, which are easily overlooked due to their large number and the low awareness of them. The use of DDSS should therefore be carefully considered by doctors on a case-by-case basis.

Treating pain in patients with Ehlers-Danlos syndrome : Multidisciplinary management of a multisystemic disease.

BACKGROUND: The clinical picture of people with Ehlers-Danlos syndromes (EDS) is complex and involves a variety of potential causes of pain. This poses major challenges to patients and healthcare professionals alike in terms of diagnosis and management of the condition. OBJECTIVES: The aim of the article was to provide an overview of the specific pain management needs of patients with EDS and address their background. MATERIAL AND METHODS: A selective literature search was performed to highlight the current state of research on pain management in EDS patients. RESULTS: Affected patients require multimodal pain management considering their individual needs, disease-specific features, and comorbidities. CONCLUSION: Medical awareness and evidence need to be further improved to enhance the medical care situation of these patients with complex needs.

Originalbeiträge (Originals). Altered microvascular density in patients with anorexia nervosa ­ an optical coherence tomography angiography (OCTA) pilot study.

OBJECTIVES: To investigate macular and peripapillary vascular density (VD) in patients with anorexia nervosa (AN) compared to healthy controls. Methods:Whole face scans of the superficial and deep macular layers and whole face and peripapillary scans of the radial peripapillary capillaries (RPC) were obtained using optical coherence tomography angiography (OCTA, AngioVueR, Optovue) in ten patients with AN and ten age-matched controls.The primary objective was to determine whether there was a difference between the vessel density (VD) in the above areas in AN and controls. P-values ≤ 0.0125 were considered statistically significant. Results: VD in the superficialmacular en-face OCTA image was significantly lower in the study group compared to the control group. Neither the deepmacula nor the radial peripapillary capillary (RPC) in the whole-face image nor the RPC-peripapillary imaging appeared to be significantly different. Conclusion: Patients with AN showed reduced VD in the superficialmacular layers compared to healthy controls, which can be discussed as a consequence of the malnutrition. OCTA could be a useful non- invasive tool to detect reduced peripheral blood supply to show vascular changes that occur before ocular symptoms.

Cluster-Analytic Identification of Clinically Meaningful Subtypes in MCAS: The Relevance of Heat and Cold.

BACKGROUND: Mast cell activation syndrome (MCAS) is a clinically heterogeneous disease with allergy-like symptoms and abdominal complaints. Its etiology is only partially understood and it is often overlooked. AIMS: The aim of this study was to identify subgroups of MCAS patients to facilitate diagnosis and allow a personalized therapy. METHODS: Based on data from 250 MCAS patients, hierarchical and two-step cluster analyses as well as association analyses were performed. The data used included data from a MCAS checklist asking about symptoms and triggers and a set of diagnostically relevant laboratory parameters. RESULTS: Using a two-step cluster analysis, MCAS patients could be divided into three clusters. Physical trigger factors were particularly decisive for the classification as they showed remarkable differences between the three clusters. Cluster 1, labeled high responders, showed high values for the triggers heat and cold, whereas cluster 2, labeled intermediate responders, presented with high values for the trigger heat and low values for cold. The third cluster, labeled low responders, did not react to thermal triggers. The first two clusters showed more divers clinical symptoms especially with regard to dermatological and cardiological complaints. Subsequent association analyses revealed relationships between triggers and clinical complaints: Abdominal discomfort is mainly triggered by histamine consumption, dermatological discomfort by exercise, and neurological symptoms are related to physical exertion and periods of starvation. The reasons for the occurrence of cardiological complaints are manifold and triggers for respiratory complaints still need better identification. CONCLUSION: Our study identified three distinct clusters on the basis of physical triggers, which also differ significantly in their clinical symptoms. A trigger-related classification can be helpful in clinical practice for diagnosis and therapy. Longitudinal studies should be conducted to further understand the relationship between triggers and symptoms.

Psychometric properties and normative values of the revised demoralization scale (DS-II) in a representative sample of the German general population.

BACKGROUND: Demoralization is a clinically relevant syndrome in chronic diseases. The demoralization scale (DS-II) was recently developed as an economic screening tool in clinical populations. Main aim of this study was to provide normative data of DS-II scores in the general population. METHODS: We developed a new German version, the DS-II Münster, and tested internal consistency as well as the previously proposed two-factor structure with confirmatory factor analyses. The DS-II was applied in a household survey of the general population. Associations between DS-II scores and age, gender and other sociodemographic variables were explored. RESULTS: The final sample consisted of N = 2471 participants (mean age = 49.8 years, range: 18-96; 50.1% men, 49.8% women). The DS-II Münster showed nearly excellent internal consistency. The model fit indices of the two-factor structure were not superior to those of the one-factor model. Mean scores of the DS-II were as follows. Total score: M = 3.76 (SD = 5.56), Meaning and Purpose subscale: M = 1.65 (SD = 2.77), Distress and Coping Ability subscale: M = 2.11 (SD = 3.02). DS-II scores were increased in women with an effect size of Cohen's d = 0.19. An age-related increase was specifically found for the Meaning and Purpose subscale (d = 0.21). CONCLUSIONS: The study provides normative values of the DS-II with respect to age and gender in the general population to facilitate interpretation of DS-II scores in clinical samples. A DS-II total score > 5 is suggested as a cut-off value. The findings further our understanding of significant symptom burden that was previously suggested in young patients with cancer.

Exploring different stakeholders' perspectives on ward rounds in paediatric oncology: a qualitative study.

RATIONAL/AIMS AND OBJECTIVES: Ward rounds are a core routine for interprofessional communication and clinical care planning: Health care professionals and patients meet regularly and it encourages patients to actively participate. In paediatric oncology, the long treatment process, the serious diagnosis, and involvement of both patients and their parents in shared-decision-making require specific ward round skills. Despite its high value for patient-centred care, a universal definition of ward round is lacking. Little is known about attitudes and expectations of different participants towards a 'good' ward round. This study aims to capture experiences and expectations of different stakeholders to better understand ward round needs in paediatric oncology and serve as a basis to improve future ward rounds. METHOD: Semi-structured interviews were conducted with patients, parents, nurses and medical doctors of a paediatric oncology ward until theoretical saturation (13 interviews). A standardised qualitative analysis using the phenomenological framework defined by Colaizzi was used to identify important aspects in the interviews. RESULTS: Three major themes were identified in the interviews: [1] Structure and Organisation; [2] Communication; [3] Education. Further analysis revealed 23 categories and elucidated several opportunities and unmet needs recognized by stakeholders: Ward round functions in comforting families in stressful situations, and relationship building. Interviewees expressed their concerns about missing structures. Families pleaded for smaller ward round teams and layperson language. Health care professionals underscored the lack of ward round training. Paediatric patients stated that ward round scared them without proper explanation. All interviewees emphasized the need for professionalization of the ward round in the setting of paediatric oncology. CONCLUSION: This study gives important insights into ward round functions and organisational requirements. It addresses special challenges for ward round participants in paediatric oncology, such as consideration of the emotional aspect of cancer treatment or the limits of shared decision making. Furthermore, this study underscores the great significance of ward rounds in paediatric oncology, with an emphasis on communication and relationship-building. Although performed universally, ward rounds are poorly explored or evaluated. This structured analysis synthesizes important expectations of different WR stakeholders, revealing opportunities of improvement and stressing the need for guidelines, training, and preparation.

Risk factors for pressure ulcers in adult patients: A meta-analysis on sociodemographic factors and the Braden scale.

AIMS AND OBJECTIVES: Providing the first meta-analysis of risk factors for pressure ulcer development in adult patients. BACKGROUND: Pressure ulcers remain a serious health complication for patients and nursing staff. However, there is a lack of statistical evidence for risk factors as previous research did not include any quantitative synthesis. DESIGN: Meta-analysis, using PRISMA guidelines. METHODS: Studies from PubMed, Embase, CINAHL Complete, Web of Science, Cochrane Library, and other reviews and sources were screened and checked against the inclusion criteria. The risk of bias was evaluated using a slightly modified QUIPS tool. Data regarding population, design, statistical analysis and risk factors were extracted. Meta-analysis with comparable studies was conducted for age, sex, and Braden scale. The sub-group analysis was used to account for heterogeneity. RESULTS: 28 studies with 570,162 patients were entered in meta-analysis. Older age and a low total Braden scale score increased the risk for pressure ulcers. All subscales excluding 'moisture' reached significance in meta-analysis based only on few studies, however, limiting overall evidence. Male sex achieved mixed results, too. CONCLUSION: The first meta-analytic analysis shows evidence for age and Braden scale as risk factors for pressure ulcer development. Limitations regarding study quality and heterogeneity must be considered, highlighting the need for unifying certain conditions in risk factor research. RELEVANCE TO CLINICAL PRACTICE: Patients at risk for new pressure ulcers can be identified by their total Braden score and age, whereas the latter is also connected to deeper pressure ulcers. Nurses and health personnel should pay great attention to patients in older age and undergo specific training to utilise and evaluate the Braden scale effectively, if necessary.

Coping with multiple sclerosis: reconciling significant aspects of health-related quality of life.

Multiple sclerosis (MS) symptoms and unpredictability can damage patient well-being. This study is aimed to investigate the relation between sociodemographic and clinical characteristics and the use of coping strategies as well as social support on health-related quality of life (HRQOL). We evaluated 314 MS outpatients of Virgen Macarena University Hospital in Sevilla/Spain (mean age 45 years, 67.8% women) twice over an 18-months period by Brief COPE Questionnaire (COPE-28), Multidimensional Scale of Perceived Social Support (MSPSS) and 12-Item Short Form Health Survey (SF-12). Female gender was significantly related to religion (r= 0.175, p< 0.001), self-distraction (r= 0.160, p< 0.001) and self-blame (r= 0.131, p< 0.05). Age correlated positively with religion (r= 0.240, p< 0.001), and self-blame (r= 0.123, p< 0.05). Progressive MS as well as functional impairment (EDSS) showed a positive relation with denial (r= 0.125, p< 0.05; r= 0.150, p< 0.001). Longer duration since diagnosis was related to lower perceived support from family (r= -0.123, p< 0.05). EDSS (ß= -0.452, p< 0.001) was the strongest negative predictor of physical HRQOL followed by age (ß= -0.123, p< 0.001), whereas family support was a protective factor (ß= 0.096, p< 0.001). Denial (ß= -0.132, p< 0.05), self-blame (ß= -0.156, p< 0.05), female gender (ß= -0.115, p< 0.05) and EDSS (ß= -0.108, p< 0.05) negatively impacted on mental HRQOL 18 months later, whereas positive reframing (ß= 0.142, p< 0.05) was a protective factor. Our study could identify sociodemographic and clinical variables associated with dysfunctional coping strategies, such as self-blame and denial, which specifically predict worse mental HRQOL as opposed to positive reframing. Diminishing dysfunctional coping and supporting cognitive reframing may contribute to improve HRQOL in MS.

[Postoperative pain experience after proximal femur fracture in dementia]. / Postoperatives Schmerzerleben nach proximaler Femurfraktur bei Demenz.

BACKGROUND: The present study aimed to assess the postoperative pain experience in cognitive deficit patients with special reference to sensory or affective pain quality. METHODS: Nineteen patients with normal cognition up to cognitive impairments according to the DemTect screening-tool were studied regarding their postoperative pain experience after proximal femur fracture. The numerical rating scale (NRS), the cognitive DemTect questionnaire, the pain sensation questionnaire (SES), and a quantitative sensory test (QST) were used as examination instruments. RESULTS: The mean ± SD age of the patients was 83.8 ± 10.0 years. Of the 19 patients, 6 (31.6%) had normal cognitive abilities. In 4 patients (21.1%) there were indications of mild cognitive impairments, and in 9 patients (47.4%) the suspicions of the presence of dementia arose. The mean postoperative pain intensity (NRS) was 4.0 (1.6). With comparable analgesic therapy, the reported pain intensities did not differ between the three patient groups with different cognitive impairments and the first three postoperative treatment days. There were no statistically significant differences between the groups for the sensory or affective total scores of the pain sensation scale. The QST parameters deep pain (PPT), superficial mechanical pain after needle stimulation (MPT), and the superficial sensitivity to light touch stimuli (MDT) showed a significantly increased sensitivity of the operated side. For the sensation of vibration (VDT) no differences between operated and healthy extremities could be proven. DISCUSSION: The postoperative pain experience does not differ between patients with normal and limited cognition. The quantitative sensory testing showed mechanical hyperalgesia in the operated area. The study points to the importance of adequate postoperative pain management even in those with dementia.

Development of Care Pathway for Assessment and Treatment of Fatigue in Palliative Care.

Objectives: Fatigue is a frequent and burdensome symptom in patients with advanced disease in palliative care. However, it is under-assessed and undertreated in clinical practice, even though many treatment options have been identified in systematic reviews. Care pathways with defined and standardised steps have been recommended for effective management in the clinical setting. This paper describes a care pathway for managing fatigue in palliative care patients. This study aims to develop a care pathway with detailed guidance for screening, assessment, diagnosis, and treatment of fatigue in palliative care patients. Material and methods: A collaborative effort of multidisciplinary clinicians participated in constructing the care pathway. The care pathway was developed using the following steps: (a) Developing an intervention; (b) piloting and feasibility; (c) evaluating the intervention; (d) reporting; and (e) implementation. This paper covers the first step, which includes the evidence base identification, theory identification/development, and process/outcomes modeling. A literature search was conducted to understand the extent of the fatigue problem in the palliative care setting and identify existing guidelines and strategies for managing fatigue. Consistent recommendations emanating from the included papers were then contributed to a care pathway. Patient representatives and palliative care professionals provided feedback on the draft. Results: The care pathway address the following care processes: (1) Screening for the presence of fatigue; (2) assessment to evaluate the severity of fatigue; (3) diagnostic procedure, including history, physical examination, and laboratory finding; (4) therapeutic management pathway for clinical decision-making; and (5) valuation of treatment effect, using questionnaires, diaries and physical activity monitoring with body-worn sensors. Conclusion: The development of a care pathway will help to implement regular and structured assessment, diagnosis, and treatment of fatigue for healthcare professionals treating palliative care patients. Reviewing the pathway with a multidisciplinary expert group and field testing the pathway will be the next steps toward implementation.

Effect of a Biofeedback Intervention on Heart Rate Variability in Individuals With Panic Disorder: A Randomized Controlled Trial.

OBJECTIVE: Some individuals with panic disorder (PD) display reduced heart rate variability (HRV), which may result in an increased risk of cardiovascular mortality. Heart rate variability-biofeedback (HRV-BF) training has been shown to improve the modulation of the autonomic activity. Therefore, this randomized controlled trial was conducted to investigate the effect of a 4-week HRV-BF intervention in individuals with PD. HRV-BF training improved the modulation of the autonomic activity. Therefore, with this randomized controlled trial, we aimed to investigate the effect of a 4-week HRV-BF intervention in people with PD. METHODS: Thirty-six women and 16 men with PD (mean age = 35.85 [15.60] years) were randomly allocated either to HRV-BF with 0.1-Hz breathing as intervention group or to HRV-Sham-BF as active control group. HRV-BF was performed for 4 weeks, whereas HRV was measured both during a short-term resting condition and during a paced breathing condition before and after intervention. RESULTS: HRV-BF with 0.1-Hz breathing increased HRV and reduced panic symptoms in individuals with PD. HRV-BF with 0.1-Hz breathing demonstrated an increase in the time and frequency domain parameters of HRV during the short-term resting condition (ΔPost-Pre root mean square successive differences: 5.87 [14.03] milliseconds; ΔPost-Pre standard deviation of all NN intervals: 11.63 [17.06] milliseconds; ΔPost-Pre total power: 464.88 [1825.47] milliseconds2; ΔPost-Pre power in low-frequency range 0.04-0.15 Hz: 312.73 [592.71] milliseconds2), a decrease in the heart rate during the paced breathing condition (ΔPost-Pre: -5.87 [9.14] beats/min), and a decrease in the Panic and Agoraphobia Scale (ΔPost-Pre: -3.64 [6.30]). There was no intervention effect in the HRV-Sham-BF group. CONCLUSIONS: HRV-BF as a noninvasive and nonpharmacological treatment seems to be an important intervention option to improve reduced HRV and decrease panic symptoms in individuals with PD. Future studies are needed to establish whether these effects translate to reductions in the risk of cardiovascular disease in PD.

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.

Prospective analysis of pain expectancy and experience during MR-fusion prostate biopsy: does reality match patients' expectancy?

PURPOSE: Multiparametric magnetic resonance imaging fusion targeted prostate biopsy (MR-TB) has emerged to the biopsy technique of choice for evaluation of patients with suspected prostate cancer (PCA). The study aimed to determine expected and experienced pain during MR-TB depending on patients' psychological state. METHODS: We prospectively enrolled 108 men with suspicion of PCA who underwent MR-TB. All patients completed self-reported validated questionnaires assessing pain, stress, self-efficacy, anxiety and study-specific questionnaires on expected and experienced pain before, during and after MR-TB. Patient characteristics and survey scores were obtained. RESULTS: Overall, pain levels during MR-TB were low (mean 2.8/10 ± 2.5 Numerical Rating Scale, NRS). 10/86 (11.6%) participants reported severe pain (≥ 7/10 NRS). Pain correlated significantly with anxiety (r = 0.42), stress (r = 0.22) and pain expectancy (r = 0.58). High self-efficacy did not show increased pain resilience. Participants anticipated more pain than experienced during each step of MR-TB with significant differences concerning local anesthesia and core sampling (both p < 0.001), among others. Expectancy and actual pain did not match regarding severity and impact of the total amount of cores taken (p < 0.05). Independent predictors of increased pain at biopsy were prostate volume > 50 ml (p = 0.0179) and expected pain during rectal manipulation (p < 0.001). CONCLUSION: Pain during MR-TB can be positively influenced by reducing men's anxiety, stress and pain expectancy. To meet the needs of the audience, clinicians should address concrete pain levels of each procedural step and consider special treatment for patients with prostate volume > 50 ml and men reporting on increased rectal sensitivity.

Personality subtypes in adults with social anxiety disorder - novelty seeking makes the difference.

BACKGROUND: Up to now several subtypes of social anxiety disorder (SAD) have been proposed. METHODS: In the present study, we used a cluster analytic approach to identify qualitatively different subgroups of SAD based on temperament characteristics, that is, harm avoidance (HA) and novelty seeking (NS) dimensions of Cloninger's Temperament and Character Inventory. RESULTS: Based on a large, diverse clinical sample (n = 575), we found evidence for two distinct subgroups of SAD: a larger (59%) prototypic, inhibited cluster characterized by high HA and low NS, and a smaller atypic, and comparatively more impulsive cluster characterized by medium to high HA and increased NS. The subgroups differed regarding a variety of sociodemographic and clinical variables. While the prototypic SAD subtype suffered from more severe SAD and depressive symptoms, suicidal ideation, and reduced social functioning, the atypic NS subtype showcased higher reproductive behaviour, self-directedness and -transcendence, comparatively. Additional hierarchical logistic regression highlights the contribution of age and education. CONCLUSIONS: Our results valuably extend previous evidence for the existence of at least two distinct subtypes of SAD. A better knowledge of the characteristic differences in prototypic behaviour, personality, coping strategies and comorbidities between the identified (and further) subtypes can contribute to the development of effective prevention interventions and promotes the conceptualization of tailored treatments.

Improving quality of life in pancreatic cancer patients following high-intensity focused ultrasound (HIFU) in two European centers.

OBJECTIVES: Pancreatic cancer patients often have a high symptom burden, significantly impairing patients' quality of life (QOL). Nevertheless, there are hardly any reports on the impact of high-intensity focused ultrasound (HIFU) on the QOL of treated patients. For the first time, this study evaluated the effect of HIFU on QOL and compared these results in two European centers. METHODS: Eighty patients with advanced pancreatic cancer underwent HIFU (50 in Germany, 30 in Bulgaria). Clinical assessment included evaluation of QOL and symptoms using the EORTC QLQ-C30 questionnaire at baseline and 1, 3, and 6 months after HIFU. Pain intensity was additionally evaluated with the numerical rating score (NRS). RESULTS: Compared to baseline, global health significantly improved 3 and 6 months after HIFU treatment (p = 0.02). Functional subscales including physical, emotional, and social functioning were considerably improved at 6 months (p = 0.02, p = 0.01, and p = 0.01, respectively) as were leading symptom pain (p = 0.04 at 6 months), fatigue (p = 0.03 at 3 and p = 0.01 at 6 months), and appetite loss (p = 0.01 at 6 months). Moreover, pain intensity measured by NRS revealed effective and strong pain relief at all time points (p < 0.001). Reported effects were independent of tumor stage, metastatic status, and country of treatment. CONCLUSIONS: This study showed that HIFU represents an effective treatment option of advanced pancreatic cancer improving QOL by increasing global health and mitigation of physical complaints with a low rate of side effects, independent of the examiner. Therefore, HIFU is a worthwhile additional treatment besides systemic palliative chemotherapy or best supportive care in management of this aggressive disease. KEY POINTS: • In a prospective two-center study, it was shown that HIFU represents an effective treatment option of advanced pancreatic cancer improving QOL. • HIFU in pancreatic cancer patients is associated with a low rate of side effects, independent of the performer. • HIFU is a worthwhile additional treatment besides systemic palliative chemotherapy or best supportive care in management of this aggressive disease.

US-guided high-intensity focused ultrasound (HIFU) of abdominal tumors: outcome, early ablation-related laboratory changes and inflammatory reaction. A single-center experience from Germany.

INTRODUCTION: High-intensity focused ultrasound (HIFU) is an innovative noninvasive procedure for local ablation of different benign and malignant tumors. Preliminary data of animal studies suggest an ablation-associated immune response after HIFU that is induced by cell necrosis and release of intracellular components. The aim of this study is to evaluate if a HIFU-induced early sterile inflammatory reaction is initiated after ablation of uterine fibroids (UF) and pancreatic carcinoma (PaC) which might contribute to the therapeutic effect. MATERIAL AND METHODS: A hundred patients with PaC and 30 patients with UF underwent US-guided HIFU treatment. Serum markers of inflammation (leukocytes, CRP, IL-6) and LDH in both collectives as well as tumor markers CA 19-9, CEA and CYFRA in PaC patients were determined in sub-cohorts before and directly after HIFU (0, 2, 5 and 20 h post-ablation) as well as at 3, 6, 9 and 12 months follow-up. Peri-/post interventional imaging included contrast-enhanced MRI of both cohorts and an additional CT scan of PaC patients. RESULTS: An early post-ablation inflammatory response was observed in both groups with a significant increase of leukocytes, CRP and LDH within the first 20 h after HIFU. Interestingly, IL-6 was increased at 20 h after HIFU in PaC patients. A significant reduction of tumor volumes was observed during one year follow-up (p < .001) for both tumor entities demonstrating effective treatment outcome. CONCLUSION: Tumor ablation with HIFU induces an early sterile inflammation that might serve as a precondition for long-term tumor immunity and a sustainable therapeutic effect.

Efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for uterine fibroids: an observational single-center study.

INTRODUCTION: To evaluate treatment response of uterine fibroids after ultrasound guided high-intensity focused ultrasound (USgHIFU) with a special focus on fibroid size and characterization based on Funaki classification scheme, as well as clinical response to treatment of leading fibroid-associated symptoms. MATERIALS AND METHODS: Uterine fibroids treated by USgHIFU were assigned to Funaki type 1-3 based on T2-w-MRI. Differences in size, non-perfused volume ratio (NPVR) and volume reduction over time were determined using T1-/T2-w MRI sequences and contrast-enhanced sonography. Treatment effects on three leading fibroid-associated symptoms were also evaluated. Measurements were compared by mixed model, Bland-Altman's plot and Spearman's correlation. RESULTS: In this prospective single-center study, 35 patients with 44 symptomatic uterine fibroids were treated by USgHIFU (n = 22, n = 12 and n = 10 assigned to Funaki type 1, 2 and 3, respectively). NPVRs of Funaki type 1 and 2 fibroids were significantly higher compared to type 3 (p = .0023). A significant fibroid shrinkage was observed independent of Funaki type compared to baseline: 38.8 ± 26.9%, 46.7 ± 30.3% and 54.5 ± 29.3% at 3, 6 and 12 months, respectively (each p < .05). Moreover, patients experienced a significant improvement of fibroid-associated hypermenorrhea (3.9 ± 1.3 vs. 2.3 ± 1.3), pressure in the pelvic area (3.5 ± 1.3 vs. 2.1 ± 0.9) and frequent urination (2.8 ± 1.5 vs. 1.9 ± 0.8) one year post-procedure (each p < .05), regardless of fibroid Funaki type. CONCLUSION: Following USgHIFU, a significant shrinkage of uterine fibroids and improvement of leading fibroid-associated symptoms were demonstrated regardless of the Funaki type.

Significance of anger suppression and preoccupied attachment in social anxiety disorder: a cross-sectional study.

BACKGROUND: There is evidence for the relevance of attachment style and anger expression for the manifestation of social anxiety disorder (SAD). METHOD: In a cross-sectional study 321 individuals with social anxiety disorder (41% men, age 38.8 ± 13.9) were compared with 94 healthy controls (37% men, age 35.8 ± 15.1) on several questionnaires (Attachment Styles Questionnaire, State Trait Anger Inventory, Social Phobia Inventory, Beck Depression Inventory). RESULTS: Individuals with SAD showed moderate-sized reduced levels of secure and large-sized increased levels of fearful and preoccupied attachment style compared to healthy controls (all p < 0.001) as well as small-sized increased levels of trait anger (p = 0.03) and moderate-sized increased levels of anger-in (p < 0.001). Attachment style and anger regulation could predict 21% (R2 = 0.21, p < 0.001) of the extent of social anxiety (SPIN) in SAD; secure (ß = - 0.196, p < 0.01) and preoccupied attachment style (ß = 0.117, p < 0.05), as well as anger-in (ß = 0.199, p < 0.01) were significant cross-sectional predictors. Further analysis revealed that the relationship between preoccupied attachment and social anxiety is partially mediated by anger-in. CONCLUSION: Study findings confirm the relevance of preoccupied attachment style and anger suppression for social anxiety. Disentangling the role of anger regulation in early attachment patterns has significant therapeutic implications in SAD.

Fatigue in advanced disease associated with palliative care: A systematic review of non-pharmacological treatments.

BACKGROUND: Fatigue is a common complaint reported by patients with advanced disease, impacting their daily activities and quality of life. The pathophysiology is incompletely understood, and evidence-based treatment approaches are needed. AIM: This systematic review aims to evaluate the efficacy of non-pharmacological interventions as treatment for fatigue in advanced disease. DESIGN: The review design follows the Cochrane guidelines for systematic reviews of interventions. DATA SOURCES: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, ClinicalTrials.gov and a selection of journals up to February 28th 2019, for randomised controlled trials (RCTs) investigating the effect of non-pharmacological treatments for fatigue in advanced disease associated with palliative care. Further potentially relevant studies were identified from the reference lists in relevant reviews, and in studies considered for this review. RESULTS: We screened 579 publications; 15 met the inclusion criteria, with data from 1179 participants: 815 were treated with physical exercise, 309 with psycho-educational therapy and 55 with an energy restoration approach. Sources of potential bias included lack of description of blinding and allocation concealment methods, and small study sizes. Physical exercise as treatment for fatigue in patients with advanced cancer was supported by moderate-quality evidence. CONCLUSION: Physical exercise should be considered as a measure to reduce fatigue in patients with advanced cancer, but data on other advanced diseases is lacking. Due to the differences between studies, no clear recommendations can be made with respect to the best type of physical therapy. Restoration exercise and psycho-educational therapy are promising treatment options, although further research is needed.