Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study.

BACKGROUND: Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci. METHODS: We collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings. FINDINGS: We included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10-8; OR 1·19 [95% CI 1·12-1·26]) and VTN (rs704; p=2·75 × 10-9; OR 0·84 [0·79-0·89]), were related to angiogenesis pathways and the third locus, CCDC25 (rs11782624; p=1·28 × 10-8; OR 1·18 [1·12-1·25]), was related to neutrophil extracellular traps (NETs). We also found an association between this vasculitis and HLA region and PLG. Variants associated with giant cell arteritis seemed to fulfil a specific regulatory role in crucial immune cell types. Furthermore, we identified several drugs that could represent promising candidates for treatment of this disease. The polygenic risk score model was able to identify individuals at increased risk of developing giant cell arteritis (90th percentile OR 2·87 [95% CI 2·15-3·82]; p=1·73 × 10-13). INTERPRETATION: We have found several additional loci associated with giant cell arteritis, highlighting the crucial role of angiogenesis in disease susceptibility. Our study represents a step forward in the translation of genomic findings to clinical practice in giant cell arteritis, proposing new treatments and a method to measure genetic predisposition to this vasculitis. FUNDING: Institute of Health Carlos III, Spanish Ministry of Science and Innovation, UK Medical Research Council, and National Institute for Health and Care Research.

Three-dimensional electron diffraction on clinkers: the belite α'H incommensurate modulated structure.

Traditional X-ray methods are extensively applied to commercial cement samples in order to determine their physical and chemical properties. Powder patterns are routinely used to quantify the composition of these phase mixtures, but structure determination becomes difficult because of reflection overlapping caused by the high number of different crystal structures. The fast-growing 3D electron diffraction technique and its related automated acquisition protocols arise as a potentially very interesting tool for the cement industry, since they enable the fast and systematic acquisition of diffraction data from individual particles. In this context, electron diffraction has been used in the investigation of the different crystalline phases present in various commercial clinkers for cement. Automated data collection procedures and subsequent data processing have enabled the structural characterization of the different crystal structures from which the α'H polymorph of Ca2SiO4 (belite) exhibited satellite reflections. Its average crystal structure has been known since 1971 and satellite reflections have been reported previously, yet the modulation was never fully described by means of the superspace formalism. Here, the incommensurately modulated structure is solved and refined using harmonic and crenel functions in the superspace group Pnma(α00)0ss, showing the potential of 3D electron diffraction for systematic crystallographic characterizations of cement. A full description of the different belite polymorphs is provided considering this modulated structure.

Pulmonary Vein Isolation Followed by Biatrial Ablation of Rotational Activity in Patients with Persistent Atrial Fibrillation: Results of the Cryo-Vest Study.

Background and Aims: Noninvasive mapping allows the identification of patient-specific atrial rotational activity (RA) that might play a key role in the perpetuation of persistent atrial fibrillation (PsAF). So far, the impact of pulmonary vein isolation by cryoballoon (Cryo-PVI) on RA is unclear. Moreover, the long-term effect of periprocedural termination of AF during the ablation procedure is controversial. Methods: Noninvasive electrocardiographic mapping with a 252-electrode vest was performed in 42 patients with PsAF. After the first analysis, Cryo-PVI was performed. The RA was analyzed again and then targeted by radiofrequency catheter ablation. The primary clinical endpoint was periprocedural termination of AF. The secondary endpoint was freedom from any atrial arrhythmia >30 s during a 12-month follow-up. Results: In 33 patients (79%), right atrial RA was identified leading to biatrial ablation, and nine patients (21%) had left atrial RA only. Twelve patients (28.6%) converted from AF to sinus rhythm (SR) (Group A). Thirteen patients (30.9%) converted to atrial tachycardia (AT) (Group B). In 17 patients (40.5%), AF was not terminated by ablation (Group C). After a mean follow-up time of 13.8 months, 26 patients were free from AF and AT (61.9%). In terms of rhythm, control Group A (75%) and B (83.3%) showed higher success rates than Group C (33.3%) (p < 0.01). Cryo-PVI had no substantial impact on RA. Conclusions: The RA-based ablation approach showed acceptable success rates. Periprocedural termination of AF had a positive predictive impact on the outcome. No difference was observed between conversion to SR or to AT. Cryo-PVI had no impact on RA.

A tetravalent bispecific antibody outperforms the combination of its parental antibodies and neutralizes diverse SARS-CoV-2 variants.

The devastating impact of COVID-19 on global health shows the need to increase our pandemic preparedness. Recombinant therapeutic antibodies were successfully used to treat and protect at-risk patients from COVID-19. However, the currently circulating Omicron subvariants of SARS-CoV-2 are largely resistant to therapeutic antibodies, and novel approaches to generate broadly neutralizing antibodies are urgently needed. Here, we describe a tetravalent bispecific antibody, A7A9 TVB, which actively neutralized many SARS-CoV-2 variants of concern, including early Omicron subvariants. Interestingly, A7A9 TVB neutralized more variants at lower concentration as compared to the combination of its parental monoclonal antibodies, A7K and A9L. A7A9 also reduced the viral load of authentic Omicron BA.1 virus in infected pseudostratified primary human nasal epithelial cells. Overall, A7A9 displayed the characteristics of a potent broadly neutralizing antibody, which may be suitable for prophylactic and therapeutic applications in the clinics, thus highlighting the usefulness of an effective antibody-designing approach.

Enforcement of Fairness Norms by Punishment: A Comparison of Gains and Losses.

Although in everyday life decisions about losses are prevalent (e.g., the climate crisis and the COVID-19 crisis), there is hardly any research on decisions in the loss domain. Therefore, we conducted online experiments with a sample of 672 participants (mostly students), using third-party punishment dictator games (DGs) in the loss domain to explore the impact of losses and punishment threats on the conformity to the fairness norm. Subjects in the treatment condition have to divide a loss of -10 € with the threat of a third-party punishment with different strengths (control: gains, no punishment). Overall, the statistical evidence seems rather weak, but when it comes to losses, subjects are more rational and straightforward with their words and deeds than with gains. Therefore, in the loss domain, subjects are more likely to believe that the fairness norm should be followed, and they subjectively perceive that the others do as well. Furthermore, although dictators' decisions are more selfish in the loss domain, dictators there react more strongly to the punishment threat by reducing their demands than in the gains domain. This holds as long as the punishment threat is strong enough, as judged from a rational perspective.

Non-Invasive Wearable Devices for Monitoring Vital Signs in Patients with Type 2 Diabetes Mellitus: A Systematic Review.

Type 2 diabetes mellitus (T2D) poses a significant global health challenge and demands effective self-management strategies, including continuous blood glucose monitoring (CGM) and lifestyle adaptations. While CGM offers real-time glucose level assessment, the quest for minimizing trauma and enhancing convenience has spurred the need to explore non-invasive alternatives for monitoring vital signs in patients with T2D. Objective: This systematic review is the first that explores the current literature and critically evaluates the use and reporting of non-invasive wearable devices for monitoring vital signs in patients with T2D. Methods: Employing the PRISMA and PICOS guidelines, we conducted a comprehensive search to incorporate evidence from relevant studies, focusing on randomized controlled trials (RCTs), systematic reviews, and meta-analyses published since 2017. Of the 437 publications identified, seven were selected based on predetermined criteria. Results: The seven studies included in this review used various sensing technologies, such as heart rate monitors, accelerometers, and other wearable devices. Primary health outcomes included blood pressure measurements, heart rate, body fat percentage, and cardiorespiratory endurance. Non-invasive wearable devices demonstrated potential for aiding T2D management, albeit with variations in efficacy across studies. Conclusions: Based on the low number of studies with higher evidence levels (i.e., RCTs) that we were able to find and the significant differences in design between these studies, we conclude that further evidence is required to validate the application, efficacy, and real-world impact of these wearable devices. Emphasizing transparency in bias reporting and conducting in-depth research is crucial for fully understanding the implications and benefits of wearable devices in T2D management.

Cluster Analysis to Explore Clinical Subphenotypes of Eosinophilic Granulomatosis With Polyangiitis.

OBJECTIVE: Previous studies suggested that distinct phenotypes of eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) could be determined by the presence or absence of antineutrophil cytoplasmic antibodies (ANCA), reflecting predominant vasculitic or eosinophilic processes, respectively. This study explored whether ANCA-based clusters or other clusters can be identified in EGPA. METHODS: This study used standardized data of 15 European centers for patients with EGPA fulfilling widely accepted classification criteria. We used multiple correspondence analysis, hierarchical cluster analysis, and a decision tree model. The main model included 10 clinical variables (musculoskeletal [MSK], mucocutaneous, ophthalmological, ENT, cardiovascular, pulmonary, gastrointestinal, renal, central, or peripheral neurological involvement); a second model also included ANCA results. RESULTS: The analyses included 489 patients diagnosed between 1984 and 2015. ANCA were detected in 37.2% of patients, mostly perinuclear ANCA (85.4%) and/or antimyeloperoxidase (87%). Compared with ANCA-negative patients, those with ANCA had more renal (P < 0.001) and peripheral neurological involvement (P = 0.04), fewer cardiovascular signs (P < 0.001), and fewer biopsies with eosinophilic tissue infiltrates (P = 0.001). The cluster analyses generated 4 (model without ANCA) and 5 clusters (model with ANCA). Both models identified 3 identical clusters of 34, 39, and 40 patients according to the presence or absence of ENT, central nervous system, and ophthalmological involvement. Peripheral neurological and cardiovascular involvement were not predictive characteristics. CONCLUSION: Although reinforcing the known association of ANCA status with clinical manifestations, cluster analysis does not support a complete separation of EGPA in ANCA-positive and -negative subsets. Collectively, these data indicate that EGPA should be regarded as a phenotypic spectrum rather than a dichotomous disease.

Lidar attenuation coefficient in the global oceans: insights from ICESat-2 mission.

The attenuation coefficient of natural waters plays a significant role in our understanding of hydrology from both the oceanographic and biological point of view. The advent of near-continuous observations by sophisticated space-based lidars now offers an unprecedented opportunity to characterize attenuation coefficients over open oceans on global and regional scales. At present, however, literature reports of lidar-derived attenuation coefficient estimates (klidar, m-1) in oceanic waters are very limited. In this study, we present a global survey of klidar derived from ATLAS/ICESat-2 nighttime measurements. Our results augment the existing passive sensor ocean color data set with a new diurnal component and extend the record to now include previously unavailable polar nighttime observations. The values of ATLAS measured klidar at 532 nm are between 0.045 and 0.39 m-1 with the higher values (>0.15 m-1) correlated with coastal waters and sea ice covered oceans. The average klidar in clearest oligotrophic ocean gyres is ∼0.058 ± 0.012 m-1 at 532 nm. The results reported here demonstrate the feasibility of using ATLAS/ICESat-2 lidar measurements for global klidar studies, which will in turn provide critical insights that enable climate models to correctly describe the amount of light present under sea ice, and for heat deposition studies in the upper ocean.

Patients receiving allogeneic haematopoietic stem-cell transplantation and clinical outcomes after early access to palliative care.

Allogeneic haematopoietic stem-cell transplantation is a potential curative therapy for otherwise fatal haematological diseases. This treatment modality is complex, burdensome, and can involve considerable or life-threatening adverse events requiring high-quality symptom control. In contrast to patients with solid tumours, the transition to end-of-life care can be abrupt if the underlying disease relapses or other severe transplantation-related complications occur. This Viewpoint elucidates the relationships between transplantation and palliative care teams and discusses why patients who have undergone transplantation might benefit considerably from early admittance to palliative care, even when the treatment goal is clearly curative. Close and early collaboration between transplantation teams and palliative care teams is clearly endorsed.

Patient-Reported Outcome Measures in Liver and Gastrointestinal Cancer Randomized Controlled Trials.

OBJECTIVE: For many years, outcomes such as mortality and morbidity were the standard for evaluating oncological treatment effectiveness. With the introduction of patient-reported outcome measures (PROMs), the focus shifted from a mere extension of a patient's life or release from disease to the improvement of a multilayered concept of health, decisively affecting life satisfaction. In this study, we deal with the topic of PROMs in liver and gastrointestinal randomized controlled trials. RESULTS: The final database included 43 papers reporting results of randomized controlled trials (RCTs) for liver or gastrointestinal cancer interventions where one of the primary or secondary outcomes was a health-related quality of life measure. The most often used PROM was the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) for both liver cancer and gastrointestinal cancer (in 62% of gastrointestinal cancer studies and 57% of liver cancer studies). For the gastrointestinal cancer group, the QLQ-STO22, a cancer-specific extension of the QLQ-C30, was the second most commonly used PROM. In liver cancer, the generic PROM Short Form 36 and the EORTC QLQ-HCC18, a cancer-specific extension of the QLQ-C30, were the second most commonly used PROMs. CONCLUSION: We found that RCTs often do not include comprehensive quality-of-life measures. When quality of life is part of an RCT, it is often only a secondary outcome. For a holistic view of the patient, a stronger integration and weighting of patient-reported outcomes in RCTs would be desirable.

Evidence-Based Guideline for the diagnosis and management of eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, characterized by asthma, eosinophilia and granulomatous or vasculitic involvement of several organs. The diagnosis and management of EGPA are often challenging and require an integrated, multidisciplinary approach. Current practice relies on recommendations and guidelines addressing the management of ANCA-associated vasculitis and not specifically developed for EGPA. Here, we present evidence-based, cross-discipline guidelines for the diagnosis and management of EGPA that reflect the substantial advances that have been made in the past few years in understanding the pathogenesis, clinical subphenotypes and differential diagnosis of the disease, as well as the availability of new treatment options. Developed by a panel of European experts on the basis of literature reviews and, where appropriate, expert opinion, the 16 statements and five overarching principles cover the diagnosis and staging, treatment, outcome and follow-up of EGPA. These recommendations are primarily intended to be used by healthcare professionals, pharmaceutical industries and drug regulatory authorities, to guide clinical practice and decision-making in EGPA. These guidelines are not intended to limit access to medications by healthcare agencies, nor to impose a fixed order on medication use.

Management of giant-cell arteritis in Switzerland: an online national survey.

AIMS OF THE STUDY: To assess current practices in diagnosing, treating, and following-up giant-cell arteritis by specialists in Switzerland and to identify the main barriers to using diagnostic tools. METHODS: We performed a national survey of specialists potentially caring for patients with giant-cell arteritis. The survey was sent by email to all members of the Swiss Societies of Rheumatology and for Allergy and Immunology. A reminder was sent to nonresponders after 4 and 12 weeks. Its questions covered the following dimensions: respondents' main characteristics, diagnosis, treatment, and imaging's role during follow-up. The main study results were summarized using descriptive statistics. RESULTS: Ninety-one specialists, primarily aged 46-65 years (n = 53/89; 59%), working in academic or nonacademic hospitals or private practice, and treating a median of 7.5 (interquartile range [IQR]: 3-12) patients with giant-cell arteritis per year participated in this survey. Ultrasound of temporal arteries/large vessels (n = 75/90; 83%) and positron-emission-tomography-computed tomography (n = 52/91; 57%) or magnetic resonance imaging (n = 46/90; 51%) of the aorta/extracranial arteries were the most common techniques used to diagnose giant-cell arteritis with cranial or large vessel involvement, respectively. Most participants reported a short time to obtain imaging tests or arterial biopsy. The glucocorticoid tapering scheme, glucocorticoid-sparing agent, and glucocorticoid-sparing treatment duration varied among the participants. Most physicians did not follow a predefined repeat imaging scheme for follow-up and mainly relied on structural changes (vascular thickening, stenosis, or dilatation) to drive treatment choice. CONCLUSIONS: This survey indicates that imaging and temporal biopsy are rapidly accessible for diagnosing giant-cell arteritis in Switzerland but highlights heterogeneous practice in many disease management areas.

A worldwide survey on incidence, management, and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: the POTTER-AF study.

AIMS: Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse. METHODS AND RESULTS: This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553 729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed, at 214 centres in 35 countries. In 78 centres 138 patients [0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (P < 0.0001)] were diagnosed with an oesophageal fistula. Peri-procedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8% and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) [odds ratio 7.463 (2.414, 23.072) P < 0.001]. CONCLUSION: Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high.

Which Expectations to Follow: The Impact of First- and Second-Order Beliefs on Strategy Choices in a Stag Hunt Game.

Many situations require coordinated actions of individuals to achieve common goals. Such situations include organizing mass protests or adjusting behavior to new behavioral recommendations that aim to slow down the spread of a contagious disease. However, there is a risk of coordination failure in such situations that can lead to a worse outcome for those who acted in a coordinated manner than for those who chose not to. In this paper, we investigate the main determinant of individuals' decisions in these situations to determine whether beliefs regarding the action of others (empirical expectations), beliefs regarding others' beliefs (normative expectations), or risk attitudes are dominant determinants. To this end, we conducted an experiment analyzing the relationship between an individual's choices in a stag hunt game, their probabilistic empirical and normative expectations (i.e., first-order and second-order beliefs, respectively), and their risk attitudes. Our central finding is that expectations, not risk attitudes, explain individuals' strategy selection. In addition, we found evidence that normative expectations are a better predictor of strategy selection than empirical expectations. This could have implications for developing more targeted strategies intended to promote new behavioral standards and to guide individuals' behavior toward a welfare-maximizing equilibrium.

[Do we need to treat asymptomatic bacteriuria in immunocompromised patients? : A rapid review]. / Soll die asymptomatische Bakteriurie bei Immunsupprimierten antibiotisch therapiert werden? : Ein Rapid Review.

BACKGROUND: Antimicrobial resistance (AMR), especially multidrug resistant Escherichia coli strains, is a problem even in Europe. That is why inadequate usage of antibiotic therapy should be avoided, especially in the treatment of asymptomatic bacteriuria (ASB). OBJECTIVES: Should ASB be treated with antibiotics in immunocompromized patients, namely solid organ transplant, especially kidney transplant or stem cell transplant recipients? MATERIALS AND METHODS: A rapid review based on a systematic literature search in MEDLINE between 1980 and 2022 was performed. For evidence synthesis, only randomized controlled trials (RCTs) or quasi-RCTs were considered. RESULTS: No studies were identified for the search term solid organ and stem cell transplantation. Three RCTs (antibiotic therapy versus no therapy) were included for adult kidney transplantation. None of the studies showed a benefit for antibiotic therapy of ASB in reduction of symptomatic urinary tract infections, especially in the late transplantation phase two months after kidney transplantation; furthermore, this therapy may promote AMR development. In addition, there are numerous gaps of evidence, e.g., in pediatric transplantation or regarding the influence of special immunosuppressants. CONCLUSION: There is no evidence for antibiotic therapy of ASB in adult kidney transplantation two months after the surgery. Further studies addressing the identified evidence gaps are essential for the prevention of further AMR development.

A rare case of right heart failure with the necessity for veno-arterial extracorporeal membrane oxygenation following pulmonary vein stenosis after radiofrequency ablation for atrial fibrillation.

Pulmonary vein stenosis (PVS) after radiofrequency energy-mediated percutaneous pulmonary vein isolation as a treatment option for atrial fibrillation is a serious complication and the prevalence in historical reports varies between 0% and 42%. Symptoms of PVS are nonspecific and can include general symptoms such as dyspnea, cough, recurrent pneumonia, and chest pain. Pathophysiologically it increases the postcapillary pressure in the pulmonary circuit and may result in pulmonary hypertension (PH). Misdiagnosis and delayed treatment are common. We here report a case of a 59-year-old female with a history of pulmonary vein ablation followed by progressive dyspnea (New York Heart Association IV), right heart failure, CPR, and the need for extracorporeal membrane oxygenation (ECMO). Further treatment strategy includes pulmonary vein dilatation and stenting of both the left superior pulmonary vein and left inferior pulmonary vein, as well as balloon dilatation of RIPV under temporary ECMO support. Symptomatic, severe PVS is a rare complication after catheter ablation of atrial fibrillation. PVS can result in life-threatening complications such as PH with acute right heart failure. Early diagnosis is crucial but challenging. Mechanical cardiopulmonary support by veno-arterial ECMO for bridging to angioplasty could be a lifesaving option.

Comparison of inpatient and outpatient palliative sedation practice - A prospective observational study.

INTRODUCTION: Palliative sedation (PS) is an intrusive measure to relieve patients at the end of their life from otherwise untreatable symptoms. Intensive discussion of the advantages and limitations of palliative care with the patients and their relatives should precede the initiation of PS since PS is terminated by the patient's death in most cases. Drugs for PS are usually administered intravenously. Midazolam is widely used, either alone or in combination with other substances. PS can be conducted in both inpatient and outpatient settings; however, a quality analysis comparing both modalities was missing so far. PATIENTS AND METHODS: This prospective observational study collected data from patients undergoing PS inpatient at the palliative care unit (PCU, n = 26) or outpatient at a hospice (n = 2) or at home (specialized outpatient palliative care [SAPV], n = 31) between July 2017 and June 2018. Demographical data, indications for PS, and drug protocols were analyzed. The depth of sedation according to the Richmond Agitation Sedation Scale (RASS) and the degree of satisfaction of staff members and patient's relatives were included as parameters for quality assessment. RESULTS: Patients undergoing PS at the PCU were slightly younger compared to outpatients (hospice and SAPV combined). Most patients suffered from malignant diseases, and midazolam was the backbone of sedation for inpatients and outpatients. The median depth of sedation was between +1 and -3 according to the RASS with a trend to deeper sedation prior to death. The median degree of satisfaction was "good," scored by staff members and by patient's relatives. Significant differences between inpatients and outpatients were not seen in protocols, depth of sedation, and degree of satisfaction. CONCLUSION: The data support the thesis that PS is possible for inpatients and outpatients with comparable results. For choosing the best place for PS, other aspects such as patient's and relative's wishes, stress, and medical reasons should be considered.

Identification of Relevant Attributes for Liver Cancer Therapies (IRALCT): a maximum-difference-scaling analysis.

The Identification of Relevant Attributes for Liver Cancer Therapies (IRALCT) project is intended to provide new insights into the relevant utility attributes regarding therapy choices for malignant primary and secondary liver tumors from the perspective of those who are involved in the decision-making process. It addresses the potential value of taking patients' expectations and preferences into account during the decision-making and, when possible, adapting therapies according to these preferences. Specifically, it is intended to identify the relevant clinical attributes that influence the patients', medical laymen's, and medical professionals' decisions and compare the three groups' preferences. We conducted maximum difference (MaxDiff) scaling among 261 participants (75 physicians, 97 patients with hepatic malignancies, and 89 medical laymen) to rank the importance of 14 attributes previously identified through a literature review. We evaluated the MaxDiff data using count analysis and hierarchical Bayes estimation (HB). Physicians, patients, and medical laymen assessed the same 7 attributes as the most important: probability (certainty) of a complete removal of the tumor, probability of reoccurrence of the disease, pathological evidence of tumor removal, possible complications during the medical intervention, welfare after the medical intervention, duration and intensity of the pain, and degree of difficulty of the medical intervention. The cumulative relative importance of these 7 attributes was 88.3%. Our results show that the physicians', patients', and medical laymen's preferences were very similar and stable.Trial registration DRKS-ID of the study: DRKS00013304, Date of Registration in DRKS: 2017/11/16.

Neurological Outpatients Prefer EEG Home-Monitoring over Inpatient Monitoring-An Analysis Based on the UTAUT Model.

Home monitoring examinations offer diagnostic and economic advantages compared to inpatient monitoring. In addition, these technical solutions support the preservation of health care in rural areas in the absence of local care providers. The acceptance of patients is crucial for the implementation of home monitoring concepts. The present research assesses the preference for a health service that is to be introduced, namely an EEG home-monitoring of neurological outpatients-using a mobile, dry-electrode EEG (electroencephalography) system-in comparison to the traditional long-time EEG examination in a hospital. Results of a representative study for Germany (n = 421) reveal a preference for home monitoring. Importantly, this preference is partially driven by a video explaining the home monitoring system. We subsequently analyzed factors that influence the behavioral intention (BI) to use the new EEG system, drawing on an extended Unified Theory of Acceptance and Use of Technology (UTAUT) model. The strongest positive predictor of BI is the belief that EEG home-monitoring will improve health quality, while computer anxiety and effort expectancy represent the strongest barriers. Furthermore, we find the UTAUT model's behavioral intention construct to predict the patients' decision for or against home monitoring more strongly than any other patient's characteristic such as gender, health condition, or age, underlying the model's usefulness.

Guideline Directed Medical Therapy at Discharge and Further Uptitration Leading to Reduction in Indication for Prophylactic ICD Implantation during Protected Waiting Period.

Heart failure with reduced ejection fraction (LV-EF < 35%) is diagnosed in app. 11,000,000 patients worldwide. For the treatment of these patients, guideline directed medical therapy has proven to reduce mortality and rehospitalization regardless of the disease's etiology. It is implemented to treat clinical symptoms by improving the left ventricular ejection fraction. Patients with a transient risk of ventricular tachycardia and sudden cardiac death can be protected by a defibrillator vest. The defibrillator vest is capable to detect and terminate ventricular arrhythmias during Guideline Directed Medical Therapy (GDMT). It is based on the recommendations of the European society of cardiology for 3 months. Afterwards, the WCD wear time could be prolonged, or, in case of persistent low ejection fraction (LV-EF ≤ 35%), an implantable cardioverter defibrillator (ICD) should be implanted, as shown in the WEARIT-II-registry. Our goal was to evaluate the effects of GDMT on LV-recovery and reduction of ICD implantations under protection with a defibrillator vest­depending on the uptitration of GDMT. Methods: 339 consecutive patients between August 2017 and September 2020 with newly diagnosed cardiomyopathy and an EF ≤ 35% were analyzed retrospectively by chart review. All patients were protected by a wearable cardioverter defibrillator (WCD). GDMT as recommended by the ESC started at discharge from hospital. The left ventricular ejection fraction (LV-EF) was determined by transthoracic echocardiography at week 4, 8 and at week 12 (in case of prolonged WCD wear time). Uptitration was performed after 4 and 8 weeks during patient visits. We focused on baseline medication as per GDMT and the dosage increase at week 4, 8 and 12. The aim was the uptitration to the maximum dosage tolerated by the patient. We also compared the LV-EF improvement in the group with and without uptitration of medication dosage. Results: The patient age was, on average, 63.2 years (SD ± 11.9 years). A total of 129 pts (38%) had ICM, 196 (58%) had NICM (incl 66 pts (19%) with DCM and 51 pts (15%) with Myocarditis, 79 pts (24%) with unknown origin) and 14 pts (4%) had other entities (e.g., Tachycardiomyopathy). In total, 21 pts (6%) had an LV-EF of less than 16%, 130 pts (38%) between 16−25% and 183 pts (54%) between 26−35%. GDMT started at discharge from the hospital included treatment with beta blocker for 327 pts (96.5%), ACE-inhibitors/Angiotensin/ARNI for 283 pts (83.5%) and Mineralcorticoid receptor antagonists (MRA) for 334 pts (88.4%). Uptitration was performed in all groups at a rate of 82.3%, 91.1% and 81.0% after 4 weeks and 64.7%, 50.3% and 66.3% after 8 weeks, respectively. After 4 weeks, 25 pts (7.4%) and, after 8 weeks, 171 pts (50.4%) had an EF increase of 5% or more (mean 14.2%). After 4 weeks, 81 patients had an LV-EF more than 35%. A total of 169 pts had a wear time of 12 weeks and an improvement of LVEF of more than 35%. Interestingly, in our study we did not find a significant difference in LV-EF improvement between the group with no uptitration and the group with uptitration. Conclusions: Guideline-directed medical therapy under protection with a WCD from ventricular arrhythmia can reduce the need for implantation of an ICD and can lead to an improvement of ejection fraction. Interestingly, the LV-EF improvement depends on the GDMT at discharge. Current guidelines recommend an initiation of all therapy columns of GDMT (sacubitril/valsartan, ACE-inhibitor/AT1-blocker, mineralcorticoidreceptorblocker, beta blocker) at once and further uptitration to the maximal dosage (ESC Guidelines 2021). A further uptitration of all drugs of GDMT should lead to improvement of LV-EF and consequently to a reduction in ICD implantations.