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[Aims] Patients with adult congenital heart disease (ACHD) are a potentially vulnerable patient cohort in case of COVID-19. Some cardiac defects may be associated with a poor COVID-19 outcome. Risk estimation in ACHD is currently based on expert opinion. The aim of this study was to collect clinical outcome data and to identify risk factors for a complicated course of COVID-19 in patients with ACHD., [Methods] Twenty-five ACHD centres in nine European countries participated in the study. Consecutive patients with ACHD diagnosed with COVID-19 presenting to one of the participating centres between 27 March and 6 June 2020 were included. A complicated disease course was defined as hospitalisation for COVID-19 requiring non-invasive or invasive ventilation and/or inotropic support, or a fatal outcome., [Results] Of 105 patients with a mean age of 38±13 years (58% women), 13 had a complicated disease course, of whom 5 died. In univariable analysis, age (OR 1.3, 95% CI 1.1 to 1.7, per 5 years), ≥2 comorbidities (OR 7.1, 95% CI 2.1 to 24.5), body mass index of >25 kg/m2 (OR 7.2, 95% CI 1.9 to 28.3) and cyanotic heart disease (OR 13.2, 95% CI 2.5 to 68.4) were associated with a complicated disease course. In a multivariable logistic regression model, cyanotic heart disease was the most important predictor (OR 60.0, 95% CI 7.6 to 474.0)., [Conclusions] Among patients with ACHD, general risk factors (age, obesity and multiple comorbidities) are associated with an increased risk of complicated COVID-19 course. Congenital cardiac defects at particularly high risk were cyanotic lesions, including unrepaired cyanotic defects or Eisenmenger syndrome., The European Collaboration for Prospective Outcome Research in Congenital Heart Disease is funded by internal grants without support from the pharmaceutical industry.

AimAssessing the distribution and persistence of species across their range is a crucial component of wildlife conservation. It demands data at adequate spatial scales and over extended periods of time, which may only be obtained through collaborative efforts, and the development of methods that integrate heterogeneous datasets. We aimed to combine existing data on large carnivores to evaluate population dynamics and improve knowledge on their distribution nationwide.LocationBotswana.MethodsBetween 2010 and 2016, we collated data on African wild dog, cheetah, leopard, brown and spotted hyaena and lion gathered with different survey methods by independent researchers across Botswana. We used a multi-species, multi-method dynamic occupancy model to analyse factors influencing occupancy, persistence and colonization, while accounting for imperfect detection. Lastly, we used the gained knowledge to predict the probability of occurrence of each species countrywide.ResultsWildlife areas and communal rangelands had similar occupancy probabilities for most species. Large carnivore occupancy was low in commercial farming areas and where livestock density was high, except for brown hyaena. Lion occupancy was negatively associated with human density; lion and spotted hyaena occupancy was high where rainfall was high, while the opposite applied to brown hyaena. Lion and leopard occupancy remained constant countrywide over the study period. African wild dog and cheetah occupancy declined over time in the south and north, respectively, whereas both hyaena species expanded their ranges. Countrywide predictions identified the highest occupancy for leopards and lowest for the two hyaena species.Main ConclusionsWe highlight the necessity of data sharing and propose a generalizable analytical method that addresses the challenges of heterogeneous data common in ecology. Our approach, which enables a comprehensive multi-species assessment at large spatial and temporal scales, supports the development of data-driven conservation guidelines and the implementation of evidence-based management strategies nationally and internationally. published

Embaràs i malaltia cardíaca; Resultats de l’embaràs; Transposició de les grans artèries Embarazo y enfermedad cardíaca; Resultados del embarazo; Transposición de las grandes arterias Pregnancy and cardiac disease; Pregnancy outcomes, Transposition of the great arteries Background In the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk. Methods and Results The ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed. Conclusions Women after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate. Funding from “Zabawas Foundation” and “De Hoop Foundation” in addition to the support from EURObservational Research Programme (EORP) is greatly acknowledged. Since the start of EORP, the following companies have supported the program: Abbott Vascular Int (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer AG (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2019), Daiichi Sankyo Europe GmbH (2011–2020), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2014–2017), Edwards (2016–2019), Gedeon Richter Plc (2014–2016), Menarini Int Op (2009–2012), MSD‐Merck & Co (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2009–2021), and Vifor (2019–2022).

Background: Long-term outcomes in adults with prior arterial switch operation (ASO) have not yet been well defined. The aim of this study is to elucidate incidence and predictors of adverse cardiac outcomes in a prospectively followed cohort of adults after their ASO. Methods: The comprehensive long-term follow up of adults with ASO is a project within the European collaboration for prospective outcome research in congenital heart disease (EPOCH). It is designed as a prospective, international multicenter cohort study. Consecutive patients (age ≥ 16 years) with prior ASO will be included at 11 European tertiary care centers. Participants will be followed according to a standardized protocol following international recommendations, including standardized protocols for imaging and for exercise testing. Results: Main outcome measures are all-cause and cardiac-related mortality, rate of cardiac re-intervention, neo-aortic dissection, myocardial infarction, stroke, infective endocarditis, sustained atrial and ventricular arrhythmias, new-onset or worsening pulmonary hypertension or heart failure. Secondary endpoints are frequency and progression of right ventricular outflow stenosis, neo-aortic root dilatation, neo-aortic valve regurgitation and ventricular dysfunction. The impact of demographic, anatomic (e.g., coronary artery anato-my) and functional variables on the above-mentioned outcomes, as well as quality of life and incidence of pregnancy related complications will also be assessed. Conclusion: The prospective, international, multicenter EPOCH-ASO study will provide a better understanding of adverse outcomes and their predictors in adults after ASO. The results of the EPOCH-ASO study may help to optimize future care of this novel patient cohort in adult cardiology.

The aim of this study was to evaluate the reproducibility of voxel-wise temporal signal-to-noise ratio (tSNR) on repeated scans across runs, sessions, and days. A group of 21 participants was scanned 16 times (4 runs per session, 2 sessions per day, 2 separate days) in a functional magnetic resonance imaging (fMRI) study on a 3T Philips Achieva scanner. For each run, we calculated t-value and tSNR maps. To ascertain that the results were not specific to the scanner, one volunteer was scanned with four fMRI runs in a single session on the above 3T Philips scanner as well as a 3T Siemens Prisma scanner. The coefficient of variation of voxel-wise tSNR across the 16 repeats was up to 25%, while the range relative to the mean of all observations was up to 80%. The voxel-wise variability of tSNR on the two different scanners was similar, indicating a general issue. Despite its use in evaluating the quality of fMRI data, we found only a weak relationship between tSNR and t-values. There is very high variability in voxel-wise tSNR, which should be considered while planning future studies that aim to identify small and focal fMRI effects or the benefits of incremental improvement in methods.

Editor’s notes: A group of academicians from the University of Virginia has developed a graduate curriculum for cyber-physical systems education. The curriculum follows the National Academy of Engineering report on the need for such content consisting of multidisciplinary classes and professional development skills. — Mohammad Abdullah Al Faruque, University of California Irvine

Background Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. Objectives This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. Methods Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. Results From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. Conclusions COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity., Central Illustration

Background/objective: Constant pain causes suffering and affects performance of activities of daily living (ADL). In clients with chronic musculoskeletal pain, we wanted to determine (i) the relationship between the perceived burden of suffering (measured with the Pictorial Representation of Illness and Self Measure (PRISM)) and the observed quality of ADL task performance (measured with the Assessment of Motor and Process Skills (AMPS)); and (ii) the change in these assessments before and after a 12-week pain programme. Methods: In this cross-sectional cohort study, we retrospectively collected data from participants in a Swiss pain management programme. We calculated the relationship, correlations and effect sizes for the PRISM and AMPS using non-parametric tests. We set the level of significance at α = 0.05. Results: Out of 138 clients, 74 participated. We found no significant correlations between the PRISM and AMPS (p = 0.55–0.36), except for the PRISM and AMPS process ability measure after the pain management programme (p = 0.023). Pre-post-correlations of the AMPS and PRISM were significant, with medium to strong effect sizes (−0.48–0.66). Conclusion: Participation in this pain programme improved both, the PRISM and AMPS scores. The lack of correlation between these assessments in clients with chronic musculoskeletal pain, however, strongly argues for a thorough clinical assessment.

The prone position is frequently used for breast irradiation in an effort to minimize dose to normal tissue and reduce skin toxicities. Immobilization required for prone breast irradiation can cause collision issues with the linear accelerator, disrupting treatment and negatively affecting the patient experience. The purpose of this retrospective study was to determine if an isocenter location guideline could be developed to prevent collisions with the prone breast immobilization device and gantry head, while still creating a clinically acceptable treatment plan. Clearance isocenter guidelines were established by measuring clearance between the Civco Horizon breast board and Varian linear accelerator. Fourteen patients with known clearance issues at a single institution were selected for this study and re-planned using clearance isocenter guidelines. Collision plans were compared to clearance plans created within the established clearance threshold through the institutions breast treatment guidelines based on arm II of the Radiation Therapy Oncology Group (RTOG) 1005 recommendations. Researchers in this study demonstrated clinical relevance by establishing that a clearance isocenter location guideline can be developed to prevent collisions with the prone breast immobilization and gantry head, while still creating a clinically acceptable treatment plan.

Musculoskeletal disorders (MSDs) account for almost 70 million physician office visits per year in the United States and are the most common workplace injuries. These are conditions involving the nerves, tendons, muscles, and supporting structures of the body. Previous studies have concluded that computer users are at high risk of developing work-related musculoskeletal disorders (WRMSDs). As computer users, medical dosimetrists are at risk of developing WRMSDs, yet there is a lack of information regarding the incidence of WRMSDs among medical dosimetrists. The purpose of this study was to determine the incidence of WRMSDs and variables of workstation ergonomics that contribute to the increased risk of WRMSDs in medical dosimetrists. A Qualtrics survey was created to support the 3 research questions guiding this study. The survey was distributed to 2,646 full members of the American Association of Medical Dosimetrists (AAMD), which included only certified medical dosimetrists (CMDs), via email. The distribution of email surveys sent through the AAMD email distribution list resulted in 988 emails opened, for a contact rate of 37% (988/2646). One hundred sixty-four responses were recorded yielding a completion rate of 17% (164/988). Fifty-five percent (90/163) of participants responded that they have experienced WRMSDs. Forty-four percent (289/652) of responses indicated WRMSDs have a slight or moderate interference on work. Sixty-two percent (94/152) of participants felt that their workstations were not ergonomically designed; even greater 68% (104/153) did not feel their workstations were designed for their individually needs. Of those respondents 64% (98/152) would like to see further adaptations made to their workspaces.

Radiation pneumonitis (RP) is a potential toxic side effect of thoracic radiotherapy. Optimal planning techniques must maintain tumor coverage while limiting dose to normal lung tissue to reduce the risk of patients developing RP. The addition of a noncoplanar arc may be beneficial by increasing treatment angles and providing an ideal dose distribution for tumor coverage while decreasing dose to organs at risk (OAR). The purpose of this research was to compare the effects on the normal bilateral lung tissue receiving 20 Gy, 10 Gy and 5 Gy (V20, V10, V5) and the mean lung dose (MLD) values when medial lung tumors are treated with 3 partial coplanar arcs vs 2 partial coplanar arcs combined with a partial sagittal arc. Researchers hypothesized that a beam arrangement of 2 partial coplanar arcs and 1 partial sagittal arc would reduce V20, V10, V5, and MLD values when compared to a 3 partial coplanar arc plan. In a retrospective study of 5 patients with bulky, medial right lung lesions without nodal involvement, cases were planned with both a noncoplanar and a coplanar arc geometry. Results were evaluated using a two-tailed t-test to determine the statistical significance (p < 0.05) of changes to total lung volume analyzation metrics when a noncoplanar sagittal arc was incorporated compared to the standard lung treatment using only coplanar arcs. Although some patient cases showed minor improvement in the V20, V10, V5, and MLD metrics, the study results were not statistically significant and showed no advantage with the introduction of an anterior sagittal arc over a coplanar beam arrangement.

ObjectivePregnancy in women with aortic coarctation (CoA) has an estimated moderately increased risk (mWHO II–III) of adverse cardiovascular, obstetric or fetal events, but prospective data to validate this risk classification are scarce. We examined pregnancy outcomes and identified associations with adverse outcomes.MethodsPregnancies in women with CoA were selected from the worldwide prospective Registry of Pregnancy and Cardiac Disease (ROPAC, n=303 out of 5739), part of the European Society of Cardiology EURObservational Research Programme. The frequency of and associations with major adverse cardiac events (MACE) and hypertensive disorders (pregnancy-induced hypertension, (pre-)eclampsia or haemolysis, elevated liver enzymes and low platelets syndrome) were analysed.ResultsOf 303 pregnancies (mean age 30 years, pregnancy duration 39 weeks), 9.6% involved unrepaired CoA and 27.1% were in women with pre-existing hypertension. No maternal deaths or aortic dissections occurred. MACE occurred in 13 pregnancies (4.3%), of which 10 cases were of heart failure (3.3%). Univariable associations with MACE included prepregnancy clinical signs of heart failure (OR 31.8, 95% CI 6.8 to 147.7), left ventricular ejection fraction 1 (OR 11.4, 95% CI 3.6 to 36.3) and cardiac medication use (OR 4.9, 95% CI 1.3 to 18.3). Hypertensive disorders of pregnancy occurred in 16 (5.3%), cardiac medication use being their only predictor (OR 3.2, 95% CI 1.1 to 9.6). Premature births were 9.1%, caesarean section was performed in 49.7% of pregnancies. Of 4 neonatal deaths, 3 were after spontaneous extreme preterm birth.ConclusionsThe ROPAC data show low MACE and hypertensive disorder rates during pregnancy in women with CoA, suggesting pregnancy to be more safe and better tolerated than previously appreciated.

PurposeA common way to handle quality problems and increasing costs of modern health care systems is more transparency through public reporting. Thereby, patient satisfaction is seen as one main reported outcome. Previous studies proposed several associated factors. Only a few of them included organizational determinants with potential to inform the health care provider's management. Therefore, the aim of this study was to investigate the influence of organizational contingency factors on patient satisfaction.Design/methodology/approachAs a case, Switzerland's inpatient rehabilitation sector was used. Therein, a cross-sectional study of public released secondary data with an exploratory multiple linear regression (MLR) modeling approach was conducted.FindingsFive significant influencing factors on patient satisfaction were found. They declared 42.2% of the variance in satisfaction on provider level. The organizations' supplementary insured patients, staff payment, outpatients, extracantonal patients and permanent resident population revealed significant correlations with patient satisfaction.Research limitations/implicationsDrawing on publicly available cross-sectional data, statistically no causality can be proved. However, integration of routine data and organization theory can be useful for further studies.Practical implicationsRegarding inpatient satisfaction, improvement levers for providers' managers are as follow: first, service provision should be customized to patients' needs, expectations and context; second, employees' salary should be adequate to prevent dissatisfaction; third, the main business should be prioritized to avoid frittering.Originality/valueFormer studies regarding public reporting are often atheoretical and rarely used organizational variables as determinants for relevant outcomes. Therefore, uniformed data are useful.

A pregnant patient with shortness of breath and arterial oxygen desaturation is presented. The primary and tentative initial diagnosis was pulmonary embolism. Her desaturation and dyspnea were aggravated in the upright compared with the supine position. The minimal response to supplemental oxygen suggested right-to-left shunting, which was confirmed by echocardiography. Shunting was minimal in the supine and maximal in the upright position, leading to the diagnosis of platypnea-orthodeoxia syndrome. By two weeks postpartum the patient's symptoms had resolved and shunting was undetectable.

Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes, cardiovascular diseases, and cancer. Obesity rates are on the rise worldwide with women more frequently affected than men. Hedonic responses to food seem to play a key role in obesity, but the exact mechanisms and relationships are still poorly understood. In this study, we investigate the perceived pleasantness of food rewards in relation to satiety and calories consumed during an ad libitum meal in women. Using functional magnetic resonance imaging (fMRI) and a milkshake consumption task, we studied how experienced food values are encoded in women with healthy weight, overweight or obesity. Participants rated the pleasantness and intensity of high and low caloric milkshakes in the fMRI scanner during both the fasted and fed states. We found differences in the neural responses and experienced pleasantness of high and low caloric milkshakes depending on satiety and Body Mass Index (BMI). Women with both high ad libitum consumption levels and high BMI reported greater experienced pleasantness for milkshakes. In contrast, among women with low ad libitum consumption levels, greater BMI was associated with less experienced pleasantness. At the neural level, satiety affected women with obesity to a lesser degree than women with healthy weight. Thus, having obesity was associated with altered relationships between food consumption and the hedonic responses to food rewards as well as reduced satiety effects in women.

Objectives Supine lumbar spine examinations underestimate body weight effects on neuroforaminal size. Therefore, our purpose was to evaluate size changes of the lumbar neuroforamina using supine and upright 3D tomography and to initially assess image quality compared with computed tomography (CT). Methods The lumbar spines were prospectively scanned in 48 patients in upright (3D tomographic twin robotic X-ray) and supine (30 with 3D tomography, 18 with CT) position. Cross-sectional area (CSA), cranio-caudal (CC), and ventro-dorsal (VD) diameters of foramina were measured by two readers and additionally graded in relation to the intervertebral disc height. Visibility of bone/soft tissue structures and image quality were assessed independently on a 5-point Likert scale for the 18 patients scanned with both modalities. Descriptive statistics, Wilcoxon’s signed-rank test (p < 0.05), and interreader reliability were calculated. Results Neuroforaminal size significantly decreased at all levels for both readers from the supine (normal intervertebral disc height; CSA 1.25 ± 0.32 cm2; CC 1.84 ± 0.24 cm2; VD 0.88 ± 0.16 cm2) to upright position (CSA 1.12 ± 0.34 cm2; CC 1.78 ± 0.24 cm2; VD 0.83 ± 0.16 cm2; each p < 0.001). Decrease in intervertebral disc height correlated with decrease in foraminal size (supine: CSA 0.88 ± 0.34 cm2; CC 1.39 ± 0.33 cm2; VD 0.87 ± 0.26 cm2; upright: CSA 0.83 ± 0.37 cm2, p = 0.010; CC 1.32 ± 0.33 cm2, p = 0.015; VD 0.80 ± 0.21 cm2, p = 0.021). Interreader reliability for area was fair to excellent (0.51–0.89) with a wide range for cranio-caudal (0.32–0.74) and ventro-dorsal (0.03–0.70) distances. Image quality was superior for CT compared with that for 3D tomography (p < 0.001; κ, CT = 0.66–0.92/3D tomography = 0.51–1.00). Conclusions The size of the lumbar foramina is smaller in the upright weight-bearing position compared with that in the supine position. Image quality, especially nerve root delineation, is inferior using 3D tomography compared to CT. Key Points • Weight-bearing examination demonstrates a decrease of the neuroforaminal size. • Patients with higher decrease in intervertebral disc showed a narrower foraminal size. • Image quality is superior with CT compared to 3D tomographic twin robotic X-ray at the lumbar spine.

ZusammenfassungDie Patientengruppe der Erwachsenen mit angeborenen Herzfehlern (EMAH) ist mittlerweile bereits größer als die der Kinder mit angeborenen Herzfehlern. EMAH-Patienten weisen auch nach Reparaturoperationen oft komplexe pathophysiologische und anatomische Verhältnisse auf. Bei Komplikationen kann es sehr rasch zu Notfallsituationen auch bei ansonsten asymptomatischen oder nur wenig symptomatischen Patienten kommen. Gemessen an der Gesamtzahl der Patienten, die von Notärzten und in den Notaufnahmen versorgt werden, sind EMAH-Notfallsituationen nach wie vor sehr selten. Diese Übersicht soll die Notfallbetreuung von EMAH-Patienten erleichtern. Für ca. zwei Drittel aller Notfälle sind Rhythmusstörungen und akute Herzinsuffizienz verantwortlich. Rhythmusstörungen müssen in der Regel zügig terminiert werden, weil sie unbehandelt rasch zur kardialen Dekompensation führen können. Bei Scheitern der medikamentösen Therapie oder hämodynamischer Instabilität müssen EMAH-Patienten mit tachykarden Rhythmusstörungen rasch elektrisch kardiovertiert werden. Symptomatische Bradykardien können eine rasche Schrittmacherversorgung erforderlich machen. Aufgrund der komplexen Anatomie kann das Einschwemmen eines transvenösen Interim-Schrittmachers bei einzelnen Vitien unmöglich sein. Die akute kardiale Dekompensation bei EMAH ist oft durch ein akutes Rechtsherzversagen verursacht. Weitere relativ häufige Aufnahmegründe sind Infektionen, Synkopen, Thromboembolien und Aortendissektion. Der Herzpass der Patienten informiert über das vorliegende Vitium. Die umgehende Kontaktaufnahme mit dem behandelnden EMAH-Zentrum wird dringend empfohlen.

Zusammenfassung. Schmerzen beeinträchtigen den Alltag von Betroffenen massiv. Ist ein Nerv verletzt, sind die Schmerzen zudem oft komplexer, da sie neben der Einschränkung der Sensibilität und / oder der Motorik auch die Trophik des betroffenen Hautareals massgeblich verändern können. Schmerz zu objektivieren ist schwierig. Dennoch gibt es einige Möglichkeiten, diesen in der Handtherapie zu erfassen. Eine umfassende Dokumentation von Schmerzen, speziell den neurogen verursachten, und deren Auswirkungen ist deshalb eine unabdingbare Voraussetzung, um die Therapie individuell gestalten zu können. Guidelines empfehlen einen frühen Therapiestart, ein multimodales Vorgehen sowie eine Mischung aus medikamentösen und nicht medikamentösen Massnahmen. Empfehlungen sind aufgrund eines vielfach komplexen Verlaufs individuell anzupassen. Daher bilden eine offene und transparente Kommunikation, eine stabile therapeutische Beziehung sowie die aktive Mitarbeit der Betroffenen neben dem fachlichen Wissen eine Grundvoraussetzung für eine erfolgreiche Therapie. In diesem Artikel werden die häufigsten handtherapeutischen Assessments bei neurogenen Schmerzen vorgestellt, wie sie zum Beispiel bei einem Complex Regional Pain Syndrome angewendet werden. Anhand eines Patientenbeispiels wird die klinische Untersuchung einer Allodynie genauer beschrieben. Mögliche Therapieziele und -inhalte werden aufgezeigt. Trotz aller eingeleiteter Massnahmen bleibt die Behandlung von Schmerzen eine Herausforderung, welche nur im interdisziplinären Setting und mit Hilfe der Betroffenen angegangen werden kann.

Surgical intervention for severe lymphedema is reserved for failure of conservative management. The reductive approach aims to remove fibrosclerotic tissue acquired from prolonged lymphatic stasis. One such reductive approach is the modified Charles procedure, direct circumferential excision down to fascia followed by split-thickness skin graft application. The 1-year outcomes in our patients suggest that a multidisciplinary approach to the modified Charles procedure is an effective management option for severe lymphedema refractory to conservative therapy.

Purpose: The purpose of this qualitative study was to explore how stroke patients with unilateral spatial neglect experience; (a) performance in activities of daily living; (b) alterations in bodily perceptions; and (c) personal hopes and expectations, looking at the period between stroke onset and discharge from inpatient rehabilitation. Materials and methods: We conducted individual semi-structured interviews with 7 (5 men, 2 women, mean age 69 years) consecutively sampled participants. All interviews were transcribed verbatim and analyzed using thematic analysis. Findings: Participants' experiences were captured in three over-arching themes: "unawareness of neglect," "emergent awareness for neglect-related difficulties," and "comparing the new life with the old one." Findings showed that participants progressed from initial unawareness to emergent awareness for their neglect-related difficulties over the course of rehabilitation. Comparing their current life situation with the one before their stroke triggered feelings of uncertainty and regret, with associated decreased pleasure in meaningful activities. Conclusions: This study informs health professionals regarding personal experiences of orientation in and reorganization of life of stroke patients with unilateral spatial neglect. The findings highlight that being aware of neglect-related deficits is a prerequisite for using coping strategies and incorporating them in daily life. Possible therapeutic strategies that fit the current stage of recovery and level of awareness are discussed.

Background Activation of D1 receptors has been related to successful goal-directed behavior, but it remains unclear whether D1 receptor activation causally tips the balance of weighing costs and benefits in humans. Here, we tested the impact of pharmacologically stimulated D1 receptors on sensitivity to risk, delay, and effort costs in economic choice and investigated whether D1 receptor stimulation would bias preferences toward options with increased costs in a cost-specific manner. Methods In a randomized, double-blind, placebo-controlled, parallel-group phase 1 study, 120 healthy young volunteers received either placebo or 1 of 3 doses (6 mg, 15 mg, or 30 mg) of a novel, selective D1 agonist (PF-06412562). After drug administration, participants performed decision tasks measuring their preferences for risky, delayed, and effortful outcomes. Results Higher doses of the D1 agonist increased the willingness to exert physical effort for reward as well as reduced the preference for risky outcomes. We observed no effects on preferences for delayed rewards. Conclusions The current results provide evidence that D1 receptor stimulation causally affects core aspects of cost-benefit decision making in humans.

Background The arterial switch operation (ASO) for repair of transposition of the great arteries (TGA) requires transection of the great arterial trunks and re-implantation of the coronary arteries into the neoaortic root resulting in cardiac sympathetic denervation which may affect myocardial blood flow (MBF) regulation. The aims of the present study were to evaluate sympathetic (re-)innervation in young adults after ASO and its impact on MBF. Methods Twelve patients (age 22.5 ± 2.6 years) after ASO for TGA in the neonatal period and ten healthy controls (age 22.0 ± 1.7 years) were included. Positron emission tomography (PET) was used for measuring cardiac sympathetic innervation with [11C]meta-hydroxyephedrine (mHED) and MBF with [15O]H2O PET at rest, during adenosine stimulation, and during sympathetic stimulation with cold pressor test. Cold pressor-induced MBF response capacity was calculated as maximal global MBF over peak rate-pressure product multiplied by 10′000. Results Global [11C]mHED uptake was significantly lower in patients compared to controls (7.0 ± 2.3 versus 11.8 ± 2.1%/min, p Conclusions With only partial sympathetic re-innervation of the coronary arteries, maximal dilator capacity of the coronary microvasculature and cold pressor-induced MBF response capacity remain substantially impaired in young adults after ASO compared to healthy controls.

Applying dual, or mixed photon energies during radiation therapy is a common practice in 3-dimensional conformal radiation therapy (3D-CRT). Mixed photon energies are used to provide uniform dose coverage to a planning target volume (PTV) that ranges in depth from the skin surface. Though the application of mixed photon energies in 3D-CRT was once the convention for treating anal cancers with lymph node involvement (AC-LNI), the advantages offered by volumetric modulated arc therapy (VMAT) prove to be the optimal form of therapy for AC-LNI. Recently, multiple researchers have uncovered benefits in employing multiple photon energies in VMAT planning for prostate cancer. A retrospective study was completed to assess the impact of implementing mixed energy VMAT planning in comparison to conventional single energy VMAT planning for AC-LNI. Data from 20 patients with AC-LNI was collected to analyze the dosimetric effects of mixed energy VMAT treatments in terms of PTV conformity index, PTV homogeneity index, monitor unit usage, and organs at risk sparing. For each patient 3 treatment plans were created: a single energy 6 MV plan, a single energy 10 MV plan, and a mixed 6 MV and 10 MV energy plan. Analysis of the resulting dosimetric outcomes showed statistical significance. The current study concluded that mixed energy VMAT plans have some effect on treating AC-LNI when compared to single energy VMAT plans.

[Objective] Adults with congenital heart disease (ACHD) may be at a higher risk of a fatal outcome in case of COVID-19. Current risk stratification among these patients relies on personal experience and extrapolation from patients with acquired heart disease. We aimed to provide an expert view on risk stratification while awaiting results from observational studies., [Methods] This study was an initiative of the EPOCH (European Collaboration for Prospective Outcome Research in Congenital Heart disease). Among nine European countries (Austria, Belgium, Denmark, France, Germany, Italy, the Netherlands, Spain and Switzerland), 24 experts from 23 tertiary ACHD centres participated in the survey. ACHD experts were asked to identify ACHD-specific COVID-19 risk factors from a list of potential outcome predictors and to estimate the risk of adverse COVID-19 outcomes in seven commonly seen patient scenarios., [Results] 82% of participants did not consider all ACHD patients at risk of COVID-19 related complications. There was a consensus on pulmonary arterial hypertension, Fontan physiology and cyanotic heart disease as risk factors for adverse outcomes. Among different ACHD scenarios, a patient with Eisenmenger syndrome was considered to be at the highest risk. There was a marked variability in risk estimation among the other potential outcome predictors and ACHD scenarios., [Conclusions] Pulmonary arterial hypertension, Fontan palliation and cyanotic heart disease were widely considered as risk factors for poor outcome in COVID-19. However, there was a marked disparity in risk estimation for other clinical scenarios. We are in urgent need of outcome studies in ACHD suffering from COVID-19., EPOCH-ASO is funded by internal grants without support from the pharmaceutical industry.

OBJECTIVES The aim of this study was to evaluate the effects of the coronavirus 2019 pandemic on elective and acute thoracic aortic surgery in the Netherlands. METHODS The Netherlands Heart Registration database was used to compare the volume of elective and acute surgery on the thoracic aorta in 2019 and 2020, starting from week 11 in both years. A sub-analysis was done to assess the impact of the pandemic on high-volume and low-volume aortic centres. RESULTS During the pandemic, the number of elective thoracic aortic operations declined by 18% [incidence rate ratio (IRR) 0.82 [0.73–0.91]; P < 0.01]. The decline in volume of elective surgery was significant in both high-volume (IRR 0.82 [0.71–0.94]; P < 0.01) and low-volume aortic centres (IRR 0.81 [0.68–0.98]; P = 0.03). The overall number of acute aortic operations during the pandemic remained similar to that in 2019 (505 vs 499; P = 0.85), but an increased share of these operations occurred at high-volume centres. The number of acute operations performed in high-volume centres increased by 20% (IRR 1.20 [1.01–1.42]; P = 0.04), while the number of acute operations performed in low-volume centres decreased by 17% (IRR 0.83 [0.69–1.00]; P = 0.04). CONCLUSIONS The coronavirus 2019 pandemic led to a significant decrease in elective thoracic aortic surgery but did not cause a change in the volume of acute thoracic aortic surgery in the Netherlands. Moreover, the pandemic led to a centralization of care for acute thoracic aortic surgery., The coronavirus disease 19 (COVID-19) pandemic has impacted the delivery of health care around the world.

Deficits in goal-directed decision making and motivation are hallmark characteristics of several neuropsychiatric disorders, including schizophrenia (SZ) and major depressive disorder (MDD). Studies using effort-based decision-making tasks have shown that both patients with SZ and MDD invest less physical effort in order to obtain rewards. However, how these motivational deficits relate to clinically assessed symptom dimensions such as apathy remains controversial. Using a grip-strength-based effort discounting task we assessed effort-based decision-making behavior in healthy controls (HC) (N = 18), patients with SZ (N = 42), and MDD (N = 44). We then investigated how effort discounting relates to different symptom dimensions. There were no differences in effort discounting between HC participants and patients with SZ or MDD. In addition, we did not observe a correlation between effort discounting and negative symptoms (NS) in patients with SZ or MDD. In conclusion, the current study does not support an association between effort discounting and NS in SZ or MDD. Further studies are needed to investigate effort discounting and its relation to psychopathological dimensions across different neuropsychiatric disorders.

Background:Infective endocarditis is a major threat after prosthetic pulmonary valve replacement. Early diagnosis may improve outcomes.Methods:A structured patient education programme for prevention and early diagnosis of infective endocarditis was developed at our institution since 2016. Time delay between onset of symptoms of prosthetic pulmonary valve endocarditis and its diagnosis (defined as initiation of appropriate high-dose intravenous antibiotic treatment) was compared for patients presenting before (cohort 1) and after (cohort 2) initiation of the patient education programme.Results:Between 2008–2019, 26 patients (median age 24.9, range: 16.8–62.0 years, 73% male) were diagnosed with prosthetic pulmonary valve endocarditis, 13 patients (cohort 1) before (1.7 cases/year) and 13 patients (cohort 2) after June 2016 (3.7 cases/year). There were no differences in baseline characteristics or clinical presentation between the study cohorts. Overall, the median delay between onset of symptoms and diagnosis of infective endocarditis was 6 days (range: 0–133 days) with a significantly longer delay among patients in cohort 1, compared to cohort 2 (25 days, range: 5–133 days versus 3 days, range: 0–13 days, p < 0.0001). A delay of >7 days was documented in 11/13 patients (85%) in cohort 1 as compared to 1/13 (8%) in cohort 2 (p < 0.001). Need for urgent valve replacement or permanent deterioration of prosthetic valve function was higher in cohort 1, compared to cohort 2 (11/13, 85% versus 5/13, 39%; p = 0.041).Conclusions:Prosthetic pulmonary valve endocarditis is increasingly recognised. A structured patient education programme may improve early diagnosis and clinical outcomes.

Background Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. Objective and rationale We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE. Search methods Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review. Outcomes We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a central action of estrogens to increase the satiating potency of the gastrointestinal hormone cholecystokinin. Another mechanism involves a decrease in the preference for sweet foods during the follicular phase. Genetic defects in brain α-melanocycte-stimulating hormone-melanocortin receptor (melanocortin 4 receptor, MC4R) signaling lead to a syndrome of overeating and obesity that is particularly pronounced in women and in female animals. The syndrome appears around puberty in mice with genetic deletions of MC4R, suggesting a role of ovarian hormones. Emerging functional brain-imaging data indicates that fluctuations in ovarian hormones affect eating by influencing striatal dopaminergic processing of flavor hedonics and lateral prefrontal cortex processing of cognitive inhibitory controls of eating. There is a dearth of research on the neuroendocrine control of eating after menopause. There is also comparatively little research on the effects of ovarian hormones on EE, although changes in ovarian hormone levels during the menstrual cycle do affect resting EE. Wider implications The markedly greater obesity burden in women makes understanding the diverse effects of ovarian hormones on eating, EE and body adiposity urgent research challenges. A variety of research modalities can be used to investigate these effects in women, and most of the mechanisms reviewed are accessible in animal models. Therefore, human and translational research on the roles of ovarian hormones in women's obesity and its causes should be intensified to gain further mechanistic insights that may ultimately be translated into novel anti-obesity therapies and thereby improve women's health.

Learning objectives Simple shunt lesions are among the most common forms of congenital heart disease.1 Depending on location and size of the shunts, haemodynamic effects and presentation vary considerably. For example, while haemodynamically relevant ventricular septal defects (VSDs) nowadays typically are managed during childhood, atrial septal defects (ASDs) often escape diagnosis in childhood and many patients are diagnosed in adult life.2 Therefore, general cardiologists are frequently confronted with diagnosis and management of interatrial communications. This article focuses on anatomy, pathophysiology, natural history and common complications of simple shunt lesions; discusses imaging techniques and invasive procedures to diagnose and manage ASDs and VSDs and provides a practical algorithm on how to manage patients with ASDs with and without pulmonary hypertension. ### Atrial septal defects #### ​Anatomy of ASDs ASD are defined as direct communications on the atrial level. The ostium secundum ASD (figure 1A1) is located within the fossa ovalis but may extend in any direction. In contrast to a patent foramen ovale (PFO), which is a flap-valve of tissue formed by the septum primum and septum secundum, an ostium secundum ASD is characterised by a true tissue defect of variable size. Occasionally, there may be multiple defects or a combination of an ostium secundum ASD in addition to a PFO with or without an associated atrial septal aneurysm. Figure 1 Anatomy and haemodynamic consequences of simple shunt lesions. Panels (1A and 1B) anatomy of secundum atrial septal defects and haemodynamic consequences of relevant left-to-right shunting in interatrial communications. Panels (2A and 2B) anatomy of muscular ventricular septal defects and haemodynamic consequences of relevant left-to-right shunting. Panels (3A and 3B) anatomy of patent ductus arteriosus and the …

Significance In recent years, models have played an increasingly important role for understanding the brain in cognitive, behavioral, and systems neuroscience. Decision neuroscience in particular has benefitted greatly from the application of economic models of choice preferences to neural data. However, an often-overlooked aspect is that many models of preferences have a generic problem—they make extremely similar behavioral predictions. Here, we demonstrate that to understand the mechanisms of valuation in the brain, it is useful to compare models of choice preferences not only at the behavioral but also at the neural level., Decisions are based on the subjective values of choice options. However, subjective value is a theoretical construct and not directly observable. Strikingly, distinct theoretical models competing to explain how subjective values are assigned to choice options often make very similar behavioral predictions, which poses a major difficulty for establishing a mechanistic, biologically plausible explanation of decision-making based on behavior alone. Here, we demonstrate that model comparison at the neural level provides insights into model implementation during subjective value computation even though the distinct models parametrically identify common brain regions as computing subjective value. We show that frontal cortical regions implement a model based on the statistical distributions of available rewards, whereas intraparietal cortex and striatum compute subjective value signals according to a model based on distortions in the representations of probabilities. Thus, better mechanistic understanding of how cognitive processes are implemented arises from model comparisons at the neural level, over and above the traditional approach of comparing models at the behavioral level alone.

In highly security-critical network environments, it is a popular design decision to offload cryptographic tasks like encryption or signature generation to a dedicated trusted module or key server with paramount security features, we in this paper refer to with the general term Cryptographic Key Management Device (CKMD). While this network design yields several benefits, we demonstrate that the use of popular counter mode encryption modes like CTR or GCM can show substantial shortcomings in terms of security when used in conjunction with this network design. In particular, we show how the use of authenticated encryption using GCM enables the possibility of establishing a subliminal channel by exploiting the authentication information within messages. We show how decoding of hidden information can proceed in addition to decryption of overt information without raising authentication failures. With an exemplary but typical infrastructure, we show how the subliminal channel might be exploited and discuss approaches to mitigating the threat by preventing the ability to embed hidden information. In contrast to previous work, we conclude that, when using an infrastructure involving a CKMD and GCM is deployed, the use of random, CKMD-generated Initialization Vectors (IVs) is beneficial to avoid the subliminal channel described in this paper. However, the most potent remedy is deploying a different operational mode like GCM-SIV.

Mild diseases and moderate stressors are seemingly harmless and are therefore often assumed to have negligible impact on Darwinian fitness. Here we argue that the effects of “benign” parasites and other moderate stressors may have a greater impact on lifespan and other fitness traits than generally thought. We outline the “accumulating costs” hypothesis which proposes that moderate strains on the body caused by mild diseases and other moderate stressors that occur throughout life will result in small irreversible “somatic lesions” that initially are invisible (i.e., induce “hidden” costs). However, over time these somatic lesions accumulate until their summed effect reaches a critical point when cell senescence and malfunction begin to affect organ functionality and lead to the onset of degenerative diseases and aging. We briefly discuss three potential mechanisms through which the effects of moderate strains (e.g., mild diseases) could accumulate: Accelerated telomere shortening, loss of repetitious cell compartments and other uncorrected DNA damage in the genome. We suggest that telomere shortening may be a key candidate for further research with respect to the accumulating costs hypothesis. Telomeres can acquire lesions from moderate strains without immediate negative effects, lesions can be accumulated over time and lead to a critically short telomere length, which may eventually cause severe somatic malfunctioning, including aging. If effects of mild diseases, benign parasites and moderate stressors accrued throughout life can have severe delayed consequences, this might contribute to our understanding of life history strategies and trade-offs, and have important implications for medicine, including consideration of treatment therapies for mild (chronic) infections such as malaria.

Background There is growing evidence that equine papillomavirus type 2 (EcPV2) infection is causally associated with the development of equine genital squamous cell carcinomas (SCCs). Early stages of disease present clinically as plaques or wart-like lesions which can gradually progress to tumoural lesions. Histologically these lesions are inconsistently described as benign hyperplasia, papilloma, penile intraepithelial neoplasia (PIN), carcinoma in situ (CIS) or SCC. Guidelines for histological classification of early SCC precursor lesions are not precisely defined, leading to potential misdiagnosis. The aim of this study was to identify histologic criteria and diagnostic markers allowing for a more accurate diagnosis of EcPV2-associated equine penile lesions. Results A total of 61 archived equine penile lesions were histologically re-assessed and classified as benign hyperplasia, papilloma, CIS or SCC. From these, 19 representative lesions and adjacent normal skin were comparatively analysed for the presence of EcPV2 DNA and transcripts using PCR and RNA in situ hybridisation (RISH). All lesional samples were positive by EcPV2 PCR and RISH, while adjacent normal skin was negative. RISH analysis yielded signal distribution patterns that allowed distinction of early (hyperplasia, papilloma) from late stage lesions (CIS, SCC). Subsequently, the 19 lesions were further assessed for expression of p53, Ki67, MCM7 and MMP1 by immunohistochemistry (IHC). All four proteins were expressed in both normal and lesional tissue. However, p53 expression was up-regulated in basal keratinocyte layers of papillomas, CIS and SCCs, as well as in upper keratinocyte layers of CIS and SCCs. MCM7 expression was only up-regulated in upper proliferating keratinocyte layers of papillomas, CIS and SCCs. Conclusion This study proposes combining a refined histological protocol for analysis of equine penile lesions with PCR- and/or RISH based EcPV2-screening and p53/MCM7 IHC to more accurately determine the type of lesion. This may help to guide the choice of optimum treatment strategy, especially at early stages of disease.

Umbilical preservation can be challenging, particularly in complex cases involving simultaneous ventral hernia repair and abdominoplasty. Although the umbilicus serves no functional purpose, removal of the umbilicus can draw unwanted attention to the abdominal area and can cause emotional distress to patients. There are several well documented options for umbilical reconstruction. We present a new umbilical reconstruction technique relevant for such cases. This neoumbilicoplasty allows for preservation of the original umbilicus with relocation and reconstruction using local flaps. The technique is relatively simple and the time needed is minimal. The result is a natural, well positioned umbilicus using the principles of spare part surgery.

We sought to investigate whether robotic pancreatoduodenectomy (RPD) mitigates adverse outcomes in patients with high-risk morphometric features compared to the open approach (OPD).Morphometric parameters for RPD and OPDs were measured by two blinded radiologists. The morphometric parameter best correlating with adverse outcomes was identified and used in multivariable models to evaluate the impact of surgical approach (open vs. robotic) on outcomes of patients with high-risk morphometric features.Of 282 PDs available for morphometric analysis, 134 (47.5%) underwent RPD. Average Psoas Density demonstrated the most frequent association with adverse outcomes, with correlations to prolonged LOS (ρ= -0.154, p=0.01), severe complications (ρ= -0.159, p=0.007), readmission (ρ= -0.16, p=0.007), and discharge to home (ρ= 0.2, p0.001). On multivariable analysis of patients with high-risk morphometric features (defined as APD ≤ 50This study confirms the association between morphometrics and outcomes following PD, and suggests that the robotic approach may be associated with improved outcomes in PD patients with high-risk morphometric features.

The tropical archipelago of Wallacea contains thousands of individual islands interspersed between mainland Asia and Near Oceania, and marks the location of a series of ancient oceanic voyages leading to the peopling of Sahul—i.e., the former continent that joined Australia and New Guinea at a time of lowered sea level—by 50,000 years ago. Despite the apparent deep antiquity of human presence in Wallacea, prior population history research in this region has been hampered by patchy archaeological and genetic records and is largely concentrated upon more recent history that follows the arrival of Austronesian seafarers ~3000–4000 years ago (3–4 ka). To shed light on the deeper history of Wallacea and its connections with New Guinea and Australia, we performed phylogeographic analyses on 656 whole mitogenomes from these three regions, including 186 new samples from eight Wallacean islands and three West Papuan populations. Our results point to a surprisingly dynamic population history in Wallacea, marked by two periods of extensive demographic change concentrated around the Last Glacial Maximum ~15 ka and post-Austronesian contact ~3 ka. These changes appear to have greatly diminished genetic signals informative about the original peopling of Sahul, and have important implications for our current understanding of the population history of the region. 1. Introduction 2. Materials and Methods 2.1. Sample Collection and Ethics 2.2. Mitochondrial Sequence Generation 2.3. Combined Wallacea–Sahul Dataset 2.4. Phylogenetic Parameter Estimation 2.5. Using Ancestral Node Dates from Geographically Exclusive Clades to Infer Demographic History 2.6. Migration Model Inference and Testing 2.7. Simulating and Estimating the Timing of Migration Events 3. Results 3.1. Summary of New Mitochondrial Haplogroups from Wallacea and West Papua 3.2. Phylogeographic Analyses 4. Discussion 4.1. Post-LGM Population Expansions and Movements 4.2. Redistribution of Papuan mtDNA Lineages Following Austronesian Contact 4.3. Comparison with Wallacean Archaeological and Linguistic Records 5. Conclusions

Background Maternal congenital heart disease (CHD) is the most common cardiac condition to complicate pregnancy and women now become pregnant even with complex CHD. The Registry Of Pregnancy And Cardiac disease (ROPAC) examines the relationship between maternal heart disease and pregnancy outcome. Methods The ESC EORP ROPAC is a worldwide prospective registry of pregnancies in women with structural heart disease (n=5739, recruiting between 2007-2018), including CHD. Maternal and fetal outcomes were examined in all women with CHD. Multivariable regression was used to identify associations with a composite endpoint of maternal mortality and/or heart failure. Results In CHD pregnancies (n=3295, mean age 29 years), maternal mortality was 0.3% and heart failure occurred in 6.6%. Preterm births (16%) and Caesarean section (46.3%) were higher than global averages, but otherwise cardiac, obstetric and fetal outcomes were good. The composite endpoint was highest in complex CHD: Eisenmenger syndrome (58.1%), congenitally corrected transposition of the great arteries (12.8%), Fontan circulation (11.2%), double outlet right ventricle (11.1%). Pre-pregnancy signs of heart failure (OR 10.6, 95% CI 7.1-16), multiple gestation (4.6, 2-10.8), pulmonary hypertension (2.5, 1.5-4), estimated LVEF Conclusion Overall pregnancy outcomes for women with CHD are good but women with complex CHD are at increased risk of complications. Pre-pregnancy assessment can identify women at increased risk of an adverse outcome and should be used to counsel women appropriately.

The National Association for Quality Development in Hospitals and Clinics (ANQ) has conducted patient satisfaction measurements in the inpatient sector in Switzerland since 2009. Specifically designed for this measurement, an instrument consisting of five questions was evaluated on an 11-point rating scale. Nevertheless, the instrument showed substantial ceiling effects, which did not allow for hospital discrimination. Therefore, ANQ initiated a revision testing different scales in a pilot study. The results showed that a 5-point verbal scale displayed good psychometric properties. Compared to the 7- or 11-point scales, the 5-point verbal scale exhibited reduced ceiling effects, which was more appropriate to compare hospitals. For the national public reporting of hospitals and clinics, risk adjustment by age and self-reported health status was recommended, which was not the case for gender, principal diagnosis, type of admission and insurance status.

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat psychiatric disorders with affective biases such as depression and anxiety. How SSRIs exert a beneficial action on emotions associated with life events is still unknown. Here we ask whether and how the effectiveness of the SSRI fluoxetine is underpinned by neural mechanisms in the ventral striatum. To address these issues, we studied the spiking activity of neurons in the ventral striatum of monkeys during an approach-avoidance task in which the valence assigned to sensory stimuli was manipulated. Neural responses to positive and negative events were measured before and during a 4-week treatment with fluoxetine. We conducted PET scans to confirm that fluoxetine binds within the ventral striatum at a therapeutic dose. In our monkeys, fluoxetine facilitated approach of rewards and avoidance of punishments. These beneficial effects were associated with changes in tonic and phasic activities of striatal neurons. Fluoxetine increased the spontaneous firing rate of striatal neurons and amplified the number of cells responding to rewards versus punishments, reflecting a drug-induced positive shift in the processing of emotionally valenced information. These findings reveal how SSRI treatment affects ventral striatum neurons encoding positive and negative valence and striatal signaling of emotional information. In addition to a key role in appetitive processing, our results shed light on the involvement of the ventral striatum in aversive processing. Together, the ventral striatum appears to play a central role in the action of SSRIs on emotion processing biases commonly observed in psychiatric disorders.

Repetitive transcranial magnetic stimulation (rTMS) is now widely used as a means of neuromodulation, but the details of the mechanisms by which rTMS works remain unclarified. As a step forward to unveiling the neural phenomena occurring underneath the TMS coil, we conducted an electrophysiological study using awake and unanesthetized monkeys with subdural electrocorticogram (ECoG) electrodes implanted over the primary motor cortex (MI). We evaluated the effects of low-frequency (1 Hz) and high-frequency (10 Hz) rTMS on the resting-state ECoG signals in the stimulated MI, as well as the motor evoked potentials (MEPs) in the contralateral hand. Following the 1-Hz rTMS application, the ECoG beta band power and the MEP amplitude were significantly decreased. Following the 10-Hz rTMS application, the ECoG high-gamma power and the MEP amplitude significantly increased. Given that beta and high-gamma activities in the ECoG reflect the synchronous firing and the firing frequency of cell assemblies, respectively, in local neural circuits, these results suggest that low-frequency rTMS inhibits neural activity by desynchronizing the firing activity of local circuits, whereas high-frequency rTMS facilitates neural activity by increasing the firing rate of cell assemblies in the local circuits.

Background: The purpose of this study was to investigate whether patients with adult congenital heart disease (ACHD) benefit from exercise-based cardiac rehabilitation (CR) short- and long-term with regard to improvement of cardiorespiratory fitness. Methods: Cardiopulmonary exercise tests (CPET) completed by ACHD patients between January 2000 and October 2019 were analysed retrospectively. Linear mixed models were performed for peak oxygen consumption (VO2) with patients as random effect and age, sex, disease classification, preceding surgery (≤3 months) and preceding CR (≤4 weeks for short term and >4 weeks for long term) as fixed effects. Results: 1056 CPETs of 311 ACHD patients with simple (7), moderate (188) or great (116) complexity heart defects were analysed. The 59 patients who completed a CR (median age 27 yrs, 38% females) increased peak VO2 from before to after CR by a median of 2.7 (IQR –0.6 to 5.5) ml/kg/min. However, in the multivariate mixed model, peak VO2 was non-significantly increased short-term after CR (β 0.8, 95%CI –0.7 to 2.4), not maintained long-term after CR (β 0.0, 95%CI –1.7 to 1.6) but significantly reduced after surgery (β –5.1, 95%CI –7.1 to –3.1). The 20 CR patients after surgery increased their peak VO2 by 6.2 (IQR 3.6–9.5) ml/kg/min, while the 39 CR patients without preceding surgery increased it by 0.9 (IQR –1.5 to 3.1) ml/kg/min. Conclusions: The increase in peak VO2 with CR was mainly due to recovery from surgical intervention. The small independent benefit from CR was not maintained long-term, highlighting the potential to improve current CR concepts in ACHD populations.

BACKGROUND Patients with systemic right ventricle (sRV), including transposition of great arteries (TGA) after atrial switch procedure and congenitally corrected transposition of great arteries (ccTGA), may require anticoagulation for thromboembolism (TE) prevention. In the absence of data on non-vitamin K antagonist oral anticoagulants (NOACs), vitamin K antagonists (VKAs) remain the agent of choice. We investigated the safety, efficacy and feasibility of NOACs treatment in adults with sRV in a worldwide study. METHODS This is an international multicentre prospective study, using data from the NOTE registry on adults with sRV taking NOACs between 2014 and 2019. The primary endpoints were TE and major bleeding (MB). The secondary endpoint was minor bleeding. RESULTS A total of 76 patients (42.5��������10.0���years, 76% male) with sRV (74% TGA, 26% ccTGA) on NOACs were included in the study. During a median follow-up of 2.5���years (IQR1.5-3.9), TE events occurred in 3 patients (4%), while no MB episodes were reported. Minor bleeding occurred in 9 patients (12%). NOAC treatment cessation rate was 1.4% (95%CI:0.3-4%) during the first year of follow-up. All the patients with TE events had a CHA2DS2-VASc score���������2 and impaired sRV systolic function at baseline. The total incidence of major events during follow-up was significantly lower compared to historical use of VKAs or aspirin before study inclusion (1.4% (95%CI:0.29-4%) vs 6,9% (95%CI:2.5-15.2%); p���=���.01). CONCLUSIONS In this prospective study, NOACs appear to be well-tolerated, with excellent efficacy and safety at mid-term in patients with sRV.

Importance: Therapeutic inertia (TI) is the failure to escalate therapy when treatment goals are unmet and is associated with low tolerance to uncertainty and aversion to ambiguity in physician decision-making. Limited information is available on how physicians handle therapeutic decision-making in the context of uncertainty. Objective: To evaluate whether an educational intervention decreases TI by reducing autonomic arousal response (pupil dilation), a proxy measure of how physicians respond to uncertainty during treatment decisions. Design, setting, and participants: In this randomized clinical trial, 34 neurologists with expertise in multiple sclerosis (MS) practicing at 15 outpatient MS clinics in academic and community institutions from across Canada were enrolled. Participants were randomly assigned to receive an educational intervention that facilitates treatment decisions (active group) or to receive no exposure to the intervention (usual care [control group]) from December 2017 to March 2018. Participants listened to 20 audio-recorded simulated case scenarios as pupil responses were assessed by eye trackers. Autonomic arousal was assessed as pupil dilation in periods in which critical information was provided (first period [T1]: clinical data, second period [T2]: neurologic status, and third period [T3]: magnetic resonance imaging data). Data were analyzed from September 2018 to March 2020. Interventions: The traffic light system (TLS)–based educational intervention vs usual care (unexposed). The TLS (use of established associations between traffic light colors and actions to stop or proceed) assists participants in identifying factors associated with worse prognosis in MS care, thereby facilitating the treatment decision-making process by use of established associations between red, green, and yellow colors and risk levels, and actions (treatment decisions). Main outcomes and measures: Pupil assessment was the primary autonomic outcome. To test the treatment effect of the educational intervention (TLS), difference-in-differences models (also called untreated control group design with pretest and posttest) were used. Results: Of 38 eligible participants, 34 (89.4%) neurologists completed the study. The mean (SD) age was 44.6 (11.6) years; 38.3% were female and 20 (58.8%) were MS specialists. Therapeutic inertia was present in 50.0% (17 of 34) of all participants and was associated with greater pupil dilation. For every additional SD of pupil dilation, the odds of TI increased by 51% for T1 (odds ratio, 1.51; 95% CI, 1.12-2.03), by 31% for T2 (odds ratio, 1.31; 95% CI, 1.08-1.59), and by 49% for T3 (odds ratio, 1.49; 95% CI, 1.13-1.97). The intervention significantly reduced TI (risk reduction, 31.5%; 95% CI, 16.1%-47.0%). Autonomic arousal responses mediated 29.0% of the effect of the educational intervention on TI. Conclusions and relevance: In this randomized clinical trial, the TLS intervention decreased TI as measured by pupil dilation, which suggests that individual autonomic arousal is an indicator of how physicians handle uncertainty when making live therapeutic decisions. Pupil response, a biomarker of TI, may eventually be useful in medical education. Trial registration: ClinicalTrials.gov Identifier: NCT03134794

Introduction Partial anomalous pulmonary venous connection (PAPVC) is a rare congenital heart disease, characterized by one or some but not all pulmonary veins anomalously connected to the right atrium or a systemic vein. PAPVC is either an isolated shunt lesion or associated with an atrial septal defect (ASD). This study compares the arrhythmic outcome of patients treated surgically with those clinically monitored. Method Clinical, surgical, imaging and invasive data of PAPVC patients were retrospectively reviewed from 7 centers from the Swiss Adult Congenital HEart disease Registry (SACHER) and one French center. Results A total of 168 patients with PAPVC were identified. Most (77%) patients underwent surgery, while the remaining (23%) ones were treated conservatively with clinical monitoring. The operated group (OG) had a significantly higher number of associated ASD (N=106, 82%) (p Age did not differ at latest follow-up (table). Holter recordings revealed a higher prevalence of arrhythmia in the OG (p=0.031), mainly of supraventricular tachyarrhythmias (table). The occurrence of ventricular non-sustained tachycardia and of bradyarrhythmia did not statistically differ between groups. Patients in the OG required more often medical treatment for arrhythmias: 12 (9%) needed electrophysiological study in the OG and none in the NOG (p=0.057). The amount of patients requiring a pacemaker implantation in the OG (11%) was significantly higher than that of NOG (0%) (p=0.039). Conclusion Patients after PAPVC repair present with a significant higher burden of arrhythmia than conservatively treated patients, either due to a larger shunt pre-operatively and/or as a late complication of the corrective surgery itself. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Unrestricted grant from Actelion, Switzerland

Introduction Total anomalous pulmonary venous connection is a rare cyanotic congenital heart disease, where all pulmonary veins aberrantly connect to a systemic vein or the right atrium. The only curative treatment is surgery allowing the patients to reach adulthood. This study describes the long-term outcome of these individuals focusing on arrhythmias. Methods Clinical, surgical, imaging and invasive data were retrospectively reviewed from 7 centers participating in the Swiss Adult Congenital Heart disease Registry (SACHER) and one French center. Results A total of 57 patients were identified and analyzed 22±8 years after surgery. At last follow-up, 21% of patients presented cardiac symptoms, mainly palpitations. No patient had pulmonary hypertension or a relevant valvulopathy. Echocardiography revealed in 5 (8.8%) patients a dilated right ventricle (RV) and in 3 (5.3%) patients a diminished RV systolic function. Exercise capacity was normal in most patients (table). Cardiac magnetic resonance imaging found in 2 (4%) had a residual shunt with an mean Qp:Qs of 1.25, due to a single anomalously connected pulmonary vein. Holter recordings revealed arrhythmias in 23% of patient. Ten (17.5%) had atrial fibrillation, flutter or tachycardia. Three (5%) patients presented ventricular arrhythmias: two patients showed non-sustained ventricular tachycardia and one patient complex ventricular extrasystoles. Four patients (7%) were on antiarrhythmic medication for supraventricular arrhythmias. Three patients (5%) underwent an electrophysiological study with a mean time since surgery of 20 years. Three (5%) patients underwent pacemaker implantation within 3 weeks to 36 months after surgical correction, which were removed in 2 patients after 7 years. Age and the presence of a valvulopathy at follow-up predicted tachyarrhythmia on binomial logistic regression analysis (p Conclusions In adult survivors after TAPVC repair, supraventricular but also ventricular arrhythmias are frequently observed which appears to be related to age and valvular lesions at follow-up. This study underlies the importance of long-term follow-up as some of the patients currently without arrhythmia will probably develop rhythm disorders in the future. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Unrestricted grant by Actelion SA, Switzerland

Background Pregnancy in women with repaired aortic coarctation (CoA) has a moderately increased risk (mWHO II-III) of an adverse cardiovascular, obstetric or fetal event, but prospective data to validate this estimated risk is scarce. Purpose We examined maternal and fetal outcomes in pregnant women with unrepaired and repaired CoA to identify predictors of adverse outcomes. Methods Pregnancies in women with CoA were selected from the worldwide prospective Registry of Pregnancy and Cardiac Disease (ROPAC, n=5739). The frequency and predictors of major adverse cardiac events (MACE, defined as maternal cardiac death, heart failure, atrial fibrillation/flutter, ventricular tachyarrhythmia, endocarditis, thromboembolic events, aortic dissection and acute coronary syndrome), and hypertensive complications (defined as pregnancy-induced hypertension, (pre)eclampsia or HELLP syndrome) were analyzed. Results Of 303 pregnancies in women with CoA (median age 30 years, median pregnancy duration 39 weeks), 10% were in women with unrepaired CoA and 27% in women with pre-existing hypertension. There were no maternal deaths. There were 4 neonatal deaths of which 3 occurred after a spontaneous extreme preterm birth. MACE occurred in 4.3% of pregnancies, predominantly involving heart failure (3.3%). MACE rate was similar in unrepaired vs repaired CoA (3.4% vs 4.4%, p=0.814). Predictors of MACE included pre-pregnancy clinical signs of heart failure (OR 31.8, 95% CI 6.8–147.7), LVEF 1 (OR 11.4, 95% CI 3.6–36.3), cardiac medication use (OR 4.9, 95% CI 1.3–18.3) and living in an emerging country (OR 4.88, 95% CI 1.58–15.07). Hypertensive complications occurred in 6.3%, more often in the subgroup with pre-existing hypertension (11% vs 5%, p=0.040). Pre-existing hypertension was the only predictor (OR 2.6, 95% CI 1.01–6.6). Caesarean section was performed in 50% of the total cohort. Conclusions Pregnancies in women with CoA are safe, well tolerated and MACE and hypertensive complication rates are low. These findings support mWHO risk score reevaluation to mWHO II for women with CoA without cardiac impairment. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): ESC EURObservational Research Programme (EORP)